Name: 1445-69-8|2,3-Dihydrophthalazine-1,4-dione|99%
Brand: Ambeed
SKU: A145357
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1
[ 85-44-9 ]
[ 1445-69-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With acetic acid; hydrazine at 120℃;
97.9%	With tetrabutylammomium bromide; hydrazine hydrate In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; Green chemistry;	1-9 Example 5: 400 g of recovered solvent xylene was added to a 1000 mL four-necked flask equipped with a stirring, a condenser and a thermometer.118.4 g (0.80 mol) of raw material, 1.84 g of phase transfer catalyst tetrabutylammonium bromide, and the temperature was raised to 120 ° C or higher.Adding 60% hydrazine hydrate 73.3g (0.088 mol), while distilling out the azeotrope of solvent xylene and the formed water,After the water is separated into water, the reaction is carried out for 2-3 hours, the reaction is completed, and the mixture is cooled to room temperature. After the reaction is completed,After cooling and suction filtration, 126.9 g of phthaloyl hydrazide was obtained, and the yield was 97.9%.High performance liquid chromatography (HPLC) purity of 98.7%.
96%	With hydrazine hydrate; acetic acid at 0 - 125℃; for 2h; Inert atmosphere;	1; 2 Phthalic anhydride (1a, purchased from Shanghai Shaoyuan Co. Ltd.) (10g, 67.6 mmol) was dissolved in glacial acetic acid (100 mL), hydrazine hydrate (20 mL) was added dropwise under the condition of ice bath (0°C) and stirring, and then refluxed for two hours at 125°C. The reaction was monitored by TLC. The solution was cooled to room temperature, filtrated and washed with water until the pH of the filtrate was 6.0, and then dried to give phthalhydrazide (1b), 10.5g white solid (yield 96%). ESI-MS m/z calculated for: 162.04, found: 173.15 [M+H]+.

96%	With hydrazine hydrate; acetic acid In acetic acid at 0 - 125℃; for 2h;	2 Phthalic anhydride (la, purchased from Shanghai Shaoyuan Co. Ltd.) (10 g, 67.6 mmol) was dissolved in glacial acetic acid (100 mE), hydrazine hydrate (20 mE) was added dropwise under the condition of ice bath (0° C.) and stirring, and then refluxed for two hours at 125° C. The reaction was monitored by TEC. The solution was cooled to room temperature, filtrated and washed with water until the pH of the filtrate was 6.0, and then dried to give phthalhydrazide (lb), 10.5 g white solid (yield 96%). ESI-MS mlz calculated for: 162.04. found: 173.15 [M+H].
95%	With hydrazine hydrate In ethanol for 5h; Reflux;
95.4%	With hydrazine hydrate; acetic acid In water at 20 - 95℃; for 3h;	I.1 in room temperature,1.2 L of acetic acid was added to 3 L of a three-necked flask,Followed by addition of raw material phthalic anhydride 120.0 g (0.81 moll.0 eq)And hydrazine hydrate 52.4 g (85% aqueous solution 0.81 mol l.Oeq),After finishing,Start heating to 95 ° C to reflux,After stirring for 3 hours,After the reaction was complete by TLC,Cooled to room temperature,Precipitated a large amount of white solid,filter,The filter cake was rinsed with 200 mL of ethyl acetate,To give 125.0 gThe first step of the product hydrazide (yield: 95.4
93%	With hydrazine hydrate; acetic acid at 120℃; for 4h;
90.5%	With hydrazine hydrate In ethanol at 20℃; for 2h;
90%	With hydrazine hydrate; acetic acid at 120℃; for 4h;	4.2 Preparation of 2,3-dihydrophthalazine-1,4-dione (1) Hydrazine hydrate (2.8mL, 44mmol) was added to a stirred solution of phthalic anhydride (6.01g, 40mmol) in acetic acid (22mL). The mixture was heated to 120°C for 4h. The reaction mixture was cooled to room temperature and filtered through a buchner funnel. Then the filter cake was washed with petroleum ether (2×10mL) and dried in vacuum. 1 (5.91g, 90%) was obtained as a white solid. Mp: 181-182°C. 1H NMR (400MHz, DMSO) δ 11.55 (s, 2H, NH), 8.08 (dd, J=5.7, 3.4Hz, 2H, ArH), 7.96-7.76 (m, 2H, ArH).
89.8%	With hydrazine hydrate In acetic acid at 120℃; for 4h;	1. Preparation of 2, 3-dihydrophthalazine-1, 4-dione (1) Hydrazine hydrate (2.8 ml, 44 mmol) was added to a stirred solution of phthalic anhydride (6.01 g, 40 mmol) in acetic acid (22 ml). The mixture was heated to 120°C for 4 h. The reaction mixture was cooled to room temperature and filtered through a buchner funnel. Then the filter cake was washed with petroleum ether (2×10 ml) and dried in a vacuum. 1 (5.91 g, 89.8 %) was obtained as a white solid.
88%	With hydrazine In acetic acid for 3h; Heating / reflux;	23 A mixture of phthalic anhydride (1.0 g, 6.7 mmol), hydrazine hydrate (0.36 mL,7.4 mmol, 1.1 eq) and acetic acid (10 mL) was refluxed for 3 h. Upon heating the suspension went clear initially and then a solid precipitated from solution. After 3 h the mixture was cooled to rt and the solid collected via vacuum filtration to provide 0.96 g (88 %) of the title compound as a white solid was obtained. 1H NMR (DMSO-J6) δ 11.5 (br s, 2 H), 8.08 (br s, 2 H), 7.80 - 7.95 (m, 2 H). MS (ES) 263 (M + H).
85%	With hydrazine hydrate; acetic acid at 120℃;
82%	With hydrazine hydrate In ethanol for 1h; Reflux;	8 5.2.8 2,3-Dihydrophthalazine-1,4-dione (6) Phthalic anhydride (1.48 g, 10 mmol) was dissolved in ethanol (20 mL), then to this mixture was added hydrazine hydrate (2 mL, 50%, 20 mmol) dropwise. The reaction mixture was refluxed 1 h. After cooled to room temperature, the white solid was collected through filtration. Yield: 1.32 g, 82%, white solid. 1H NMR (400 MHz, CDCl3) δ: 11.52 (s, 2H), 8.10 (m, 2H), 7.90 (m, 2H). TOF MS (EI+): C8H6N2O2, found 161.04. Mp: >300 °C.
78.5%	With hydrazine In ethanol at 20℃; Cooling with ice;
69%	With hydrazine hydrate; acetic acid Reflux;	2,3-dihydro-1,4-phthalazine (98) (0379) To a solution of phthalic anhydride (500 mg, 3.38 mmol) in acetic acid (5 mL) was added hydrazine monohydrate (200 μ, 4.17 mmol) was added, the mixture was refluxed overnight, cooled to room temperature. The reaction mixture was diluted with water, participation was filtered out and washed with water and DCM, then dried by vacuum to yield white solid (376mg 69%). 1H NMR (400 MHz, DMSO-cfc) δ 11.55 (s, 2H), 8.25- 7.99 (m, 2H), 7.88 (m, 2H).
	With ethanol; hydrazine hydrate Eindampfen des ausgeschiedenen Produkts wiederholt mit Wasser;
	With sodium acetate; acetic acid; hydrazinium sulfate
	Multi-step reaction with 2 steps 1: 140 °C 2: N₂H₄+H₂O; acetic acid
	Multi-step reaction with 2 steps 1: acetic acid 2: N₂H₄+H₂O; acetic acid
	Multi-step reaction with 2 steps 1: 140 °C 2: N₂H₄+H₂O; acetic acid
	Multi-step reaction with 2 steps 1: acetic acid; hydrazine hydrate / in geringer Menge 2: 200 °C
	Multi-step reaction with 3 steps 1: acetic acid; hydrazine hydrate / in geringer Menge 2: acetic acid 3: N₂H₄+H₂O; acetic acid
	Multi-step reaction with 2 steps 1: potassium acetate / 200 - 220 °C 2: alcohol; hydrazine hydrate
	Multi-step reaction with 5 steps 1: triethylamine / toluene / 130 °C 2: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 20 °C 3: sodium metabisulfite; sodium bromate / cyclohexane; water; ethyl acetate / 20 °C 4: 1,4-dioxane; water / 20 h / Reflux 5: hydrazine hydrate; acetic acid / ethanol / 5 h / Reflux
	Multi-step reaction with 7 steps 1: triethylamine / toluene / 130 °C 2: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 20 °C 3: aluminum (III) chloride / dichloromethane / Reflux 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / Reflux 5: sodium metabisulfite; sodium bromate / cyclohexane; water; ethyl acetate / 20 °C 6: 1,4-dioxane; water / 20 h / Reflux 7: hydrazine hydrate; acetic acid / ethanol / 5 h / Reflux
	With hydrazine hydrate at 100℃; for 0.166667h;
	With hydrazine hydrate at 20℃; for 0.0333333h;	General procedure for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives General procedure for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives Hydrazine monohydrate (1.4 mmol), phthalic anhydride (1.2 mmol) reacted at room temperature until a white precipitated of phthalhydrazide was obtained (< 2 min).
	With hydrazine at 100℃; for 0.166667h;
	With hydrazine hydrate In ethanol for 12h; Reflux;
	With hydrazine hydrate at 80℃; for 0.166667h;
	With hydrazine hydrate In neat (no solvent) at 60℃; for 0.2h;
	With hydrazine hydrate In neat (no solvent) at 70℃; for 0.166667h;	Typical procedure for the preparation of tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione Hydrazine hydrate (1.2 mmol) and phthalic anhydride (1 mmol) were mixed at 70°C until a white solid phthalhydrazide was formed (10 min). Then, barbituric acid (1 mmol), benzaldehyde (1 mmol) and VB1-Al2O3 (0.8 g, 5 mol %) was added to this solid-state mixture. The completionof reaction is monitored on TLC. After completion of reaction, the mixture cooled to room temperature. Then, EtOAc (30 mL)was added and the catalyst was recovered by simple filtration. The catalyst was washed with EtOAc and dried at 100 °C for 3 h, which could be reused without loss of its activity. The filtrate solution was concentrated and the solid product was recrystallized in EtOH to give pure products (Fig. 1).
	With hydrazine hydrate In ethanol Heating;
	With hydrazine hydrate; acetic acid at 120℃; for 4h; Reflux;	1 Example 1 Phthalic anhydride, 6.00g (40mmol) in 100mL single neck flask was added 22mL of glacial acetic acid was stirred, as the temperature rises gradually accelerated dissolution rate to 120 material dissolved, hydrazine hydrate was slowly added dropwise 2.81mL (44mmol) , pale yellow reaction solution becomes milky, and later became milky white, and heating continued under reflux for about 4h. The reaction was cooled to room temperature, suction filtered, washed twice with petroleum ether, and dried in vacuo to give a white product of 2,3-dihydro-phthalazine-1,4-dione.
	With hydrazine hydrate; acetic acid In water for 4h; Reflux;	1 Take phthalic anhydride 6.00g(40mmol) at 100ml bottle add 22mL acetic acid stirring with the temperature the dissolution rate increased gradually accelerated to 120 , raw material all dissolved and slowly, dropping water hydrazine hydrate, 2.81mL(44mmol)The reaction solution became a pale yellow emulsion and then become white emulsion, Continue to heat reflux about 4h , The reaction liquid cooled to room temperature, filtered, washed with petroleum ether two times , vacuum drying, get the White product 2,3-dihydrophthalazine-1,4-dione
	With hydrazine hydrate In neat (no solvent) at 110℃; for 0.333333h;
	With hydrazine hydrate; acetic acid
	With 2,3,4,5,7,8,9,10-octahydropyrimido[1,2-a]azepin-1-ium acetate; hydrazine hydrate at 60 - 65℃; for 0.166667h;	General procedure of synthesis of 3-amino-1-(1H-indol-2-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo-[1,2-b]phthalazine derivatives (5). Phthalic anhydride (1) (10 mM) and hydrazine hydrate (2) (10 mM) were added to [DBUH][OAc] (50 mM) and heated for 10 min at 60-65 °C to form phthalhydrazide as an intermediate.
	With hydrazine hydrate In ethanol
	With hydrazine hydrate; acetic acid for 3h; Reflux;
	With hydrogenchloride; hydrazine hydrate In quinoline for 24h; Reflux;	General Procedure I (GP I) for the Preparation of 2,3-Dihydrophthalazine-1,4-diones (S2) General procedure: A stirred solution of phthalic anhydride (S1, 1.0 equiv), HCl (10 wt% aq), and N2H4*H2O (1.5 equiv) was refluxed in an oil bath for 24 hours under air. Then, the reaction mixture was cooled to room temperature and filtered through filter paper.The filter cake was washed with H2O and dried under reduced pressure to give 2,3-dihydrophthalazine-1,4-dione (S2). The crude material was used for the next step without further purification.
	With hydrazine hydrate In 1,4-dioxane Reflux;
	With hydrazine hydrate In ethanol for 5h; Reflux;
	With hydrazine hydrate; acetic acid Reflux;

Reference： [1]Wang, Wei; Feng, Xiu; Liu, Huan-Xiang; Chen, Shi-Wu; Hui, Ling [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3217 - 3226]
[2]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD - CN108675962, 2018, A Location in patent: Paragraph 0011-0019
[3]Current Patent Assignee: CHENGDU DIAO PHARMACEUTICAL GROUP CO LTD - EP2799435, 2014, A1 Location in patent: Paragraph 0049; 0068; 0069
[4]Current Patent Assignee: CHENGDU DIAO PHARMACEUTICAL GROUP CO LTD - US2015/51211, 2015, A1 Location in patent: Paragraph 0094; 0095
[5]El-Helby, Abdel Ghany A.; Ayyad, Rezk R.; Sakr, Helmy M.; Abdelrahim, Adel S.; El-Adl; Sherbiny, Farag S.; Eissa, Ibrahim H.; Khalifa, Mohamed M. [Journal of Molecular Structure, 2017, vol. 1130, p. 333 - 351]
[6]Current Patent Assignee: ACCELA CHEMBIO - CN103864696, 2016, B Location in patent: Paragraph 0015-0018
[7]Vuong, Thi Minh Ha; Weimmerskirch-Aubatin, Jennifer; Lohier, Jean-François; Bar, Nathalie; Boudin, Sophie; Labbé, Christophe; Gourbilleau, Fabrice; Nguyen, Hien; Dang, Tung Thanh; Villemin, Didier [New Journal of Chemistry, 2016, vol. 40, # 7, p. 6070 - 6076]
[8]Location in patent: experimental part Cheng-Xi, Wei; Zhou, Guo; Fu-Nan, Li; Zhe-Shan, Quan [Asian Journal of Chemistry, 2011, vol. 23, # 1, p. 127 - 131]
[9]Xue, Deng-Qi; Zhang, Xu-Yao; Wang, Chao-Jie; Ma, Li-Ying; Zhu, Nan; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Zhang, Xiao-Song; Wang, Cai-Feng; Ji, Cong-Hui; Zhang, Qiu-Rong; Liu, Hong-Min [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 235 - 244]
[10]Zhang, Qiu-Rong; Xue, Deng-Qi; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Ren, Jing-Li; Shan, Li-Hong; Liu, Hong-Min [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1236 - 1238]
[11]Current Patent Assignee: MYREXIS, INC. - WO2006/74223, 2006, A2 Location in patent: Page/Page column 32; 59
[12]Abulkhair, Hamada S.; Ahmed, Hany E. A.; Bayoumi, Ashraf H.; Ghiaty, Adel; Turky, Abdallah [Bioorganic Chemistry, 2020, vol. 100] Turky, Abdallah; Bayoumi, Ashraf H.; Ghiaty, Adel; El-Azab, Adel S.; A.-M. Abdel-Aziz, Alaa; Abulkhair, Hamada S. [Bioorganic Chemistry, 2020, vol. 101]
[13]Li, Xiangqian; Liang, Xiaomeng; Song, Ting; Su, Pengchen; Zhang, Zhichao [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 21, p. 5738 - 5746]
[14]Location in patent: experimental part Sun, Xian-Yu; Hu, Chuan; Deng, Xian-Qing; Wei, Cheng-Xi; Sun, Zhi-Gang; Quan, Zhe-Shan [European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 4807 - 4812]
[15]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - WO2019/89648, 2019, A1 Location in patent: Page/Page column 52
[16]Curtius; Foersterling [Journal fur praktische Chemie (Leipzig 1954), 1895, vol. <2> 51, p. 376]
[17]Radulescu; Georgescu [Bulletin de la Societe Chimique de France, 1925, vol. <4> 37, p. 889] Radulescu [Chemisches Zentralblatt, 1927, vol. 98, # II, p. 258] Mihailescu; Florescu [Bull. Sect. Sci. Acad. Roum., vol. 8, p. 310][Chemisches Zentralblatt, 1924, vol. 95, # II, p. 1590] Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[18]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[19]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[20]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[21]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[22]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[23]Wislicenus; Neber [Justus Liebigs Annalen der Chemie, 1919, vol. 418, p. 291]
[24]Catalano, Alessia; Carocci, Alessia; Cavalluzzi, Maria M.; Di Mola, Antonia; Lentini, Giovanni; Lovece, Angelo; Dipalma, Antonella; Costanza, Teresa; Desaphy, Jean-Francois; Camerino, Diana Conte; Franchini, Carlo [Archiv der Pharmazie, 2010, vol. 343, # 6, p. 325 - 332]
[25]Catalano, Alessia; Carocci, Alessia; Cavalluzzi, Maria M.; Di Mola, Antonia; Lentini, Giovanni; Lovece, Angelo; Dipalma, Antonella; Costanza, Teresa; Desaphy, Jean-Francois; Camerino, Diana Conte; Franchini, Carlo [Archiv der Pharmazie, 2010, vol. 343, # 6, p. 325 - 332]
[26]Location in patent: experimental part Shaterian, Hamid Reza; Mohammadnia, Majid [Journal of Molecular Liquids, 2012, vol. 173, p. 55 - 61]
[27]Shaterian, Hamid Reza; Aghakhanizadeh, Morteza [Comptes Rendus Chimie, 2012, vol. 15, # 11-12, p. 1060 - 1064]
[28]Shaterian, Hamid Reza; Mohammadnia, Majid [Research on Chemical Intermediates, 2014, vol. 40, # 1, p. 371 - 383]
[29]Ma, Long-Xu; Cui, Bai-Ri; Wu, Yan; Liu, Jia-Chun; Cui, Xun; Liu, Li-Ping; Piao, Hu-Ri [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1737 - 1741]
[30]Shaterian, Hamid Reza; Rigi, Fatemeh [Research on Chemical Intermediates, 2014, vol. 40, # 5, p. 1989 - 1995]
[31]Shaterian, Hamid Reza; Mollashahi, Ebrahim; Biabangard, Asiyeh [Journal of the Chemical Society of Pakistan, 2013, vol. 35, # 2, p. 329 - 332]
[32]Biabangard, Asiyeh; Shaterian, Hamid Reza [Journal of the Iranian Chemical Society, 2015, vol. 12, # 9, p. 1529 - 1534]
[33]Hemdan, Magdy M.; El-Sayed, Amira A. [Journal of Heterocyclic Chemistry, 2016, vol. 53, # 2, p. 487 - 492]
[34]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN104016986, 2016, B Location in patent: Paragraph 0036
[35]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN103694244, 2016, B Location in patent: Paragraph 0043
[36]Ghorbani-Vaghei, Ramin; Mahmoodi, Jafar; Maghbooli, Yaser [Applied Organometallic Chemistry, 2017, vol. 31, # 10]
[37]El-Helby, Abdel-Ghany A.; Ayyad, Rezk R. A.; Sakr, Helmy; El-Adl, Khaled; Ali, Mamdouh M.; Khedr, Fathalla [Archiv der Pharmazie, 2017, vol. 350, # 12]
[38]Jeevan Raghavendra; Siddaiah [Russian Journal of General Chemistry, 2018, vol. 88, # 9, p. 1892 - 1898][Zh. Obshch. Khim., 2018, vol. 88, # 9, p. 1892 - 1898,7]
[39]El-Helby, Abdel-Ghany A.; Ayyad, Rezk R. A.; El-Adl, Khaled; Elkady, Hazem [Molecular Diversity, 2019, vol. 23, # 2, p. 283 - 298]
[40]Elmeligie, Salwa; Aboul-Magd, Asmaa M.; Lasheen, Deena S.; Ibrahim, Tamer M.; Abdelghany, Tamer M.; Khojah, Sohair M.; Abouzid, Khaled A. M. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, vol. 34, # 1, p. 1347 - 1367]
[41]Im, Jeong Kyun; Yang, ByeongDo; Jeong, Ilju; Choi, Jun-Ho; Chung, Won-jin [Tetrahedron Letters, 2020, vol. 61, # 26]
[42]Hekal, Mohamed H.; Ali, Yasmeen M.; Abu El-Azm, Fatma S. M. [Synthetic Communications, 2020, vol. 50, # 18, p. 2839 - 2852]
[43]Khalifa, mohamed m.; Radwan, mohamed m.; Rashed, mahmoud; Sakr, Helmy; ayyad, Rezk R.; belal, amany; eissa, Ibrahim H.; el-Helby, abdel-Ghany a.; el-Sharkawy, abdou; elSohly, mahmoud a.; elhendawy, mostafa a.; mahdy, Hazem a.; metwaly, ahmed m. [Bioorganic Chemistry, 2020, vol. 103] Sakr, Helmy; Ayyad, Rezk R.; El-Helby, Ali A.; Khalifa, Mohamed M.; Mahdy, Hazem A. [Archiv der Pharmazie, 2021, vol. 354, # 6]
[44]Chen, Shi-Wu; Hao, Shu-Yi; Mou, Hong-Xia; Wang, Shuai; Xu, Yu; Zhang, Xiu-Juan [Bioorganic and Medicinal Chemistry Letters, 2020, vol. 30, # 23]

2
[ 1445-69-8 ]
[ 4752-10-7 ]

Yield	Reaction Conditions	Operation in experiment
97.9%	With chlorine; phosphorus trichloride In chloroform at 105℃;	1-19 Example 1-19: (1) Install Corning Microchannel Reactor as shown in Figure 1.(2 In a 3L four-necked bottle equipped with a stirring tube, a condenser tube and a thermometer, add the phthalic hydrazide powder, trichloromethane, and phosphorus trichloride milled in advance in proportion, and stir to form a stable suspension.(3) Set the flow rate of the diaphragm diaphragm metering pump so that the phthalic hydrazide,Ratio of phosphorus trichloride to chlorine,The quality of the suspension was controlled and passed into a microchannel reactor for preheating to a reaction temperature of 105 ° C, and then passed into the first microchannel reaction module for a mixed reaction.The system pressure in the microchannel reactor was controlled to 1.0Mpa.The obtained mixture is completely reacted in a subsequent microchannel reaction module or a series of 2-5 microchannel reaction modules to obtain a mixture containing 1,4-dichlorophthalazine.Simple separation and purification of the mixture containing 1,4-dichlorophthalazine.
93%	With pyridine; trichlorophosphate for 1h; Reflux;	5.1.20. 1,4-Dichlorophthalazine (12a) A mixture of phthalhydrazide 11a (2.50 g,15.42 mmol,1.0 equiv.)and pyridine (2.49 mL, 30.80 mmol, 2.0 equiv.) in POCl3 (50.3 mL)was heated at reflux for 1 h. After cooling, the reaction mixture wasconcentrated under vacuum. The residue was dissolved in cooledDCM and poured slowly into ice-cold water. The organic phase wasseparated and the aqueous phase was extracted twice with DCM.The combined organic layers were washed with a saturated solutionof NaHCO3 and brine, dried over Na2SO4, filtered, concentratedunder vacuum and purified by silica gel column chromatography(heptanes:EtOAc 3:2), to yield 12a as a white solid (2.84 g,14.27 mmol, 93%). 1H NMR (400 MHz, CDCl3) δ ppm 8.05-8.07 (m,2H), 8.30-8.32 (m, 2H); 13C NMR (101 MHz, CDCl3) δ ppm 126.2,127.7, 134.8, 155.4.
90.1%	With trichlorophosphate at 110℃; for 1h;	2. Preparation of 1, 4-dichlorophthalazine (2) The compound 1 (1.68 g, 10 mmol) was added to a stirred solution of phosphoruso xychloride (15 ml). The mixture was heated to 110°C for 1 h. After the reaction was complete (monitored by TLC), The reaction mixture was cooled to room temperature. The mixture was added dropwise to crushed ice with stirring for 10 minutes. Then the mixture was filtered through a buchner funnel. the filter cake was washed with H2O until neutral and dried in a vacuum. 2 (1.85 g, 90.1 %) was obtained as a white solid.

90%	With trichlorophosphate at 110℃; for 1h;	4.3 Preparation of 1,4-dichlorophthalazine (2) The compound 1 (1.68g, 10mmol) was added to a stirred solution of phosphorus oxychloride (15mL). The mixture was heated to 110°C for 1h. After the reaction was complete (monitored by TLC), the reaction mixture was cooled to room temperature. The mixture was added dropwise to crushed ice with stirring for 10min. Then the mixture was filtered through a buchner funnel. The filter cake was washed with H2O until neutral and dried in vacuum. 2 (1.85g, 90%) was obtained as a white solid. Mp: 192-193°C; 1H NMR (400MHz, DMSO) δ 8.29 (d, J=7.6Hz, 1H, ArH), 8.11-7.94 (m, 3H, ArH)
90%	With trichlorophosphate at 110℃;
90%	With trichlorophosphate at 106℃;
90%	With N,N-dimethyl-formamide; trichlorophosphate Heating;	3.5. Standard Procedure for Preparation of Chlorination Products 5, and 11-15 from Phthalazine1,4-Diones 3a-f with Vilsmeier Reagent (POCl3/DMF) General procedure: The reliable procedure that involved phthalazine 1,4-diones 3a-f (1.0 equiv.) wasindividually treated with ~3.0 equivalent amount of POCl3 in N, N-dimethylformamidesolution (DMF, 2.0 mL) at 65 C or 80 C for 2-4 h. When the reaction was completed, thereaction mixture was added to saturate sodium bicarbonate (15 mL) and extracted withdichloromethane (15 mL). The organic extracts were dried over MgSO4, filtered, and concentratedunder reduced pressure. The residues were purified by column chromatographyon silica gel to give the corresponding chlorinated products 5 in 80% yield and 11-15 in31-90% yields.
90%	With N,N-dimethyl-formamide; trichlorophosphate Heating;	3.5. Standard Procedure for Preparation of Chlorination Products 5, and 11-15 from Phthalazine1,4-Diones 3a-f with Vilsmeier Reagent (POCl3/DMF) General procedure: The reliable procedure that involved phthalazine 1,4-diones 3a-f (1.0 equiv.) wasindividually treated with ~3.0 equivalent amount of POCl3 in N, N-dimethylformamidesolution (DMF, 2.0 mL) at 65 C or 80 C for 2-4 h. When the reaction was completed, thereaction mixture was added to saturate sodium bicarbonate (15 mL) and extracted withdichloromethane (15 mL). The organic extracts were dried over MgSO4, filtered, and concentratedunder reduced pressure. The residues were purified by column chromatographyon silica gel to give the corresponding chlorinated products 5 in 80% yield and 11-15 in31-90% yields.
90%	With trichlorophosphate at 110℃; for 1h;	1 Example 1 1.68 g (10 mmol) of phthalic hydrazide was added to 15 mL of a 98% mass concentration of phosphoryl trichloride solution with constant stirring, and the coupling reaction was carried out at 110 ° C for 1 h (TLC monitoring), and the reaction solution was cooled to 25 ° C. Add dropwise to ice water to quench and stir, Filtration and washing with water to neutrality gave Intermediate 1 as a white solid (1.85 g, 90% yield)
85%	With trichlorophosphate In ethanol for 4h; Reflux;
84%	With trichlorophosphate Reflux;	1,4-dichlorophthalazine (99) (0381) Compound 98 (100 mg, 0.51 mmol) was reflux in POCl3 overnight, then poured on ice and neutralized, filtered out, the light yellow solid was dried by pulling air through (112mg, 84%) 1H NMR (400 MHz, chloroform-c ) δ 8.38 - 8.34 (m, 2H), 8.15- 8.09 (m, 2H).
83%	With trichlorophosphate at 110℃; for 1h;
83.5%	With trichlorophosphate for 4h; Reflux;	Synthesis of 1,4-dichlorophthalazine (2) The starting compound 2, 3-dihydrophthalazine-1,4-dione (compound 1) (10.0g, 61.7 mmol) was dissolved in phosphorus oxychloride (45 mL) and stirred under reflux for 4 h. Then most of solvent was removed under vacuum. The residual mixture was poured into ice water (300 ml) and stirred rapidly, and a lot of white solid precipitate out. Then the white solid was collected through filtration and dried in a vacuum to give the compound 2 (10.3 g, 51.5 mmol). M.p. 190-192, yield = 83.5%. 1H-NMR (CDCl3), δ: 7.93-8.01 (m, 2H, phthalizine-H), 7.60 (d, 2H, J = 7.9 Hz, phthalizine-H).
81%	With phosphorus(V) chloride; N,N-dimethyl-formamide for 7h; Heating; Inert atmosphere;
81.2%	With trichlorophosphate for 4h; Reflux;
81.99%	With trichlorophosphate for 4h; Reflux;
81%	With phosphorus(V) chloride; N,N-dimethyl-formamide at 145℃; for 8h; Inert atmosphere;
81%	With trichlorophosphate Reflux;	General procedure for preparation of compounds 3 and 5 General procedure: A mixture of phosphorous oxychloride and compound 2 or 4 was heated under reflux overnight. The mixture was cooled to room temperature and excess phosphorous oxychloride was evaporated under reduced pressure. The residue was poured on ice and extracted with DCM. The organic layer was extracted with Na2CO3 solution. The extracted organic layer was dried over anhydrous sodium sulfate, filtered, evaporated under reduced pressure giving compound 3 or 5.
80%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; phosphorus trichloride In acetonitrile at 50 - 72℃; for 10h; Autoclave; Large scale;	1-3 Embodiment 3 In a 50L reactor, 2KG diketophthalazine was added.0.15KG 1,8-diazabicycloundec-7-ene,10KG acetonitrile, start stirring; heat up to 50 ° C,At the beginning, 3.38 kg of phosphorus trichloride was slowly added dropwise, and the addition was completed in 6 hours.The reaction temperature in the autoclave was controlled at 72 ° C. After the completion of the dropwise addition, the reaction was refluxed for 4 hours.The reaction is complete; during this process, the vented gas is absorbed by the alkaline absorption cell.The reaction solution is drawn into a quenching kettle and quenched, and the solid is precipitated, and then centrifuged to collect a solid;The solid was added to the reaction vessel, stirred with 20 L of dichloromethane, and then added with water (5 L), stirred, and then allowed to stand. The organic phase was added to activated carbon and anhydrous sodium sulfate and stirred for 13 hours. The filtrate is concentrated under reduced pressure until some of the product is precipitated, and the crystal is cooled and crystallized in a cold storage.The crude product was 4.8 kg by suction filtration; the crude product was recrystallized from 10 L of a mixed solvent of dichloromethane and ethyl acetate to obtain a qualified product of 1.27 KG;Dichloromethane is added, the crystal is cooled and crystallized in a cold storage, and the filter cake is dried under reduced pressure.Another part of the qualified product was obtained 706g, and the two products obtained were 1.976kg.The content is 98.1%, and the yield is 80%.
78%	With phosphorus(V) chloride; N,N-dimethyl-formamide 1.) r.t. -> 145 deg C, 60 min, 2.) 145 deg C, 4 h;
78%	With trichlorophosphate In neat (no solvent) at 80℃; for 4h;
39%	With trichlorophosphate In N,N-dimethyl-formamide for 2h; Heating / reflux;	24 A mixture of 2,3-dihydro-ρhthalazine-l,4-dione (185 mg, 1.1 mmol) and DMF (5 drops) in POCl3 (5 mL) was refluxed for 2 h. The solution was then cooled to rt and quenched by careful dropwise addition into ice. The product was then collected via vacuum filtration to provide 88.5 mg (39 %) of the title compound as a white solid. 1H NMR (DMSO-J6) δ 8.34 - 8.42 (m, 2 H), 8.25 - 8.32 (m, 2 H). HRMS (ES) calcd for C8H5Cl2N2 (M + H) 198.9824, found 198.9832.
22.8%	With N,N-dimethyl-formamide; trichlorophosphate for 2h; Inert atmosphere; Reflux;	2; 3 Phthalhydrazide (1b) (1g, 6.2 mmol), phosphorus oxychloride (2.8 g, 18.6 mmol) and N, N-dimethylformamide were added into a reaction flask successively and refluxed for two hours, and then the reaction solution was carefully and slowly poured into ice water, and then warmed to room temperature, filtrated to remove the solid, the filtrate was concentrated under decreased pressure, and rapid column chromatography was performed with dichloromethane to give 1,4-dichlorophthalazine (2a), 281 mg pale yellow solid (yield 22.8%).
22.8%	With trichlorophosphate In N,N-dimethyl-formamide for 2h; Reflux;	3 Phthalhydrazide (lb) (1 g, 6.2 mmol), phosphorus oxychloride(2.8 g, 18.6 mmol) and N,N-dimethylformamide were added into a reaction flask successively and refluxed for two hours, and then the reaction solution was carefully and slowly poured into ice water, and then warmed to room temperature, filtrated to remove the solid, the filtrate was concentrated under decreased pressure, and rapid column chromatography was performed with dichloromethane to give 1,4- dichlorophthalazine (2a), 281 mg pale yellow solid (yield22.8%).
	With phosphorus(V) chloride
	With trichlorophosphate
	With trichlorophosphate Reflux;
	With trichlorophosphate at 110℃; for 4h;
9 g	With trichlorophosphate for 4h; Reflux;
	With triethylamine; trichlorophosphate for 4h; Reflux;
	With trichlorophosphate at 110℃; for 3h;	10.1.a (a) 1 ,4-dichlorophthalazine (a) 1,4-dichlorophthalazine Isobenzofuran (5.92 g, 0.04 mol) was dissolved in acetic acid (22 mL) and hydrazine (2.8 mL, 0.044 mol) was added dropwise. The solution was refluxed for 4 hours and cooled to room temperature; then filtered and washed by ethanol. Then the solution was evaporated in vacuum and the product 2,3-dihydrophathalazine-1,4-dione (6.13 g, yield rate 94.6%) was obtained. The product was a white solid. The product was dissolved in POCl3 (50 mL), mixing for 3 hours at 110° C. After cooling to room temperature, it was poured into cold water slowly. After filtration and washing by water, 1,4-dichlorophthalazine, a white solid, was obtained through recrystallization under the condition of THF.
	With trichlorophosphate at 80 - 110℃; for 1h;	1 Example 1 Take 1.68g (10mmol) of 2,3-dihydro-phthalazine said 1,4-dione in 50mL three bottles, 15mL was added phosphorus oxychloride was stirred until the temperature of the raw material completely dissolved at 80 , then slowly heated to 110 , after reaction for about 1h TLC (V petroleum ether: ethyl acetate and the V = 3: 1) showed the reaction was complete. The reaction was cooled to room temperature, added dropwise to crushed ice, was added dropwise with stirring, the precipitated milky white solid was suction filtered, washed with water until neutral, and dried in vacuo to give the product 1,4-dichloro phthalazine
	With trichlorophosphate at 80 - 110℃; for 1h;	1 Take 1.68g(10mmol) Mentioned above 2,3- Dihydro-phthalazine-l, 4-dione at 50mL Three bottles added phosphorus oxychloride 15mL stirring and the temperature to 80 When the raw material is completely dissolved, then slow temperature rise to 110, The reaction about 1h after TLC(V petroleum ether: V ethyl acetate =3:1) showing the reaction was completed , The reaction liquid cooled to room temperature and added dropwise into the mush ice and the Edge drop, stirring Precipitation of milky white solid filtration, washing to neutral, vacuum drying get products 1,4-Dichlorophthalazine
	With trichlorophosphate
	With trichlorophosphate at 110℃; for 1h;
	With trichlorophosphate for 3h; Inert atmosphere; Reflux;	General Procedure II (GP II) for the Preparation of 1,4-Dichlorophthalazines (S3) General procedure: A stirred solution of 2,3-dihydrophthalazine-1,4-dione (S2, 1.0 equiv) and POCl3 (4.0 equiv) was refluxed in an oil bath under Ar for 3 hours. Then, the reaction mixture was cooled to room temperature and poured into crushed ice. After filtration of the precipitate through filter paper, the filter cake was washed with H2O until the pH of filtrate was neutral. The residue was dried under reduced pressure to give 1,4-dichlorophthalazine (S3). The crude material was used for the next step without further purification.
	With trichlorophosphate for 1h; Heating;

