4-Chlorobenzoic acid hydrazide

white to light beige crystals, flakes or

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).(10.83 mmol) of ethyl 4-chlorobenzoate and 50 mL of absolute ethanol were added to a 100 mL round-bottomed flask and 1.08 g (21.67 mmol) of 80percent hydrazine hydrate was added. The temperature of the oil bath was 80General 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.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: 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 (2) (0.1 mol) was taken in a round-bottom flaskwith methanol (100 mL). Hydrazine hydrate (99percent) (0.15mol, 5.7 mL) was added drop wise with gentle stirring. Thereaction mixture was refluxed for 4–6 h. Excess of methanolwas distilled off under reduced pressure. The precipitatedhydrazide was dried and re-crystallized from methanol(Zamani and Faghihi 2003).General procedure: Pathway A-Hydrazine hydrate 64percent (v/v) (30.0 mL, 0.33 mol) was heated up to 50-60 °C. The methyl ester previously isolated (0.01 mol) was added and the mixture was refluxed during 10 min. The cooling down was proceeded sequentially in a water bath, followed by ice bath and dry ice - ethanol bath. The solid was filtered and washed with cold water. Different conditions were needed to obtain 4-nitro-3-(trifluoromethyl)benzhydrazide (3d) and 4-nitrobenzhydrazide (3 h). Hydrazine hydrate 64percent (v/v) (30.0 mL, 0.33 mol) was cooled down in ice bath to -3 to 2 °C. The respective methyl ester (0.01 mol) was added and the mixture was stirred during 1 hour. The cooling down was proceeded in dry ice - ethanol bath. The solid was filtered and washed with cold water. Pathway B-each substituted benzoic acid (0.01 mol) was refluxed during 4 h in 20.0 mL (0.50 mol) of anhydrous methanol and 0.5 mL (1.0 mmol) of sulfuric acid. The reaction mixture was cooled down to room temperature. and the hydrazine hydrate 80percent (v/v) (10.0 mL, 0.11 mol) was added. The system was maintained into vigorously stirring for more 30 minutes. In the case of compounds with 4-nitro and 4-nitro-3-trifluoromethyl substituent groups attached in the benzene moiety, after the addition of hydrazine hydrate 80percent (v/v) at room temperature, the reaction mixture was cooled down in ice bath and maintained into stirring during 1 hour. After these periods, the mixture was maintained at cold temperature to give 3.General 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.Dissolve 4-chlorobenzoic acid (3. 2g, 20mmol) in methanol (30mL) and slowly add 2mL of thionyl chloride in an ice bath. Heat at 50 ° C for 4h (15mLX3), spin-dried for use; the previous step in 30mL ethanol, 80percent hydrazine hydrate added 4mL, reflux reaction heating (15mLX3), the mixture was cooled to room temperature, 4h, cooling, precipitation of white solid, filter drying, a white solid 2. 5g, yield 74percent.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.The methyl ester of indomethacin (0.01 mol) and hydrazine hydrate (99percent) (0.2 mol) in presence of absolute ethanol (50 mL) were refluxed for 30 h. The reaction mixture was concentrated by using rota vapor and poured in a beaker containing ice while stirring and kept for 4 h at room temperature.The solid was separated out by filtration. The product was dried and recrystallized from ethanol.The product was carefully checked by thin layer chromatography. Two compounds were isolated by column chromatography by using different fractions of n-hexane and ethyl acetate. The first compound was 2-(6-methoxy-2-methyl-1H-indol-3-yl) acetohydrazide compound (1) and was obtained as the major product. The second compound, 4-chlorobenzohydrazide (2) was obtained as minor product. Both the compounds were fully characterized by the spectral data. 2-(6-methoxy-2-methyl-1H-indol-3-yl) acetohydrazide (1). Color: white; Yield: 70percent; m.p.: 168–170 °C; UV max (Methanol) = 280 nm;

Molecular Weight:170.59
XLogP3:1.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:170.0246905
Monoisotopic Mass:170.0246905
Topological Polar Surface Area:55.1
Heavy Atom Count:11
Complexity:143
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes