Name: 339-59-3|4-(Trifluoromethyl)benzohydrazide|98%
Brand: Ambeed
SKU: A204157
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1
[ 583-02-8 ]
[ 339-59-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In ethanol; at 20℃; for 3h;	General procedure: A mixture of substituted ethyl benzoate 2 (10 mmol) and hydrazinehydrate (20 mmol) in ethanol was stirred at room temperaturefor 3 h and then filtered. The crude product recrystallizedfrom absolute alcohol to give 3a-l, which were used directly forthe next step. Under this same condition, the intermediate compounds 8a-d were also prepared.
	With hydrazine hydrate; In ethanol; toluene; at 40℃; for 16h;	General procedure: Hydrazine monohydrate (355 mg, 7.09 mmol, 3.2 equiv.) was added to a solution of crude methyl 4-chloro-3-(trifluoromethyl)benzoate in ethanol (4 ml.) and toluene (2 ml_). The mixture was heated to 40 C for 16 hours, cooled to room temperature and concentrated under reduced pressure. The crude residue was azeotroped with ethanol and toluene to provide crude 4-chloro-3-(trifluoromethyl)benzohydrazide as an off-white solid, which was used without further purification.

Reference： [1]Ukrainskij Khimicheskij Zhurnal,1957,vol. 23,p. 634
Chem.Abstr.,1958,p. 9979
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2006,vol. 45,p. 483 - 488
[3]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2278 - 2282
[4]Bioorganic Chemistry,2016,vol. 65,p. 126 - 136
[5]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1879 - 1888
[6]RSC Advances,2018,vol. 8,p. 6306 - 6314
[7]Turkish Journal of Chemistry,2019,vol. 43,p. 1075 - 1085
[8]Patent: WO2020/43866,2020,A1 .Location in patent: Page/Page column 32; 88

2
[ 75-15-0 ]
[ 339-59-3 ]
[ 389120-03-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium hydroxide In ethanol; water at 95℃; for 16h; Inert atmosphere;
71%	With N,N-dimethyl-formamide for 23h; Sonication; Green chemistry;
	With potassium hydroxide In ethanol Heating;

	With potassium hydroxide In ethanol for 8h; Heating;
	With potassium phosphate In water at 20℃; Reflux;	4.2. General procedure for the synthesis of 5-substituted-1,3,4-oxadiazole-2(3H)-ones (10) General procedure: A mixture of the corresponding acylhydrazine (3 mmol), potassium phosphate (1.02 g, 3 mmol), and carbon disulfide (0.23 g, 3 mmol) in water (15 mL) was stirred at rt for 10 min. After refluxing for an additional 2-3 h, propylene oxide (0.18 g, 3 mmol) was added. Stirring was continued at rt until the intermediate convert completely (monitored by TLC, about 0.5-1 h), the mixture was extracted with EtOAc (3×10 mL). The combined organic layer was washed with water and dried over Na2SO4. The solvent was evaporated under reduced pressure, and the residue was purified by recrystallization or silica gel column to afford the corresponding product 10a-l.
	With potassium hydroxide In ethanol; water for 24h; Reflux;	Step 1: To a solution of 4-(trifluoromethyl)benzhydrazide (1.00 g, 4.9 mmol, 1.0 eq.) inEtCH (17 mL), carbon disulfide (0.33 mL, 5.4 mmol, 1.1 eq.) and a solution of KCH (275mg, 4.9 mmol, 1.0 eq.) in water (2.5 mL) were added in sequence. The reaction mixturewas refluxed for 24 hours. The reaction mixture was concentrated in vacuo. The residue was dissolved in excess water and acidified with 2M aq. HCI to pH 2-3. The resulting suspension was filtered. The solid was dissolved in AcCEt and the solution was dried over MgSC4 and evaporated in vacuo to give 5-(4-trifluoromethyl-phenyl)-[1 ,3,4]oxadiazole-2-thiol as a white solid. The product was used without further purification. LC-MS 4: tR = 1 .18 mm; [M+H] = no ionization
	Stage #1: carbon disulfide; 4-(trifluoromethyl)benzoic acid hydrazide With potassium hydroxide In ethanol; water for 8h; Reflux; Stage #2: With hydrogenchloride In water	5.3. General procedure for preparation of 4a-l General procedure: Substituted benzohydrazide 3 (5 mmol) was dissolved in a solutionof potassium hydroxide (6 mmol) in water (4 mL) and ethanol(20 mL). Carbon disulfide (10 mmol) was then added while stirringand the reaction mixture was heated under reflux for 8 h. The solventswere removed under reduced pressure; the residue was treatedwith water and then filtered. The filtrate was cooled, and thenneutralized to pH 3 using dilute hydrochloric acid and the separatedproduct thiol 4a-l was filtered, washed with water, driedand recrystallised from benzene as yellow crystals, which wereused directly for the next step. Under this same condition, theintermediate compounds 9a-d were also prepared.
	Stage #1: carbon disulfide; 4-(trifluoromethyl)benzoic acid hydrazide With potassium hydroxide In ethanol Stage #2: With hydrogenchloride In water
	Stage #1: carbon disulfide; 4-(trifluoromethyl)benzoic acid hydrazide With sodium hydroxide Stage #2: With hydrogenchloride

Reference： [1]Kahl, Dylan J.; Hutchings, Kim M.; Lisabeth, Erika Mathes; Haak, Andrew J.; Leipprandt, Jeffrey R.; Dexheimer, Thomas; Khanna, Dinesh; Tsou, Pei-Suen; Campbell, Phillip L.; Fox, David A.; Wen, Bo; Sun, Duxin; Bailie, Marc; Neubig, Richard R.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4350 - 4369]
[2]Yarmohammadi, Elahe; Beyzaei, Hamid; Aryan, Reza; Moradi, Ashraf [Molecular Diversity, 2021, vol. 25, # 4, p. 2367 - 2378]
[3]Dodd, Dharmpal S.; Shen, Zhongqi; Nishi, Takao; Graber, Norma; Bealls, Dawson; Fong, Miranda; Ebert, Tracy [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 22, p. 2693 - 2698]
[4]Li, Yan; Liu, Jie; Zhang, Hongquan; Yang, Xiangping; Liu, Zhaojie [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 8, p. 2278 - 2282]
[5]Location in patent: experimental part Yan, Xu; Zhou, Shuo; Wang, Yuanqiang; Ge, Zemei; Cheng, Tieming; Li, Runtao [Tetrahedron, 2012, vol. 68, # 38, p. 7978 - 7983]
[6]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2015/28989, 2015, A1 Location in patent: Page/Page column 82
[7]He, Haifeng; Wang, Wei; Zhou, Yuan; Xia, Qin; Ren, Yanliang; Feng, Jiangtao; Peng, Hao; He, Hongwu; Feng, Lingling [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 8, p. 1879 - 1888]
[8]Wang, Pei-Yi; Wang, Ming-Wei; Zeng, Dan; Xiang, Meng; Rao, Jia-Rui; Liu, Qing-Qing; Liu, Li-Wei; Wu, Zhi-Bing; Li, Zhong; Song, Bao-An; Yang, Song [Journal of Agricultural and Food Chemistry, 2019, vol. 67, # 13, p. 3535 - 3545]
[9]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085]

3
[ 2967-66-0 ]
[ 339-59-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrazine monohydrate In ethanol Reflux;
86%	With hydrazine hydrate monohydrate In methanol at 80℃; for 4h;	preparation of intermediate 2 General procedure: At the 250 cm3double-mouth bottle, 13.5 mmol of themethyl benzoate derivatives was added to 100 cm3of methanol,added 6.75 cm3of hydrazine hydrate (108 mmol) tothe reaction mixture slowly. After that warming to 80 °Cand reflux for 4 h until the reaction was completed, thenconcentrated under reducing pressure to remove methanol,filtering and drying to get white solid 2. 4-(Trifluoromethyl)benzohydrazide (2a, C8H7F3N2O)Whitesolid; yield: 86%; m.p.: 145-148 °C; 1H NMR (400 MHz,CDCl3):δ = 9.64 (t, J = 7.1 Hz, 1H, NH), 7.61 (d, J = 8.5 Hz,2H, ArH), 7.51 (d, J = 7.3 Hz, 2H, ArH), 4.46 (d, J = 4.2 Hz,2H, NH2)ppm; 13C NMR (100 MHz, CDCl3):δ = 178.4(CF3), 167.9 (C=O), 160.7 (CH), 159.1 (CH), 147.6(CH), 146.1 (CH) ppm; IR (KBr): = 3416, 3064, 2916,1725, 1661, 1557, 1448 cm-1; HRMS (EI): m/z calcd. forC8H7F3N2O(M+) 205.0514, found 205.0517
85%	With hydrazine monohydrate In methanol for 5h; Reflux;	General procedure for the preparation of acid hydrazides(18a-j) General procedure: To a solution of an appropriate methyl esters17(a-j) (1.0 mmol) in 50 mL of methanol was added 99 %hydrazine hydrate (4.0 mmol) and the mixture was refluxedfor 5 h up to reaction completed (TLC). After completionof reaction, it was allowed to cool and the obtained solidwas washed with methanol. The crude products wererecrystallized from ethanol.

65%	With hydrazine hydrate monohydrate Ambient temperature;
59%	With hydrazine hydrate monohydrate In water monomer at 50 - 60℃; for 0.166667h;	5.1.2. General procedure for the preparation of benzhydrazides (3) General procedure: Pathway A-Hydrazine hydrate 64% (v/v) (30.0 mL, 0.33 mol) was heated up to 50-60 °C. The methyl ester previously isolated (0.01 mol) was added and the mixture was refluxed during 10 min. The cooling down was proceeded sequentially in a water bath, followed by ice bath and dry ice - ethanol bath. The solid was filtered and washed with cold water. Different conditions were needed to obtain 4-nitro-3-(trifluoromethyl)benzhydrazide (3d) and 4-nitrobenzhydrazide (3 h). Hydrazine hydrate 64% (v/v) (30.0 mL, 0.33 mol) was cooled down in ice bath to -3 to 2 °C. The respective methyl ester (0.01 mol) was added and the mixture was stirred during 1 hour. The cooling down was proceeded in dry ice - ethanol bath. The solid was filtered and washed with cold water. Pathway B-each substituted benzoic acid (0.01 mol) was refluxed during 4 h in 20.0 mL (0.50 mol) of anhydrous methanol and 0.5 mL (1.0 mmol) of sulfuric acid. The reaction mixture was cooled down to room temperature. and the hydrazine hydrate 80% (v/v) (10.0 mL, 0.11 mol) was added. The system was maintained into vigorously stirring for more 30 minutes. In the case of compounds with 4-nitro and 4-nitro-3-trifluoromethyl substituent groups attached in the benzene moiety, after the addition of hydrazine hydrate 80% (v/v) at room temperature, the reaction mixture was cooled down in ice bath and maintained into stirring during 1 hour. After these periods, the mixture was maintained at cold temperature to give 3.
	With hydrazine hydrate monohydrate
	With hydrazine In water monomer at 60℃;
	With hydrazine hydrate monohydrate for 0.166667h; Reflux;
	With hydrazine hydrate monohydrate In ethanol for 10h; Reflux; Inert atmosphere;
	With hydrazine hydrate monohydrate at 80℃; for 2h;
	In isopropanol	1 More specifically, to prepare ST-246 monohydrate, Form I, cycloheptatriene is reacted with maleic anhydride in the presence of toluene to yield the major product, endo isomer. The exo isomer is further produced from about 7% to 0.6% by crystallization from toluene/heptane. Further, hydrazine in the anhydrous or hydrate form is reacted with Methyl 4-(trifluoromethyl)benzoate in the presence of isopropanol to yield (4-(trifluoromethyl)-benzhydrazide. The product is then crystallized from isopropanol.The next step of the synthesis involves condensing endo-tricyclo[3.2.2.0]non-8-endo-6,7-dicarboxylic anhydride and (4-(trifluoromethyl)-benzhydrazide) in isopropanol. The product is isolated by crystallization from isopropanol and the slurry is further heated to reflux and held. The resulting solution is cooled and sampled for reaction completion. After analysis shows reaction completion, carbon and celite are charged and the batch is heated to reflux and held. After cooling, the batch is filtered to remove these solid materials, followed by a filter chase with IPA. The batch is cooled and held while slurry is formed. The batch is further cooled and held. Contents are centrifuged and the wet cake containing synthesis product is washed with heptane. The wet cake is dried and is referred to as partially hydrated form of ST-246 (SG3).The SG3 is charged followed by ethyl acetate. The mixture is heated and held to ensure dissolution of SG3. A polish filtration is performed on the batch and an extraneous material check confirms that the filtration was successful. Ethyl acetate is used to charge the filter. After heating the batch to reflux, Endotoxin reduced (ER) water is charged. The batch is seeded and the final ER water is charged. The batch is held at reflux and a slurry check is performed.Further, the batch is cooled, at which time a sample of the slurry is obtained for verification of correct polymorph. The batch is cooled further and is held until final isolation on the centrifuge. The final API is dried, milled using a Fitz Mill as described in WO 02/00196. Form I can be prepared by crystallization of ST-246 from a variety of solvents and solvent combinations as further summarized in Tables 2 and 3:
	With hydrazine hydrate monohydrate In water monomer at 75℃; for 0.166667h;	4.1.2. General procedure for the synthesis of benzhydrazides (3a-o) General procedure: Hydrazine hydrate 64% (v/v) (30.0 mL, 0.33 mol) was heated up to 50-60 °C. The methyl ester 3 (0.01 mol) was added and the mixture was heated at reflux for 10 min. The cooling was performed sequentially in water bath, followed by ice bath and dry ice-ethanol bath. The precipitate was filtered and washed with cold water.
	With hydrazine
	With hydrazine hydrate monohydrate In water monomer for 0.5h; Reflux;	4.1.1. General procedure for the synthesis of benzhydrazides (2a-j) General procedure: Each substituted benzoic acid (1) (0.02 mol) was refluxed for 4 h in 20.0 mL (0.49 mol) of anhydrous methanol and 0.5 mL (0.01 mol) of sulphuric acid. The reaction mixture was cooled down to room temperature and the hydrazine hydrate 80% (v/v) (10.0 mL, 0.13 mol) was added. The system was maintained by vigorously stirring for more 30 min in reflux. In the case of compound with 4-nitro substituent group attached to the benzene moiety, after the addition of hydrazine hydrate 80% (v/v) at room temperature, the reaction mixture was cooled down in ice bath and maintained into stirring during 1 h. After this period, the mixture was maintained at low temperature to give 2.19,22
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine hydrate monohydrate In methanol for 8h; Reflux;	General Procedure for the Synthesis of Acid Hydrazides (3a-t) General procedure: To a solution of methyl ester of aromatic carboxylic acid 2 (0.1 mol) in methanol (30 mL), hydrazine hydrate (0.2 mol) was added drop wise with stirring. The resulting mixture was allowed to reflux for 8 h. After the completion of the reaction as monitored by TLC, the excess methanol was distilled off under reduced pressure. The resulting acid hydrazide 3 was washed with cold water, dried and recrystallized from ethanol.
	Stage #1: methyl 4-(trifluoromethyl)benzoate In methanol at 0℃; for 0.166667h; Stage #2: With hydrazine monohydrate In methanol for 8h; Reflux;	Step 2. General Procedure for Preparation of the Benzoyl Hydrazines General procedure: A mixture of methyl benzoates (15.0 mmol), CH3OH (30.0 mL) wereplaced in a 100mL round-bottomed flask equipped with a magnetic stirrer.Stirring for 10 minutes in 0 °C. Then hydrazine hydrate (4.0 eq.) was added to the flask. Afterword the mixture was stirred under reflux 8 h, the reaction system was concentrated to remove CH3OH and most of hydrazine hydrate. After cooling, the contents were added petroleum-ether (50 mL) by stirring, then the white solids would be separated, washed with water and dried under vacuum. The yield was 65%~80%.
	With hydrazine hydrate monohydrate In ethanol at 70℃;
	With hydrazine In toluene for 18h; Reflux; Inert atmosphere;	43.2 EXAMPLE 43: Step 2: To a solution of anhydrous hydrazine in anhydrous toluene is added methyl 4-(trifluoromethyl) benzoate (4). The reaction solution is heated at reflux for 18 hours under a nitrogen atmosphere. After cooling to 40-50°C, the solvent is evaporated under reduced pressure. The resulting solid is recrystallized from tert-butyl methyl ether to give hydrazide (5) as a white solid.
	With hydrazine hydrate monohydrate In methanol at 85℃; for 14h;
	With hydrazine monohydrate In methanol at 65℃; for 4h;	General Procedure 2: The Formation of Hydrazide General procedure: To a solution of esters (2a~2t, 1.0 equiv.), furan-2-carbonyl chloride (7a, 1.0 equiv.) orthiophene-2-carbonyl chloride (7b, 1.0 equiv.) in MeOH (2 mL/1 mmol) was added hydrazine hydrate(1 mL/1 mmol), then the mixture was allowed to reach 65 C and stirred for 4 h. After completion(monitored by TLC), the organic solvent was removed and extracted three times with ethyl acetate,the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to givethe corresponding hydrazides (3a~3t, 8a, or 8b) in high yields, which were taken up for the next stepwithout any purification.
	With hydrazine hydrate monohydrate In methanol Reflux;
	With hydrazine hydrate monohydrate In ethanol for 10h; Sealed tube; Reflux; Inert atmosphere;
	With hydrazine hydrate monohydrate In ethanol
	With hydrazine monohydrate In ethanol; water monomer for 4h; Reflux;	2.1 Synthesis of acyl hydrazine General procedure: Hydrazine hydrate (55% in water, 8.5 mL, 146 mmol, 5.0 equiv) was added to a stirring solutionof methyl benzoate (4.0 g, 29.4 mmol) in ethanol (20 mL, 1.5 M). The mixture was heated toreflux and stirred for 4 hours. After cooling to room temperature, the mixture was diluted withEtOAc (20 mL) and washed with water (20 mL). The aqueous phase was washed with EtOAc (3 ×20 mL). The combined organic phases were washed with brine solution (20 mL) and dried overanhydrous Na2SO4. The solvent was evaporated in vacuo affording the desired product as awhite solid. The material was used for subsequent reactions without further purification.

Reference： [1]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]
[2]Li, Yitao; Yao, Wenqiang; Lin, Jian; Gao, Guoliang; Huang, Chang; Wu, Yang [Monatshefte fur Chemie, 2021, vol. 152, # 1, p. 121 - 135]
[3]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]
[4]Tavares; Penna; Amaral [Bollettino Chimico Farmaceutico, 1997, vol. 136, # 3, p. 244 - 249]
[5]Jorge, Salomao Doria; Palace-Berl, Fanny; Masunari, Andrea; Cechinel, Cleber Andre; Ishii, Marina; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 5031 - 5038]
[6]Palmer, James T.; Hirschbein, Bernard L.; Cheung, Harry; McCarter, John; Janc, James W.; Yu, Z. Walter; Wesolowski, Gregg [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2909 - 2914]
[7]Rando, Daniela G.; Avery, Mitchell A.; Tekwani, Babu L.; Khan, Shabana I.; Ferreira, Elizabeth I. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6724 - 6731]
[8]Location in patent: experimental part Jorge, Salomao Doria; Masunari, Andrea; Rangel-Yagui, Carlota Oliveira; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 8, p. 3028 - 3036]
[9]Kawano, Tsuyoshi; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro [Journal of the American Chemical Society, 2010, vol. 132, # 20, p. 6900 - 6901]
[10]Vechorkin, Oleg; Hirt, Nathalie; Hu, Xile [Organic Letters, 2010, vol. 12, # 15, p. 3567 - 3569]
[11]Current Patent Assignee: SIGA TECHNOLOGIES INC - US2011/236434, 2011, A1 Location in patent: Page/Page column 12-14
[12]Location in patent: experimental part Ishii, Marina; Jorge, Salomão Dória; De Oliveira, Alex Alfredo; Palace-Berl, Fanny; Sonehara, Ieda Yuriko; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 21, p. 6292 - 6301]
[13]Location in patent: scheme or table Gierczyk, Blazej; Zalas, MacIej; Kazmierczak, Marcin; Grajewski, Jakub; Pankiewicz, Radoslaw; Wyrzykiewicz, Bozena [Magnetic Resonance in Chemistry, 2011, vol. 49, # 10, p. 648 - 654]
[14]Palace-Berl, Fanny; Jorge, Salomão Dória; Pasqualoto, Kerly Fernanda Mesquita; Ferreira, Adilson Kleber; Maria, Durvanei Augusto; Zorzi, Rodrigo Rocha; De Sá Bortolozzo, Leandro; Lindoso, José Ângelo Lauletta; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5395 - 5406]
[15]Yu, Bole; Chen, Ying; Hong, Mei; Duan, Pingping; Gan, Shifeng; Chao, Hui; Zhao, Zujin; Zhao, Jing [Chemical Communications, 2015, vol. 51, # 76, p. 14365 - 14368]
[16]Murty, Madugula S.R.; Katiki, Mohana R.; Rao, Busam R.; Narayanan, Sai S.; Anto, Ruby J.; Buddana, Sudhreer K.; Prakasham, Reddy S.; Devi, Bethala L.A.P.; Prasad, Rachapudi B.N. [Letters in drug design and discovery, 2016, vol. 13, # 9, p. 968 - 981]
[17]Zhang, Guofu; Yu, Yidong; Zhao, Yiyong; Xie, Xiaoqiang; Ding, Chengrong [Synlett, 2017, vol. 28, # 11, p. 1373 - 1377]
[18]Meira, Cássio S.; dos Santos Filho, José Maurício; Sousa, Caroline C.; Anjos, Pâmela S.; Cerqueira, Jéssica V.; Dias Neto, Humberto A.; da Silveira, Rafael G.; Russo, Helena M.; Wolfender, Jean-Luc; Queiroz, Emerson F.; Moreira, Diogo R.M.; Soares, Milena B.P. [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1971 - 1985]
[19]Current Patent Assignee: SIGA TECHNOLOGIES INC - EP3006425, 2016, A1 Location in patent: Paragraph 0123
[20]Kahl, Dylan J.; Hutchings, Kim M.; Lisabeth, Erika Mathes; Haak, Andrew J.; Leipprandt, Jeffrey R.; Dexheimer, Thomas; Khanna, Dinesh; Tsou, Pei-Suen; Campbell, Phillip L.; Fox, David A.; Wen, Bo; Sun, Duxin; Bailie, Marc; Neubig, Richard R.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4350 - 4369]
[21]Yuan, Chen; Yan, Jie; Song, Chen; Yang, Fan; Li, Chao; Wang, Cheng; Su, Huiling; Chen, Wei; Wang, Lijiao; Wang, Zhouyu; Qian, Shan; Yang, Lingling [Molecules, 2020, vol. 25, # 1]
[22]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]
[23]Zou, Liang-Hua; Reball, Jens; Mottweiler, Jakob; Bolm, Carsten [Chemical Communications, 2012, vol. 48, # 92, p. 11307 - 11309,3]
[24]Tang, Xu; Wang, Zhongbo; Zhong, Xinmin; Wang, Xiaobin; Chen, Lijuan; He, Ming; Xue, Wei [Phosphorus, Sulfur and Silicon and the Related Elements, 2019, vol. 194, # 3, p. 241 - 248]
[25]Baumann, Marcus; Donnelly, Kian [Beilstein Journal of Organic Chemistry, 2022, vol. 18, p. 232 - 239]

4
[ 339-59-3 ]
[ 92-55-7 ]
4-trifluoromethyl-N’-((5-nitrofuran-2-yl)methylene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With sulfuric acid; acetic acid; In methanol; water; for 1h;Reflux;	General procedure: Compounds of series I were synthesized by refluxing <strong>[92-55-7]5-nitro-2-furaldehyde diacetate</strong> 98% (5 mmol) and benzhydrazides (3) (5 mmol) in water, sulphuric acid, acetic acid, and methanol (8:7:8:20 v/v) for 1 h. After cooling, the mixture was poured into cold water to precipitate the azomethine derivatives 20(see structural elucidation of the compounds of series I in Supplementary data, p. S2).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 5395 - 5406
[2]Bollettino Chimico Farmaceutico,1997,vol. 136,p. 244 - 249

5
[ 455-24-3 ]
[ 339-59-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: 4-trifluoromethylbenzoic acid With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at 20℃; for 1.5h; Stage #2: With hydrazine In tetrahydrofuran for 5h;
78.9%	Stage #1: 4-trifluoromethylbenzoic acid With sulfuric acid In methanol at 0℃; for 16h; Reflux; Stage #2: With hydrazine hydrate In methanol at 0 - 20℃; for 1h;	1.5 H2SO4(3 mL) was added dropwise to 4-(trifluoromethyl)benzoic acid (10.000 g, 52.598 mmol) in MeOH (250 mL) at 0 °C and the mixture refluxed for 16 h. On cooling, hydrazine monohydrate (73.700 mL) was added and the mixture stirred at rt for 1 h. The solution was then concentrated under reduced pressure. Ice water was added and the resulting precipitate was filtered and washed with H2O (10 mL) and Et2O (3 mL), giving 4- (trifluoromethyl)benzohydrazide as a white crystalline solid (0.847 g, 78.9% yield).1H NMR (400 MHz, DMSO-d6) d 9.90 (s, 1H), 7.94 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 4.68 (s, 2H).13C NMR (101 MHz, DMSO-d6) d 164.6, 150.1, 132.4, 129.2, 121.2, 120.6. LCMS Rf (min) = 5.29, MS m/z = 220.1 [M + H]+.
	Multi-step reaction with 2 steps 1: hydrazine / ethanol; H₂O / Heating

	Multi-step reaction with 2 steps 1: 80 percent / H₂SO₄ 2: 65 percent / 35percent aq. hydrazine / Ambient temperature
	Multi-step reaction with 2 steps 1: sulfuric acid / 4 h / Reflux 2: hydrazine hydrate / water / 0.17 h / 50 - 60 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 4 h / Reflux 2: hydrazine hydrate / water / 0.17 h / 75 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 4 h / Reflux 2: hydrazine hydrate / water / 0.5 h / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride 2: hydrazine hydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 0.01 h / 20 °C / Sonication 2: hydrazine hydrate / 0.02 h / Sonication
	Multi-step reaction with 2 steps 1: sulfuric acid / 3 h / 70 °C 2: H₄N₂*5H₂O / ethanol / 6 h / 70 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / Reflux 2: hydrazine hydrate / methanol / 5 h / Reflux
	Multi-step reaction with 2 steps 1: glycerol-based sulfonic acid functionalized carbon catalyst / 6 h / Reflux; Green chemistry 2: hydrazine hydrate / methanol / 8 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / 70 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 85 °C 2: hydrazine hydrate / methanol / 14 h / 85 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / acetonitrile / 2 h / 20 °C 2: hydrazine hydrate / acetonitrile / 0 - 20 °C
	Multi-step reaction with 2 steps 1: thionyl chloride / 1 h / 40 °C 2: hydrazine hydrate / methanol / 4 h / 65 °C
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 10 h / 20 °C / Inert atmosphere; Sealed tube 2: hydrazine hydrate / ethanol / 10 h / Sealed tube; Reflux; Inert atmosphere
	With benzotriazol-1-ol; hydrazine hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 0 - 20℃;
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate / ethanol