Reference： [1]Current Patent Assignee: SINOCHEM HOLDINGS CORPORATION LTD - CN110305068, 2019, A Location in patent: Paragraph 0007; 0023-0027
[2]Bollenbach, Maud; Lugnier, Claire; Kremer, Mélanie; Salvat, Eric; Megat, Salim; Bihel, Frédéric; Bourguignon, Jean-Jacques; Barrot, Michel; Schmitt, Martine [European Journal of Medicinal Chemistry, 2019, vol. 177, p. 269 - 290]
[3]Zhang, Qiu-Rong; Xue, Deng-Qi; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Ren, Jing-Li; Shan, Li-Hong; Liu, Hong-Min [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1236 - 1238]
[4]Xue, Deng-Qi; Zhang, Xu-Yao; Wang, Chao-Jie; Ma, Li-Ying; Zhu, Nan; He, Peng; Shao, Kun-Peng; Chen, Peng-Ju; Gu, Yi-Fei; Zhang, Xiao-Song; Wang, Cai-Feng; Ji, Cong-Hui; Zhang, Qiu-Rong; Liu, Hong-Min [European Journal of Medicinal Chemistry, 2014, vol. 85, p. 235 - 244]
[5]Abulkhair, Hamada S.; Ahmed, Hany E. A.; Bayoumi, Ashraf H.; Ghiaty, Adel; Turky, Abdallah [Bioorganic Chemistry, 2020, vol. 100]
[6]Turky, Abdallah; Bayoumi, Ashraf H.; Ghiaty, Adel; El-Azab, Adel S.; A.-M. Abdel-Aziz, Alaa; Abulkhair, Hamada S. [Bioorganic Chemistry, 2020, vol. 101]
[7]Chung, Cheng-Yen; Tseng, Ching-Chun; Li, Sin-Min; Tsai, Shuo-En; Lin, Hui-Yi; Wong, Fung Fuh [Molecules, 2021, vol. 26, # 10]
[8]Chung, Cheng-Yen; Tseng, Ching-Chun; Li, Sin-Min; Tsai, Shuo-En; Lin, Hui-Yi; Wong, Fung Fuh [Molecules, 2021, vol. 26, # 10]
[9]Current Patent Assignee: SHANDONG FIRST MEDICAL UNIVERSITY & SHANDONG ACADAMY OF MEDICAL SCIENCES - CN114014814, 2022, A Location in patent: Paragraph 0073; 0080-0081
[10]Wu, Yan; Sun, Liang-Peng; Ma, Long-Xu; Che, Jian; Song, Ming-Xia; Cui, Xun; Piao, Hu-Ri [Chemical Biology and Drug Design, 2013, vol. 81, # 5, p. 591 - 599]
[11]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM) - WO2019/89648, 2019, A1 Location in patent: Page/Page column 52
[12]Vuong, Thi Minh Ha; Weimmerskirch-Aubatin, Jennifer; Lohier, Jean-François; Bar, Nathalie; Boudin, Sophie; Labbé, Christophe; Gourbilleau, Fabrice; Nguyen, Hien; Dang, Tung Thanh; Villemin, Didier [New Journal of Chemistry, 2016, vol. 40, # 7, p. 6070 - 6076]
[13]Liu, Da-Chuan; Gong, Guo-Hua; Wei, Cheng-Xi; Jin, Xue-Jun; Quan, Zhe-Shan [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 6, p. 1576 - 1579]
[14]Luniwal, Amarjit; Khupse, Rahul S.; Reese, Michael; Fang, Lei; Erhardt, Paul W. [Journal of Natural Products, 2009, vol. 72, # 11, p. 2072 - 2075]
[15]Location in patent: experimental part Sun, Xian-Yu; Hu, Chuan; Deng, Xian-Qing; Wei, Cheng-Xi; Sun, Zhi-Gang; Quan, Zhe-Shan [European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 4807 - 4812]
[16]Location in patent: experimental part Cheng-Xi, Wei; Zhou, Guo; Fu-Nan, Li; Zhe-Shan, Quan [Asian Journal of Chemistry, 2011, vol. 23, # 1, p. 127 - 131]
[17]Luniwal, Amarjit; Malik, Neha; Erhardt, Paul; Khupse, Rahul; Reese, Michael; Liu, Jidong; El-Dakdouki, Mohammad; Fang, Lei [Organic process research and development, 2011, vol. 15, # 5, p. 1149 - 1162]
[18]Elagawany, Mohamed; Ibrahim, Mohamed A.; Ali Ahmed, Hany Emary; El-Etrawy, A.Sh.; Ghiaty, Adel; Abdel-Samii, Zakaria K.; El-Feky, Said A.; Bajorath, Juergen [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 7, p. 2007 - 2013]
[19]Current Patent Assignee: HAIMEN RUIYI MEDICAL TECH - CN110156696, 2019, A Location in patent: Paragraph 0016-0018
[20]Amberg; Bennani; Chadha; Crispino; Davis; Hartung; Jeong; Ogino; Shibata; Sharpless [Journal of Organic Chemistry, 1993, vol. 58, # 4, p. 844 - 849]
[21]Basistyi, Vitalii S.; Frederich, James H. [Organic Letters, 2022, vol. 24, # 10, p. 1907 - 1912]
[22]Current Patent Assignee: MYREXIS, INC. - WO2006/74223, 2006, A2 Location in patent: Page/Page column 59
[23]Current Patent Assignee: CHENGDU DIAO PHARMACEUTICAL GROUP CO LTD - EP2799435, 2014, A1 Location in patent: Paragraph 0050; 0072; 0073
[24]Current Patent Assignee: CHENGDU DIAO PHARMACEUTICAL GROUP CO LTD - US2015/51211, 2015, A1 Location in patent: Paragraph 0098; 0099
[25]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]
[26]Joshi; Upadhyay; Baxi [Journal of the Indian Chemical Society, 1990, vol. 67, # 9, p. 779 - 780]
[27]Location in patent: body text Sun, Xian-Yu; Wei, Cheng-Xi; Deng, Xian-Qing; Sun, Zhi-Gang; Quan, Zhe-Shan [Arzneimittel-Forschung/Drug Research, 2010, vol. 60, # 6, p. 289 - 292]
[28]Location in patent: experimental part Wang, Shi-Ben; Deng, Xian-Qing; Song, Ming-Xia; Quan, Zhe-Shan [Letters in drug design and discovery, 2012, vol. 9, # 4, p. 409 - 414]
[29]Bian, Ming; Deng, Xian-Qing; Gong, Guo-Hua; Wei, Cheng-Xi; Quan, Zhe-Shan [Journal of Enzyme Inhibition and Medicinal Chemistry, 2013, vol. 28, # 4, p. 792 - 800]
[30]Ma, Long-Xu; Cui, Bai-Ri; Wu, Yan; Liu, Jia-Chun; Cui, Xun; Liu, Li-Ping; Piao, Hu-Ri [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 7, p. 1737 - 1741]
[31]Current Patent Assignee: SHANGHAI SIMRD BIOTECHNOLOGY; SHANGHAI SIMR BIOTECHNOLOGY - US2015/374705, 2015, A1 Location in patent: Paragraph 0289; 0290
[32]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN104016986, 2016, B Location in patent: Paragraph 0037
[33]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN103694244, 2016, B Location in patent: Paragraph 0044
[34]El-Helby, Abdel-Ghany A.; Ayyad, Rezk R. A.; Sakr, Helmy; El-Adl, Khaled; Ali, Mamdouh M.; Khedr, Fathalla [Archiv der Pharmazie, 2017, vol. 350, # 12]
[35]Elmeligie, Salwa; Aboul-Magd, Asmaa M.; Lasheen, Deena S.; Ibrahim, Tamer M.; Abdelghany, Tamer M.; Khojah, Sohair M.; Abouzid, Khaled A. M. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, vol. 34, # 1, p. 1347 - 1367]
[36]Im, Jeong Kyun; Yang, ByeongDo; Jeong, Ilju; Choi, Jun-Ho; Chung, Won-jin [Tetrahedron Letters, 2020, vol. 61, # 26]
[37]Khalifa, mohamed m.; Radwan, mohamed m.; Rashed, mahmoud; Sakr, Helmy; ayyad, Rezk R.; belal, amany; eissa, Ibrahim H.; el-Helby, abdel-Ghany a.; el-Sharkawy, abdou; elSohly, mahmoud a.; elhendawy, mostafa a.; mahdy, Hazem a.; metwaly, ahmed m. [Bioorganic Chemistry, 2020, vol. 103] Sakr, Helmy; Ayyad, Rezk R.; El-Helby, Ali A.; Khalifa, Mohamed M.; Mahdy, Hazem A. [Archiv der Pharmazie, 2021, vol. 354, # 6]

3
[ 1445-69-8 ]
[ 3660-90-0 ]
[ 19064-73-4 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1932,vol. <2> 135,p. 128,131
[2]Journal fur praktische Chemie (Leipzig 1954),1932,vol. <2> 135,p. 128,131
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 312 - 319

4
[ 1445-69-8 ]
[ 627-42-9 ]
2-(2-methoxyethyl)-2,3-dihydrophthalazine-1,4-dione [ No CAS ]
2-(2-methoxyethyl)-4-(2-methoxyethoxy)phthalazine-1(2H)one [ No CAS ]

Reference： [1]Journal of Pharmaceutical Sciences,1989,vol. 78,p. 903 - 909
[2]Journal of Pharmaceutical Sciences,1989,vol. 78,p. 903 - 909

5
[ 1445-69-8 ]
[ 69189-19-1 ]
[ 99878-95-2 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1985,p. 1418 - 1421
Zhurnal Organicheskoi Khimii,1985,vol. 21,p. 1556 - 1560

6
[ 1445-69-8 ]
[ 4752-10-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	With dmap; thionyl chloride; bis(trichloromethyl) carbonate for 8h; Reflux; Green chemistry;
75%	With phosphorus pentachloride; N,N-dimethyl-formamide at 145℃; for 4h; Inert atmosphere;
6.3 g	With phosphorus pentachloride; trichlorophosphate for 5h; Heating;

With trichlorophosphate In 1,2-dichloro-ethane

a Preparation of phthalazine P2* derivatives: In general, both 1-chlorophthalazine and 1, 4-dichlorophthalazine undergo alkylation smoothly to give the desired products. However, the commercially available1- chlorophthalazine and 1, 4-dichlorophthalazine are often contaminated with some hydrolyzed materials. A pre-treatment with POC13 followed by alkylation immediately afterward furnished more consistent results. Reaction Conditions: (a) POC13 in DCE; (b) Alkylation with tripeptide; (c) sodio derivatives of imidazole (R = CH), triazole (R = N)

Reference： [1]Wang, Jian; Li, Yan-Hui; Pan, Song-Cheng; Li, Ming-Fang; Du, Wenting; Yin, Hong; Li, Jing-Hua [Organic Process Research and Development, 2020, vol. 24, # 2, p. 146 - 153]
[2]Choudhury, Abhijnan Ray; Mukherjee, Santanu [Organic and Biomolecular Chemistry, 2012, vol. 10, # 36, p. 7313 - 7320]
[3]Barlin; Ireland [Australian Journal of Chemistry, 1985, vol. 38, # 11, p. 1685 - 1691]
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2003/99274, 2003, A1 Location in patent: Page 277-278

7
[ 77959-62-7 ]
[ 1445-69-8 ]
[ 610-93-5 ]
3-nitro-8H-<1,2-b>-isoindolo-2,3-benzodiazepin-5(6H),8,13(12bH)-trione [ No CAS ]

Reference： [1]Heterocycles,1982,vol. 18,p. 327 - 341
[2]Heterocycles,1982,vol. 18,p. 327 - 341

8
[ 1445-69-8 ]
[ 2257-69-4 ]

Yield	Reaction Conditions	Operation in experiment
94.4%	With trichlorophosphate at 110℃; for 4h;	1.1 (1) Weigh phthaloyl hydrazide (8 · lg, 0 · 05 mol) and add P0C13 (50 mL, 0.25 mol), and react at 110 ° C for 4 h. After the reaction system is cooled, the reaction system is poured into ice water. A white solid was precipitated, stirred overnight, suction filtered, and the filter cake was dried. The filter cake was washed with ethyl acetate to obtain 8.5 g of 1-chloro-4-carbonylpyridazine in a yield of 94.4%.
	Multi-step reaction with 2 steps 1: PCl₅ 2: nitrobenzene / 180 °C

Reference： [1]Current Patent Assignee: BEIJING YAOCHENG HUIREN TECH - CN108129397, 2018, A Location in patent: Paragraph 0044; 0046; 0051; 0053; 0056; 0057; 0059
[2]Drew; Hatt [Journal of the Chemical Society, 1937, p. 16,25]

9
[ 112424-29-0 ]
[ 1445-69-8 ]
[ 582-22-9 ]

Yield	Reaction Conditions	Operation in experiment
94.9%	With hydrazine; In toluene; at 20 - 95℃; for 5h;	EXAMPLE 3 [0101] Alternative Preparation of ((2R)-2-phenylpropyl)[(methylethyl)sulfonyl]amine. [CHEMMOL-00022] [0102] Preparation of (2R)-2-phenylpropan-1-ol. [0103] An oven dried 500.0 mL three necked round bottom flask equipped with a mechanical stirrer, thermometer, addition funnel with a continuous nitrogen blanket is charged with 2.0 M solution of trimethylaluminum (65.6 mL, 131.2 mmol) and toluene (75.0 mL). Reaction solution was then chilled to -60 C. with dry ice/acetone bath. To this solution was then added R-styrene oxide dissolved in 100.0 mL of toluene over a period of 50.0 minutes (reaction is quite exothermic and can be controlled by the rate of addition of substrate). After stirring at this temperature for 60.0 minutes, reaction was brought to room temperature and stirred for 4.0 hours. Reverse quenched reaction at room temperature into a slurry of THF (100.0 mL) and sodium sulfate decahydrate (46.0 g) very cautiously over a period of 90.0 minutes (quenching was quite exothermic with evolution of gas). Filtered the precipitate formed over hyflo, then concentrated filtrate to provide the intermediate title compound, (2R)-2-phenylpropan-1-ol, (11.03 g, 92.6%) as an oil; 1H nmr (CDCl3) delta 1.28-1.29 (d, 3H, J=6.9 Hz), 1.5 (b, 1H), 2.9-3.0 (m, 1H), 3.69-3.70 (d, 2H, J=6.64 Hz), 7.24-7.35 (aromatic); 13C nmr (CDCl3) delta 18.31, 43.15, 69.40, 127.38, 128.20, 129.26144.39. [0104] Preparation of 2-((2R)-2-phenylpropyl)isoindoline-1,3-dione [0105] An oven dried 250.0 mL three necked round bottom flask equipped with a mechanical stirrer, thermometer, addition funnel with a continuous nitrogen blanket is charged with (2R)-2-phenylpropan-1-ol (2.0 mL, 14.32 mmol), phthalimide (2.1 g, 14.32 mmol), triphenylphosphine (5.63 g, 21.48 mmol) and THF (70.0 mL). To this solution at room temperature was then added a solution of diethylazodicarboxylate (3.38 mL, 21.48 mmol) dissolved in THF (10.0 mL) over a period of 15-20 minutes (reaction exothermed slightly to 50 C. by the end of addition went from clear to reddish color). Stirred reaction to room temperature overnight). To the red solution was added water (50.0 mL) and the organic extracted with chloroform (140.0 mL). Dried the organic solution with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to an oil. To the oil was added heptane (150.0 mL) with stirring. Filtered of precipitates, then concentrated filtrate to an oil. Plug filtration of the oil over silica gel with 1:1 ethylacetate/hexane and concentrating product fractions afforded the intermediate title compound, 2-((2R)-2-phenylpropyl)isoindoline-1,3-dione, (4.27 g, 96%) as an oil which solidified on equilibrating to room temperature; 1H nmr (CDCl3) delta 1.3 (d, 3H), 3.34.0 (m, 1H), 3.7-3.9 (m, 2H), 7.1-7.3 (aromat. m, 2H), 7.63-7.7 (aromat. m, 2H), 7.8-7.85 (aromat. m, 4H). [0106] Preparation of (2R)-2-phenylpropylamine. [0107] A 500 mL three necked round bottom flask equipped with a mechanical stirrer, thermometer and addition funnel is charged with 2-((2R)-2-phenylpropyl)isoindoline-1,3-dione (11.54 g, 43.49 mmol), toluene (200.0 mL) and anhydrous hydrazine (2.73 mL, 86.99 mmol). Reaction is then stirred at room temperature for 3.0 hours and then heated at 90 C.-95 C. for 2.0 hours. Cooled the slurry to room temperature, filtered precipitates, then concentrated filtrate to provide the intermediate title compound, (2R)-2-phenylpropylamine, (5.58 g, 94.9%) an oil; 1H nmr (CDCl3) delta 1.21 (d, 3H), 1.40-1.60 (b, 2H), 2.68-2.80 (m, 1H), 2.81-2.87 (m, 2H) 7.20 (m, 2H), 7.32 (m, 2H). [0108] Preparation of Final Title Compound. [0109] To a solution of the (2R)-2-phenylpropylamine (1.2 g, 8.87 mmol) in hexane (16.0 mL) was added triethylamine (2.47 mL, 17.74 mmol) and dimethylaminopyridine (0.30 g, 2.47 mmol). Cooled reaction to 5 C., then added a solution of isopropylsulfonyl chloride (0.97 mL, 8.69 mmol) dissolved in methylene chloride (6.0 mL) over a period of 15.0 minutes. Stirred for 45.0 minutes, then stirred at room temperature for 120.0 minutes. Quenched reaction with 1 N HCl (20.0 mL) and extracted organic with methylene chloride (25.0 mL). Dried organic layer with anhydrous magnesium sulfate, filtered and concentrated filtrate to provide the final title compound, ((2R)-2-phenylpropyl)[(methylethyl)sulfonyl]amine, (1.93 g, 90.1%) an oil; 1H nmr (CDCl3) delta 1.25 (d, 3H, J=6.9 Hz), 1.29(d, 3H, J=6.9 Hz), 1.30 (d, 3H, J=7.2 Hz), 2.98 (m, 1H), 3.05 (m, 1H), 3.22 (m, 1H), 3.36 (m, 1H), 3.89 (b, 1H), 7.23 (m, 2H), 7.34 (m, 2H).

Reference： [1]Patent: US2003/225163,2003,A1 .Location in patent: Page 13-14

10
[ 37418-88-5 ]
[ 1445-69-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine	Synthesis of the Phthalhydrazide or 2,3-benzodiazine-1,4(2H,3H)-dione Derivative (see FIG. 2E) Synthesis of the Phthalhydrazide or 2,3-benzodiazine-1,4(2H,3H)-dione Derivative (see FIG. 2E) 3-Hydroxyphthalhydrazide made from the reaction of 3-hydroxyphthalic anhydride (Aldrich Chemical Company, Milwaukee, Wis.) with hydrazine is coupled with benzidine or its derivative via the same procedure used for salicylic acid derivatives and then converted to the tri-alkyl tin and iodo-derivatives as described above.
		1 Radio-Iodination or Radio-Bromination of Tri-Alkyl Tin Derivatives 3-Hydroxyphthalimide made from 3-hydroxyphthalic anhydride (Aldrich Chemical Company, Milwaukee, Wis.) is converted to the formyl derivative and coupled to the appropriate tetraethyl diphosphonate (which in some cases may be brominated) as described above under the synthesis of alkenyl derivatives. The bromo derivatives can then converted to the tri-alkyl tin and iodo-derivatives as described above. Synthesis of the phthalhydrazide or 2,3-benzodiazine-1,4(2H,3H)-dione derivative (see FIG. 2E) 3-Hydroxyphthalhydrazide made from the reaction of 3-hydroxyphthalic anhydride (Aldrich Chemical Company, Milwaukee, Wis.) with hydrazine is converted to the formyl derivative and coupled to the appropriate tetraethyl diphosphonate (which in some cases may be brominated) as described above under the synthesis of alkenyl derivatives.

Reference： [1]Current Patent Assignee: COMMONWEALTH SYSTEM OF HIGHER EDUCATION - US6417178, 2002, B1
[2]Current Patent Assignee: University of Pittsburgh - US6168776, 2001, A

11
[ 1445-69-8 ]
[ 7789-69-7 ]
[ 3660-90-0 ]
[ 19064-73-4 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane; for 48h;Heating / reflux;	Example E- 1 : 2-Benzyl-4- f 5-methyl- lH-pyrazol-3-ylaminalpha V2H-phthalazin- 1 -one4-Bromo-2H-phthalazin- 1 -one2,3-Dihydro-l,4-phthalazinedione (12.5g, 78mmol) was suspended in dichloroethane (200ml) and phosphorous pentabromide (50.Og, 116mmol) was added in one portion and the reaction heated to reflux for 24 hours. A further portion of phosphorous pentabromide (20.Og, 70mol) was added and the reaction heated for a further 24 hours. The reaction was cooled to room temperature and poured into ice water. The resulting precipitate was filtered and washed with water to give a crude mixture of mono and dibrominated product (22.8g).

Reference： [1]Patent: WO2006/32518,2006,A1 .Location in patent: Page/Page column 154

12
[ 1445-69-8 ]
[ 19064-73-4 ]

Yield	Reaction Conditions	Operation in experiment
60%		4-Bromo-2H-phthalazin-1-one: 2,3-Dihydro-1,4-phthalazinedione (12.5 g, 78 mmol) was suspended in DCE (200 ml) and phosphorous pentabromide (50.0 g, 116 mmol) was added in one portion and the reaction heated to reflux for 24 hours. A further portion of phosphorous pentabromide (20.0 g, 70 mol) was added and the reaction heated for a further 24 hours. The reaction was cooled to RT and poured into ice water. The resulting precipitate was filtered and washed with water to give a crude mixture of mono and dibrominated product (22.8 g). This crude material was suspended in HOAc (230.0 mL) and heated to 120 C. for 2 hrs. The reaction was cooled to RT and poured into ice water and the resulting precipitate filtered. The solid was washed with water and dried to give the title compound (10.4 g, 60% yield) as a white solid. 1H-NMR: (400 MHz, D6-DMSO), 12.95 (1H, s), 8.25 (1H, dd), 8.03 (1H, ddd), 7.96-7.90-(2H, m); MS (ESI+)=(M+H)+ 225 & 227
	With phosphorus pentabromide; In carbon tetrabromide;	PREPARATION 10 1-Bromo-phthalazin-4-one STR44 A mixture of phthalhydrazide (3.2 g) and phosphorus pentabromide (19.0 g) was heated with stirring in carbon tetrabromide (50 g) at 125 for 16 hours. The cooled mixture was poured into water (50 cm3) and the product collected by filtration. The solid product was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluding with diethyl ether:dichloromethane, 1:3 by volume. Combination and evaporation of appropriate fractions afforded the title compound, m.p. 268-271 (1.5 g). Analysis %: Found: C, 42.1; H, 2.2; N, 12.2; Calculated for C8 H5 N2 OBr: C, 42.7; H, 2.2; N, 12.4.

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 12363 - 12370
[2]Patent: US2007/219195,2007,A1 .Location in patent: Page/Page column 39
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 312 - 319
[4]Patent: US4898872,1990,A
[5]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 2801 - 2805
[6]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 3217 - 3226

13
[ 1445-69-8 ]
[ 104-87-0 ]
[ 105-56-6 ]
[ 1044549-08-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With C₈H₁₅N₂⁽¹⁺⁾*Cl^(1-) In ethanol at 25℃; for 5h; Inert atmosphere;	16 In a three-necked flask,Add p-methylbenzaldehyde (120.1 mg, 1 mmol),Cyanoacetic acid acetonitrile (113.2 mg, 1 mmol),Phthalate(178.4 mg, 1.1 mmol),[Bmim]Cl (52.4 mg, 0.3 mol) and anhydrous ethanol (3 mL),Under nitrogen atmosphere,Stir at 25 ° C under normal pressure for 5 h.After the reaction is completed,After the reaction solution is simply treated, a solid precipitates.Filtration and washing, recrystallization and purification to obtain the yellow target product:3-amino-5,10-dioxo-1-(4-methylphenyl)-5,10-dihydro-1H-pyrazolo[1,2-b]pyridazine-2-carboxylic acid ester,The yield was 96%.
92%	With ammonium cerium (IV) nitrate at 45℃; for 1h;
90%	at 45℃; for 0.0833333h; Ionic liquid; Microwave irradiation;	28 General procedure for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione: General procedure: Phthalhydrazide (1 mmol), aromatic aldehyde (1 mmol), malononitrile (1 mmol) and [Bmim]OH (0.2 mL) were put in a pressure regulation 10-mL pressurized vial with 'snap-on' cap and the reaction mixture was subjected to irradiation in a single-mode microwave synthesis system at 100 W power and 45 °C for 4-5 min. After completion of the reaction as indicated by TLC, water (5 mL) was added and the product was extracted with EtOAc (3 × 10 mL). The combined organic phase was dried over anhydrous Na2SO4, evaporated under reduced pressure and recrystallized from ethanol to afford pure 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4. After isolation of the product, the remaining aqueous layer containing the ionic liquid was washed with ether (10 mL) to remove any organic impurity, and then dried under vacuum at 90-95 °C for 15 h to afford [Bmim]OH, which was used in the subsequent runs without further purification.

