Name: 456-06-4|4-Fluorobenzohydrazide|97%
Brand: Ambeed
SKU: A233821
Price: 5.0 USD
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1
[ 451-46-7 ]
[ 456-06-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrazine hydrate monohydrate In ethanol at 20 - 85℃; for 10h; Reflux;	31.1 Step 1: 4-fluorobenzohydrazide To a stirred solution of 4-flouroethylbenzoate (4.5 g, 26.7 mmol) in EtOH (30 mL) was added NH2NH2.H20 (6.67 g, 133.5 mmol) at room temperature and the solution refluxed at 85°C for 10 h. The reaction was cooled to room temperature, concentrated under reduced pressure, and the solid washed with n-hexane (50 mL) and then dried to obtain 4-fluorobenzohydrazide as a solid (4.2 g, quantitative yield). 1H NMR (400 MHz, DMSO-d6): δ 9.85 (s, 1H), 7.86 (dd, 2H), 7.25 (t, 3H), 4.46 (s, 1H), 3.47 (br s, 1H).
100%	With hydrazine hydrate monohydrate In ethanol; water monomer at 85℃; for 10h;	4.2.1. The preparation of 4-fluorobenzohydrazide (11) To a stirred solution of 4-fluoroethylbenzoate (4.5g, 26.7 mmol)in EtOH (30 mL) was added NH2NH2H2O (6.67g, 133.5 mmol) (80%in H2O) at room temperature and refluxed at 85 C for 10 h. Thereaction was cooled to room temperature, and evaporated in vacuoto afford a crude reside which was washed with n-hexane (50 mL)and then dried to obtain compound. Yield: (4.2g, quantitativeyield), white solid. MS (ESI) m/z (%): 155.4 [MH]. 1H NMR(400 MHz, DMSO-d6): d 9.85 (s, 1H), 7.86 (dd, 2H), 7.25 (t, 3H), 4.46(s, 1H), 3.47 (br s, 1H).
97%	With hydrazine hydrate monohydrate In ethanol; water monomer Reflux;	Synthesis of benzohydrazides General procedure: Hydrazides (30-58) were synthesized by one pot conventionalmethod24 Benzoic acid or its derivative (10 mmol) was dissolvedin ethanol (20 mL). Sulfuric acid (3 N, 2 mL) was added and thereaction contents were refluxed for six hours. The reaction wasmonitored with TLC. After the completion of the reaction, the reactionmixture was neutralized by adding solid NaHCO3, and filteredto remove excess of NaHCO3. In the neutralized reaction mixture which contains ethyl ester, hydrazine monohydrate (1.5 mL,3 mmol) was added and refluxed for 3-6 h to complete the reaction.Ethanol and unreacted hydrazine were removed by distillationupto 1/3 volume. The reaction contents were cooled, filteredand recrystallized from methanol to obtain the desired hydrazidecrystals (see Supporting information).

83%	With hydrazine hydrate monohydrate In ethanol at 80℃; for 4h;	2.1 First, 10 g of 4-fluoroethyl benzoate and 30 mL of ethanol were put in a 100 mL three-neck flask, and stirred. Then, 10 mL of hydrazine monohydrate was added to this mixed solution, and heated and stirred at 80 °C for 4 hours to be reacted. The reaction mixture was added to 100 mL of water, and a solid was precipitated. This solid was subjected to suction filtration and washed with a mixed solvent of ethanol and hexane, so that 4-fluorobenzoylhydrazine was prepared (a white solid, yield: 83 %). The synthetic scheme of Step 1 is shown by (a-2).
83%	With hydrazine hydrate monohydrate In ethanol for 5h; Inert atmosphere; Reflux;
74%	With hydrazine hydrate monohydrate Reflux; Alcoholic solution;
57%	With hydrazine hydrate monohydrate In ethanol Heating;
57%	With hydrazine hydrate monohydrate In ethanol at 80℃; for 6h;	1.1.1 Synthesis of 4-fluorobenzoylhydrazine First, 25 g of 4-fluoroethyl benzoate and 100 mL of ethanol were put in a 500 mL three-neck flask and stirred. Then, 20 mL of hydrazine monohydrate was added to this mixed solution, and heated and stirred at 80° C. for 6 hours. After the stirring, the reacted mixture was added to 250 mL of water, and a white solid was precipitated. Ethyl acetate was added to this mixture, and the solid was dissolved. An organic layer and an aqueous layer were separated, and the aqueous layer was extracted with ethyl acetate. The resulting extract and organic layer were together washed with a saturated aqueous sodium chloride solution, and then anhydrous magnesium sulfate was added to the organic layer for drying. After the drying, this mixture was subjected to gravity filtration, and the resulting filtrate was concentrated to give a white solid. The given white solid was washed with hexane, so that 4-fluorobenzoylhydrazine was prepared (a white solid, yield: 57%).
	With hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate In ethanol Heating;
	With hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate In methanol for 6h; Heating;
	With hydrazine hydrate monohydrate In ethanol for 17h; Heating;
	With hydrazine hydrate monohydrate for 8h; Reflux;
	With hydrazine In water monomer
	With hydrazine In ethanol for 6h; Reflux;
	With hydrazine hydrate monohydrate for 0.05h; Microwave irradiation;
	With hydrazine In ethanol for 16h; Reflux; Inert atmosphere;
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine hydrate monohydrate for 0.05h; Microwave irradiation;
	With hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine monohydrate for 2h; Reflux;
	With hydrazine hydrate monohydrate for 6h; Reflux;
	With hydrazine hydrate monohydrate Microwave irradiation;
	With hydrazine hydrate monohydrate In ethanol Reflux;	General procedure: Then, the corresponding ester was refluxed with 85% hydrazine monohydrate in ethanol to get hydrazide 1.
	With hydrazine hydrate monohydrate In ethanol
	With hydrazine monohydrate In ethanol Reflux;	General procedure for synthesis of benzohydrazidederivatives (4a-m): General procedure: To a stirred solution of ethyl benzoate (3 mmol) derivatives in ethanol was added hydrazine-hydrate (5.44 mmol) and refluxed for 6-12 h. The reaction mixture was diluted with ethyl acetate followed by water. The organic layer was dried over sodium sulphate, filtered and evaporated to obtain the respective benzohydrazide derivatives (4a-m)15,16. The yields of the products varied from 80-85 %.
	With hydrazine hydrate monohydrate In ethanol for 8h; Reflux;	General procedure for the synthesis of benzohydrazides7a-k [12,13] General procedure: A mixture of benzoic acid (6.42 mmol), catalytic quantity of conc. H2SO4 in ethanol was heated to reflux for 10 h. The reaction mixture was diluted with ethyl acetate followed by water. The organic layer was washed with saturated NaHCO3 followed by water and brine solution. The organic layer was dried over sodium sulphate, filtered and evaporated to obtain respective ethyl benzoates. To a stirred solution of ethyl benzoates (5 mmol) in ethanol was added hydrazine-hydrate (12.5 mmol) and refluxed for 8 h. The reaction mixture was diluted with ethyl acetate followed by water. The organic layer was dried over sodium sulphate, filtered and evaporated to obtain respective benzohydrazides 7a-k.
	With H₄N₂*5H₂O In ethanol at 70℃; for 6h;
	With hydrazine hydrate monohydrate In ethanol at 20℃; for 3h;	5.2. General procedure for preparation of 3a-l 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 monohydrate for 5h; Reflux;	To the (un)substituted or substituted aromatic ester (III), hydrazine hydrate was slowly added. The mixture was refluxed for about 5 hrs, when solid hydrazide (IV) separated out. The excess reagent was distilled off. To the slurry of hydrazide in ethanolic potassium hydroxide, carbon disulfide was added drop wise and the reaction mixture was allowed to stir for 24 hrs at ambient temperature. After completion of reaction, the solvent was evaporated. The reaction mixture was acidified with 10% HCl solution. The precipitate was filtered, washed with water and dried to give 1,3,4-oxadiazolethiol (IX).
	With hydrazine hydrate monohydrate In ethanol for 6h; Reflux;	General methods for synthesis of substituted aryl acidhydrazides (31-45)24 General procedure: The substituted ethyl benzoates (16-30) (0.01 mol)dissolved in dry ethanol (25 mL), hydrazine hydrate (99%,0.01 mol) was added and the mixture was reuxed for 6 h.The reaction mixture was cooled and the solid obtained wasltered and recrystallized from dilute ethanol or from water.Details of these compounds are available in SupplementaryInformation.
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine hydrate monohydrate In ethanol for 5h; Reflux;	5.4 General procedure for preparation of 4 General procedure: 5mL of hydrazine monohydrate (80%) was added to a solution of intermediate 3 (5mmol) in ethanol (5mL). The reaction mixture was maintained under reflux for 5h. was then concentrated under reduced pressure and the resulting solid was collected by filtration, washed with cold water and dried to give the desired intermediate 4 as a white solid.
	With hydrazine monohydrate In ethanol Reflux;
	With hydrazine In ethanol Inert atmosphere;
	With hydrazine monohydrate Reflux;
	With hydrazine hydrate monohydrate In ethanol Heating;	8.2 Step 2: Add 9g of hydrazine hydrate to a three-necked flask with a thermowell.Stir by adding 15 ml of absolute ethanol.Slowly add 17 g of ethyl 4-fluorobenzoate and heat.The TLC traces the reaction until the starting point of the raw material disappears, stops the reaction, cools and crystallizes, suctions, and washes with a small amount of ethanol and n-hexane to dry the intermediate.
	With hydrazine monohydrate In ethanol for 12h; Reflux;
	With hydrazine hydrate monohydrate for 1h; Reflux;	4.2.3. General procedure for preparation of aromatic acidhydrazides (5a-5e) General procedure: Substituted aromatic ester (1 mmol) was heated to reflux withhydrazine hydrate (2 mL) for 1 h. Upon completion of the reaction,the reaction mixture was quenched with water and extracted withethyl acetate. The combined organic layer was washed with brine solution, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure.
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine monohydrate In ethanol Reflux;	2.1.1.2. General procedure for the synthesis of (2/3/4) un/substitutedbenzhydrazides (3a-3g). General procedure: As displayed in Scheme 2, the un/substitutedester derivative (2a-2g, 1.0 mmol), hydrazine hydrate (1.2 mmol)were taken in ethyl alcohol (10 mL) and the reaction mixture washeated to reflux temperature and maintained until the reaction wascompleted (Checked by TLC) [50a]. After achievement of the reaction,the reaction was progressively cooled to room temperature. Slowly,solid precipitated out in the reaction mass, was filtered, washed withcold ethanol, and dried to afford a product (2/3/4) un/substituted-Benz hydrazides with 80-87% yield (3a-3g).
	With hydrazine hydrate monohydrate In ethanol at 78℃; for 6h;
	With hydrazine hydrate monohydrate In ethanol Reflux;
	With hydrazine hydrate monohydrate at 80℃; for 12h;
	With hydrazine hydrate monohydrate Reflux;
	With hydrazine hydrate monohydrate In methanol Reflux;	2.2. Synthesis and Characterization of Hydrazide Ligands General procedure: All the ligands (1-13) were synthesized by the reported method [31, 32]. Hydrazine hydrate (100 mmol) was added to the solution of ethyl benzoate in methanol (25 mmol) and then refluxed for 3-5 hours on a water bath. The resulting solid was washed with hexane to obtain pure hydrazide. Respective esters were used to prepare all the ligands. The synthesized ligands (1-13) were characterized with the help of elemental (C,Hand N) analysis, 1H NMR, 13C NMR, IR,and EI-Mass spectroscopy which was reported previously as well [31-33].
	With hydrazine hydrate monohydrate In methanol Reflux;	2.2. Synthesis and Characterization of Hydrazide Ligands General procedure: All the ligands (1-13) were synthesized by the reported method [31, 32]. Hydrazine hydrate (100 mmol) was added to the solution of ethyl benzoate in methanol (25 mmol) and then refluxed for 3-5 hours on a water bath. The resulting solid was washed with hexane to obtain pure hydrazide. Respective esters were used to prepare all the ligands. The synthesized ligands (1-13) were characterized with the help of elemental (C,Hand N) analysis, 1H NMR, 13C NMR, IR,and EI-Mass spectroscopy which was reported previously as well [31-33].