Reference： [1]Romine, Jeffrey L.; Martin, Scott W.; Meanwell, Nicholas A.; Gribkoff, Valentin K.; Boissard, Christopher G.; Dworetzky, Steven I.; Natale, Joanne; Moon, Sandra; Ortiz, Astrid; Yeleswaram, Swamy; Pajor, Lorraine; Gao, Qi; Starrett Jr., John E. [Journal of Medicinal Chemistry, 2007, vol. 50, # 3, p. 528 - 542]
[2]Current Patent Assignee: CINCERA THERAPEUTICS - WO2021/12018, 2021, A1 Location in patent: Page/Page column 63; 71-72
[3]Li, Ming; Wen, Lirong; Wang, Xiao; Yao, Changsheng; Fu, Weijun; Zhao, Guilong; Hu, Fangzhong; Yang, Huazheng [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 2, p. 483 - 488]
[4]Tavares; Penna; Amaral [Bollettino Chimico Farmaceutico, 1997, vol. 136, # 3, p. 244 - 249]
[5]Jorge, Salomao Doria; Palace-Berl, Fanny; Masunari, Andrea; Cechinel, Cleber Andre; Ishii, Marina; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 5031 - 5038]
[6]Ishii, Marina; Jorge, Salomão Dória; De Oliveira, Alex Alfredo; Palace-Berl, Fanny; Sonehara, Ieda Yuriko; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 21, p. 6292 - 6301]
[7]Palace-Berl, Fanny; Jorge, Salomão Dória; Pasqualoto, Kerly Fernanda Mesquita; Ferreira, Adilson Kleber; Maria, Durvanei Augusto; Zorzi, Rodrigo Rocha; De Sá Bortolozzo, Leandro; Lindoso, José Ângelo Lauletta; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 17, p. 5395 - 5406]
[8]Yu, Bole; Chen, Ying; Hong, Mei; Duan, Pingping; Gan, Shifeng; Chao, Hui; Zhao, Zujin; Zhao, Jing [Chemical Communications, 2015, vol. 51, # 76, p. 14365 - 14368]
[9]Khan, Khalid Mohammed; Salar, Uzma; Fakhri, Muhammad Imran; Taha, Muhammad; Hameed, Abdul; Perveen, Shahnaz; Voelter, Wolfgang [Letters in Organic Chemistry, 2015, vol. 12, # 9, p. 637 - 644]
[10]Kamal, Ahmed; Srikanth; Vishnuvardhan; Kumar, G. Bharath; Suresh Babu, Korrapati; Hussaini, S.M. Ali; Kapure, Jeevak Sopanrao; Alarifi, Abdullah [Bioorganic Chemistry, 2016, vol. 65, p. 126 - 136]
[11]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]
[12]Murty, Madugula S.R.; Katiki, Mohana R.; Rao, Busam R.; Narayanan, Sai S.; Anto, Ruby J.; Buddana, Sudhreer K.; Prakasham, Reddy S.; Devi, Bethala L.A.P.; Prasad, Rachapudi B.N. [Letters in drug design and discovery, 2016, vol. 13, # 9, p. 968 - 981]
[13]Xu; Wang; Luo; Yu; Guo; Fu; Zhao; Wu [RSC Advances, 2018, vol. 8, # 12, p. 6306 - 6314]
[14]Meira, Cássio S.; dos Santos Filho, José Maurício; Sousa, Caroline C.; Anjos, Pâmela S.; Cerqueira, Jéssica V.; Dias Neto, Humberto A.; da Silveira, Rafael G.; Russo, Helena M.; Wolfender, Jean-Luc; Queiroz, Emerson F.; Moreira, Diogo R.M.; Soares, Milena B.P. [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1971 - 1985]
[15]Kahl, Dylan J.; Hutchings, Kim M.; Lisabeth, Erika Mathes; Haak, Andrew J.; Leipprandt, Jeffrey R.; Dexheimer, Thomas; Khanna, Dinesh; Tsou, Pei-Suen; Campbell, Phillip L.; Fox, David A.; Wen, Bo; Sun, Duxin; Bailie, Marc; Neubig, Richard R.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4350 - 4369]
[16]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085]
[17]Sharma, Piyoosh; Tripathi, Avanish; Tripathi, Prabhash Nath; Singh, Saumitra Sen; Singh, Surya Pratap; Shrivastava, Sushant Kumar [ACS Chemical Neuroscience, 2019, vol. 10, # 10, p. 4361 - 4384]
[18]Yuan, Chen; Yan, Jie; Song, Chen; Yang, Fan; Li, Chao; Wang, Cheng; Su, Huiling; Chen, Wei; Wang, Lijiao; Wang, Zhouyu; Qian, Shan; Yang, Lingling [Molecules, 2020, vol. 25, # 1]
[19]Zou, Liang-Hua; Reball, Jens; Mottweiler, Jakob; Bolm, Carsten [Chemical Communications, 2012, vol. 48, # 92, p. 11307 - 11309,3]
[20]Choubey, Priyanka Kumari; Tripathi, Avanish; Tripathi, Manish Kumar; Seth, Ankit; Shrivastava, Sushant Kumar [Bioorganic Chemistry, 2021, vol. 111]
[21]Tang, Xu; Wang, Zhongbo; Zhong, Xinmin; Wang, Xiaobin; Chen, Lijuan; He, Ming; Xue, Wei [Phosphorus, Sulfur and Silicon and the Related Elements, 2019, vol. 194, # 3, p. 241 - 248]

6
[ 339-59-3 ]
[ 530-62-1 ]
[ 202823-22-1 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 528 - 542

7
[ 339-59-3 ]
[ 860262-22-2 ]

Yield	Reaction Conditions	Operation in experiment
65.6%	Stage #1: 2-(4-methoxyphenoxy)propanoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With pyridine In dichloromethane at 20℃;	27 Dissolve preparation 26 (100mg, 0.5mmol) in dichloromethane (10ml) and add EDC (117mg, 0.6mmol) followed by HOBT (83mg, 0.6mmol) and stir for for 5 min. Then, add 4-(trifluoromethyl)benzhydrazine (104mg, 0.5mmol) in one portion followed by pyridine (0.124ml, 1.5mmol) and stir at room temperature overnight. After this time, wash the reaction with saturated sodium bicarbonate solution and 1N HCl. Dry the organics over MgS. and evaporate. Purify the residue via silica gel chromatography (50% ethyl acetate in hexanes) to give the 127.8mg of preparation 27 as white solid (65.6%). MS = 383 (M+H+) ; 381 (M-H-).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/65683, 2005, A1 Location in patent: Page/Page column 82

8
[ 329-15-7 ]
[ 339-59-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	With hydrazine hydrate monohydrate In ethanol; dichloromethane at 0 - 20℃; Cooling with ice;
	With pyridine; hydrazine In tetrahydrofuran at 70℃; for 17h;	2 ; In a 500 ml four-necked flask were placed 25 g of 4-trifluoromethylbenzoyl chloride, 38 g of anhydrous hydrazine, 14 g of pyridine, and 70 ml of tetrahydrofuran. The mixture in the four-necked flask was heated to 70°C in a silicone oil bath and allowed to react for 17 hours at around the temperature. After the termination of the reaction, the solvent was distilled away with an evaporator. Solids were obtained. Acolumn, which had been filled with silica gel, was charged with the solids, and the solids were purified with chloroform as a developer. 7.5 g of a white solid matter, which was a hydrazide represented by formula (22), was obtained.
	Multi-step reaction with 2 steps 1: sodium hydroxide 2: hydrazine hydrate monohydrate / methanol

	Multi-step reaction with 2 steps 1: sodium hydroxide 2: hydrazine hydrate monohydrate
	With dmap; triethylamine; hydrazine In dichloromethane at 20℃; for 0.5h;
	Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / 60 °C 2: hydrazine hydrate monohydrate / 12 h / 80 °C
	Multi-step reaction with 2 steps 1: sodium hydroxide 2: hydrazine monohydrate / methanol / 0.5 h / Reflux

Reference： [1]Fugard, Alison J.; Thompson, Bethany K.; Slawin, Alexandra M. Z.; Taylor, James E.; Smith, Andrew D. [Organic Letters, 2015, vol. 17, # 23, p. 5824 - 5827]
[2]Current Patent Assignee: HIROSE ELECTRIC COMPANY LIMITED - EP1607392, 2005, A1 Location in patent: Page/Page column 22
[3]Karaman, Nurcan; Sıcak, Yusuf; Taşkın-Tok, Tuğba; Öztürk, Mehmet; Karaküçük-İyidoğan, Ayşegül; Dikmen, Miris; Koçyiğit-Kaymakçıoğlu, Bedia; Oruç-Emre, Emine Elçin [European Journal of Medicinal Chemistry, 2016, vol. 124, p. 270 - 283]
[4]Öztürk, Mehmet; Demirtaş, Ibrahim; Iyidoğan, Ayşegül Karaküçük; Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Sıcak, Yusuf; Tok, Tuğba Taşkın; Yağlıoğlu, Ayse Şahin [Journal of Molecular Structure, 2020, vol. 1211]
[5]Zhao, Yating; Shi, Chengcheng; Su, Xing; Xia, Wujiong [Chemical Communications, 2020, vol. 56, # 39, p. 5259 - 5262]
[6]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]
[7]Kurşun Aktar, Bedriye Seda; Sicak, Yusuf; Tatar, Gizem; Oruç-Emre, Emine Elçin [Turkish Journal of Chemistry, 2022, vol. 46, # 1, p. 236 - 252]

9
[ 339-59-3 ]
N'-benzylidene-4-trifluoromethylbenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With sulfuric acid; benzaldehyde In methanol	R.12 Reference Example 12 Reference Example 12 To a solution (50 ml) of 4-trifluoromethylbenzohydrazide (3.06 g) and benzaldehyde (1.52 ml) in methanol was added dropwise conc. sulfuric acid (0.5 ml), and this mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated, and the residue was washed with hexane-ethanol (1:1, volume ratio) and recrystallized from ethanol to give N'-benzylidene-4-trifluoromethylbenzohydrazide (3.23 g, yield 74%) as colorless needle crystals. melting point: 216-217°C.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1405636, 2004, A1

10
[ 339-59-3 ]
[ 19164-42-2 ]
[ 1160163-32-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sulfuric acid; acetic acid In methanol; water for 1h; Reflux;	5.1.3. General procedure for the preparation of benzofuroxans derivatives (4a-h) General procedure: A mixture of 5-formylbenzofuroxan (1.0 mmol) and benzhydrazides (1.0 mmol) in water, sulfuric acid, acetic acid and methanol (8:7:8:20 v/v) was heated under reflux during 1 h. After cooling down, the mixture was poured into cold water to give 4.
82%	With sulfuric acid; acetic acid In methanol; water for 1h; Reflux;

Reference： [1]Jorge, Salomao Doria; Palace-Berl, Fanny; Masunari, Andrea; Cechinel, Cleber Andre; Ishii, Marina; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 16, p. 5031 - 5038]
[2]Location in patent: experimental part Jorge, Salomao Doria; Masunari, Andrea; Rangel-Yagui, Carlota Oliveira; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 8, p. 3028 - 3036]

11
[ 1182366-63-7 ]
[ 339-59-3 ]
[ 1182368-96-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran at -45 - 20℃;	68.68a Example 68; 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile; Intermediate 68a; N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(trifluoromethyl)benzohydrazide; To a pre-cooled (-45° C.) solution of (2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (intermediate 1a) (1.97 g, 7.35 mmol) and 4-(trifluoromethyl)benzohydrazide (1.50 g, 7.35 mmol) in anhydrous THF (80 mL) was added 1-Hydroxybenzotriazole monohydrate (1.13 g, 7.35 mmol) and N-(3-Dimethylaminopropyl)-N'-ethylcarbodimide-HCl (2.82 g, 14.7 mmol) at -45° C. followed by triethylamine (2.0 mL, 14.7 mmol). The reaction mixture warmed to room temperature and stirred for 23 h, then quenched with 5% aq. citric acid (300 mL). The solution was extracted with EtOAc (300 mL). The organic extract was washed with 5% aq. citric acid (2×150 mL), sat. aq. NaHCO3 (3×150 mL), H2O (2×150 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as a off white solid (3.09 g, 92%): 1H NMR (400 MHz, d6-DMSO, δ in ppm) 10.71 (s, 1H), 10.31 (s, 1H), 8.05 (d, J=8.2 Hz, 2H), 7.89 (d, J=8.2 Hz, 2H), 7.61 (d, J=8.6 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.67 (d, J=7.6 Hz, 1H), 5.31 (d, J=5.7 Hz, 1H), 4.14 (sextet, J=6.1 Hz, 1H), 3.94 (dd, J=5.7, 7.2 Hz, 1H), 2.30 (s, 3H), 1.28 (d, J=6.3 Hz, 3H).

