67608-58-6

The general procedure for the synthesis of 4-amino-2-hydroxybenzonitrile from 2-hydroxy-4-nitrobenzonitrile is as follows: 1. 5-Amino-2-chlorophenol was synthesized from 2-amino-5-nitrophenol by a two-step reaction: a) Formation of diazonium salt using NaNO2 and subsequent reaction with CuCl to produce 2-chloro-5-nitrophenol in 68% yield. b) Careful reduction of nitro with H2 (1 atm) in the presence of Adam's catalyst gave the final amine derivative in 57% yield. 2. Synthesis of 5-amino-2-ethyl/n-propyl/cyclopropyl phenol was carried out in four steps starting from the corresponding 2-ethyl/cyclopropyl/n-propyl amine: a) Nitration reaction with potassium nitrate in the presence of sulfuric acid to give the corresponding 5-nitro-2-alkylaniline. b) Reaction with NaNO2 followed by reaction with H2O at 80°C for 2 hours to produce the corresponding 5-nitro-2-alkylphenol derivatives. c) Finally, the corresponding amine derivatives were obtained by hydrogenation of the nitro group. 3. Synthesis of 2-methoxy-4-hydroxybenzyl cyanide: a) Obtained by hydrolysis of methyl ether of 2-methoxy-4-nitrobenzonitrile with LiCl. b) Subsequently, the nitro group was reduced with SnCl2-2H2O in the presence of 6N HCl.

[1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 1, p. 132 - 135
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 3, p. 668 - 671
[3] Patent: WO2007/38387, 2007, A2. Location in patent: Page/Page column 24; 25
[4] Justus Liebigs Annalen der Chemie, 1912, vol. 390, p. 23
[5] Patent: US6140353, 2000, A