90%	With C₅H₉N₂O₆S₂⁽¹⁺⁾*Cl₃HSn at 60℃; for 0.5h; Green chemistry;	Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones (4a-4m) catalyzed by IL1 or IL2 General procedure: A mixture of phthalhydrazide (1 mmol) with a desired aromatic aldehyde (1 mmol), malononitrile or ethyl cyanoacetate (1 mmol), and IL1 or IL2 (5 mol% based on aromatic aldehyde) was heated in an oil bath at 60°C for 10-30 min. The reaction was monitored by TLC. Upon completion of the process, the reaction mixture was cooled down to room temperature, distilled water (5 mL) was added to it, and the mixture was stirred for 5 min. The precipitated product was fi ltered off, washed with distilled water repeatedly and then recrystallized from ethanol (96%) to give the corresponding pure product 4a-4m. The catalyst that remained in water was reused in another cycle after evaporation of water.
88%	With triethylamine In ethanol at 50℃; for 1h; Ultrasonic irradiation;
86%	With sodium hydrogencarbonate In neat (no solvent) at 120℃; for 0.833333h; Green chemistry;	General Procedure for the Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a-m catalyzed by NaHCO3 General procedure: A mixture of phthalhydrazide (1 mmol), anaromatic aldehyde (1 mmol), malononitrile or ethylcyanoacetate (1 mmol), and NaHCO3 (1 mmol) washeated in an oil bath at 120 °C for 15-50 min. Thereaction was monitored by TLC. Upon completionof the transformation, the reaction mixture was cooled to room temperature and warm water wasadded. This resulted in the precipitation of theproduct, which was collected by filtration. The crudeproduct was washed with warm water repeatedlyand then with warm ethanol to give compounds 4amin high yields.
84%	With 1-butyl-3-methylimidazolium hydroxide In ethanol at 60℃; for 3h; Green chemistry;	1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives 4 General procedure: A mixture of the aromatic aldehyde 1 (1 mmol), malononitrile or ethylcyanoacetate 2 (1 mmol), phthalhydrazide 3 (1 mmol), [bmim]OH (0.1mmol) in EtOH (5 mL) was stirred at 60 °C for the appropriate time(monitored by thin-layer chromatography [TLC]). After completion ofthe reaction, the mixture was cooled to room temperature and pouredinto water (10 mL). The solid product was collected by filtration andrecrystallised from ethanol to give the pure compound 4. The filtratewas extracted with diethyl ether several times to remove unreactedstarting materials and other organic contaminations. Then the waterwas evaporated under reduced pressure and dried to recover the ionicliquid for subsequent use.
79%	With Al-KIT-6 ⁽³³⁾ In ethanol at 60℃; for 4h;
73%	With toluene-4-sulfonic acid at 100℃; for 5h; Ionic liquid;

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN108707152, 2018, A Location in patent: Paragraph 0062; 0063; 0064
[2]Kidwai, Mazaahir; Chauhan, Ritika [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1689 - 1696]
[3]Location in patent: experimental part Raghuvanshi, Dushyant Singh; Singh, Krishna Nand [Tetrahedron Letters, 2011, vol. 52, # 43, p. 5702 - 5705]
[4]Vafaee; Davoodnia; Nakhaei; Yadegarian; Nejatianfar [Russian Journal of General Chemistry, 2021, vol. 91, # 2, p. 273 - 278]
[5]Location in patent: experimental part Nabid, Mohammad Reza; Rezaei, Seyed Jamal Tabatabaei; Ghahremanzadeh, Ramin; Bazgir, Ayoob [Ultrasonics Sonochemistry, 2010, vol. 17, # 1, p. 159 - 161]
[6]Vafaee, Asieh; Davoodnia, Abolghasem; Pordel, Mehdi; Bozorgmehr, Mohammad Reza [Oriental Journal of Chemistry, 2015, vol. 31, # 4, p. 2153 - 2158]
[7]Wang, Wang; Cong-Hao, Li; Yi, Yu; Xiao-Jun, Li; Hong-Yun, Guo [Journal of Chemical Research, 2016, vol. 40, # 6, p. 354 - 357]
[8]Location in patent: experimental part Karthikeyan; Pandurangan [Journal of Molecular Catalysis A: Chemical, 2012, vol. 361-362, p. 58 - 67]
[9]Location in patent: scheme or table Ghahremanzadeh, Ramin; Shakibaei, Ghazaleh Imani; Bazgir, Ayoob [Synlett, 2008, # 8, p. 1129 - 1132]

14
[ 1445-69-8 ]
[ 104-88-1 ]
[ 105-56-6 ]
[ 1044549-02-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With C₅H₉N₂O₆S₂⁽¹⁺⁾*Cl₃HSn at 60℃; for 0.416667h; Green chemistry;	Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones (4a-4m) catalyzed by IL1 or IL2 General procedure: A mixture of phthalhydrazide (1 mmol) with a desired aromatic aldehyde (1 mmol), malononitrile or ethyl cyanoacetate (1 mmol), and IL1 or IL2 (5 mol% based on aromatic aldehyde) was heated in an oil bath at 60°C for 10-30 min. The reaction was monitored by TLC. Upon completion of the process, the reaction mixture was cooled down to room temperature, distilled water (5 mL) was added to it, and the mixture was stirred for 5 min. The precipitated product was fi ltered off, washed with distilled water repeatedly and then recrystallized from ethanol (96%) to give the corresponding pure product 4a-4m. The catalyst that remained in water was reused in another cycle after evaporation of water.
93%	at 45℃; for 0.0666667h; Ionic liquid; Microwave irradiation;	28 General procedure for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione: General procedure: Phthalhydrazide (1 mmol), aromatic aldehyde (1 mmol), malononitrile (1 mmol) and [Bmim]OH (0.2 mL) were put in a pressure regulation 10-mL pressurized vial with 'snap-on' cap and the reaction mixture was subjected to irradiation in a single-mode microwave synthesis system at 100 W power and 45 °C for 4-5 min. After completion of the reaction as indicated by TLC, water (5 mL) was added and the product was extracted with EtOAc (3 × 10 mL). The combined organic phase was dried over anhydrous Na2SO4, evaporated under reduced pressure and recrystallized from ethanol to afford pure 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4. After isolation of the product, the remaining aqueous layer containing the ionic liquid was washed with ether (10 mL) to remove any organic impurity, and then dried under vacuum at 90-95 °C for 15 h to afford [Bmim]OH, which was used in the subsequent runs without further purification.
90%	With toluene-4-sulfonic acid at 100℃; for 3.3h; Ionic liquid;

90%	With triethylamine In ethanol at 50℃; for 1h; Ultrasonic irradiation;
90%	With ammonium cerium (IV) nitrate at 45℃; for 1h;
86%	With sodium hydrogencarbonate In neat (no solvent) at 120℃; for 0.666667h; Green chemistry;	General Procedure for the Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a-m catalyzed by NaHCO3 General procedure: A mixture of phthalhydrazide (1 mmol), anaromatic aldehyde (1 mmol), malononitrile or ethylcyanoacetate (1 mmol), and NaHCO3 (1 mmol) washeated in an oil bath at 120 °C for 15-50 min. Thereaction was monitored by TLC. Upon completionof the transformation, the reaction mixture was cooled to room temperature and warm water wasadded. This resulted in the precipitation of theproduct, which was collected by filtration. The crudeproduct was washed with warm water repeatedlyand then with warm ethanol to give compounds 4amin high yields.
82%	With Al-KIT-6 ⁽³³⁾ In ethanol at 60℃; for 4h;

Reference： [1]Vafaee; Davoodnia; Nakhaei; Yadegarian; Nejatianfar [Russian Journal of General Chemistry, 2021, vol. 91, # 2, p. 273 - 278]
[2]Location in patent: experimental part Raghuvanshi, Dushyant Singh; Singh, Krishna Nand [Tetrahedron Letters, 2011, vol. 52, # 43, p. 5702 - 5705]
[3]Location in patent: scheme or table Ghahremanzadeh, Ramin; Shakibaei, Ghazaleh Imani; Bazgir, Ayoob [Synlett, 2008, # 8, p. 1129 - 1132]
[4]Location in patent: experimental part Nabid, Mohammad Reza; Rezaei, Seyed Jamal Tabatabaei; Ghahremanzadeh, Ramin; Bazgir, Ayoob [Ultrasonics Sonochemistry, 2010, vol. 17, # 1, p. 159 - 161]
[5]Kidwai, Mazaahir; Chauhan, Ritika [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1689 - 1696]
[6]Vafaee, Asieh; Davoodnia, Abolghasem; Pordel, Mehdi; Bozorgmehr, Mohammad Reza [Oriental Journal of Chemistry, 2015, vol. 31, # 4, p. 2153 - 2158]
[7]Location in patent: experimental part Karthikeyan; Pandurangan [Journal of Molecular Catalysis A: Chemical, 2012, vol. 361-362, p. 58 - 67]

15
[ 1445-69-8 ]
[ 104-88-1 ]
[ 504-02-9 ]
[ 1187744-33-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With [4-(1,10-phenanthrolin-1-ium-1-yl)butane-1-sulfonate]₃PW₁₂O₄₀ In water for 0.1h; Reflux; Green chemistry;	General procedure for synthesis of 2H-indazolo[2,1-b]phthalazine-trionederivatives using PhBS+3PW12O3-40 as catalyst General procedure: Aromatic aldehyde 5 (1 mmol), 5,5-dimethylcyclohexane-1,3-dione and or cyclohexane-1,3-dione 6 (1 mmol), and 2,3-dihydro-1,4-phthalazinedione (phthalhydrazide) 7 (1 mmol) were placed together in a 25 mL canonical flask containing10 mL of H2O.[PhBS]+3PW12O3-40 catalyst (0.10 g) was added to the mixture.The suspension was magnetically stirred under reflux condition for appropriate time according to Table 2. After completion of the reaction as followed byTLC (n-hexane: ethyl acetate; 3:1), the mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 × 25 mL) to provide the pure crystals of 2H-indazolo[2,1-b]phthalazinetrione derivatives. The filtered was evaporated under vacuum to precipitate the [PhBS]+3PW12O3-40 catalyst. The recovered catalyst was washed with acetone, dried and stored for other similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds.Their melting points are compared with reported values
94%	With sulfuric acid In [bmim]BF₄ at 80℃; for 0.5h; Ionic liquid;
93%	In neat (no solvent) at 80℃; for 0.1h;	2.4. General procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedone and/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide (1.0 mmol) and [DABCO](SO3H)2(HSO4)2 (0.014 g, 0.03 mmol) was heated in an oil bath (80 °C) under solvent free conditions for the appropriate time. The reaction was monitored by TLC (n-hexane: ethyl acetate). After completion, the reaction mass was cooled to room temperature and washed with water for the separation of the catalyst. The solid product was purified by re-crystallization in aqueous EtOH (25%). The products were characterized by comparison of their physical data with those of known compounds.

93%	With 4,4'-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) tetrachloride In neat (no solvent) at 80℃; for 0.1h;	2.6. General Procedure for the Preparation of 2HIndazolo[2,1-b]Phthalazine-1,6,11(13H)-Triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedoneand/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide(1.0 mmol) and NS-[C4(DABCO-SO3H)2] · 4Cl (0.010 g, 5 mol%) was heated in an oil bath (80 C)under solvent-free conditions for the appropriate time. The reaction was monitored by TLC [n-hexane:ethylacetate(10:2)]. After completion, the reaction mass was cooledto room temperature and washed with water for the separationof the catalyst. The solid product was purified byre-crystallization in aqueous EtOH (25%). The productswere characterized by comparison of their physical datawith those of known compounds.
93%	With C₁₆H₃₂N₄⁽²⁺⁾4HO₄S^(1-)2H⁽¹⁺⁾ at 80℃; for 0.2h;	3.3. General procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: A mixture of aldehyde (1 mmol), dimedone (1 mmol), phthalhydrazide(1 mmol), and [C4(H-DABCO)2][HSO4]4 (16 mg) washeated in an oil bath (80° C) under solvent-free conditions, until thecompletion of the reaction as monitored by TLC [ n-hexane: EtOAc(7:3). 10 mL of water was added and stirred for 10 min. The catalystwas dissolved in water and the solid product was filtered andrecrystallized from aqueous EtOH to afford the pure product.
92%	With chloro-trimethyl-silane In N,N-dimethyl-formamide; acetonitrile at 80℃;
91%	With β‑cyclodextrin sulfonic acid In neat (no solvent) at 80℃; for 0.166667h; Green chemistry;	General procedure for the synthesis of 2H-indazolo [2,1-b] phthalazinetrionesderivatives (1-25) General procedure: A mixture of phthalhydrazide (1.0 mmol), aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione or 1,3-cyclohexanedione (1.0 mmol),β -cyclodextrin-SO3H (10 mol %) was heated at 80 °C under solvent free condition for an appropriate time as mentioned in Table 1. After completion of the reaction as monitored by TLC the reaction mixture was allowed to cool to room temperature and the residue was diluted with water. The precipitate formed was collected by filtration at pump,washed with water, and dried. The residue recrystallized from ethanol to afford the pure product of 2H-indazolo[2,1-b]phthalazine-trione derivatives. 3,3-Dimethyl-13-phenyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-trione (1) Yellow powder, mp: 200-202 C; 1H NMR (400 MHz, CDCl3) d (ppm)1.23 (s, 6H, -(CH3)2), 2.35 (s, 2H, -CH2-C=), 3.26 and 3.41 (2H, AB system,J = 16 Hz, CHaHbCO), 6.47 (s,1H, -CH-N), 7.61 (d, J = 8 Hz, 2H, Ar-H),7.90-7.85 (m, 2H, Ar-H), 8.37-8.16 (m, 5H, Ar-H); 13C NMR (CDCl3, 100 MHz)d (ppm) 28.5 (-CH3), 28.7 (-CH3), 34.7 (-C(CH3)2), 38.1 (-CH2-C=), 50.9(-CH2CO), 64.9 (-CH-N), 118.6 (-HC-C-CO-), 127.1 (Ar-C), 127.7 (Ar-C),127.9 (Ar-C), 128.7 (Ar-C), 128.9 (Ar-C), 129.1 (Ar-C), 133.6 (Ar-C), 134.5(Ar-C), 136.4(-N-C-CH2-), 150.9 (Ar-C), 154.3 (-N-CO-), 156.1 (-N-CO-),192.2 (-CO-); HRMS m/z calcd for C23H20N2O3 [M?] 372.4165, found 372.4167.
90%	With (S)-1-(trifluoroacetyl)pyrrolidine-2-carboxylic acid at 80℃; for 3h; neat (no solvent);
89%	With 2Fe⁽²⁺⁾(x)H₂O3O₄S^(2-) In ethanol for 2h; Reflux;	General experimental procedure for the Synthesis of2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: Hydrated ferric sulfate (0.20 mol, 0.084 g) was added toa mixture of an aromatic aldehyde (1.2 mmol), a cyclic1,3-dicarbonyl compound (1.0 mmol) and phthalhydrazide(1.0 mmol) in 3 mL of ethanol. The reaction mixture was kept for refluxing in a preheated oil-bath. After completion of the reaction (as monitored by TLC), it was brought to room temperature. The solid product precipitated out after adding 6 mL of water into it and it was filtered off through a Büchner funnel. The precipitate was washed with ethanol (2 mL) and dried in a vacuum pump.
86%	With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 120℃; for 0.5h;
	With trifluoroacetic acid In acetic acid for 4h; Reflux;	Representative procedure for the synthesis of 16-phenyl-1,16-dihydrophthalazino[2',3':1,2]pyrazolo[4,3-a]carbazole-9,14-dione 2a General procedure: To a mixture of acetic acid (5 mL) and trifluoroacetic acid (2 mL) in a 50 mL round-bottomed flask, benzaldehyde (1.1 mmol), 1,3-cyclohexadione (1.2 mmol) and phthalhydrazide (1 mmol) were added. The resulting mixture was magnetically stirred at reflux for 4 h. After completion (TLC), the reaction mixture was cooled and phenylhydrazine (1.7 eq.) and trifluoroacetic acid (2 mL) were added. The reaction mixture was heated at reflux for 24 h. Upon completion, the solvents were removed under reduced pressure and the product was isolated by chromatography. Compounds 2b-c, 2e, 2j-i were obtained analogously to 2a. Compounds 2d and 2f precipitated during solvent evaporation and were isolated by filtration then washed with AcOH.

Reference： [1]Iravani, Nasir; Keshavarz, Mosadegh; Parhami, Abolfath [Research on Chemical Intermediates, 2019, vol. 45, # 10, p. 5045 - 5066]
[2]Location in patent: scheme or table Khurana, Jitender M.; Magoo, Devanshi [Tetrahedron Letters, 2009, vol. 50, # 52, p. 7300 - 7303]
[3]Shirini, Farhad; Langarudi, Mohaddeseh Safarpoor Nikoo; Goli-Jolodar, Omid [Dyes and Pigments, 2015, vol. 123, p. 186 - 195]
[4]Goli-Jolodar, Omid; Shirini, Farhad; Seddighi, Mohadeseh [Journal of Nanoscience and Nanotechnology, 2018, vol. 18, # 1, p. 591 - 603]
[5]Safari, Niloufar; Shirini, Farhad; Tajik, Hassan [Journal of Molecular Structure, 2020, vol. 1201]
[6]Location in patent: experimental part Nagarapu, Lingaiah; Bantu, Rajashaker; Mereyala, Hari Babu [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 4, p. 728 - 731]
[7]Atar, Amol B.; Lee, Sang Dong; Cho, Byung Gwon; Cho, Dae Won; Jeong, Yeon Tae [Research on Chemical Intermediates, 2016, vol. 42, # 3, p. 1707 - 1728]
[8]Location in patent: experimental part Li, Jianjun; Shi, Xiangjun; Zhong, Weihui; Li, Jia [Journal of Chemical Research, 2012, vol. 36, # 1, p. 17 - 20]
[9]Choudhury, Abhik; Ali, Shahzad; Khan, Abu T. [Journal of the Korean Chemical Society, 2015, vol. 59, # 4, p. 280 - 283]
[10]Song, Shihua; Deng, Xiang; Guan, Zhi; He, Yanhong [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2012, vol. 67, # 7, p. 717 - 724]
[11]Lamera, Esma; Bouacida, Sofiane; Le Borgne, Marc; Bouaziz, Zouhair; Bouraiou, Abdelmalek [Tetrahedron Letters, 2017, vol. 58, # 13, p. 1305 - 1307]

16
[ 1445-69-8 ]
[ 89-98-5 ]
[ 504-02-9 ]
[ 1187744-32-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	With 4,4'-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) tetrachloride In neat (no solvent) at 80℃; for 0.25h;	2.6. General Procedure for the Preparation of 2HIndazolo[2,1-b]Phthalazine-1,6,11(13H)-Triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedoneand/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide(1.0 mmol) and NS-[C4(DABCO-SO3H)2] · 4Cl (0.010 g, 5 mol%) was heated in an oil bath (80 C)under solvent-free conditions for the appropriate time. The reaction was monitored by TLC [n-hexane:ethylacetate(10:2)]. After completion, the reaction mass was cooledto room temperature and washed with water for the separationof the catalyst. The solid product was purified byre-crystallization in aqueous EtOH (25%). The productswere characterized by comparison of their physical datawith those of known compounds.
93%	With C₁₀H₂₃N₂O₃S⁽¹⁺⁾*ClO₄^(1-) In neat (no solvent) at 110℃; for 0.333333h;	3.1.5. General procedure for novel introduced BAILs catalyzed synthesis of 2 H -indazolo[2,1-b ]phthalazine-triones General procedure: Aromatic aldehyde 1 (1 mmol), 5,5-dimethylcyclohexane-1,3- dione or cyclohexane-1,3-dione 2 (1 mmol) and 2,3-dihydro-1,4-phthalazinedione 3 (1 mmol) were placed together in a 25 mL canonical flask and an optimized amount of BAIL on the base of Table 2 was added to the mixture (7 mmol% of [PhBs 1 ]ClO 4 or [PipBs 1 ]ClO 4 , 3 mmol% of [PiPBs 2 ](ClO 4 ) 2 catalyst). The tempera- ture was increased to 110 C, and then the Mixture was magneti- cally stirred for appropriate time according to Table 3 . After com- pletion of the reaction as monitored by TLC ( n -hexane: ethyl ac- etate; 3:1), the mixture was cold to room temperature and then 10 ml of H 2 O was added and stirred for 5 min. The mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 ×25 mL) to provide the pure crystals of 2 H -indazolo[2,1- b ]phthalazine-trione derivatives. The filtered was evaporated under vacuum to precip- itate the BAIL catalyst. The recovered catalyst was washed with ether, dried and stored for further similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds. Their melt- ing points are compared with reported values [28] .
91.1%	With chloro-trimethyl-silane In N,N-dimethyl-formamide; acetonitrile at 80℃;

91%	With (S)-1-(trifluoroacetyl)pyrrolidine-2-carboxylic acid at 80℃; for 3h; neat (no solvent);
85%	With [4-(1,10-phenanthrolin-1-ium-1-yl)butane-1-sulfonate]₃PW₁₂O₄₀ In water for 0.2h; Reflux; Green chemistry;	General procedure for synthesis of 2H-indazolo[2,1-b]phthalazine-trionederivatives using PhBS+3PW12O3-40 as catalyst General procedure: Aromatic aldehyde 5 (1 mmol), 5,5-dimethylcyclohexane-1,3-dione and or cyclohexane-1,3-dione 6 (1 mmol), and 2,3-dihydro-1,4-phthalazinedione (phthalhydrazide) 7 (1 mmol) were placed together in a 25 mL canonical flask containing10 mL of H2O.[PhBS]+3PW12O3-40 catalyst (0.10 g) was added to the mixture.The suspension was magnetically stirred under reflux condition for appropriate time according to Table 2. After completion of the reaction as followed byTLC (n-hexane: ethyl acetate; 3:1), the mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 × 25 mL) to provide the pure crystals of 2H-indazolo[2,1-b]phthalazinetrione derivatives. The filtered was evaporated under vacuum to precipitate the [PhBS]+3PW12O3-40 catalyst. The recovered catalyst was washed with acetone, dried and stored for other similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds.Their melting points are compared with reported values

Reference： [1]Goli-Jolodar, Omid; Shirini, Farhad; Seddighi, Mohadeseh [Journal of Nanoscience and Nanotechnology, 2018, vol. 18, # 1, p. 591 - 603]
[2]Arian, Fatemeh; Keshavarz, Mosadegh; Sanaeishoar, Haleh; Hasanzadeh, Neda [Journal of Molecular Structure, 2021, vol. 1229]
[3]Location in patent: experimental part Nagarapu, Lingaiah; Bantu, Rajashaker; Mereyala, Hari Babu [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 4, p. 728 - 731]
[4]Location in patent: experimental part Li, Jianjun; Shi, Xiangjun; Zhong, Weihui; Li, Jia [Journal of Chemical Research, 2012, vol. 36, # 1, p. 17 - 20]
[5]Iravani, Nasir; Keshavarz, Mosadegh; Parhami, Abolfath [Research on Chemical Intermediates, 2019, vol. 45, # 10, p. 5045 - 5066]

17
[ 1445-69-8 ]
[ 504-02-9 ]
[ 874-42-0 ]
[ 1187744-31-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	With chloro-trimethyl-silane In N,N-dimethyl-formamide; acetonitrile at 80℃;
93%	With sulfuric acid In [bmim]BF₄ at 80℃; for 0.5h; Ionic liquid;
90%	With (S)-camphorsulfonic acid at 80℃; for 0.333333h; Neat (no solvent);	General procedure for the synthesis of compounds 4 and 6: (I) Conventional Method: General procedure: To a thoroughly homogenated mixture of phthalhydrazide 1 (1.0 mmol), cyclic/acyclic 1,3-diketone 2 (1.1 mmol), and aldehyde 3 (1.1 mmol), (S)-CSA (0.046 g, 0.2 mmol) was added. The reaction mixture was heated at 80 °C for a stipulated period of time (refPreviewPlaceHolderTable 2). After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature and washed twice with water. The product obtained was purified by crystallization from ethyl acetate-n-hexane (1:3) or by column chromatography (in case of acyclic 1,3-diketones) over silica gel (Merck, 60-120 mesh, ethyl acetate-n-hexane, 1:3).

90%	With β‑cyclodextrin sulfonic acid In neat (no solvent) at 80℃; for 0.333333h; Green chemistry;	General procedure for the synthesis of 2H-indazolo [2,1-b] phthalazinetrionesderivatives (1-25) General procedure: A mixture of phthalhydrazide (1.0 mmol), aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione or 1,3-cyclohexanedione (1.0 mmol),β -cyclodextrin-SO3H (10 mol %) was heated at 80 °C under solvent free condition for an appropriate time as mentioned in Table 1. After completion of the reaction as monitored by TLC the reaction mixture was allowed to cool to room temperature and the residue was diluted with water. The precipitate formed was collected by filtration at pump,washed with water, and dried. The residue recrystallized from ethanol to afford the pure product of 2H-indazolo[2,1-b]phthalazine-trione derivatives. 3,3-Dimethyl-13-phenyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-trione (1) Yellow powder, mp: 200-202 C; 1H NMR (400 MHz, CDCl3) d (ppm)1.23 (s, 6H, -(CH3)2), 2.35 (s, 2H, -CH2-C=), 3.26 and 3.41 (2H, AB system,J = 16 Hz, CHaHbCO), 6.47 (s,1H, -CH-N), 7.61 (d, J = 8 Hz, 2H, Ar-H),7.90-7.85 (m, 2H, Ar-H), 8.37-8.16 (m, 5H, Ar-H); 13C NMR (CDCl3, 100 MHz)d (ppm) 28.5 (-CH3), 28.7 (-CH3), 34.7 (-C(CH3)2), 38.1 (-CH2-C=), 50.9(-CH2CO), 64.9 (-CH-N), 118.6 (-HC-C-CO-), 127.1 (Ar-C), 127.7 (Ar-C),127.9 (Ar-C), 128.7 (Ar-C), 128.9 (Ar-C), 129.1 (Ar-C), 133.6 (Ar-C), 134.5(Ar-C), 136.4(-N-C-CH2-), 150.9 (Ar-C), 154.3 (-N-CO-), 156.1 (-N-CO-),192.2 (-CO-); HRMS m/z calcd for C23H20N2O3 [M?] 372.4165, found 372.4167.
90%	In neat (no solvent) at 100℃; for 0.166667h; Green chemistry;	General Procedure for the Preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones (4a-k) General procedure: First, a mixture of aldehyde (1 mmol), dimedone or 1,3-cyclohexadione (1 mmol) with phthalhydrazide (1 mmol, 0.162 g), and nano-MoO3/a-Al2O3 (0.01 g) was stirred magnetically under solvent-free for an appropriate time as mentioned in Table 2. After completion of the reaction (silica gel; hexane-ethyl acetate, 4:1) the reaction mixture was diluted with hot ethanol (96%, 3 ml). Next, the catalyst was separated by simple filtration. Then, the resulting crude product was poured into crushed ice and the solid product, which separated, was filtered. After that, the catalyst was dried in an oven at 70°C for 6 h. Recovered catalyst was reused in subsequent reactions. Finally, the solid product was recrystallized from ethanol (96%, 5 ml) to get pure 4a-k derivatives.
83%	With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate at 120℃; for 0.5h;
75%	With 1,1,1,3',3',3'-hexafluoro-propanol at 55℃; for 8h; Green chemistry;
	With trifluoroacetic acid In acetic acid for 4h; Reflux;	Representative procedure for the synthesis of 16-phenyl-1,16-dihydrophthalazino[2',3':1,2]pyrazolo[4,3-a]carbazole-9,14-dione 2a General procedure: To a mixture of acetic acid (5 mL) and trifluoroacetic acid (2 mL) in a 50 mL round-bottomed flask, benzaldehyde (1.1 mmol), 1,3-cyclohexadione (1.2 mmol) and phthalhydrazide (1 mmol) were added. The resulting mixture was magnetically stirred at reflux for 4 h. After completion (TLC), the reaction mixture was cooled and phenylhydrazine (1.7 eq.) and trifluoroacetic acid (2 mL) were added. The reaction mixture was heated at reflux for 24 h. Upon completion, the solvents were removed under reduced pressure and the product was isolated by chromatography. Compounds 2b-c, 2e, 2j-i were obtained analogously to 2a. Compounds 2d and 2f precipitated during solvent evaporation and were isolated by filtration then washed with AcOH.

Reference： [1]Location in patent: experimental part Nagarapu, Lingaiah; Bantu, Rajashaker; Mereyala, Hari Babu [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 4, p. 728 - 731]
[2]Location in patent: scheme or table Khurana, Jitender M.; Magoo, Devanshi [Tetrahedron Letters, 2009, vol. 50, # 52, p. 7300 - 7303]
[3]Location in patent: experimental part Shukla, Gaurav; Verma, Rajiv K.; Verma, Girijesh K.; Singh, Maya Shankar [Tetrahedron Letters, 2011, vol. 52, # 52, p. 7195 - 7198]
[4]Atar, Amol B.; Lee, Sang Dong; Cho, Byung Gwon; Cho, Dae Won; Jeong, Yeon Tae [Research on Chemical Intermediates, 2016, vol. 42, # 3, p. 1707 - 1728]
[5]Maleki, Behrooz; Ashrafi, Samaneh Sedigh; Tayebee, Reza [Organic Preparations and Procedures International, 2017, vol. 49, # 6, p. 542 - 548]
[6]Song, Shihua; Deng, Xiang; Guan, Zhi; He, Yanhong [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2012, vol. 67, # 7, p. 717 - 724]
[7]Maleki, Behrooz; Ashrafi, Samaneh Sedigh; Tayebee, Reza [RSC Advances, 2014, vol. 40, # 78, p. 41521 - 41528] Maleki, Behrooz; Ashrafi, Samaneh Sedigh; Tayebee, Reza [RSC Advances, 2014, vol. 4, # 78, p. 41521 - 41528]
[8]Lamera, Esma; Bouacida, Sofiane; Le Borgne, Marc; Bouaziz, Zouhair; Bouraiou, Abdelmalek [Tetrahedron Letters, 2017, vol. 58, # 13, p. 1305 - 1307]

18
[ 1445-69-8 ]
[ 504-02-9 ]
[ 591-31-1 ]
[ 1187744-38-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With C₁₄H₃₂N₂O₆S₂⁽²⁺⁾*2ClO₄^(1-) In neat (no solvent) at 110℃; for 0.333333h;	3.1.5. General procedure for novel introduced BAILs catalyzed synthesis of 2 H -indazolo[2,1-b ]phthalazine-triones General procedure: Aromatic aldehyde 1 (1 mmol), 5,5-dimethylcyclohexane-1,3- dione or cyclohexane-1,3-dione 2 (1 mmol) and 2,3-dihydro-1,4-phthalazinedione 3 (1 mmol) were placed together in a 25 mL canonical flask and an optimized amount of BAIL on the base of Table 2 was added to the mixture (7 mmol% of [PhBs 1 ]ClO 4 or [PipBs 1 ]ClO 4 , 3 mmol% of [PiPBs 2 ](ClO 4 ) 2 catalyst). The tempera- ture was increased to 110 C, and then the Mixture was magneti- cally stirred for appropriate time according to Table 3 . After com- pletion of the reaction as monitored by TLC ( n -hexane: ethyl ac- etate; 3:1), the mixture was cold to room temperature and then 10 ml of H 2 O was added and stirred for 5 min. The mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 ×25 mL) to provide the pure crystals of 2 H -indazolo[2,1- b ]phthalazine-trione derivatives. The filtered was evaporated under vacuum to precip- itate the BAIL catalyst. The recovered catalyst was washed with ether, dried and stored for further similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds. Their melt- ing points are compared with reported values [28] .
90%	With (S)-1-(trifluoroacetyl)pyrrolidine-2-carboxylic acid at 80℃; for 3h; neat (no solvent);
90%	With [4-(1,10-phenanthrolin-1-ium-1-yl)butane-1-sulfonate]₃PW₁₂O₄₀ In water for 0.3h; Reflux; Green chemistry;	General procedure for synthesis of 2H-indazolo[2,1-b]phthalazine-trionederivatives using PhBS+3PW12O3-40 as catalyst General procedure: Aromatic aldehyde 5 (1 mmol), 5,5-dimethylcyclohexane-1,3-dione and or cyclohexane-1,3-dione 6 (1 mmol), and 2,3-dihydro-1,4-phthalazinedione (phthalhydrazide) 7 (1 mmol) were placed together in a 25 mL canonical flask containing10 mL of H2O.[PhBS]+3PW12O3-40 catalyst (0.10 g) was added to the mixture.The suspension was magnetically stirred under reflux condition for appropriate time according to Table 2. After completion of the reaction as followed byTLC (n-hexane: ethyl acetate; 3:1), the mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 × 25 mL) to provide the pure crystals of 2H-indazolo[2,1-b]phthalazinetrione derivatives. The filtered was evaporated under vacuum to precipitate the [PhBS]+3PW12O3-40 catalyst. The recovered catalyst was washed with acetone, dried and stored for other similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds.Their melting points are compared with reported values

88.2%	With chloro-trimethyl-silane In N,N-dimethyl-formamide; acetonitrile at 80℃;
	With trifluoroacetic acid In acetic acid for 4h; Reflux;	Representative procedure for the synthesis of 16-phenyl-1,16-dihydrophthalazino[2',3':1,2]pyrazolo[4,3-a]carbazole-9,14-dione 2a General procedure: To a mixture of acetic acid (5 mL) and trifluoroacetic acid (2 mL) in a 50 mL round-bottomed flask, benzaldehyde (1.1 mmol), 1,3-cyclohexadione (1.2 mmol) and phthalhydrazide (1 mmol) were added. The resulting mixture was magnetically stirred at reflux for 4 h. After completion (TLC), the reaction mixture was cooled and phenylhydrazine (1.7 eq.) and trifluoroacetic acid (2 mL) were added. The reaction mixture was heated at reflux for 24 h. Upon completion, the solvents were removed under reduced pressure and the product was isolated by chromatography. Compounds 2b-c, 2e, 2j-i were obtained analogously to 2a. Compounds 2d and 2f precipitated during solvent evaporation and were isolated by filtration then washed with AcOH.

