Name: 577-56-0|2-Acetylbenzoic acid|97%
Brand: Ambeed
SKU: A237741
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1
[ 577-56-0 ]
[ 64-17-5 ]
[ 103935-10-0 ]

Reference： [1]Helvetica Chimica Acta,1941,vol. 24,p. 158,166
[2]Chemische Berichte,1896,vol. 29,p. 2521
[3]Green Chemistry,2019,vol. 21,p. 5368 - 5373

2
[ 577-56-0 ]
[ 3453-63-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With N,N,N',N'-tetramethyl-O-(N-succinimidyl)uronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 6h; Inert atmosphere;	Typical procedure for the synthesis of (Z)-3-ylidenephthalide 1a General procedure: To a solution of2-acetyl-benzoic acid (164 mg, 1.0 mmol) and TSTU (301 mg, 1.0 mmol) inCH2Cl2 (5.0 mL) was added DIEA (2.0 mmol). The reaction was allowed to stir atroom temperature for 6 h. Then, the reaction mixture was poured into water(10 mL), extracted using EtOAc (3 10 mL). The combined organic layers werewashed by brine with water (3 10 mL) and NaHCO3 aqueous (3 10 mL) anddried over Na2SO4. The solvent was removed by rotary evaporation to yield (Z)-3-ylidenephthalide 1a as a white solid (144 mg, 0.99 mmol, 99%): 1H NMR(400 MHz, CDCl3) d 7.88-7.86 (d, J = 8.0 Hz, 1H), 7.71-7.70 (m, 2H), 7.58-7.53(m, 1H), 5.21 (s, 2H). 13C NMR (100 MHz, CDCl3) d 166.8, 151.8, 139.0, 134.5,130.5, 125.2, 120.6, 91.3. LC-MS (M+Na+) calcd for C9H6NaO2 169, found 169
99%	With N,N,N',N'-tetramethyl-O-(N-succinimidyl)uronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 6h;
89%	With thionyl chloride In N,N-dimethyl-formamide at 60℃; for 2h;

61%	With thionyl chloride In N,N-dimethyl-formamide at 60℃; for 2h;
60%	With thionyl chloride
60%	With thionyl chloride In N,N-dimethyl-formamide at 60 - 62℃;	Synthesis of methylidene phthalide (MP) The synthesis of MP was carried out using an earlier described procedure.17 o-Acetylbenzoic acid (20.00 g, 0.12 mol) was placed in a four-necked round-bottom flask equipped with a stirrer, a thermometer, a reflux condenser, and a dropping funnel and dissolved in DMF (80 mL). The formed yellow-green solution was heated to 60 °C , and then thionyl chloride (13.04 mL, 0.18 mol) was added dropwise with such a rate that the temperature of the reaction medium did not exceed 62 °C. The solution was stirred for 2 h. Then the reaction mixture was cooled to ~20 °C and poured into an ice-water (1 : 1) mixture by small portions (5-7 mL). This resulted in the formation of a pale yellow precipitate, which was filtered off and thoroughly washed with water to the neutral pH of the medium. The filtered off precipitate was dried in vacuo for 2 h at 12 Torr and for 3 h at 1 Torr over P2O5. The dried product was sublimed in vacuo (10-3 Torr) at 40-42 °C. The final product (white crystals) were dried at ~20 °C in vacuo (1 Torr). The yield was 10.68 g (60%), m.p. 59 °C. Found (%): C, 74.02; H, 4.15; C, 74.09; H, 4.17. C9H6O2(146.15). Calculated (%): C, 73.97; H, 4.14. 1H NMR (400.13 MHz, CDCl3), δ: 7.83 (d, 1 H, (1), Ar, JHH = 8 Hz); 7.69-7.67 (d, 2 H, H(2), H(4), Ar); 7.57-7.52 (m, 1 H, H(3), Ar); 5.21-5.18 (2 H, CH2=, 5JHH = 8 Hz, 2JHH = 3 Hz). 13C NMR (100.61 MHz, CDCl3), δ: 166.8 (C=O); 151.8 (C=CH2); 138.9 (C(6), Ar); 134.5 (C(5), Ar); 130.5 (C(4), Ar); 125.1 (C(3), Ar); 124.9 (C(2), Ar); 120.6 (C(6), Ar); 91.3 (C=CH2). IR (KBr), ν/cm-1: 3518 (s); 3434 (s); 3126 (m); 3058 (m); 3013 (m); 2015 (w); 1919 (w); 1780 (vs, νC=O); 1663 (vs, νC=C); 1613 (s); 1594 (s); 1474 (s); 1392 (m); 1386 (m); 1343 (s); 1274 (vs, νC(O)-O), 1185 (s); 1126 (s); 1092 (s); 1010 (vs); 952 (vs); 887 (s); 861 (s); 765 (vs);695 (vs); 647 (s); 617 (s); 606 (s); 544 (s); 518 (s); 432 (s); 406 (s).
	With acetyl chloride
	With sulfuric acid

Reference： [1]He, Xinhua; Xue, Fengtian [Tetrahedron Letters, 2014, vol. 55, # 11, p. 1956 - 1958]
[2]Yang, Guoping; Li, Ke; Lin, Xiaoling; Li, Yijin; Cui, Chengxing; Li, Shixiong; Cheng, Yuanyuan; Liu, Yufeng [Chinese Journal of Chemistry, 2021, vol. 39, # 11, p. 3017 - 3022] Liu, Yu-Feng; Cao, Gang-Ming; Chen, Lei; Li, Ke; Lin, Xiao-Ling; Xu, Xin-Xin; Le, Zhang-Gao; Yang, Guo-Ping [Advanced Synthesis and Catalysis, 2022, vol. 364, # 8, p. 1460 - 1464]
[3]Liu, Kou-Chang; Howe, Robert K. [Journal of Organic Chemistry, 1983, vol. 48, # 24, p. 4590 - 4592]
[4]Ram, Shankar; Sharma, Ajay Kumar; Chauhan, Arvind Singh; Das, Pralay [Chemical Communications, 2020, vol. 56, # 73, p. 10674 - 10677]
[5]Puzin; Chebaeva; Egorov; Khatchenko [Russian Journal of Applied Chemistry, 2003, vol. 76, # 8, p. 1299 - 1303]
[6]Zdvizhkov; Novikov; Peregudov; Buzin; Nikiforova; Korlyukov; Papkov; Salazkin [Russian Chemical Bulletin, 2014, vol. 63, # 11, p. 2509 - 2514][Izv. Akad. Nauk, Ser. Khim., 2014, # 11, p. 2509 - 2514,6]
[7]Yale [Journal of the American Chemical Society, 1947, vol. 69, p. 1547]
[8]Kariyone; Shimizu [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1953, vol. 73, p. 336][Chem.Abstr., 1954, p. 2661]

3
[ 577-56-0 ]
[ 3453-64-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium hydroxide; sodium tetrahydroborate
93%	With iridium(lll) bis[2-(2,4-difluorophenyl)-5-methylpyridine-N,C₂₀]-4,40-di-tert-butyl-2,20-bipyridine hexafluorophosphate; triphenylphosphine In N,N-dimethyl-formamide; toluene Irradiation;
75%	With 1,2-bis(dimethylsilyl)ethane; tris(pentafluorophenyl)borate In dichloromethane at 20℃; for 0.166667h; Inert atmosphere;	2.3 General procedure to synthesize lactones from keto acids. General procedure: To a solution of levulinic acid (LA) (40 mg, 0.34 mmol) and (HMe2SiCH2)2 (55mg, 0.38 mmol) in anhydrous CH2Cl2 (4 mL) under argon atmosphere was addedB(C6F5)3 (1.8 mg, 0.0035 mmol) at room temperature. The resulting mixture wasstirred at the same temperature for 10 min before quenching with H2O (2 mL) andextraction with CH2Cl2 (3 × 3 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification of the crudeproduct by silica gel flash column chromatography (gradient eluent: 0-3% ofEtOAc/petroleum ether) afforded GVL (29 mg, 86% yield) as a colorless oil.

51%	With tris(triphenylphosphine)ruthenium(II) chloride; hydrogen In toluene at 180℃; for 24h;
	With sodium amalgam Behandeln mit Salzsaeure;
	With hydrogenchloride; ethanol; zinc
	With potassium hydroxide	19 Reference Example 19 Reference Example 19 (see Reaction Scheme 3) 100.96 g of 2-acetylbenzoic acid (3-1) was dissolved in 500 ml of aqueous solution of 41.37 g of potassium hydroxide, to which 20.35 g of sodium boron hydride was added little by little at a room temperature. The resulting mixture was stirred at a room temperature for 2 days, and thereafter, the resulting mixture was adjusted to pH 1 with concentrated hydrochloric acid and extracted with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and thereafter, the solvent was distilled off under reduced pressure. The resulting residue was purified by distilling under reduced pressure (117-121° C./3-5 mmHg) to obtain 86.45 g of 3-methylphthalide (3-2). 1H-NMR(CDCl3) δ: 1.64(3H, dd, J=1.2 Hz, 6.6 Hz), 5.58(1H, q, J=6.6 Hz), 7.45-7.90(4H, m)
	With sodium tetrahydroborate
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: sodium tetrahydroborate
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: sodium tetrahydroborate
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: sodium tetrahydroborate
	Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 24 h / 0 - 20 °C / Inert atmosphere 1.2: 0 °C / Inert atmosphere 2.1: 10% Pt/activated carbon; oxygen / water / 12 h / 80 °C / 760.05 Torr / Sealed tube
	With hydrogen; potassium hydroxide In isopropyl alcohol at 100℃; for 24h; Schlenk technique; Green chemistry;

Reference： [1]Tobia, David; Rickborn, Bruce [Journal of Organic Chemistry, 1986, vol. 51, # 20, p. 3849 - 3858]
[2]Stache, Erin E.; Ertel, Alyssa B.; Rovis, Tomislav; Doyle, Abigail G. [ACS Catalysis, 2018, vol. 8, # 12, p. 11134 - 11139]
[3]Xie, Hengmu; Lu, Ji; Gui, Yingying; Gao, Lu; Song, Zhenlei [Synlett, 2017, vol. 28, # 18, p. 2453 - 2459]
[4]Osakada, Kohtaro; Ikariya, Takao; Yoshikawa, Sadao [Journal of Organometallic Chemistry, 1982, vol. 231, # 1, p. 79 - 90]
[5]Gabriel; Michael [Chemische Berichte, 1877, vol. 10, p. 2209] Giebe [Chemische Berichte, 1896, vol. 29, p. 2534]
[6]Gabriel; Michael [Chemische Berichte, 1877, vol. 10, p. 2209]
[7]Current Patent Assignee: AVERY DENNISON CORPORATION - US2002/173517, 2002, A1
[8]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[9]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[10]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[11]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[12]Ban, Kazuho; Sajiki, Hironao; Sawama, Yoshinari; Takakura, Ryoya [Synlett, 2019, vol. 30, # 16, p. 1919 - 1923]
[13]Liu, Yaoqi; Lu, Zeye; Shen, Lingyun; Tu, Tao; Wu, Jiajie; Zheng, Qingshu [Green Chemistry, 2021, vol. 23, # 14, p. 5037 - 5042]

4
[ 577-56-0 ]
[ 5004-48-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrazine hydrate In isopropyl alcohol at 85℃; for 1h;
97%	With carbazic acid at 90℃; for 3h; Green chemistry;	3. General procedure for the solid state or solvent-free reactions between 1a and di-carbonyl compounds. General procedure: A 10.0 mmol for α-keto acid compound or a 5.2 mmol for β-diketones or α-keto acids was mixed with 0.40 g of hydrazinium carboxylate (1a, 5.2 mmol), respectively. (For solid di-carbonyl compound, the mixture was ground using a pestle and a mortar.) The mixture was stored in a closed vial, and then heated to 70 - 90 °C until the reaction was complete. Complete conversion to related product was dependent upon the nature of di-carbonyl compounds. Typically, those di-carbonyl compounds take about <3 h to complete the reactions. CO2 and water were released during the reaction. All products obtained from the reactions of 1a with di-carbonyl compounds were basically characterized by 1H and 13C NMR spectroscopy. The products have over 97% of purity of reaction mixture based on 1H NMR spectroscopy and isolation yields are over 97% based on di-carbonyl compounds. The melting points, elemental analysis and UV-Vis spectra for all azines, pyrazoles and pyridazinones, were measured after purification using appropriate solvent.
97%	With carbazic acid In neat (no solvent) at 90℃; for 3h;	65 Example 65 2-acetylbenzoic acid (8.2 g) at 90 °C for 3 hours. The remainder was the same as in Example 1. The obtained compound was 4-methylphthalazine-1(2H)-one, with a selectivity of 99% and a yield of 97%. The analytical results of this compound are shown below.

