Nitriles, acid catalyzed addition reactions

SCHMIDT REACTION. Acid catalyzed addition of hydrazonic acid to carboxylic acids, aldehydes, and ketones to give amines, nitriles, and amides, respectively. 

Acid-catalyzed addition of water to an amide, though itself a slow reaction, is inherently faster than acid-catalyzed addition of water to a nitrile, even though the equilibrium constant for the latter reaction is much less unfavorable. This is again a result of the difference in angular distortion see Fig. 9. For the amide reaction, the distortions are the same as for the ester example above three times... 

Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Review the mechanism of base-catalyzed nitrile hydrolysis in Section 20.7, and then write all the steps involved in the acicl-catalyzed reaction, using curved arrows to represent electron flow in each step. 

In addition, the mechanism of the zinc-catalyzed [3+2] dipolar cycloaddition of azides and nitriles to form tetrazoles was examined <2003JA9983>. The energy barrier of the reaction is lowered by 5-6kcalmol 1 which corresponds to an acceleration of 3 1 orders of magnitude. The source of the catalytic activity seems to be the coordination of the Lewis acidic zinc halide to the nitrile, which is supported by model calculations. Also AICI3 was examined as another Lewis acid which catalyzes the reaction to a greater extent than ZnBr2-... 

An alternate route to substituted tetrahydrobenzazepines (Scheme 33) commenced with the Michael addition of the ester 351 to acrylonitrile in the presence of Triton B, and the intermediate cyanoester was converted to 352 by reduction of the ester function with lithium borohydride and O-benzylation (168). Base-induced hydrolysis of the nitrile group of 352 delivered the corresponding acid, which was transformed to 353 via a Curtius rearrangement. Subjection of 353 to a modified two-step Tschemiac-Einhom reaction involving AMiydroxymethyla-tion and subsequent acid-catalyzed cyclization gave 354. 

It is now believed that the acid-catalyzed reaction of the aldehydes with nitriles leads first to Af-acyliminium ions 2 which can undergo both addition to the nucleophilic... 

Acid-catalyzed nucleophilic addition of a nitrile to a carbenium ion generated from alcohol (usually tertiary primary alcohols other than benzyl alcohol will not react), yielding an amide. Sanguigni, J.A. and Levine, R., Amides from nitriles and alcohols by the Ritter reaction, J. Med. Chem. 53, 573-574, 1964 Radzicka, A. and Konieczny, M., Studies on the Ritter reaction. I. Synthesis of 3-/5-bartbituryl/-Ipropanesulfonic acids with anti-inflammatory activity, ArcA Immunol. Ther. Exp. 30,421 32,1982 Van Emelen, K., De Wit, T., Hoomaert, G.J., and Compemolle, R, Diastereoselective intramolecular... 

Cationic palladium-catalyzed addition of arylboronic acids to nitriles for the formation of benzo[h]furans was reported <06OL5987>, an example of which is illustrated in the following scheme. The palladium-catalyzed cross coupling of alkynes with appropriately substituted aryl iodides for the synthesis of substituted dibenzofurans in moderate to excellent yields was also achieved <06JOC5341>. The benzo[fc]furan core of heliannuls G and H were constructed by a palladium-catalyzed Ji-allyl cyclization reaction <06TL7353>. The palladium-catalyzed oxidative activation of arylcyclopropanes was applied to the synthesis of 2-substituted benzo[Z>]furans <06OL5829>. 

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