Reference： [1]Arian, Fatemeh; Keshavarz, Mosadegh; Sanaeishoar, Haleh; Hasanzadeh, Neda [Journal of Molecular Structure, 2021, vol. 1229]
[2]Location in patent: experimental part Li, Jianjun; Shi, Xiangjun; Zhong, Weihui; Li, Jia [Journal of Chemical Research, 2012, vol. 36, # 1, p. 17 - 20]
[3]Iravani, Nasir; Keshavarz, Mosadegh; Parhami, Abolfath [Research on Chemical Intermediates, 2019, vol. 45, # 10, p. 5045 - 5066]
[4]Location in patent: experimental part Nagarapu, Lingaiah; Bantu, Rajashaker; Mereyala, Hari Babu [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 4, p. 728 - 731]
[5]Lamera, Esma; Bouacida, Sofiane; Le Borgne, Marc; Bouaziz, Zouhair; Bouraiou, Abdelmalek [Tetrahedron Letters, 2017, vol. 58, # 13, p. 1305 - 1307]

19
[ 1445-69-8 ]
[ 86-81-7 ]
[ 126-81-8 ]
[ 1173891-40-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With Phenyl sulfonic acid functionalized mesoporous SBA-15 silica In neat (no solvent) at 80℃; for 0.166667h;
92%	With (4-sulfobutyl)-tris(4-sulfophenyl)phosphonium hydrogen sulfate at 80℃; for 0.1h; Green chemistry;
91%	With [4-(1,10-phenanthrolin-1-ium-1-yl)butane-1-sulfonate]₃PW₁₂O₄₀ In water for 0.333333h; Reflux; Green chemistry;	General procedure for synthesis of 2H-indazolo[2,1-b]phthalazine-trionederivatives using PhBS+3PW12O3-40 as catalyst General procedure: Aromatic aldehyde 5 (1 mmol), 5,5-dimethylcyclohexane-1,3-dione and or cyclohexane-1,3-dione 6 (1 mmol), and 2,3-dihydro-1,4-phthalazinedione (phthalhydrazide) 7 (1 mmol) were placed together in a 25 mL canonical flask containing10 mL of H2O.[PhBS]+3PW12O3-40 catalyst (0.10 g) was added to the mixture.The suspension was magnetically stirred under reflux condition for appropriate time according to Table 2. After completion of the reaction as followed byTLC (n-hexane: ethyl acetate; 3:1), the mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 × 25 mL) to provide the pure crystals of 2H-indazolo[2,1-b]phthalazinetrione derivatives. The filtered was evaporated under vacuum to precipitate the [PhBS]+3PW12O3-40 catalyst. The recovered catalyst was washed with acetone, dried and stored for other similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds.Their melting points are compared with reported values

91%	With silica-supported tungstic acid In neat (no solvent) at 80℃; for 0.65h; Green chemistry;	General procedure for the synthesis of 13-(4-chlorophenyl)-3,3-dimethyl-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]phthalazine-1,6,11-trione (4a) General procedure: A mixture of phthalhydrazide (1, 1 mmol), 4-chlorobenzaldehydes (2, 1 mmol), dimedone (3, 1 mmol) and silica-supported tungstic acid (STA 10 mol%) was stirred at 80 °C under solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was washed with ethanol. The residue dissolved in DCM, and the insoluble STA was separated by simple filtration and washed with DCM. The solvent was evaporated under reduced pressure and the obtained crude was recrystallized from ethanol to afford the pure yellow product 4a. The recovered catalyst was washed with ethanol and acetone, dried and reused. Compounds 4a-4w were also synthesized by adopting this procedure.
90%	With montmorillonite K-10 at 80℃; for 0.2h; Neat (no solvent); Microwave irradiation;	4.2. Synthesis of 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione (4b) General procedure: A mixture of phthalhydrazide (1, 162 mg, 1 mmol), 3-fluorobenzaldehyde (2b, 105 mg, 1 mmol), 5,5-dimethyl-cyclohexane-1,3-dione (3, 140 mg, 1 mmol) and K-10 (5 mol %, 50 mg) was taken in an open vessel and irradiated at 80 °C in solvent-free condition for 5 min. The reactions were followed by thin layer chromatography (TLC) using hexane/ethyl acetate (3:1) as an eluent (Rf=0.70). After completion of the reaction, the mixture was washed with ethyl acetate and filtered to recover the catalyst. The filtrate was evaporated, and the crude product was recrystallized from ethanol to afford pure 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo-[2,1-b]phthalazine-1,6,11(13H)-trione (4b) in excellent yield (380 mg).
90%	With KHSO₄-SiO₂ In neat (no solvent) at 80℃; for 0.166667h;	General Experimental Procedure General procedure: A mixture of aldehydes 1 (1.2 mmol), dimedone 2(1 mmol), phthalhydrazide 3 (1 mmol) and KHSO4-SiO2(100 mg) was heated in a 25 mL round bottom flask at80°C for 10 min (monitored by TLC). The resultantmixture was cooled to RT, stirred with ethyl acetate(30 mL) and then filtered through Celite under suction.The filtrate was washed with cold water (10 mL), driedover anhydrous Na2SO4 and evaporated under vacuumto afford a residue which was recrystallized fromethanol to get the pure product 4a-p.
90%	With β‑cyclodextrin sulfonic acid In neat (no solvent) at 80℃; for 0.333333h; Green chemistry;	General procedure for the synthesis of 2H-indazolo [2,1-b] phthalazinetrionesderivatives (1-25) General procedure: A mixture of phthalhydrazide (1.0 mmol), aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione or 1,3-cyclohexanedione (1.0 mmol),β -cyclodextrin-SO3H (10 mol %) was heated at 80 °C under solvent free condition for an appropriate time as mentioned in Table 1. After completion of the reaction as monitored by TLC the reaction mixture was allowed to cool to room temperature and the residue was diluted with water. The precipitate formed was collected by filtration at pump,washed with water, and dried. The residue recrystallized from ethanol to afford the pure product of 2H-indazolo[2,1-b]phthalazine-trione derivatives. 3,3-Dimethyl-13-phenyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-trione (1) Yellow powder, mp: 200-202 C; 1H NMR (400 MHz, CDCl3) d (ppm)1.23 (s, 6H, -(CH3)2), 2.35 (s, 2H, -CH2-C=), 3.26 and 3.41 (2H, AB system,J = 16 Hz, CHaHbCO), 6.47 (s,1H, -CH-N), 7.61 (d, J = 8 Hz, 2H, Ar-H),7.90-7.85 (m, 2H, Ar-H), 8.37-8.16 (m, 5H, Ar-H); 13C NMR (CDCl3, 100 MHz)d (ppm) 28.5 (-CH3), 28.7 (-CH3), 34.7 (-C(CH3)2), 38.1 (-CH2-C=), 50.9(-CH2CO), 64.9 (-CH-N), 118.6 (-HC-C-CO-), 127.1 (Ar-C), 127.7 (Ar-C),127.9 (Ar-C), 128.7 (Ar-C), 128.9 (Ar-C), 129.1 (Ar-C), 133.6 (Ar-C), 134.5(Ar-C), 136.4(-N-C-CH2-), 150.9 (Ar-C), 154.3 (-N-CO-), 156.1 (-N-CO-),192.2 (-CO-); HRMS m/z calcd for C23H20N2O3 [M?] 372.4165, found 372.4167.
89%	With 1,3,5-trichloro-2,4,6-triazine; water at 100℃; for 0.416667h; Neat (no solvent);
89%	With H₃PO₄/Al₂O₃ In neat (no solvent) at 100℃; for 0.133333h;
87%	With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide at 100℃; for 0.25h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2, 1-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 1) General procedure: A mixture of dimedone (0.28 g, 2 mmol), phthalhydrazide (0.32 g, 2 mmol), benzaldehyde (0.24 g, 2.2 mmol), and TBBDA (0.05 g) or PBBS (0.1 g) was heated at 100 °C for 10 min. After completion of the reaction [TLC acetone/n-hexane (3:10)]. The reaction mixture was cooled, filtered and washed with acetone (15 mL). Removal of the solvent under reduced pressure gave the catalyst. The crude product was recrystallized from ethyl acetate/n-hexane (1:3) to afford the pure product.
86.2%	With chloro-trimethyl-silane In N,N-dimethyl-formamide; acetonitrile at 80℃;
86%	With iodine In ethanol for 0.5h; Reflux;
84%	With 2Fe⁽²⁺⁾(x)H₂O3O₄S^(2-) In ethanol for 4h; Reflux;	General experimental procedure for the Synthesis of2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: Hydrated ferric sulfate (0.20 mol, 0.084 g) was added toa mixture of an aromatic aldehyde (1.2 mmol), a cyclic1,3-dicarbonyl compound (1.0 mmol) and phthalhydrazide(1.0 mmol) in 3 mL of ethanol. The reaction mixture was kept for refluxing in a preheated oil-bath. After completion of the reaction (as monitored by TLC), it was brought to room temperature. The solid product precipitated out after adding 6 mL of water into it and it was filtered off through a Büchner funnel. The precipitate was washed with ethanol (2 mL) and dried in a vacuum pump.
78%	With diatomite-SO₃H In ethanol at 80℃; for 3h;	2.3 General procedure for the synthesis of2H-indazolo (2, 1-b) phthalazine-triones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) and diatomite-SO3H (0.3 g) in ethanol was heated at 80 °C. The progressof the reaction was monitored by TLC ethyl acetate:n-hexane(1:1). After completion of the reaction, the diatomite-SO3H was filtered from the reaction mixture. After evaporation ofthe solvent, the crude productwas purified by recrystallizationin aqueous ethanol to afford the pure product.
	With zinc(II) oxide In neat (no solvent) at 60℃; for 0.0666667h; Green chemistry;

Reference： [1]Veisi, Hojat; Sedrpoushan, Alireza; Faraji, Ali Reza; Heydari, Masoud; Hemmati, Saba; Fatahi, Behnaz [RSC Advances, 2015, vol. 5, # 84, p. 68523 - 68530]
[2]Shaterian, Hamid Reza; Aghakhanizadeh, Morteza [Comptes Rendus Chimie, 2012, vol. 15, # 11-12, p. 1060 - 1064]
[3]Iravani, Nasir; Keshavarz, Mosadegh; Parhami, Abolfath [Research on Chemical Intermediates, 2019, vol. 45, # 10, p. 5045 - 5066]
[4]Jadhav, Amol Maruti; Balwe, Sandip Gangadhar; Jeong, Yeon Tae [Phosphorus, Sulfur and Silicon and the Related Elements, 2020, vol. 195, # 3, p. 201 - 210]
[5]Location in patent: experimental part Veeranarayana Reddy, Mudumala; Reddy, Gangireddy Chandra Sekhar; Jeong, Yeon Tae [Tetrahedron, 2012, vol. 68, # 34, p. 6820 - 6828]
[6]Raghuvanshi, Dushyant Singh; Kumari, Kumkum; Allam, Bharat Kumar; Singh, Krishna Nand [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53B, # 11, p. 1462 - 1467]
[7]Atar, Amol B.; Lee, Sang Dong; Cho, Byung Gwon; Cho, Dae Won; Jeong, Yeon Tae [Research on Chemical Intermediates, 2016, vol. 42, # 3, p. 1707 - 1728]
[8]Location in patent: experimental part Wang, Xiao; Ma, Wei-Wei; Wu, Li-Qiang; Yan, Fu-Lin [Journal of the Chinese Chemical Society, 2010, vol. 57, # 6, p. 1341 - 1345]
[9]Shaterian, Hamid Reza; Fahimi, Nafiseh; Azizi, Kobra [Research on Chemical Intermediates, 2014, vol. 40, # 5, p. 1879 - 1898]
[10]Location in patent: experimental part Ghorbani-Vaghei, Ramin; Karimi-Nami, Rahman; Toghraei-Semiromi, Zahra; Amiri, Mostafa; Ghavidel, Mehdi [Tetrahedron, 2011, vol. 67, # 10, p. 1930 - 1937]
[11]Location in patent: experimental part Nagarapu, Lingaiah; Bantu, Rajashaker; Mereyala, Hari Babu [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 4, p. 728 - 731]
[12]Location in patent: experimental part Wang, Xiao; Lu, Guangzhou; Ma, Weiwei; Wu, Liqzang [E-Journal of Chemistry, 2011, vol. 8, # 3, p. 1000 - 1005]
[13]Choudhury, Abhik; Ali, Shahzad; Khan, Abu T. [Journal of the Korean Chemical Society, 2015, vol. 59, # 4, p. 280 - 283]
[14]Abbasi, Marzieh; Nazifi, Seyed Mohamad Reza; Nazifi, Zahra Sadat; Massah, Ahmad Reza [Journal of Chemical Sciences, 2017, vol. 129, # 8, p. 1257 - 1266]
[15]Shaterian, Hamid Reza; Mollashahi, Ebrahim; Biabangard, Asiyeh [Journal of the Chemical Society of Pakistan, 2013, vol. 35, # 2, p. 329 - 332]

20
[ 1445-69-8 ]
[ 504-02-9 ]
[ 100-10-7 ]
[ 1204395-17-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With succinimidinium N-sulfonic acid hydrogen sulfate In neat (no solvent) at 100℃; for 0.25h;	synthesis of 2H-indazolo[1,2-b]phthalazine-triones General procedure: A mixture of aldehyde (1 mmol), 1,3-cyclic diketone (1 mmol),phthalhydrazide (1 mmol) and [SuSA-H]HSO4 (27.7 mg, 0.1 mmol,10 mol%) was stirred in an oil-bath at 100 °C under solvent-free conditions. After completion of the reaction [monitored by TLC: nhexane:ethyl acetate (8:2)], the reaction mixture was cooled, H2O(5 mL) was added to it and filtered to separate the catalyst. The solidresidue was recrystallized from ethanol to give the pure product.
90%	With β‑cyclodextrin sulfonic acid In neat (no solvent) at 80℃; for 0.333333h; Green chemistry;	General procedure for the synthesis of 2H-indazolo [2,1-b] phthalazinetrionesderivatives (1-25) General procedure: A mixture of phthalhydrazide (1.0 mmol), aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione or 1,3-cyclohexanedione (1.0 mmol),β -cyclodextrin-SO3H (10 mol %) was heated at 80 °C under solvent free condition for an appropriate time as mentioned in Table 1. After completion of the reaction as monitored by TLC the reaction mixture was allowed to cool to room temperature and the residue was diluted with water. The precipitate formed was collected by filtration at pump,washed with water, and dried. The residue recrystallized from ethanol to afford the pure product of 2H-indazolo[2,1-b]phthalazine-trione derivatives. 3,3-Dimethyl-13-phenyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-trione (1) Yellow powder, mp: 200-202 C; 1H NMR (400 MHz, CDCl3) d (ppm)1.23 (s, 6H, -(CH3)2), 2.35 (s, 2H, -CH2-C=), 3.26 and 3.41 (2H, AB system,J = 16 Hz, CHaHbCO), 6.47 (s,1H, -CH-N), 7.61 (d, J = 8 Hz, 2H, Ar-H),7.90-7.85 (m, 2H, Ar-H), 8.37-8.16 (m, 5H, Ar-H); 13C NMR (CDCl3, 100 MHz)d (ppm) 28.5 (-CH3), 28.7 (-CH3), 34.7 (-C(CH3)2), 38.1 (-CH2-C=), 50.9(-CH2CO), 64.9 (-CH-N), 118.6 (-HC-C-CO-), 127.1 (Ar-C), 127.7 (Ar-C),127.9 (Ar-C), 128.7 (Ar-C), 128.9 (Ar-C), 129.1 (Ar-C), 133.6 (Ar-C), 134.5(Ar-C), 136.4(-N-C-CH2-), 150.9 (Ar-C), 154.3 (-N-CO-), 156.1 (-N-CO-),192.2 (-CO-); HRMS m/z calcd for C23H20N2O3 [M?] 372.4165, found 372.4167.
86%	With sulfuric acid In [bmim]BF₄ at 80℃; for 0.583333h; Ionic liquid;

86%	Stage #1: 1,3-cylohexanedione; 4-dimethylamino-benzaldehyde With dodecylphosphonic acid for 0.0833333h; Neat (no solvent); Stage #2: 2,3-dihydrophthalazine-1,4-dione at 80℃; for 0.166667h; Neat (no solvent);	General procedure for the synthesis of 2H-indazolo[2,1-b]phthalazine-trione derivatives: General procedure: In a 50 mL round bottom flask, the required amount of aromatic aldehydes (1 mmol), 1,3-dicarbonyl compounds (1 mmol), and dodecylphosphonic acid (DPA) (10 mol %) were added and the mixture was stirred over a magnetic stirrer. After 5 min, to this stirred mixture, phthalhydrazide (1.5 mmol) was added and the contents were stirred at 80 °C for an appropriate time. The progress of reaction was monitored by TLC. After completion of the reaction, the reaction mixture was allowed to cool at room temperature and washed with water. The crude product was crystallized with ethanol, which was further purified by silica gel column chromatography (hexane/ethylacetate 70:30) to give the desired products. All the products were characterized by comparing their physical (MPs) and spectral data with those reported earlier. After the evaporation of aqueous layer, the catalyst was recovered and reused for next reaction.
86%	With 1,1,1,3',3',3'-hexafluoro-propanol at 55℃; for 12h; Green chemistry;
85%	In neat (no solvent) at 80℃; for 0.283333h;	2.4. General procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedone and/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide (1.0 mmol) and [DABCO](SO3H)2(HSO4)2 (0.014 g, 0.03 mmol) was heated in an oil bath (80 °C) under solvent free conditions for the appropriate time. The reaction was monitored by TLC (n-hexane: ethyl acetate). After completion, the reaction mass was cooled to room temperature and washed with water for the separation of the catalyst. The solid product was purified by re-crystallization in aqueous EtOH (25%). The products were characterized by comparison of their physical data with those of known compounds.
85%	With 4,4'-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) tetrachloride In neat (no solvent) at 80℃; for 0.283333h;	2.6. General Procedure for the Preparation of 2HIndazolo[2,1-b]Phthalazine-1,6,11(13H)-Triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedoneand/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide(1.0 mmol) and NS-[C4(DABCO-SO3H)2] · 4Cl (0.010 g, 5 mol%) was heated in an oil bath (80 C)under solvent-free conditions for the appropriate time. The reaction was monitored by TLC [n-hexane:ethylacetate(10:2)]. After completion, the reaction mass was cooledto room temperature and washed with water for the separationof the catalyst. The solid product was purified byre-crystallization in aqueous EtOH (25%). The productswere characterized by comparison of their physical datawith those of known compounds.

Reference： [1]Abedini, Masoumeh; Shirini, Farhad; Omran, Javad Mohammad-Alinejad [Journal of Molecular Liquids, 2015, vol. 212, p. 405 - 412]
[2]Atar, Amol B.; Lee, Sang Dong; Cho, Byung Gwon; Cho, Dae Won; Jeong, Yeon Tae [Research on Chemical Intermediates, 2016, vol. 42, # 3, p. 1707 - 1728]
[3]Location in patent: scheme or table Khurana, Jitender M.; Magoo, Devanshi [Tetrahedron Letters, 2009, vol. 50, # 52, p. 7300 - 7303]
[4]Kidwai, Mazaahir; Jahan, Anwar; Chauhan, Ritika; Mishra, Neeraj Kumar [Tetrahedron Letters, 2012, vol. 53, # 14, p. 1728 - 1731]
[5]Maleki, Behrooz; Ashrafi, Samaneh Sedigh; Tayebee, Reza [RSC Advances, 2014, vol. 40, # 78, p. 41521 - 41528] Maleki, Behrooz; Ashrafi, Samaneh Sedigh; Tayebee, Reza [RSC Advances, 2014, vol. 4, # 78, p. 41521 - 41528]
[6]Shirini, Farhad; Langarudi, Mohaddeseh Safarpoor Nikoo; Goli-Jolodar, Omid [Dyes and Pigments, 2015, vol. 123, p. 186 - 195]
[7]Goli-Jolodar, Omid; Shirini, Farhad; Seddighi, Mohadeseh [Journal of Nanoscience and Nanotechnology, 2018, vol. 18, # 1, p. 591 - 603]

21
[ 1445-69-8 ]
[ 126-81-8 ]
[ 120-14-9 ]
[ 1204395-09-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With Ni(II)-schiff base complex grafted in mesoporous silica MCM-41 at 100℃; for 3.66667h;
92%	With triphenyl(propyl-3-sulphonyl)phosphonium toluenesulfonate at 80℃; for 0.116667h; Green chemistry;
92%	With nano-silica supported 3-(3-sulfopropyl)-1-[3-(trimethoxysilyl)propyl]-1H-imidazol-3-ium hydrogen sulfate In neat (no solvent) at 80℃; for 0.166667h;

90%	With nano (SO₃H functionalized mesoporous silica) In neat (no solvent) at 110℃; for 0.4h; Sealed tube; Green chemistry;
88%	With Fe₃O₄ nanoparticles-supported N-propylsulfamic acid In neat (no solvent) at 100℃; for 0.5h; Green chemistry;	General Procedure for Synthesis of 1H-indazolo[1,2-b]phthalazine-triones catalyzed by MNPs-PSA General procedure: To a mixture of aromatic aldehyde (1.1 mmol), phthalhydrazide (1 mmol) and cyclic 1,3-diones compound (1 mmol), MNPs-PSA (30 mg) was added and the mixture was stirred and heated in an oil bath at 100 °C for appropriate time. Completion of the reaction was indicated by TLC (n-hexane/ethylacetate 60:40). After the indicated reaction time, the reaction mixture was cooled to room temperature. Et2O (25 mL) was added and the catalyst was separated by an external magnet. The resulting solution was concentrated under reduced pressure to afford the essentially pure products. In some cases, for further purication, the product was recrystallized from ethanol.
88%	With MNPs-guanidine (guanidine supported on magnetic nanoparticles Fe₃O₄) In neat liquid at 70℃; for 0.5h;
87%	With H₃PO₄/Al₂O₃ In neat (no solvent) at 100℃; for 0.15h;
87%	With sulfonic acid grafted onto TiO₂-coated nickel ferrite nanoparticles In neat (no solvent) at 80℃; for 0.583333h;	General procedure for synthesisof 2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol), and nanocatalyst(0.03 g) was heated at 80 °C for 10 min (TLC). Aftercooling, the reaction mixture was poured in 10 mL of DMFand the catalyst was separated easily by an external magnet.The saturated sodium chloride solution was then added to precipitate the pure product.
86%	With 2Fe⁽²⁺⁾(x)H₂O3O₄S^(2-) In ethanol for 4h; Reflux;	General experimental procedure for the Synthesis of2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: Hydrated ferric sulfate (0.20 mol, 0.084 g) was added toa mixture of an aromatic aldehyde (1.2 mmol), a cyclic1,3-dicarbonyl compound (1.0 mmol) and phthalhydrazide(1.0 mmol) in 3 mL of ethanol. The reaction mixture was kept for refluxing in a preheated oil-bath. After completion of the reaction (as monitored by TLC), it was brought to room temperature. The solid product precipitated out after adding 6 mL of water into it and it was filtered off through a Büchner funnel. The precipitate was washed with ethanol (2 mL) and dried in a vacuum pump.
85%	With polymer-supported sulfonic acid (PSSA) In glycerol at 80℃; for 1h;
83%	With sulfuric acid In [bmim]BF₄ at 80℃; for 0.666667h; Ionic liquid;
80%	With 1-sulfonic acid-3,5,7-trimethylpurinium-5,7-dione hydrogen sulfate In neat (no solvent) at 100℃; for 0.333333h; Green chemistry;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione General procedure: A mixture of dimedone (0.035 g, 0.25 mmol), phthalhydrazide (0.040 g, 0.25 mmol), benzaldehyde (0.026 g, 1 mmol), and 3-sulfonic acid imidazopyridinium hydrogen sulfate (10 mmol) was heated at 100°C for 10 min. After cooling, the residue was re-crystallized from ethanol to afford the corresponding pure product.
78%	With diatomite-SO₃H In ethanol at 80℃; for 3h;	2.3 General procedure for the synthesis of2H-indazolo (2, 1-b) phthalazine-triones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) and diatomite-SO3H (0.3 g) in ethanol was heated at 80 °C. The progressof the reaction was monitored by TLC ethyl acetate:n-hexane(1:1). After completion of the reaction, the diatomite-SO3H was filtered from the reaction mixture. After evaporation ofthe solvent, the crude productwas purified by recrystallizationin aqueous ethanol to afford the pure product.

Reference： [1]Nikoorazm, Mohsen; Ghorbani-Choghamarani, Arash; Khanmoradi, Maryam [RSC Advances, 2016, vol. 6, # 61, p. 56549 - 56561]
[2]Shaterian, Hamid Reza; Aghakhanizadeh, Morteza [Comptes Rendus Chimie, 2012, vol. 15, # 11-12, p. 1060 - 1064]
[3]Safaei, Shirin; Mohammadpoor-Baltork, Iraj; Khosropour, Ahmad Reza; Moghadam, Majid; Tangestaninejad, Shahram; Mirkhani, Valiollah [Catalysis science and technology, 2013, vol. 3, # 10, p. 2717 - 2722]
[4]Amiri, Ali Alinasab; Javanshir, Shahrzad; Dolatkhah, Zahra; Dekamin, Mohammad G. [New Journal of Chemistry, 2015, vol. 39, # 12, p. 9665 - 9671]
[5]Rostami, Amin; Tahmasbi, Bahman; Yari, Ako [Bulletin of the Korean Chemical Society, 2013, vol. 34, # 5, p. 1521 - 1524]
[6]Atashkar, Bahareh; Rostami, Amin; Gholami, Hoshyar; Tahmasbi, Bahman [Research on Chemical Intermediates, 2015, vol. 41, # 6, p. 3675 - 3681]
[7]Shaterian, Hamid Reza; Fahimi, Nafiseh; Azizi, Kobra [Research on Chemical Intermediates, 2014, vol. 40, # 5, p. 1879 - 1898]
[8]Hamidinasab, Mahdia; Mobinikhaledi, Akbar [Journal of the Iranian Chemical Society, 2019, vol. 16, # 6, p. 1255 - 1263]
[9]Choudhury, Abhik; Ali, Shahzad; Khan, Abu T. [Journal of the Korean Chemical Society, 2015, vol. 59, # 4, p. 280 - 283]
[10]Mulik, Abhijeet; Chandam, Dattatraya; Patil, Prasad; Patil, Dayanand; Jagdale, Suryabala; Sankpal, Sandip; Deshmukh, Madhukar [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 3, p. 931 - 937]
[11]Location in patent: scheme or table Khurana, Jitender M.; Magoo, Devanshi [Tetrahedron Letters, 2009, vol. 50, # 52, p. 7300 - 7303]
[12]Tayebee, Reza; Jomei, Malihe; Maleki, Behrooz; Razi, Maryam Kargar; Veisi, Hojat; Bakherad, Mohammad [Journal of Molecular Liquids, 2015, vol. 206, p. 119 - 128]
[13]Abbasi, Marzieh; Nazifi, Seyed Mohamad Reza; Nazifi, Zahra Sadat; Massah, Ahmad Reza [Journal of Chemical Sciences, 2017, vol. 129, # 8, p. 1257 - 1266]

22
[ 1445-69-8 ]
[ 126-81-8 ]
[ 66-99-9 ]
[ 1204395-08-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With nano-silica supported 3-(3-sulfopropyl)-1-[3-(trimethoxysilyl)propyl]-1H-imidazol-3-ium hydrogen sulfate In neat (no solvent) at 80℃; for 0.333333h;
90%	With sulfuric acid In ethanol; water for 0.416667h; Reflux;
89%	With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide at 100℃; for 0.166667h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2, 1-b]phthalazine-1,6,11(13H)-trione (Table 2, entry 1) General procedure: A mixture of dimedone (0.28 g, 2 mmol), phthalhydrazide (0.32 g, 2 mmol), benzaldehyde (0.24 g, 2.2 mmol), and TBBDA (0.05 g) or PBBS (0.1 g) was heated at 100 °C for 10 min. After completion of the reaction [TLC acetone/n-hexane (3:10)]. The reaction mixture was cooled, filtered and washed with acetone (15 mL). Removal of the solvent under reduced pressure gave the catalyst. The crude product was recrystallized from ethyl acetate/n-hexane (1:3) to afford the pure product.