91%	With hydrazine hydrate In ethanol Reflux;
89%	With hydrazine hydrate In ethanol for 5h; Heating;
87%	With hydrazine hydrate In propan-1-ol for 2h; on boiling water bath;
50%	Stage #1: 2-acetyl-benzoic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.833333h; Inert atmosphere; Stage #2: With hydrazine In water; N,N-dimethyl-formamide at 20 - 25℃; for 13.5h; Inert atmosphere;
	With sodium hydroxide; hydrazinium sulfate
	With hydrazine hydrate In propan-1-ol Heating;
	With hydrazine hydrate In ethanol for 3h; Reflux;	Synthesis of 4-methyl/phenyl-1(2H)-phthalazinones (2, 3) General procedure: 2-Acetyl or 2-benzoylbenzoic acid derivatives (0.01 mol) and hydrazine hydrate (0.01 mol) in 30 mL of ethanol were refluxed for 3 hours. At the end of this period, the reaction mixture was cooled and the resulting precipitate was filtered to give compounds 2 and 3 respectively.
	With hydrazine hydrate In isopropyl alcohol at 85℃; for 1h;	1.1 Intermediate 1: 4-methyl-2H-phthalazin-1-one Hydrazine hydrate 78% (41 mL, 635 mmol, 1.3 eq) is added to a solution of2-acetylbenzoic acid(80 g, 488 mmol, 1 eq) in iPrOH (488 mL). The mixture is stirred at 85° C for 1 h. A precipitate is formedand filtered off. The filtrate is concentrated to give a precipitate which is filtered off. The two precipitatesare combined and the resulting solid is washed abundantly with H20 (3 x 3 L). To remove the residualwater, the solid is dissolved in THF and the solvent is removed under reduced pressure (2 x 1L) to yield thedesired product.
	With hydrazine hydrate In propan-1-ol for 2h;

Reference： [1]Allart, Brigitte; Auberval, Marielle; Blanc, Javier; Borgonovi, Monica; Brys, Reginald; Bucher, Denis; Christophe, Thierry; Coornaert, Beatrice; De Wachter, Maxim; Duys, Inge; El Bkassiny, Sandy; Heckmann, Bertrand; Houvenaghel, Nicolas; Jagerschmidt, Catherine; Jans, Mia; Jansen, Koen; Jaunet, Alex; Lecru, Lola; Letfus, Vatroslav; Mammoliti, Oscar; Marsais, Florence; Menet, Christel; Oste, Line; Palisse, Adeline; Poljak, Tanja; Pujuguet, Philippe; Rupcic, Renata; Saniere, Laurent; Smehil, Mario; Sonck, Kathleen; Triballeau, Nicolas; Tricarico, Giovanni; Waeckel, Ludovic; Wakselman, Emanuelle [Journal of Medicinal Chemistry, 2021, vol. 64, # 19, p. 14557 - 14586]
[2]Lee, Byeongno; Kang, Philjun; Lee, Kyu Hyung; Cho, Jaeheung; Nam, Wonwoo; Lee, Won Koo; Hur, Nam Hwi [Tetrahedron Letters, 2013, vol. 54, # 11, p. 1384 - 1388]
[3]Current Patent Assignee: SOGANG UNIVERSITY - KR101483445, 2015, B1 Location in patent: Paragraph 0308; 0349-0351
[4]Vila, Noemí; Besada, Pedro; Viña, Dolores; Sturlese, Mattia; Moro, Stefano; Terán, Carmen [RSC Advances, 2016, vol. 6, # 52, p. 46170 - 46185]
[5]Yamaguchi; Kamei; Koga; Akima; Kuroki; Ohi [Journal of Medicinal Chemistry, 1993, vol. 36, # 25, p. 4052 - 4060]
[6]Smolyar; Yutilov [Russian Journal of Organic Chemistry, 2008, vol. 44, # 2, p. 274 - 281]
[7]Mennen, Steven M.; Mak-Jurkauskas, Melody L.; Bio, Matthew M.; Hollis, L. Steven; Nadeau, Kelly A.; Clausen, Andrew M.; Hansen, Karl B. [Organic Process Research and Development, 2015, vol. 19, # 7, p. 884 - 891]
[8]Gabriel; Neumann [Chemische Berichte, 1893, vol. 26, p. 708]
[9]Location in patent: scheme or table Pakulska, Wanda; Malinowski, Zbigniew; Szczesniak, Aleksandra K.; Czarnecka, Elzbieta; Epsztajn, Jan [Archiv der Pharmazie, 2009, vol. 342, # 1, p. 41 - 47]
[10]Kiliç, Burcu; Gülcan, Hayrettin Ozan; Yalçin, Mertcan; Aksakal, Fatma; Dimoglo, Anatoli; Şahin, Mustafa Fethi; Doǧruer, Deniz Songül [Letters in drug design and discovery, 2017, vol. 14, # 2, p. 159 - 166]
[11]Current Patent Assignee: GALAPAGOS - WO2019/7696, 2019, A1 Location in patent: Paragraph 0221
[12]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]

5
[ 577-56-0 ]
[ 1077-79-8 ]

Reference： [1]Helvetica Chimica Acta,1941,vol. 24,p. 158,166

6
[ 577-56-0 ]
[ 7399-67-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	With bromine In acetic acid; toluene at 60℃; for 0.5h;
93%	With pyridinium hydrobromide perbromide In acetic acid for 4h;
	With bromine; acetic acid Eindampfen im Vakuum bei ca. 60grad und Aufkochen des Rueckstandes mit Chloroform;

	With bromine In acetic acid at 110℃; for 0.166667h;
	With bromine; acetic acid In toluene at 50℃; for 18h;
32 g	Stage #1: 2-acetyl-benzoic acid With acetic acid at 20℃; for 0.166667h; Stage #2: With pyridinium hydrobromide perbromide at 40℃; for 7h;	1-2 Step (1-2): Preparation of (2-(2-bromoacetyl) benzoic acid) Take a two-necked 500 ml flask as a reaction flask, which was added in the step (1-1) was obtained 2-acetyl benzoic acid (Compound 2) (23.8 g, 0.145 mol) and acetic acid (CAS N0. 64-19 -7; 15 ml) and stirred at room temperature for 10 minutes. Then the reaction flask was added pyridinium tribromide (CAS NO 39416-48-3;.. 1 3 equiv, 67 g) and heated to 40 ° C, to obtain a red homogeneous solution. The reaction for 7 hours at 40 ° C (reaction completion by NMR analysis instrument judgment). After completion of the reaction the reaction solution was poured into ice-water at 0 ° C, and the resulting mixture was stirred for 30 minutes. thenExtracted with ethyl acetate, and the organic layer was collected, the organic layer with 5% sodium thiosulfate (CAS N0. 7772-98-7)Solution and saturated brine, dried over anhydrous sodium sulfate to remove water and finally, concentrated in vacuo and the residual material was 32 g.
	With N-Bromosuccinimide; toluene-4-sulfonic acid In water; acetonitrile Reflux;

Reference： [1]Barcia, José C; Cruces, Jacobo; Estévez, Juan C; Estévez, Ramón J; Castedo, Luis [Tetrahedron Letters, 2002, vol. 43, # 29, p. 5141 - 5144]
[2]Krafft,G.A.; Katzenellenbogen,J.A. [Journal of the American Chemical Society, 1981, vol. 103, p. 5459]
[3]Gabriel [Chemische Berichte, 1907, vol. 40, p. 73]
[4]Chihiro; Nagamoto; Takemura; Kitano; Komatsu; Sekiguchi; Tabusa; Mori; Tominaga; Yabuuchi [Journal of Medicinal Chemistry, 1995, vol. 38, # 2, p. 353 - 358]
[5]Yang, Rui-Yang; Kizer, Darin; Wu, Hui; Volckova, Erika; Miao, Xiu-Sheng; Ali, Syed M.; Tandon, Manish; Savage, Ronald E.; Chan, Thomas C.K.; Ashwell, Mark A. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 10, p. 5635 - 5643]
[6]Current Patent Assignee: EVERFRONT BIOTECH - CN105524032, 2016, A Location in patent: Paragraph 0074; 0075; 0076; 0077; 0078
[7]Zermeño-Macías, María de los Ángeles; González-Chávez, Marco Martín; Méndez, Francisco; Richaud, Arlette; González-Chávez, Rodolfo; Ojeda-Fuentes, Luis Enrique; Niño-Moreno, Perla Del Carmen; Martínez, Roberto [Molecules, 2021, vol. 26, # 16]

7
[ 577-56-0 ]
[ 612-19-1 ]

Reference： [1]Chemische Berichte,1877,vol. 10,p. 2209
[2]Justus Liebigs Annalen der Chemie,1961,vol. 641,p. 51 - 62
[3]Acta Chemica Scandinavica,1989,vol. 43,p. 381 - 385
[4]Chemische Berichte,1896,vol. 29,p. 2534

8
[ 577-56-0 ]
[ 100-52-7 ]
[ 245328-53-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide In ethanol at 20℃; for 20h;
83%	With sodium hydroxide In ethanol for 24h; Ambient temperature;
	With sodium hydroxide

With sodium hydroxide In ethanol; water at 0 - 25℃; Inert atmosphere;

Reference： [1]Wang, Shaozhong; Cao, Liya; Shi, Haijian; Dong, Yanmei; Sun, Jianwei; Hu, Yuefei [Chemical and Pharmaceutical Bulletin, 2005, vol. 53, # 1, p. 67 - 71]
[2]Batt; Goodman; Jones; Kerr; Mantegna; McAllister; Newton; Nurnberg; Welch; Covington [Journal of Medicinal Chemistry, 1993, vol. 36, # 10, p. 1434 - 1442]
[3]Gutsche et al. [Journal of the American Chemical Society, 1958, vol. 80, p. 5756,5766] Hanson; Tarte [Bulletin des Societes Chimiques Belges, 1957, vol. 66, p. 619,627]
[4]Massaro, Nicholas P.; Stevens, Joseph C.; Chatterji, Aayushi; Sharma, Indrajeet [Organic Letters, 2018, vol. 20, # 23, p. 7585 - 7589]

9
[ 577-56-0 ]
[ 100-63-0 ]
[ 6941-96-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	In neat (no solvent, solid phase) at 70℃; for 3h;	105 Example 105 phenyl hydrazine 5.4 g was used, the reaction was stirred for 3 hours, and the rest is the same as in Example 101. Selectivity is 94%, the yield was 92%.
	With ethanol
	With methanol

With acetic acid

Reference： [1]Current Patent Assignee: SOGANG UNIVERSITY - KR101483445, 2015, B1 Location in patent: Paragraph 0461
[2]Rowe; Peters [Journal of the Chemical Society, 1931, p. 1918,1924]
[3]Rowe; Peters [Journal of the Chemical Society, 1931, p. 1918,1924]
[4]Rowe; Peters [Journal of the Chemical Society, 1931, p. 1918,1924]

10
[ 186581-53-3 ]
[ 577-56-0 ]
[ 1077-79-8 ]

Reference： [1]Journal of the American Chemical Society,1968,vol. 90,p. 4410 - 4413

11
[ 577-56-0 ]
[ 132-98-9 ]
[ 55361-58-5 ]

Reference： [1]Journal of Medicinal Chemistry,1976,vol. 19,p. 1385 - 1391

12
[ 577-56-0 ]
[ 57259-71-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	With lithium aluminium tetrahydride In diethyl ether
76%	Stage #1: 2-acetyl-benzoic acid With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 24h; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; water at 0℃; Inert atmosphere;	2-acetylbenzoic acid To a solution of 2-acetylbenzoic acid (1.31 g, 8.0 mmol) in THF (32 mL) was added lithiumaluminum hydride (0.45 g, 12.0 mmol) at 0 C under argon. After stirring for 24 h at 0 C to roomtemperature, H2O (1.5 mL) and 15 % NaOH aq. (0.5 mL) were added to the reaction mixture at 0 C.After further stirring for 2 h, the mixture was filtrated through celite pad with Et2O (200 mL), andthe filtrate was concentrated in vacuo. The residue was purified by silica-gel columnchromatography (n-hexane/EtOAc = 1/2 to 1/3) to give 1g (1.00 g, 6.1 mmol) in 76% yield.1H NMR (500 MHz, CDCl3): δ 7.48 (d, J = 7.0 Hz, 1H), 7.37-7.27 (m, 3H), 5.21-5.18 (m, 1H), 4.83(d, J = 12.0 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 1.60 (d, J = 6.0 Hz, 3H). Spectroscopic data of 1HNMR of 1g was identical to that of reference 7.
30%	With lithium aluminium tetrahydride In tetrahydrofuran at -1 - 20℃;

	With lithium aluminium tetrahydride In diethyl ether
	With lithium aluminium tetrahydride
	With sodium hydroxide In tetrahydrofuran; diethyl ether; water	X.1 1-(1-hydroxyethyl)-2-hydroxymethylbenzene EXAMPLE X 1 1-(1-hydroxyethyl)-2-hydroxymethylbenzene To a suspension of 12 g of lithium aluminium hydride in 50 ml of dry diethyl ether was added dropwise with stirring a solution of 25 g (152.4 mM) of 2-acetylbenzoic acid in 120 ml of dry tetrahydrofuran. After heating under reflux for 6 hours, the mixture was cooled and treated carefully with 12 ml of water, 12ml of 10% sodium hydroxide solution and 24 ml of water. The solution was filtered, the filtrate was dried over magnesium sulphate, filtered and evaporated to yield the title compound as a colourless waxy solid. 1 H nmr δ (CDCl3) 7.4-7.0 (4H,m); 4.9(1H,q); 4.48(1H, broad s); 3.98(2H, broad s, exchanges with D2 O); 1.4(3H,d).

