In this reaction, the nucleophilicCN− ion attacks the electrophilic carbonyl carbon in the ketone, followed by protonation by HCN, thereby regenerating the cyanide anion. Cyanohydrins are also prepared by displacement of sulfite by cyanide salts:[2]
Acetone cyanohydrin, (CH3)2C(OH)CN is the cyanohydrin of acetone. It is generated as an intermediate in the industrial production of methyl methacrylate.[3] In the laboratory, this liquid serves as a source of HCN, which is inconveniently volatile.[4] Thus, acetone cyanohydrin can be used for the preparation of other cyanohydrins, for the transformation of HCN to Michael acceptors, and for the formylationofarenes. Treatment of this cyanohydrin with lithium hydride affords anhydrous lithium cyanide:
Cyanohydrins were first prepared by the addition of HCN and a catalyst (base or enzyme) to the corresponding carbonyl.[5] On a laboratory scale the use of HCN (toxic) is largely not encouraged, for this reason other less dangerous cyanation reagents are sought out. In situ formation of HCN can be sourced using precursors such as acetone cyanohydrin. Alternatively, cyano-silyl derivatives such as TMS-CN allows for both the cyanation and protection in one step without the need for HCN.[6] Similar procedures relying on ester, phosphate and carbonate formation have been reported.[7][8][9]
Different reactions for the preparation of cyanohydrin
Mandelonitrile, with the formula C6H5CH(OH)CN, occurs in small amounts in the pits of some fruits.[2] Related cyanogenic glycosides are known, such as amygdalin.[1]
Amygdalin is one of several naturally occurring cyanogenic glycosides.
Glycolonitrile, also called hydroxyacetonitrile or formaldehyde cyanohydrin, is the organic compound with the formula HOCH2CN. It is the simplest cyanohydrin, being derived from formaldehyde.[10]
^ abCorson, B. B.; Dodge, R. A.; Harris, S. A.; Yeaw, J. S. (1941). "Mandelic Acid". Organic Syntheses; Collected Volumes, vol. 1, p. 336.
^William Bauer, Jr. "Methacrylic Acid and Derivatives" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a16_441. Article Online Posting Date: June 15, 2000
^Haroutounian, S. A. "Acetone Cyanohydrin" Encyclopedia of Reagents for Organic Synthesis 2001, John Wiley & Sons. doi:10.1002/047084289X.ra014
^North, M.; Usanov, D. L.; Young, C. Lewis Acid Catalyzed Asymmetric Cyanohydrin Synthesis. Chem. Rev. 2008, 108 (12), 5146–5226. doi:10.1021/cr800255k.
^Lidy, W.; Sundermeyer, W. Spaltungsreaktionen Des Trimethylsilylcyanids, Eine Neue Darstellungsmethode Für O-(Trimethylsilyl)Cyanhydrine. Chem. Ber. 1973, 106 (2), 587–593. doi:10.1002/cber.19731060224
^Scholl, M.; Lim, C. K.; Fu, G. C. Convenient and Efficient Conversion of Aldehydes to Acylated Cyanohydrins Using Tributyltin Cyanide as a Catalyst. J. Org. Chem. 1995, 60 (19), 6229–6231. doi: 10.1021/jo00124a052.
^Yoneda, R.; Harusawa, S.; Kurihara, T. Cyano Phosphate: An Efficient Intermediate for the Chemoselective Conversion of Carbonyl Compounds to Nitriles. J. Org. Chem. 1991, 56 (5), 1827–1832. doi: 10.1021/jo00005a031.
^Juhl, M.; Petersen, A. R.; Lee, J.-W. CO2‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions. Chem. – A Eur. J. 2020. doi: 10.1002/chem.202003623.