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2
[ 2058-72-2 ]
[ 456-06-4 ]
4-Fluoro-benzoic acid [5-bromo-1-methyl-2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-hydrazide [ No CAS ]

Reference： [1]Journal of the Indian Chemical Society,1982,vol. 59,p. 1174 - 1176

3
[ 15513-48-1 ]
[ 456-06-4 ]
4-Fluoro-benzoic acid N'-(2,6-dimethyl-3-nitro-pyridin-4-yl)-hydrazide; hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2474 - 2485

4
[ 403-33-8 ]
[ 456-06-4 ]

Yield	Reaction Conditions	Operation in experiment
93.5%	With hydrazine hydrate; In methanol; for 0.08333330000000001h;Microwave irradiation;	General procedure: The benzoic acid hydrazides, 3a-h were prepared accordingto reported method in literature28,29 with some desirablemodifications. The ester (2a-h, 0.1 mol) dissolved inappropriate volume of methanol was transferred to a flaskwith a reflux condenser. Hydrazine hydrate (99%, 0.15 mol) was slowly added to the mixture and then kept on reflux forabout 5-6 h. The excess of solvent and hydrazine hydratewere distilled off. On addition of water the product separatedout which was washed several times with distilled water anddried. The product was recrystallized from 80% aqueous ethanoland melting points determined (Table 2).Microwave method: The same procedure as stated abovewas adopted using 100 ml methanol following the other conditionsof microwave in a microwave reactor at 350 Watt(power) for 3-5 min. Precipitation and separation of precipitatewas done as for conventional method (Table 2).
83%	With hydrazine hydrate; In methanol; for 5.0h;Reflux;	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.
80%	With hydrazine hydrate; In ethanol; at 40℃;	General procedure: Various methyl benzoate 8A-V (1.0 equiv) reacted with hydrazine hydrate (excess amount) in anhydrous ethanol. The reaction was stirred at 40 C for overnight. The ethanol was removed under reduced pressure. The products were purified by recrystallization, which were washed with ethyl ether. The products were obtained as white solid.

75%	With hydrazine hydrate; In ethanol; for 5.0h;Reflux;	General procedure: Compound 12 (0.013 mol) and 80% NH2NH2H2O (5 mL) wereadded to EtOH (10 mL), the mixturewas stirred under reflux for 5 h.After being cooled to room temperature, the precipitate was obtainedby filtration, and was dried to give the title compounds,respectively.4.1.7.1. 4-Fluorobenzohydrazide (13a). A white solid. Yield: 75%. Mp161.9e164.4 C. 1H NMR (400 MHz, DMSO-d6) d 9.78 (s, 1H,eNHeN), 7.83e7.93 (m, 2H, ArH), 7.22e7.33 (m, 2H, ArH), 4.48 (s,2H, eNHeNH2). ESI-MS m/z: 155.1 [M H].
50%	With hydrazine hydrate; In ethanol; under 760.051 Torr; for 24.0h;Reflux;	General procedure: Various benzohydrazides 5-7 and 9-13 were obtained accordingto known procedures [40,65] except for benzohydrazides 4and 8 which were commercially available. A solution of the methylbenzoate (1 equiv) in ethanol was added dropwise to 65% hydrazinemonohydrate (5 equiv). The reaction mixture was then heatedunder reflux and stirred overnight. The reaction progress was followedup by TLC. Crude product was collected by filtration aftercooling of the reaction medium and finally washed with coldethanol unless specified otherwise. The desired benzohydrazides were used without any further purification.The analysis of spectral data (1H and 13C NMR), the yields, HRMS,Mp and Rf of these precursors are presented in SupplementaryInformation.
	With hydrazine hydrate; In methanol;Reflux;	General procedure: Methyl benzoates were synthesized from their respective p-substituted benzoic acids, using excess dry methanol in the presence of H2SO4. para-Substituted benzoic hydrazides (2a-i) were prepared by reaction of the corresponding methyl benzoates (10 mmol) with hydrazine hydrate 99% (50 mmol) in methanol under reflux for 4-6 h. The excess solvent was removed under vacuum and the residue was filtered under suction, washed with water, and dried. The spectral and analytical data of benzoic hydrazide (2a) [26], 4-bromobenzoic hydrazide (2b) [27], 4-chlorobenzoic hydrazide (2c) [28], 4-fluorobenzoic hydrazide (2d) [26], 4-hydroxybenzoic hydrazide (2e) [29], 4-methoxybenzoic hydrazide (2f) [30], 4-methylbenzoic hydrazide (2g) [28], 4-nitrobenzoic hydrazide (2h) [28] and 4-aminobenzoic hydrazide (2i)[28] are in good agreement with literature values.
	With hydrazine hydrate; In methanol;Reflux;	General procedure: Methyl benzoates were synthesized from their respective p-substituted benzoic acids, using excess of dry methanol in presence of H2SO4. p-Substituted benzoic acid hydrazides (2a-i) were prepared by reaction of the corresponding methyl benzoates (10 mmol) with hydrazine hydrate 99% (50 mmol) in methanol under reflux for 4-6 h. The excess solvent was removed under vacuum and the residue was filtered under suction, washed with water and dried. The spectral and analytical data of benzoic hydrazide (2a) [35], 4-bromobenzoic hydrazide (2b) [36], 4-chlorobenzoic hydrazide (2c) [37], 4-fluorobenzoic hydrazide (2d) [35], 4-hydroxybenzoic hydrazide (2e) [38], 4-methoxybenzoic hydrazide (2f) [39], 4-methylbenzoic hydrazide (2g) [37], 4-nitrobenzoic hydrazide (2h) [37] and 4-aminobenzoic hydrazide (2i) [38] are in good agreement with literature values.
	With hydrazine hydrate; In ethanol;Reflux;	General procedure: Different substituted carboxylic acids (20 mmol) (A) were stirred with thionyl chloride (100 mmol) in dry methanol (75 ml) or 5-6 h to synthesize corresponding methyl esters (B) (Scheme1). After extraction of esters in chloroform, solvent was evaporated and esters (66 mmol) were refluxed with hydrazine hydrate(330 mmol) in ethanol (75 ml) for 4-5 h. A solid was obtained upon removal of the solvent by rotary evaporation. The resulting solid was washed with hexane to afford hydrazide ligand (C). The spectral and analytical data are given below.
	With hydrazine hydrate; In methanol; for 5.0h;Reflux;	General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5C.
	With hydrazine hydrate; In methanol; for 8.0h;Reflux;	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.
	With hydrazine hydrate; In methanol;Reflux;	Methyl acetate dissolved in different methanol, and then slowly add 40% - 80% hydrazine hydrate, reflux reaction is complete until the precipitation of different substituted formyl hydrazide
	With hydrazine hydrate; In methanol;Reflux;	General procedure: Methyl formate was dissolved in methanol,Then slowly add 40% -80% hydrazine hydrate,Reflux reaction is complete,After cooling, different substituted formylhydrazides are precipitated;
	With hydrazine hydrate; In methanol; for 7.0h;Reflux;	0.05 mol of methyl p-fluorobenzoate and methanol were added50 mL was cast in a 100 mL three-necked round bottom flask,80% hydrazine hydrate (0.06 mol) was added slowly at room temperature,The temperature was refluxed for 7 hours to complete.Decompression recovery of methanol, cooling and standing after the precipitation of white crystals, pumping rate, the methanol recrystallization.
280 mg	With hydrazine hydrate;Reflux;	General procedure: 4-fluorobenzoic acid as the raw material, methanol as a reaction solvent, a small amount of concentrated sulfuric acid catalyst, followed by stirring under heating at reflux, thin layer chromatography (TLC) to track progress of the reaction, a certain amount after the completion of the reaction NaHCO3Solution for hydrazine and the reaction liquid solution to give ester intermediate (3-1), continue to add more than the corresponding proportion of hydrazine hydrate reaction mixture was heated with stirring at reflux, thin layer chromatography (TLC) to track progress of the reaction, the reaction after completion of the reaction solution was added to a certain amount of water, then a large amount of white sink to the bottom, suction filtration to afford intermediate hydrazides (3-2)
	With hydrazine hydrate; at 80℃; for 5.0h;	1) In a 100 ml round bottom flask,12.32 g (80.0 mmol) of methyl p-fluorobenzoate was added,And hydrazine hydrate 30ml (excess) at 80 for 5h,After the reaction was completely cooled, the solid was precipitated at low temperature,Filter,Dried to give p-fluorobenzoyl hydrazide.
	With hydrazine hydrate; In methanol;Reflux;	Methyl formate was dissolved in methanol, Then slowly add 40% -80% hydrazine hydrate, reflux reaction is complete, after cooling out of different substituted formyl hydrazide;
	With hydrazine; In ethanol; water; for 10.0h;Reflux;	General procedure: The oil was thendissolved in EtOH, and NH2NH2.H2O (3 eq) was added.The mixture was refluxed for 10 h. CH2Cl2 (30 mL) was thenadded and extracted with distilled H2O (3 × 20 mL). Theorganic phase was separated, dried on anhydrous Na2SO4,and evaporated under vacuum to afford correspondinghydrazide 7a in very good yield (white solid, 1.02g, 93%)
	With hydrazine hydrate; In ethanol; at 85℃; for 1.0h;	A solution of methyl 4-fluorobenzoate (3.4 g, 22.06 mmol, 1 equiv.) and hydrazine hydrate(10 mL) in EtOH (10 mL) was stirred at 85 C for 1 hour. The resulting mixture wasconcentrated under vacuum. The residue was purified by silica gel column chromatography,eluted with CH2C12 / MeOH (0 to 10:1) to afford product (2.5 g) as a white solid. ESI-MS m/z= 540.15 [M+Hj . ESI MS m/z= 154.95 [M+Hj
	With hydrazine hydrate; In methanol;Reflux;	General procedure: Carboxylic acid hydrazides are synthesized following a modifiedprocedure from one already reported in the literature [22]. Hydrazinehydrate (80%, 0.06 mol) is added slowly to a solution ofcarboxylate esters (0.02 mol) in methanol (30 mL). The reactionmixture is subjected to reflux for 6-8 h. Upon completion of reaction,the mixture is cooled down to the room temperature and icewater is added. The precipitated solid product obtained wasfiltered, dried and recrystallized from methanol.
	With hydrazine hydrate; In methanol; at 65℃; for 4.0h;	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; In methanol;Reflux; Inert atmosphere;	General procedure: Hydrazine hydrate (5 mL, 40%) was added to a solution of requiredester (5.0 mmol) in methanol (20 mL). The solution was refluxed for12-24 h and monitored by TLC until starting material was completelyconsumed. After that, solvent was evaporated under reduced pressureand a small amount of water (5 mL) was added to precipitate the hydrazide,which was filtered and dried in vacuum to give a shiny white toyellow solid in excellent yields, without further purification.