Reference： [1]Klimovitskii, E.N.; Sergeeva, G.N.; Strel'nik, D.Yu.; Arbuzov, B.A. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1984, vol. 33, # 10, p. 2060 - 2065][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1984, # 10, p. 2259 - 2265]
[2]Ban, Kazuho; Sajiki, Hironao; Sawama, Yoshinari; Takakura, Ryoya [Synlett, 2019, vol. 30, # 16, p. 1919 - 1923]
[3]Miziak, Piotr; Zon, Jerzy; Amrhein, Nikolaus; Gancarz, Roman [Phytochemistry, 2007, vol. 68, # 4, p. 407 - 415]
[4]Pifferi; Monguzzi; Consonni [Farmaco, Edizione Scientifica, 1972, vol. 27, # 1, p. 30 - 45]
[5]Berner, Endre [Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1982, vol. 36, # 10, p. 729 - 731]
[6]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4918083, 1990, A

13
[ 577-56-0 ]
[ 75-03-6 ]
[ 103935-10-0 ]

Reference： [1]ChemCatChem,2017,vol. 9,p. 3989 - 3996
[2]Journal of Organic Chemistry,1971,vol. 36,p. 2740 - 2743
[3]Organic Letters,2009,vol. 11,p. 4712 - 4715

14
[ 577-56-0 ]
[ 598-99-2 ]
[ 1077-79-8 ]

Reference： [1]Synthetic Communications,1984,vol. 14,p. 77 - 82

15
[ 577-56-0 ]
[ 3453-64-3 ]
[ 57259-71-9 ]
[ 767-90-8 ]

Reference： [1]Chemistry Letters,1993,p. 1495 - 1498

16
[ 577-56-0 ]
(S)-3-methylisobenzofuran-1(3H)-one [ No CAS ]
[ 3413-14-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen In tetrahydrofuran; methanol for 15h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
	With sodium hydroxide; dihydrogen peroxide; dimethyl sulfate; diisopinocampheylborane 1.) 25 deg C, 12 h; 2.) 3 h; 3.) 2 h; Yield given. Multistep reaction;
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: dichloro(benzene)ruthenium(II) dimer; hydrogen; (S)-C₃-TUNEPHOS / methanol / 12 h / 50 °C / 30402 Torr / Autoclave

Reference： [1]Kitamura, M.; Ohkuma, T.; Inoue, S.; Sayo N.; Kumobayashi, H.; et al. [Journal of the American Chemical Society, 1988, vol. 110, # 2, p. 629 - 631]
[2]Ramachandran, P. Veeraraghavan; Chen, Guang-Ming; Brown, Herbert C. [Tetrahedron Letters, 1996, vol. 37, # 13, p. 2205 - 2208]
[3]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]

17
[ 577-56-0 ]
[ 95-54-5 ]
[ 6029-64-7 ]

Yield	Reaction Conditions	Operation in experiment
58%	In toluene for 6h; Heating;
52%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
52%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

31%

In toluene for 6h; Heating;

Reference： [1]Louvet; Thomasson; Luu-Duc [Journal of Heterocyclic Chemistry, 1994, vol. 31, # 1, p. 39 - 44]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[3]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[4]Hadfield; Pavlidis; Roffey [Synthetic Communications, 1995, vol. 25, # 9, p. 1319 - 1329]

18
[ 577-56-0 ]
[ 5233-04-5 ]
6,8-dichloro-4b,5-dihydro-4b-methyl-11H-isoindolo<2,1-a>benzimidazol-11-one [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1994,vol. 31,p. 39 - 44

19
[ 577-56-0 ]
[ 74-88-4 ]
[ 1077-79-8 ]

Yield	Reaction Conditions	Operation in experiment
		Example 8 Methyl 2-acetylbenzoate Methyl iodide (66.85 g) and potassium carbonate (118.40 g) were added to a solution of 2-acetylbenzoic acid (70.29 g) in dimethylformamide (500 mL) on ice bath, and the reaction mixture was stirred for an hour. The reaction mixture was filtered with Celite (trade name), and the filtrate was concentrated under reduced pressure. A saturated aqueous solution of ammonium chloride was added to the obtained residue, and the reaction mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and a saturated salt solution, and concentrated under reduced pressure after drying with anhydrous sodium sulfate. The title compound (72.24 g) having the following physical data was obtained. TLC: Rf 0.40 (hexane:ethyl acetate=3:1); 1H-NMR (CDCl3): delta 2.54 (s, 3H), 3.90 (s, 3H), 7.41 (dd, 1H), 7.45-7.61 (m, 2H), 7.84 (dd, 1H).
	With potassium carbonate; In acetone; at 60℃; for 16h;	2-Acetylbenzoic acid (0.98 g, 6 mmol), anhydrous potassiumcarbonate (1.93 g, 14 mmol) and iodomethane (1.13 g,8 mmol) were stirred at 60oC for 16 hours in acetone (30 mL).Next, the reaction was cooled to room temperature, acetoneremoved on a rotary evaporator and the solid was dissolvedin ethyl acetate (25 mL) and mixed with distilled water(25 mL) in a separatory funnel. The organic phase wasworked up in the usual way and methyl 2-acetylbenzoate waspurified by column chromatography (20% AcOEt in Hexane)to afford a pale yellow oil. NMR 1H (300 MHz, CDCl3) delta2.54 (s, 3H); 3.89 (s, 3H), 7.42 (d, J = 7.5, 1H), 7.85 (d,J = 7.5, 1H), 7.47-7.58 (m, 2H); NMR 13C (75 MHz, CDCl3)delta 29, 52, 126, 128, 129, 130, 132, 142, 167, 202; EM, m/z =178 (5%); 163 (100%); 147 (30%); 105 (15%), 77 (65%).

Reference： [1]ChemCatChem,2017,vol. 9,p. 3989 - 3996
[2]Organic Letters,2020
[3]Journal of Organic Chemistry,1962,vol. 27,p. 863 - 865
[4]Journal of Chemical Research, Miniprint,1986,p. 3020 - 3036
[5]Patent: US2012/94944,2012,A1 .Location in patent: Page/Page column 20
[6]Letters in Organic Chemistry,2016,vol. 13,p. 657 - 660
[7]Journal of the American Chemical Society,2019

20
[ 577-56-0 ]
[ 2921-14-4 ]
2-{1-[(E)-Carboxymethoxyimino]-ethyl}-benzoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1977,vol. 20,p. 1199 - 1206

21
[ 67-56-1 ]
[ 577-56-0 ]
[ 1077-79-8 ]

Reference： [1]Tetrahedron Asymmetry,1997,vol. 8,p. 3765 - 3774

22
[ 577-56-0 ]
[ 7726-95-6 ]
[ 5693-27-6 ]

Reference： [1]Journal of the Chemical Society,1963,p. 402 - 410

23
[ 67-56-1 ]
[ 577-56-0 ]
[ 1077-59-4 ]
[ 1077-79-8 ]

Reference： [1]Tetrahedron,2000,vol. 56,p. 5523 - 5534

24
[ 1077-79-8 ]
[ 67-56-1 ]
[ 577-56-0 ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),2001,p. 438 - 440

25
[ 577-56-0 ]
[ 426-65-3 ]
1-(2-carboxyphenyl)-4,4,5,5,5-pentafluoropentane-1,3-dione [ No CAS ]

Reference： [1]Australian Journal of Chemistry,2001,vol. 54,p. 335 - 341

26
[ 1077-79-8 ]
[ 577-56-0 ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 5141 - 5144

27
[ 577-56-0 ]
[ 1966-16-1 ]
[ 329922-58-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sulfuric acid In ethanol Heating;
70%	With sulfuric acid In ethanol at 100 - 120℃; for 1h;
70%	With sulfuric acid In ethanol for 1h; Reflux;

65%

With sulfuric acid In ethanol Heating;

Reference： [1]Kuznetsov; Shubin; Petrov [Russian Journal of Organic Chemistry, 2004, vol. 40, # 11, p. 1702 - 1704]
[2]Kuznetsov, Viktor A.; Shubin, Kirill M.; Schipalkin, Andrej A.; Petrov, Mikhail L. [Tetrahedron, 2006, vol. 62, # 42, p. 10018 - 10030]
[3]Location in patent: experimental part Kuznetsov; Shubin; Shchipalkin; Teplyakov; Petrov [Russian Journal of Organic Chemistry, 2008, vol. 44, # 5, p. 731 - 735]
[4]Shubin, Kirill M.; Kuznetsov, Viktor A.; Galishev, Vladimir A. [Tetrahedron Letters, 2004, vol. 45, # 7, p. 1407 - 1408]

28
[ 577-56-0 ]
[ 3034-19-3 ]
[ 297132-10-6 ]

Reference： [1]Russian Journal of Organic Chemistry,2004,vol. 40,p. 1702 - 1704
[2]Tetrahedron,2006,vol. 62,p. 10018 - 10030
[3]Russian Journal of Organic Chemistry,2008,vol. 44,p. 731 - 735

29
[ 85-44-9 ]
[ 141-82-2 ]
[ 577-56-0 ]

Yield	Reaction Conditions	Operation in experiment
68%	With pyridine for 3h; Heating;
68%	Stage #1: phthalic anhydride; malonic acid With triethylamine at 80℃; for 10h; Stage #2: With hydrogenchloride In water for 0.5h;	1 Example 1 : Preparation of 2-acetyl benzoic acid (Compound of formula (XI))A stirred mixture of phthalic anhydride (compound of formula (XII)) (2.3 kg, 1 eq) (commercially available), malonic acid (compound of formula (XIII)) (389g) (commercially available) and triethylamine (3.2 L) were heated to 80 °C. Further portions of malonic acid (5 x 389g; 1.94 kg total) were charged at 15 minute intervals and the reaction mixture maintained at 80 °C for 10 hrs. 4M hydrochloric acid (12.2L) was charged and the reaction stirred for a further 30 minutes before being cooled to 25°C and the resulting slurry filtered. The damp cake was washed with water (2 x 4 L) before being dried in vacuo at 50°C to give the title compound (1.73 kg, 68 %); 1 H NMR (400MHz, CDCI3): δ 1.97 (3H, s, CH3), 4.13 (1 H, br s, OH) 7.52 - 7.63 (2H, m, CH Ar), 7.69 - 7.73 (1 H, t, CH Ar), 7.84 - 7.86 (1 H, d, CH Ar); 13C NMR (100MHz, CDCI3) δ 26.0, 106.6, 122.1 , 125.4, 126.0, 130.5, 134.8, 149.8 and 169.3.
67%	Stage #1: phthalic anhydride With triethylamine at 80℃; Inert atmosphere; Heating; Large scale; Stage #2: malonic acid at 80℃; for 14h; Large scale;

52%	Stage #1: phthalic anhydride; malonic acid With triethylamine at 80℃; Stage #2: With sodium hydroxide In water
40%	Stage #1: phthalic anhydride; malonic acid With pyridine for 3h; Inert atmosphere; Reflux; Stage #2: With water at 30℃; for 0.5h; Inert atmosphere; Stage #3: In water at 10℃; for 16h; Inert atmosphere;
39%	With triethylamine at 65 - 80℃; for 20.8333h;	1-1 Step (1-1): Preparation of acetyl-2-acid (2-acetylbenzoic acid) Take a 1 liter three-necked flask as a reaction flask, to which was added phthalic anhydride was added (CAS NO 85-44-9;. 100 g, 0.67 mol)., Part of malonic acid (CAS NO 141- 82-2; 0 3 eq, 21 g) and part of the triethylamine (CASNO 121-44-8;. 1.5 eq., 140 ml), heated to an inner temperature was maintained at 65 ° C, the reaction at 65 ° C for 20 minutes,To obtain a yellow transparent homogeneous solution.The remaining malonic acid (1 equiv, 70 g) in three portions over 30 minutes was slowly added to the reaction flask, respectively, andThe remaining triethylamine (0.5 equiv., 50 ml) and the reaction was washed into the reaction flask on a solution. Followed by heating to a reaction flaskThe temperature was maintained at 80 ° C, the reaction at 80 ° C for 20 hours (the reaction completion by NMR analysis instrument judgment). Reacting Flow. The crude product was added ethyl acetate (107 ml) and heated to 55 ° C so that it dissolved to form a homogeneous solution, theThis homogeneous solution was slowly cooled to room temperature, followed by addition of n-hexane (107 ml), to give 2-acetyl benzoic acid crystallized, overBy filtration to give 43.6 g of 2-acetyl benzoic acid, a yield of about 39% .
	With triethylamine at 80℃; for 3h;	Synthesis of 2-Acetylbenzoic Acid The procedure was based on the protocol described byBritton et al. [26]. In a 50 mL round bottom flask equippedwith stir bar was added phthalic anydride (1.48 g, 10 mmol),malonic acid (2.60 g, 25 mmol) and triethyl amine (4 mL).The temperature was raised to 80oC and a further 0.56 g ofmalonic acid was added to the reaction after the first hourand 0.56 g of malonic acid was added again after the secondhour. The reaction was heated for a total of 3 hours at 80°C.Upon completion, the mixture was allowed to cool and thenstirred in distilled water (25 mL) for 30 minutes. The solutionwas acidified to pH 3-4 with 1M HCl, transferred toseparatory funnel and extracted with ethyl acetate (2 x 20 mL).The organic layers were combined, dried over Na2SO4, concentratedand the resulting oily residue was agitated with aglass rod in a 1:3 mixture of chloroform and n-hexanes toprecipitate a white solid. mp: 113-114°C (Lit.[27] mp. 114-115°C); 1H NMR (300 MHz, CDCl3): δ 1.88 (s, 3H), 4.50(brs, 1H), 7.52-7.58 (m, 2H), 7.69 (t, J = 7.2, 1H), 7.80 (d,J = 7.2, 1H); 13C NMR (75 MHz, CDCl3): δ 26, 122, 125,126, 130, 134, 149, 168.
	Stage #1: phthalic anhydride; malonic acid With triethylamine at 80℃; for 14h; Stage #2: With hydrogenchloride at 80℃; for 0.5h;

Reference： [1]Li, Juan; Zhao, Yan-Fang; Yuan, Xiao-Ye; Xu, Jing-Xiong; Gong, Ping [Molecules, 2006, vol. 11, # 7, p. 574 - 582]
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2012/80243, 2012, A2 Location in patent: Page/Page column 15
[3]Britton, Hugh; Catterick, David; Dwyer, Andrew N.; Gordon, Andrew H.; Leach, Stuart G.; McCormick, Chris; Mountain, Clive E.; Simpson, Alec; Stevens, David R.; Urquhart, Michael W. J.; Wade, Charles E.; Warren, John; Wooster, Nick F.; Zilliox, Audrey [Organic Process Research and Development, 2012, vol. 16, # 10, p. 1607 - 1617]
[4]Asano, Yuya; Nagasawa, Yoshitomo; Yamaguchi, Eiji; Itoh, Akichika [Chemistry - An Asian Journal, 2018, vol. 13, # 4, p. 409 - 412]
[5]Greszler, Stephen N.; Johnson, Jeffrey S. [Angewandte Chemie - International Edition, 2009, vol. 48, # 20, p. 3689 - 3691]
[6]Current Patent Assignee: EVERFRONT BIOTECH - CN105524032, 2016, A Location in patent: Paragraph 0067; 0068; 0069; 0070; 0071; 0072; 0073
[7]De Souza, Aline Aparecida Nunes; Taylor, Jason Guy [Letters in Organic Chemistry, 2016, vol. 13, # 9, p. 657 - 660]
[8]Jiang, Hongshuo; Mao, Guijie; Wu, Hongfeng; An, Qi; Zuo, Minghui; Guo, Weihao; Xu, Chunzhao; Sun, Zhizhong; Chu, Wenyi [Green Chemistry, 2019, vol. 21, # 19, p. 5368 - 5373]

30
[ 577-56-0 ]
[ 77-78-1 ]
[ 1077-79-8 ]

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 3689 - 3691
[2]Molecules,2006,vol. 11,p. 574 - 582

