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.

摘要

4-氨基丁腈（1）是神经疾病治疗剂（包括帕金森氏病和阿尔茨海默氏病）的重要合成中间体，并且是吡咯啉和吡咯烷的工业前体。通过Co（II）催化用NaBH ₄还原4-叠氮基丁腈（2）或通过在THF中一锅法将Staudinger还原2合成1的收率低。Staudinger还原的¹ H-NMR分析表明，在室温下22 h后形成亚氨基膦烷中间体（3），并且将反应温度从rt升高至40°C促进了3到1的水解。改良的Staudinger还原反应（包括吡啶作为溶剂）还原为2，在三苯膦后3 h加入水，温度升至40°C，产率为69％（1）。1在室温下不稳定，因此通过将HCl _（g）鼓泡通过1在氯仿中的溶液来制备1的盐酸盐（1⋅HCl）。1⋅HCl在室温下稳定，因此是储存的首选形式。