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5
[ 456-22-4 ]
[ 456-06-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 4-Fluorobenzoic acid With sulfuric acid In ethanol for 6h; Reflux; Stage #2: With hydrazine monohydrate; Sodium hydrogenocarbonate; acetic acid Reflux;
84%	With acetic acid; acetic acid hydrazide for 0.1h; Microwave irradiation;
79%	Stage #1: 4-Fluorobenzoic acid With pyridine-3-carboxylic acid; sulfuric acid In methanol for 6h; Reflux; Stage #2: With hydrazine monohydrate In methanol at 65℃; for 4h;	5.1.3. General procedure for the synthesis of acyl hydrazideintermediates (44-50) General procedure: Method C. To a stirred solution of substituted benzoic acid/substituted phenylacetic acids/nicotinic acid (1 equiv.) inmethanol (20 mL), conc. sulfuric acid in a catalytic amountwas added. The resulting mixture was refluxed for 6 h. Aftercompletion of the reaction (confirmed by TLC), the mixturewas concentrated to a volume of 10 mL and partitionedbetween chloroform (30 mL) and water. The organic phasewas washed with water, dried over anhydrous sodium sulfateand evaporated under reduced pressure to obtain liquidproduct. The resulting liquid was further added to a solutionof hydrazine hydrate (3 equiv.) in methanol (20 mL). Thereaction mixture was heated up to 65 C for 4 h. After completionof the reaction as checked by TLC, the reaction mixturewas allowed to cool to RT and the solid precipitates soobtained were filtered and washed with cold methanol toobtain the desired acyl hydrazides (44-50). 5.1.3.1. 2-Phenylacetohydrazide (44). The intermediate (44)was synthesized as per the general Method C from 2-phenylaceticacid (24) (1.0 g, 7.36 mmol) as white solid (Zimin et al.,2018). (Yield: 75%)

	Stage #1: 4-Fluorobenzoic acid With thionyl chloride Stage #2: With hydrazine hydrate monohydrate; ethyl acetate
	Multi-step reaction with 2 steps 1: H₂SO₄ / Heating 2: 57 percent / hydrazine mono-hydrate / ethanol / Heating
	Multi-step reaction with 2 steps 1: thionyl chloride / Microwave irradiation 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride / 0.07 h / Microwave irradiation 2: hydrazine hydrate monohydrate / 0.05 h / Microwave irradiation
	Multi-step reaction with 2 steps 1: Reflux; Acidic conditions 2: hydrazine hydrate monohydrate / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate
	Multi-step reaction with 2 steps 1: thionyl chloride 2: hydrazine hydrate monohydrate
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / methanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / methanol
	Multi-step reaction with 2 steps 1: sulfuric acid / 4 h / Reflux 2: hydrazine hydrate monohydrate / methanol / Reflux
	Multi-step reaction with 2 steps 1: Acidic conditions; Reflux 2: hydrazine hydrate monohydrate / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate
	Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 6 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: 8 h / Reflux 2: hydrazine hydrate monohydrate / 6 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / methanol
	Multi-step reaction with 3 steps 1: thionyl chloride / 5 h / Reflux 2: triethylamine / dichloromethane / 0 °C 3: hydrazine hydrate monohydrate / methanol / 5 h / Reflux
	With chloroformic acid ethyl ester; hydrazine hydrate monohydrate In dichloromethane at 0 - 5℃;
	Multi-step reaction with 3 steps 1: thionyl chloride / Microwave irradiation 2: Microwave irradiation 3: hydrazine hydrate monohydrate / Microwave irradiation
	Multi-step reaction with 2 steps 1: sulfuric acid / 4 h / Reflux 2: hydrazine monohydrate / methanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / Reflux 2: hydrazine hydrate monohydrate / methanol / 8 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Stage #1: 4-Fluorobenzoic acid In methanol Acidic conditions; Stage #2: With hydrazine In methanol
	Multi-step reaction with 2 steps 1: sulfuric acid / 12 h / 70 - 80 °C / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / ethanol
	Multi-step reaction with 2 steps 1: sulfuric acid / water monomer / 6 h / Reflux 2: hydrazine hydrate monohydrate / water monomer; ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / methanol
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: hydrazine hydrate monohydrate / tetrahydrofuran / 20 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / 10 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 8 h / Reflux
	Multi-step reaction with 2 steps 1: Acidic conditions 2: hydrazine hydrate monohydrate / Reflux
	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 monohydrate / methanol / 5 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / 20 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 8 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 6 h / Reflux
	Multi-step reaction with 2 steps 1: glycerol-based sulfonic acid functionalized carbon catalyst / 6 h / Reflux; Green chemistry 2: hydrazine hydrate monohydrate / methanol / 8 h / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride / 20 °C 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Stage #1: 4-Fluorobenzoic acid With sulfuric acid In ethanol Stage #2: With hydrazine hydrate monohydrate
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / ethanol
	Multi-step reaction with 2 steps 1: sulfuric acid / water monomer / 12 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / 8 h / Reflux 2: hydrazine monohydrate / methanol / 7 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine / water monomer; methanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / ethanol / 5 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Inert atmosphere 2: hydrazine / ethanol / Inert atmosphere
	Multi-step reaction with 2 steps 1: sulfuric acid / 4 h / 65 - 67 °C 2: hydrazine hydrate monohydrate / methanol / 9 h / 65 - 67 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine monohydrate / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / 12 h / Reflux 2: hydrazine / ethanol; water monomer / 10 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Heating 2: hydrazine hydrate monohydrate / ethanol / Heating
	Multi-step reaction with 2 steps 1: sulfuric acid / 16 h / 20 °C / Reflux 2: hydrazine hydrate monohydrate / 1 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / methanol / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride / 1 h / 40 °C 2: hydrazine monohydrate / methanol / 4 h / 65 °C
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine monohydrate
	Multi-step reaction with 2 steps 1: sulfuric acid / 0.1 h / Microwave irradiation 2: hydrazine hydrate monohydrate / methanol / 0.08 h / Microwave irradiation
	Multi-step reaction with 2 steps 1: sulfuric acid / toluene / 48 h / 110 °C 2: hydrazine monohydrate / ethanol / 6 h / 80 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / methanol / Reflux
	Stage #1: 4-Fluorobenzoic acid With sulfuric acid In ethanol Reflux; Stage #2: With hydrazine hydrate monohydrate In ethanol Reflux;
	With benzotriazol-1-ol; hydrazine hydrate monohydrate; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In acetonitrile at 0 - 20℃;
	Multi-step reaction with 2 steps 1: sulfuric acid / 2 h / 78 °C 2: hydrazine hydrate monohydrate / ethanol / 6 h / 78 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 12 h / Reflux 2: hydrazine monohydrate / methanol / 16 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / 24 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / ethanol
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux

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[15]Kaushik, Darpan; Kumar, Rajnish; Khan, Suroor Ahmed; Chawla, Gita [Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3646 - 3655]
[16]Siddiqui, Shadab Miyan; Salahuddin, Attar; Azam, Amir [Medicinal Chemistry Research, 2013, vol. 22, # 3, p. 1305 - 1312]
[17]Du, Qian-Ru; Li, Dong-Dong; Pi, Ya-Zhou; Li, Jing-Ran; Sun, Jian; Fang, Fei; Zhong, Wei-Qing; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297]
[18]Deora, Girdhar Singh; Karthikeyan, Chandrabose; Moorthy, N. S. Hari Narayana; Rathore, Vandana; Rawat, Arun K.; Tamrakar, Akhilesh K.; Srivastava; Trivedi, Piyush [Medicinal Chemistry Research, 2013, vol. 22, # 11, p. 5344 - 5348]
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[21]Moger, Manjunath; Satam, Vijay; Govindaraju, Darshan Raj C.; Paniraj; Gopinath, Vadiraj S.; Hindupur, Rama Mohan; Pati, Hari N. [Journal of the Brazilian Chemical Society, 2014, vol. 25, # 1, p. 104 - 111]
[22]Wang, Xiaohong; Liu, Xingli; Jiang, Yujia; Zhao, Zhigang [Journal of Chemical Research, 2014, vol. 38, # 5, p. 300 - 303]
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[25]Zhang, Kai; Wang, Peng; Xuan, Li-Na; Fu, Xiao-Yun; Jing, Fen; Li, Sha; Liu, Yu-Ming; Chen, Bao-Quan [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 22, p. 5154 - 5156]
[26]Mumtaz, Amara; Saeed, Aamer; Malik, Imran [Journal of the Chemical Society of Pakistan, 2014, vol. 36, # 5, p. 852 - 857]
[27]Li, Chao; Liu, Jia-Chun; Li, Ya-Ru; Gou, Cheng; Zhang, Mei-Ling; Liu, Hong-Yan; Li, Xiao-Zhen; Zheng, Chang-Ji; Piao, Hu-Ri [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 15, p. 3052 - 3056]
[28]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]
[29]Shen, Shengqiang; Sun, Xiaohong; Liu, Yuanfa; Chen, Bang; Jin, Ruyi; Ma, Haixia [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 5, p. 1296 - 1301]
[30]Mehr-Un-Nisa; Munawar, Munawar A.; Chattha, Fauzia A.; Kousar, Samina; Munir, Jawaria; Ismail, Tayaba; Ashraf, Muhammad; Khan, Misbahul A. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 6014 - 6024]
[31]Shi, Zhichuan; Zhao, Zhigang; Huang, Meiwei; Fu, Xiaolin [Comptes Rendus Chimie, 2015, vol. 18, # 12, p. 1320 - 1327] Dong, Liangrun; Song, Baojing; Wu, Jian; Wu, Zengxue; Zhu, Yunying; Chen, Xuewen; Hu, Deyu [Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 6, p. 904 - 907]
[32]Li, Ziqiang; Liu, Yishuang; Bai, Xiaoguang; Deng, Qi; Wang, Juxian; Zhang, Guoning; Xiao, Chunling; Mei, Yaning; Wang, Yucheng [RSC Advances, 2015, vol. 5, # 118, p. 97089 - 97101]
[33]Prasanna, V. Laxmi; Narender [Asian Journal of Chemistry, 2015, vol. 27, # 10, p. 3605 - 3608]
[34]Saidugari, Swamy; Rao, V. Lakshmana; Vidya; Ram; Balram [Asian Journal of Chemistry, 2016, vol. 28, # 3, p. 639 - 643]
[35]Khan, Mahmood-Ul-Hassan; Hameed, Shahid; Farman, Muhammad; Al-Masoudia, Najim A.; Stoeckli-Evans, Helen [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2015, vol. 70, # 8, p. 609 - 616]
[36]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]
[37]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]
[38]Pidugu, Vijaya Rao; Yarla, Nagendra Sastry; Pedada, Srinivasa Rao; Kalle, Arunasree M.; Satya, A. Krishna [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 21, p. 5611 - 5617]
[39]Kerzare, Deweshri; Chikhale, Rupesh; Bansode, Ratnadeep; Amnerkar, Nikhil; Karodia, Nazira; Paradkar, Anant; Khedekar, Pramod [Journal of the Brazilian Chemical Society, 2016, vol. 27, # 11, p. 1998 - 2010]
[40]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]
[41]Qurrat-Ul-Ain; Rasheed, Saima; Mahroof-Tahir, Mohammad; Ashiq, Uzma; Jamal, Rifat Ara; Khurshid, Sumaira; Mustafa, Sana [Journal of the Chemical Society of Pakistan, 2016, vol. 38, # 5, p. 864 - 881]
[42]Chen, Ling; Wang, Peiyi; Li, Zhenxing; Zhou, Lei; Wu, Zhibing; Song, Baoan; Yang, Song [Chinese Journal of Chemistry, 2016, vol. 34, # 12, p. 1236 - 1244]
[43]Zhou, Wen-Juan; Zhang, Li; Xiao, Wei; Chen, He-Ju; Wu, Wen-Neng; Ouyang, Gui-Ping [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1423 - 1429]
[44]Wang, Zi-Zhen; Sun, Wen-Xue; Wang, Xue; Zhang, Ya-Han; Qiu, Han-Yue; Qi, Jin-Liang; Pang, Yan-Jun; Lu, Gui-Hua; Wang, Xiao-Ming; Yu, Fu-Gen; Yang, Yong-Hua [Chemical Biology and Drug Design, 2017, vol. 90, # 2, p. 236 - 243]
[45]Current Patent Assignee: GUIZHOU UNIVERSITY - CN104672162, 2017, B
[46]Channar, Pervaiz Ali; Saeed, Aamer; Larik, Fayaz Ali; Rashid, Sajid; Iqbal, Qaiser; Rozi, Maryam; Younis, Saima; Mahar, Jamaluddin [Biomedicine and Pharmacotherapy, 2017, vol. 94, p. 499 - 513]
[47]He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5652 - 5661]
[48]Kumar Reddy; Kathale, Niren E [Oriental Journal of Chemistry, 2017, vol. 33, # 6, p. 2930 - 2936]
[49]Ganesh Kumar; Gautham Shenoy; Kar, Sidhartha Sankar; Shenoy, Vishnu; Bairy, Indira [Pharmaceutical Chemistry Journal, 2018, vol. 51, # 10, p. 907 - 917]
[50]Xu; Wang; Luo; Yu; Guo; Fu; Zhao; Wu [RSC Advances, 2018, vol. 8, # 12, p. 6306 - 6314]
[51]Vu, Vu Van; Nhung, Trinh Thi; Thanh, Nguyen Thi; Chinh, Luu Van; Tien, Vu Dinh; Thuy, Vu Thu; Thi Thao, Do; Nam, Nguyen Hai; Koeckritz, Angela; Vu, Tran Khac [Journal of Chemistry, 2017, vol. 2017]
[52]Current Patent Assignee: GUIZHOU UNIVERSITY - CN108218848, 2018, A
[53]Lakshmithendral; Saravanan; Elancheran; Archana; Manikandan; Arjun; Ramanathan; Lokanath; Kabilan [European Journal of Medicinal Chemistry, 2019, vol. 168, p. 1 - 10]
[54]Guo, Yong; Xu, Ting; Bao, Chongnan; Liu, Zhiyan; Fan, Jiangping; Yang, Ruige; Qin, Shangshang [European Journal of Pharmaceutical Sciences, 2019, vol. 136]
[55]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085] Adole, Vishnu A.; Chobe, Santosh S.; Dhonnar, Sunil L.; Jagdale, Bapu S.; More, Rahul A.; Sadgir, Nutan V. [Journal of Molecular Structure, 2022, vol. 1253]
[56]Hamdani, Syeda Shamila; Khan, Bilal Ahmad; Ahmed, Muhammad Naeem; Hameed, Shahid; Akhter, Kulsoom; Ayub, Khurshid; Mahmood, Tariq [Journal of Molecular Structure, 2020, vol. 1200]
[57]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]
[58]Bai, Xue-Qian; Cui, Ming-Yue; Li, Chun-Shi; Liang, Cheng-Wu; Song, Ze-Wen; Wang, Hui-Yan; Zhang, Tian-Yi; Zheng, Xian-Jing [Bioorganic and medicinal chemistry letters, 2020]
[59]Upadhyay, Prabhat Kumar; Mishra, Pradeep [Journal of the Indian Chemical Society, 2018, vol. 95, # 6, p. 661 - 666]
[60]Barbosa, Juliana M. C.; Bernardino, Patrícia; Decoté-Ricardo, Débora; Fraga, Carlos A. M.; Freitas, Rosana H. C. N.; Melo, Tatiana G.; Salomão, Kelly; Sueth-Santiago, Vitor; Wardell, James L.; Wardell, Solange M. S. V.; da Silva, Edson F. [Biomedicine and Pharmacotherapy, 2020, vol. 127]
[61]Dige, Nilam C.; Hassan, Mubashir; Lee, Ki Hwan; Mahajan, Prasad G.; Raza, Hussain; Seo, Sung-Yum; Vanjare, Balasaheb D. [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2020, vol. 241]
[62]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]
[63]Ma, Weifeng; Chen, Peng; Huo, Xiansen; Ma, Yufeng; Li, Yanhong; Diao, Pengcheng; Yang, Fang; Zheng, Shengquan; Hu, Mengjin; You, Wenwei; Zhao, Peiliang [European Journal of Medicinal Chemistry, 2020, vol. 208]
[64]Choubey, Priyanka Kumari; Tripathi, Avanish; Tripathi, Manish Kumar; Seth, Ankit; Shrivastava, Sushant Kumar [Bioorganic Chemistry, 2021, vol. 111]
[65]Liu, Jie; Zhang, Guang-Yu; Zhang, Zhe; Li, Bo; Chai, Fei; Wang, Qi; Zhou, Zi-Dan; Xu, Ling-Ling; Wang, Shou-Kai; Jin, Zhen; Tang, You-Zhi [Bioorganic Chemistry, 2021, vol. 112]
[66]Bettoni, Léo; Joly, Nicolas; Lohier, Jean-François; Gaillard, Sylvain; Poater, Albert; Renaud, Jean-Luc [Advanced Synthesis and Catalysis, 2021, vol. 363, # 16, p. 4009 - 4017]
[67]Guo, Yong; Meng, Jie-Ru; Liu, Jia-Zheng; Xu, Ting; Zheng, Zhi-Yuan; Jiang, Zhi-Hong; Bai, Li-Ping [Pharmaceuticals, 2021, vol. 14, # 9]
[68]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]
[69]Cheng, Wanqing; Fan, Jiangping; Guo, Yong; Han, Meiyue; Ma, Nannan; Yan, Xiaoting; Yang, Ruige [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 51, p. 15544 - 15553]
[70]Hassan, Mubashir; Hwan Lee, Ki; Ja Kim, Song; Raza, Hussain; Seok Eom, Young; Vanjare, Balasaheb D. [Bioorganic and Medicinal Chemistry, 2022, vol. 63]

6
[ 456-06-4 ]
[ 79-04-9 ]
[ 499129-05-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	In ethyl acetate Reflux;
	In tetrahydrofuran
	In ethyl acetate Reflux;

	In ethyl acetate Reflux;
	With sodium hydroxide In acetonitrile at 0℃;
	In ethyl acetate Reflux;

Reference： [1]Location in patent: experimental part Sutherland, Hamish S.; Blaser, Adrian; Kmentova, Iveta; Franzblau, Scott G.; Wan, Baojie; Wang, Yuehong; Ma, Zhenkun; Palmer, Brian D.; Denny, William A.; Thompson, Andrew M. [Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 855 - 866]
[2]Chai, Bing; Cao, Song; Liu, Haidong; Song, Gonghua; Qian, Xuhong [Heterocyclic Communications, 2002, vol. 8, # 6, p. 601 - 606]
[3]Cao, Song; Qian, Xuhong; Song, Gonghua; Chai, Bing; Jiang, Zhisheng [Journal of Agricultural and Food Chemistry, 2003, vol. 51, # 1, p. 152 - 155]
[4]Moger, Manjunath; Satam, Vijay; Govindaraju, Darshan Raj C.; Paniraj; Gopinath, Vadiraj S.; Hindupur, Rama Mohan; Pati, Hari N. [Journal of the Brazilian Chemical Society, 2014, vol. 25, # 1, p. 104 - 111]
[5]Guo, Yong; Xu, Ting; Bao, Chongnan; Liu, Zhiyan; Fan, Jiangping; Yang, Ruige; Qin, Shangshang [European Journal of Pharmaceutical Sciences, 2019, vol. 136]
[6]Fang, Lincheng; Hu, Zhaoxue; Yang, Yifei; Chen, Pan; Zhou, Jinpei; Zhang, Huibin [Bioorganic and Medicinal Chemistry, 2021, vol. 39]
[7]Guo, Yong; Meng, Jie-Ru; Liu, Jia-Zheng; Xu, Ting; Zheng, Zhi-Yuan; Jiang, Zhi-Hong; Bai, Li-Ping [Pharmaceuticals, 2021, vol. 14, # 9]

7
[ 456-06-4 ]
[ 78-39-7 ]
[ 145694-80-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	at 150℃; for 24h;	83 Preparation 83 2-(4-Fluoro-3-nitrophenyl)-5-methyl-l,3,4-oxadiazole To a suspension of 4-fluorobenzohydrazide (18 g, 117 mmol) in 1, 1,1- triethoxy ethane (85 ml, 467 mmol) was heated at 150 °C. After refluxing for 24 hr at 150 °C, the reaction solution was cooled down to room temperature, then a solid precipitated out. After flushing with nitrogen for 2-3 minutes, the resultant solid was treated with 1-2% ethyl ether in hexane. After collecting and washing solid with hexane followed by drying in vacuo at 50°C, 2-(4-fluorophenyl)-5-methyl-l,3,4-oxadiazole (17.80 g, 99 mmol, 85 % yield) was obtained as light brown solid: MS (m/z) 179.0 (M+H+); 1H MR (DMSO-d6) δ: 7.97 - 8.10 (m, 2H), 7.38 - 7.51 (m, 2H), 2.58 (s, 3H).
48%	With ammonium chloride In ethanol at 80℃; for 6h; Inert atmosphere;	1 Step 1: Synthesis of 2-(4-fluorophenyl)-5-methyl-1,3,4-oxadiazole Under the protection of nitrogen, dissolve 4-fluorobenzoyl hydrazide (9.66g, 54mmol) and triethyl orthoacetate (50mL, 270mmol) in absolute ethanol (150mL),Ammonium chloride (1.45g, 27mmol) was added, and the mixture was heated to reflux at 80°C for 6 hours.The ethanol was removed by concentration under reduced pressure, and the residue was subjected to column chromatography [petroleum ether/ethyl acetate (v/v)=10/1] to obtain 4.65 g of white solid with a yield of 48%.
	In xylene Heating;

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2014/125444, 2014, A1 Location in patent: Page/Page column 115
[2]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - CN112110894, 2020, A Location in patent: Paragraph 0120-0121
[3]Barrett, David G.; Boncek, Virginia M.; Catalano, John G.; Deaton, David N.; Hassell, Anne M.; Jurgensen, Cynthia H.; Long, Stacey T.; McFadyen, Robert B.; Miller, Aaron B.; Miller, Larry R.; Payne, J. Alan; Ray, John A.; Samano, Vicente; Shewchuk, Lisa M.; Tavares, Francis X.; Wells-Knecht, Kevin J.; Willard Jr., Derril H.; Wright, Lois L.; Zhou, Hui-Qiang Q. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 15, p. 3540 - 3546]

8
[ 456-06-4 ]
[ 74974-54-2 ]
[ 721428-34-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With acetic acid at 160℃; for 0.5h; Microwave;	1.C C. Preparation of a Compound of Formula (4a) in which R is 4-Fluorophenyl 4-Fluorobenzenecarbohydrazide (0.3 g, 2mmol) was suspended in chloro-1,1,1-trimethoxyethane (2 ml). To the suspension was added acetic acid (1 ml), and the solution was heated in a microwave for 30minutes at 160° C. The solvent was removed under reduced pressure, and the residue purified using Biotage, eluding with 20% ethyl acetate/hexanes, to provide 5-(chloromethyl)-3-(4-fluorophenyl)-1,2,4-oxadiazole in 89% yield.
89%	With acetic acid at 160℃; for 0.5h; Microwave irradiation;	1.C C. Preparation of a Compound of Formula (4a) in which R is 4-Fluorophenyl[0157] 4-Fluorobenzenecarbohydrazide (0.3 g, 2mmol) was suspended in chloro- 1,1,1 - trimethoxyethane (2 ml). To the suspension was added acetic acid (1 ml), and the solution was heated in a microwave for 30inutes at 1600C. The solvent was removed under reduced pressure, and the residue purified using Biotage, eluting with 20% ethyl acetate/hexanes, to provide 5-(chloromethyl)-3-(4-fluorophenyl)-l,2,4-oxadiazole in 89% yield.