Reference： [1]Current Patent Assignee: ELLIPSES PHARMA LIMITED - US2009/253758, 2009, A1 Location in patent: Page/Page column 123

12
[ 339-59-3 ]
[ 122-51-0 ]
[ 477886-85-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	at 140℃; for 18h;
60%	at 140℃; for 8h;
50%	for 12h; Reflux; Inert atmosphere;

	With toluene-4-sulfonic acid at 140℃;
	at 120℃;	A. Typical procedure for synthesis of 1, 3, 4-oxadiazoles:¹ General procedure: Benzhydrazide (2 g, 14.6 mmol) and triethyl orthoformate (10 mL) were placed in a 50 mL round bottom flask, and the mixture was vigorously stirred at 120°C over night. The excess triethyl orthoformate was removed by evaporation under reduced pressure. The resulting oil was purified by column chromatography (hexane: ethyl acetate = 70:30) to afford 2-phenyl-1, 3, 4-oxadiazole (1a, 2 g, 10 mmol) in 96% yield.
	Heating;
	at 120℃;
	In neat (no solvent) at 120℃;	A. Typical procedure for synthesis of 1,3,4-oxadiazoles¹ General procedure: Benzhydrazide (2 g, 14.6 mmol) and triethyl orthoformate (10 mL) were placed in a 50 mL round bottom flask, and the mixture was vigorously stirred at 120°C over night. The excess triethyl orthoformate was removed by evaporation under reduced pressure. The resulting oil was purified by column chromatography (hexane: ethyl acetate = 70:30) to afford 2-phenyl-1, 3, 4-oxadiazole (1a, 2 g, 10 mmol) in 96% yield.
	In ethanol at 140℃; for 8h; Inert atmosphere; Sealed tube;
	at 120℃; for 12h; Inert atmosphere; Schlenk technique;
	for 12h; Reflux;

Reference： [1]Wertz, Sebastian; Kodama, Shintaro; Studer, Armido [Angewandte Chemie - International Edition, 2011, vol. 50, # 48, p. 11511 - 11515]
[2]Joseph, Jomy; Kim, Ji Young; Chang, Sukbok [Chemistry - A European Journal, 2011, vol. 17, # 30, p. 8294 - 8298]
[3]Hédouin, Jonathan; Schneider, Cédric; Gillaizeau, Isabelle; Hoarau, Christophe [Organic Letters, 2018, vol. 20, # 19, p. 6027 - 6032]
[4]Vechorkin, Oleg; Hirt, Nathalie; Hu, Xile [Organic Letters, 2010, vol. 12, # 15, p. 3567 - 3569]
[5]Das, Biswanath; Reddy, Gandolla Chinna; Balasubramanyam, Penagaluri; Salvanna [Tetrahedron, 2012, vol. 68, # 1, p. 300 - 305]
[6]Location in patent: scheme or table Gierczyk, Blazej; Zalas, MacIej; Kazmierczak, Marcin; Grajewski, Jakub; Pankiewicz, Radoslaw; Wyrzykiewicz, Bozena [Magnetic Resonance in Chemistry, 2011, vol. 49, # 10, p. 648 - 654]
[7]Reddy, Gandolla Chinna; Balasubramanyam, Penagaluri; Salvanna; Das, Biswanath [European Journal of Organic Chemistry, 2012, # 3, p. 471 - 474]
[8]Salvanna; Reddy, Gandolla Chinna; Das, Biswanath [Tetrahedron, 2013, vol. 69, # 9, p. 2220 - 2225]
[9]Zou, Liang-Hua; Reball, Jens; Mottweiler, Jakob; Bolm, Carsten [Chemical Communications, 2012, vol. 48, # 92, p. 11307 - 11309,3]
[10]Chang, Xiao-Yong; Chen, Ji-Jun; Gu, Qiang-Shuai; Jiang, Sheng-Peng; Li, Zhong-Liang; Liu, Lin; Liu, Xiao-Dong; Liu, Xin-Yuan; Su, Xiao-Long; Wang, Fu-Li; Yang, Chang-Jiang; Ye, Liu [Angewandte Chemie - International Edition, 2021, vol. 60, # 1, p. 380 - 384][Angew. Chem., 2021, vol. 133, # 1, p. 384 - 388,5]
[11]Chen, Su; Ranjan, Prabhat; Ramkumar, Nagarajan; Van Meervelt, Luc; Van der Eycken, Erik V.; Sharma, Upendra K. [Chemistry - A European Journal, 2020, vol. 26, # 62, p. 14075 - 14079]

13
[ 22980-09-2 ]
[ 339-59-3 ]
[ 1312761-40-2 ]

Yield	Reaction Conditions	Operation in experiment
39%	With triethylamine In tert-butyl methyl ether at 0 - 20℃; for 6.75h;	5.1.8. General procedure B for the preparation of the N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazides 7 General procedure: Triethylamine (153 μL, 1.10 mmol) was added dropwise at 0 °C to a stirred suspension of 2-(1H-indol-3-yl)-2-oxoacetyl chloride (5; 208 mg, 1.00 mmol) and the appropriate benzohydrazide 6 (1.00 mmol) in anhydrous tert-butyl methyl ether (20 mL). The reaction mixture was stirred at 0 °C for 15 min and then for 1-26 h at room temperature, monitoring the reaction by TLC analysis. After completion of the reaction the solvent was removed in vacuo and the residue was washed with a saturated NaHCO3 aqueous solution, water (3 × 20 mL in each case) and petroleum ether. The crude product was purified by recrystallization from the given solvent.

Reference： [1]Location in patent: experimental part Schmidt, Stefanie; Preu, Lutz; Lemcke, Thomas; Totzke, Frank; Schächtele, Christoph; Kubbutat, Michael H.G.; Kunick, Conrad [European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 2759 - 2769]

14
[ 14036-06-7 ]
[ 339-59-3 ]
[ 1340587-12-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	In acetonitrile at 20℃; for 0.166667h;	4.1.1. General procedure for the synthesis of ethyl benzoylhydrazonoformate 2a-2e (for the atom numbering scheme for ¹H NMR spectra assignment, see Fig. 2) General procedure: Diethoxymethyl acetate (243 mg, 1.5 mmol) was added at room temperature to the mixture of a substituted benzoic acid hydrazide 1 (1 mmol) in acetonitrile (10 mL). Reaction mixture was then stirred for 10 min at room temperature and evaporated to dryness. A crude product was recrystallized from the appropriate solvent.

Reference： [1]Location in patent: experimental part Vavříková, Eva; Polanc, Slovenko; Kočevar, Marijan; Horváti, Kata; Bsze, Szilvia; Stolaříková, Jiřina; Vávrová, Kateřina; Vinšová, Jarmila [European Journal of Medicinal Chemistry, 2011, vol. 46, # 10, p. 4937 - 4945]

15
[ 339-59-3 ]
[ 24662-37-1 ]
[ 1284312-38-4 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate In butan-1-ol at 160℃; for 8h;

Reference： [1]Location in patent: experimental part Kumar, Dalip; Narayanam, Maruthi Kumar; Chang, Kuei-Hua; Shah, Kavita [Chemical Biology and Drug Design, 2011, vol. 77, # 3, p. 182 - 188]

16
[ 75-15-0 ]
[ 339-59-3 ]
4-amino-5-(4-(trifluoromethyl)phenyl)-4H-1,2,4-triazole-3-thiol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: carbon disulfide; 4-(trifluoromethyl)benzoic acid hydrazide With potassium hydroxide In ethanol at 20℃; for 36h; Stage #2: With hydrazine In water for 4h; Reflux;	4.1.2. General procedures for the synthesis of 4-amino-5-(4-substituted)phenyl)-4H-1,2,4-triazole-3-thiols (5a-b) General procedure: 4-Fluorobenzoyl hydrazine (3a) (15.4 g, 0.1 mol) was added to a solution of potassium hydroxide (6.72 g, 0.12 mol) and absolute ethanol (200 mL) under stirring. After 3a was dissolved, carbon disulfide (9.12 g, 0.12 mol) was added dropwise into the solution, the mixture was kept stirring at room temperature for 36 h. The precipitate was filtered and washed with dry ether (75 mL). The crude product potassium salt 4a (13.4 g, 0.05 mol) was dissolved in hot water (50 mL) and filtered. Then, 85% hydrazine (5.8 g, 0.1 mol) and the filtrate containing the compound 4a were refluxed for 4 h until the reaction mixture changed its color to green. A yellow solid was precipitated by diluting with cold water (150 mL) and acidifying with concentrated hydrochloric acid. After filtering, the solid was washed with cold water (20 mL), and recrystallized from ethanol to give the analytically pure compound 5a.

Reference： [1]Location in patent: experimental part Chen, Min; Wang, Xian-Feng; Wang, Si-Si; Feng, Yi-Xiao; Chen, Feng; Yang, Chun-Long [Journal of Fluorine Chemistry, 2012, vol. 135, p. 323 - 329]

17
[ 339-59-3 ]
[ 202823-22-1 ]

Reference： [1]Tetrahedron,2012,vol. 68,p. 7978 - 7983

18
[ 623-26-7 ]
[ 339-59-3 ]
[ 1181214-46-9 ]

Yield	Reaction Conditions	Operation in experiment
51%	With potassium carbonate In butan-1-ol at 150℃; for 0.5h; Microwave irradiation;	21 Terephthalonitrile (115 mg, 0.90 mmol), 4-trifluoromethylbenzoic acid hydrazide (92 mg, 0.450 mmol), K2CO3 (31 mg, 0.225 mmol), and n-butyl alcohol (~2 mL) were combined in a 10 mL CEM Microwave reaction vial fitted with magnetic stir bar and subjected to microwave irradiation at 150 0C for 30 min. The contents were then filtered and concentrated to dryness. Chromatography (3:1 hexanes/EtOAc) afforded the 1,2,4-triazole nitrile (72 mg, 0.230 mmol, 51%). Reduction with DIBAL then generated the corresponding aldehyde.
51%	With potassium carbonate In butan-1-ol at 150℃; for 0.5h; Microwave irradiation;	23 Example 23: Preparation of 4-[5-(4-trifluoromethylphenyl)-lH-[l,2,4]triazol-3-yl]- benzonitrile.Terephthalonitrile (115 mg, 0.90 mmol), 4-trifluoromethylbenzoic acid hydrazide (92 mg, 0.450 mmol), K2Cθ3 (31 mg, 0.225 mmol), and n-butyl alcohol (~2 mL) were combined in a 10 mL CEM Microwave reaction vial fitted with magnetic stir bar and subjected to microwave irradiation at 150 0C for 30 min. The contents were then filtered and concentrated to dryness. Chromatography (3:1 hexanes/EtOAc) afforded the 1,2,4-triazole nitrile (72 mg,

Reference： [1]Current Patent Assignee: CORTEVA INC - WO2011/17504, 2011, A1 Location in patent: Page/Page column 32
[2]Current Patent Assignee: CORTEVA INC - WO2011/17513, 2011, A1 Location in patent: Page/Page column 32-33

19
[ 52817-12-6 ]
[ 339-59-3 ]
[ 1436436-05-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	With acetic acid In ethanol at 20℃; for 6h;	General procedure: to a mixture solution of 3-formylchromone d1 (174 mg, 1 mmol) and benzohydrazide e1 (136 mg, 1 mmol) in 25 mL ethanol was added three drops of acetic acid with stirring for 6 h at room temperature. Insoluble solid was gradually generated, then filtered and washed several times with ethanol. After drying, pure target compound f1 was afforded (227 mg, yield 78%).
	With acetic acid In ethanol at 20℃; for 6h;	1 General procedure: Take 1mmol substituted benzoyl hydrazide and 1mmol 6-substituted-3-formylchromone and dissolve in 25mL ethanol, add 3 drops of HOAc, and stir at room temperature for 6h. White turbidity is formed, and TLC monitors until the reaction is complete and new compounds are formed. Filter with suction and wash with ethanol several times until TLC detects that there are no more reactants substituted for benzoylhydrazine and 6-substituted-3-formylchromone in the filtrate, indicating that it has been washed and the filter cake is a pure compound. Dry the filter cake to obtain a pure powder product.

Reference： [1]Tu, Qi-Dong; Li, Ding; Sun, Yao; Han, Xin-Ya; Yi, Fan; Sha, Yibamu; Ren, Yan-Liang; Ding, Ming-Wu; Feng, Ling-Ling; Wan, Jian [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 11, p. 2826 - 2831]
[2]Current Patent Assignee: JIANGXI SCIENCE & TECHNOLOGY NORMAL UNIVERSITY - CN113563321, 2021, A Location in patent: Paragraph 0021-0024

20
[ 506-68-3 ]
[ 339-59-3 ]
2-amino-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium hydrogencarbonate In 1,4-dioxane; water at 20℃; for 15h;	291 Example 2916-(2-(5-(4-(trifluoromethyl)phenyl)- 1.3.4-oxadiazol-2-ylamino)ethoxy)-3.4- dihydroquinolin-2(lH)-one5-(4-(trifluoromethyl)phenyl)-l, 3, 4-oxadiazol-2-amine To a solution of 4-(trifluoromethyl)benzohydrazide (0.5 g, 2.449 mmol) in dioxane (10 mL) and water (2 mL) was added sodium bicarbonate (0.617 g, 7.35 mmol) and cyanic bromide (0.519 g, 4.90 mmol). The reaction was stirred at room temperature for 15 h. The reaction mixture was diluted with water (50 mL), extracted with EtOAc, dried over sodium sulfate, and evaporated to yield 5-(4- (trifluoromethyl)phenyl)-l,3,4-oxadiazol-2-amine (0.28, 50%). 1H MR: 400 MHz, DMSO-d6: δ 7.43 (s, 2H), 7.91 (d, J = 8.40 Hz, 2H), 8.00 (d, J = 8.40 Hz, 2H).LCMS: RT 1.55 min. LCMS (ES-API), m/z 230.0 (M+H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; BIOCON LIMITED - WO2013/49119, 2013, A1 Location in patent: Page/Page column 272

21
[ 16034-46-1 ]
[ 339-59-3 ]
[ 1356997-71-1 ]

Yield	Reaction Conditions	Operation in experiment
707 mg	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 19h;	19.1 1) 1-Methyl-N′-[4-(trifluoromethyl)benzoyl]-1H-pyrazol-5-carbohydrazide 1) 1-Methyl-N'-[4-(trifluoromethyl)benzoyl]-1H-pyrazol-5-carbohydrazide 4-(Trifluoromethyl)benzohydrazide (583 mg) was added to a dimethylformamide (6.8 mL) solution that contained 1-methyl-1H-pyrazol-5-carboxylic acid (300 mg), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.09 g) and diisopropylethylamine (830 μL) at a room temperature, and the obtained solution was then stirred for 19 hours. Thereafter, water was added to the reaction solution, and the obtained mixture was then extracted with ethyl acetate. The organic layer was washed with water and a saturated saline, and was then dried over anhydrous magnesium sulfate, followed by vacuum concentration. The obtained solid was washed with ethyl acetate/hexane (1:1), so as to obtain the title compound (598 mg) in the form of a colorless solid. The filtrate was concentrated under a reduced pressure, and the residue was then purified by column chromatography (silica gel cartridge, chloroform:methanol=10:0 to 9:1), so as to further obtain the title compound (109 mg) in the form of a colorless solid.
109 mg	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 19h;	12.1 1) 1-Methyl-N′-[4-(trifluoromethyl)benzoyl]-1H-pyrazol-5-carbohydrazide 1) 1-Methyl-N'-[4-(trifluoromethyl)benzoyl]-1H-pyrazol-5-carbohydrazide 4-(Trifluoromethyl)benzohydrazide (583 mg) was added to an N,N-dimethylformamide (6.8 mL) solution that contained 1-methyl-1H-pyrazol-5-carboxylic acid (300 mg), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.09 g) and diisopropylethylamine (830 μL) at a room temperature, and the obtained solution was then stirred for 19 hours. Thereafter, water was added to the reaction solution, and the obtained mixture was then extracted with ethyl acetate. The organic layer was washed with water and a saturated saline, and was then dried over anhydrous magnesium sulfate, followed by vacuum concentration. The obtained solid was washed with ethyl acetate/hexane (1:1), so as to obtain the title compound (598 mg) in the form of a colorless solid. The filtrate was concentrated under a reduced pressure, and the residue was then purified by column chromatography (silica gel cartridge, chloroform:methanol=10:0 to 9:1), so as to further obtain the title compound (109 mg) in the form of a colorless solid.

Reference： [1]Current Patent Assignee: TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - US2013/123500, 2013, A1 Location in patent: Paragraph 0273; 0274
[2]Current Patent Assignee: TAISHO PHARMACEUTICAL HOLDINGS CO., LTD. - US2013/137865, 2013, A1 Location in patent: Paragraph 0336; 0337; 0338

22
[ 339-59-3 ]
[ 34940-47-1 ]
C₁₈H₁₅F₃N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With acetic acid In methanol at 20℃; for 0.5h;	3 Production of Compound (I-3) First, 0.48 g of 3-cyano-5-(N,N-dimethylaminomethylene)-1-ethyl-4-methyl-2,6-dioxo-1,2,5,6-tetrahydropyridine, 3.15 g of acetic acid, 0.42 g of 4-(trifluoromethyl)benzhydrazide and 5 mL of methanol were mixed and stirred at a room temperature for 30 minutes. A precipitated solid was collected by filtration and washed with methanol, followed by drying, and 0.80 g of Compound (1-3) (99% yield) was obtained. [0153] 1H-NMR (400 MHz) δ (DMSO-d6) ppm: 1.09 (3H, t, J=7.1 Hz), 2.43 (3H, s), 3.88-3.93 (2H, m), 7.87 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz), 8.43 (1H, s).

Reference： [1]Current Patent Assignee: KH NEOCHEM CO.,LTD. - US2013/123494, 2013, A1 Location in patent: Paragraph 0152; 0153

23
[ 339-59-3 ]
[ 92-55-7 ]
[ 1449763-70-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 5395 - 5406

24
[ 339-59-3 ]
[ 14527-26-5 ]
C₉H₉F₃N₄O [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 67,p. 325 - 334

25
[ 698-63-5 ]
[ 339-59-3 ]
4-trifluoromethyl-N’-((5-nitrofuran-2-yl)methylene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With sulfuric acid In methanol; water; acetic acid for 1h; Reflux;	4.1.1. General procedure for synthesis of 4-substituted-((5-nitrofuran-2-yl)methylene)benzohydrazide General procedure: The twenty-two substituted-benzhydrazides (1a-v) described in this study were available to be used since they were recently synthesized and reported elsewhere.35,37 An equimolar mixture of 5-nitrofuran-2-carbaldehyde (0.05 mol) and benzhydrazides (1a-v) in water, sulfuric acid, acetic acid, and methanol, (8:7:8:20 v/v) was heated under reflux during 1 h. After cooling down, the mixture was poured into cold water to give 2a-v.

Reference： [1]Zorzi, Rodrigo Rocha; Jorge, Salomao Doria; Palace-Berl, Fanny; Pasqualoto, Kerly Fernanda Mesquita; Bortolozzo, Leandro De Sa; De Castro Siqueira, Andre Murillo; Tavares, Leoberto Costa [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 10, p. 2844 - 2854]

26
[ 1445-45-0 ]
[ 339-59-3 ]
[ 497946-53-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With Al³⁺-K₁₀ montmorillonite clay In neat (no solvent) at 55℃; for 0.25h; Microwave irradiation;	General procedure for 1,3,4-oxadiazole synthesis General procedure: A 5 mL microwave vial was charged with acidhydrazide (100 mg, 1 eq), trimethyl orthoester (2 eq) and Al3+-K10 clay (75 mg). The resulting mixture was kept under microwave irradiation maintaining the temperature at 55 °C for 15 min (Microwave irradiations were performed on CEM-discover model No. 908010). The reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with ethyl acetate stirred well, filtered, washed well with ethyl acetate. Filtrate was evaporated under reduced pressure to obtain highly pure product. In some cases, products were purified by column chromatography using 60-120 mesh silica with 20-100 % ethyl acetate in pet ether as eluting solvents. The catalyst recovered by filtration was reused for another 5 more times.

Reference： [1]Suresh, Dhanusu; Kanagaraj, Kuppusamy; Pitchumani, Kasi [Tetrahedron Letters, 2014, vol. 55, # 27, p. 3678 - 3682]

27
[ 339-59-3 ]
[ 90-02-8 ]
[ 849-93-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
89%	In methanol for 1h; Reflux;	Synthesis of the hydrazone compound BH 4-Trifluoromethylbenzohydrazide (10 mmol, 2.04 g) andsalicylaldehyde (10 mmol, 1.22 g) were refluxed in methanol (50 mL). The reaction was continued for 1 h in an oil bath during which a solid compound was separated. It was filtered and washed with cold methanol. The crude product wasrecrystallized from methanol and dried over anhydrous CaCl2. Yield: 2.75 g (89%). IR data (KBr pellet, cm-1): 3337 (O-H),3223 (N-H), 1655 (C=O), 1613 (C=N). UV-Vis data in methanol (nm): 275, 350, 430. Analysis: found (%): C 58.31,H 3.72, N 9.23; calculated for C15H11F3N2O2 (%): C 58.45, H 3.60, N 9.09. 1H NMR (300 MHz, d6-DMSO): δ 12.26 (s, 1H,OH), 11.53 (s, 1H, NH), 8.72 (s, 1H, CH=N), 7.92 (d, 2H, ArH), 7.81 (d, 2H, ArH), 7.63 (d, 1H, ArH), 7.54 (t, 1H, ArH),7.10-7.01 (m, 2H, ArH).
0.2 g	With hydrogenchloride In ethanol; water at 20℃; for 16h;	7 SYNTHESIS EXAMPLE 7 SYNTHESIS EXAMPLE 7 Preparation of (0324) (0325) To a mixture of 0.52 g of 4-trifluoromethyl-benzhydrazide in 15 mL ethanol 0.31 g of salicyl aldehyde is added dropwise at room temperature. Immediately a colorless suspension is formed. After addition of 0.5 mL of concentrated hydrochloric acid the suspension is stirred for 16 hours at room temperature. The precipitate is then filtrated off, washed with 5 mL of ethanol and dried in the vacuum at 50° C. yielding 0.20 g of the desired product as a colorless powder. Melting point: 230.6° C.

In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Cui; Wang; Su; Huang; Zhang [Journal of Structural Chemistry, 2019, vol. 60, # 8, p. 1299 - 1305][Zh. Strukt. Kim., 2019, vol. 60, # 8, p. 1351 - 1357,7]
[3]Current Patent Assignee: BASF SE - US8791298, 2014, B2 Location in patent: Page/Page column 52
[4]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

28
[ 673-22-3 ]
[ 339-59-3 ]
[ 1190934-74-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	In methanol for 1h; Reflux;	Synthesis of the Aroylhydrazone Schiff Base H2L The aroylhydrazone Schiff base H2L was synthesized byrefluxing a methanolic solution (30 mL) of 4-methoxysalicylaldehyde (10 mmol, 1.52 g) with 4-trifluoromethylbenzohydrazide (10 mmol, 2.04 g). Reflux was continued for 1 h atoily bath during which a solid compound separated. It wasfiltered and washed with cold methanol. The crude productwas recrystallized from methanol and dried over anhydrousCaCl2. Yield: 2.87 g (85%). Elemental analysis: Anal. Calcd.for C16H13F3N2O3: C, 56.81; H, 3.87; N, 8.28. Found: C,56.72; H, 3.95; N, 8.16%. IR data (KBr pellet, cm1): 3413n(O-H), 3218n(N-H), 1645n(CHO), 1611n(CHN). UV-Visdata in methanol (nm): 289, 353, 421.
0.51 g	With hydrogenchloride In ethanol; water at 20℃; for 16h;	8 SYNTHESIS EXAMPLE 8 SYNTHESIS EXAMPLE 8 Preparation of (0326) (0327) To a mixture of 0.52 g of 4-trifluoromethyl-benzhydrazide in 15 mL ethanol 0.39 g of 2-hydroxy-4-methoxy-benzaldehyde is added dropwise at room temperature. After addition of 0.5 mL of concentrated hydrochloric acid a yellow suspension is formed which is stirred for 16 hours at room temperature. The precipitate is then filtrated off, washed with 5 mL of ethanol and dried in the vacuum at 50° C. yielding 0.51 g of the desired product as a yellow powder. Melting point: 200° C. (under decomposition).

Reference： [1]Liu, Jing; Lin, Jiahui; Liu, Juan; Chen, Wu; Cui, Yongming [Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 2016, vol. 46, # 12, p. 1871 - 1878]
[2]Current Patent Assignee: BASF SE - US8791298, 2014, B2 Location in patent: Page/Page column 52-53

29
[ 10320-42-0 ]
[ 339-59-3 ]
C₁₂H₈F₃N₅O₃ [ No CAS ]

Reference： [1]RSC Advances,2014,vol. 4,p. 30638 - 30643

30
[ 201230-82-2 ]
[ 339-59-3 ]
[ 202823-22-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	With palladium(II) trifluoroacetate; trifluoroacetic acid; In acetonitrile; at 60.0℃; for 12h;	To a 25 mL test tube was added 2 mmol of 4-trifluoromethylbenzohydrazide,0.1 mmol of palladium trifluoroacetate, 3 mmol of copper oxide,Trifluoroacetic acid 6 mmol,Add acetonitrile as solvent, put carbon monoxide balloon as carbonyl source, stir at 60 degrees Celsius,Reaction for about 12 h.TLC (Thin Layer Chromatography) After the reaction was completed, the reaction solution was cooled to room temperature, the carbon monoxide balloon was removed, and the unreacted carbon monoxide was slowly vented.The reaction solution was filtered, the filtrate was distilled under reduced pressure to remove the solvent, and then purified by column chromatography,Get the target product5- (4- (trifluoromethyl) phenyl) -1,3,4-oxadiazol-2 (3-hydro) -one(Compound 2),The column chromatography eluent used was a 4: 1 by volume petroleum ether:Ethyl acetate mixed solvent in 73% yield.

