Benzocaine → Ethyl 4-hydrazinylbenzoate hydrochloride

Participants

Reaction Conditions

Reaction Steps

To a cooled (-13° C.) and stirred suspension of ethyl 4-aminobenzoate (100 g, 605.3 mmol) in concentrated hydrochloric acid (780 ml) was added dropwise a solution of sodium nitrite (43.9 g, 635.9 mmol) in water (312 ml) at such a rate as to keep the temperature below -4° C. (ca 50 minutes). After being stirred for further 10 minutes at -5° C., the mixture was quickly filtered to remove solids and the clear yellow filtrate was added portionwise to a cooled (-20° C.) and stirred solution of tin (II) chloride dihydrate (682.9 g, 3.02 mmol) in concentrated hydrochloric acid (470 ml) at such a rate as to maintain the temperature below -10° C. (ca 25 minutes). The resulting mixture was allowed to warm to -5° C. over 25 min and the solid was collected by filtration, washed with diethyl ether (2×300 ml) and dried over phosphorous pentoxide-potassium hydroxide at 60° C. in vacuum oven to give 131.8 g (100%) of the title compound as a white solid. A sample recrystallized from absolute ethanol showed: mp 208°-212° C. (needles); δH (360 MHz, DMSO-d6) 10.42 (3H, br s, --N+H3), 8.92 (1H, br s, --NH--), 7.86 (2H, d, J=8.8 Hz, Ar-H), 7.01 (2H, d, J=8.8 Hz, Ar-H), 4.26 (2H, q, J=7.1 Hz, --OCH2 --), 1.30 (3H, t, J=7.1 Hz, --CH3); m/z (CI) 181 (M+ +1).

Provenance & Evidence