Reference： [1]Current Patent Assignee: AMYGDALA NEUROSCIENCES INC - US2008/32995, 2008, A1 Location in patent: Page/Page column 21-22
[2]Current Patent Assignee: GILEAD SCIENCES INC; THE ENDOWMENT FOR RESEARCH IN HUMAN BIOLOGY INC - WO2009/94028, 2009, A1 Location in patent: Page/Page column 54

9
[ 456-06-4 ]
[ 114058-91-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 25 percent / pyridine / Ambient temperature 2: 71 percent / NaOH / H₂O / 4 h / Heating
	Multi-step reaction with 2 steps 1: hydrogenchloride / methanol / 1 h / Reflux 2: sodium hydroxide / methanol / Reflux
	Multi-step reaction with 2 steps 1: hydrogenchloride / methanol; water / 1 h / Reflux 2: sodium hydroxide / methanol / Reflux

Reference： [1]Gulerman; Rollas [Il Farmaco, 1997, vol. 52, # 11, p. 691 - 695]
[2]Murty; Ram, Kesur R.; Rao, Rayudu Venkateswara; Yadav; Rao, Janapala Venkateswara; Pamanji; Velatooru [Letters in drug design and discovery, 2012, vol. 9, # 3, p. 276 - 281]
[3]Murty; Ram, Kesur R.; Rao, B. Ramalingeswara; Rao, Rayudu Venkateswara; Katiki, Mohana Rao; Rao, Janapala Venkateswara; Pamanji; Velatooru [Medicinal Chemistry Research, 2014, vol. 23, # 4, p. 1661 - 1671]

10
[ 456-06-4 ]
[ 138417-35-3 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 125 - 132

11
[ 101-99-5 ]
[ 456-06-4 ]
[ 103-03-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate In tetrahydrofuran	4.7 (7) The solvent is then evaporated and the residue purified by liquid-gel partition chromatography using a 400*15 mm column of Sephadex LH20 substituted with Nedox 1114 olefin oxide to 20% w/w and eluding with dichloroethane/hexane/ethanol (100:100:5 v/v/v) containing 0.1% v/v of acetic acid. The chromatography gives the title compound as an oil (87 mg), δ(CDCl3) 9.60 (br, 1H), 8.10 (br, 1H), 7.7-7.1 (m, 5H), 5.35 (m, 2H). The phenyl semicarbazide is prepared as follows. Ethyl-N-phenyl carbamate (8.25 g) is refluxed with hydrazine hydrate (3.75 g) for 3 hours. The mixture is evaporated to dryness and the residue is treated with ether, and the solid phenyl semicarbazide (1.5 g) is filtered off, washed with ether and dessicated, m.p. 122°-124° C. Note: In a variant of the procedure described in this Example the acid/aldehyde (6) (100 mg) is reacted with p-fluorobenzoic hydrazide STR24 (45 mg) in place of the phenyl semicarbazide STR25 the reaction being carried out in tetrahydrofuran for 1.5 hours at 40° C. to yield the alternative bicyclo[2,2,2]octane derivative, trans-5-(6'-carboxyhex-2'Z-enyl)-6-[N-(p-fluorobenzoyl)-hydrazono methyl]-bicyclo[2,2,2]octane.

Reference： [1]Current Patent Assignee: BOSTON SCIENTIFIC CORP - US4596823, 1986, A

12
[ 456-06-4 ]
[ 37091-73-9 ]
4-(5-{1-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclopropyl}-4-phenylisoxazol-3-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To the each acylhydrazide (150 mumol, see structures on table) is added {1-[3-(4-hydroxy-phenyl)-4-phenyl-isoxazol-5-yl]-cyclopropyl}-imidazol-1-yl-methanone (150 mumol) in acetonitrile (2.5 mL). The mixtures are heated in the cavity of a microwave to 140° C. for 600 seconds. 2-Chloro-1,3-dimethylimidazolinium chloride (450 mumoles) and triethylamine (900 mumoles) is added and the reactions are heated in the cavity of a microwave to 140° C. for 600 seconds. The solvent is removed in vacuo using a Genevac EZ-2. To each reaction mixture is added methylene chloride (2 mL) and water (2 mL). The layers are separated by filtering through Phase Separator SPE (solid phase extraction) Columns. Each organic layer is filtered through a Silica (500 mg) SPE column and eluted with methylene chloride (6 mL). The solvent is removed in vacuo using a Genevac EZ-2 to obtain a sample that is then purified by reverse phase HPLC.

Reference： [1]Patent: US2007/149564,2007,A1 .Location in patent: Page/Page column 45

13
[ 456-06-4 ]
[ 116096-91-4 ]
[ 878987-00-9 ]

Yield	Reaction Conditions	Operation in experiment
48.6%	In ethanol at 20℃; for 3h;

Reference： [1]Location in patent: experimental part He, Lingyan; Zhang, Liang; Liu, Xiaofeng; Li, Xianghua; Zheng, Mingyue; Li, HongLin; Yu, Kunqian; Chen, Kaixian; Shen, Xu; Jiang, Hualiang; Liu, Hong [Journal of Medicinal Chemistry, 2009, vol. 52, # 8, p. 2465 - 2481]

14
[ 456-06-4 ]
[ 1243204-92-3 ]
[ 1262193-41-8 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate; In butan-1-ol; at 120℃; for 12h;Microwave irradiation;	Example B3 a) Preparation of compound 4 A mixture of intermediate 1 (443 mg, 2.08 mmol), 4-fluorobenzoic acid hydrazide (320 mg, 2.08 mmol) and K2CO3 (143 mg, 1.04 mmol) in n-BuOH (15 ml) was heated in the microwave at 120 0C for 12 h. The solvent was removed under reduced pressure and the resulting residue partitioned between EtOAc/H2O. The phases were separated. The aq. phase was extracted with EtOAc, and the combined organic extracts were washed with brine and dried (MgSO^. Filtration and concentration under reduced pressure gave the crude product which was purified by column chromatography over silica gel (eluent: 100:0 to 90: 10 DCM/MeOH, gradient elution). The product fractions were collected and evaporated to yield 450 mg of compound 4 (62.0 %).

Reference： [1]Patent: WO2011/6903,2011,A1 .Location in patent: Page/Page column 162
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 4794 - 4800

15
[ 456-06-4 ]
[ 1243204-92-3 ]
[ 1262193-42-9 ]

Reference： [1]Patent: WO2011/6903,2011,A1

16
[ 456-06-4 ]
[ 24662-37-1 ]
[ 1284312-37-3 ]

Yield	Reaction Conditions	Operation in experiment
65%	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]

17
[ 456-06-4 ]
[ 3140-75-8 ]
[ 1363379-34-3 ]

Yield	Reaction Conditions	Operation in experiment
89.7%	In tetrahydrofuran;Reflux;	General procedure: Tripod (1) (0.106 g, 0.24 mmol) was added to a solution of benzoic hydrazide (2a) (0.109 g, 0.8 mmol) in tetrahydrofuran (75 mL) and the reaction mixture was stirred under reflux for 15-18 h. The solvent was removed by evaporation under reduced pressure. The residue was filtered under suction and washed several times withhot tetrahydrofuran. The resulting solid (3a) was dried in vacuo at 40 C for 4 h. The same general procedure was followed for the compounds 3b-i.

Reference： [1]Journal of Molecular Structure,2012,vol. 1011,p. 121 - 127

18
[ 456-06-4 ]
[ 14527-26-5 ]
[ 591246-75-2 ]

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

19
[ 456-06-4 ]
[ 51908-29-3 ]
[ 891624-81-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	In ethanol;Reflux;	General procedure: General procedure: A mixture of 8 (1mmol) and aromatic acid hydrazide was refluxed in absolute ethanol for 3-4h. After the completion of the reaction the solid precipitated was filtered off, washed with cold ethanol, dried and recrystallized from ethanol which afforded the pure products 9a-9g.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1873 - 1882

20
[ 13481-25-9 ]
[ 456-06-4 ]
[ 1571911-51-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium methylate In methanol at 20℃; chemoselective reaction;	N′-(7-Amino-5H-pyrrolo[3,4-b]pyrazin-5-ylidene)carbohydrazides 3a-m; General Procedure General procedure: To a stirred solution of the respective acid hydrazide (3.5 mmol) in anhydrous MeOH (30 mL) was added NaOMe (0.35 mL, 1 N solution in MeOH). After 5 min, pyrazine-2,3-dicarbonitrile (1; 0.46 g,3.5 mmol) was added in one portion and the stirring was continued for 0.5-1.5 h at r.t. The precipitate formed was collected by filtration, washed with hexane (5 mL), recrystallized from MeOH or EtOH, and dried under vacuum.

Reference： [1]Hordiyenko, Olga V.; Rudenko, Igor V.; Zamkova, Irina A.; Denisenko, Oleksandr V.; Biitseva, Angelina V.; Arrault, Axelle; Tolmachev, Andrei A. [Synthesis, 2013, vol. 45, # 24, p. 3375 - 3382]

21
[ 124-38-9 ]
[ 456-06-4 ]
[ 121649-18-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium hydroxide In ethanol at 50℃; for 4h; Green chemistry;

Reference： [1]Brahmayya; Dai, Shenghong A.; Suen [RSC Advances, 2015, vol. 5, # 80, p. 65351 - 65357]

22
[ 201230-82-2 ]
[ 456-06-4 ]
[ 121649-18-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With palladium(II) trifluoroacetate; acetonitrile; trifluoroacetic acid; copper(II) oxide at 60℃; for 12h;

Reference： [1]Ji, Fanghua; Li, Xianwei; Guo, Wei; Wu, Wanqing; Jiang, Huanfeng [Journal of Organic Chemistry, 2015, vol. 80, # 11, p. 5713 - 5718]

23
[ 456-06-4 ]
[ 219861-08-2 ]
[ 1802255-33-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In butan-1-ol at 150℃;	19 Synthesis of escitalopram triazoles General procedure: The triazoles of escitalopram (60-88) were synthesized byfollowing a reported method for triazole formation.25 A mixtureof a benzohydrazide (33 mmol), escitalopram (59-oxalate,10 mmol) and K2CO3 (0.5 mmol) in n-butanol (2 mL) was heatedat 150 C for 5-6 h. The reaction was monitored with TLC. Afterthe completion of the reaction, the solvent was removed underreduced pressure. Finally, the triazole derivatives of escitalopram(60-88) were purified with column chromatography using solventsystem CH3OH/CH3Cl = 60:40 and finally with preparative thinlayer chromatography.