Reference： [1]Journal of Organic Chemistry,2015,vol. 80,p. 5713 - 5718
[2]Patent: CN104710379,2017,B .Location in patent: Paragraph 0040-0042

31
[ 339-59-3 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	11 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.11 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole 16 1H NMR (DMSO-d6, 250 MHz): δ = 8.30 (d, J = 8.1 Hz, 2H), 8.02 (d, J = 8.3 Hz, 2H), 7.93 (d, J = 16.2 Hz, 1H), 7.45 (d, J = 4.0 Hz, 1H), 7.33 (d, J = 3.9 Hz, 1H), 7.09 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.71, 162.82, 141.81, 132.48, 132.25, 132.12, 132.03, 127.98, 127.62, 126.95, 126.91, 125.65, 122.93, 115.53, 109.34; LC/MS (APCI): 400.86 [M+H]+ and isotopic peak: 402.72; HRMS (TOF, ESI+) cald for C15H9N2OF3SBr (M + H)+ 400.9571, found 400.9574; yellow powder.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

32
[ 58267-95-1 ]
[ 339-59-3 ]
2-[(E)-2-(5-phenylthiophen-2-yl)ethenyl]-5-(4-trifluoromethylphenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	12 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.12 2-[(E)-2-(5-phenylthiophen-2-yl)ethenyl]-5-(4-trifluoromethylphenyl)-1,3,4-oxadiazole 17 1H NMR (DMSO-d6, 250 MHz): δ = 8.21 (d, J = 7.9 Hz, 2H), 7.97-7.83 (m, 3H), 7.64 (d, J = 7.1 Hz, 2H), 7.52 (bs, 2H), 7.38 (t, J = 6.9 Hz, 2H), 7.30 (d, J = 7.0 Hz, 1H), 6.97 (d, J = 16.0 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.84, 162.71, 146.70, 139.19, 133.47, 132.93, 129.80, 129.77, 129.74, 129.03, 128.90, 127.93, 126.98, 126.95, 126.91, 126.88, 126.13, 126.08, 125.62, 108.38, 105.32; LC/MS (ESI): 398.98 [M+H]+; HRMS (TOF, ESI+) cald for C21H14N2OF3S (M + H)+ 399.0779, found 399.0775; yellow powder.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

33
[ 5926-51-2 ]
[ 339-59-3 ]
C₁₂H₆BrF₃N₂O₃ [ No CAS ]

Reference： [1]Journal of Chemical Information and Modeling,2016,vol. 56,p. 73 - 81

34
[ 339-59-3 ]
[ 141172-33-0 ]
(E)-2-(2-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)vinyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With trichlorophosphate at 70℃; Reflux;	4.2. Chemistry experimental procedure for the synthesis of Combretastatin linked 1,3,4-oxadiazole conjugates (5a-p) General procedure: A mixture of (E)-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid (8, 688.8 mg, 2 mmol) and substituted hydrazide(11) (2 mmol) in POCl3 (10 ml) was refluxed for 5-6 h. The reaction mixture was cooled to room temperature and then the contents were poured on to crushed ice and neutralized with bicarbonate solution. The resulting solid collected and washed with water extracted with EtOAc dried over Na2SO4. The residue obtained was purified by column chromatography by using ethyl acetate and hexane to afford the desired compounds combretastatin linked oxadiazoles (5a-p)

Reference： [1]Kamal, Ahmed; Srikanth; Vishnuvardhan; Kumar, G. Bharath; Suresh Babu, Korrapati; Hussaini, S.M. Ali; Kapure, Jeevak Sopanrao; Alarifi, Abdullah [Bioorganic Chemistry, 2016, vol. 65, p. 126 - 136]

35
[ 75-15-0 ]
[ 339-59-3 ]
[ 389120-03-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide In ethanol Reflux;	General procedure for the preparation of 1,3,4-oxadiazole-2-thiones (19a-j) General procedure: Acid hydrazides 18(a-j) (1.0 mmol)were dissolved in ethanol (50 mL),and to this potassiumhydroxide was added (1.49 mmol) which is dissolved inwater (2 mL), and then carbondisulfide was added(4.0 mmol). Then, the reaction mixture was heated at reflux for 10-12 h. Solvent was evaporated, and the residue wasacidified with 10 % HCl. The precipitate was collected byfiltration, washed with water and dried. The products 19(a-j) were used without further purification.
	With potassium hydroxide In ethanol; water at 80℃; for 24h;	9 The preparation steps of 1-Ethyl-6-fluoro-7-(4-((5-(4-(trifluoromethyl)phenyl)-2-sulfanyl-1,3,4-oxadiazole-3(2H) -Yl)methyl)piperazin-1-yl)-4-oxy-1,4-dihydroquinoline-3-carboxylic acid (IIi) Put 5.0mmol of 4-(trifluoromethyl)benzoyl hydrazide,7.5mmol carbon disulfide, 5.0mmol potassium hydroxide,Add 10 mL of 50% ethanol aqueous solution to a 100 mL flask, stir and react at 80°C for 24 hours. After the reaction is complete, adjust the pH to neutral.Let stand to precipitate solids, filter, and air-dry to obtain intermediate Ii,That is 5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2(3H)-thione.

Reference： [1]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]
[2]Current Patent Assignee: GUANGDONG ACADEMY OF SCIENCES - CN112592339, 2021, A Location in patent: Paragraph 0063-0065; 0067

36
[ 590-92-1 ]
[ 339-59-3 ]
C₁₁H₈BrF₃N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; In toluene; at 100℃; for 2h;	General procedure: A mixture of benzoylhydrazine 23 (0.68 g, 5 mmol), 3-<strong>[590-92-1]bromopropionic acid</strong> (1.2 g, 7.5 mmol), POCl3 (4 mL) in toluene (20 mL) was stirred at 100 C for 2 h. After cooling to room temperature, the mixture was poured into ice water slowly, and extracted with ethyl acetate (20 mL* 3). The organic layer was combined, dried over Na2SO4, and concentrated to afford crude 2-(2-bromoethyl)-5-phenyl-1,3,4- oxadiazole 19o as a yellow solid in 41% of yield. This crude product was used without purification. Following the same procedure for the synthesis of 17a, targetcompound 17o was obtained using crude 2-(2-bromoethyl)-5-phenyl-1,3,4-oxadiazole 19o as halide.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 112,p. 217 - 230

37
[ 339-59-3 ]
7-[1-(tert-butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid [ No CAS ]
tert-butyl 4-[5-oxo-3-({2-[4-(trifluoromethyl)benzoyl]hydrazino}carbonyl)-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49.7%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	185A Example 185A tert-butyl 4-[5-oxo-3-({2-[4-(trifluoromethyl)benzoyl]hydrazino}carbonyl)-4,5-dihydropyrazolo[l,5- a]pyrimidin-7-yl]piperidine- 1 -carboxylate -[l-(te^butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[l,5-a]pyrimidine-3-carboxylic acid (150 mg, 0.41 mmol) and 4-(trifluoromethyl)benzohydrazide (127 mg, 0.6 mmol) were dissolved in N,N-Dimethylformamide (1,5 ml). N,N-Diisopropylethylamin (0.22 ml, 1.24 mmol) and N- [(Dimethylamino)(3H-[l,2,3]triazolo[4,5-b]pyridin-3-yloxy)methyliden]-N-methyl-methanaminium- - - hexafluorophosphate (266 mg, 0.62 mmol) were added and the mixture was stirred for 16h at RT. Water was added and the resulting precipitate was filtered, washed with acetonitrile, and dried to afford the title compound (144.5 mg, 49.7% of theory). LC-MS (Method 5B): Rt = 0.92 min, MS (ESIPos): m/z = 549.3 [M+H]+

Reference： [1]Current Patent Assignee: BAYER AG - WO2016/71216, 2016, A1 Location in patent: Page/Page column 247-248

38
[ 90-59-5 ]
[ 339-59-3 ]
N'-(3,5-dibromo-2-hydroxybenzylidene)-4-trifluoromethylbenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With acetic acid In methanol at 20℃;
80%	In methanol for 1h; Reflux;	Synthesis of the Aroylhydrazone SchiffBases General procedure: The aroylhydrazone Schiff bases H2L1 and H2L2 weresynthesized in a similar way by refluxing a methanolic solution(30 mL) of 4-trifluoromethylbenzohydrazide (10 mmol,2.04 g) with 3,5-dibromosalicylaldehyde (10 mmol, 2.80 g)and 3-bromo-5-chlorosalicylaldehyde (10 mmol, 2.35 g),respectively. Reflux was continued for 1 h in oil bath duringwhich a solid compound separated. It was filtered and washedwith cold methanol. The crude product was recrystallizedfrom methanol and dried over anhydrous CaCl2. H2L1: Yield: 3.73 g (80%). IR data (KBr pellet,cm-1): 3351 ν(O-H), 3218 ν(N-H), 1653 ν(C=O), 1615ν(C=N). UV-Vis data in methanol (nm): 283, 362, 425.Analysis: Found: C 38.50, H 2.02, N 5.93%. Calculatedfor C15H9Br2F3N2O2: C 38.66, H 1.95, N 6.01%. 1H NMR(300 MHz, d6-DMSO): δ 12.13 (s, 1H, OH), 11.22 (s, 1H,NH), 8.71 (s, 1H, CH=N), 7.92 (d, 2H, ArH), 7.72-7.85(m, 4H, ArH).

Reference： [1]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]
[2]Liu, Qing; Lin, Jiahui; Liu, Juan; Chen, Wu; Cui, Yongming [Acta Chimica Slovenica, 2016, vol. 63, # 2, p. 279 - 286]

39
[ 339-59-3 ]
[ 19652-32-5 ]
[ 1235562-98-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	In methanol; for 1h;Reflux;	General procedure: The aroylhydrazone Schiff bases H2L1 and H2L2 weresynthesized in a similar way by refluxing a methanolic solution(30 mL) of 4-trifluoromethylbenzohydrazide (10 mmol,2.04 g) with 3,5-dibromosalicylaldehyde (10 mmol, 2.80 g)and <strong>[19652-32-5]3-bromo-5-chlorosalicylaldehyde</strong> (10 mmol, 2.35 g),respectively. Reflux was continued for 1 h in oil bath duringwhich a solid compound separated. It was filtered and washedwith cold methanol. The crude product was recrystallizedfrom methanol and dried over anhydrous CaCl2. H2L2: Yield: 3.85 g (91%).

Reference： [1]Acta Chimica Slovenica,2016,vol. 63,p. 279 - 286

40
[ 339-59-3 ]
[ 611-73-4 ]
2-phenyl-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 24h; Sealed tube; Irradiation;	General procedure for synthesis of 2,5-diaryl 1,3,4-oxadiazoles and reuse of the catalyst: General procedure: A sealed tube equipped with a magnetic stir bar was charged with acylhydrazine 1 (0.5 mmol), α-keto acid 2 (0.5 mmol), K2CO3 (1 mmol), PANI-g-C3N4-TiO2 (40 mg) and DMF (5.0 mL). The mixture was then irradiated with a 14 W CFL and stirred at room temperature (25 °C) for 24 h. The distance of the reaction vial from the light is about 5 centimeters. After reaction, the mixture was diluted with EtOAc (10 mL) and H2O (5 mL), and the solid catalyst was recovered by centrifugation. The aqueous phase was extracted with EtOAc (5 mL × 3). The collected organic extracts were dried on Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography on silica gel using a mixture of PE/EA (20:1) to give the pure product 3.
55%	With tert.-butylhydroperoxide; sodium carbonate; potassium iodide In 1,4-dioxane at 120℃; for 5h; Sealed tube;	2.Experimental Procedures General procedure: In a 35 mL sealed tube, a solution of 3 mL of 1,4-dioxane, acyhydrazines 1 (0.5mmol), α-ketoacids 2 (0.5 mmol) , Na2CO3 (0.6 mmol), KI (0.05 mmol) and TBHP (2.0 mmol) was sequentially added. The reaction mixture was stirred at 120 °C for 5 h and then cooled to room temperature. Then, the mixture extracted with ethyl acetate (2 × 10 mL), and the organic layer was combined and dried with anhydrous Na2SO4. After removal of the solvent under reduced pressure, the residue was separated by flash column chromatography to afford the pure product 3 (PE:EA = 20:1).

Reference： [1]Wang, Liang; Wang, Yaoyao; Chen, Qun; He, Mingyang [Tetrahedron Letters, 2018, vol. 59, # 15, p. 1489 - 1492]
[2]Gao, Peng; Wang, Juan; Bai, Zijing; Cheng, Hualei; Xiao, Jian; Lai, Mengnan; Yang, Desuo; Fan, Mingjin [Tetrahedron Letters, 2016, vol. 57, # 41, p. 4616 - 4619]

41
[ 339-59-3 ]
1-[4-hydroxy-3-(2-methyl-benzofuran-5-yl)phenyl]-2-propanone [ No CAS ]
1-[4-hydroxy-3-(2-methylbenzofuran-5-yl)phenyl]-2-propanone 4-trifluoromethylbenzoylhydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.1%	With acetic acid In ethanol at 20℃; for 4h;	4 Example 4 1- [4-hydroxy-3- (2-methyl-benzofuran-5-yl) phenyl] -2-propanone hydrazone Preparation of 4-trifluoromethylbenzoyl 0.5mmol1- [4- hydroxy-3- (2-methyl-benzofuran-5-yl) phenyl] -2-propanone, 0.55mmol4- trifluoromethylbenzoyl hydrazine, dissolved with 20ml of ethanol was added 0.2 ml glacial acetic acid, stirred at room temperature after 4h, add 50ml ethanol distilled under reduced pressure to a residual solution 5ml, TLC monitoring completion of the reaction; adding water, fully shock, standing, the precipitated solid was filtered, the filter cake washed with water and washed with 50% ethanol, dried as a white solid 1- [4-hydroxy-3- (2-methyl-benzofuran-5-yl) phenyl] -2-propanone hydrazone 4-trifluoromethylbenzoyl, yield 90.1%
90%	With acetic acid In ethanol for 5h; Reflux;	General procedure for the synthesis of substitutedbenzoylhydrazone (7-23) General procedure: To a solution of 5 (0.5 mmol) and substituted benzoylhydrazide (0.55 mmol) in EtOH(20 ml) acetic acid (0.2 ml) was added. After stirred and refluxed for 5 h, the reactionwas concentrated, poured into saturated salt water, shocked, and placed until precipitation.Then the precipitate was separated by filtration, washed with water, and driedto afford substituted benzoylhydrazone (7-23).

