4-(Benzoylamino)benzoic acid

b) 4-Benzamidobenzoic acid (A 13) To a solution of methyl 4-benzamidobenzoate A12 (1.00 g, 3.92 mmol) in 4: 1 : 1 v/v THF/MeOH/water (30 mL) was added LiOH H20. Og (0. 16MOL) of benzoic acid was dissolved in 250M. OF PYRIDINE and then was cooled in a ice bath of 10C. Thereto, 23. 1g (0. 21MOL) of ethyl CHLOROFORMATE was added dropwise for 30 minutes. The mixture was stirred at room temperature for 2 hours and then filtered to remove salts, to give an anhydride (30.2g, 0. 15MOL). 24. 1G (0. 16MOL) of metyl aminobenzoate was dissolved in 250MQ of pyridine and then was cooled in a ice bath of 10 C. Thereto, the anhydride formed in the previous step was added dropwise for 30 minutes. The mixture was stirred for another 2 hours. After distillation of the solvent, the residue was dissolved in 300MQ of ethyl acetate. The ethyl acetate solution was washed with 5percent hydrochloric acid and with distilled water, dried over magnesium sulfate, decolorized with active charcoal, and then filtered. The filtrate was dried under reduced pressure, to give methyl 4- (PHENYLCARBONYLAMINO) benzoate (34.7g, 85percent yield) as a pale yellow solid. Subsequently, 34.7g of methyl 4- (phenylcarbonylamino) benzoate was dissolved in 500MQ of methanol and thereto 50MQ OF 10percent KOH was added. After stirring for 3 hours, the mixture was neutralized with hydrochloric acid and then filtered, to give an acid compound, 4- (phenylcarbonylamino) benzoic acid (26.2g, 80percent yield). 4- (phenylcarbonylamino) benzoic acid formed (24. 1g, 0. 10MOL) was dissolved in 200MQ of pyridine and then was cooled in a ice bath of 10C. Thereto, 22.9g (0. 13MOL) of ethyl CHLOROFORMATE was added dropwise for 30 minutes. The mixture was stirred at room temperature for 2 hours and then filtered to remove salts, to give an anhydride (38. 7g, 0. 12MOL). 6.9g (0. LOMOL) of hydroxylamine hydrochloride was dissolved in LOOM-C of pyridine and then was cooled in a ice bath of 10C. Thereto, the anhydride formed in the previous step was added dropwise for 30 minutes. The mixture was stirred for another 2 hours. After distillation of the solvent, the residue was dissolved in 300MQ of ethyl acetate. The ethyl acetate solution was washed with 5percent hydrochloric acid and with distilled water, dried over magnesium sulfate, decolorized with active charcoal, and then filtered. The filtrate was dried under reduced pressure, to give a final product, N- [4- (N-HYDROXYCARBAMOYL) phenyl] benzamide (16. 6g, 65percent yield) as a pale yellow solid. TLC (in ethyl acetate: hexane = 1: 1); RF= 0. 53 H-NMR (DMSO-d6): 611. 23 (s, 1H), 10.39 (s, 1H), 9.04 (s, 1H), 8.01 (m, 5H), 7.64 (m, 4H).PREPARATION EXAMPLE EX45 (0284) This example demonstrates the production of 4-benzoylamino benzoic acid having the following structure (0285) (0286) In a 1 L beaker with mechanical stirring, 27.4 g of 4-aminobenzoic acid (0.2 mol) was mixed in 300 mL of DI HGeneral procedure: Aromatic halides (1.0 equivalent) were added dropwise to the stirred solution of aminobenzoic acids (200 mg) in pyridine. Mixtures were stirred at room temperature for about all target derivatives except of benzyl based derivative. The pH of reaction mixtures was kept basic using pyridine. Progress of the reaction was monitored using TLC plates. Upon complete formation of target compounds, the desired products were filtered as white precipitates. For benzyl based derivatives reaction mixture was refluxed for more than 24 hours and product was obtained by evaporating the solvent under vacuum.PREPARATION EXAMPLE EX45 (0284) This example demonstrates the production of 4-benzoylamino benzoic acid having the following structure (0285) (0286) In a 1 L beaker with mechanical stirring, 27.4 g of 4-aminobenzoic acid (0.2 mol) was mixed in 300 mL of DI H2O. Then, 21.2 g (0.2 mol) of sodium carbonate was added until the pH value became 9.1 and all the 4-amino benzoic acid dissolved in the water. (0287) Then, 56.24 g (0.4 mol) of benzoyl chloride was added dropwise to the beaker at room temp. The reaction was stirred overnight. A solid formed during the reaction, and the pH stabilized at 4.0. The pH was further lowered to about 2 with hydrochloric acid. The product was collected by filtration and washed with hot water to remove excess benzoic acid. The solid product was dried in an oven at 110° C. and 44.21 g of the product was obtained (yield 96.7percent).General procedure: Aromatic halides (1.0 equivalent) were added dropwise to the stirred solution of aminobenzoic acids (200 mg) in pyridine. Mixtures were stirred at room temperature for about all target derivatives except of benzyl based derivative. The pH of reaction mixtures was kept basic using pyridine. Progress of the reaction was monitored using TLC plates. Upon complete formation of target compounds, the desired products were filtered as white precipitates. For benzyl based derivatives reaction mixture was refluxed for more than 24 hours and product was obtained by evaporating the solvent under vacuum.General procedure: A solution of aminobenzoic acid in dichloromethane at room temperature was treated with triethylamine and stirred for 30 min to obtain a pellucid solution. The substituted benzoyl chloride was then slowly added. After precipitates were observed, the mixture was stirred at room temperature for another 2 h. The suspension was concentrated under reduced pressure, and the residue was purified by hot acetic acid to give compounds 4a-f.

Molecular Weight:241.24
XLogP3:2.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:241.07389321
Monoisotopic Mass:241.07389321
Topological Polar Surface Area:66.4
Heavy Atom Count:18
Complexity:302
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes