Hydrochloric Acid → 4-Chloro-3-cyanobenzoic acid

Participants

Reaction Conditions

Reaction Steps

3-Amino-4-chlorobenzoic acid (18.72 g, 109.1 mmol), commercially available, was added to a mixture of water (200 mL) and 37% HCl (35 mL), and the resulting slurry was cooled to 5° C. A solution of NaNO2 (8.65 g, 125 mmol) in water (70 mL) was added dropwise, and the solution stirred at 5° C for 30 min. The solution was then added to a slurry consisting of water (400 mL), CuCN (9.85 g, 109 mmol),and KCN(12.06g, 185 mmol), while maintaining the temperature at5°-10° C. The mixture was stirred at 10° C. for another 30 min, and then heated to 80° C. for 1 hour. The reaction was cooled, and the pH adjusted to ~1 by addition of concentrated HCl. The solution was extracted with 5× CHCl3, and the combined extracts were rinsed with 1M HCl and brine, and dried over MgSO4. The solvent was removed in vacuo, and the crude product was recrystallized from CHCl3 /EtOAc to yield 15.9 g (80%) of the title compound. m.p. 180° C. 1H NMR (300 MHz, CDCl3) δ 10.55 (br s, 1H), 8.42 (d, 1H), 8.26 (dd, 1H), 7.68 (d, 1H). MS (DCI/NH3) m/e 213 (M+NH4)+.

Provenance & Evidence