31
[ 577-56-0 ]
[ 98-86-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With copper(I) oxide; 1,10-Phenanthroline In 1-methyl-pyrrolidin-2-one; quinoline at 190℃; for 0.0833333h; Microwave irradiation;
79%	In quinoline at 170℃; for 6h;
72%	With [Au(1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene)(O₂CAd)] In toluene at 120℃; for 16h;

58%	With silver(I) acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 16h; Inert atmosphere;
98 %Chromat.	With copper(I) oxide; N,N,N,N,-tetramethylethylenediamine In 1-methyl-pyrrolidin-2-one at 140℃; for 0.333333h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Goossen, Lukas J.; Manjolinho, Filipe; Khan, Bilal A.; Rodriguez, Nuria [Journal of Organic Chemistry, 2009, vol. 74, # 6, p. 2620 - 2623]
[2]Goossen, Lukas J.; Rodriguez, Nuria; Melzer, Bettina; Linder, Christophe; Deng, Guojun; Levy, Laura M. [Journal of the American Chemical Society, 2007, vol. 129, # 15, p. 4824 - 4833]
[3]Dupuy, Stéphanie; Nolan, Steven P. [Chemistry - A European Journal, 2013, vol. 19, # 42, p. 14034 - 14038]
[4]Goossen, Lukas J.; Linder, Christophe; Rodriguez, Nuria; Lange, Paul P.; Fromm, Andreas [Chemical Communications, 2009, # 46, p. 7173 - 7175]
[5]Cahiez, Gerard; Moyeux, Alban; Gager, Olivier; Poizat, Mael [Advanced Synthesis and Catalysis, 2013, vol. 355, # 4, p. 790 - 796]

32
[ 577-56-0 ]
[ 106-38-7 ]
[ 16927-79-0 ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 2-acetyl-benzoic acid With potassium carbonate In various solvent(s) at 120℃; for 0.5h; Stage #2: para-bromotoluene With 1,10-Phenanthroline In various solvent(s) at 170℃; for 24h; Further stages.;
83 %Chromat.	With potassium carbonate In 1-methyl-pyrrolidin-2-one at 160℃; for 24h; Molecular sieve;	50 EXAMPLES 26-55; Examples 26-55 from Table 3, which were performed according to scheme 5 on a scale of 1 mmol, demonstrate the wide applicability of the process according to the invention. To determine the yields, after aqueous workup, the products were chromatographed on silica gel and characterized unambiguously with the aid of NMR, MS, HRMS.
66 %Chromat.	With caesium carbonate Molecular sieve;	56 Examples with a Catalytic Amount of Copper and a Catalytic Amount of Palladium; Examples 56-71 from Table 4, which were performed according to scheme 5 with 1 mmol of aryl bromide and 1.2 mmol of carboxylic acid, demonstrate that the two transition metals are required only in catalytic amounts irrespective of the substrates. To determine the yields, after aqueous workup, the products were chromatographed on silica gel and characterized unambiguously with the aid of NMR, MS, HRMS.

Reference： [1]Goossen, Lukas J.; Rodriguez, Nuria; Melzer, Bettina; Linder, Christophe; Deng, Guojun; Levy, Laura M. [Journal of the American Chemical Society, 2007, vol. 129, # 15, p. 4824 - 4833]
[2]Current Patent Assignee: EVONIK INDUSTRIES AG - US2008/177114, 2008, A1 Location in patent: Page/Page column 4; 7
[3]Current Patent Assignee: EVONIK INDUSTRIES AG - US2008/177114, 2008, A1 Location in patent: Page/Page column 8

33
[ 577-56-0 ]
[ 7460-55-1 ]

Reference： [1]Molecules,2006,vol. 11,p. 574 - 582
[2]Journal of the American Chemical Society,2019

34
[ 577-56-0 ]
(S)-3-methylisobenzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With [RuCl(benzene){(2,2,2',2'-tetramethyl[4,4'-bibenzo[d][1,3]dioxole]-5,5'-diyl)bis(diphenylphosphine)}]Cl; hydrogen In methanol at 50℃; for 12h; Autoclave; enantioselective reaction;
	Multi-step reaction with 2 steps 1: 53 percent / 97percent H₂SO₄ / 1 h / Heating 2: 92 percent / Geotrichum candidum IFO₃₄₆₁₄, H₂₀ / 24 h / 30 °C
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: [RuCl(benzene){(2,2,2',2'-tetramethyl[4,4'-bibenzo[d][1,3]dioxole]-5,5'-diyl)bis(diphenylphosphine)}]Cl; hydrogen / methanol / 12 h / 50 °C / 30402 Torr / Autoclave

	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: [RuCl(benzene){(2,2,2',2'-tetramethyl[4,4'-bibenzo[d][1,3]dioxole]-5,5'-diyl)bis(diphenylphosphine)}]Cl; hydrogen / methanol / 12 h / 50 °C / 30402 Torr / Autoclave
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 2: [RuCl(benzene){(2,2,2',2'-tetramethyl[4,4'-bibenzo[d][1,3]dioxole]-5,5'-diyl)bis(diphenylphosphine)}]Cl; hydrogen / methanol / 12 h / 50 °C / 30402 Torr / Autoclave

Reference： [1]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[2]Kitayama, Takashi [Tetrahedron Asymmetry, 1997, vol. 8, # 22, p. 3765 - 3774]
[3]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[4]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]
[5]Lu, Bin; Zhao, Mengmeng; Ding, Guangni; Xie, Xiaomin; Jiang, Lili; Ratovelomanana-Vidal, Virginie; Zhang, Zhaoguo [ChemCatChem, 2017, vol. 9, # 20, p. 3989 - 3996]

36
[ 92594-46-2 ]
[ 577-56-0 ]
compound 9 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 24h;	9 Example 9; Compound 9: (Formula [I ;] M = [M1,] L [=L2,] D = D6) To a solution of acetylsalicylic acid (D6) (52 mg; 0.29 mmole) in dry [CH2CI2] (5 ml) under argon, 0.380 mL (2.73 mmole) of triethylamine, 80 mg (0.59 mmole) of 1-hydroxybenzotriazole, 230 mg (0.29 mmole) of [ML2] and 235 mg (1.23 mmole) of [1- (3-DIMETHYLAMINOPROPYL)-3-ETHYL-CARBODIIMIDE] hydrochloride were added. The reaction mixture was stirred for 24 hours at room temperature in a flow of argon and concentrated under reduced pressure. Purification on a silica gel column eluting with CHCI3 : MeOH: NH40H = 6: 1: 0.1 gave 127 mg of compound 9. MS (m/z) : 955 [[MH] +.]

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2004/5309, 2004, A2 Location in patent: Page 50

37
[ 577-56-0 ]
[ 109-76-2 ]
[ 6166-34-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
98%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.
		24 EXAMPLE 24 EXAMPLE 24 16.4 Parts of o-acetyl-benzoic acid and 8 parts of 1,3-propanediamine are heated for 2 hours at 150°-160°. The reaction mixture is then distilled under high vacuum. The 10b-methyl-1,3,4,10b-tetrahydro-pyrimido[2,1-a]isoindol -6(2H)-one obtained of the formula STR35 boils at 120°-123°/0.1 Torr. After recrystallising from ethyl acetate/benzine, it melts at 64.5°.

Reference： [1]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[3]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - US4058529, 1977, A

38
[ 577-56-0 ]
[ 18107-18-1 ]
[ 1077-79-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	In methanol; hexane; benzene; at 0℃;	1.5 mL (3.0 mmole) of 2M trimethylsilyldiazomethane in hexane was gradually added dropwise at 0 C. to a mixed solution (1 mL of methanol, and 9 mL of benzene) of 328 mg (2.0 mmoles) of 2-acetylbenzoic acid. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography, yielding 330 mg (93 percent) of a methyl ester compound. 793 mg (2.04 mmole) of benzyl trimethyl ammonium tribromide was added to a 10 mL tetrahydrofuran solution of 330 mg (1.85 mmoles) of the above intermediate and the mixture was stirred for 14 hours at room temperature. Sodium hydrogencarbonate aqueous solution was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with anhydrous magnesium sulfate. The solvent was removed under reduced pressure, yielding 890 mg of crude phenylbromide compound. This compound was employed without purification in the subsequent reaction. Employing 250 mg (0.922 mmole) of the synthetic intermediate of Embodiment 13-III as starting material, 302 mg (quant.) of thioamide compound was obtained by the same procedure as in Embodiment 62-III. Employing 63 mg (0.246 mmole) of the above intermediate and 50 mg (0.164 mmole) of the above intermediate as starting materials, 39 mg (51 percent) of thiazole compound was obtained by the same procedure as in Embodiment 38-III. Employing 31 mg (0.067 mmole) of the above intermediate as starting material, 17 mg (57 percent) of Compound 35-III was obtained by the same procedure as in Embodiment 13-III.

Reference： [1]Patent: US2007/105899,2007,A1 .Location in patent: Page/Page column 75-76

39
[ 577-56-0 ]
1(R)-(4-methoxyphenyl)-ethylamine [ No CAS ]
[ 1036389-27-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	In toluene at 200℃; for 0.416667h; Microwave irradiation;	13.A To a 20 mL microwave vial was added 2-acetylbenzoic acid (1.8 g, 10.97 mmol), (R)-l-(4-methoxyphenyl)ethanamine (2 mL, 13.23 mmol) and toluene (2 mL) The reaction was heated 25 min. at 200 0C in the microwave. The crude reaction was concentrated and purified on SiC^, eluting w/ 0-100% EtO Ac/Hex to yield 13A (3.0 g, 10.74 mmol) in 98% yield as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.82 (d, J=7.47 Hz, 3 H) 3.78 (s, 3 H) 4.60 (d, J=2.20 Hz, 1 H) 5.07 (d, J=2.20 Hz, 1 H) 5.87 (q, J=7.47 Hz, 1 H) 6.85 (d, 2 H) 7.50 (t, J=6.15 Hz, 1 H) 7.55 (t, J=6.81 Hz, 1 H) 7.61 (d, 1 H) 7.85 (d, J=7.47 Hz, 1 H), MS (ESI) m/z 280.3 (M+H).
98%	In toluene at 200℃; for 0.416667h; Microwave irradiation;

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2008/79759, 2008, A1 Location in patent: Page/Page column 114-115
[2]Wurtz, Nicholas R.; Parkhurst, Brandon L.; Jiang, Wen; DeLucca, Indawati; Zhang, Xiaojun; Ladziata, Vladimir; Cheney, Daniel L.; Bozarth, Jeffrey R.; Rendina, Alan R.; Wei, Anzhi; Luettgen, Joseph M.; Wu, Yiming; Wong, Pancras C.; Seiffert, Dietmar A.; Wexler, Ruth R.; Priestley, E. Scott [ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1077 - 1081]

40
[ 577-56-0 ]
[ 16727-00-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium hydroxide In ethanol at 20℃; for 2h;
81%	With potassium <i>tert</i>-butylate In ethanol at 20℃; for 3h;
	With potassium <i>tert</i>-butylate In ethanol at 20℃; for 3h;

With potassium <i>tert</i>-butylate In ethanol for 3h; Inert atmosphere;

Reference： [1]Gooßen, Lukas J.; Rodríguez, Nuria; Linder, Christophe; Zimmermann, Bettina; Knauber, Thomas; Denmark, Scott E.; Werner, Nathan S. [Organic Syntheses, 2008, vol. 85, p. 196 - 208]
[2]Goossen, Lukas J.; Rodriguez, Nuria; Linder, Christophe [Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15248 - 15249]
[3]Location in patent: experimental part Goossen, Lukas J.; Linder, Bettina Zimmermanns Christophe; Rodriguez, Nuria; Lange, Paul P.; Hartung, Jens [Advanced Synthesis and Catalysis, 2009, vol. 351, # 16, p. 2667 - 2674]
[4]Tang, Jie; Goossen, Lukas J. [Organic Letters, 2014, vol. 16, # 10, p. 2664 - 2667]

41
[ 577-56-0 ]
[ 1015230-86-0 ]
[ 1023304-93-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With [bis(acetoxy)iodo]benzene; palladium diacetate In acetonitrile at 80℃; for 2h;

Reference： [1]Tang, Shi; Peng, Peng; Wang, Zhi-Qiang; Tang, Bo-Xiao; Deng, Chen-Liang; Li, Jin-Heng; Zhong, Ping; Wang, Nai-Xing [Organic Letters, 2008, vol. 10, # 9, p. 1875 - 1878]

42
[ 577-56-0 ]
[ 17264-81-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydrogencarbonate In water	7.A Step A: Sodium 2-acetylbenzoate (7a) Adapting procedures or variations thereof according to Howe, et al., J. Heterocyclic Chem. 1982, 19, 721-726; and Bonnaud, et al., Eur. J. Org. Chem. 2005, 3360-3369, a 250 mL round-bottomed flask was charged with 2.55 g (15.52 mmol) of 2-acetyl benzoic acid and 1.030 g (15.52 mmol) of sodium bicarbonate (NaHCO3). Ca. 50 mL of de-ionized water was added and the reaction mixture was gently heated until the solution became clear and the gas evolution subsided. The solvent was lyophilized of to yield a colorless solid. The material thus obtained was further dried under reduced pressure at 80° C. overnight and residual water was azeotropically removed with toluene to yield 2.89 g (quant.) of the title compound (7a) as a colorless solid, which was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ=2.34 (s, 3H), 7.00-7.07 (m, 1H), 7.25-7.34 (m, 2H), 7.68-7.74 (m, 1H) ppm. MS (ESI) m/z 164.82 (M+H)+; 186.86 (M+Na)+, 162.88 (M-H)-.

