An improved synthesis of 4-aminobutanenitrile from 4-azidobutanenitrile and comments on room temperature stability

Abstract

4-Aminobutanenitrile (1) is an important synthetic intermediate for neurological disorder therapeutics including Parkinson’s and Alzheimer’s diseases, and is an industrial precursor to pyrroline and pyrrolidine. Synthesis of 1 by Co(II) catalyzed reduction of 4-azidobutanenitrile (2) with NaBH4, or by a one-pot Staudinger reduction of 2 in THF, was low yielding. 1H-NMR analysis of the Staudinger reduction revealed the formation of iminophosphorane intermediate (3) after 22 h at rt, and that increasing the reaction temperature from rt to 40 °C promoted hydrolysis of 3 to 1. A modified Staudinger reduction of 2 involving pyridine as solvent, addition of water 3 h after triphenylphosphine, and a temperature increase to 40 °C, gave rise to 1 in 69% yield. 1 is unstable at rt, thus the hydrochloride salt of 1 (1⋅HCl) was prepared by bubbling HCl(g) through a solution of 1 in chloroform. 1⋅HCl is stable at rt and is hence the preferred form for storage.