89%	With boron tri(hydrogen sulphate) In neat (no solvent) at 100℃; for 0.166667h;
85%	With Pentaerythritol In neat (no solvent) at 80℃; for 0.75h; Green chemistry;	General procedure for synthesis of 2H-indazolo[1,2-b]phthalazine-triones General procedure: To a mixture consisting of 4-chlorobenzaldehyde (1 mmol, 0.14 g), dimedone (1 mmol, 0.14 g), and phthalhydrazine (1 mmol, 0.16 g) in a 10-ml round-bottomed flask was added pentaerythritol (0.1 mmol, 0.01 g), and the resulting mixture was stirred magnetically at 80 °C. After reaction completion as monitored by thin-layer chromatography (TLC), the reaction mixture was cooled, and acetone (10 ml) was added to it. After separation of catalyst, the solvent was removed under vacuum from the clear reaction mixture. The crude product was recrystallized from EtOH/H2O (3:2) to afford pure product.
84%	With aminosulfonic acid In neat (no solvent) at 100℃; for 0.35h; Green chemistry;	General Procedure for Synthesis of 1H-indazolo[1,2-b]phthalazine-triones Catalyzed by SA General procedure: To a mixture of aromatic aldehyde (1.1 mmol), phthalhydrazide (1 mmol) and cyclic 1,3-diones compound (1 mmol), SA (10 mg, 0.1 mmol) was added and the mixture was stirred and heated in an oil bath at 100 °C for appropriate time. Completion of the reaction was indicated by TLC (stationary phase: silica gel polygram SIL G/UV 254 plates and mobile phase: n-hexane/ethylacetate 60:40). After the reaction was completed, the reaction mixture was cooled to room temperature, and then the solid residue was washed by H2O:EtOH (90:10). The solid product was purified by recrystallization procedure from ethanol (85%).
84%	With MNPs-guanidine (guanidine supported on magnetic nanoparticles Fe₃O₄) In neat liquid at 70℃; for 0.5h;

Reference： [1]Safaei, Shirin; Mohammadpoor-Baltork, Iraj; Khosropour, Ahmad Reza; Moghadam, Majid; Tangestaninejad, Shahram; Mirkhani, Valiollah [Catalysis science and technology, 2013, vol. 3, # 10, p. 2717 - 2722]
[2]Location in patent: scheme or table Khurana, Jitender M.; Magoo, Devanshi [Tetrahedron Letters, 2009, vol. 50, # 52, p. 7300 - 7303]
[3]Location in patent: experimental part Ghorbani-Vaghei, Ramin; Karimi-Nami, Rahman; Toghraei-Semiromi, Zahra; Amiri, Mostafa; Ghavidel, Mehdi [Tetrahedron, 2011, vol. 67, # 10, p. 1930 - 1937]
[4]Soheilizad, Mehdi; Adib, Mehdi; Sajjadifar, Sami [Monatshefte fur Chemie, 2014, vol. 145, # 8, p. 1353 - 1356]
[5]Farahmand, Shohreh; Ayazi-Nasrabadi, Roya; Mokhlesi, Mohammad; Zolfigol, Mohammad Ali [Research on Chemical Intermediates, 2019, vol. 45, # 7, p. 3795 - 3807]
[6]Rostami, Amin; Tahmasbi, Bahman; Yari, Ako [Bulletin of the Korean Chemical Society, 2013, vol. 34, # 5, p. 1521 - 1524]
[7]Atashkar, Bahareh; Rostami, Amin; Gholami, Hoshyar; Tahmasbi, Bahman [Research on Chemical Intermediates, 2015, vol. 41, # 6, p. 3675 - 3681]

23
[ 1445-69-8 ]
[ 126-81-8 ]
[ 6630-33-7 ]
[ 1245471-19-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	With silica-supported tungstic acid In neat (no solvent) at 80℃; for 0.566667h; Green chemistry;	General procedure for the synthesis of 13-(4-chlorophenyl)-3,3-dimethyl-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]phthalazine-1,6,11-trione (4a) General procedure: A mixture of phthalhydrazide (1, 1 mmol), 4-chlorobenzaldehydes (2, 1 mmol), dimedone (3, 1 mmol) and silica-supported tungstic acid (STA 10 mol%) was stirred at 80 °C under solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was washed with ethanol. The residue dissolved in DCM, and the insoluble STA was separated by simple filtration and washed with DCM. The solvent was evaporated under reduced pressure and the obtained crude was recrystallized from ethanol to afford the pure yellow product 4a. The recovered catalyst was washed with ethanol and acetone, dried and reused. Compounds 4a-4w were also synthesized by adopting this procedure.
89%	With nickel at 80℃; for 0.216667h; Green chemistry;
89%	With N-propyliminodiacetic acid (PIDA) organocatalyst supported on mesoporous SBA-15 In water at 100℃; for 0.333333h;

88%	With Pentaerythritol In neat (no solvent) at 80℃; for 0.7h; Green chemistry;	General procedure for synthesis of 2H-indazolo[1,2-b]phthalazine-triones General procedure: To a mixture consisting of 4-chlorobenzaldehyde (1 mmol, 0.14 g), dimedone (1 mmol, 0.14 g), and phthalhydrazine (1 mmol, 0.16 g) in a 10-ml round-bottomed flask was added pentaerythritol (0.1 mmol, 0.01 g), and the resulting mixture was stirred magnetically at 80 °C. After reaction completion as monitored by thin-layer chromatography (TLC), the reaction mixture was cooled, and acetone (10 ml) was added to it. After separation of catalyst, the solvent was removed under vacuum from the clear reaction mixture. The crude product was recrystallized from EtOH/H2O (3:2) to afford pure product.
85%	With phosphomolybdic acid - SiO₂ at 80℃; for 0.666667h; Neat (no solvent);

Reference： [1]Jadhav, Amol Maruti; Balwe, Sandip Gangadhar; Jeong, Yeon Tae [Phosphorus, Sulfur and Silicon and the Related Elements, 2020, vol. 195, # 3, p. 201 - 210]
[2]Saha, Mithu; Phukan, Smritakshi; Jamatia, Ramen; Mitra, Sivprasad; Pal, Amarta Kumar [RSC Advances, 2013, vol. 3, # 6, p. 1714 - 1721]
[3]Doustkhah, Esmail; Baghban, Ali; Assadi, M. Hussein N.; Luque, Rafael; Rostamnia, Sadegh [Catalysis Letters, 2019, vol. 149, # 2, p. 591 - 600]
[4]Farahmand, Shohreh; Ayazi-Nasrabadi, Roya; Mokhlesi, Mohammad; Zolfigol, Mohammad Ali [Research on Chemical Intermediates, 2019, vol. 45, # 7, p. 3795 - 3807]
[5]Location in patent: experimental part Sabitha, Gowravaram; Srinivas, Chitti; Raghavendar, Avula; Yadav, Jhillu Singh [Helvetica Chimica Acta, 2010, vol. 93, # 7, p. 1375 - 1380]

24
[ 1445-69-8 ]
[ 126-81-8 ]
[ 122-03-2 ]
[ 1245471-24-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With beta?cyclodextrin sulfonic acid; In neat (no solvent); at 80℃; for 0.166667h;Green chemistry;	General procedure: A mixture of phthalhydrazide (1.0 mmol), aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione or 1,3-cyclohexanedione (1.0 mmol),beta -cyclodextrin-SO3H (10 mol %) was heated at 80 C under solvent free condition for an appropriate time as mentioned in Table 1. After completion of the reaction as monitored by TLC the reaction mixture was allowed to cool to room temperature and the residue was diluted with water. The precipitate formed was collected by filtration at pump,washed with water, and dried. The residue recrystallized from ethanol to afford the pure product of 2H-indazolo[2,1-b]phthalazine-trione derivatives. 3,3-Dimethyl-13-phenyl-3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-trione (1) Yellow powder, mp: 200-202 C; 1H NMR (400 MHz, CDCl3) d (ppm)1.23 (s, 6H, -(CH3)2), 2.35 (s, 2H, -CH2-C=), 3.26 and 3.41 (2H, AB system,J = 16 Hz, CHaHbCO), 6.47 (s,1H, -CH-N), 7.61 (d, J = 8 Hz, 2H, Ar-H),7.90-7.85 (m, 2H, Ar-H), 8.37-8.16 (m, 5H, Ar-H); 13C NMR (CDCl3, 100 MHz)d (ppm) 28.5 (-CH3), 28.7 (-CH3), 34.7 (-C(CH3)2), 38.1 (-CH2-C=), 50.9(-CH2CO), 64.9 (-CH-N), 118.6 (-HC-C-CO-), 127.1 (Ar-C), 127.7 (Ar-C),127.9 (Ar-C), 128.7 (Ar-C), 128.9 (Ar-C), 129.1 (Ar-C), 133.6 (Ar-C), 134.5(Ar-C), 136.4(-N-C-CH2-), 150.9 (Ar-C), 154.3 (-N-CO-), 156.1 (-N-CO-),192.2 (-CO-); HRMS m/z calcd for C23H20N2O3 [M?] 372.4165, found 372.4167.
91%	With silica-supported tungstic acid; In neat (no solvent); at 80℃; for 0.55h;Green chemistry;	General procedure: A mixture of phthalhydrazide (1, 1 mmol), 4-chlorobenzaldehydes (2, 1 mmol), dimedone (3, 1 mmol) and silica-supported tungstic acid (STA 10 mol%) was stirred at 80 C under solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was washed with ethanol. The residue dissolved in DCM, and the insoluble STA was separated by simple filtration and washed with DCM. The solvent was evaporated under reduced pressure and the obtained crude was recrystallized from ethanol to afford the pure yellow product 4a. The recovered catalyst was washed with ethanol and acetone, dried and reused. Compounds 4a-4w were also synthesized by adopting this procedure.
87%	With 1-sulfonic acid-3,5,7-trimethylpurinium-5,7-dione hydrogen sulfate; In neat (no solvent); at 100℃; for 0.666667h;Green chemistry;	General procedure: A mixture of dimedone (0.035 g, 0.25 mmol), phthalhydrazide (0.040 g, 0.25 mmol), benzaldehyde (0.026 g, 1 mmol), and 3-sulfonic acid imidazopyridinium hydrogen sulfate (10 mmol) was heated at 100C for 10 min. After cooling, the residue was re-crystallized from ethanol to afford the corresponding pure product.

86%	With yttrium(III) trifluoromethanesulfonate; In ethanol; water; at 80℃; for 0.5h;Green chemistry;	General procedure: A mixture of 1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione (1,3-dicarbonyl compounds) 1 (2 mmol) with p-substituted benzaldehyde 2 (2 mmol), phthalhydrazide 3 (2 mmol), and 20 mol % of Y(OTf)3 in 10 mL of EtOH-H2O (1 : 1, v/v) was stirred magnetically upon refluxing till completion of the reaction (monitored by TLC) (Table 1). The raw product was filtered off, washed with water and crystallized from EtOH to give the corresponding pure product 4a-4e.
85%	With Fe3O4-SiO2 core-shell nanoparticles; at 120℃; for 0.333333h;Green chemistry;	General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide (0.16 g, 1 mmol), aldehyde (1 mmol), and Fe3O4 SiO2 (0.0 23 gr, 0.8 mmol, 8 mol%) was heated at 120C for 10-20 min. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature and the solid obtained was dissolved in dichloromethane; the catalyst was insoluble in CH2Cl2 and separated by using an external magnet. The solvent was evaporated and the residue was recrystallized from ethanol to afford the pure indazolo[1,2-b]-phthalazinetriones.

Reference： [1]Research on Chemical Intermediates,2016,vol. 42,p. 1707 - 1728
[2]Phosphorus, Sulfur and Silicon and the Related Elements,2020,vol. 195,p. 201 - 210
[3]Helvetica Chimica Acta,2010,vol. 93,p. 1375 - 1380
[4]Journal of Molecular Liquids,2015,vol. 206,p. 119 - 128
[5]Russian Journal of Organic Chemistry,2019,vol. 55,p. 250 - 253
[6]Research on Chemical Intermediates,2015,vol. 41,p. 7703 - 7714

25
[ 1445-69-8 ]
[ 1515-75-9 ]
[ 32692-31-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hypochlorite In dichloromethane; water at 0℃;	3 EXAMPLE 3: EXAMPLE 3: PREPARATION OF 6,11-DIOXO-1,4,6,11-TETRAHYDRO-PYRIDAZINO[1,2-B]PHTHALAZINE-1-CARBOXYLIC ACID METHYL ESTER. Water (711 mL) and concentrated HCl (284 mL) are placed into a round-bottom flask. 2,3-Dihydrophthalazine-1,4-dione (288 g) is added at 25-35°C. The mass is cooled to -10 to 0°C and 2,4-pentadienylmethyl ester (142.2 g) in dichloromethane is added at the same temperature. Sodium hypochlorite solution (12% w/w, 1140 g) is added slowly over about 7 hours, below 0°C. The reaction is maintained for about 2 hours. A solution of 30 g of sodium bisulfite in 207 mL of water is added below 5°C, stirred for 15 minutes, and the organic layer is separated. The aqueous layer pH is adjusted to about 5 by adding a solution of 128 g of NaOH in 640 mL water at 0-5°C, and is stirred for 30 minutes. Undissolved solid is filtered and the solid is washed with dichloromethane (284 mL). The aqueous layer is separated from the filtrate and is washed with dichloromethane (284 mL). The combined organic layer is washed with water (711 mL) and the final organic layer is distilled. Acetone (426 mL) is added to the residue and the acetone is distilled. Acetone (284 mL) is charged to the reaction mixture and 142 mL is distilled. The residue is cooled to 0-5°C and stirred for about 2 hours. The formed solid is filtered and washed with chilled acetone (213 mL). The wet solid is dried under vacuum at 25-35°C for 30 minutes, and then at 50-55°C for 7 hours, to obtain the title compound. Approximate yield: 171 g. Purity by HPLC: 98.8%.

Reference： [1]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - EP2221299, 2010, A2 Location in patent: Page/Page column 8

26
[ 1445-69-8 ]
[ 3132-99-8 ]
[ 109-77-3 ]
[ 1206604-86-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With 1-butyl-3-methylimidazolium hydroxide In ethanol at 60℃; for 0.8h; Green chemistry;	1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives 4 General procedure: A mixture of the aromatic aldehyde 1 (1 mmol), malononitrile or ethylcyanoacetate 2 (1 mmol), phthalhydrazide 3 (1 mmol), [bmim]OH (0.1mmol) in EtOH (5 mL) was stirred at 60 °C for the appropriate time(monitored by thin-layer chromatography [TLC]). After completion ofthe reaction, the mixture was cooled to room temperature and pouredinto water (10 mL). The solid product was collected by filtration andrecrystallised from ethanol to give the pure compound 4. The filtratewas extracted with diethyl ether several times to remove unreactedstarting materials and other organic contaminations. Then the waterwas evaporated under reduced pressure and dried to recover the ionicliquid for subsequent use.
93%	at 45℃; for 0.0833333h; Ionic liquid; Microwave irradiation;	28 General procedure for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione: General procedure: Phthalhydrazide (1 mmol), aromatic aldehyde (1 mmol), malononitrile (1 mmol) and [Bmim]OH (0.2 mL) were put in a pressure regulation 10-mL pressurized vial with 'snap-on' cap and the reaction mixture was subjected to irradiation in a single-mode microwave synthesis system at 100 W power and 45 °C for 4-5 min. After completion of the reaction as indicated by TLC, water (5 mL) was added and the product was extracted with EtOAc (3 × 10 mL). The combined organic phase was dried over anhydrous Na2SO4, evaporated under reduced pressure and recrystallized from ethanol to afford pure 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4. After isolation of the product, the remaining aqueous layer containing the ionic liquid was washed with ether (10 mL) to remove any organic impurity, and then dried under vacuum at 90-95 °C for 15 h to afford [Bmim]OH, which was used in the subsequent runs without further purification.
90%	With triethylamine In ethanol at 50℃; for 1h; Ultrasonic irradiation;

88%	With β‐cyclodextrin In ethanol; water at 100℃; for 3.5h; Green chemistry;	2.1 General Procedure for Synthesis of 1H-Pyrazolo[1,2-b]phthalazine-5,10-diones General procedure: The mixture of carbonyl compound aldehyde (2 mmol), phthalhydrazide (2 mmol) and malononitrile (2 mmol) were added in β-cyclodextrin (0.4mmol) solution containing H2O-EtOH (4:1, 10 mL). The resulting mixture was stirred at 100 °C. After completion of the reaction (monitored by TLC), the reaction mixture was poured into 20mL water. Filtered the product and washed with hot water. The crude product was recrystallized with 30% aqueous ethanol to afford the desired product. The filtered aqueous layer was cooled at 5 °C to recovery of β-CD by filtration. The recovered β-CD was reused for 3-4 consecutive runs in this reaction without any significant loss in yield and activity.
86%	With Eosin Y In water at 20℃; for 4h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
85%	In water at 20℃; for 5h; Irradiation; Green chemistry;	2.3. The overall process of preparing (7a-r) General procedure: Multifarious reagents including phthalhydrazide (5, 1.0 mmol),malononitrile (2, 1.0 mmol) and aromatic aldehydes (6a-r, 1.0 mmol)were reacted opposed to CFL (23 W) irradiation at room temperature inaqueous ethyl lactate (2:1, 3 mL) (Scheme 2). This was observed by TLCthat employed (ethyl acetate/n-hexane (1:3)). Afterwards, the filteringof the acquired solid was conducted, then the solid was rinsed water (2 ×3 mL) and ethanol (2 × 3 mL) and solid composition became recrystallizedby EtOH. The products were classified after the comparison ofspectroscopic information (1H NMR). Support for this manuscript can befound in the online version.
83%	With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 0.25h; Green chemistry;
81%	With N,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide In water at 80℃; for 0.5h; Green chemistry;
	With pyrrolidinium formate at 20℃; for 0.116667h; Neat (no solvent);
	With magnetic Fe₃O₄ nanoparticles coated by (3-aminopropyl)triethoxysilane at 20℃; for 0.266667h;
354 mg	With piperidinium benzene-1,3-disulfonate Fe₃O₄ magnetic nanoparticle ionic liquid In neat (no solvent) at 110℃; for 0.666667h;

Reference： [1]Wang, Wang; Cong-Hao, Li; Yi, Yu; Xiao-Jun, Li; Hong-Yun, Guo [Journal of Chemical Research, 2016, vol. 40, # 6, p. 354 - 357]
[2]Location in patent: experimental part Raghuvanshi, Dushyant Singh; Singh, Krishna Nand [Tetrahedron Letters, 2011, vol. 52, # 43, p. 5702 - 5705]
[3]Location in patent: experimental part Nabid, Mohammad Reza; Rezaei, Seyed Jamal Tabatabaei; Ghahremanzadeh, Ramin; Bazgir, Ayoob [Ultrasonics Sonochemistry, 2010, vol. 17, # 1, p. 159 - 161]
[4]Tayade, Yogesh A.; Dalal, Dipak S. [Catalysis Letters, 2017, vol. 147, # 6, p. 1411 - 1421]
[5]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[6]Mohamadpour, Farzaneh [Journal of Photochemistry and Photobiology A: Chemistry, 2021, vol. 407]
[7]Ghorbani-Vaghei, Ramin; Noori, Samira; Toghraei-Semiromi, Zahra; Salimi, Zahra [RSC Advances, 2014, vol. 4, # 89, p. 47925 - 47928]
[8]Khazaei, Ardeshir; Zolfigol, Mohammad Ali; Karimitabar, Fatemeh; Nikokar, Iraj; Moosavi-Zare, Ahmad Reza [RSC Advances, 2015, vol. 5, # 87, p. 71402 - 71412]
[9]Location in patent: experimental part Shaterian, Hamid Reza; Mohammadnia, Majid [Journal of Molecular Liquids, 2012, vol. 173, p. 55 - 61]
[10]Shaterian, Hamid Reza; Mohammadnia, Majid [Research on Chemical Intermediates, 2014, vol. 40, # 1, p. 371 - 383]
[11]Ghorbani-Vaghei, Ramin; Mahmoodi, Jafar; Maghbooli, Yaser [Applied Organometallic Chemistry, 2017, vol. 31, # 10]

27
[ 1445-69-8 ]
[ 3660-90-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With phosphorus pentabromide at 140℃; Sealed tube;	4 Preparation 41,4-DibromophthalazineCharge a pressure tube with phosphorus pentabromide (24.5 g, 54 1 mmol) and 2,3-dihydro-phthalazine-1,4-dione (5.00 g, 30.8 mmol). Seal the tube and heat at 140° C. for 6-7 h. Allow to cool overnight. Carefully open the tube due to pressure. Chisel out the solid and pour into ice water. Allow to stir in ice water and collect the resulting solid by vacuum filtration. Dry in a vacuum oven to obtain the final product (8.31 g, 93%). ES/MS (79Br, 81Br) m/z 288.8 (M+). Ref.: Can. J. Chem. 1965, 43, 2708.
88%	With phosphorus(V) oxybromide In 1,2-dichloro-ethane at 100℃; for 18h;	4.1.1. Synthesis of 1,4-dibromophthalazine (2) Phosphorus oxybromide (861 mg, 3.0 mmol) was added to a stirred suspension of 2,3-dihydrophthalazine-1,4-dione (162 mg, 1.0 mmol) in 1,2-dichloroethane (5 mL). The mixture was heated to 100 °C for 18 h and poured into water (100 mL) upon cooling to rt The aqueous layer was neutralized with saturated Na2CO3 solution and concentrated to give a residue, which was washed with water to afford the product as a white solid. Yield: 88%, m.p. 160.1-161.6 °C. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.37-8.33 (m, 2H), 8.12-8.08 (m, 2H). GC-MS (EI): m/z calc. 285.8, m/z found 285.8.
83%	With phosphorus(V) oxybromide In 1,2-dichloro-ethane at 100℃; for 18h;	1.1 1) Intermediate product synthesis phosphorus oxybromide (53.1 g, 185.0 mmol) was slowly added dropwise. For 18 hours and the mixture was stirred for 100 deg C . The reaction solution was cooled to room temperature, and the reaction solution was poured into distilled water. The aqueous solution was neutralized with saturated Na2CO3 solution and the product was washed several times with distilled water to give a yield of 83% white solid.

71%	With carbon tetrabromide; phosphorus pentabromide at 80 - 130℃; for 6h;	2 Synthesis of 1,4-dibromophthalazine The title compound was prepared using a modification of a previously reported procedure [30]. To a round bottomed flask equipped with a stir bar and reflux condenser was added a mixture of 1,4-phthalahydrazide (1.375g, 8.49mmol) and carbon tetrabromide (85g). The reaction mixture was heated to 80°C and phosphorous pentabromide (9.135g, 21.2mmol, 2.5eq.) introduced. The temperature was then raised to 130°C and stirred at this temperature for 6h. After cooling to room temperature, the solid mass was treated with CH2Cl2 (60mL) until all lumps had been disintegrated to form a suspension. This mixture was then added to ice water (250mL) and stirred overnight. The organic layer was extracted and dried over magnesium sulfate. Following filtration, the filtrate was concentrated until a paste was formed; the paste was filtered and washed with copious amounts of hexane. The crude product was recrystallised from hot THF and left to stand at -30°C overnight. The yellow needles were collected and dried; additional crops of the product were combined (71%, 1.721g). Mp: 156-158°C (lit. [30]: 160°C). 1H NMR (300MHz, CDCl3, 298K): δ 8.05 (dd, J(HH) 6.3, 3.0, Ar-H), 8.29 (dd, J(HH) 6.3, 3.0, Ar-H). IR (cm-1) 2353 (br s), 1873 (br m), 1601 (w), 1558 (m), 1496 (w), 1471 (s), 1404 (s), 1344 (m), 1295 (s), 1255 (s), 1151 (w), 1139 (w), 1055 (w), 993 (s), 944 (m), 796 (s), 773 (s). FABMS: m/z 288 [M]+. HRMS (FAB): calcd for C8H5N279Br2 [M+H]+ 286.88195, found 286.88190.
	With phosphorus(V) oxybromide In 1,2-dichloro-ethane Reflux;
	With phosphorus(V) oxybromide In 1,2-dichloro-ethane Reflux;

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US2010/324048, 2010, A1 Location in patent: Page/Page column 4
[2]Gao, Rui; Liao, Sha; Zhang, Chen; Zhu, Weilong; Wang, Liyan; Huang, Jin; Zhao, Zhenjiang; Li, Honglin; Qian, Xuhong; Xu, Yufang [European Journal of Medicinal Chemistry, 2013, vol. 62, p. 597 - 604]
[3]Current Patent Assignee: LG DISPLAY CO.,LTD. - KR2017/79353, 2017, A Location in patent: Paragraph 0256; 0257-0259
[4]Savjani, Nicky; Singh, Kuldip; Solan, Gregory A. [Inorganica Chimica Acta, 2015, vol. 436, p. 184 - 194]
[5]Wang, Wei; Feng, Xiu; Liu, Huan-Xiang; Chen, Shi-Wu; Hui, Ling [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3217 - 3226]
[6]Chen, Shi-Wu; Hao, Shu-Yi; Mou, Hong-Xia; Wang, Shuai; Xu, Yu; Zhang, Xiu-Juan [Bioorganic and Medicinal Chemistry Letters, 2020, vol. 30, # 23]

28
(1R,3S)-2-(3-hydroxycyclohexyl)isoindole-1,3-dione [ No CAS ]
[ 1445-69-8 ]
[ 1110772-04-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 892 - 898

29
[ 1445-69-8 ]
[ 126-81-8 ]
[ 6334-18-5 ]
[ 1278520-01-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With N,N,N?,N?-tetrabromobenzene-1,3-disulfonamide; at 100℃; for 0.166667h;	General procedure: A mixture of dimedone (0.28 g, 2 mmol), phthalhydrazide (0.32 g, 2 mmol), benzaldehyde (0.24 g, 2.2 mmol), and TBBDA (0.05 g) or PBBS (0.1 g) was heated at 100 C for 10 min. After completion of the reaction [TLC acetone/n-hexane (3:10)]. The reaction mixture was cooled, filtered and washed with acetone (15 mL). Removal of the solvent under reduced pressure gave the catalyst. The crude product was recrystallized from ethyl acetate/n-hexane (1:3) to afford the pure product.
80%	With SBA-Pr-NH2; In neat (no solvent); at 80℃; for 0.166667h;Green chemistry;	General procedure: The SBA-Pr-NH2 (0.02 g) was activated under vacuum at 100 C and, after cooling to room temperature, aromatic aldehyde 1 (1 mmol), dimedone 2 (1 mmol, 0.14 g), and phthalhydrazide 3 (1 mmol, 0.16 g) were added. The mixture was heated at 80 C under solvent-free conditions until reaction was complete (monitored byTLC; petroleum ether-EtOAc, 4:1). The resulting solid product was dissolved in hot ethanol and the heterogeneous solid-base catalyst was removed by simple filtration. The filtrate was cooled to give the pure products 4a-j. The recovered catalyst washed consecutively with dilute Et3N solution, water, and acetone, then dried under vacuum.
70%	With sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H); In neat (no solvent); at 80℃; for 0.0833333h;Green chemistry;	General procedure: The SBA-Pr-SO3H (0.02 g) was activated in vacuum at 100 C. After cooling to room temperature, phthalhydrazide 1 (1 mmol, 0.16 g), aromatic aldehyde 2 (1 mmol), and dimedone 3 (1 mmol, 0.14 g) were added to it. The mixture was heated at 80 C under solvent-free condition until the reaction was completed. After completion of the reaction (monitored by TLC), the solid product was dissolved in hot ethanol (2 × 10 mL) and the heterogeneous solid catalyst was removed by simple filtration. Then, the filtrate was cooled to give the pure products 4a-k.

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2012,vol. 67,p. 717 - 724
[2]Tetrahedron,2011,vol. 67,p. 1930 - 1937
[3]Research on Chemical Intermediates,2015,vol. 41,p. 7581 - 7591
[4]Journal of the Chilean Chemical Society,2014,vol. 59,p. 2271 - 2274

30
[ 1445-69-8 ]
[ 454-89-7 ]
[ 126-81-8 ]
[ 1235563-45-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With phospho sulphonic acid In neat (no solvent) at 100℃; for 0.133333h;	Typical procedure for the preparation of indazolo[1,2-b]phthalazinetriones General procedure: A mixture of dimedone (0.14 g, 1.0 mmol), phthalhydrazide (0.16 g, 1.0 mmol), anaromatic aldehyde (1.1 mmol) and PSA (0.05 g) was heated at 100 °C for 10 min. Completion of the reaction was indicated by TLC [TLC acetone/n-hexane (3:10)]. After completion of the reaction, the insoluble crude product was dissolved in hot ethanol and phospho sulfuric acid was filtered off. The crude product was purified by recrystallization from ethanol to afford the pure product.
94%	With Fe₃O₄-SiO₂ core-shell nanoparticles at 120℃; for 0.2h; Green chemistry;	General procedure for the preparation of indazolo[1,2-b]-phthalazinetriones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide (0.16 g, 1 mmol), aldehyde (1 mmol), and Fe3O4 SiO2 (0.0 23 gr, 0.8 mmol, 8 mol%) was heated at 120°C for 10-20 min. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature and the solid obtained was dissolved in dichloromethane; the catalyst was insoluble in CH2Cl2 and separated by using an external magnet. The solvent was evaporated and the residue was recrystallized from ethanol to afford the pure indazolo[1,2-b]-phthalazinetriones.
89%	With 1,4'-(butane-1,4-diyl)bis(3-methylimidazolium)bis-[tetrachloroferrate(ΙΙΙ)] at 100℃; for 0.166667h; Green chemistry;

89%	With poly(ethylene glycol)-MDIL In neat (no solvent) at 100℃; for 0.166667h; Green chemistry;	Synthesis of 2H-indazolo [2, 1-b] phthalazinetriones derivatives: General Procedure General procedure: A mixture of dimedone (0.14 g, 1 mmol),phthalhydrazide (0.16 g, 1 mmol), an aromaticaldehyde (1.1 mmol) and PEG-MDIL (0.1 g) washeated at 100 °C for 10 min. Completion of the reactionwas indicated by TLC. After completion of the reaction,water (20 mL) was added to the mixture, and extractedproduct the insoluble crude product was dissolved inby ethyl acetate (3×10 mL). The organic phase wasseparated and evaporation of the solvent underreduced pressure. The solid product recrystallizedfrom ethanol to afford the pure product 4a-k.
85%	With dodecatungstosilic acid at 100℃; for 0.216667h; neat (no solvent);

Reference： [1]Kiasat, Ali Reza; Mouradzadegun, Arash; Saghanezhad, Seyyed Jafar [Journal of the Serbian Chemical Society, 2013, vol. 78, # 4, p. 469 - 476]
[2]Mirhosseini-Eshkevari, Boshra; Ghasemzadeh, Mohammad Ali; Safaei-Ghomi, Javad [Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7703 - 7714]
[3]Godajdar, Bijan Mombani; Kiasat, Ali Reza; Hashemi, Mohammad Mahmoodi [Heterocycles, 2013, vol. 87, # 3, p. 559 - 570]
[4]Godajdar, Bijan Mombani; Etamad, Masoumeh; Soliemani, Soghra [Oriental Journal of Chemistry, 2015, vol. 31, # 2, p. 1231 - 1236]
[5]Location in patent: experimental part Wang, Hong-Juan; Zhang, Xiao-Nan; Zhang, Zhan-Hui [Monatshefte fur Chemie, 2010, vol. 141, # 4, p. 425 - 430]

31
[ 1445-69-8 ]
[ 126-81-8 ]
[ 39515-51-0 ]
[ 1235563-43-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With dodecatungstosilic acid at 100℃; for 0.416667h; neat (no solvent);
85%	With Pentaerythritol In neat (no solvent) at 80℃; for 0.916667h; Green chemistry;	General procedure for synthesis of 2H-indazolo[1,2-b]phthalazine-triones General procedure: To a mixture consisting of 4-chlorobenzaldehyde (1 mmol, 0.14 g), dimedone (1 mmol, 0.14 g), and phthalhydrazine (1 mmol, 0.16 g) in a 10-ml round-bottomed flask was added pentaerythritol (0.1 mmol, 0.01 g), and the resulting mixture was stirred magnetically at 80 °C. After reaction completion as monitored by thin-layer chromatography (TLC), the reaction mixture was cooled, and acetone (10 ml) was added to it. After separation of catalyst, the solvent was removed under vacuum from the clear reaction mixture. The crude product was recrystallized from EtOH/H2O (3:2) to afford pure product.
84%	With citric acid at 80℃; for 0.333333h; Green chemistry;

Reference： [1]Location in patent: experimental part Wang, Hong-Juan; Zhang, Xiao-Nan; Zhang, Zhan-Hui [Monatshefte fur Chemie, 2010, vol. 141, # 4, p. 425 - 430]
[2]Farahmand, Shohreh; Ayazi-Nasrabadi, Roya; Mokhlesi, Mohammad; Zolfigol, Mohammad Ali [Research on Chemical Intermediates, 2019, vol. 45, # 7, p. 3795 - 3807]
[3]Zolfigol, Mohammad Ali; Mokhlesi, Mohammad; Farahmand, Shohreh [Journal of the Iranian Chemical Society, 2013, vol. 10, # 3, p. 577 - 581]

32
[ 1445-69-8 ]
[ 126-81-8 ]
[ 620-23-5 ]
[ 1235563-41-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With phospho sulphonic acid In neat (no solvent) at 100℃; for 0.166667h;	Typical procedure for the preparation of indazolo[1,2-b]phthalazinetriones General procedure: A mixture of dimedone (0.14 g, 1.0 mmol), phthalhydrazide (0.16 g, 1.0 mmol), anaromatic aldehyde (1.1 mmol) and PSA (0.05 g) was heated at 100 °C for 10 min. Completion of the reaction was indicated by TLC [TLC acetone/n-hexane (3:10)]. After completion of the reaction, the insoluble crude product was dissolved in hot ethanol and phospho sulfuric acid was filtered off. The crude product was purified by recrystallization from ethanol to afford the pure product.
90%	With dodecatungstosilic acid at 100℃; for 0.266667h; neat (no solvent);
88%	With sulfuric acid functionalized silica-coated magnetite nanoparticles with core-shell structure In neat (no solvent) at 100℃; for 0.583333h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2 H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol), benzaldehyde (0.13 g, 1.2 mmol), and Fe3O4(at)silica sulfuric acid (0.1 g) was heated at 100 °C for 35 min (TLC). After satisfactory completion of the reaction and cooling, the reaction mixture was washed with hot ethanol and the catalyst was removed by a magnetic field. The solid residue was isolated and purified by recrystallization in hot EtOH. The desired pure product(s) was characterized by comparison of their physical data with those of known.