Reference： [1]Mehr-Un-Nisa; Munawar, Munawar A.; Chattha, Fauzia A.; Kousar, Samina; Munir, Jawaria; Ismail, Tayaba; Ashraf, Muhammad; Khan, Misbahul A. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 6014 - 6024]

24
[ 456-06-4 ]
[ 129765-95-3 ]
tert-butyl 4-(2-(4-fluorobenzoyl)hydrazinyl)-2-methyl-4-oxobutan-2-yl-carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;	4-Fluorobenzohydrazide (CAN 456-06-4, 2.13 g, 13.8 mmol) was added to a solution of 3- (tert-butoxycarbonylamino)-3-methylbutanoic acid (CAN 129765-95-3, 3 g, 13.8 mmol), DIPEA (5.35 g, 7.23 mL, 41.4 mmol) and HBTU (5.24 g, 13.8 mmol) in DMF (100 mL). The reaction mixture was stirred for 18 h at ambient temperature and subsequently concentrated in vacuo. EtOAc (150 mL) was added and the solution was washed with sat. aqueous NaHC03 (2 x 50 mL), 1 M HCl (2 x 50 mL) and brine (2 x 50 mL). The aqueous layer was back-extracted with EtOAc (100 mL). The organic layers were combined, dried over MgS04 and concentrated in vacuo. The crude material was purified by (0260) chromatography (silica gel, 300 g, EtOAc:heptane 1: 1) to obtain the title compound (1.29 g, 26%) as colorless oil, MS (ISP): 354.3 [MH+].

Reference： [1]Patent: WO2015/150438,2015,A1 .Location in patent: Page/Page column 38; 39

25
[ 456-06-4 ]
[ 56248-10-3 ]
(E)-4-fluoro-N'-[(4-phenyl-1H-imidazol-2-yl)methylene]benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	In ethanol; for 1h;Reflux;	General procedure: To a stirred solution of compound 3 (100mg, 0.40 mmol) in ethanol was added corresponding benzohydrazides (4a-m) (1.0 mmol) and refluxed for 1 h. The reaction mass was washed with pet ether, filtered and dried undervacuum to obtain the pure hydrazone compounds. Yields ofthe products varied between 78 and 88 %.

Reference： [1]Asian Journal of Chemistry,2015,vol. 27,p. 3605 - 3608

26
[ 456-06-4 ]
[ 50868-68-3 ]
C₁₄H₁₀BrFN₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate Reflux; Inert atmosphere;	1 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 A; 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 (2.5 eq, 50% solution in EtOAc) and triethylamine (3 eq), and the mixture was refluxed under argon atmosphere for 1h-24h. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature, and poured into ice/water. The precipitating solid was filtered off, washed with water, cyclohexan and dried under pressure to give the pure diacylhydrazine derivative.; The corresponding diacylhydrazine derivative was placed under argon atmosphere and POCl3 was added dropwise (10 mL). The mixture was refluxed for 1h30. The mixture was cooled to room temperature, and poured into ice/water. The precipitating solid was filtered off, washed with water, cyclohexane and dried under pressure to give the desired 1,3,4-oxadiazole derivative.

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]

27
[ 456-06-4 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	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;	7 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.; 4.1.2.7 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole 12 1H NMR (DMSO-d6, 400 MHz): δ = 8.15 (dd, J = 8.8 Hz, 1H), 8.13 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 16.2 Hz, 1H), 7.48 (t, J = 8.8 Hz, 2H), 7.41 (d, J = 3.9 Hz, 1H), 7.31 (d, J = 3.9 Hz, 1H), 7.04 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.11, 163.02, 141.82, 132.38, 131.74, 131.52, 129.85, 129.76, 120.48, 120.46, 117.29, 117.07, 115.23, 109.42; LC/MS (ESI): 350.99 [M+H]+ and isotopic peak: 352.98; HRMS (TOF, ESI+) cald for C14H9N2OFSBr (M + H)+ 350.9303, found 350.9599; 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]

28
[ 42348-86-7 ]
[ 456-06-4 ]
[ 106-95-6 ]
N'-(1-allyl-5-chloro-2,3-dihydro-1H-inden-1-yl)-4-fluorobenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With tin; In tetrahydrofuran; for 3h;Inert atmosphere; Reflux;	General procedure: A solution of a ketone 1 (1.0 mmol), an acylhydrazine 2 (1.5 mmol), allyl bromide (3; 2.0 mmol) and Sn powder (2.5 mmol) in THF (5 mL) was stirred under reflux for 3-10 h (monitored by TLC). Then, the reaction mixture was quenched with saturated aq NH4Cl (10 mL). The organic layer was separated, and the aqueous phase was extracted with EtOAc (3 × 15 mL). The combined organic layers were dried over anhydrous MgSO4 and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether-EtOAc) to afford the desired product.

Reference： [1]Synthesis,2016,vol. 48,p. 293 - 301

29
[ 456-06-4 ]
[ 2144-08-3 ]
(E)-4-fluoro-N'-(2,3,4-trihydroxybenzylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	In ethanol at 30℃;	1 General procedure C for synthesis of 2,3,4-trihydroxybenzylidene)hydrazide derivatives 10A-B 2,3,4-trihydroxybenzaldehyde (1.5 equiv) and synthesized hydrazides (9A-T) were dissolved in anhydrous ethanol (10 mL) and stirred at 30 °C for overnight. The reaction monitored by TLC (thin layer chromatography). The crude reaction mixture was concentrated under vacuum and the product was obtained as yellow solid. The remained benzaldehyde was washed out by ethyl ether. (Yield 80-85%). Following the general procedure C, 10A was synthesized from 4-fluorobenzohydrazide 9A (77.0 mg, 0.5 mmol, 1.0 equiv) and 2, 3, 4-trihydroxybenzaldehyde (115.6 mg, 0.75 mmol, 1.5 equiv). Yield 82%; 1H NMR (400 MHz, DMSO-d6) δ 6.28-6.50 (m, 2H) 6.79 (d, J = 8.55 Hz, 1H) 6.93 (d, J = 8.55 Hz, 1H) 7.32-7.42 (m, 1H) 7.96-8.05 (m, 1H) 8.29-8.49 (m, 1H) 8.49-8.64 (m, 1H) 8.76 (s, 1H) 9.63-9.86 (m, 2H) 11.27 (s, 1H) 11.49-12.11 (m, 1H); MS (ESI): m/z = 291.00 [M+H].
62.5%	In methanol at 20℃; for 12h; Inert atmosphere;	2.1.2. General procedure for the synthesis of hydrazides 3a-3z General procedure: 2,3,4-Trihydroxybenzaldehyde (0.55 g, 3.6 mmol) was added to asolution of hydrazides (3.0 mmol) in methanol (20 mL). The solutionwas stirred for 12 h under room temperature, which was then filteredand finally recrystallized from ethanol, to give the target hydrazonederivatives as white to gray powdered solid.

Reference： [1]Kim, Bo-Kyoung; Ko, Hyojin; Jeon, Eun-Seok; Ju, Eun-Seon; Jeong, Lak Shin; Kim, Yong-Chul [European Journal of Medicinal Chemistry, 2016, vol. 120, p. 202 - 216]
[2]Chen, Lixia; Gao, Suyu; Li, Hua; Li, Mingxue; Li, Xingzhou; Liu, Yang; Wu, Canrong; Yang, Kaiyin; Zhang, Yujie; Zheng, Mengzhu [Bioorganic Chemistry, 2020, vol. 96]

30
[ 120-72-9 ]
[ 456-06-4 ]
[ 782-17-2 ]

Yield	Reaction Conditions	Operation in experiment
77%	With copper(l) iodide; oxygen; toluene-4-sulfonic acid; palladium dichloride In nitromethane; dimethyl sulfoxide at 100℃; for 10h;

Reference： [1]Liu, Congrong; Yang, Fulai [Chinese Journal of Chemistry, 2016, vol. 34, # 12, p. 1213 - 1217]

31
[ 456-06-4 ]
[ 16357-83-8 ]
N’-((4-aminopyrimidine-5-yl)methylene)-4-fluorobenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With acetic acid; In ethanol; for 3h;	General procedure: Appropriate substituted benzoyl hydrazine 4 (1 equiv) was added to a solution of intermediate 2 (1mmol) in ethanol (10mL). The reaction mixture was stirred for 3h at reflux under the condition of the presence of acetic acid as catalyzer, then poured into cold water and the resulting solid was collected by filtrated, washed with EtOH (10mL), and dried in the atmospheric pressure to give the desired title compounds A, B, and C.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5652 - 5661

32
[ 80194-68-9 ]
[ 456-06-4 ]
2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-(4-fluorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; for 10h;Heating;	Step 3: Add 0.25g to the three-necked flask3-chloro-5-(trifluoromethyl)pyridinecarboxylic acid,0.19g 4-fluorobenzoic acid hydrazide, 3ml POCl3 heated and stirred,After 10 hours of reaction, pour the liquid into a beaker containing ice water.Add Na2CO3 to adjust pH = 9-10, suction filtration, drying, and column chromatography to obtain the target compound.

Reference： [1]RSC Advances,2018,vol. 8,p. 6306 - 6314
[2]Patent: CN108218848,2018,A .Location in patent: Paragraph 0152; 0153; 0156

33
[ 103854-64-4 ]
[ 456-06-4 ]
C₁₈H₁₄FN₃O₂ [ 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

34
[ 456-06-4 ]
[ 4209-02-3 ]
3-(4-fluorophenyl)-6-(4-bromophenyl)-1,2,4-triazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With ammonium acetate; acetic acid; at 150℃; for 18h;	In the reactor by adding alpha-chloro-4-bromoacetophenone (23.3 g, 0.1 muM), 4-fluorobenzoylhydrazine(15.4 g, 0.1 muM), acetic acid (36 g, 0.6 muM), ammonium acetate (46.2 g, 0.6 muM) and ethylene glycol monobutyl ether (500 ml), the reaction mixture is heated to 150 C, reaction 18 h, the product precipitated, filtering, drying, to obtain 3-(4-fluorophenyl)-6-(4-bromophenyl)-1,2,4-triazine(31.4 g, yield 95%, purity (HPLC)>99.0%), directly used for the next step reaction.

Reference： [1]Patent: CN108586369,2018,A .Location in patent: Paragraph 0113; 0114

35
[ 456-06-4 ]
[ 4209-02-3 ]
2-(4-fluorophenyl)-5-(4-bromophenyl)pyridine [ No CAS ]

Reference： [1]Patent: CN108586369,2018,A

36
[ 456-06-4 ]
[ 143982-40-5 ]
4-fluoro-N'-((imidazo[1,2-a]pyrimidin-2-yl)methylene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; for 5.0h;Reflux;	General procedure: To a stirred solution of compound 3 (100 mg, 0.30 mmol) in ethanol was added corresponding benzohydrazides (1.0 mmol) and refluxed for 5 h. The reaction medium was poured into water and extracted with ethyl acetate. The organic layer was washed with water followed by brine solution, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure, to obtain the pure compounds.