Reference： [1]Current Patent Assignee: HUNAN UNIVERSITY - CN105693665, 2016, A Location in patent: Paragraph 0054; 0055; 0056; 0057
[2]Lin, Ding; Yi, Yang-Jie; Xiao, Meng-Wu; Chen, Jia; Ye, Jiao; Hu, Ai-Xi; Lian, Wen-Wen; Liu, Ai-Lin; Du, Guan-Hua [Journal of Asian Natural Products Research, 2019, vol. 21, # 11, p. 1052 - 1067]

42
[ 339-59-3 ]
[ 100-52-7 ]
[ 1550-89-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary. N'-Benzylidene-4-(trifluoromethyl)benzohydrazide 2a. White solid; yield 91 %; mp 204-206.5 °C (lit.[i] 216-217 °C). IR (ATR): 3174, 3033, 1645, 1606, 1556, 1493, 1408, 1367, 1326, 1303, 1289, 1171, 1141, 1121, 1068, 1019, 964, 916, 858, 843, 775, 753, 699, 690 cm-1. 1H NMR (500 MHz, DMSO-d6): δ 11.97 (1H, bs, NH), 8.49 (1H, s, CH=N), 8.12 (2H, d, J = 8.0 Hz, H2, H6), 7.90 (2H, d, J = 8.0 Hz, H3, H5), 7.74 (2H, d, J = 6.8 Hz, H2, H6), 7.48-7.42 (3H, m, H3, H4, H5). 13C NMR (126 MHz, DMSO): δ 162.05, 148.71, 137.32, 134.22, 131.62 (q, J = 31.9 Hz), 130.36, 128.95, 128.65, 127.29, 125.56 (q, J = 3.7 Hz), 123.97 (q, J = 272.6 Hz). Anal. Calcd. for C15H11F3N2O (292.26): C, 61.64; H, 3.79; N, 9.59. Found: C, 61.74; H, 3.55; N, 9.82. [i] Maekawa T, Kunitomo J, Odaka H, Kimura H. Function regulator for retinoid relative receptor. EP1405636 A1, 2004.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

43
[ 339-59-3 ]
[ 104-88-1 ]
N'-(4-chlorobenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

44
[ 339-59-3 ]
[ 587-04-2 ]
N'-(3-chlorobenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

45
[ 339-59-3 ]
[ 89-98-5 ]
N'-(2-chlorobenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

46
[ 339-59-3 ]
[ 123-08-0 ]
N'-(4-hydroxybenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

47
[ 339-59-3 ]
[ 100-83-4 ]
N'-(3-hydroxybenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

48
[ 339-59-3 ]
[ 635-93-8 ]
[ 1235563-04-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

49
[ 339-59-3 ]
[ 104-87-0 ]
N'-(4-methylbenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

50
[ 339-59-3 ]
[ 123-11-5 ]
[ 1255639-64-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
92%	In ethanol Reflux;	2.2 Synthesis of acyl hydrazones 1a-j General procedure: Aldehyde (3 mmol) was slowly added to a solution of acyl hydrazine (3 mmol) in EtOH (5 mL,0.6 M). The mixture was heated to reflux and stirred until completion as indicated by TLCanalysis. Upon cooling to 0 °C a precipitate formed, which was isolated via vacuum filtration.The solid was washed using cold EtOH and dried under suction. The resulting material was usedfor subsequent reactions without further purification.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Baumann, Marcus; Donnelly, Kian [Beilstein Journal of Organic Chemistry, 2022, vol. 18, p. 232 - 239]
[3]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

51
[ 339-59-3 ]
[ 1122-91-4 ]
N'-(4-bromobenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

52
[ 455-19-6 ]
[ 339-59-3 ]
4-(trifluoromethyl)-N'-[4-(trifluoromethyl)benzylidene]benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

53
[ 339-59-3 ]
[ 555-16-8 ]
N'-(4-nitrobenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

54
[ 339-59-3 ]
[ 67-64-1 ]
[ 92574-03-3 ]

Yield	Reaction Conditions	Operation in experiment
76%	With sulfuric acid In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	With sulfuric acid In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

55
[ 339-59-3 ]
[ 120-92-3 ]
N'-cyclopentylidene-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sulfuric acid In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	With sulfuric acid In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

56
[ 339-59-3 ]
[ 108-94-1 ]
N'-cyclohexylidene-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sulfuric acid In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	With sulfuric acid In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

57
[ 787517-91-3 ]
[ 339-59-3 ]
4-(trifluoromethyl)-N'-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With sulfuric acid In methanol at 20℃; for 2.08333h; Reflux;	Synthesis of hydrazones 2 General procedure: 4-(Trifluoromethyl)benzohydrazide 1 (1 mmol, 204.1 mg) was dissolved in 6 mL of MeOH and then an appropriate carbonyl compound was added in one portion (1.1 of equivalents) under vigorous stirring. If the carbonyl compound was a ketone, it followed the addition of 2 drops of concentrated sulphuric acid (96 %). The reaction mixture was stirred at rt for 5 minutes and then refluxed for 2 hours. Resulting suspension was let to stay overnight at +4 °C and then was filtered off. The resulting crystals were washed with a small volume of cold MeOH and dried to obtain final hydrazones 2. The recrystallization was performed from EtOAc/n-hexane if necessary.
	With sulfuric acid In methanol Reflux;

Reference： [1]Krátký, Martin; Bősze, Szilvia; Baranyai, Zsuzsa; Stolaříková, Jiřina; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5185 - 5189]
[2]Štěpánková, Šárka; Krátký, Martin; Svrčková, Katarína; Vinšová, Jarmila; Vu, Quynh Anh [Molecules, 2021, vol. 26, # 4]

58
[ 80194-68-9 ]
[ 339-59-3 ]
2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazole [ No CAS ]

Reference： [1]RSC Advances,2018,vol. 8,p. 6306 - 6314

59
[ 339-59-3 ]
[ 18804-75-6 ]
N'-[(1E)-3-(4-nitrophenylhydrazono)]-(2E)-propan-2-ylidene-4-trifluoromethylbenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With cerium(III) chloride heptahydrate In ethanol at 65℃;	4.1.3. General procedure for the synthesis of hydrazone-N-acylhydrazones SintMed(54-74) General procedure: To a stirred suspension of α-oxopropane-4-nitrophenylhydrazone(5) (0.48 mmol) and the appropriate hydrazide (0.48 mmol)in 4.0 mL of ethanol, cerium (III) chloride heptahydrate (10 mol%)was added and the reaction mixture was stirred at 65° C during 1-3 h. Reaction’s completion was monitored by TLC, using appropriate eluent system. Once concluded, the heating was put away, and the reaction mixture was allowed to reach room temperature, giving yellow to orange precipitates. After cooling, the solids were filtered off under vacuum, and washed with cold ethanol. 1H NMR analysis of all products confirmed their purity. Recrystallization from ethanol afforded the samples for biological purposes, which were dried in an Abderhalden’s apparatus to remove traces of solvent. Yields, melting points, spectroscopic and spectrometric data are listed below for each new compound

Reference： [1]Meira, Cássio S.; dos Santos Filho, José Maurício; Sousa, Caroline C.; Anjos, Pâmela S.; Cerqueira, Jéssica V.; Dias Neto, Humberto A.; da Silveira, Rafael G.; Russo, Helena M.; Wolfender, Jean-Luc; Queiroz, Emerson F.; Moreira, Diogo R.M.; Soares, Milena B.P. [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 8, p. 1971 - 1985]

60
[ 103854-64-4 ]
[ 339-59-3 ]
C₁₉H₁₄F₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 80℃; for 3h;	General procedure: 8-Methoxyquinoline-2-carbaldehyde (25, 0.534 mmol) was refluxedwith various substituted acylhydrazines (0.587 mmol, 1.1 eq) in ethanol(5-10 mL) to get acyl hydrazides of 8-hydroxyquinoline. After completionof reaction, quinoline acyl hydrazides were found as precipitateson cooling to -15 C. Precipitates were washed with coldethanol and dried under vacuum. These acyl hydrazides were used directlyfor one pot synthesis of 2,5-disubstituted-1,3,4-oxadiazole usingiodine/K2CO3 catalysed oxidative cyclization. To the acyl hydrazides(1.0 eq) in DMSO (5-10 mL), K2CO3 (3.0 eq) and iodine (1.2 eq) wereadded in sequence and refluxed at 110 C. After the completion, thereaction mixture was cooled and saturated solution of sodium thiosulfatewas added. The precipitates were collected and dried under highvacuum to get the respective compounds (33-50).

Reference： [1]Bioorganic Chemistry,2018,vol. 80,p. 591 - 601

61
[ 339-59-3 ]
[ 90-60-8 ]
[ 1235562-80-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	In ethanol at 20℃; for 0.5h;	2.2. Synthesis of the hydrazones General procedure: To the ethanolic solution (30 mL) of 3,5-dichlorosalicylaldehyde(0.01 mol, 1.91 g) was added an ethanolic solution (20 mL) of benzohydrazide(0.01 mol, 1.36 g), 4-fluorobenzohydrazide (0.01 mol,1.54 g) or 4-trifluoromethylbenzohydrazide (0.01 mol, 2.04 g) withstirring. The mixtures were stirred for 30 min at room temperature,and left to slowly evaporate to give colorless crystalline product,which were recrystallized from ethanol and dried in vacuumcontaining anhydrous CaCl2.

Reference： [1]He, Ling-Yan; Qiu, Xiao-Yang; Cheng, Jun-Yan; Liu, Shu-Juan; Wu, Su-Min [Polyhedron, 2018, vol. 156, p. 105 - 110]

62
[ 339-59-3 ]
1-(3-methylbut-2-en-1-yl)indoline-2,3-dione [ No CAS ]
N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.4%	With acetic acid In ethanol at 20℃; for 2h;	General method of synthesis of N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene) hydrazine derivatives (S1-S20) General procedure: To intermediate B (0.5 mmol, 109.5 mg) in ethanol (5 mL), substituted benzoyl hydrazine or phenylhydrazine (0.5 mmol) was added. Then 200 μL glacial acetic acid was dripped in. After 2 h, the mixture was filtered and dried. The target compounds S1-S20 was then obtained through silica column (PE:EA = 4:1 v/v). In some cases, ultrasonic vibration can contribute to precipitation. No cis-trans isomerism was found during reaction and NMR data indicated all this series were trans configuration.

Reference： [1]Yang, Yu-Shun; Su, Mi-Mi; Zhang, Xu-Ping; Liu, Qi-Xing; He, Zhen-Xiang; Xu, Chen; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 19, p. 3182 - 3186]

63
[ 339-59-3 ]
[ 33513-42-7 ]
[ 477886-85-4 ]

Yield	Reaction Conditions	Operation in experiment
57%	With dipotassium peroxodisulfate; copper(l) iodide at 120℃;	1 Example 1: In a 25 mL tube, 0.2 mmol of p-trifluoromethylbenzohydrazide, 0.05 mmol of cuprous iodide, and 0.2 mmol of potassium persulfate were added. DMF (N,N-dimethylformamide) was added as a solvent and stirred at 120 °C. After the TLC (thin layer chromatography) detection reaction, the reaction solution was cooled to room temperature, and the reaction solution was filtered and extracted. The filtrate is evaporated under reduced pressure to remove the solvent, and then separated and purified by column chromatography. Get the target product 2-(4-trifluoromethylphenyl)-1,3,4-oxadiazole,C olumn chromatography eluent useda petroleum ether: ethyl acetate mixture with a volume ratio of 3:1,The yield was 57%.
57%	With dipotassium peroxodisulfate; copper(l) iodide In neat liquid at 120℃; for 1h; Inert atmosphere; Sealed tube;

Reference： [1]Current Patent Assignee: GUILIN UNIVERSITY OF TECHNOLOGY - CN109160905, 2019, A Location in patent: Paragraph 0012; 0016; 0023
[2]Wang, Shoucai; Wang, Kai; Kong, Xiangfei; Zhang, Shuhua; Jiang, Guangbin; Ji, Fanghua [Advanced Synthesis and Catalysis, 2019, vol. 361, # 17, p. 3986 - 3990]

64
[ 339-59-3 ]
[ 195253-49-7 ]
(E)-N'-(5-bromo-1-ethyl-3-oxoindolin-2-ylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 3543 - 3547

65
[ 14568-13-9 ]
[ 339-59-3 ]
trans-[PtCl₂(DMSO)(4-(trifluoromethyl)benzhydrazide)] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	In methanol at 60 - 70℃; for 48.33h;	a) trans-[PtCl2 (DMSO) (L)] complexes General procedure: To a methanolic solution (5 mL, 60e70 C) containing cis-[PtCl2(DMSO)2] (0.25 mmol), 0.25 mmol of hydrazide in methanol (3 mL)was added. After 20 min, the heatwas stopped and the mixturewasstirred for 48 h when the solid was separated by filtration, washedwith water and methanol and dried under reduced pressure.

Reference： [1]de Oliveira, Leticia P.; de Souza, Ívina P.; Paixão, Drielly A.; Sousa, Luana M.; Lima, Maurício F.; de S. Pereira, Caroline; Silva, Heveline; Pereira-Maia, Elene C.; Guerra, Wendell [Journal of Molecular Structure, 2019, vol. 1192, p. 76 - 81]

66
[ 339-59-3 ]
3-fluoro-4-(α-D-mannopyranosyloxy)benzaldehyde [ No CAS ]
(E)-N'-[3-fluoro-4-(α-D-mannopyranosyloxy)benzylidene]-4-(trifluoromethyl)benzo hydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With acetic acid In water; acetonitrile at 20℃;	General procedure A for acylhydrazone formation General procedure: flask was charged with a magnetic stirrer, then aldehyde 121 and hydrazide 2a,c-e,g-h,j-t were dissolved in H2O/MeCN (2 mL, 7:3). AcOH (100 μL) was added and the mixture was stirred at r.t. for 5-22 h until only product was detected by MS. Then, the mixture was neutralized with 1 M aq. NaOH and the solvents were removed under reduced pressure. The residue was purified by MPLC on RP-18 (H2O/MeCN, 5:95 to 20:80) to give the desired products 3a,c-e,g-h,j-t. For synthesis of 3b, 3f, 3i and3u, please see reference 21.