88%	at 90℃; for 0.5h; Ionic liquid; Green chemistry;
88%	With 1,4-diazabicyclo[2.2.2]octane on amorphous silica from rice husk ash In ethanol for 0.666667h; Reflux; Green chemistry;	General procedure for the synthesis of phthalazine-trione derivatives General procedure: A mixture of phthalhydrazide (1mmol), dimedone (1mmol), aldehyde (1.2mmol), and RHDABCO (0.1g) was heated in ethanol for the time shown in Table3. The completion of the reaction was indicated by TLC. After satisfactory completion of the reaction, the reacted mixture was washed using hot ethanol, and the catalyst was fltered. The solid residue was purifed by recrystallization in aqueous EtOH.
87%	With Fe₃O₄-SiO₂ core-shell nanoparticles at 120℃; for 0.283333h; Green chemistry;	General procedure for the preparation of indazolo[1,2-b]-phthalazinetriones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide (0.16 g, 1 mmol), aldehyde (1 mmol), and Fe3O4 SiO2 (0.0 23 gr, 0.8 mmol, 8 mol%) was heated at 120°C for 10-20 min. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature and the solid obtained was dissolved in dichloromethane; the catalyst was insoluble in CH2Cl2 and separated by using an external magnet. The solvent was evaporated and the residue was recrystallized from ethanol to afford the pure indazolo[1,2-b]-phthalazinetriones.

Reference： [1]Kiasat, Ali Reza; Mouradzadegun, Arash; Saghanezhad, Seyyed Jafar [Journal of the Serbian Chemical Society, 2013, vol. 78, # 4, p. 469 - 476]
[2]Location in patent: experimental part Wang, Hong-Juan; Zhang, Xiao-Nan; Zhang, Zhan-Hui [Monatshefte fur Chemie, 2010, vol. 141, # 4, p. 425 - 430]
[3]Kiasat, Ali Reza; Davarpanah, Jamal [Journal of Molecular Catalysis A: Chemical, 2013, vol. 373, p. 46 - 54]
[4]Patil, Audumbar; Lohar, Trushant; Mane, Ananda; Kamat, Siddharth; Salunkhe, Rajashri [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 11, p. 3145 - 3151]
[5]Davarpanah, Jamal; Davoodi, Ghazal; Ghahremani, Mahboubeh; Rezaee, Parizad [Research on Chemical Intermediates, 2020]
[6]Mirhosseini-Eshkevari, Boshra; Ghasemzadeh, Mohammad Ali; Safaei-Ghomi, Javad [Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7703 - 7714]

33
[ 6341-92-0 ]
[ 1445-69-8 ]
[ 13361-30-3 ]
[ 1334176-11-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With nickel dichloride In PEG 600 at 100℃; for 3.5h;	4.2. General procedure for synthesis of pyrazolophthalazinyl spirooxindoles General procedure: A mixture of isatin 1 (1.0 mmol), malononitrile or cyanoacetic ester 2 (1.0 mmol), phthalhydrazide (1.0 mmol), and NiCl2 (0.2 mmol) in PEG 600 (5 mL) was stirred at 100 °C for the appropriate time (refPreviewPlaceHolderTable 2). After complete conversion as indicated by TLC, water was added and the product was extracted with ethyl acetate (2×10 ml). The organic phase was dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was recrystallized from ethanol to afford the pure product.

Reference： [1]Location in patent: experimental part Zhang, Xiao-Nan; Li, Yong-Xiao; Zhang, Zhan-Hui [Tetrahedron, 2011, vol. 67, # 38, p. 7426 - 7430]

34
[ 6326-79-0 ]
[ 1445-69-8 ]
[ 13361-30-3 ]
[ 1334176-12-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	With nickel dichloride In PEG 600 at 100℃; for 3.5h;	4.2. General procedure for synthesis of pyrazolophthalazinyl spirooxindoles General procedure: A mixture of isatin 1 (1.0 mmol), malononitrile or cyanoacetic ester 2 (1.0 mmol), phthalhydrazide (1.0 mmol), and NiCl2 (0.2 mmol) in PEG 600 (5 mL) was stirred at 100 °C for the appropriate time (refPreviewPlaceHolderTable 2). After complete conversion as indicated by TLC, water was added and the product was extracted with ethyl acetate (2×10 ml). The organic phase was dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was recrystallized from ethanol to afford the pure product.

Reference： [1]Location in patent: experimental part Zhang, Xiao-Nan; Li, Yong-Xiao; Zhang, Zhan-Hui [Tetrahedron, 2011, vol. 67, # 38, p. 7426 - 7430]

35
[ 20780-77-2 ]
[ 1445-69-8 ]
[ 105-56-6 ]
[ 1334176-09-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With nickel dichloride; In PEG 600; at 100℃; for 2.3h;	General procedure: A mixture of isatin 1 (1.0 mmol), malononitrile or cyanoacetic ester 2 (1.0 mmol), phthalhydrazide (1.0 mmol), and NiCl2 (0.2 mmol) in PEG 600 (5 mL) was stirred at 100 C for the appropriate time (refPreviewPlaceHolderTable 2). After complete conversion as indicated by TLC, water was added and the product was extracted with ethyl acetate (2×10 ml). The organic phase was dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was recrystallized from ethanol to afford the pure product.

Reference： [1]Tetrahedron,2011,vol. 67,p. 7426 - 7430

36
[ 20780-77-2 ]
[ 1445-69-8 ]
[ 109-77-3 ]
[ 1334175-99-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With nickel dichloride; In PEG 600; at 100℃; for 1.0h;	General procedure: A mixture of isatin 1 (1.0 mmol), malononitrile or cyanoacetic ester 2 (1.0 mmol), phthalhydrazide (1.0 mmol), and NiCl2 (0.2 mmol) in PEG 600 (5 mL) was stirred at 100 C for the appropriate time (refPreviewPlaceHolderTable 2). After complete conversion as indicated by TLC, water was added and the product was extracted with ethyl acetate (2×10 ml). The organic phase was dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was recrystallized from ethanol to afford the pure product.

Reference： [1]Tetrahedron,2011,vol. 67,p. 7426 - 7430

37
[ 20780-77-2 ]
[ 1445-69-8 ]
[ 105-34-0 ]
[ 1334176-04-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With nickel dichloride; In PEG 600; at 100℃; for 3.0h;	General procedure: A mixture of isatin 1 (1.0 mmol), malononitrile or cyanoacetic ester 2 (1.0 mmol), phthalhydrazide (1.0 mmol), and NiCl2 (0.2 mmol) in PEG 600 (5 mL) was stirred at 100 C for the appropriate time (refPreviewPlaceHolderTable 2). After complete conversion as indicated by TLC, water was added and the product was extracted with ethyl acetate (2×10 ml). The organic phase was dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was recrystallized from ethanol to afford the pure product.

Reference： [1]Tetrahedron,2011,vol. 67,p. 7426 - 7430

38
[ 1445-69-8 ]
[ 555-16-8 ]
[ 123-54-6 ]
[ 1350913-03-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With diethanolammonium chloroacetate at 140℃; for 6h;
88%	With sulfuric acid functionalized silica-coated magnetite nanoparticles with core-shell structure In neat (no solvent) at 100℃; for 0.583333h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2 H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol), benzaldehyde (0.13 g, 1.2 mmol), and Fe3O4(at)silica sulfuric acid (0.1 g) was heated at 100 °C for 35 min (TLC). After satisfactory completion of the reaction and cooling, the reaction mixture was washed with hot ethanol and the catalyst was removed by a magnetic field. The solid residue was isolated and purified by recrystallization in hot EtOH. The desired pure product(s) was characterized by comparison of their physical data with those of known.
88%	With SBA-15 modified by 1-(triethoxysilylpropyl)-3-methylimidazolium hydrogen sulfate In ethanol for 0.5h; Reflux;	Typical procedure for preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol),benzaldehyde (0.13 g, 1.2 mmol), and [SBA-Im]HSO4 (0.1 g) was heated under reflux in ethanol for 30 min. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was washed with hot ethanol and the catalyst was isolated by filtration. The crude product was purified by recrystallization in aqueous ethanol to afford the pure product, which was characterized by comparison of its physical properties with those of a standard.

85%	With (S)-camphorsulfonic acid at 80℃; for 0.583333h; Neat (no solvent);	General procedure for the synthesis of compounds 4 and 6: (I) Conventional Method: General procedure: To a thoroughly homogenated mixture of phthalhydrazide 1 (1.0 mmol), cyclic/acyclic 1,3-diketone 2 (1.1 mmol), and aldehyde 3 (1.1 mmol), (S)-CSA (0.046 g, 0.2 mmol) was added. The reaction mixture was heated at 80 °C for a stipulated period of time (refPreviewPlaceHolderTable 2). After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature and washed twice with water. The product obtained was purified by crystallization from ethyl acetate-n-hexane (1:3) or by column chromatography (in case of acyclic 1,3-diketones) over silica gel (Merck, 60-120 mesh, ethyl acetate-n-hexane, 1:3).
82%	With 1,4-diazabicyclo[2.2.2]octane on amorphous silica from rice husk ash In ethanol for 0.75h; Reflux; Green chemistry;	General procedure for the synthesis of phthalazine-dione derivatives General procedure: Under ethanol refux, a mixture of phthalhydrazide (0.16g, 1mmol), acetyl acetone (0.14g, 2mmol), aldehyde (1mmol), and RHDABCO (0.1g) was heated for the appropriate time (Table3). The completion of the reaction was indicated by TLC. After satisfactory completion of the reaction, the reacted mixture was washed using hot ethanol, and the catalyst was fltered. The solid residue was purifed by recrystallization in aqueous EtOH.
70%	With nano-γ-aluminasulforic acid at 110℃; for 1h;	Typical procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-triones A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) or acetyl acetone(0.20 g, 2 mmol), phthalhydrazide (0.16 g, 1 mmol), aromatic aldehyde(1 mmol) together with Nano-ASA (0.04 g) was heated at 110 C for the corresponding time (see Table 2 and 3). Completion of the reaction was indicated by TLC [TLC acetone/n-hexane (3:10)]. After completion of the reaction, the solid residue was dissolved in ethanol and nano-alumina sulfuric acid was filtered. The crude product was purified by recrystallization in aqueous ethanol to afford the pure product

Reference： [1]Simijonović, Dušica; Petrović, Zorica D.; Milovanović, Vesna M.; Petrović, Vladimir P.; Bogdanović, Goran A. [RSC Advances, 2018, vol. 8, # 30, p. 16663 - 16673]
[2]Kiasat, Ali Reza; Davarpanah, Jamal [Journal of Molecular Catalysis A: Chemical, 2013, vol. 373, p. 46 - 54]
[3]Davarpanah, Jamal; Rezaee, Parizad; Elahi, Somayeh [Research on Chemical Intermediates, 2015, vol. 41, # 12, p. 9903 - 9915]
[4]Location in patent: experimental part Shukla, Gaurav; Verma, Rajiv K.; Verma, Girijesh K.; Singh, Maya Shankar [Tetrahedron Letters, 2011, vol. 52, # 52, p. 7195 - 7198]
[5]Davarpanah, Jamal; Davoodi, Ghazal; Ghahremani, Mahboubeh; Rezaee, Parizad [Research on Chemical Intermediates, 2020]
[6]Kiasat, Ali Reza; Noorizadeh, Siamak; Ghahremani, Mahboubeh; Saghanejad, Seyed Jafar [Journal of Molecular Structure, 2013, vol. 1036, p. 216 - 225]

39
[ 179820-15-6 ]
[ 1445-69-8 ]
[ 31576-51-9 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 1152 - 1155

40
[ 1445-69-8 ]
[ 90-02-8 ]
[ 126-81-8 ]
[ 1365999-54-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	With succinimidinium N-sulfonic acid hydrogen sulfate In neat (no solvent) at 100℃; for 0.333333h;	synthesis of 2H-indazolo[1,2-b]phthalazine-triones General procedure: A mixture of aldehyde (1 mmol), 1,3-cyclic diketone (1 mmol),phthalhydrazide (1 mmol) and [SuSA-H]HSO4 (27.7 mg, 0.1 mmol,10 mol%) was stirred in an oil-bath at 100 °C under solvent-free conditions. After completion of the reaction [monitored by TLC: nhexane:ethyl acetate (8:2)], the reaction mixture was cooled, H2O(5 mL) was added to it and filtered to separate the catalyst. The solidresidue was recrystallized from ethanol to give the pure product.
93%	With nano (SO₃H functionalized mesoporous silica) In neat (no solvent) at 110℃; for 0.4h; Sealed tube; Green chemistry;
92%	With montmorillonite K-10 at 80℃; for 0.216667h; Neat (no solvent); Microwave irradiation;	4.2. Synthesis of 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione (4b) General procedure: A mixture of phthalhydrazide (1, 162 mg, 1 mmol), 3-fluorobenzaldehyde (2b, 105 mg, 1 mmol), 5,5-dimethyl-cyclohexane-1,3-dione (3, 140 mg, 1 mmol) and K-10 (5 mol %, 50 mg) was taken in an open vessel and irradiated at 80 °C in solvent-free condition for 5 min. The reactions were followed by thin layer chromatography (TLC) using hexane/ethyl acetate (3:1) as an eluent (Rf=0.70). After completion of the reaction, the mixture was washed with ethyl acetate and filtered to recover the catalyst. The filtrate was evaporated, and the crude product was recrystallized from ethanol to afford pure 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo-[2,1-b]phthalazine-1,6,11(13H)-trione (4b) in excellent yield (380 mg).

91%	With sulfonic acid grafted onto TiO₂-coated nickel ferrite nanoparticles In neat (no solvent) at 80℃; for 0.333333h;	General procedure for synthesisof 2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol), and nanocatalyst(0.03 g) was heated at 80 °C for 10 min (TLC). Aftercooling, the reaction mixture was poured in 10 mL of DMFand the catalyst was separated easily by an external magnet.The saturated sodium chloride solution was then added to precipitate the pure product.
90%	With 4,4'-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium) tetrachloride In neat (no solvent) at 80℃; for 0.333333h;	2.6. General Procedure for the Preparation of 2HIndazolo[2,1-b]Phthalazine-1,6,11(13H)-Triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedoneand/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide(1.0 mmol) and NS-[C4(DABCO-SO3H)2] · 4Cl (0.010 g, 5 mol%) was heated in an oil bath (80 C)under solvent-free conditions for the appropriate time. The reaction was monitored by TLC [n-hexane:ethylacetate(10:2)]. After completion, the reaction mass was cooledto room temperature and washed with water for the separationof the catalyst. The solid product was purified byre-crystallization in aqueous EtOH (25%). The productswere characterized by comparison of their physical datawith those of known compounds.
85%	In neat (no solvent) at 80℃; for 0.333333h;	2.4. General procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones General procedure: A mixture of the requested aldehyde (1.0 mmol), dimedone and/or 1,3-cyclohexadione (1.0 mmol), phthalhydrazide (1.0 mmol) and [DABCO](SO3H)2(HSO4)2 (0.014 g, 0.03 mmol) was heated in an oil bath (80 °C) under solvent free conditions for the appropriate time. The reaction was monitored by TLC (n-hexane: ethyl acetate). After completion, the reaction mass was cooled to room temperature and washed with water for the separation of the catalyst. The solid product was purified by re-crystallization in aqueous EtOH (25%). The products were characterized by comparison of their physical data with those of known compounds.
83%	Stage #1: salicylaldehyde; dimedone With dodecylphosphonic acid for 0.0833333h; Neat (no solvent); Stage #2: 2,3-dihydrophthalazine-1,4-dione at 80℃; for 0.166667h; Neat (no solvent);	General procedure for the synthesis of 2H-indazolo[2,1-b]phthalazine-trione derivatives: General procedure: In a 50 mL round bottom flask, the required amount of aromatic aldehydes (1 mmol), 1,3-dicarbonyl compounds (1 mmol), and dodecylphosphonic acid (DPA) (10 mol %) were added and the mixture was stirred over a magnetic stirrer. After 5 min, to this stirred mixture, phthalhydrazide (1.5 mmol) was added and the contents were stirred at 80 °C for an appropriate time. The progress of reaction was monitored by TLC. After completion of the reaction, the reaction mixture was allowed to cool at room temperature and washed with water. The crude product was crystallized with ethanol, which was further purified by silica gel column chromatography (hexane/ethylacetate 70:30) to give the desired products. All the products were characterized by comparing their physical (MPs) and spectral data with those reported earlier. After the evaporation of aqueous layer, the catalyst was recovered and reused for next reaction.
80%	With sulfonic acid functionalized nanoporous silica (SBA-Pr-SO₃H) In neat (no solvent) at 80℃; for 0.25h; Green chemistry;	General Procedure for the Synthesis of 2H-Indazolo[1,2-b]phthalazinetrione Derivatives (4a-k) General procedure: The SBA-Pr-SO3H (0.02 g) was activated in vacuum at 100 °C. After cooling to room temperature, phthalhydrazide 1 (1 mmol, 0.16 g), aromatic aldehyde 2 (1 mmol), and dimedone 3 (1 mmol, 0.14 g) were added to it. The mixture was heated at 80 °C under solvent-free condition until the reaction was completed. After completion of the reaction (monitored by TLC), the solid product was dissolved in hot ethanol (2 × 10 mL) and the heterogeneous solid catalyst was removed by simple filtration. Then, the filtrate was cooled to give the pure products 4a-k.
65%	With 1-sulfonic acid-3,5,7-trimethylpurinium-5,7-dione hydrogen sulfate In neat (no solvent) at 100℃; for 0.25h; Green chemistry;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione General procedure: A mixture of dimedone (0.035 g, 0.25 mmol), phthalhydrazide (0.040 g, 0.25 mmol), benzaldehyde (0.026 g, 1 mmol), and 3-sulfonic acid imidazopyridinium hydrogen sulfate (10 mmol) was heated at 100°C for 10 min. After cooling, the residue was re-crystallized from ethanol to afford the corresponding pure product.

Reference： [1]Abedini, Masoumeh; Shirini, Farhad; Omran, Javad Mohammad-Alinejad [Journal of Molecular Liquids, 2015, vol. 212, p. 405 - 412]
[2]Amiri, Ali Alinasab; Javanshir, Shahrzad; Dolatkhah, Zahra; Dekamin, Mohammad G. [New Journal of Chemistry, 2015, vol. 39, # 12, p. 9665 - 9671]
[3]Location in patent: experimental part Veeranarayana Reddy, Mudumala; Reddy, Gangireddy Chandra Sekhar; Jeong, Yeon Tae [Tetrahedron, 2012, vol. 68, # 34, p. 6820 - 6828]
[4]Hamidinasab, Mahdia; Mobinikhaledi, Akbar [Journal of the Iranian Chemical Society, 2019, vol. 16, # 6, p. 1255 - 1263]
[5]Goli-Jolodar, Omid; Shirini, Farhad; Seddighi, Mohadeseh [Journal of Nanoscience and Nanotechnology, 2018, vol. 18, # 1, p. 591 - 603]
[6]Shirini, Farhad; Langarudi, Mohaddeseh Safarpoor Nikoo; Goli-Jolodar, Omid [Dyes and Pigments, 2015, vol. 123, p. 186 - 195]
[7]Kidwai, Mazaahir; Jahan, Anwar; Chauhan, Ritika; Mishra, Neeraj Kumar [Tetrahedron Letters, 2012, vol. 53, # 14, p. 1728 - 1731]
[8]Ziarani, Ghodsi Mohammadi; Badiei, Alireza; Mohtasham, Nina Hosseini; Lashgari, Negar [Journal of the Chilean Chemical Society, 2014, vol. 59, # 1, p. 2271 - 2274]
[9]Tayebee, Reza; Jomei, Malihe; Maleki, Behrooz; Razi, Maryam Kargar; Veisi, Hojat; Bakherad, Mohammad [Journal of Molecular Liquids, 2015, vol. 206, p. 119 - 128]

41
[ 1445-69-8 ]
[ 135-02-4 ]
[ 109-77-3 ]
[ 1384462-33-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With Caesium carbonate supported on hydroxyapatite-encapsulated Ni_0.5Zn_0.5Fe₂O₄ nanocrystallites In neat (no solvent) at 110℃; for 0.25h;
97%	With 4-dimethylaminopyridine In ethanol for 1h; Reflux; Green chemistry;	4.1 General procedure General procedure: A mixture of aromatic aldehyde 1 (1.1mmol), malononitrile2 (1.1 mmol), phthalhydrazide 3 (1.0 mmol), and DMAP (20mol%) was placed in 10mL of ethanol. The reactionmixture was then refluxed for appropriate time (the reactionwas monitored by thin-layer chromatography; seeTable 1). After completion, ethanol was evaporated undervacuum and 10mL of water was added. The resulting solidwas filtered, and washed with water and then hexane. Thestructures of the products were fully established on thebasis of their 1H NMR, 13C NMR, and IR spectra as well asMS spectral analysis.
95%	With sodium bromide In propyl alcohol at 20℃; for 0.0833333h; Electrolysis;	5 General procedure for electrochemical synthesis of pyrazolo[1,2-b]phthalazines General procedure: A solution of phthalhydrazide (1.0 mmol), various arylaldehydes (1.0 mmol), and malononitrile (1.0 mmol) andsodium bromide (0.1 mmol) in n-propanol (10 mL) waselectrolyzed in an undivided cell equipped with a magneticstirrer, a platinum anode and an iron cathode at roomtemperature under a constant current density of 12 mA/cm2 (I = 60 mA, electrodes square 5 cm2).The progress of the reaction was monitored by thinlayer chromatography. After completion of the reaction (4-8 minutes), the obtained precipitate was filtered, and thefilter cake was washed with ethanol to yield pure products(4a-k).

95%	With N,N,N-tributylbutan-1-aminium fluoride In lithium hydroxide monohydrate at 75℃; for 0.666667h; Sonication;	General procedure for compounds 4a-4l and 5a-5c General procedure: A mixture of phthalhydrazide (1.0 mmol), an arylaldehyde (1.0 mmol) or isatin derivative (1.0 mmol), and malononitrile (1.0 mmol) in 5 mL of water was subjected to ultrasound irradiation (45 kHz) in the presence of TBAF (0.4 mmol) at 75°C for the appropriate time (Table 3). Upon completion of the reaction (monitored by TLC), the reaction mixture was cooled down to room temperature. The precipitate was filtered off and washed with ethanol to yield pure products 4a-4l and 5a-5c.
94%	With Bromoeosine In lithium hydroxide monohydrate at 20℃; for 3h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
91%	In lithium hydroxide monohydrate at 20℃; for 4h; Irradiation; Green chemistry;	2.3. The overall process of preparing (7a-r) General procedure: Multifarious reagents including phthalhydrazide (5, 1.0 mmol),malononitrile (2, 1.0 mmol) and aromatic aldehydes (6a-r, 1.0 mmol)were reacted opposed to CFL (23 W) irradiation at room temperature inaqueous ethyl lactate (2:1, 3 mL) (Scheme 2). This was observed by TLCthat employed (ethyl acetate/n-hexane (1:3)). Afterwards, the filteringof the acquired solid was conducted, then the solid was rinsed water (2 ×3 mL) and ethanol (2 × 3 mL) and solid composition became recrystallizedby EtOH. The products were classified after the comparison ofspectroscopic information (1H NMR). Support for this manuscript can befound in the online version.
90%	With Al-KIT-6 ⁽³³⁾ In ethanol at 60℃; for 4h;
89%	With N,N,2,2,6,6-hexamethyl-N-(3-(trimethoxysilyl)propyl)piperidin-4-ammonium iodide grafted onto TiO₂-coated NiFe₂O₄ nanocatalyst at 80℃; for 0.75h; Green chemistry;
86%	With copper(II) oxide In neat (no solvent) at 100℃; for 0.5h; Green chemistry;	General procedure for synthesis 1H-pyrazolo[1,2-b]phthalazine-5,10-diones General procedure: A mixture of phthalhydrazide (1 mmol), malononitrile(1 mmol), aldehyde (1 mmol) and CuO NPs (10 mol%) wasstirred at 100 °C under solvent-free condition for requiredtime. The progress of the reaction was monitored by thinlayerchromatography (TLC, petroleum ether:ethyl acetate,8:2). After completion, the reaction mixture was cooled andresidue obtained was solved in 10 mL of ethyl acetate andcentrifuged to separate the CuO NPs. Evaporation of solventleft the crude solid product which was recrystallized fromethanol to afford the pure 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives.
85%	With piperazine immobilized on shell of NiFe₂O₄-TiO₂core-shell nanoparticles via propylsilyl linkage at 80℃; for 1h;	General procedure for the preparation of mono- and bispyrazolophthalazinederivatives (compounds 4 and 6) General procedure: A mixture of malononitrile (0.099 g, 1.5 mmol), phthalhydrazide(0.194 g, 1.2 mmol), appropriate aldehydes (1 mmol), and the nanocatalyst(0.03 g) was heated in PEG400 at 80 C for approximately 60min. After completion of the reaction monitored by TLC, the mixturewas cooled down to room temperature. Initially, the nanocatalyst wasseparated easily by an external magnet and reused for the reaction.Afterwards, the mixture was quenched by iced water. The precipitate was filtered and recrystallized in EtOH to afford the pure products. Itshould be noted that for preparation of bis-pyrazolephthalazine derivatives,malononitrile (0.198 g, 3.0 mmol), phthalhydrazide (0.388 g,2.4 mmol), nanocatalyst (0.05 g) and dialdehydes (1.0 mmol) were usedand the reaction was performed at 90 C for 90 min.
85%	With diethylenetriamine functionalized Zeolite HY In ethanol for 1h; Reflux; Green chemistry;	General procedure for the synthesis of mono 3-amino-1-aryl-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitriles General procedure: A mixture of malononitrile (0.1 g, 1.5 mmol), phthalhydrazide 0.16 g, 1 mmol), aryl aldehyde (1 mmol), and Zeolite HY(at)DETA as catalyst (15 mg) was refluxed in EtOH (15 mL) as a solvent. The reaction progress was followed using the TLC technique (20-30 min). Finally, the reaction mixture was filtered to separate the catalyst, then the filtrate was evaporated and the solid residue recrystallized from ethanol to give the pure product.
81%	In neat (no solvent) at 100℃; for 0.5h;	Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and pyrazolo[1,2-a][1,2,4]triazole-1,3-diones General procedure: A mixture of aldehyde 2 (1.0 mmol), malononitrile 1 (1.0 mmol), phthalhydrazide 3(1.0 mmol) or phenylurazole 5 (1.0 mmol) and Cu-ZnO hollow spheres (0.02 g) wereplaced in a test tube. The reaction mixture was then heated at 100 C for an appropriatetime (Tables 2 and 3) until the completion of the reaction was achieved as monitoredby TLC. Then, the crude product was dissolved in hot ethyl acetate and then filtered toremove the solid catalyst. The filtrate was cooled to give the pure organic product, identifiedby comparison of the observed melting point with the literature value.Representative spectroscopic data for selected examples are shown below, for the sakeof completeness.
80%	With N,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide In lithium hydroxide monohydrate at 80℃; for 0.5h; Green chemistry;
	With pyrrolidine acetic acid at 20℃; for 0.166667h; Neat (no solvent);
	With magnetic Fe₃O₄ nanoparticles coated by (3-aminopropyl)triethoxysilane at 20℃; for 0.233333h;
277 mg	With piperidinium benzene-1,3-disulfonate Fe₃O₄ magnetic nanoparticle ionic liquid In neat (no solvent) at 110℃; for 1h;
	With guanidine-modified SiO₂/perlite nanoparticles In ethanol at 78℃; Green chemistry;	2.5. General procedure for the preparation of 1H-pyrazolo[1,2-b] phthalazine-5,10-dione derivatives General procedure: In a general procedure, a mixture of phtalimide (1 mmol), hydrazinehydrate (1 mmol) and optimized amount of perlite NPs/SiO 2 /guanidine (0.009 g) was stirred in a 50 mL round-bottom flask containing 5 mL ethanol as solvent, under conventional heat- ing conditions at 78 °C for 90 min to obtain the white precipi- tate of phtalhydrazide. Then malononitrile (or ethyl cyano acetate) (1 mmol) and aldehyde derivative (1 mmol) were added to the mixture. After completion of the reaction (controlled by TLC: n- hexane/ethyl acetate 2:1), hot methanol was added and catalyst was separated by filtration. After evaporation of solvent, the pure product was obtained. The results of one-pot synthesis of 1H- pyrazolo[1,2-b] phthalazine-5,10-dione derivatives in the presence of perlite NPs/SiO 2 /guanidine are summarized in Table 2 .

Reference： [1]Maleki, Behrooz; Barat Nam Chalaki, Samaneh; Sedigh Ashrafi, Samaneh; Rezaee Seresht, Esmail; Moeinpour, Farid; Khojastehnezhad, Amir; Tayebee, Reza [Applied Organometallic Chemistry, 2015, vol. 29, # 5, p. 290 - 295]
[2]Lamera, Esma; Bouacida, Sofiane; Merazig, Hocine; Chibani, Aissa; Le Borgne, Marc; Bouaziz, Zouhair; Bouraiou, Abdelmalek [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2017, vol. 72, # 5, p. 361 - 368]
[3]Kefayati, Hassan; Amlashi, Shadi Homayoon; Kazemi-Rad, Reyhaneh; Delafrooz, Adeleh [Comptes Rendus Chimie, 2014, vol. 17, # 9, p. 894 - 898]
[4]Kefayati; Delafrooz; Homayoon [Russian Journal of General Chemistry, 2016, vol. 86, # 7, p. 1735 - 1740][Zh. Obshch. Khim., 2016, vol. 86, # 7, p. 1735 - 1740]
[5]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[6]Mohamadpour, Farzaneh [Journal of Photochemistry and Photobiology A: Chemistry, 2021, vol. 407]
[7]Location in patent: experimental part Karthikeyan; Pandurangan [Journal of Molecular Catalysis A: Chemical, 2012, vol. 361-362, p. 58 - 67]
[8]Hamidinasab, Mahdia; Bodaghifard, Mohammad Ali; Mobinikhaledi, Akbar [Applied Organometallic Chemistry, 2020, vol. 34, # 2]
[9]Patil, Sonatai; Mane, Ananda; Dhongade-Desai, Savita [Journal of the Iranian Chemical Society, 2019, vol. 16, # 8, p. 1665 - 1675]
[10]Hamidinasab, Mahdia; Ameri, Alieh; Hekmat, Azadeh; Forootanfar, Hamid; Mortezazadeh, Tohid; Bodaghifard, Mohammad Ali; Peytam, Fariba; Esmaeili, Rezvan; Foroumadi, Alireza; Sharifzadeh, Mohammad; Mobinikhaledi, Akbar; Khoobi, Mehdi [Bioorganic and Medicinal Chemistry, 2021, vol. 30]
[11]Hamidinasab, Mahdia; Ghasemi, Meisam; Bodaghifard, Mohammad Ali [Synthetic Communications, 2021, vol. 51, # 22, p. 3435 - 3448]
[12]Maleki, Behrooz; Nejat, Razieh; Alinezhad, Heshmatollah; Mousavi, Seyed Mohsen; Mahdavi, Behnam; Delavari, Maryam [Organic Preparations and Procedures International, 2020, p. 1 - 12]
[13]Khazaei, Ardeshir; Zolfigol, Mohammad Ali; Karimitabar, Fatemeh; Nikokar, Iraj; Moosavi-Zare, Ahmad Reza [RSC Advances, 2015, vol. 5, # 87, p. 71402 - 71412]
[14]Location in patent: experimental part Shaterian, Hamid Reza; Mohammadnia, Majid [Journal of Molecular Liquids, 2012, vol. 173, p. 55 - 61]
[15]Shaterian, Hamid Reza; Mohammadnia, Majid [Research on Chemical Intermediates, 2014, vol. 40, # 1, p. 371 - 383]
[16]Ghorbani-Vaghei, Ramin; Mahmoodi, Jafar; Maghbooli, Yaser [Applied Organometallic Chemistry, 2017, vol. 31, # 10]
[17]Mirzaei, Mahdi; Moradi, Leila; Sasi, Hamideh Rouhi [Journal of Molecular Structure, 2022, vol. 1263]

42
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[ 1445-69-8 ]
[ 5622-83-3 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 3502 - 3505

43
[ 1445-69-8 ]
[ 126-81-8 ]
[ 177756-62-6 ]
[ 1392815-43-8 ]

Yield	Reaction Conditions	Operation in experiment
96%	With montmorillonite K-10; at 80℃; for 0.0833333h;Neat (no solvent); Microwave irradiation;	General procedure: A mixture of phthalhydrazide (1, 162 mg, 1 mmol), 3-fluorobenzaldehyde (2b, 105 mg, 1 mmol), 5,5-dimethyl-cyclohexane-1,3-dione (3, 140 mg, 1 mmol) and K-10 (5 mol %, 50 mg) was taken in an open vessel and irradiated at 80 C in solvent-free condition for 5 min. The reactions were followed by thin layer chromatography (TLC) using hexane/ethyl acetate (3:1) as an eluent (Rf=0.70). After completion of the reaction, the mixture was washed with ethyl acetate and filtered to recover the catalyst. The filtrate was evaporated, and the crude product was recrystallized from ethanol to afford pure 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo-[2,1-b]phthalazine-1,6,11(13H)-trione (4b) in excellent yield (380 mg).