Reference： [1]Current Patent Assignee: AZURITY PHARMACEUTICALS INC - US2009/99253, 2009, A1 Location in patent: Page/Page column 43

43
[ 577-56-0 ]
potassium phenyltrifluoborate [ No CAS ]
C₁₅H₁₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With dipotassium hydrogenphosphate; oxygen; palladium diacetate; p-benzoquinone In <i>tert</i>-butyl alcohol at 100℃; for 24h;

Reference： [1]Wang, Dong-Hui; Mei, Tian-Sheng; Yu, Jin-Quan [Journal of the American Chemical Society, 2008, vol. 130, # 52, p. 17676 - 17677]

44
[ 577-56-0 ]
[ 1077-79-8 ]
[ 99-61-6 ]
[ 1236299-44-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3841 - 3859

45
[ 577-56-0 ]
[ 292638-85-8 ]
[ 112212-88-1 ]

Yield	Reaction Conditions	Operation in experiment
30%	With oxygen; palladium diacetate In dimethyl sulfoxide; N,N-dimethyl-formamide at 120℃; for 10h; optical yield given as %de; diastereoselective reaction;

Reference： [1]Fu, Zhengjiang; Huang, Shijun; Su, Weiping; Hong, Maochun [Organic Letters, 2010, vol. 12, # 21, p. 4992 - 4995]

46
[ 577-56-0 ]
[ 120-14-9 ]
[ 1259022-89-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 2-acetyl-benzoic acid; 3,4-dimethoxy-benzaldehyde With potassium hydroxide In methanol; water for 16h; Reflux; Stage #2: With hydrogenchloride In water	1 (E)-2-[3-(3, 4-Dimethoxyphenyl)-1-oxo-2-propenyl]benzoic acid (FT114)A solution of 3,4-dimethoxybenzldehyde (0.37 g, 2.2 mmol) and 2-acetylbenzoic acid (0.33 g, 2.0 mmol) was dissolved in MeOH (10 mL) and treated with 50% aqueous KOH (1 mL). The mixture was heated to reflux for 16 h and then concentrated under reduced pressure to remove the MeOH. Water was added and the aqueous phase was acidified with 1 M HCI. The crude product was collected by filtration and recrystallised from EtOH providing (E)-2-[3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]benzoic acid (0.45 g, 72%) as a yellow crystalline solid; mp 221-223 0C; δH (500 MHz, DMSO-d6) 3.79 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 6.96 (d, J5,6. = 8.0 Hz, 1 H, H51), 7.09 (d, J = 17.0 Hz, 1H, CH=CHCO), 7.13 (d, J = 17.0 Hz, 1 H, CH=CHCO), 7.20 (d, = 8.0 Hz, 1H, H61), 7.32 (s, 1 H, H21), 7.45 (d, J3,4 = 8.0 Hz, 1H, H3), 7.60 (t, J45 = J5β = 8.0 Hz, 1H, H5), 7.67 (t, •AM = As = 8.0 Hz, 1 H, H4), 7.90 (d, J5β = 8.0 Hz, 1H, H6), 13.10 (br s, 1H, CO2H); δc (125 MHz1 DMSO-cfc) 55.5, 55.6, 110.5, 111.5, 123.2, 125.1 , 127.0, 127.4, 129.6, 130.3, 131.8, 141.8, 144.6, 149.0, 151.1, 167.5, 195.5; HRMS (ESI) calculated for C18H16O5 [M+H]+ 313.1071, found 313.1071 ; vmax 1138, 1251 , 1584, 1707, 2844, 2913 cm"1.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2010/144959, 2010, A1 Location in patent: Page/Page column 49

47
[ 577-56-0 ]
[ 127842-54-0 ]
[ 1259022-93-9 ]

Yield	Reaction Conditions	Operation in experiment
40%		(E)-2-[3,4-Bis(difluoromethoxy)phenyl)-1-oxo-2-propenyl]benzoic acid (FT116)A solution of <strong>[127842-54-0]3,4-bis(difluoromethoxy)benzaldehyde</strong> (0.52 g, 2.2 mmol) and 2- acetylbenzoic acid (0.33 g, 2.0 mmol) was dissolved in MeOH (10 ml_) and treated with 50% aqueous KOH (1 ml_). The mixture was stirred at rt for 16 h and then concentrated under reduced pressure to remove the MeOH. Water was added and the aqueous phase was acidified with 25% AcOH. The crude product was collected by filtration and recrystallised from toluene/petrol providing (£)-2-[3,4-bis(difluoromethoxy)phenyl)-1-oxo- 2-propenyl]benzoic acid (0.31 g, 40%) as a colourless crystalline solid; mp 118-119 0C; 7.18 (d, J = 15.6 Hz, 1H, CH=CHCO), 7.23 (d, J = 15.6 Hz, 1H, CH=CHCO), 7.24 (t, J = 73 Hz, 1H, OCHF2), 7.26 (t, J = 73 Hz, 1 H, OCHF2), 7.35 (d, J5',* = 8.0 Hz, 1H, H5'), 7.45 (d, J3,4 = 8.0 Hz, 1 H, H3), 7.61-7.71 (m, 3H, H4, H5, H61), 7.75 (s, 1H, H2"), 7.91 (d, J5\|6 = 8.0 Hz, 1H, H6), 13.10 (br s, 1 H, CO2H); deltac (125 MHz, DMSO-d6) 55.5, 55.6, 116.2 (t, J = 268 Hz), 116.4 (t, J = 268 Hz)1 120.2, 120.6, 126.8, 127.5, 128.4, 129.7, 129.9, 130.2, 132.0, 132.6, 141.4, 141.6, 141.8, 143.0, 167.4, 195.5; HRMS (ESI) calculated for C18H12F4O5 [M+H]+ 385.0694, found 385.0694; vmax 1072, 1035, 1277, 1667, 1688, 2833, 3011 cm"1.

Reference： [1]Patent: WO2010/144959,2010,A1 .Location in patent: Page/Page column 50

48
[ 577-56-0 ]
[ 5651-83-2 ]
[ 1259022-95-1 ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: 2-acetyl-benzoic acid; 3-methoxy-4-(prop-2-ynyloxy)benzaldehyde With potassium hydroxide In methanol; water at 20℃; for 16h; Stage #2: With acetic acid In water	1 (E)-2-[3-Methoxy-4-(propargyloxy)phenyl)-1-oxo-2-propenyl]benzoic acid (FT117)A solution of 3-methoxy-4-propargyloxybenzaldehyde (0.21 g, 1.1 mmol) and 2- acetylbenzoic acid (0.16 g, 1.0 mmol) was dissolved in MeOH (10 ml.) and treated with 50% aqueous KOH (1 mL). The mixture was stirred at rt for 16 h and then concentrated under reduced pressure to remove the MeOH. Water was added and the aqueous phase was acidified with 25% AcOH. The crude product was collected by filtration and recrystallised from toluene providing (E)-2-[3-Methoxy-4-(propargyloxy)phenyl)-1-oxo-2- propenyl]benzoic acid (0.17 g, 52%) as a colourless crystalline solid; mp 146-147 0C; δH (500 MHz, DMSO-Cf6) 3.67 (t, J = 2.4 Hz, 1 H, C≡CH), 3.90 (s, 3H, OCH3), 4.93 (d, J = 2.4 Hz, 2H, OCH2), 7.12 (d, J5 ,6. = 8.0 Hz, 1 H, H5'),7.23 (s, 2H, CH=CHCO, CH=CHCO), 7.31 (dd, J5 , 6. = 8.0 Hz, J2 , 6. = 2.0 Hz), 7.45 (d, J26. = 2.0 Hz, 1H, H21), 7.56 (d, J3,4 = 8.0 Hz, 1H, H3), 7.70 (t, J4,5 = J5,6 = 8.0 Hz, 1H, H5), 7.78 (t, J3,4 = J4,5 = 8.0 Hz, 1 H, H4), 8.00 (d, J56 = 8.0 Hz1 1H, H6), 13.12 (br s, 1 H, CO2H); δc (125 MHz, DMSO-cfe) 55.7, 55.9, 78.5, 78.9, 111.0, 113.5, 122.6, 125.6, 127.4, 128.0, 129.6, 129.7, 130.3, 131.9, 141.7, 144.3, 148.7, 149.3, 167.5, 195.5; HRMS (ESI) calculated for C20H16O5 [M+H]+ 337.1070, found 337.1070; vmax 1141, 1253, 1507, 1585, 1701, 2960, 3290 cm"1.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2010/144959, 2010, A1 Location in patent: Page/Page column 50-51

49
[ 577-56-0 ]
[ 5693-27-6 ]

Yield	Reaction Conditions	Operation in experiment
75%		Example 2: Preparation of 1 /-/-2-benzopyran-1 ,4(3/-/)-dione (Compound of formula (III))A stirred mixture of 2-acetylbenzoic acid (compound of formula (XI)) (1.00 Kg, 6.09 mol) and chlorobenzene (10.0 L) was treated with 5.5 molar hydrobromic acid in acetic acid (55 ml_) and bromine (310 ml_) then warmed to approximately 30 C. After 3 hours water (10.0 L) was added and the reaction heated to reflux. After 3 hours the reaction was cooled to 60 C and the organic layer removed. The aqueous layer was extracted with chlorobenzene (2.0 L) and the combined organic layers concentrated under reduced pressure to approximately 3.0 L. Propan-2-ol (5.0 L) was charged and the slurry cooled to 0 C before being filtered and washed with propan-2-ol (2.0 L). The resulting solid was dried in vacuo at 50 C to give the title compound (736 g, 75%); 1 H NMR (400MHz, CDCI3): delta 5.14 (2H, s, H-9), 7.82 - 7.91 (2H, m, H-2 and 3), 8.08 - 8.10 (1 H, m, H-1), 8.28 - 8.30 (1 H, m, H-4); 13C NMR (100MHz, CDCIs) delta 73.4, 125.6, 128.0, 130.9, 131.8, 134.7, 135.9, 161.4 and 189.5.
63%	With hydrogen bromide; bromine; acetic acid; at 40℃; for 0.5h;	Step 1: lH-Isochromene-l,4(3H)-dione [00369] To a solution of 2-acetylbenzoic acid (8.458 g, 51.52 mmol) in acetic acid (50.0 mL, 879 mmol) was added 30 ml of 33% HBr in acetic acid. Bromine (8.646 g, 54.10 mmol) was next added to the solution, and the reaction was heated to 40 C with stirring for 30 min. The reaction mixture was poured into 300 ml water, the layers were separated, and the aqueous layer was extracted with 3 x 100ml DCM. Combined the organic layers and concentrated in vacuo to yield crude intermediate, which was dissolved in 25 ml acetic acid, 130ml toluene and 30 ml water. The resulting mixture was stirred at reflux overnight. The reaction was cooled to rt, and the layers were separated. The organic layer was concentrated in vacuo and purified by flash column ( 120g column, eluent 0-55% EtOAc in hexane)to afford 5.24g (63%) of title compound. NMR (400 MHz, Chloroform-d) delta 8.36 - 8.28 (m, 1 H), 8.17 - 8.07 (m, 1 H), 7.95 - 7.79 (m, 2H), 5.16 (s, 2H).

Reference： [1]Patent: WO2012/80243,2012,A2 .Location in patent: Page/Page column 15-16
[2]Antimicrobial Agents and Chemotherapy,2017,vol. 61
[3]Patent: WO2016/4136,2016,A1 .Location in patent: Paragraph 00369
[4]Organic Process Research and Development,2012,vol. 16,p. 1607 - 1617

50
[ 577-56-0 ]
3-formylphthalide [ No CAS ]
[ 5693-27-6 ]

Reference： [1]Organic Process Research and Development,2012,vol. 16,p. 1607 - 1617

51
[ 577-56-0 ]
[ 109853-38-5 ]
(1S*,4R*,4aR*,6aR*,12aS*)-1,4-methano-6,6a-dimethyl-1,4,4a,6,6a,12a-hexahydroisoindolo[2,1-a]quinazoline-5,11-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With toluene-4-sulfonic acid In toluene for 16h; Reflux; diastereoselective reaction;
83%	With toluene-4-sulfonic acid In toluene at 110℃; for 6h; Flow reactor;

Reference： [1]Miklos, Ferenc; Toth, Zita; Haenninen, Mikko M.; Sillanpaeae, Reijo; Forro, Eniko; Fueloep, Ferenc [European Journal of Organic Chemistry, 2013, # 22, p. 4887 - 4894]
[2]Nekkaa, Imane; Palkó, Márta; Mándity, István M.; Miklós, Ferenc; Fülöp, Ferenc [European Journal of Organic Chemistry, 2018, vol. 2018, # 32, p. 4456 - 4464]

52
[ 577-56-0 ]
[ 3182-95-4 ]
[ 1431509-13-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	In toluene for 16h; Inert atmosphere; Dean-Stark; Reflux;
92%	In toluene for 16h; Reflux; Dean-Stark; Inert atmosphere; enantioselective reaction;	General preparation of compounds 1a-c, 2a-b, 3a-b and 4a-b General procedure: To a stirred solution of the appropriate aminoalcohol (0.1 g,0.66 mmol) in toluene (10 mL), it was added 1.1 eq of the appropriateb-oxo-acid. The mixture was then refluxed under a dean-starkapparatus and in an inert atmosphere. After cooling the reaction to room temperature the solvent was evaporated to dryness. Thecrude residue obtained was adsorbed onto silica and purified byflash chromatography with the adequate solvent system.