Reference： [1]Indian Journal of Heterocyclic Chemistry,2015,vol. 25,p. 119 - 122

37
[ 506-68-3 ]
[ 456-06-4 ]
[ 7659-07-6 ]

Yield	Reaction Conditions	Operation in experiment
95%		To a solution of sodium bicarbonate (5.45g, 64.9mmol) in 1:1 water:dioxane (100 mLtotal volume) was added 4-fluorobenzohydrazide (10.Og, 64.9mmol) and the resulting suspension stirred for 10 mm at 25 C. To this was added cyanogen bromide (6.87g, 64.9mmol) in threeportions over 15 mm. After stirring at 25 C for 18 hrs, the reaction was diluted with water (200mL), filtered, and the resultant solid rinsed with water. The solid was dried in vacuo (12 hrs) to provide a light brown powder (1 1.Og, 95%); ‘H NMR (DMSO): 7.87-7.82 (m, 2H), 7.4 1-7.35(m, 2H), 7.24 (br s, 2H); LCMS: 180.2 (M+1).
83%	In ethanol; at 20℃;Inert atmosphere;	General procedure: A mixture of corresponding hydrazine (1mmol), BrCN (1.2mmol), and EtOH (10 mL) was degassed with argon and stirred at room temperature overnight. The solvent was evaporated and the residue was purified by flash chromatography (DCM : MeOH = 20:1) to give the product.

Reference： [1]Patent: WO2019/40404,2019,A1 .Location in patent: Page/Page column 100
[2]Tetrahedron Letters,2019,vol. 60,p. 1359 - 1362

38
[ 456-06-4 ]
[ 4559-70-0 ]
[ 18437-73-5 ]

Yield	Reaction Conditions	Operation in experiment
43%	With sodium persulfate; palladium diacetate; benzenesulfonic acid; bis-diphenylphosphinomethane In N,N-dimethyl acetamide; dimethyl sulfoxide at 100℃; for 20h; Inert atmosphere; Schlenk technique;

Reference： [1]Dong, Jianyu; Liu, Long; Ji, Xuyu; Shang, Qian; Liu, Lixin; Su, Lebin; Chen, Bing; Kan, Ruifeng; Zhou, Yongbo; Yin, Shuang-Feng; Han, Li-Biao [Organic Letters, 2019, vol. 21, # 9, p. 3198 - 3203]

39
[ 456-06-4 ]
[ 121649-18-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: copper(l) iodide; dipotassium peroxodisulfate / neat liquid / 1 h / 120 °C / Inert atmosphere; Sealed tube 2: oxygen; copper dichloride; lithium tert-butoxide / N,N-dimethyl-formamide / 25 °C / Schlenk technique

Reference： [1]Wang, Shoucai; Wang, Kai; Kong, Xiangfei; Zhang, Shuhua; Jiang, Guangbin; Ji, Fanghua [Advanced Synthesis and Catalysis, 2019, vol. 361, # 17, p. 3986 - 3990]

40
[ 456-06-4 ]
[ 950259-82-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 12 h / 20 °C 2: p-toluenesulfonyl chloride / 12 h / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 8 h / 20 °C / Cooling with ice 2: trichlorophosphate / 3 h / 85 °C

Reference： [1]Tresse, Cédric; Radigue, Richard; Gomes Von Borowski, Rafael; Thepaut, Marion; Hanh Le, Hong; Demay, Fanny; Georgeault, Sylvie; Dhalluin, Anne; Trautwetter, Annie; Ermel, Gwennola; Blanco, Carlos; van de Weghe, Pierre; Jean, Mickaël; Giard, Jean-Christophe; Gillet, Reynald [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 21]
[2]Xu, Congjun; Han, Yufei; Xu, Sicong; Wang, Ruxin; Yue, Ming; Tian, Yu; Li, Xiaofan; Zhao, Yanfang; Gong, Ping [European Journal of Medicinal Chemistry, 2020, vol. 186]

41
[ 2985-33-3 ]
[ 456-06-4 ]
C₁₃H₁₅FN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 8h;	General procedure: Ethyl hydrogen malonate (0.70g, 5.25 mmol) was added dropwiseto a solution of 4-fluoro-N-hydroxybenzimidamide (17,0.78g, 5.0 mmol), EDCI (1.5eq.) and triethylamine (1.01g,10.0 mmol) in dichloromethane in an ice bath. Upon completion ofthe addition, the reaction mixture was removed from the ice bathand placed in room temperature for 8h and monitored by thin-layerchromatography (TLC). The mixture was washed with 10% K2CO3(150 mL3) followed by brine (150 mL1), and the organic phasewas separated, dried and evaporated to yield ethyl 3-((4-fluorobenzimidamido)oxy)-3-oxopropanoate as yellow solid.

Reference： [1]Xu, Congjun; Han, Yufei; Xu, Sicong; Wang, Ruxin; Yue, Ming; Tian, Yu; Li, Xiaofan; Zhao, Yanfang; Gong, Ping [European Journal of Medicinal Chemistry, 2020, vol. 186]

42
[ 456-06-4 ]
[ 3697-66-3 ]
C₁₄H₁₅FN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 8h;	General procedure: Ethyl hydrogen malonate (0.70g, 5.25 mmol) was added dropwiseto a solution of 4-fluoro-N-hydroxybenzimidamide (17,0.78g, 5.0 mmol), EDCI (1.5eq.) and triethylamine (1.01g,10.0 mmol) in dichloromethane in an ice bath. Upon completion ofthe addition, the reaction mixture was removed from the ice bathand placed in room temperature for 8h and monitored by thin-layerchromatography (TLC). The mixture was washed with 10% K2CO3(150 mL3) followed by brine (150 mL1), and the organic phasewas separated, dried and evaporated to yield ethyl 3-((4-fluorobenzimidamido)oxy)-3-oxopropanoate as yellow solid.

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 186

43
[ 456-06-4 ]
[ 1147550-11-5 ]
[ 114058-91-2 ]

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]

44
[ 456-06-4 ]
[ 611-74-5 ]
[ 1580-50-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With titanium tetrachloride at 110℃; for 1.5h;	General procedure for the synthesis of 1,3,4-oxadiazole derivatives (2a-2o) General procedure: To a 10mL three-necked round bottle was charged with benzoylhydrazine (0.30 g,2.2 mmol), TiCl4 (0.83 g, 4.4 mmol) and DMA (3 mL, 32.1 mmol). The resulting solutionwas warmed to 110 C and stirred at this temperature for 1.5 h. When the reaction wascompleted, 50mL water was added and the resulting mixture was extracted with 50mLethyl acetate three times. The combined organic layer was successively washed withH2O (50 mL) and then brine (50 mL), then dried over anhydrous Na2SO4, filtered andconcentrated under reduced pressure. The residue was purified by column chromatographyon silica gel with petroleum ether and ethyl acetate to give the title products.

Reference： [1]Zhang, Lin; Yu, Yu; Tang, Qiang; Yuan, Jianyong; Ran, Dongzhi; Tian, Binghua; Pan, Tao; Gan, Zongjie [Synthetic Communications, 2020, vol. 50, # 3, p. 423 - 431]

45
[ 456-06-4 ]
[ 765-87-7 ]
N,N'-cyclohexane-1,2-diylidene-bis(4-fluorobenzoylhydrazide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With acetic acid In methanol for 4h; Reflux;	2.2.1. Synthesis of N,N'-cyclohexane-1,2-diylidene-bis(4-fluorobenzoylhydrazide) (L) This compound was prepared following the synthetic procedure that described in our previous works [19-22]: To a mixture of 1,2-cyclohexanedione (1.2 g, 10.7 mmol) and 4-fluorobenzoic hyrazide (3.3 g, 21.4 mmol) in methanol (50 ml), was added glacial acetic acid (1.2 ml). The reaction mixture was stirred under reflux for 4 h. Upon cooling, a yellow precipitate was appeared which containing few crystals suitable for single-crystal X-ray crystallography. The precipitate was removed by filtration, washed subsequently with water and some organic solvents (methanol and diethyl ether), and finally dried in vacuo, yield 3.7 g, 90.% based on 1,2-cyclohexanedione.

Reference： [1]Abdulkareem D. Ithawi, Hiba; Bariz OmarAli, Al-Ameen; Dege, Necmi; Jasim M. Al-Karawi, Ahmed; Kansız, Sevgi [Journal of Molecular Structure, 2020, vol. 1217]

46
[ 456-06-4 ]
[ 765-87-7 ]
N,N'-(cyclohexane-1,2-diylidene)bis(4-fluorobenzohydrazide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.38%	With acetic acid In methanol for 4h; Reflux;	2.2.1. N,N'-(Cyclohexane-1,2-diylidene)bis(4-fluorobenzohydrazide),(LF). This compound was prepared according to the synthetic procedure described in our previous work (AlKarawi et al., 2016). To cyclohexane-1,2-dione (1 g, 8.92 mmol) dissolved in methanol (50 ml) was added 4-fluorobenzohyrazide(2.75 g, 17.84 mmol) as a solid. Glacial acetic acid (1 ml) was then added and the mixture was refluxed for 4 h. A yellow precipitate formed upon cooling and contained some crystals suitable for single-crystal X-ray crystallography. This solid was filtered off, washed successively with water, cold methanol and diethyl ether, and ultimately dried in vacuo (yield 3.1 g,90.38%). 1H NMR (400 MHz, DMSO-d6): δ 14.44 (s, 1H)(OH), 11.17 (s, 1H) (NH), 8.265 (d, J = 8.8 Hz, 2H) (CH),8.055 (d, J = 8.7 Hz, 2H) (CH), 7.37 (d, J = 8.6 Hz, 2H) (CH),7.325 (d, J = 8.6 Hz, 2H) (CH), 4.10 (q, J = 5.3 Hz, 1H) (OH), 3.18 (d, J = 5.3 Hz, 3H) (CH3), 2.82 (t, 2H) (CH2), 2.63 (t, 2H)(CH2), 1.75 (m, 4H) (CH2). 13C NMR (100 MHz, DMSO-d6): δ 166.14 (C=O), 162.74 (C=N), 153.59 (C), 143.51 (C), 131.83(CH), 131.26 (CH), 129.76 (C), 115.96 (CH), 115.74 (CH),49.08 (OCH3), 34.19 (CH2), 27.32 (CH2), 22.77 (CH2), 21.48(CH2). IR (cm-1): ν(N-H) = 3302, ν(C-H aromatic) = 3050,νas(C-H) of CH2 = 2943, νs(C-H) of CH2 = 2825, ν(C=O) =1672, ν(C=C aromatic) = 1597 and 1575, ν(C=N) = 1520.Elemental analysis calculated (%): C 62.49, H 4.72, N 14.58;found: C 62.58, H 4.68, N 14.65.
	In methanol

Reference： [1]Agar, Erbil; Al-Karawi, Ahmed Jasim M.; Awad, Adil A.; Dege, Necmi; Hussein, Zaman Ahmed; Kansiz, Sevgi; Mohammed, Iman Rajab; OmarAli, Al-Ameen Bariz [Acta Crystallographica Section C: Structural Chemistry, 2020, vol. 76, p. 476 - 482]
[2]Al-Karawi, Ahmed Jasim M.; OmarAli, Al-Ameen Bariz; Mangelsen, Sebastian; Dege, Necmi; Kansız, Sevgi; Breuninger, Philipp; Baydere, Cemile; OmarAli, Omar Bariz [Polyhedron, 2021, vol. 198]

47
[ 32315-10-9 ]
[ 456-06-4 ]
[ 121649-18-1 ]

Yield	Reaction Conditions	Operation in experiment
10%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 1h;

Reference： [1]Mahy, William; Willis, Nicky J.; Zhao, Yuguang; Woodward, Hannah L.; Svensson, Fredrik; Sipthorp, James; Vecchia, Luca; Ruza, Reinis R.; Hillier, James; Kjær, Svend; Frew, Sarah; Monaghan, Amy; Bictash, Magda; Salinas, Patricia C.; Whiting, Paul; Vincent, Jean-Paul; Jones, E. Yvonne; Fish, Paul V. [Journal of Medicinal Chemistry, 2020, vol. 63, # 21, p. 12942 - 12956]

48
[ 2631-77-8 ]
[ 456-06-4 ]
C₁₄H₁₁FI₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With sodium cyanoborohydride; acetic acid; In tetrahydrofuran; methanol; for 52h;Reflux;	An appropriate 4-halogenobenzohydrazide (1 mmol) was dissolved in 7 mL of a mixture of THF with MeOH (1:1, v/v), followed by addition of <strong>[2631-77-8]3,5-diiodosalicylaldehyde</strong> (411.3 mg, 1.1 mmol). After a complete dissolution, sodium cyanoborohydride (100 mg; 1.6 mmol) and glacial acetic acid (100 µL) were added. The mixture was heated under reflux for 4 h and then let stir for 48 h at room temperature. After this time, the reaction mixture was diluted with distilled water and let stir for 30 min. Then, the mixture was evaporated to dryness and suspended in a small volume of MeOH. After additional 2 h, the resulted precipitate was filtered off and dried to provide pure product.