Reference： [1]Tetrahedron,2012,vol. 68,p. 6820 - 6828

44
[ 1445-69-8 ]
[ 126-81-8 ]
[ 456-48-4 ]
[ 1392815-41-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With montmorillonite K-10 at 80℃; for 0.0833333h; Neat (no solvent); Microwave irradiation;	4.2. Synthesis of 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione (4b) General procedure: A mixture of phthalhydrazide (1, 162 mg, 1 mmol), 3-fluorobenzaldehyde (2b, 105 mg, 1 mmol), 5,5-dimethyl-cyclohexane-1,3-dione (3, 140 mg, 1 mmol) and K-10 (5 mol %, 50 mg) was taken in an open vessel and irradiated at 80 °C in solvent-free condition for 5 min. The reactions were followed by thin layer chromatography (TLC) using hexane/ethyl acetate (3:1) as an eluent (Rf=0.70). After completion of the reaction, the mixture was washed with ethyl acetate and filtered to recover the catalyst. The filtrate was evaporated, and the crude product was recrystallized from ethanol to afford pure 13-(3-fluorophenyl)-3,4-dihydro-3,3-dimethyl-2H-indazolo-[2,1-b]phthalazine-1,6,11(13H)-trione (4b) in excellent yield (380 mg).
93%	With 1,4-diazabicyclo[2.2.2]octane on amorphous silica from rice husk ash In ethanol for 0.5h; Reflux; Green chemistry;	General procedure for the synthesis of phthalazine-trione derivatives General procedure: A mixture of phthalhydrazide (1mmol), dimedone (1mmol), aldehyde (1.2mmol), and RHDABCO (0.1g) was heated in ethanol for the time shown in Table3. The completion of the reaction was indicated by TLC. After satisfactory completion of the reaction, the reacted mixture was washed using hot ethanol, and the catalyst was fltered. The solid residue was purifed by recrystallization in aqueous EtOH.
91%	With nickel at 80℃; for 0.166667h; Green chemistry;

90%	With sulfuric acid functionalized silica-coated magnetite nanoparticles with core-shell structure In neat (no solvent) at 100℃; for 0.583333h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2 H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol), benzaldehyde (0.13 g, 1.2 mmol), and Fe3O4(at)silica sulfuric acid (0.1 g) was heated at 100 °C for 35 min (TLC). After satisfactory completion of the reaction and cooling, the reaction mixture was washed with hot ethanol and the catalyst was removed by a magnetic field. The solid residue was isolated and purified by recrystallization in hot EtOH. The desired pure product(s) was characterized by comparison of their physical data with those of known.
89%	With silica-supported tungstic acid In neat (no solvent) at 80℃; for 0.733333h; Green chemistry;	General procedure for the synthesis of 13-(4-chlorophenyl)-3,3-dimethyl-2,3,4,13-tetrahydro-1H-indazolo[1,2-b]phthalazine-1,6,11-trione (4a) General procedure: A mixture of phthalhydrazide (1, 1 mmol), 4-chlorobenzaldehydes (2, 1 mmol), dimedone (3, 1 mmol) and silica-supported tungstic acid (STA 10 mol%) was stirred at 80 °C under solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was washed with ethanol. The residue dissolved in DCM, and the insoluble STA was separated by simple filtration and washed with DCM. The solvent was evaporated under reduced pressure and the obtained crude was recrystallized from ethanol to afford the pure yellow product 4a. The recovered catalyst was washed with ethanol and acetone, dried and reused. Compounds 4a-4w were also synthesized by adopting this procedure.
88%	With SBA-15 modified by 1-(triethoxysilylpropyl)-3-methylimidazolium hydrogen sulfate In ethanol for 0.416667h; Reflux;	Typical procedure for preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol),benzaldehyde (0.13 g, 1.2 mmol), and [SBA-Im]HSO4 (0.1 g) was heated under reflux in ethanol for 30 min. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was washed with hot ethanol and the catalyst was isolated by filtration. The crude product was purified by recrystallization in aqueous ethanol to afford the pure product, which was characterized by comparison of its physical properties with those of a standard.
85%	With polymer-supported sulfonic acid (PSSA) In glycerol at 80℃; for 0.666667h;

Reference： [1]Location in patent: experimental part Veeranarayana Reddy, Mudumala; Reddy, Gangireddy Chandra Sekhar; Jeong, Yeon Tae [Tetrahedron, 2012, vol. 68, # 34, p. 6820 - 6828]
[2]Davarpanah, Jamal; Davoodi, Ghazal; Ghahremani, Mahboubeh; Rezaee, Parizad [Research on Chemical Intermediates, 2020]
[3]Saha, Mithu; Phukan, Smritakshi; Jamatia, Ramen; Mitra, Sivprasad; Pal, Amarta Kumar [RSC Advances, 2013, vol. 3, # 6, p. 1714 - 1721]
[4]Kiasat, Ali Reza; Davarpanah, Jamal [Journal of Molecular Catalysis A: Chemical, 2013, vol. 373, p. 46 - 54]
[5]Jadhav, Amol Maruti; Balwe, Sandip Gangadhar; Jeong, Yeon Tae [Phosphorus, Sulfur and Silicon and the Related Elements, 2020, vol. 195, # 3, p. 201 - 210]
[6]Davarpanah, Jamal; Rezaee, Parizad; Elahi, Somayeh [Research on Chemical Intermediates, 2015, vol. 41, # 12, p. 9903 - 9915]
[7]Mulik, Abhijeet; Chandam, Dattatraya; Patil, Prasad; Patil, Dayanand; Jagdale, Suryabala; Sankpal, Sandip; Deshmukh, Madhukar [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 3, p. 931 - 937]

45
[ 1445-69-8 ]
[ 529-20-4 ]
[ 109-77-3 ]
[ 1417454-83-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	With Bromoeosine In lithium hydroxide monohydrate at 20℃; for 2h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
95%	With 4-dimethylaminopyridine In ethanol for 2h; Reflux; Green chemistry;	4.1 General procedure General procedure: A mixture of aromatic aldehyde 1 (1.1mmol), malononitrile2 (1.1 mmol), phthalhydrazide 3 (1.0 mmol), and DMAP (20mol%) was placed in 10mL of ethanol. The reactionmixture was then refluxed for appropriate time (the reactionwas monitored by thin-layer chromatography; seeTable 1). After completion, ethanol was evaporated undervacuum and 10mL of water was added. The resulting solidwas filtered, and washed with water and then hexane. Thestructures of the products were fully established on thebasis of their 1H NMR, 13C NMR, and IR spectra as well asMS spectral analysis.
93%	In lithium hydroxide monohydrate at 20℃; for 2.5h; Irradiation; Green chemistry;	2.3. The overall process of preparing (7a-r) General procedure: Multifarious reagents including phthalhydrazide (5, 1.0 mmol),malononitrile (2, 1.0 mmol) and aromatic aldehydes (6a-r, 1.0 mmol)were reacted opposed to CFL (23 W) irradiation at room temperature inaqueous ethyl lactate (2:1, 3 mL) (Scheme 2). This was observed by TLCthat employed (ethyl acetate/n-hexane (1:3)). Afterwards, the filteringof the acquired solid was conducted, then the solid was rinsed water (2 ×3 mL) and ethanol (2 × 3 mL) and solid composition became recrystallizedby EtOH. The products were classified after the comparison ofspectroscopic information (1H NMR). Support for this manuscript can befound in the online version.

88%	With zirconium(IV) oxide In neat (no solvent) at 100℃;
81%	In neat (no solvent) at 100℃; for 0.416667h;	Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and pyrazolo[1,2-a][1,2,4]triazole-1,3-diones General procedure: A mixture of aldehyde 2 (1.0 mmol), malononitrile 1 (1.0 mmol), phthalhydrazide 3(1.0 mmol) or phenylurazole 5 (1.0 mmol) and Cu-ZnO hollow spheres (0.02 g) wereplaced in a test tube. The reaction mixture was then heated at 100 C for an appropriatetime (Tables 2 and 3) until the completion of the reaction was achieved as monitoredby TLC. Then, the crude product was dissolved in hot ethyl acetate and then filtered toremove the solid catalyst. The filtrate was cooled to give the pure organic product, identifiedby comparison of the observed melting point with the literature value.Representative spectroscopic data for selected examples are shown below, for the sakeof completeness.
	at 20℃; Neat (no solvent); Ionic liquid;
	With magnetic Fe₃O₄ nanoparticles coated by (3-aminopropyl)triethoxysilane at 20℃; for 0.266667h;
	With guanidine-modified SiO₂/perlite nanoparticles In ethanol at 78℃; Green chemistry;	2.5. General procedure for the preparation of 1H-pyrazolo[1,2-b] phthalazine-5,10-dione derivatives General procedure: In a general procedure, a mixture of phtalimide (1 mmol), hydrazinehydrate (1 mmol) and optimized amount of perlite NPs/SiO 2 /guanidine (0.009 g) was stirred in a 50 mL round-bottom flask containing 5 mL ethanol as solvent, under conventional heat- ing conditions at 78 °C for 90 min to obtain the white precipi- tate of phtalhydrazide. Then malononitrile (or ethyl cyano acetate) (1 mmol) and aldehyde derivative (1 mmol) were added to the mixture. After completion of the reaction (controlled by TLC: n- hexane/ethyl acetate 2:1), hot methanol was added and catalyst was separated by filtration. After evaporation of solvent, the pure product was obtained. The results of one-pot synthesis of 1H- pyrazolo[1,2-b] phthalazine-5,10-dione derivatives in the presence of perlite NPs/SiO 2 /guanidine are summarized in Table 2 .

Reference： [1]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[2]Lamera, Esma; Bouacida, Sofiane; Merazig, Hocine; Chibani, Aissa; Le Borgne, Marc; Bouaziz, Zouhair; Bouraiou, Abdelmalek [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2017, vol. 72, # 5, p. 361 - 368]
[3]Mohamadpour, Farzaneh [Journal of Photochemistry and Photobiology A: Chemistry, 2021, vol. 407]
[4]Piltan, Mohammad [Heterocyclic Communications, 2017, vol. 23, # 5, p. 401 - 403]
[5]Maleki, Behrooz; Nejat, Razieh; Alinezhad, Heshmatollah; Mousavi, Seyed Mohsen; Mahdavi, Behnam; Delavari, Maryam [Organic Preparations and Procedures International, 2020, p. 1 - 12]
[6]Location in patent: experimental part Shaterian, Hamid Reza; Mohammadnia, Majid [Journal of Molecular Liquids, 2012, vol. 173, p. 55 - 61]
[7]Shaterian, Hamid Reza; Mohammadnia, Majid [Research on Chemical Intermediates, 2014, vol. 40, # 1, p. 371 - 383]
[8]Mirzaei, Mahdi; Moradi, Leila; Sasi, Hamideh Rouhi [Journal of Molecular Structure, 2022, vol. 1263]

46
[ 1445-69-8 ]
[ 126-81-8 ]
[ 105-07-7 ]
[ 1415214-13-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	With nano-silica supported 3-(3-sulfopropyl)-1-[3-(trimethoxysilyl)propyl]-1H-imidazol-3-ium hydrogen sulfate In neat (no solvent) at 80℃; for 0.166667h;
94%	With Fe₃O₄-SiO₂ core-shell nanoparticles at 120℃; for 0.233333h; Green chemistry;	General procedure for the preparation of indazolo[1,2-b]-phthalazinetriones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide (0.16 g, 1 mmol), aldehyde (1 mmol), and Fe3O4 SiO2 (0.0 23 gr, 0.8 mmol, 8 mol%) was heated at 120°C for 10-20 min. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature and the solid obtained was dissolved in dichloromethane; the catalyst was insoluble in CH2Cl2 and separated by using an external magnet. The solvent was evaporated and the residue was recrystallized from ethanol to afford the pure indazolo[1,2-b]-phthalazinetriones.
94%	With 1,4-diazabicyclo[2.2.2]octane on amorphous silica from rice husk ash In ethanol for 0.5h; Reflux; Green chemistry;	General procedure for the synthesis of phthalazine-trione derivatives General procedure: A mixture of phthalhydrazide (1mmol), dimedone (1mmol), aldehyde (1.2mmol), and RHDABCO (0.1g) was heated in ethanol for the time shown in Table3. The completion of the reaction was indicated by TLC. After satisfactory completion of the reaction, the reacted mixture was washed using hot ethanol, and the catalyst was fltered. The solid residue was purifed by recrystallization in aqueous EtOH.

93%	With nickel at 80℃; for 0.166667h; Green chemistry;
92%	With sulfuric acid functionalized silica-coated magnetite nanoparticles with core-shell structure In neat (no solvent) at 100℃; for 0.5h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2 H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol), benzaldehyde (0.13 g, 1.2 mmol), and Fe3O4(at)silica sulfuric acid (0.1 g) was heated at 100 °C for 35 min (TLC). After satisfactory completion of the reaction and cooling, the reaction mixture was washed with hot ethanol and the catalyst was removed by a magnetic field. The solid residue was isolated and purified by recrystallization in hot EtOH. The desired pure product(s) was characterized by comparison of their physical data with those of known.
90%	With [4-(1,10-phenanthrolin-1-ium-1-yl)butane-1-sulfonate]₃PW₁₂O₄₀ In water for 0.133333h; Reflux; Green chemistry;	General procedure for synthesis of 2H-indazolo[2,1-b]phthalazine-trionederivatives using PhBS+3PW12O3-40 as catalyst General procedure: Aromatic aldehyde 5 (1 mmol), 5,5-dimethylcyclohexane-1,3-dione and or cyclohexane-1,3-dione 6 (1 mmol), and 2,3-dihydro-1,4-phthalazinedione (phthalhydrazide) 7 (1 mmol) were placed together in a 25 mL canonical flask containing10 mL of H2O.[PhBS]+3PW12O3-40 catalyst (0.10 g) was added to the mixture.The suspension was magnetically stirred under reflux condition for appropriate time according to Table 2. After completion of the reaction as followed byTLC (n-hexane: ethyl acetate; 3:1), the mixture was filtered and the filtrate precipitate was washed several times with hot water and then recrystallized from hot EtOH (2 × 25 mL) to provide the pure crystals of 2H-indazolo[2,1-b]phthalazinetrione derivatives. The filtered was evaporated under vacuum to precipitate the [PhBS]+3PW12O3-40 catalyst. The recovered catalyst was washed with acetone, dried and stored for other similar consecutive runs. The products are known compounds and are characterized by IR and NMR spectroscopy and CHN data for new compounds.Their melting points are compared with reported values
89%	With nano-γ-aluminasulforic acid at 110℃; for 0.333333h;	Typical procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-triones A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) or acetyl acetone(0.20 g, 2 mmol), phthalhydrazide (0.16 g, 1 mmol), aromatic aldehyde(1 mmol) together with Nano-ASA (0.04 g) was heated at 110 C for the corresponding time (see Table 2 and 3). Completion of the reaction was indicated by TLC [TLC acetone/n-hexane (3:10)]. After completion of the reaction, the solid residue was dissolved in ethanol and nano-alumina sulfuric acid was filtered. The crude product was purified by recrystallization in aqueous ethanol to afford the pure product
82%	With yttrium(III) trifluoromethanesulfonate In ethanol; water at 80℃; for 0.5h; Green chemistry;	Synthesis of indazolo[2,1-b]phthalazine-triones (4a-4e). General procedure: A mixture of 1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione (1,3-dicarbonyl compounds) 1 (2 mmol) with p-substituted benzaldehyde 2 (2 mmol), phthalhydrazide 3 (2 mmol), and 20 mol % of Y(OTf)3 in 10 mL of EtOH-H2O (1 : 1, v/v) was stirred magnetically upon refluxing till completion of the reaction (monitored by TLC) (Table 1). The raw product was filtered off, washed with water and crystallized from EtOH to give the corresponding pure product 4a-4e.
82%	With yttrium(III) trifluoromethanesulfonate In ethanol; water at 80℃; for 0.5h;
78%	With diatomite-SO₃H In ethanol at 80℃; for 2.5h;	2.3 General procedure for the synthesis of2H-indazolo (2, 1-b) phthalazine-triones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) and diatomite-SO3H (0.3 g) in ethanol was heated at 80 °C. The progressof the reaction was monitored by TLC ethyl acetate:n-hexane(1:1). After completion of the reaction, the diatomite-SO3H was filtered from the reaction mixture. After evaporation ofthe solvent, the crude productwas purified by recrystallizationin aqueous ethanol to afford the pure product.
	With 25,26,27,28-terahydroxycalix[4]arene-5,11,7,23-tetrasulfonic acid at 130℃; for 0.166667h; Microwave irradiation;

Reference： [1]Safaei, Shirin; Mohammadpoor-Baltork, Iraj; Khosropour, Ahmad Reza; Moghadam, Majid; Tangestaninejad, Shahram; Mirkhani, Valiollah [Catalysis science and technology, 2013, vol. 3, # 10, p. 2717 - 2722]
[2]Mirhosseini-Eshkevari, Boshra; Ghasemzadeh, Mohammad Ali; Safaei-Ghomi, Javad [Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7703 - 7714]
[3]Davarpanah, Jamal; Davoodi, Ghazal; Ghahremani, Mahboubeh; Rezaee, Parizad [Research on Chemical Intermediates, 2020]
[4]Saha, Mithu; Phukan, Smritakshi; Jamatia, Ramen; Mitra, Sivprasad; Pal, Amarta Kumar [RSC Advances, 2013, vol. 3, # 6, p. 1714 - 1721]
[5]Kiasat, Ali Reza; Davarpanah, Jamal [Journal of Molecular Catalysis A: Chemical, 2013, vol. 373, p. 46 - 54]
[6]Iravani, Nasir; Keshavarz, Mosadegh; Parhami, Abolfath [Research on Chemical Intermediates, 2019, vol. 45, # 10, p. 5045 - 5066]
[7]Kiasat, Ali Reza; Noorizadeh, Siamak; Ghahremani, Mahboubeh; Saghanejad, Seyed Jafar [Journal of Molecular Structure, 2013, vol. 1036, p. 216 - 225]
[8]Turhan; Turgut [Russian Journal of Organic Chemistry, 2019, vol. 55, # 2, p. 250 - 253]
[9]Gulcin, İlhami; Karaman, Halide Sedef; Türkan, Fikret; Taslimi, Parham; Turgut, Zuhal; Turhan, Kadir [Journal of Heterocyclic Chemistry, 2020, vol. 57, # 8, p. 3116 - 3125]
[10]Abbasi, Marzieh; Nazifi, Seyed Mohamad Reza; Nazifi, Zahra Sadat; Massah, Ahmad Reza [Journal of Chemical Sciences, 2017, vol. 129, # 8, p. 1257 - 1266]
[11]Martins, Felipe Terra; Maia, Lauro June Queiroz; Gasparotto, Gisane; Valdo, Ana Karoline Silva Medanha; Nascimento Neto, José Antônio; Ribeiro, Leandro; De Freitas Rego, Yuri; Da Silva, Cleiton Moreira; De Fátima, Ângelo [New Journal of Chemistry, 2019, vol. 43, # 3, p. 1313 - 1321]

47
[ 1445-69-8 ]
[ 104-88-1 ]
[ 123-54-6 ]
[ 1426998-75-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With diethanolammonium chloroacetate at 140℃; for 6h;
86%	With SBA-15 modified by 1-(triethoxysilylpropyl)-3-methylimidazolium hydrogen sulfate In ethanol for 0.583333h; Reflux;	Typical procedure for preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol),benzaldehyde (0.13 g, 1.2 mmol), and [SBA-Im]HSO4 (0.1 g) was heated under reflux in ethanol for 30 min. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was washed with hot ethanol and the catalyst was isolated by filtration. The crude product was purified by recrystallization in aqueous ethanol to afford the pure product, which was characterized by comparison of its physical properties with those of a standard.
84%	With sulfuric acid functionalized silica-coated magnetite nanoparticles with core-shell structure In neat (no solvent) at 100℃; for 0.666667h;	Typical procedure for the preparation of 3,4-dihydro-3,3-dimethyl-13-phenyl-2 H-indazolo[2,1-b]phthalazine-1,6,11-trione General procedure: A mixture of phthalhydrazide (0.16 g, 1 mmol), dimedone (0.14 g, 1 mmol), benzaldehyde (0.13 g, 1.2 mmol), and Fe3O4(at)silica sulfuric acid (0.1 g) was heated at 100 °C for 35 min (TLC). After satisfactory completion of the reaction and cooling, the reaction mixture was washed with hot ethanol and the catalyst was removed by a magnetic field. The solid residue was isolated and purified by recrystallization in hot EtOH. The desired pure product(s) was characterized by comparison of their physical data with those of known.

80%	With 1,4-diazabicyclo[2.2.2]octane on amorphous silica from rice husk ash In ethanol for 0.75h; Reflux; Green chemistry;	General procedure for the synthesis of phthalazine-dione derivatives General procedure: Under ethanol refux, a mixture of phthalhydrazide (0.16g, 1mmol), acetyl acetone (0.14g, 2mmol), aldehyde (1mmol), and RHDABCO (0.1g) was heated for the appropriate time (Table3). The completion of the reaction was indicated by TLC. After satisfactory completion of the reaction, the reacted mixture was washed using hot ethanol, and the catalyst was fltered. The solid residue was purifed by recrystallization in aqueous EtOH.
60%	With nano-γ-aluminasulforic acid at 110℃; for 1h;	Typical procedure for the preparation of 2H-indazolo[2,1-b]phthalazine-triones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) or acetyl acetone(0.20 g, 2 mmol), phthalhydrazide (0.16 g, 1 mmol), aromatic aldehyde(1 mmol) together with Nano-ASA (0.04 g) was heated at 110 C for the corresponding time (see Table 2 and 3). Completion of the reaction was indicated by TLC [TLC acetone/n-hexane (3:10)]. After completion of the reaction, the solid residue was dissolved in ethanol and nano-alumina sulfuric acid was filtered. The crude product was purified by recrystallization in aqueous ethanol to afford the pure product

Reference： [1]Simijonović, Dušica; Petrović, Zorica D.; Milovanović, Vesna M.; Petrović, Vladimir P.; Bogdanović, Goran A. [RSC Advances, 2018, vol. 8, # 30, p. 16663 - 16673]
[2]Davarpanah, Jamal; Rezaee, Parizad; Elahi, Somayeh [Research on Chemical Intermediates, 2015, vol. 41, # 12, p. 9903 - 9915]
[3]Kiasat, Ali Reza; Davarpanah, Jamal [Journal of Molecular Catalysis A: Chemical, 2013, vol. 373, p. 46 - 54]
[4]Davarpanah, Jamal; Davoodi, Ghazal; Ghahremani, Mahboubeh; Rezaee, Parizad [Research on Chemical Intermediates, 2020]
[5]Kiasat, Ali Reza; Noorizadeh, Siamak; Ghahremani, Mahboubeh; Saghanejad, Seyed Jafar [Journal of Molecular Structure, 2013, vol. 1036, p. 216 - 225]

48
[ 1445-69-8 ]
[ 446-52-6 ]
[ 109-77-3 ]
[ 1443004-17-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With Eosin Y In water at 20℃; for 2h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
93%	In water at 20℃; for 2h; Irradiation; Green chemistry;	2.3. The overall process of preparing (7a-r) General procedure: Multifarious reagents including phthalhydrazide (5, 1.0 mmol),malononitrile (2, 1.0 mmol) and aromatic aldehydes (6a-r, 1.0 mmol)were reacted opposed to CFL (23 W) irradiation at room temperature inaqueous ethyl lactate (2:1, 3 mL) (Scheme 2). This was observed by TLCthat employed (ethyl acetate/n-hexane (1:3)). Afterwards, the filteringof the acquired solid was conducted, then the solid was rinsed water (2 ×3 mL) and ethanol (2 × 3 mL) and solid composition became recrystallizedby EtOH. The products were classified after the comparison ofspectroscopic information (1H NMR). Support for this manuscript can befound in the online version.
92%	With indium(III) chloride In neat (no solvent) at 80℃; for 0.416667h;	General procedure for the synthesis of 3-amino-1-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 4b General procedure: Amixture of phthalhydrazide (1, 1 mmol), 3-fluorobenzaldehyde (2b, 1 mmol),malononitrile (3, 1 mmol) and InCl3 (10 mol %) was stirred at 80 C undersolvent-free condition for 25 min (Table 3, entry 2). The progress of thereaction was monitored by TLC. After completion of reaction, the reactionmixture was washed with water and ethanol and residue recrystallized fromethanol to afford the pure product 4b (94%).

88%	With β‐cyclodextrin In ethanol; water at 100℃; for 3h; Green chemistry;	2.1 General Procedure for Synthesis of 1H-Pyrazolo[1,2-b]phthalazine-5,10-diones General procedure: The mixture of carbonyl compound aldehyde (2 mmol), phthalhydrazide (2 mmol) and malononitrile (2 mmol) were added in β-cyclodextrin (0.4mmol) solution containing H2O-EtOH (4:1, 10 mL). The resulting mixture was stirred at 100 °C. After completion of the reaction (monitored by TLC), the reaction mixture was poured into 20mL water. Filtered the product and washed with hot water. The crude product was recrystallized with 30% aqueous ethanol to afford the desired product. The filtered aqueous layer was cooled at 5 °C to recovery of β-CD by filtration. The recovered β-CD was reused for 3-4 consecutive runs in this reaction without any significant loss in yield and activity.
88%	With (3-propyltrimethoxysilane)imidazolium hydroxide supported on magnetic nanoparticles In neat (no solvent) at 20℃; for 0.283333h; Green chemistry;	General procedure for the synthesis of cyano-substituted pyrazolo[1,2-b]phthalazinediones derivatives catalyzed by the [SiPMIM]OH(at)MNPs General procedure: A mixture of aromatic aldehyde (1 mmol), malononitrile(1 mmol), phthalhydrazide (1 mmol) and [SiPMIM]OH(at)MNPs (0.5 mol%, 50 mg) was stirred at ambient temperature for the appropriate time according to Table 3 under solvent free conditions. The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 2:1). After completion of the reaction, ethyl acetate (25 mL) was added, and the catalyst was easily separated by a permanent magnet and washed with ethyl acetate (10 mL × 2). The solvent was evaporated, and the resulting crude product was purified by recrystallization from acetone and ethanol (1:2) to affordthe pure product (Table 3). Selective synthesis of the mono and bis-pyrazolo[1,2-b]phthalazinediones was achieved by controlling the molar ratio of dialdehyde, malononitrile and phthalhydrazide (Scheme 4). After completion of the reaction,if necessary, the product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate,5:2) to afford the pure product.
294 mg	With piperidinium benzene-1,3-disulfonate Fe₃O₄ magnetic nanoparticle ionic liquid In neat (no solvent) at 110℃; for 0.75h;

Reference： [1]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[2]Mohamadpour, Farzaneh [Journal of Photochemistry and Photobiology A: Chemistry, 2021, vol. 407]
[3]Veeranarayana Reddy, Mudumala; Jeong, Yeon Tae [Tetrahedron Letters, 2013, vol. 54, # 27, p. 3546 - 3549]
[4]Tayade, Yogesh A.; Dalal, Dipak S. [Catalysis Letters, 2017, vol. 147, # 6, p. 1411 - 1421]
[5]Hatami Sabour, Fereshteh; Nasr-Esfahani, Mahboobeh; Mohammadpoor-Baltork, Iraj; Tangestaninejad, Shahram; Moghadam, Majid; Mirkhani, Valiollah [Journal of the Iranian Chemical Society, 2018, vol. 15, # 3, p. 671 - 683]
[6]Ghorbani-Vaghei, Ramin; Mahmoodi, Jafar; Maghbooli, Yaser [Applied Organometallic Chemistry, 2017, vol. 31, # 10]

49
[ 1445-69-8 ]
[ 42564-51-2 ]
[ 109-77-3 ]
[ 1443004-19-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With indium(III) chloride; In neat (no solvent); at 80℃; for 0.5h;	General procedure: Amixture of phthalhydrazide (1, 1 mmol), 3-fluorobenzaldehyde (2b, 1 mmol),malononitrile (3, 1 mmol) and InCl3 (10 mol %) was stirred at 80 C undersolvent-free condition for 25 min (Table 3, entry 2). The progress of thereaction was monitored by TLC. After completion of reaction, the reactionmixture was washed with water and ethanol and residue recrystallized fromethanol to afford the pure product 4b (94%).

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 3546 - 3549

50
[ 1445-69-8 ]
[ 177756-62-6 ]
[ 109-77-3 ]
[ 1443004-20-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With indium(III) chloride; In neat (no solvent); at 80℃; for 0.433333h;	General procedure: Amixture of phthalhydrazide (1, 1 mmol), 3-fluorobenzaldehyde (2b, 1 mmol),malononitrile (3, 1 mmol) and InCl3 (10 mol %) was stirred at 80 C undersolvent-free condition for 25 min (Table 3, entry 2). The progress of thereaction was monitored by TLC. After completion of reaction, the reactionmixture was washed with water and ethanol and residue recrystallized fromethanol to afford the pure product 4b (94%).
90%	With silica gel supported tungstic acid; In neat (no solvent); at 70℃; for 0.433333h;Green chemistry;	General procedure: A mixture of phthalhydrazide (1, 1 mmol, 162 mg), 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde (2a, 1 mmol,164 mg), malononitrile (3a, 1 mmol, 66 mg) and STA(5 mol%, 21 mg) was stirred at 70 8C under solvent-freeconditions for 20 min (Table 3, entry 1). The progress of thereaction was monitored by TLC. After completion of thereaction, the mixture was dissolved in hot ethanol and the catalyst was filtered. The residue was crystallized fromethanol to afford product 4a (93%). The catalyst waswashed with diethylether, dried at 100 8C for 2 h, andreused in another reaction.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 3546 - 3549
[2]Comptes Rendus Chimie,2014,vol. 17,p. 1250 - 1256

51
[ 1445-69-8 ]
[ 105-56-6 ]
[ 177756-62-6 ]
[ 1443004-33-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With silica gel supported tungstic acid; In neat (no solvent); at 70℃; for 0.5h;Green chemistry;	General procedure: A mixture of phthalhydrazide (1, 1 mmol, 162 mg), 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde (2a, 1 mmol,164 mg), malononitrile (3a, 1 mmol, 66 mg) and STA(5 mol%, 21 mg) was stirred at 70 8C under solvent-freeconditions for 20 min (Table 3, entry 1). The progress of thereaction was monitored by TLC. After completion of thereaction, the mixture was dissolved in hot ethanol and the catalyst was filtered. The residue was crystallized fromethanol to afford product 4a (93%). The catalyst waswashed with diethylether, dried at 100 8C for 2 h, andreused in another reaction.
87%	With indium(III) chloride; In neat (no solvent); at 80℃; for 0.583333h;	General procedure: Amixture of phthalhydrazide (1, 1 mmol), 3-fluorobenzaldehyde (2b, 1 mmol),malononitrile (3, 1 mmol) and InCl3 (10 mol %) was stirred at 80 C undersolvent-free condition for 25 min (Table 3, entry 2). The progress of thereaction was monitored by TLC. After completion of reaction, the reactionmixture was washed with water and ethanol and residue recrystallized fromethanol to afford the pure product 4b (94%).

