4-Fluorobenzoic acid hydrazide

White solid

To a stirred solution of 4-flouroethylbenzoate (4.5 g, 26.7 mmol) in EtOH (30 mL) was added NHGeneral 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).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).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: 57percent).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.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.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].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.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 NaHCO

Molecular Weight:154.14
XLogP3:0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:154.05424101
Monoisotopic Mass:154.05424101
Topological Polar Surface Area:55.1
Heavy Atom Count:11
Complexity:143
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes