4-Chlorobutyronitrile is the organic compound with the formula ClCH2CH2CH2CN. With both chloro and cyano functional groups, it is a bifunctional molecule. It is a colorless liquid.
Cyclopropyl cyanide is prepared by reaction of 4-chlorobutyronitrile with sodium amide in liquid ammonia.[2] However an increased yield was reported when the base/solvent mixture was changed to NaOH/DMSO.[3]
4-Chlorobutyronitrile has been used as a starting material to prepare 2-phenylpyrrolidine [registry number 1006-64-0]. This in turn is a chief precursor to a family of compounds called pyrroloisoquinolines. These are valuable agents in medicinal chemistry that are endowed with BAT substrate reuptake inhibitor properties, elevating the synaptic concentration of serotonin and/or catecholamines. They therefore have application in the treatment of CNS diseases and eating disorders. A list of all of the known codenamed examples includes the following: JNJ-7925476, McN5652, Mcn-5292, Mcn 5707, McN-5908, McN 4612-z, McN-5558 & McN-5847.
More recently, an alternative synthetic protocol was also reported by Maryanoff.[7]
^Craig, Lyman C.; Bulbrook, Helen.; Hixon, R. M. (May 1931). "A General Method of Synthesis for Alpha-Substituted Pyrrolines and Pyrrolidines". Journal of the American Chemical Society. 53 (5): 1831–1835. doi:10.1021/ja01356a028.
^Zhang, Ying; Kong, Duanyang; Wang, Rui; Hou, Guohua (2017). "Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines". Organic & Biomolecular Chemistry. 15 (14): 3006–3012. doi:10.1039/C7OB00442G. PMID28294268.
^"N-Vinylpyrrolidin-2-One as a 3-Aminopropyl Carbanion Equivalent in the Synthesis of Substituted 1-Pyrrolines: 2-Phenyl-1-Pyrroline". Organic Syntheses. 75: 215. 1998. doi:10.15227/orgsyn.075.0215.
