4-Methoxybenzohydrazide

4-Methoxybenzohydrazide was synthesized according to the literature[22]. A mixture of methylmethoxybenzoate (1.66 g, 0.01 mol) andhydrazine hydrate (3.6 ml, 0.06 mol) in ethanol (20 mL) was heatedunder reflux for 6 h. The solvent was removed and the precipitate wasobtained. The solid product was recrystallized with ethanol to give 4-methoxybenzohydrazide as colorless crystals. Yield 96percent, mp 138–139 °C.Example I 4-methoxy-benzoic acid hydrazide A solution of methyl 4-methoxybenzoate, (5.0 g, 0.03 mol) in methanol (20 mL) was treated with hydrazine hydrate (12.0 g, 0.24 mol) and the mixture stirred at 45° C. for 24 hours. The reaction mixture was concentrated and the residue partitioned between EtOAc (50 mL) and water (20 mL). The aqueous layer was extracted with EtOAc (3.x.20 mL), and the combined organic extracts washed with brine (20 mL), dried over NaIn the 500 ml round bottom flask is added 53.15g (0.32 µM) 4 - methoxybenzoic acid methyl ester, 300ml50percent hydrazine hydrate reflux 4h, changing device, for the majority of the solvent water pump by reducing pressure, the residual liquid is separated out light yellow crystal after cooling, filtering, drying, and for using ethanol to recrystallize the decolorize with active carbon, to obtain white crystal, yield 88percentGeneral procedure: To a solution of the appropriate methyl benzoate ester (1.0 mmol) in ethanol (30 mL), hydrazine monohydrate (0.15 g, 3.0 mmol) was added. The reaction mixture was heated under reflux overnight. After completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was washed with water (2 x 3 mL), and the obtained solid was filtered and dried to give benzohydrazide derivatives 3a-c.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: A solution of hydrazine hydrate (20.00 mmol) in 2 mL EtOH was added dropwise to the ester 2 (5.00 mmol). The mixture was refluxed for 5 h and filtered, and the corresponding acid hydrazide 3 was obtained by washing the residue with ice water.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.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).General procedure: Ethylbenzoates (11-15, 1.5g, 9.98 mmol)and ethyl-2-phenylacetates (16-20, 1.5g, 9.13 mmol)were dissolved in ethanol and then hydrazine-hydrate(99percent) was added and reux for 8-12h. Ethanol wasconcentrated and the resultant residue was pouredin ice cold water and stirred for 15 -20 min, the solidsthat were thrown out was fltered at the pump anddried to obtain the corresponding benzohydrazides(21-25) and 2-phenylacetohydrazides (26-30) in 80-82percent yield.To a mixture of 2 (25.0 g, 0.1387 mol) in ethanol (200mL) at 0-5 °C, hydrazine hydrate (13.87 mL, 0.2774 mol) was added. The reaction mass was heated to reflux for 2.0 h. The reaction completion was monitored by TLC. The reactionmixture was cooled to 0-5 °C stirred for 60 min. The solid formed was filtered and dried to get compound 3 as white solid (Yield: 18.4 g, 80percent).General procedure: A solution of the isolated esters 2a–e (10mmol) in ethanol (20mL), hydrazine hydrate (97percent, 3mL) was added and heated under reflux for 5–8h. After cooling, the formed precipitate was filtered off, washed with water, dried, and crystallized from ethanol.General procedure: Hydrazine hydrate (97percent, 30 mmol, 1.5 mL) was added to a solutionof the isolated esters 2a–e (10 mmol) in ethanol (20 mL), and themixture was heated at reflux for 5–8 h. After cooling, the resultingprecipitate was filtered off, washed with water, dried, and crystallizedfrom ethanol.General procedure: Hydrazine monohydrate (5 mmol) was added dropwise to a solution of compounds 1A-C (1mmol) in EtOH. The mixture was refluxed for 12 h, and then the solvent was removed by rotary evaporation. The residue was treated with water and extracted with CHGeneral procedure: Acyl hydrazides were synthesized in excellent yields from thereaction of substituted aryl acids (0.010 mol) with hydrazine hydrate(0.012 mol) in absence of organic solvents under microwaveirradiation (300 W, 250 C) for 4e8 min. Spectral analysis of thesynthesized hydrazides are consistent with the proposed structuresand with those reported [58].Compound 1b is prepared by reacting compound 1a (1 mmol), 1, 2-dichloroethane (DEC) (12 mL) and chlorinating agent (0.4 mL) while refluxing for 3 hours. Then, the obtained solution was cooled at room temperature After removal of the solvent under reduced pressure, compound 1b is obtained, which is subjected to the next step without further purification . The compound Compound 1b was dissolved in acetonitrile (80 mL), and hydrazine hydrate (1 mmol), Was added dropwise to a solution containing TEA (0.5 mL) and acetonitrile (20 mL), which was monitored by TLC, Respectively. After the reactants were exhausted, the reaction mixture was cooled to room temperature. Subsequently, the solvent was evaporated under reduced pressure to give To give crude 4-methoxybenzohydrazide (Compound 1c) as a white solid, which was purified by column chromatography Purification by column chromatography and crystallization in methanol gives the product (Compound 1c).General procedure: These compounds were prepared using the standard procedure at 130°C for 20–24h. For each reaction, the crude product was adsorbed onto silica gel and purified on a 15cm×2.5cm silica gel column eluted with 80percent EtOAc in hexanes. The isolated yields are given in Table 7.

Molecular Weight:166.18
XLogP3:0.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:166.074227566
Monoisotopic Mass:166.074227566
Topological Polar Surface Area:64.4
Heavy Atom Count:12
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes