74 nitrosyl chloride, reaction with imines

The addition of nitrosyl chloride to imines and the subsequent reaction with nucleophiles provided a route to a wide variety of compounds. Since all operations are easy to carry out in a hood, this synthetic scheme is valuable because of the high carcinogenicity of these a Substituted compounds. 

Since N-nitrosoimmonium ions seem to be involved in the hydrolysis of a-acetates, it should be possible to isolate such species as stable salts. For this purpose, we selected a system such as XVII in which the phenyl group should provide further stabilization of such a carbonium ion. After the reaction of nitrosyl chloride with the corresponding imines, addition of antimony pentachloride resulted in the precipitation of pale yellow solids these could be isolated and stored under nitrogen for several days at room temperature. ... 

The key reaction, based on a method for removing glutamate residues in peptides, involves the conversion of the sole primary amine in the molecule to a diazo function. The most expeditious method consists of reacting (18-1) with nitrosyl chloride. The resulting diazo function in the product (18-2) can be displaced formally by oxygen from the enol form of the amide at the 7 position to form the iminolactone (18-3) the reaction may involve a spontaneous loss of nitrogen followed by capture of the resulting carbocation. Hydrolysis of the imine function in the product the leads to one of the key intermediates in this series, 7-ACA (18-4) [22]. 

The first effective method of side chain cleavage made use of the reaction of (179) with nitrosyl chloride (152). Loss of nitrogen from the intermediate diazo compound (181) gives imine (182) which on hydrolysis provides 7-ACA (180) and the lactone (183). This provided a route to substantial quantities of (180) thus allowing the preparation of many side chain derivatives. Later a more efficient procedure made use of phosphorus pentachloride followed by cleavage of an imino ether (153). The utility of other phosphorus halogen compounds for cleavage of the amide bond has also been described (154). 

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