Nitriles intramolecular cyclization, carbonyl

Another electrophilic reaction of the double salt is with carbonyl compounds on addition to benzophenone, the appropriate hydroxyphenylhydrazone 50 is obtained , When the electrophile is an aroyl chloride, 4-acetylpyrazole 51 is obtained whereas reaction with an cster or with an aromatic nitrile gives pyrazole derivatives by addition, followed by an intramolecular cyclization (equation 29). 

Synthetic use of the a-aminonitrile intermediates from the Strecker reaction have also been investigated.46 In this manner, it was possible to assemble the core scaffold of the indolizidine alkaloids 112. Treating 110, which contained the amine component and a dimethoxyacetal as a latent carbonyl component, with cyanide under acidic conditions initiated an intramolecular cyclization to afford the Strecker reaction intermediate a-aminonitrile 111. While one could hydrolyze the nitrile functionality to unmask a carboxylic acid, in this case, the nitrile was used to introduce the requisite sidechains needed in the construction of the indolizidine alkaloids 112. 

The first step in the mechanism is the reaction of DICY with epoxy to form the alkylated DICY. This was confirmed by the imide IR peak at 1570 cm The second step involves further alkylation of the nitrogen that reacted in step 1, to form the AA(-dialkyldicyandiamide. No alkylation of the other amino group was suggested. The third step is the intramolecular cyclization step to form a zwitteri-onic five-membered intermediate. This involves the intramolecular reaction of the secondary alcohol formed in step 2 with the imide functionality (—C=N—). This is in contrast with the Zahir mechanism (112) where the intramolecular cyclization involves the hydroxy and the nitrile groups. The fourth step involves the elimination of ammonia and the formation of 2-cyanimidooxazolidine. The formation of this heterocycle is consistent with the observed bathocromic IR shift from 1570 cm to 1650 cm The ammonia that is eliminated can then react with epoxy to form a trifimctional cross-hnk. The last step involves the hydrolysis of the oxa-zolidine to form the oxazoUdone and cyanamide. The hydrolysis step accounts for the formation of the carbonyl group. 

In general, the initial formation of the a,p-unsaturated nitrile (72) via Knoevenagel condensation of an activated nitrile (69) with a carbonyl compound (71) mediated by a base ( B) is accepted as a proposed mechanism for the three-component Gewald reaction (G-3CR) (Scheme 12.24). Then, after deprotonation of that intermediate (72), it reacts with elemental sulfur (S ) following an S X mechanism, generating sulfated compound (74), which cyclizes to 75 via an intramolecular nucleophihc attack of the sulfur anion to... 

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