Reference： [1]Bioorganic and Medicinal Chemistry,2021,vol. 41

49
[ 1948-40-9 ]
[ 456-06-4 ]
C₁₄H₉FI₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol for 2h; Heating;	2.1.2.1 Synthesis of hydrazide-hydrazones 1 and 2 General procedure: Briefly, 4-substituted benzohydrazides (1 mmol) were treated with 2- or 4-hydroxy-3,5-diiodobenzaldehyde (for hydrazones 1 and 2, respectively; 1.1 mmol; 411.3 mg) in boiling methanol for 2 h. The hydrazide-hydrazones spontaneously precipitated were crystallized from MeOH if necessary.29

Reference： [1]Krátký, Martin; Konečná, Klára; Brablíková, Michaela; Janoušek, Jiří; Pflégr, Václav; Maixnerová, Jana; Trejtnar, František; Vinšová, Jarmila [Bioorganic and Medicinal Chemistry, 2021, vol. 41]

50
[ 456-06-4 ]
[ 541-41-3 ]
[ 121649-18-1 ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine In N,N-dimethyl-formamide at 0 - 20℃; for 20h;

Reference： [1]Soldatova, Natalia S.; Semenov, Artem V.; Geyl, Kirill K.; Baykov, Sergey V.; Shetnev, Anton A.; Konstantinova, Anna S.; Korsakov, Mikhail M.; Yusubov, Mekhman S.; Postnikov, Pavel S. [Advanced Synthesis and Catalysis, 2021, vol. 363, # 14, p. 3566 - 3576]

51
[ 456-06-4 ]
[ 34595-22-7 ]
(E)-4-fluoro-N'-((2-(piperidin-1-yl)pyridin-3-yl)methylene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With acetic acid In ethanol at 20℃;	General experimental procedure for the preparationof (E)-N'-(pyridin-3-ylmethylene) benzohydrazides, 3a-y General procedure: Glacial acetic acid (0.2 mL) was added to a stirredsolution of nicotinaldehyde 1a (1.0 mmol), benzohydrazide 2a (1.0 mmol) in absolute ethanol (3 mL) at RT and the contents were stirred at the same temperature. After completion of the reaction (TLC, 1h), the reaction mixture was filtered through Whatman filter paper and compound wasrecrystallized from ethanol to afford (E)-N'-(pyridin-3-ylmethylene)benzohydrazide 3a as colourless solid.The compounds 3b-y were prepared by the reaction ofnicotinaldehydes 1a-b with benzohydrazides 2a-eunder above conditions. All the prepare compoundsare unknown and well characterized by spectral data.

Reference： [1]Anusha; Praveena; Zehra; Tiwari; Prakasham; Raju, B. China [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2021, vol. 60, # 1, p. 117 - 126]

52
[ 456-06-4 ]
[ 4755-77-5 ]
[ 950259-82-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-fluorobenzoyl hydrazide; Ethyl oxalyl chloride With triethylamine In dichloromethane at -10 - 25℃; for 9h; Stage #2: With triethylamine; p-toluenesulfonyl chloride In ethanol

Reference： [1]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]

53
[ 456-06-4 ]
[ 556-61-6 ]
[ 138417-35-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-fluorobenzoyl hydrazide; methyl thioisocyanate In ethanol at 80℃; for 3h; Stage #2: With sodium hydroxide at 100℃; for 4h;

Reference： [1]Duan, Wen-Gui; Huang, Mei; Li, Bao-Yu; Lin, Gui-Shan [Molecules, 2021, vol. 26, # 22]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	456-06-4	MDL No. :	MFCD00060562
Formula :	C₇H₇FN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UIVXXFYJRYVRKJ-UHFFFAOYSA-N
M.W :	154.14	Pubchem ID :	9972
Synonyms :

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	37.3
TPSA :	55.12 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.22 cm/s

Log Po/w (iLOGP) :	1.09
Log Po/w (XLOGP3) :	0.03
Log Po/w (WLOGP) :	0.85
Log Po/w (MLOGP) :	1.56
Log Po/w (SILICOS-IT) :	0.62
Consensus Log Po/w :	0.83

[ CAS No. 456-06-4 ] {[proInfo.proName]}

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[ 456-06-4 ] Synthesis Path-Upstream 1~8

[ 456-06-4 ] Synthesis Path-Downstream 1~53

Related Functional Groups of
[ 456-06-4 ]

Fluorinated Building Blocks

Aryls

Amides

Hydrazides

Amines

Hydrazines

Precautionary Statements-General

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.09
Solubility :	12.6 mg/ml ; 0.082 mol/l
Class :	Very soluble
Log S (Ali) :	-0.74
Solubility :	28.1 mg/ml ; 0.182 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.3
Solubility :	0.769 mg/ml ; 0.00499 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.08

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

Yield	Reaction Conditions	Operation in experiment
100%	With hydrazine hydrate In ethanol at 20 - 85℃; for 10 h; Reflux	To a stirred solution of 4-flouroethylbenzoate (4.5 g, 26.7 mmol) in EtOH (30 mL) was added NH₂NH₂.H₂0 (6.67 g, 133.5 mmol) at room temperature and the solution refluxed at 85°C for 10 h. The reaction was cooled to room temperature, concentrated under reduced pressure, and the solid washed with n-hexane (50 mL) and then dried to obtain 4-fluorobenzohydrazide as a solid (4.2 g, quantitative yield). 1H NMR (400 MHz, DMSO-d₆): δ 9.85 (s, 1H), 7.86 (dd, 2H), 7.25 (t, 3H), 4.46 (s, 1H), 3.47 (br s, 1H).
97%	With hydrazine hydrate In ethanol; waterReflux	General procedure: Hydrazides (30–58) were synthesized by one pot conventionalmethod24 Benzoic acid or its derivative (10 mmol) was dissolvedin ethanol (20 mL). Sulfuric acid (3 N, 2 mL) was added and thereaction contents were refluxed for six hours. The reaction wasmonitored with TLC. After the completion of the reaction, the reactionmixture was neutralized by adding solid NaHCO3, and filteredto remove excess of NaHCO3. In the neutralized reaction mixture which contains ethyl ester, hydrazine monohydrate (1.5 mL,3 mmol) was added and refluxed for 3–6 h to complete the reaction.Ethanol and unreacted hydrazine were removed by distillationupto 1/3 volume. The reaction contents were cooled, filteredand recrystallized from methanol to obtain the desired hydrazidecrystals (see Supporting information).
83%	With hydrazine hydrate In ethanol at 80℃; for 4 h;	First, 10 g of 4-fluoroethyl benzoate and 30 mL of ethanol were put in a 100 mL three-neck flask, and stirred. Then, 10 mL of hydrazine monohydrate was added to this mixed solution, and heated and stirred at 80 °C for 4 hours to be reacted. The reaction mixture was added to 100 mL of water, and a solid was precipitated. This solid was subjected to suction filtration and washed with a mixed solvent of ethanol and hexane, so that 4-fluorobenzoylhydrazine was prepared (a white solid, yield: 83 percent). The synthetic scheme of Step 1 is shown by (a-2).

Yield	Reaction Conditions	Operation in experiment
83%	With hydrazine hydrate In methanol for 5 h; Reflux	General procedure: To a solution of an appropriate methyl esters17(a–j) (1.0 mmol) in 50 mL of methanol was added 99 percenthydrazine 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.
80%	With hydrazine hydrate In ethanol at 40℃;	General procedure: Various methyl benzoate 8A-V (1.0 equiv) reacted with hydrazine hydrate (excess amount) in anhydrous ethanol. The reaction was stirred at 40 °C for overnight. The ethanol was removed under reduced pressure. The products were purified by recrystallization, which were washed with ethyl ether. The products were obtained as white solid.
75%	With hydrazine hydrate In ethanol for 5 h; Reflux	General procedure: Compound 12 (0.013 mol) and 80percent NH2NH2H2O (5 mL) wereadded to EtOH (10 mL), the mixturewas stirred under reflux for 5 h.After being cooled to room temperature, the precipitate was obtainedby filtration, and was dried to give the title compounds,respectively.4.1.7.1. 4-Fluorobenzohydrazide (13a). A white solid. Yield: 75percent. Mp161.9e164.4 C. 1H NMR (400 MHz, DMSO-d6) d 9.78 (s, 1H,eNHeN), 7.83e7.93 (m, 2H, ArH), 7.22e7.33 (m, 2H, ArH), 4.48 (s,2H, eNHeNH2). ESI-MS m/z: 155.1 [M H].

50%	With hydrazine hydrate In ethanol for 24 h; Reflux	General procedure: Various benzohydrazides 5-7 and 9-13 were obtained accordingto known procedures [40,65] except for benzohydrazides 4and 8 which were commercially available. A solution of the methylbenzoate (1 equiv) in ethanol was added dropwise to 65percent hydrazinemonohydrate (5 equiv). The reaction mixture was then heatedunder reflux and stirred overnight. The reaction progress was followedup by TLC. Crude product was collected by filtration aftercooling of the reaction medium and finally washed with coldethanol unless specified otherwise. The desired benzohydrazides were used without any further purification.The analysis of spectral data (1H and 13C NMR), the yields, HRMS,Mp and Rf of these precursors are presented in SupplementaryInformation.
280 mg	Reflux	General procedure: 4-fluorobenzoic acid as the raw material, methanol as a reaction solvent, a small amount of concentrated sulfuric acid catalyst, followed by stirring under heating at reflux, thin layer chromatography (TLC) to track progress of the reaction, a certain amount after the completion of the reaction NaHCO₃Solution for hydrazine and the reaction liquid solution to give ester intermediate (3-1), continue to add more than the corresponding proportion of hydrazine hydrate reaction mixture was heated with stirring at reflux, thin layer chromatography (TLC) to track progress of the reaction, the reaction after completion of the reaction solution was added to a certain amount of water, then a large amount of white sink to the bottom, suction filtration to afford intermediate hydrazides (3-2)

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