Reference： [1]Frei, Priska; Silbermann, Marleen; Mühlethaler, Tobias; Jiang, Xiaohua; Schwardt, Oliver; Hevey, Rachel; Ernst, Beat [Arkivoc, 2019, vol. 2019, # 4, p. 143 - 167]

67
[ 339-59-3 ]
[ 53566-95-3 ]
C₃₆H₂₅F₆N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With acetic acid In ethanol at 60℃; for 5h;	1.2 2. Synthesis of Compound 1 1 mmol of bis(4-benzoyl)aniline and 2 mmol of 4-trifluoromethylbenzohydrazide were added to the flask, followed by the addition of 6 ml of ethanol and 1 to 2 drops of glacial acetic acid. The reaction was stirred and refluxed at 60°C for 5 hours, then filtered, washed with ethanol and then recrystallised to afford a yellow solid.

Reference： [1]Current Patent Assignee: JIANGSU SARUISI MEDICAL TECH - CN110117235, 2019, A Location in patent: Paragraph 0053; 0057; 0058; 0064-0066

68
[ 339-59-3 ]
[ 73400-46-1 ]
N'‐[(3E)‐1‐(cyclopropylmethyl)‐2‐oxoindol‐3‐ylidene]‐4‐(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.2%	With acetic acid In ethanol at 20℃; for 2h;	General method of synthesis of N'-(1-(cyclopropylmethyl)-2-oxoindolin-3-ylidene) hydrazine derivatives (H1-H20, I1-I30) General procedure: To intermediate B (0.5 mmol) in ethanol (5 mL), substituted benzoyl hydrazine (or phenylhydrazine, thiosemicarbazide) (0.5 mmol) was added. Then 200 μL glacial acetic acid was dripped in. After 2 h, the mixture was filtered and dried. The target compounds H1-H20 and I1-I30 were then obtained through silica column (PE:EA = 4:1 v/v). In some cases, ultrasonic vibration could contribute to precipitation. No cis-trans isomerism was found during reaction and NMR data indicated all this series were trans configuration.

Reference： [1]Yang, Yu-Shun; Su, Mi-Mi; Xu, Jian-Fei; Liu, Qi-Xing; Bai, Li-Fei; Hu, Xiao-Wei; Zhu, Hai-Liang [Bioorganic Chemistry, 2019, vol. 93]

69
[ 339-59-3 ]
[ 1147550-11-5 ]
5-(4-(trifluoromethyl)phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In water at 80℃; for 6h;	General Procedure 3: Ammonium Thiocyanate-Involved Ring Closing Reaction General procedure: To a solution of hydrazides (3a~3t, 8a, or 8b, 1.0 equiv.) 10% NaOH aqueous solution(1.5 mL/1 mmol) was added ammonium thiocyanate (3.0 equiv.), then the mixture was heatedto 80 C and stirred for 6 h. The mixture was then cooled to room temperature and filtered. The filtratewas neutralized to pH 3-4 by concentrated hydrochloric acid, and the resulting white solid was collectedby filtration. The combined filter cake was dried to give the 2,4-dihydro-3H-1,2,4-triazole-3-thiones in72%-83% yields.

Reference： [1]Yuan, Chen; Yan, Jie; Song, Chen; Yang, Fan; Li, Chao; Wang, Cheng; Su, Huiling; Chen, Wei; Wang, Lijiao; Wang, Zhouyu; Qian, Shan; Yang, Lingling [Molecules, 2020, vol. 25, # 1]

70
[ 339-59-3 ]
N-succinimidyl-N-methylcarbamate [ No CAS ]
N-methyl-2-[4-(triuoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 24h;	Method C 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in acetonitrile(5 mL) and mixed with N,N-diisopropylethylamine (DIPEA; 2.0 mmol, 348 L) and N-succinimidylN-methylcarbamate (258.2 mg, 1.5 mmol). The reaction mixture was stirred at the room temperaturefor 24 h, formed precipitate was filtered o and crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

71
[ 339-59-3 ]
[ 142-61-0 ]
N'-hexanoyl-4-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 20℃; for 1h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in DCM (8 mL) togetherwith triethylamine (1.5 mmol, 209 L). Then, an acyl chloride (1.1 mmol) was added in one portion.The reaction mixture was stirred at the room temperature for 1 h. Then, resulted precipitate was filteredo, washed with a small volume of DCM and crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

72
[ 339-59-3 ]
[ 57-10-3 ]
N'-palmitoyl-4-(trifluoromethyl)benzohydrazide [ 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 48h;	Method B 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was mixed with triethylamine (1.5 mmol,209 L), 1-hydroxybenzotriazole hydrate (HOBt; 1mmol, 153.1mg) and appropriate acid (1mmol) inDCM(8 mL). The mixture was cooled down to 0 °C. Then, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimidehydrochloride (EDAC; 1.5 mmol, 287.6 mg) was added in one portion and the reaction mixture waslet stir at the room temperature. After 48 h, resulted precipitate was filtered o, washed with a smallvolume of DCM and crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

73
[ 339-59-3 ]
[ 109-90-0 ]
N-ethyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

74
[ 110-78-1 ]
[ 339-59-3 ]
N-propyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

75
[ 339-59-3 ]
[ 111-36-4 ]
N-butyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

76
[ 3954-13-0 ]
[ 339-59-3 ]
N-pentyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

77
[ 2525-62-4 ]
[ 339-59-3 ]
N-hexyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

78
[ 4747-81-3 ]
[ 339-59-3 ]
N-heptyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

79
[ 3158-26-7 ]
[ 339-59-3 ]
N-octyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

80
[ 4184-73-0 ]
[ 339-59-3 ]
N-nonyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

81
[ 2411-58-7 ]
[ 339-59-3 ]
2-[4-(trifluoromethyl)benzoyl]-N-undecylhydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

82
[ 4202-38-4 ]
[ 339-59-3 ]
N-dodecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

83
[ 339-59-3 ]
[ 39843-07-7 ]
N-tridecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

84
[ 4877-14-9 ]
[ 339-59-3 ]
N-tetradecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

85
[ 39633-51-7 ]
[ 339-59-3 ]
N-pentadecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

86
[ 1943-84-6 ]
[ 339-59-3 ]
N-hexadecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

87
[ 112-96-9 ]
[ 339-59-3 ]
N-octadecyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In acetonitrile at 20℃; for 8h;	Method A 4-(Trifluoromethyl)benzohydrazide (1, 204.2 mg, 1.0 mmol) was dissolved in anhydrous acetonitrile(MeCN, 8 mL) and then the appropriate isocyanate (1.05 mmol) was added in one portion. The reactionmixture was stirred at the room temperature for 8 h, then stored for 2 h at 20 °C. Resulting precipitatewas filtered o, washed with a small volume of MeCN and dried. The products were recrystallisedfrom ethyl acetate if necessary.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

88
[ 32315-10-9 ]
[ 339-59-3 ]
[ 74-89-5 ]
N-methyl-2-[4-(triuoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: bis(trichloromethyl) carbonate; methylamine In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

89
[ 32315-10-9 ]
[ 339-59-3 ]
[ 75-04-7 ]
N-ethyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: bis(trichloromethyl) carbonate; ethylamine In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

90
[ 107-10-8 ]
[ 32315-10-9 ]
[ 339-59-3 ]
N-propyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: propylamine; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

91
[ 32315-10-9 ]
[ 339-59-3 ]
[ 109-73-9 ]
N-butyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: bis(trichloromethyl) carbonate; N-butylamine In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

92
[ 32315-10-9 ]
[ 339-59-3 ]
[ 110-58-7 ]
N-pentyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: bis(trichloromethyl) carbonate; n-Pentylamine In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

93
[ 111-26-2 ]
[ 32315-10-9 ]
[ 339-59-3 ]
N-hexyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: hexan-1-amine; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

94
[ 111-68-2 ]
[ 32315-10-9 ]
[ 339-59-3 ]
N-heptyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-Heptylamine; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

95
[ 111-86-4 ]
[ 32315-10-9 ]
[ 339-59-3 ]
N-octyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: n-Octylamine; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

96
[ 112-20-9 ]
[ 32315-10-9 ]
[ 339-59-3 ]
N-nonyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: n-Nonylamin; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

97
[ 2016-57-1 ]
[ 32315-10-9 ]
[ 339-59-3 ]
N-decyl-2-[4-(trifluoromethyl)benzoyl]hydrazine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-aminodecane; bis(trichloromethyl) carbonate In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(trifluoromethyl)benzoic acid hydrazide With triethylamine In dichloromethane at 20℃; for 10h;	Method B General procedure: Method B is based on generation of an appropriate isocyanate in situ. Triphosgene (bis(trichloromethyl)carbonate; 118.7 mg, 0.4 mmol) was dissolved in anhydrous dichloromethane (DCM; 5 mL) undernitrogen atmosphere and the appropriate amine (1.01 mmol) dissolved in anhydrous DCM (5 mL)was added dropwise. The mixture was stirred for 30 min at room temperature, then treated withtriethylamine (TEA; 293 L, 2.1 mmol). After 30 min, 4-(trifluoromethyl)benzohydrazide (1, 204.2 mg,1.0 mmol) was added. The reaction mixture was stirred for 10 h at room temperature, then evaporatedto dryness, treated with water (10 mL) and extracted with ethyl acetate (3 15 mL). The combined organic phase was dried over anhydrous sodium sulphate, filtered o and evaporated to dryness togive the nal product, which was crystallised from ethyl acetate.

Reference： [1]Štěpánková, Šárka; Švarcová, Markéta; Baranyai, Zsuzsa; Bosze, Szilvia; Horváth, Lilla; Krátký, Martin; Stolaříková, Jiřina; Svrčková, Katarína; Vinšová, Jarmila [Molecules, 2020, vol. 25, # 10]

98
[ 339-59-3 ]
[ 4755-77-5 ]
[ 720702-68-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: 4-(trifluoromethyl)benzoic acid hydrazide; Ethyl oxalyl chloride With triethylamine In dichloromethane at 0 - 25℃; for 6h; Stage #2: With p-toluenesulfonyl chloride In dichloromethane at 25℃; for 18h;	preparation of intermediate 3 General procedure: Adding 2 (10.4 mmol), 100 cm3DCM, and 1.53 cm3triethylamine(20.8 mmol) to a 250 cm3three-neck bottle,adding ethyl oxalyl chloride monoethylate at 0 °C andreacted at 25 °C for 6 h, fellowed add 0.77 cm3triethylamine(10.4 mmol) and 1.98 g p-toluenesulfonyl chloride(10.4 mmol), keeping the reaction system at 25 °C over 18 h.After the reaction was accomplished, adding 200 cm3ofDCM, separating and washing, then concentrating underdecreased pressure to obtain the residue, after that purification by column chromatography to acquire the product 3. ethyl 5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole-2-carboxylate(3a, C12H9F3N2O3)White solid; yield: 77%; m.p.:167-169 °C; 1H NMR (400 MHz, CDCl3):δ = 7.61 (d,J = 8.5 Hz, 2H, ArH), 7.51 (d, J = 7.3 Hz, 2H, ArH), 4.16(m, 2H, CH2),3.22 (t, J = 7.5 Hz, 3H, CH3)ppm; 13C NMR(100 MHz, CDCl3):δ = 178.1 (CF3), 167.4 (C = O), 160.5(CH), 159.2 (C), 148.4 (CH), 146.6 (C), 128.1 (C), 123.1 (C),35.2 (CH3), 24.1 (CH2) ppm; IR (KBr): = 3416, 3064, 2916,1725, 1661, 1557, 1448, 1129, 671, 642 cm-1; HRMS (EI):m/z calcd. for C12H9F3N2O3(M+) 287.0565, found 287.0561.
	Stage #1: 4-(trifluoromethyl)benzoic acid hydrazide; Ethyl oxalyl chloride With triethylamine In dichloromethane at -10 - 25℃; for 9h; Stage #2: With triethylamine; p-toluenesulfonyl chloride In ethanol

Reference： [1]Li, Yitao; Yao, Wenqiang; Lin, Jian; Gao, Guoliang; Huang, Chang; Wu, Yang [Monatshefte fur Chemie, 2021, vol. 152, # 1, p. 121 - 135]
[2]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]

99
[ 339-59-3 ]
[ 98879-62-0 ]
2-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	In N,N-dimethyl-formamide at 120℃; for 15h;	2-[4-(trifluoromethyl)phenyl][1 ,2,4]triazolo[1 ,5-c]quinazolin-5(6H)-one Methyl (2-cyanophenyl)carbamate (250 mg, 1.42 mmol) and 4-(trifluoromethyl)benzohydrazide (CAS 339-59-3, 348 mg, 1.70 mmol) were stirred in N,N-dimethylformamide (3 mL) at 120 °C for 15 hours. Water was added to the mixture, precipitated product was filtered off, washed with water and dried under reduced pressure at 60 °C to give 491 mg (100 % yield) of the title compound.LC-MS (Method 2): Rt= 0.83 min; MS (ESIpos): m/z = 331 [M+H]+1H-NMR (400MHz, DMSO-d6): d [ppm]= 7.40 - 7.49 (m, 2H), 7.73 (ddd, 1H), 7.96 (d, 2H), 8.25 (dd, 1H), 8.44 (d, 2H), 12.41 (s, 1H).

Reference： [1]Current Patent Assignee: BAYER AG; Helmholtz Association - WO2021/28382, 2021, A1 Location in patent: Page/Page column 79-80

100
[ 3132-99-8 ]
[ 339-59-3 ]
N’-(3-bromobenzylidene)-4-(trifluoromethyl)benzohydrazide [ No CAS ]