Reference： [1]Pereira, Nuno A. L.; Sureda, Francesc X.; Turch, Mireia; Amat, Mercedes; Bosch, Joan; Santos, Maria M. M. [Monatshefte fur Chemie, 2013, vol. 144, # 4, p. 473 - 477]
[2]Soares, Joana; Pereira, Nuno A.L.; Monteiro, ngelo; Leo, Mariana; Bessa, Cludia; Dos Santos, Daniel J.V.A.; Raimundo, Liliana; Queiroz, Glria; Bisio, Alessandra; Inga, Alberto; Pereira, Clara; Santos, Maria M.M.; Saraiva, Luclia [European Journal of Pharmaceutical Sciences, 2015, vol. 66, p. 138 - 147]

53
[ 577-56-0 ]
[ 30235-26-8 ]
2-[(2-acetylbenzoyl)amino]-4-(pyridin-2-yl)thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%		General procedure: 5.1.3. General procedure C. To the carboxylic acid substrate (0.42 mmol, 1.2 equiv) in DMF (1.5 mL) was added CDI (0.50 mmol, 1.1equiv) and DBU (0.67 mmol, 1.9 equiv). The reaction was stirred for 30 min at 23 C. Next, 2-amino-4-(2-pyridyl)thiazole 20 (0.35 mmol, 1.0 equiv) was added and the reaction mixture was stirred for 16 h at 23 C. A small amount of silica gel was added to the reaction mixture, which was concentrated in vacuo under reduced pressure. The crude product impregnated on the silica gel was purified by silica gel flash chromatography (0-10% MeOH-CH2Cl2) to afford the title compound.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6385 - 6397

54
[ 5344-90-1 ]
[ 577-56-0 ]
10-methyl-9-oxa-1-azatetracyclo[8.7.0.0^2,7.0^11,16]heptadeca-2⁽⁷⁾,3,5,11⁽¹⁶⁾,12,14-hexaen-17-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; methyl chloroformate In toluene at 0 - 20℃; for 24h;
89%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
89%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

Reference： [1]Jha, Amitabh; Naidu, Ajaya B.; Abdelkhalik, Ashraf M. [Organic and Biomolecular Chemistry, 2013, vol. 11, # 43, p. 7559 - 7565]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[3]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]

55
[ 67-56-1 ]
[ 577-56-0 ]
[ 1602924-39-9 ]

Yield	Reaction Conditions	Operation in experiment
55%	With Oxone; ammonium chloride; trimethyl orthoformate at 20℃; for 12h;	Synthesis of α-chloroketone dimethyl acetal (2) General procedure: Ketone 1 (0.5 mmol), Oxone (0.6 mmol), NH4Cl (1.0 mmol) and HC(OMe)3 (1.0 mmol) were added to MeOH (2 mL). The mixture was stirred at room temperature and then the solvent was evaporated under reduced pressure. H2O (10 mL) were added, the mixture was extracted with CH2Cl2 (3*5 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on a silica gel plate using (4:1 hexane-ethyl acetate) as eluant to give the α-chloroketone dimethyl acetal 2.

Reference： [1]Zhou, Zhong-Shi; Li, Li; He, Xue-Han [Journal of Chemical Research, 2013, vol. 37, # 10, p. 633 - 635]

56
[ 577-56-0 ]
[ 110-82-7 ]
cyclohex-2-en-1-yl 2-acetylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With tert.-butylhydroperoxide; (6,8,15,17-tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecinato)copper(II) In neat (no solvent) at 80℃; for 24h; Schlenk technique; Inert atmosphere;	4.4. General procedures for dehydrogenative functionalization of alkanes toallylic esters (in absence of added solvent) General procedure: Under an argon atmosphere, [Cu(MeTAA)] (2.0 mg, 0.005 mmol)and benzoic acid (61 mg, 0.5 mmol) were added in an oven-dried Schlenk tube containing a magnetic stir bar. The Schlenk tube wasevacuated and back filled with argon (3 cycles). Subsequently1.50 mmol (3.0 equiv) of TBHP and 1.0 mL cyclohexane were injected to the Schlenk tube via a syringe. Then the Schlenk tube was placed intoan oil bath and heated at 80 °C for 24 h. Once the reaction was completed,the reaction mixture was concentrated in vacuum and the residuewas dissolved in dichloromethane and purified by column chromatographyusing silica and hexane was used as eluent.
59 %Spectr.	With di-tert-butyl peroxide; copper(l) chloride In benzene at 100℃; for 24h; Inert atmosphere; Sealed tube;

Reference： [1]Mondal, Rakesh; Chakraborty, Gargi; van Vliet, Kaj M.; van Leest, Nicolaas P.; de Bruin, Bas; Paul, Nanda D. [Inorganica Chimica Acta, 2020, vol. 500]
[2]Tran, Ba L.; Driess, Matthias; Hartwig, John F. [Journal of the American Chemical Society, 2015, vol. 136, # 49, p. 17292 - 17301]

57
[ 577-56-0 ]
6-chloro-5,7-dimethyl-2,3-dihydro-1H-2,4,7a,8-tetraaza-cyclopenta[a]indene hydrochloride [ No CAS ]
[ 1445803-73-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In dichloromethane at 0 - 20℃; for 2h;	6.1 Step 1: 1-(2-(3-chloro-2, 4-dimet hyl-8 , 9-dihydro- 7H-pyrrolo[3’, 4 ‘:3, 4]pyrazolo[1, 5-a]pyrimidine-8-carbonyl)phenyl)ethan- 1-one To a stirred solution of Intermediate Al (1.0 g, 3.85 mmol) and 2-acetylbenzoic acid (0.7 g, 4.24 mmol, Alfa Acer) in DCM (20 mL) was added tn ethylamine (1.7 mL, 11.5 mmol, Spectrochem) followed by T3P (3.7 mL, 5.78 mmol) at 0 00. The reaction mixture was stirred at RT for 2 h. Reaction completion was monitored by LCMS. DCMwas evaporated under vacuum. The resulting solid was washed with water. The crude product was triturated with n-hexanes and dried under vacuum, affording the title product as white solid (1 g, 79%). 1H NMR (400 MHz, DMSO-d6): 6 8.05 (d, J = 10.2 Hz, 1H), 7.72-7.58 (m, 2H), 7.49-7.46 (m, 1H), 4.84 (s, 1H), 4.82 (s, 1H), , 4.42 (s, 1H), 4.37 (s, 1H) 2.85 (s, 1.5H), 2.80 (s, 1.5H), 2.63 (s, 1.5H), 2.57 (m, 4.5H). LCMS: (Method A)369.0 (M+H), Rt. 3.5 mm, 99.2% (Max).
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In dichloromethane at 0 - 20℃; for 2h;	6.1 Step 1: 1-(2-(3-chloro-2,4-dimethyl-8,9-dihydro-7H-pyrrolo[3;4':3,4]pyrazolo[1,5-a]pyrimidine-8-carbonyl)phenyl)ethan-1-one Step 1: 1-(2-(3-chloro-2,4-dimethyl-8,9-dihydro-7H-pyrrolo[3;4':3,4]pyrazolo[1,5-a]pyrimidine-8-carbonyl)phenyl)ethan-1-one To a stirred solution of Intermediate A1 (1.0 g, 3.85 mmol) and 2-acetylbenzoic acid (0.7 g, 4.24 mmol, Alfa Acer) in DCM (20 mL) was added tri ethylamine (1.7 mL, 11.5 mmol, Spectrochem) followed by T3P (3.7 mL, 5.78 mmol) at 0 °C. The reaction mixture was stirred at RT for 2 h. Reaction completion was monitored by LCMS. DCM was evaporated under vacuum. The resulting solid was washed with water. The crude product was triturated with n-hexanes and dried under vacuum, affording the title product as white solid (1 g, 79%). 1H NMR (400 MHz, DMSO-d6): δ 8.05 (d, J = 10.2 Hz, 1 H), 7.72-7.58 (m, 2H), 7.49-7.46 (m, 1 H), 4.84 (s, 1 H), 4.82 (s, 1 H), , 4.42 (s, 1 H), 4.37 (s, 1 H) 2.85 (s, 1.5H), 2.80 (s, 1.5H), 2.63 (s, 1.5H), 2.57 (m, 4.5H). LCMS: (Method A) 369.0 (M+H)+, Rt. 3.5 min, 99.2% (Max).

Reference： [1]Current Patent Assignee: ASCENEURON SA - WO2014/198808, 2014, A1 Location in patent: Page/Page column 111
[2]Current Patent Assignee: ASCENEURON SA - EP2813505, 2014, A1 Location in patent: Paragraph 0137

58
[ 577-56-0 ]
L-tryptophanol [ No CAS ]
(3S,9bR)-3-((1H-indol-3-yl)methyl)-9b-methyl-2,3-dihydrooxazolo[2,3-a]isoindol-5(9bH)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In toluene for 16h; Reflux; Inert atmosphere; Dean-Stark; stereoselective reaction;
75%	In toluene Reflux; Dean-Stark;	Experimental procedure for the preparation of tryptophanol- derived oxazoloisoindolinones General procedure: In a preferred embodiment r the tryptophanol -derived oxazoloisoindolinones are prepared according to the following method: To a stirred solution of tryptophanol (0,842 mmol, 1.0 eq.) in 15 mL of toluene, under reflux in a Dean-Stark apparatus, was added 2-acetyl-benzoic Acid. The reaction was kept under reflux until total consumption of the starting material. The solvent was evaporated and the residue obtained was purified by flash chromatography (Ethyl Acetate/n-Hexane 3:7), followed by recrystallization in EtOAc/n-Hexane . SLMP53-1, Formula (II), was obtained starting from (S)- tryptophanol in 75% (0,2g) as a white solid. NMR (400 MHz, DMSO) δ 10.92 (s, 1H, NH) , 7.74 - 7.65 (m, 3H, H-Ar) , 7.59 (m, 2H, H-Ar), 7.40 - 7.32 (m, 2H, H-Ar), 7.08 (t, J = 7.1 Hz, 1H, H-Ar), 7.01 (t, J = 7.4 Hz, 1H, H-Ar), 4.43 - 4.27 (m, 2H, CH e OCH2), 4.14 (dd, J = 8.0, 6.1 Hz, 1H, OCH2), 3.25 (dd, J = 14.5, 5.1 Hz, 1H, CH2), 3.12 (dd, J = 14.6, 8.1 Hz, 1H, CH2), 1.67 (s, 3H, CH3) ; 13C NMR (101 MHz, DMSO) δ 173.76 (C=0) , 147.55 (Cq) , 136.63 (Cq) , 133.93 (CH- Ar) , 131.40 (Cq) , 130.81 (CH-Ar) , 127.85 (Cq) , 124.04 (CH- Ar) , 123.87 (CH-Ar), 123.25 (CH-Ar), 121.49 (CH-Ar), 118.86 (CH-Ar), 118.70 (CH-Ar), 111.88 (CH-Ar), 110.60 (Cq) , 98.87 (Cq) , 74.65 (OCH2), 55.95 (CH) , 30.84 (CH2), 22.79 (CH3) ; [ ]20D +23,7 (c 0.43 g/100 ml, CH2C12) .
	In toluene Reflux; Inert atmosphere; Dean-Stark;

Reference： [1]Pereira, Nuno A. L.; Monteiro, Ângelo; Machado, Marta; Gut, Jiri; Molins, Elies; Perry, M. Jesus; Dourado, Jorge; Moreira, Rui; Rosenthal, Philip J.; Prudêncio, Miguel; Santos, Maria M. M. [ChemMedChem, 2015, vol. 10, # 12, p. 2080 - 2089]
[2]Current Patent Assignee: FACULDADE DE FARMACIA DA UNIVERSIDADE DE LISBOA; UNIVERSITY OF PORTO - WO2014/207688, 2014, A1 Location in patent: Page/Page column 17-18
[3]Barcherini, Valentina; Almeida, Joana; Lopes, Elizabeth A.; Wang, Mi; Magalhães e Silva, Diogo; Mori, Mattia; Wang, Shaomeng; Saraiva, Lucília; Santos, Maria M. M. [ChemMedChem, 2021, vol. 16, # 1, p. 250 - 258]

59
[ 577-56-0 ]
[ 695-84-1 ]
2,3-dihydrobenzofuran-3-yl 2-acetylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In 1,2-dichloro-ethane at 60℃; for 6h;	12 The reaction flask was charged with Bu4NI (0.2 mmol, 74 mg)Compound 1a (2.8 mmol, 336 mg),Compound 2l (2 mmol, 328 mg),t-BuOOH (824 μL), 1,2-dichloroethane (4.0 mL).Then the system is in the airHeating at 60 ° C for about 6 hours, quenching with saturated sodium sulfite solution,Extracted with ethyl acetate (40 mL x 3), the solvent was removed on a rotary evaporator, adsorbed on silica gel,Through a simple column chromatography to get the product 3l,The yield was 81%.
80%	With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water; 1,2-dichloro-ethane at 60℃; for 6h;

Reference： [1]Current Patent Assignee: SOOCHOW UNIVERSITY (SUZHOU) - CN105130933, 2017, B Location in patent: Paragraph 0073-0075
[2]Chen, Jijun; Shao, Ying; Zheng, Hao; Cheng, Jiang; Wan, Xiaobing [Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 10734 - 10741]

60
[ 577-56-0 ]
[ 28719-54-2 ]
bnis-(2-acetylbenzoato)triphenylbismuth(V) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.5%	Stage #1: 2-acetyl-benzoic acid With sodium hydrogencarbonate In methanol; water at 50℃; for 3h; Stage #2: triphenyl bismuth ⁽²⁺⁾; dichloride In methanol at 20℃; for 24h; Inert atmosphere;	4.1.1. Syntheses of Triphenylbismuth(V) Complexes 1 and 3 General procedure: Sodium salt of 2-acetylbenzoic acid (2AcBH) or 4-acetylbenzoic acid (4AcBH) was obtained by adding aqueous solution of sodium bicarbonate (0.168 g, 2 mmol) to a solution of 2-acetylsalicylic acid or 4-acetylsalicylic acid (0.328 g, 2.0 mmol) in methanol and stirred for 3 h at 50° C. The transparent solution was dried under vacuum to remove the water. The dry sodium 2-acetylsalicylate or sodium 4-acetylsalicylate recovered was re-dissolved in dry methanol(30 mL) and triphenylbismuth(V) dichloride, Ph3BiCl2 (0.511 g,1.0 mmol) was added. The solution was stirred for 24 h at room temperature under nitrogen environment. A white precipitate of bis-(2-acetylbenzoate)triphenylbismuth(V) - [Ph3Bi(2AcB)2] (1) orbis-(4-acetylbenzoate)triphenylbismuth(V) - [Ph3Bi(4AcB)2] (3)was obtained after storing the solution at 4° C in a closed beaker for 2 days, recovered by filtration and dried under reduced pressure on CaCl2. The general synthetic procedures are shown in Scheme 1.

