4-Chlorobutyronitrile

4-Chlorobutyronitrile

Names
Preferred IUPAC name 4-Chlorobutanenitrile
Identifiers
CAS Number	628-20-6  Y
3D model (JSmol)	Interactive image
ChemSpider	11831
ECHA InfoCard	100.010.029
EC Number	211-031-6
PubChem CID	12336
UNII	9JDK6275GP
CompTox Dashboard (EPA)	DTXSID0060850
InChI InChI=1S/C4H6ClN/c5-3-1-2-4-6/h1-3H2 Key: ZFCFBWSVQWGOJJ-UHFFFAOYSA-N
SMILES C(CC#N)CCl
Properties
Chemical formula	C4H6ClN
Molar mass	103.55 g·mol−1
Appearance	colorless liquid
Density	1.0934 g/cm3 @15 °C
Boiling point	189–191 °C (372–376 °F; 462–464 K)
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H301, H315, H319, H335
Precautionary statements	P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
Related compounds
Related compounds	3-Chloropropionitrile Butyronitrile
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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

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. ^[2] However an increased yield was reported when the base/solvent mixture was changed to NaOH/DMSO. ^[3]

Drug use

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

Precursor

Synthesis: Stereoselective:

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, McN-5558 & McN-5847.

More recently, an alternative synthetic protocol was also reported by Maryanoff. ^[7]

References

1. Charles F. H. Allen (1928). "γ-Chlorobutyronitrile". Organic Syntheses. 8: 52. doi:10.15227/orgsyn.008.0052.
2. Schlatter, M. J. (1943). "Cyclopropyl Cyanide". Organic Syntheses. 23: 20. doi:10.15227/orgsyn.023.0020.
3. J Bacha & C Selwitz, U.S. patent 3,843,709 (1974 to Chevron USA Inc).
4. Pollak, Peter; Romeder, Gérard; Hagedorn, Ferdinand; Gelbke, Heinz-Peter (2000). "Nitriles". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_363. ISBN   3527306730.
5. 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.
6. 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. PMID   28294268.
7. "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.