Nitriles, acid catalyzed addition alcohols

Citral readily forms acetals by acid-catalyzed addition of alcohols or by the use of trialkoxyorthoformates. Citral dimethyl acetal [7549-37-3] is stable under alkaline conditions, whereas citral is not. Neryl and geranyl nitriles can be made by oximation of citral and dehydration of the intermediate oxime. For instance, geranonitrile [31983-27-4] is made as follows ... 

Acid-catalyzed addition of hydrazoic acid to carboxylic acids, aldehydes and ketones to give amines, nitriles and amides, respectively. Tertiary alcohols and substituted alkenes yield imines upon treatment with hydrazoic acid ... 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

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... 

The base-catalyzed addition of alcohols to nitriles to give imidates proceeds well, if there are electron-attracting groups in the a-position. In such cases the Pinner synthesis is less effective, because nitrile basicity is less. TTiis shows that both methods are complementary. Recently attention has been paid to the long-known addition of alcohols to trichloroacetonitrile, since it was found that imidates prepared from protected saccharides, amino alcohols etc. and trichloroacetonitrile are useful reagents for the synthesis of nucleosides, disaccharides and other natural products. The trichloroacetimidic acid esters (240 equation 131) of fluorinated, unsaturated aliphatic alcohols °° and benzyl alcohol have been prepared for synthetic purposes. 

Miscelleneous Applications. The method of choice for the regioselective opening of benzylic and tertiary epoxides with alcohols (eq 13) appears to be a reaction mediated by organ-otin phosphate condensate (OPC) , which is readily prepared from DBTO and tributyl phosphate. DBTO catalyzes rearrangement of 3-hydroxy-2-oxo carboxylic acid esters (eq 14), a reaction reminiscent of a similar one mediated by the enzyme reductoisomerase. DBTO has been used as a catalyst for the addition of Azidotrimethylsilane to nitriles for the production of tetrazoles (eq 15). 

Abstract Progress in the field of inter- and intramolecular additions of oxygen nucleophiles (water, alcohols, phenols, and carboxylic acids) to alkenes, allenes, alkynes, and nitriles catalyzed by Co, Rh, Ir, Ni, Pd, and Pt is critically reviewed. 

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