Reference： [1]Islam, Arshad; Rodrigues, Bernardo Lages; Marzano, Ivana Marques; Perreira-Maia, Elene C.; Dittz, Dalton; Lopes, Miriam Teresa Paz; Ishfaq, Muhammad; Frezard, Frederic; Demicheli, Cynthia [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 254 - 267]

61
[ 577-56-0 ]
[ 75-64-9 ]
[ 169228-67-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0 - 20℃; for 5.33333h;	Synthesis of amides 1, 5, and 8 (general procedure). General procedure: Triethylamine (2.2 g, 0.02 mol) and ethyl chloroformate (2.4 g, 0.02 mol) were added sequentially dropwise to a solution of keto acid(0.02 mol) in anhydrous THF (150 mL) cooled to 0 C. After20 min, an anhydrous amine (0.02 mol) was added. The reaction mixture was stirred for 5 h at ~20 C. The precipitate was filtered off, and the solvent was evaporated. The combined precipitates were dissolved in CH2Cl2, the solution was washed with water,a saturated aqueous NaHCO3, NaCl, and dried with MgSO4.The solvent was evaporated, the residue was crystallized from ethanol.

Reference： [1]Turova; Berezhnaya; Starodubtseva; Vinogradov [Russian Chemical Bulletin, 2015, vol. 64, # 5, p. 1065 - 1068][Izv. Akad. Nauk, Ser. Khim., 2015, # 5, p. 1065 - 1068,4]

62
[ 534-22-5 ]
[ 577-56-0 ]
[ 352540-52-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: 2-acetyl-benzoic acid With selenium(IV) oxide; ytterbium(III) chloride In water; dimethyl sulfoxide at 110℃; for 15h; Green chemistry; Stage #2: 2-methylfuran In water; dimethyl sulfoxide at 70℃; for 0.166667h; Green chemistry;	General procedure for the synthesis of compounds 4 or 5 : General procedure: A solution of acetophenone 1 (1 mmol), SeO2 (2 mmol) and ytterbium chloride (0.3 mmol) inDMSO:H2O (9:1) (3 mL) was well stirred at 110 oC for 15 h. Then the 2-methylfuran/thiophene (2or 3) was added to the reaction mixture at room temperature and stir again for 10 min at 70 oC. Aftercompletion of the reaction, the reaction mixture brought to room temperature, and it was filteredthrough a short pad of Celite, excess SeO2 and other selenium-containing byproducts were removedby adsorption on Celite. Water was added to the filtrate and the mixture was extracted withdichloromethane. The combined organic layers were dried over anhydrous Na2SO4, concentrated invacuo and purified by chromatography on silica gel to afford required products (4 or 5). Therecovered catalyst was obtained from the aqueous layer after removing water.

Reference： [1]Kumar, G. Santosh; Kumar, A. Sanjeeva; Swetha; Babu, B. Madhu; Meshram [Synlett, 2016, vol. 27, # 4, p. 631 - 639]

63
[ 577-56-0 ]
[ 1779-49-3 ]
[ 3609-46-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 0℃; Inert atmosphere;
85%	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 0 - 20℃; for 16h;
74%	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 20℃; for 1.5h; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran Reflux;

71%	Stage #1: triphenylmethylphosphonium bromide With sodium tertiary butoxide In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;
26%	Stage #1: triphenylmethylphosphonium bromide With sodium tertiary butoxide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 0 - 20℃; for 26h; Inert atmosphere;
	With potassium-t-butoxide
	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 0 - 20℃; for 16h;
	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran Reflux;
	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran Inert atmosphere; Schlenk technique;
	Stage #1: triphenylmethylphosphonium bromide With sodium tertiary butoxide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 65℃; Inert atmosphere;
	Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-acetyl-benzoic acid In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

Reference： [1]Alazet, Sébastien; Le Vaillant, Franck; Nicolai, Stefano; Courant, Thibaut; Waser, Jerome [Chemistry - A European Journal, 2017, vol. 23, # 40, p. 9501 - 9504]
[2]Cheng, Yifu; Du, Yunfei; He, Jiaxin; Jalil, Ayesha; Li, Guangchen; Yu, Zhenyang; Zhang, Jingran; Zhao, Kang [Chemical Communications, 2021, vol. 57, # 60, p. 7426 - 7429]
[3]Hemric, Brett N.; Shen, Kun; Wang, Qiu [Journal of the American Chemical Society, 2016, vol. 138, # 18, p. 5813 - 5816]
[4]Zhang, Wen; Chen, Pinhong; Liu, Guosheng [Angewandte Chemie - International Edition, 2017, vol. 56, # 19, p. 5336 - 5340][Angew. Chem., 2017, vol. 129, # 19, p. 5420 - 5424]
[5]Geary, Gemma C.; Hope, Eric G.; Stuart, Alison M. [Angewandte Chemie - International Edition, 2015, vol. 54, # 49, p. 14911 - 14914][Angew. Chem., 2015, vol. 127, # 49, p. 15124 - 15127]
[6]Ha, Tu M.; Wang, Qian; Zhu, Jieping [Chemical Communications, 2016, vol. 52, # 74, p. 11100 - 11103]
[7]Sha, Wanxing; Zhang, Wenzhong; Ni, Shengyang; Mei, Haibo; Han, Jianlin; Pan, Yi [Journal of Organic Chemistry, 2017, vol. 82, # 18, p. 9824 - 9831]
[8]Chen, Zhen-Yu; Wu, Liang-Yu; Fang, Hai-Sheng; Zhang, Ting; Mao, Zhi-Feng; Zou, Yong; Zhang, Xue-Jing; Yan, Ming [Advanced Synthesis and Catalysis, 2017, vol. 359, # 22, p. 3894 - 3899]
[9]Wang, Jinlei; Zheng, Guangfan; Li, Xingwei [Chemical Communications, 2020, vol. 56, # 56, p. 7809 - 7812]
[10]Qiao, Zhi; Wang, Peng; Ni, Jingxuan; Li, Dongwei; Sun, Yao; Li, Tiantian; Li, Ming [European Journal of Organic Chemistry, 2022, vol. 2022, # 2]
[11]Chen, Li-Na; Ding, Zhi-Jun; Geng, Shu; He, Yuan-Xiang; Hu, Kui; Huang, Feng; Lei, Zhen-Yao; Pan, Li; Zou, Shuai [Organic and Biomolecular Chemistry, 2022, vol. 20, # 12, p. 2397 - 2401]

64
[ 577-56-0 ]
[ 6638-79-5 ]
2-acetyl-N-methoxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: 2-acetyl-benzoic acid With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In tetrahydrofuran; ethyl acetate at 0 - 5℃; for 0.166667h; Inert atmosphere; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In tetrahydrofuran; ethyl acetate at 0 - 25℃; for 2h; Inert atmosphere;	General procedure for the synthesisof Weinreb amides (2a-r) General procedure: To a solution of acid 1 (1.0g, 8.9 mmol) in THF (15 mL) was added Et3N (3.1 mL, 22.2 mmol), and T3P (50% solution in EtOAc, 10.6mL, 17.7 mmol) at 0-5 °C and the solution was stirred for about 10 min under a nitrogen atmosphere. Then N,O-dimethylhydroxylaminehydrochloride salt (1.1g, 13.3 mmol) was added to the reaction mixture at 0-5 °C and the heterogeneous mixture was allowed to stir at room temperature till the completion of the reactionas indicated by TLC (see Table S-1). The mixture was then diluted with water(20 mL) followed by ethyl acetate (20 mL) and stirred for about 10 min. The separated organic layer was collected, washed with 5% citric acid (2 x10 mL),5% Na2CO3 (2 x 10 mL), and then brine solution. The collected organic layer was dried over anhydrous Na2SO4, filtered and concentrated under low vacuum. The crude product obtainedwas purified by flash column chromatography over silicagel (100-200 mesh) using 12-15% EtOAc / n-hexane as eluent to affordthe desired compound.

Reference： [1]Jammula, Subba Rao; Anna, Venkateswara Rao; Tatina, Sudhakar; Krishna, Thalishetti; Sreenivas, B. Yogi; Pal, Manojit [Tetrahedron Letters, 2016, vol. 57, # 35, p. 3924 - 3928]

65
[ 577-56-0 ]
[ 180092-32-4 ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 11100 - 11103
[2]Chemistry - An Asian Journal,2018,vol. 13,p. 409 - 412
[3]European Journal of Organic Chemistry,2022,vol. 2022

66
[ 577-56-0 ]
[ 105-07-7 ]
2-[(2E)-3-(4-cyanophenyl)prop-2-enoyl]benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1%	With sodium hydroxide In ethanol at 20℃; for 16h; Inert atmosphere; Cooling with ice;	1 Into a 50-mE round-bottom flask, was placed 2-acetyl- benzoic acid (1.64 g, 9.99 mmol, 1.00 equiv), ethanol (555mE), 4-formylbenzonitrile (1.31 g, 9.99 mmol, 1.00 equiv). To this was added sodium hydroxide(aq.) (10 mE, 1.5N) with an ice/water bath. The resulting solution was stirred for 16 h at room temperature. The reaction was then quenched by the addition of 20 mE of watet The pH value of thesolution was adjusted to 2-3 with hydrogen chloride (4 mol/E). The resulting solution was extracted with 3x20 mE of dichloromethane and the organic layers combined. The resulting mixture was washed with 1x30 mE of H20. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (250 mg) was purified by Prep-HPEC with the following conditions (1-Pre-HPEC-006(Waters)): Colunm, SunFire Prep C18, 19*150mm Sum; mobile phase, WATER WITH 0.5% TFA and CH3CN (20% CH3CN up to 60% in 10 mm, up to 100% in 2 mm); Detector, uv 254/220 nm. 16.2 mg product was obtained. This resulted in 16.2 mg (1%) of 2-[(2E)-3-(4- cyanophenyl)prop-2-enoyl]benzoic acid as a white solid.‘H-NMR (300 MHz, (CD3OD): ö 8.07 (m, 1H), 7.50-7.77 (m, 8H), 7.24 (m, 2H). MS (ESI): 278.15 [M+H+]; calcd for [C17H11N03+H+] 278.08.

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - US9464065, 2016, B2 Location in patent: Page/Page column 54; 55

67
[ 577-56-0 ]
3-phenyl-carbazic acid [ No CAS ]
[ 6941-96-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	In neat (no solvent, solid phase) at 70℃; for 1h;	101 Example 101 5.4 g (50.0 mmol) of phenylhydrazine-carbon dioxide bonding compound (C6H5NH2 + NH-CO2-) and 8.21 g of 2-acetylbenzoic acid, which were solids instead of hydrazine-carbon dioxide compound, were reacted at 70 ° C for 1 hour. This is the same as Example 1. The obtained compound was 4-methyl-2-phenylphthalazin-1(2H)-one, with a selectivity of 99% and a yield of 97%.

Reference： [1]Current Patent Assignee: SOGANG UNIVERSITY - KR101483445, 2015, B1 Location in patent: Paragraph 0451-0453

68
[ 577-56-0 ]
[ 19731-02-3 ]
1-(2-(5-((1H-benzo[d]imidazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)phenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With trichlorophosphate at 60℃; for 2h;	4.5. General procedure for the synthesis of compounds (7a-x and 8a-e) General procedure: A mixture of (6a-b) (0.001 mol), an aliphatic/aromatic acid(equimolar, 0.001 mol) and POCl3 (5 mL) was heated under refluxalong with stirring for 2 h at 60 °C. After completion of the reaction,checked by single-spot TLC using the solvent systems; chloroform:methanol (9:1), the reaction mixturewas cooled and poured slowlyonto crushed ice, neutralized with sodium bicarbonate solution. Asolid mass precipitated out, which was filtered and washed withexcess quantity of water to remove the inorganic component. Thecompound was recrystallized with ethanol water mixture.

Reference： [1]Akhtar, Md Jawaid; Siddiqui, Anees Ahmad; Khan, Ahsan Ahmed; Ali, Zulphikar; Dewangan, Rikeshwer Prasad; Pasha, Santosh; Yar, M. Shahar [European Journal of Medicinal Chemistry, 2017, vol. 126, p. 853 - 869]

69
[ 577-56-0 ]
[ 524-38-9 ]
1,3-dioxoisoindolin-2-yl 2-acetylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With dmap; dicyclohexyl-carbodiimide In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; for 2h; Schlenk technique; Inert atmosphere;

Reference： [1]Cheng, Wan-Min; Shang, Rui; Zhao, Bin; Xing, Wei-Long; Fu, Yao [Organic Letters, 2017, vol. 19, # 16, p. 4291 - 4294]

70
[ 577-56-0 ]
[ 71-43-2 ]
[ 2142-66-7 ]

Reference： [1]Chemical Science,2017,vol. 8,p. 3618 - 3622

71
[ 577-56-0 ]
[ 93-55-0 ]
C₁₈H₁₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With 2,2,6,6-tetramethyl-piperidine-N-oxyl; chloro(1,5-cyclooctadiene)rhodium(I) dimer; copper diacetate; cesium fluoride In toluene at 120℃; for 24h; Inert atmosphere;

Reference： [1]Li, Hongyi; Jiang, Quandi; Jie, Xiaoming; Shang, Yaping; Zhang, Yuanfei; Goossen, Lukas J.; Su, Weiping [ACS Catalysis, 2018, vol. 8, # 6, p. 4777 - 4782]

72
[ 577-56-0 ]
[ 775-00-8 ]
11-(trifluoromethyl)-7,8-dihydro-5H-benzo[4,5]azepino[2,1-a]-isoindol-5-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 2870 - 2878

73
[ 577-56-0 ]
[ 775-00-8 ]
3-methylene-2-(4-(trifluoromethyl)phenethyl)isoindolin-1-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 2870 - 2878

74
[ 577-56-0 ]
4-hydrazinobenzene-1-sulfonamide hydrochloride [ No CAS ]
4-(4-methyl-1-oxophthalazin-2(1H)-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate In ethanol for 8h; Reflux;	4.2.1. General procedure (GP1) for the synthesis of compounds 6ad,7a-d, 8a, 9a-c General procedure: A mixture of appropriate 1,4 - dicarbonyl compound 11, 13,14 or15 (0.001 mol) and 4-hydrazinobenzenesulfonamide hydrochloride12 (0.001 mol) in ethanol (10-40 mL) was refluxed for 8-24 h. The reaction mixture was evaporated to give a crude solid. Crudeproduct was stirred with 5-10% sodium bicarbonate solution(25 mL) for 1h. It was filtered, washed with 2% acetic acid and thenwith water. It was dried and crystallized from ethanol to give (6a-d,7a-d, 8a, 9a-c).

