4-Chlorobutyronitrile Explained

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.

Synthesis

It is prepared by the reaction of potassium cyanide with 1-bromo-3-chloropropane.

Cyclopropyl cyanide is prepared by reaction of 4-chlorobutyronitrile with sodium amide in liquid ammonia.[1] However an increased yield was reported when the base/solvent mixture was changed to NaOH/DMSO.[2]

Drug use

4-Chlorobutyronitrile is a precursor to the drugs buflomedil and buspirone.

Precursor

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.[3]

References

  1. Schlatter. M. J.. Organic Syntheses. Cyclopropyl Cyanide. 1943. 23. 20. 10.15227/orgsyn.023.0020.
  2. J Bacha & C Selwitz, (1974 to Chevron USA Inc).
  3. N-Vinylpyrrolidin-2-One as a 3-Aminopropyl Carbanion Equivalent in the Synthesis of Substituted 1-Pyrrolines: 2-Phenyl-1-Pyrroline . Organic Syntheses . 1998 . 75 . 215 . 10.15227/orgsyn.075.0215 .