A-Iminonitriles

Isothiazoles can be prepared from thionyl chloride and a-aminoketones, a-iminoketones, a-iminonitriles, or acrylonitriles the reactions concerned have been discussed.62... 

When an anion exchange resin Amberlite IRA 400 [CN-] is used as a cyanating agent, the final products of the aldonitrone cyanating reaction are a-iminonitriles (Scheme 2.173) (Table 2.14) (634). 

The syntheses by Naito and co-workers of 4-hydroxy, 4-cyano, and related isothiazoles from a-iminoketones or a-iminonitriles and sulfuryl or thionyl chloride29,30 may be envisaged as a variant of the general method if it is assumed that the reagents introduce a sulfur atom and also provide chlorine for oxidative cyclization (Scheme 10). 

The approach can be modified slightly by the use of a-keto-substituted acids or their esters 249 instead of a-iminonitriles to obtain triazines 250-252 (Scheme 148). 

A one-pot three-component synthesis of a-iminonitriles 866 via an IBX/tetrabutylammonium bromide-mediated oxidative Strecker reaction has been developed (Scheme 3.346) [1183]. This methodology was employed in a two-step synthesis of indolizidines via a microwave-assisted intramolecular cycloaddition of a-iminonitriles. 

Based on a previously developed woik by Yus and coworkers [57], Zhu s group described a novel three-component synthesis of substituted a-iminonitriles 60 using 2-iodoxybenzoic acid (IBX) as oxidant and a catalytic amount of tetrabutylammonium bromide (TBAB) and affording final products in good to excellent yields under mild conditions (Scheme 10.17) [58]. 

Electron-rich and electron-poor aromatic aldehydes and a,p-unsaturated aldehydes were all compatible with the oxidative conditions used in this approach. Additionally, Z configuration was assigned to all final a-iminonitriles 60 according to NMR smdies, except for R =Ph. Interestingly, the authors demonstrated the synthetic applicability of this developed methodology in a two-step construction of appealing indolizidine skeletons 61 (Scheme 10.18). 

SCHEME 10.17 Multicomponent Strecker synthesis for the obtainment of a-iminonitriles 60. 

SCHEME 10.18 Synthetie application of a-iminonitriles for the preparation of indohzidines 61. 

In all cases, the final addition of AI2O3 was crucial for the obtainment of the corresponding carboxamides after formation of the corresponding a-iminonitrile intermediates. 

P. Fontaine, A. Chiaroni, G. Masson, J. Zhu, Org. Lett. 2008, 10, 1509-1512. One-pot three-component synthesis of a-iminonitriles by IBX/TBAB-mediated oxidative Strecker reaction. 

J.-B. Gualtierotti, X. Schumacher, P. Fontaine, G. Masson, Q. Wang, J. Zhu, Chem. Eur. J. 2012, 18, 14812-14819. Amidation of aldehydes and alcohols through a-iminonitriles and a sequential oxidative three-component Strecker reaction/ thio-Michael addition/alumina-promoted hydrolysis process to access P-mercaptoamides iiom aldehydes, amines, and thiols. 

Dimethylformamide dimethyl acetal has been used as a methine group source for various heteroring closures, particularly for an efficient 2-step indole synthesis from nitro compounds . The investigation of 3H-1,4-benzodiazepines with their two imino functions, particularly one with an a-iminonitrile function, has been added to the highly versatile chemistry of these heterocyclics Barbituric acid and 2,3,5-trioxopyrrolidine derivatives have been obtained through easy base-catalyzed reactions of active methylene compounds with isocyanates From the neighboring biochemical area come these contributions in preparative enzyme chemistry a-Chymotrypsin as well as citrus... 

New syntheses of a-nitronitriles, 4-arylbutanenitriles, mercapto-acetonitrile, a-iminonitriles, 2-cyanopyrroles, and 3-cyano-4-azahomo-adamantanes have also been reported. 

Methyl has been proved as a practical carbon source of cyano groups. Jiao and co-workers developed a transition-metal-ffee transformation of methyl imines [123]. They employed PIDA as the oxidant and 2 equiv. of NaBr as additive. A variety of methyl imines 11 prepared by the condensation of anilines and acetophenones could work under the optimized condition to give a-iminonitriles 12 (Scheme 4.25). On the aromatic ring of acetophenones, for example, many electron-donating and—withdrawing groups were tolerated (13-15, 17-20). 

Scheme 4.25 Direct transformation of methyl imines to a-iminonitriles...

Zong H, Huang H, Liu J, Bian G, Song L (2012) Added-metal-free catalytic nucleophilic addition of grignard reagents to ketones. J Org Chem 77(10) 4645 652 Chen F, Huang X, Cui Y, Jiao N (2013) Direct transformation of methyl imines to a-iminonitriles under mild and transition-metal-free conditions. Chem Fur J 19(34) 11199-11202... 

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