Reference： [1]Krasavin, Mikhail; Shetnev, Anton; Baykov, Sergey; Kalinin, Stanislav; Nocentini, Alessio; Sharoyko, Vladimir; Poli, Giulio; Tuccinardi, Tiziano; Korsakov, Mikhail; Tennikova, Tatiana B.; Supuran, Claudiu T. [European Journal of Medicinal Chemistry, 2019, vol. 168, p. 301 - 314]

75
[ 577-56-0 ]
3-amino-N-methyl-4-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-3-yl)amino]benzamide [ No CAS ]
2-(2-acetylphenyl)-N-methyl-1-(2-oxo-3,4-dihydro-1H-quinolin-6-yl)benzimidazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.6%	With hydrogenchloride In 1,4-dioxane at 110℃; for 12h;	30 Example 302-(2-Acetylphenyl)-N-methyl- 1-(2-oxo-3,4-dihydro- 1H-quinolin-6-yl)benzimidazole-5-carboxamide To a 4 M solution of HC1 in dioxane were added 3-amino-N-methyl-4-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-3-yl)amino]benzamide (200.0 mg) and 2-acetylbenzoic acid68 (126.95 mg). The reaction mixture was stirred at 110 °C for 12 hours and was then concentrated in vacuo andpurified by preparative HPLC to afford 2-(2-acetylphenyl)-N-methyl- 1 -(2-oxo-3 ,4-dihydro- 1 H-quinolin-6-yl)benzimidazole-5-carboxamide (4.4 mg, 2.6%) as a white solid. MS (ISP): 439.3 ([M+H]j.

Reference： [1]Current Patent Assignee: C4 THERAPEUTICS INC - WO2019/43208, 2019, A1 Location in patent: Page/Page column 72; 73

76
[ 577-56-0 ]
[ 74-88-4 ]
C₂₀H₁₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 2-acetyl-benzoic acid With rhodium(III) chloride trihydrate; tetrabutylammonium acetate In N,N-dimethyl-formamide at 80℃; for 20h; Electrolysis; Stage #2: methyl iodide

Reference： [1]Zeng, Zhongyi; Goebel, Jonas F.; Liu, Xianming; Gooßen, Lukas J. [ACS Catalysis, 2021, vol. 11, p. 6626 - 6632]

77
[ 577-56-0 ]
[ 29334-16-5 ]
C₂₂H₁₅BrO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With phosphomolybdic acid In chlorobenzene at 80℃; for 3h;	4 Example 4 Add 4-bromobenzhydrol (0.2mmol), 2-acetylbenzoic acid (0.3mmol), H3PMo12O40 (1.5mol%) and chlorobenzene (1ml) into a 4mL reaction flask.Then react at 80°C for 3 hours. After the reaction is completed, the target product is separated by column chromatography with a yield of 97%.When the raw material is added at a ratio of 1:1.0, the yield is 84%.When the raw material was added at a ratio of 1:1.3, the yield was 91%.

Reference： [1]Current Patent Assignee: EAST CHINA UNIVERSITY OF TECHNOLOGY - CN113004236, 2021, A Location in patent: Paragraph 0022; 0044-0056

78
[ 577-56-0 ]
[ 91-01-0 ]
C₂₂H₁₆O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With phosphomolybdic acid In chlorobenzene at 80℃; for 3h;	1 Example 1 Add benzhydrol (0.2mmol), 2-acetylbenzoic acid (0.3mmol), H3PMo12O40 (1.5mol%) and chlorobenzene (1ml) into a 4mL reaction flask.Then react at 80°C for 3 hours. After the completion of the reaction, the target product was separated by column chromatography with a yield of 93%.When the raw material is added at a ratio of 1:1.0, the yield is 76%.When the raw material was added at a ratio of 1:1.3, the yield was 87%.

Reference： [1]Current Patent Assignee: EAST CHINA UNIVERSITY OF TECHNOLOGY - CN113004236, 2021, A Location in patent: Paragraph 0022; 0029-0035

79
[ 577-56-0 ]
[ 100867-01-4 ]
4-methoxybenzyl 2-acetylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With rhodium (II) octanoate dimer; 2,6-di-tert-butyl-4-methylpyridinium trifluoromethanesulfonate; methyl 2-(4-chlorophenyl)-2-diazoacetate In dichloromethane at 0℃; for 0.5h; Molecular sieve;	General Procedure C: in situ formed ylides 2o/2p Mediated p-methoxybenzylation and 4-(trimethylsilyl)methylbenzylation General procedure: A solution of TfOH·DTBMP (25 mol%) in DCM (0.1M) and Rh 2 (oct) 4 (0.5 mol%) in DCM (0.1 M) were successively added to the mixture of 5 (1.0 equiv), thioether S1a or S1b (1.05 equiv), diazo S2c (2.0 equiv) and 4Å MS in CH2Cl2 (C = 0.1M), the resulting mixture was stirred at corresponding temperature for 0.5 h. The reaction mixture was quenched with saturated aqueous NaHCO3, filtered through Celite and extracted with EtOAc. The organic phase was washed with brine, dried over Na 2 SO 4 , concentrated, and purified by silica gel flash column chromatography.

Reference： [1]Fang, Jing; Li, Ting; Ma, Xiang; Sun, Jiuchang; Cai, Lei; Chen, Qi; Liao, Zhiwen; Meng, Lingkui; Zeng, Jing; Wan, Qian [Chinese Chemical Letters, 2022, vol. 33, # 1, p. 288 - 292]

80
[ 577-56-0 ]
[ 932-30-9 ]
4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
86%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.

Reference： [1]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]

81
[ 34897-84-2 ]
[ 577-56-0 ]
3,6a-dimethyl-5H-benzo[4,5][1,3]oxazino[2,3-a]isoindol-11(6aH)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
88%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

Reference： [1]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]

82
[ 55414-72-7 ]
[ 577-56-0 ]
3-methoxy-6a-methyl-5H-benzo[4,5][1,3]oxazino[2,3-a]isoindol-11(6aH)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
96%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

Reference： [1]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]

83
[ 577-56-0 ]
[ 20712-12-3 ]
3-bromo-6a-methyl-5H-benzo[4,5][1,3]oxazino[2,3-a]isoindol-11(6aH)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	In toluene; for 12h;Reflux;	General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
67%	In toluene; for 12h;Reflux;	General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

Reference： [1]Tetrahedron,2022,vol. 104
[2]Tetrahedron,2022,vol. 104

84
[ 577-56-0 ]
[ 5339-85-5 ]
7a-methyl-5,6-dihydrobenzo[4,5][1,3]oxazepino[2,3-a]isoindol-12(7aH)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
98%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

Reference： [1]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]

85
[ 577-56-0 ]
[ 110-60-1 ]
[ 6029-45-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product. 4.2.1 4b-methyl-10H-benzo[5,6][1,3]oxazino[2,3-a]isoindol-12(4bH)-one (3aa) Yellow solid (216mg, 86% yield). m. p. 104-106°C; 1H NMR (500MHz, Chloroform-d) δ 7.87 (d, J=7.4Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.67 (td, J=7.4, 1.1Hz, 1H), 7.57 (td, J=7.5, 1.0Hz, 1H), 7.18 (t, J=7.5Hz, 2H), 7.00 (td, J=7.4, 1.2Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 5.30 (d, J=16.9Hz, 1H), 4.46 (d, J=16.9Hz, 1H), 1.81 (s, 3H); 13C NMR (126MHz, Chloroform-d) δ 166.1, 151.2, 145.5, 132.6, 131.2, 130.2, 128.5, 127.0, 124.0, 122.0, 121.9, 118.2, 117.7, 88.0, 36.9, 21.2; HRMS (ESI) m/z: [M+Na]+ Calcd. for C16H13NO2Na 274.0838; Found 274.0832.
90%	In toluene for 12h; Reflux;	4.2 General procedure for the synthesis of isoindolobenzoxazinones and isoindoloquinazolinones General procedure: A solution of substituted 2-acylbenzoic acid (1.0mmol) and substituted amino alcohols or diamines (1.20mmol) in toluene (10mL) was held at reflux in oil bath for 12h. After being cooled to room temperature, the solvent was evaporated in vacuo and the residue was purified by column chromatography eluted with a mixture of petroleum ether and ethyl acetate (3:1) to give the pure target product.

Reference： [1]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]
[2]Li, Wenzhong; Wan, Baibai; Shi, Ran; Chen, Si; Li, Jiazhu; Wang, Fangzhen; Niu, Hexu; Xu, Xin-Ming; Wang, Wei-Li [Tetrahedron, 2022, vol. 104]

86
[ 577-56-0 ]
[ 3893-35-4 ]
C₁₈H₁₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetrakis(trifluoroacetato)rhodium(II); C₃₁H₄₄N₄O₄; scandium tris(trifluoromethanesulfonate) In dichloromethane at -10℃; for 6h; stereoselective reaction;

Reference： [1]Feng, Xiaoming; He, Changli; Lang, Jiawen; Liu, Xiaohua; Wang, Siyuan [Chemical Science, 2022, vol. 13, # 4, p. 1163 - 1168]

87
[ 577-56-0 ]
[ 94940-35-9 ]
3-(bis(4-fluorophenyl)phosphoryl)-3-methylisobenzofuran-1(3H)-one [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2022,vol. 364,p. 1460 - 1464

88
[ 611-14-3 ]
[ 577-56-0 ]

Yield	Reaction Conditions	Operation in experiment
68%	With hydrogenchloride; tetrakis(tetrabutylammonium)decatungstate(VI); oxygen In lithium hydroxide monohydrate; acetonitrile at 20℃; for 48h; Irradiation;	6 Example 6; Preparation of compound I-6 At room temperature, o-ethyltoluene (60.1 mg, 0.5 mmol) was dissolved in acetonitrile (1.5 mL) and 1 M aqueous hydrochloric acid (1.5 mL), TBADT (82.5 mg, 0.025 mmol) was added, followed by the reaction system An oxygen balloon was attached, and the reaction system was placed under a 2×3W purple LED light and stirred for 48 hours.The reaction system was subjected to column chromatography with Vpetroleum ether/Vethyl acetate=2:1 to obtain 55.8 mg of the I-6 target product with a yield of 68%.

Reference： [1]Current Patent Assignee: UNIV CENTRAL CHINA NORMAL - CN114057569, 2022, A Location in patent: Paragraph 0058-0060

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CAS No. :	577-56-0	MDL No. :	MFCD00002475
Formula :	C₉H₈O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QDAWXRKTSATEOP-UHFFFAOYSA-N
M.W :	164.16	Pubchem ID :	68474
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.11
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.6
TPSA :	54.37 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.73 cm/s

Log Po/w (iLOGP) :	1.15
Log Po/w (XLOGP3) :	0.81
Log Po/w (WLOGP) :	1.59
Log Po/w (MLOGP) :	1.28
Log Po/w (SILICOS-IT) :	1.55
Consensus Log Po/w :	1.28

[ CAS No. 577-56-0 ] {[proInfo.proName]}

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Application In Synthesis of [ 577-56-0 ]

[ 577-56-0 ] Synthesis Path-Upstream 1~4

[ 577-56-0 ] Synthesis Path-Downstream 1~88

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Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Log S (ESOL) :	-1.61
Solubility :	4.07 mg/ml ; 0.0248 mol/l
Class :	Very soluble
Log S (Ali) :	-1.53
Solubility :	4.81 mg/ml ; 0.0293 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.1
Solubility :	1.31 mg/ml ; 0.00798 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.09

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: With hydrogen bromide; bromine; acetic acid In chlorobenzene at 30℃; for 3 h; Stage #2: With water In chlorobenzene for 3 h; Reflux	Example 2: Preparation of 1 /-/-2-benzopyran-1 ,4(3/-/)-dione (Compound of formula (III))A stirred mixture of 2-acetylbenzoic acid (compound of formula (XI)) (1.00 Kg, 6.09 mol) and chlorobenzene (10.0 L) was treated with 5.5 molar hydrobromic acid in acetic acid (55 ml_) and bromine (310 ml_) then warmed to approximately 30 °C. After 3 hours water (10.0 L) was added and the reaction heated to reflux. After 3 hours the reaction was cooled to 60 °C and the organic layer removed. The aqueous layer was extracted with chlorobenzene (2.0 L) and the combined organic layers concentrated under reduced pressure to approximately 3.0 L. Propan-2-ol (5.0 L) was charged and the slurry cooled to 0 °C before being filtered and washed with propan-2-ol (2.0 L). The resulting solid was dried in vacuo at 50 °C to give the title compound (736 g, 75percent); ¹ H NMR (400MHz, CDCI₃): δ 5.14 (2H, s, H-9), 7.82 - 7.91 (2H, m, H-2 and 3), 8.08 - 8.10 (1 H, m, H-1), 8.28 - 8.30 (1 H, m, H-4); ¹³C NMR (100MHz, CDCIs) δ 73.4, 125.6, 128.0, 130.9, 131.8, 134.7, 135.9, 161.4 and 189.5.
63%	at 40℃; for 0.5 h;	Step 1: lH-Isochromene-l,4(3H)-dione [00369] To a solution of 2-acetylbenzoic acid (8.458 g, 51.52 mmol) in acetic acid (50.0 mL, 879 mmol) was added 30 ml of 33percent HBr in acetic acid. Bromine (8.646 g, 54.10 mmol) was next added to the solution, and the reaction was heated to 40 °C with stirring for 30 min. The reaction mixture was poured into 300 ml water, the layers were separated, and the aqueous layer was extracted with 3 x 100ml DCM. Combined the organic layers and concentrated in vacuo to yield crude intermediate, which was dissolved in 25 ml acetic acid, 130ml toluene and 30 ml water. The resulting mixture was stirred at reflux overnight. The reaction was cooled to rt, and the layers were separated. The organic layer was concentrated in vacuo and purified by flash column ( 120g column, eluent 0-55percent EtOAc in hexane)to afford 5.24g (63percent) of title compound. NMR (400 MHz, Chloroform-d) δ 8.36 - 8.28 (m, 1 H), 8.17 - 8.07 (m, 1 H), 7.95 - 7.79 (m, 2H), 5.16 (s, 2H).

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