Reference： [1]Comptes Rendus Chimie,2014,vol. 17,p. 1250 - 1256
[2]Tetrahedron Letters,2013,vol. 54,p. 3546 - 3549

52
[ 1445-69-8 ]
[ 86-81-7 ]
[ 109-77-3 ]
[ 1443004-25-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With indium(III) chloride In neat (no solvent) at 80℃; for 0.466667h;	General procedure for the synthesis of 3-amino-1-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 4b General procedure: Amixture of phthalhydrazide (1, 1 mmol), 3-fluorobenzaldehyde (2b, 1 mmol),malononitrile (3, 1 mmol) and InCl3 (10 mol %) was stirred at 80 C undersolvent-free condition for 25 min (Table 3, entry 2). The progress of thereaction was monitored by TLC. After completion of reaction, the reactionmixture was washed with water and ethanol and residue recrystallized fromethanol to afford the pure product 4b (94%).
88%	With magnetite-silica core-shell nanoparticles modified with Cu-salen complex In neat (no solvent) at 80℃; for 16801.5h;	General procedure for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dionederivatives General procedure: Under the optimum reaction conditions, phthalhydrazide (1 mmol), malononi-trile (1 mmol), aldehyde (1 mmol) and the catalyst (0.02 g) were added to a testtube. The mixture was stirred magnetically and heated at 80 °C under solvent-free conditions. After completion of the reaction (judged by the TLC (n-hexane/ethyl acetate 10:3)), 10 ml of hot ethanol was added to the reaction mixture andthe catalyst was separated using an external magnet. Then, 20 ml of distilledwater was added to the reaction mixture and precipitated product isolated byfiltration. The product was washed with NaOH (0.5 mol) to produce a pure prod-uct.
87%	In water at 20℃; for 5h; Irradiation; Green chemistry;	2.3. The overall process of preparing (7a-r) General procedure: Multifarious reagents including phthalhydrazide (5, 1.0 mmol),malononitrile (2, 1.0 mmol) and aromatic aldehydes (6a-r, 1.0 mmol)were reacted opposed to CFL (23 W) irradiation at room temperature inaqueous ethyl lactate (2:1, 3 mL) (Scheme 2). This was observed by TLCthat employed (ethyl acetate/n-hexane (1:3)). Afterwards, the filteringof the acquired solid was conducted, then the solid was rinsed water (2 ×3 mL) and ethanol (2 × 3 mL) and solid composition became recrystallizedby EtOH. The products were classified after the comparison ofspectroscopic information (1H NMR). Support for this manuscript can befound in the online version.

85%	With Eosin Y In water at 20℃; for 4h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
83%	With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 0.25h; Green chemistry;
304 mg	With piperidinium benzene-1,3-disulfonate Fe₃O₄ magnetic nanoparticle ionic liquid In neat (no solvent) at 110℃; for 1.33333h;

Reference： [1]Veeranarayana Reddy, Mudumala; Jeong, Yeon Tae [Tetrahedron Letters, 2013, vol. 54, # 27, p. 3546 - 3549]
[2]Azarifar, Davood; Ebrahimiasl, Hakimeh; Nesarvand, Milad [Research on Chemical Intermediates, 2021, vol. 47, # 9, p. 3629 - 3644]
[3]Mohamadpour, Farzaneh [Journal of Photochemistry and Photobiology A: Chemistry, 2021, vol. 407]
[4]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[5]Ghorbani-Vaghei, Ramin; Noori, Samira; Toghraei-Semiromi, Zahra; Salimi, Zahra [RSC Advances, 2014, vol. 4, # 89, p. 47925 - 47928]
[6]Ghorbani-Vaghei, Ramin; Mahmoodi, Jafar; Maghbooli, Yaser [Applied Organometallic Chemistry, 2017, vol. 31, # 10]

53
[ 1445-69-8 ]
[ 59142-68-6 ]
[ 105-56-6 ]
[ 1443004-32-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With indium(III) chloride In neat (no solvent) at 80℃; for 0.5h;	General procedure for the synthesis of 3-amino-1-(3-fluorophenyl)-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile 4b General procedure: Amixture of phthalhydrazide (1, 1 mmol), 3-fluorobenzaldehyde (2b, 1 mmol),malononitrile (3, 1 mmol) and InCl3 (10 mol %) was stirred at 80 C undersolvent-free condition for 25 min (Table 3, entry 2). The progress of thereaction was monitored by TLC. After completion of reaction, the reactionmixture was washed with water and ethanol and residue recrystallized fromethanol to afford the pure product 4b (94%).

Reference： [1]Veeranarayana Reddy, Mudumala; Jeong, Yeon Tae [Tetrahedron Letters, 2013, vol. 54, # 27, p. 3546 - 3549]

54
[ 446292-08-6 ]
[ 446292-10-0 ]
[ 1445-69-8 ]

Yield	Reaction Conditions	Operation in experiment
73%; 12.7%	With hydrazine hydrate; In ethanol; at 65℃; for 3h;	20 g of 2-({(5S) -2-oxo-3-[4-(3-oxomo holin-4-yl) henyl]-1 ,3-oxazolidin-5-yl}methyl)-1H- isoindole-1,3(2H)-dione was suspended in 450 ml of ethanol, which was followed by addition of 6 ml of hydrazinehydrate in 50 ml of ethanol and the mixture was stirred and refluxed for 3 hours. Then, the suspension was cooled down to 65C and filtered and the cake was washed with 2x50 ml of nearly boiling ethanol. After drying 7.2 g of an off-white powder were obtained, which slowly melted at a temperature over 260C (this fraction contained 99.9% of 2,3-dihydrophtalazine-l,4-dione according to HPLC). After cooling of the hot filtrate another solid fraction separated. After its isolation by filtration and drying, 12.5 g of white lumpy powder with the melt, point of 141-144C was obtained (this fraction contained 86.7% of the desired product, 12.7% of 2,3-dihydrophtalazine-l,4-dione, and the rest to 100 % were other unidentifiable impurities according to HPLC). The yield of the isolated amine calculated to the pure substance was 73%.

Reference： [1]Patent: WO2013/120465,2013,A1 .Location in patent: Page/Page column 39

55
[ 1445-69-8 ]
[ 83-38-5 ]
[ 126-81-8 ]
[ 1415214-12-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With SBA-Pr-NH2; In neat (no solvent); at 80℃; for 0.416667h;Green chemistry;	General procedure: The SBA-Pr-NH2 (0.02 g) was activated under vacuum at 100 C and, after cooling to room temperature, aromatic aldehyde 1 (1 mmol), dimedone 2 (1 mmol, 0.14 g), and phthalhydrazide 3 (1 mmol, 0.16 g) were added. The mixture was heated at 80 C under solvent-free conditions until reaction was complete (monitored byTLC; petroleum ether-EtOAc, 4:1). The resulting solid product was dissolved in hot ethanol and the heterogeneous solid-base catalyst was removed by simple filtration. The filtrate was cooled to give the pure products 4a-j. The recovered catalyst washed consecutively with dilute Et3N solution, water, and acetone, then dried under vacuum.
84%	With 1-sulfonic acid-3,5,7-trimethylpurinium-5,7-dione hydrogen sulfate; In neat (no solvent); at 100℃; for 0.583333h;Green chemistry;	General procedure: A mixture of dimedone (0.035 g, 0.25 mmol), phthalhydrazide (0.040 g, 0.25 mmol), benzaldehyde (0.026 g, 1 mmol), and 3-sulfonic acid imidazopyridinium hydrogen sulfate (10 mmol) was heated at 100C for 10 min. After cooling, the residue was re-crystallized from ethanol to afford the corresponding pure product.
80%	With sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H); In neat (no solvent); at 80℃; for 0.25h;Green chemistry;	General procedure: The SBA-Pr-SO3H (0.02 g) was activated in vacuum at 100 C. After cooling to room temperature, phthalhydrazide 1 (1 mmol, 0.16 g), aromatic aldehyde 2 (1 mmol), and dimedone 3 (1 mmol, 0.14 g) were added to it. The mixture was heated at 80 C under solvent-free condition until the reaction was completed. After completion of the reaction (monitored by TLC), the solid product was dissolved in hot ethanol (2 × 10 mL) and the heterogeneous solid catalyst was removed by simple filtration. Then, the filtrate was cooled to give the pure products 4a-k.

78%

With diatomite-SO3H; In ethanol; at 80℃; for 2.5h;

General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol) and diatomite-SO3H (0.3 g) in ethanol was heated at 80 C. The progressof the reaction was monitored by TLC ethyl acetate:n-hexane(1:1). After completion of the reaction, the diatomite-SO3H was filtered from the reaction mixture. After evaporation ofthe solvent, the crude productwas purified by recrystallizationin aqueous ethanol to afford the pure product.

Reference： [1]Catalysis science and technology,2013,vol. 3,p. 2717 - 2722
[2]Research on Chemical Intermediates,2015,vol. 41,p. 7581 - 7591
[3]Journal of Molecular Liquids,2015,vol. 206,p. 119 - 128
[4]Journal of the Chilean Chemical Society,2014,vol. 59,p. 2271 - 2274
[5]Journal of Chemical Sciences,2017,vol. 129,p. 1257 - 1266

56
[ 1445-69-8 ]
[ 126-81-8 ]
[ 100-10-7 ]
C₂₅H₂₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With Fe₃O₄-SiO₂ core-shell nanoparticles at 120℃; for 0.266667h; Green chemistry;	General procedure for the preparation of indazolo[1,2-b]-phthalazinetriones General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide (0.16 g, 1 mmol), aldehyde (1 mmol), and Fe3O4 SiO2 (0.0 23 gr, 0.8 mmol, 8 mol%) was heated at 120°C for 10-20 min. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature and the solid obtained was dissolved in dichloromethane; the catalyst was insoluble in CH2Cl2 and separated by using an external magnet. The solvent was evaporated and the residue was recrystallized from ethanol to afford the pure indazolo[1,2-b]-phthalazinetriones.
88%	With sulfonic acid grafted onto TiO₂-coated nickel ferrite nanoparticles In neat (no solvent) at 80℃; for 0.333333h;	General procedure for synthesisof 2H-indazolo[2,1-b]phthalazine-trione derivatives General procedure: A mixture of dimedone (0.14 g, 1 mmol), phthalhydrazide(0.16 g, 1 mmol), aromatic aldehyde (1 mmol), and nanocatalyst(0.03 g) was heated at 80 °C for 10 min (TLC). Aftercooling, the reaction mixture was poured in 10 mL of DMFand the catalyst was separated easily by an external magnet.The saturated sodium chloride solution was then added to precipitate the pure product.
85%	With SBA-Pr-NH₂ In neat (no solvent) at 80℃; for 0.0833333h; Green chemistry;	General procedure for synthesis of 2H-indazolo[2,1-b]phthalazinetrionederivatives 4a-j General procedure: The SBA-Pr-NH2 (0.02 g) was activated under vacuum at 100 °C and, after cooling to room temperature, aromatic aldehyde 1 (1 mmol), dimedone 2 (1 mmol, 0.14 g), and phthalhydrazide 3 (1 mmol, 0.16 g) were added. The mixture was heated at 80 °C under solvent-free conditions until reaction was complete (monitored byTLC; petroleum ether-EtOAc, 4:1). The resulting solid product was dissolved in hot ethanol and the heterogeneous solid-base catalyst was removed by simple filtration. The filtrate was cooled to give the pure products 4a-j. The recovered catalyst washed consecutively with dilute Et3N solution, water, and acetone, then dried under vacuum.

81%	With nano-silica supported 3-(3-sulfopropyl)-1-[3-(trimethoxysilyl)propyl]-1H-imidazol-3-ium hydrogen sulfate In neat (no solvent) at 80℃; for 0.333333h;
70%	With sulfonic acid functionalized nanoporous silica (SBA-Pr-SO₃H) In neat (no solvent) at 80℃; for 0.25h; Green chemistry;	General Procedure for the Synthesis of 2H-Indazolo[1,2-b]phthalazinetrione Derivatives (4a-k) General procedure: The SBA-Pr-SO3H (0.02 g) was activated in vacuum at 100 °C. After cooling to room temperature, phthalhydrazide 1 (1 mmol, 0.16 g), aromatic aldehyde 2 (1 mmol), and dimedone 3 (1 mmol, 0.14 g) were added to it. The mixture was heated at 80 °C under solvent-free condition until the reaction was completed. After completion of the reaction (monitored by TLC), the solid product was dissolved in hot ethanol (2 × 10 mL) and the heterogeneous solid catalyst was removed by simple filtration. Then, the filtrate was cooled to give the pure products 4a-k.
70%	With O₄₀PW₁₂^(3-)*3C₈H₁₁N₄O₅S⁽¹⁺⁾ In neat (no solvent) at 100℃; for 1.33333h; Green chemistry;	2.4. General route for the synthesis of 2H-indazolo[1,2-b]phthalazinetriones General procedure: 1,3-Diketones (0.25mmol), phthalhydrazide (0.25mmol), aromaticaldehydes (1 mmol), and the heterogeneous catalyst [Simp]3PW12O40(0.03 g) were thoroughly mixed in a test tube and heated at 100 °C inan oil-bath under solvent-free conditions for the required time. Fulfillmentof the reaction was observed by TLC: n-hexane: ethyl acetate(8:2). After completion, the reaction mixture was cooled to room temperatureand chloroform was added. After a minute, the heterogeneouscatalystwas filtered and chloroformwas dissipated fromthe residue. Atthat point, 5 ml of hot ethanol was added to the reaction mixture andstirred for 5 min. After wards, the reaction mixture was cooled to 5 °Cand the acquired phthalazine-trione precipitate was separated. Furtherre-crystallization in ethanol afforded the highly pure product. All productswereknown compounds andwere described by FT-IR, 1HNMR, 13CNMR, and determination of their melting points [27,31,38-40].

Reference： [1]Mirhosseini-Eshkevari, Boshra; Ghasemzadeh, Mohammad Ali; Safaei-Ghomi, Javad [Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7703 - 7714]
[2]Hamidinasab, Mahdia; Mobinikhaledi, Akbar [Journal of the Iranian Chemical Society, 2019, vol. 16, # 6, p. 1255 - 1263]
[3]Mohammadi Ziarani, Ghodsi; Hosseini Mohtasham, Nina; Lashgari, Negar; Badiei, Alireza [Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7581 - 7591]
[4]Safaei, Shirin; Mohammadpoor-Baltork, Iraj; Khosropour, Ahmad Reza; Moghadam, Majid; Tangestaninejad, Shahram; Mirkhani, Valiollah [Catalysis science and technology, 2013, vol. 3, # 10, p. 2717 - 2722]
[5]Ziarani, Ghodsi Mohammadi; Badiei, Alireza; Mohtasham, Nina Hosseini; Lashgari, Negar [Journal of the Chilean Chemical Society, 2014, vol. 59, # 1, p. 2271 - 2274]
[6]Tayebee, Reza; Fattahi Abdizadeh; Maleki, Behrooz; Shahri, Elham [Journal of Molecular Liquids, 2017, vol. 241, p. 447 - 455]

57
[ 1445-69-8 ]
[ 626-19-7 ]
[ 126-81-8 ]
13-(3-(2,2-dimethyl-1,6,11-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13-yl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-indazolo[1,2-b]phthalazine-4,6,11(13H)-trione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With nano-NiFe₂O₄(at)TiO₂-DEA-OSO₃H In ethanol for 0.75h; Reflux; Green chemistry;	2.3. General procedure for the synthesis of bis 1H-Indazolo [1,2-b]phthalazine-trione derivatives General procedure: A mixture of dimedone (2 mmol), phthalhydrazide (2 mmol),diarylaldehyde (1 mmol), and nano-NiFe2O4(at)TiO2-DEA-OSO3H as acatalyst (0.03 g) was refluxed in EtOH for appropriate time (TLC).After cooling, the reaction mixture was filtered and dried at 70 °C.For separating the catalyst, the powder dissolved in DMF (10 mL)and the catalyst easily separated by an external magnet. The saturatedsodium chloride solution was then added to precipitate thepure product. For more purification the desired products recrystallizedin EtOH and dried at 70° C.
82%	With nano-silica supported 3-(3-sulfopropyl)-1-[3-(trimethoxysilyl)propyl]-1H-imidazol-3-ium hydrogen sulfate In neat (no solvent) at 80℃; for 0.333333h;
80%	With MNPs-guanidine (guanidine supported on magnetic nanoparticles Fe₃O₄) In neat liquid at 70℃; for 0.75h;

Reference： [1]Hamidinasab, Mahdia; Bodaghifard, Mohammad Ali; Mobinikhaledi, Akbar [Journal of Molecular Structure, 2020, vol. 1200]
[2]Safaei, Shirin; Mohammadpoor-Baltork, Iraj; Khosropour, Ahmad Reza; Moghadam, Majid; Tangestaninejad, Shahram; Mirkhani, Valiollah [Catalysis science and technology, 2013, vol. 3, # 10, p. 2717 - 2722]
[3]Atashkar, Bahareh; Rostami, Amin; Gholami, Hoshyar; Tahmasbi, Bahman [Research on Chemical Intermediates, 2015, vol. 41, # 6, p. 3675 - 3681]

58
[ 1445-69-8 ]
[ 66-77-3 ]
[ 109-77-3 ]
3-amino-1-(naphthalen-1-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium bromide In propan-1-ol at 20℃; for 0.0833333h; Electrolysis;	8 General procedure for electrochemical synthesis of pyrazolo[1,2-b]phthalazines General procedure: A solution of phthalhydrazide (1.0 mmol), various arylaldehydes (1.0 mmol), and malononitrile (1.0 mmol) andsodium bromide (0.1 mmol) in n-propanol (10 mL) waselectrolyzed in an undivided cell equipped with a magneticstirrer, a platinum anode and an iron cathode at roomtemperature under a constant current density of 12 mA/cm2 (I = 60 mA, electrodes square 5 cm2).The progress of the reaction was monitored by thinlayer chromatography. After completion of the reaction (4-8 minutes), the obtained precipitate was filtered, and thefilter cake was washed with ethanol to yield pure products(4a-k).
95%	With magnetite-silica core-shell nanoparticles modified with Cu-salen complex In neat (no solvent) at 80℃; for 10957.5h;	General procedure for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dionederivatives General procedure: Under the optimum reaction conditions, phthalhydrazide (1 mmol), malononi-trile (1 mmol), aldehyde (1 mmol) and the catalyst (0.02 g) were added to a testtube. The mixture was stirred magnetically and heated at 80 °C under solvent-free conditions. After completion of the reaction (judged by the TLC (n-hexane/ethyl acetate 10:3)), 10 ml of hot ethanol was added to the reaction mixture andthe catalyst was separated using an external magnet. Then, 20 ml of distilledwater was added to the reaction mixture and precipitated product isolated byfiltration. The product was washed with NaOH (0.5 mol) to produce a pure prod-uct.
85%	With ammonium cerium (IV) nitrate at 45℃; for 1.08333h;

84%	With N,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide In water at 80℃; for 0.5h; Green chemistry;
82%	With (3-propyltrimethoxysilane)imidazolium hydroxide supported on magnetic nanoparticles In neat (no solvent) at 20℃; for 0.333333h; Green chemistry;	General procedure for the synthesis of cyano-substituted pyrazolo[1,2-b]phthalazinediones derivatives catalyzed by the [SiPMIM]OH(at)MNPs General procedure: A mixture of aromatic aldehyde (1 mmol), malononitrile(1 mmol), phthalhydrazide (1 mmol) and [SiPMIM]OH(at)MNPs (0.5 mol%, 50 mg) was stirred at ambient temperature for the appropriate time according to Table 3 under solvent free conditions. The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 2:1). After completion of the reaction, ethyl acetate (25 mL) was added, and the catalyst was easily separated by a permanent magnet and washed with ethyl acetate (10 mL × 2). The solvent was evaporated, and the resulting crude product was purified by recrystallization from acetone and ethanol (1:2) to affordthe pure product (Table 3). Selective synthesis of the mono and bis-pyrazolo[1,2-b]phthalazinediones was achieved by controlling the molar ratio of dialdehyde, malononitrile and phthalhydrazide (Scheme 4). After completion of the reaction,if necessary, the product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate,5:2) to afford the pure product.

Reference： [1]Kefayati, Hassan; Amlashi, Shadi Homayoon; Kazemi-Rad, Reyhaneh; Delafrooz, Adeleh [Comptes Rendus Chimie, 2014, vol. 17, # 9, p. 894 - 898]
[2]Azarifar, Davood; Ebrahimiasl, Hakimeh; Nesarvand, Milad [Research on Chemical Intermediates, 2021, vol. 47, # 9, p. 3629 - 3644]
[3]Kidwai, Mazaahir; Chauhan, Ritika [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1689 - 1696]
[4]Khazaei, Ardeshir; Zolfigol, Mohammad Ali; Karimitabar, Fatemeh; Nikokar, Iraj; Moosavi-Zare, Ahmad Reza [RSC Advances, 2015, vol. 5, # 87, p. 71402 - 71412]
[5]Hatami Sabour, Fereshteh; Nasr-Esfahani, Mahboobeh; Mohammadpoor-Baltork, Iraj; Tangestaninejad, Shahram; Moghadam, Majid; Mirkhani, Valiollah [Journal of the Iranian Chemical Society, 2018, vol. 15, # 3, p. 671 - 683]

59
[ 1445-69-8 ]
[ 54589-54-7 ]
ethyl 3-(((4-oxo-3,4-dihydrophthalazin-1-yl)oxyl)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%		Phthalhydrazide (1b) (10g, 61.7 mmol) was dissolved in dried N,N-dimethylformamide (100 mL) in a round-bottom flask. Sodium hydride (1.63g, 67.9 mmol) was added at 0C, and then stirred for half an hour. Ethyl 3-chloromethylbenzoate (1c, purchased from Shanghai Shaoyuan Co. Ltd.) (13.49g, 67.9 mmol) dissolved in N,N-dimethylformamide (20 mL) solution was added slowly dropwise at room temperature and reacted for 24 hours, and then ethyl acetate was added. The reaction solution was successively washed with 50 mL saturated sodium bicarbonate and saturated sodium chloride solution for three times, the organic layer was dried and concentrated. Column chromatography was performed for the crude product (petroleum ether : ethyl acetate = 10:1) to give ethyl 3-(((4-oxo-3-1,4-dihydrophthalazin -1-yl)oxy)methyl)benzoate (1d), 6 g white solid (yield 30%). 1H NMR (600 MHz, DMSO-d6): delta 11.94 (s, 1H), 8.24 (d, 1H, J = 7.50 Hz), 7.97-7.95 (m, 1H),7.93-7.87 (m, 3H), 7.85-7.83 (m, 1H), 7.57-7.56 (m, 1H), 7.48-7.45 (m, 1H), 5.23 (s, 2H), 4.29-4.25 (m, 2H), 1.28-1.25 (m, 3H); ESI-MS m/z: calculated for 324.1, found 346.9 [M+Na]+.
30%		Phthalhydrazide (1b) (10 g, 61.7 mmol) was dissolved in dried N,N-dimethylformamide (100 mL) in a round-bottom flask. Sodium hydride (1.63 g, 67.9 mmol) was added at 0 C., and then stirred for half an hour. Ethyl 3-chloromethylbenzoate (1c, purchased from Shanghai Shaoyuan Co. Ltd.) (13.49 g, 67.9 mmol) dissolved in N,N-dimethylformamide (20 mL) solution was added slowly dropwise at room temperature and reacted for 24 hours, and then ethyl acetate was added. The reaction solution was successively washed with 50 mL saturated sodium bicarbonate and saturated sodium chloride solution for three times, the organic layer was dried and concentrated. Column chromatography was performed for the crude product (petroleum ether:ethyl acetate=10:1) to give ethyl 3-(((4-oxo-3-1,4-dihydrophthalazin-1-yl)oxy)methyl)benzoate (1d), 6 g white solid (yield 30%). 1H NMR (600 MHz, DMSO-d6): delta 11.94 (s, 1H), 8.24 (d, 1H, J=7.50 Hz), 7.97-7.95 (m, 1H), 7.93-7.87 (m, 3H), 7.85-7.83 (m, 1H), 7.57-7.56 (m, 1H), 7.48-7.45 (m, 1H), 5.23 (s, 2H), 4.29-4.25 (m, 2H), 1.28-1.25 (m, 3H); ESI-MS m/z: calculated for 324.1. found 346.9 [M+Na]+.

Reference： [1]Patent: EP2799435,2014,A1 .Location in patent: Paragraph 0049; 0068; 0070
[2]Patent: US2015/51211,2015,A1 .Location in patent: Paragraph 0094; 0096

60
[ 98-01-1 ]
[ 1445-69-8 ]
[ 109-77-3 ]
[ 1600504-04-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With Eosin Y In water at 20℃; for 2.5h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
91%	With tetrabutylammonium hydrogen sulfate In neat (no solvent) at 80℃; for 0.25h;	General procedure for the one-pot synthesis of 1H-pyrazolo[1,2-b]phtha-lazine-5,10-diones General procedure: To a mixture of aldehyde (2 mmol), malononitrile (2 mmol) and phthalhydrazide (2 mmol) in a round-bottom ask (25 mL), [Bu3NH][HSO4] (20 mol%) was addedand heated at 80 °C in an oil bath with proper stirring for the required time, as discussed in Table 2. The progress of the reaction was monitored by TLC (methanol: ethyl acetate: n-hexane 1:2:7). After completion of the reaction, hotwater (5 mL) was added to the reaction mixture and further stirred for 10 min. Afterthat, the reaction content was cooled to room temperature, and the precipitatedproduct was separated by simple ltration. The obtained crude product was puriedby re-crystallization in ethanol. Finally, the catalyst was recovered from the ltratesolution under reduced pressure. The recovered catalyst was washed withcyclohexane, dried and reused in subsequent runs. All products are known except(4m), and their physical and spectral data are in agreement with those reported forthe authentic samples [36, 44-49].
90%	With 1-decyl-3-methyl-imidazolium chloride coated sulfonated carbon(at)titania composite In water at 100℃; for 15h;

90%	With C₅H₉N₂O₆S₂⁽¹⁺⁾*Cl₃HSn at 60℃; for 0.333333h; Green chemistry;	Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones (4a-4m) catalyzed by IL1 or IL2 General procedure: A mixture of phthalhydrazide (1 mmol) with a desired aromatic aldehyde (1 mmol), malononitrile or ethyl cyanoacetate (1 mmol), and IL1 or IL2 (5 mol% based on aromatic aldehyde) was heated in an oil bath at 60°C for 10-30 min. The reaction was monitored by TLC. Upon completion of the process, the reaction mixture was cooled down to room temperature, distilled water (5 mL) was added to it, and the mixture was stirred for 5 min. The precipitated product was fi ltered off, washed with distilled water repeatedly and then recrystallized from ethanol (96%) to give the corresponding pure product 4a-4m. The catalyst that remained in water was reused in another cycle after evaporation of water.
86%	With ammonium cerium (IV) nitrate at 45℃; for 1.16667h;
86%	With sodium hydrogencarbonate In neat (no solvent) at 120℃; for 0.583333h; Green chemistry;	General Procedure for the Synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 4a-m catalyzed by NaHCO3 General procedure: A mixture of phthalhydrazide (1 mmol), anaromatic aldehyde (1 mmol), malononitrile or ethylcyanoacetate (1 mmol), and NaHCO3 (1 mmol) washeated in an oil bath at 120 °C for 15-50 min. Thereaction was monitored by TLC. Upon completionof the transformation, the reaction mixture was cooled to room temperature and warm water wasadded. This resulted in the precipitation of theproduct, which was collected by filtration. The crudeproduct was washed with warm water repeatedlyand then with warm ethanol to give compounds 4amin high yields.

Reference： [1]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[2]Shaikh, Mohd Akmal; Farooqui, Mazahar; Abed, Syed [Research on Chemical Intermediates, 2018, vol. 44, # 9, p. 5483 - 5500]
[3]Kour, Manmeet; Bhardwaj, Madhvi; Sharma, Harsha; Paul, Satya; Clark, James H. [New Journal of Chemistry, 2017, vol. 41, # 13, p. 5521 - 5532]
[4]Vafaee; Davoodnia; Nakhaei; Yadegarian; Nejatianfar [Russian Journal of General Chemistry, 2021, vol. 91, # 2, p. 273 - 278]
[5]Kidwai, Mazaahir; Chauhan, Ritika [Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1689 - 1696]
[6]Vafaee, Asieh; Davoodnia, Abolghasem; Pordel, Mehdi; Bozorgmehr, Mohammad Reza [Oriental Journal of Chemistry, 2015, vol. 31, # 4, p. 2153 - 2158]

61
[ 1445-69-8 ]
[ 620-23-5 ]
[ 109-77-3 ]
[ 1557278-49-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	With Eosin Y In water at 20℃; for 2h; Irradiation; Green chemistry;	2.1.2. Overall process of preparing (7a-u) General procedure: To a mixture of phthalhydrazide (5, 1.0 mmol), malononitrile (2, 1.0mmol) and aromatic aldehydes (6a-u, 1.0 mmol) in a EL/H2O (2:1) (3mL), was added Na2 eosin Y (1.5 mol%), under white light emittingdiode (LED) (18 W) irradiation (Scheme 4). The mixture was stirred for3 h at ambient temperature. The reaction progress was monitored byTLC utilizing n-hexane/EtOAc (3:1) as an eluent. After completing thereaction, the achieved solid was filtered, rinsed with water and the crudesolid was recrystallized from ethanol to provide the pure materialwithout requiring more purification
90%	In water at 20℃; for 3h; Irradiation; Green chemistry;	2.3. The overall process of preparing (7a-r) General procedure: Multifarious reagents including phthalhydrazide (5, 1.0 mmol),malononitrile (2, 1.0 mmol) and aromatic aldehydes (6a-r, 1.0 mmol)were reacted opposed to CFL (23 W) irradiation at room temperature inaqueous ethyl lactate (2:1, 3 mL) (Scheme 2). This was observed by TLCthat employed (ethyl acetate/n-hexane (1:3)). Afterwards, the filteringof the acquired solid was conducted, then the solid was rinsed water (2 ×3 mL) and ethanol (2 × 3 mL) and solid composition became recrystallizedby EtOH. The products were classified after the comparison ofspectroscopic information (1H NMR). Support for this manuscript can befound in the online version.
89%	With zirconium(IV) oxide In neat (no solvent) at 100℃;

86%	With (n-propyltrimethoxysilane-1,4-diazoniabicycle[2.2.2]octane chloride-butlylsulfonate)sulfate suppoted on nano rice husk In ethanol for 4h; Reflux;
86%	With dicationic 4,4'-bipyridinium dichloride ordered mesoporous silica nanocomposite In neat (no solvent) at 100℃; for 0.833333h;

Reference： [1]Mohamadpour, Farzaneh [Dyes and Pigments, 2021, vol. 194]
[2]Mohamadpour, Farzaneh [Journal of Photochemistry and Photobiology A: Chemistry, 2021, vol. 407]
[3]Piltan, Mohammad [Heterocyclic Communications, 2017, vol. 23, # 5, p. 401 - 403]
[4]Davarpanah, Jamal; Kiasat, Ali Reza [RSC Advances, 2015, vol. 5, # 11, p. 7986 - 7993]
[5]Bashti, Aigin; Kiasat, Ali Reza; Mokhtari, Babak [RSC Advances, 2015, vol. 5, # 33, p. 25816 - 25823]

62
[ 61127-23-9 ]
[ 1445-69-8 ]
[ 615-94-1 ]
C₃₀H₁₂N₈O₁₂ [ No CAS ]