Ritter products, tertiary

In the Ritter reaction a rather different kind of evidence for the cation is the fact that families of isomeric alcohols all give the same product. In all these cases, rearrangements of the first formed carbocation (Chapter 37) can easily account for the products. Another example in the decalin series is this Ritter reaction with KCN as the nitrile in acidic solution so that HCN is the reagent. The starting material is a spirocyclic tertiary alcohol but the product is a frans-decalin formed by... 

Tertiary alcohols tend to react without rearrangement while secondary alcohols are liable to do so, equations (14) and (15), as discussed in Section 1.9.1.2. Primary alcohols normally fail to react with nitriles even under severe conditions, but this restriction does not apply to benzylic examples (equation 16). In appropriate cases," the Ritter reaction can be stereoselective (Scheme 10). Either alcohol isomer, separately or as a mixture, gave identical mixtures of the two amine products, showing that axial attack on the cation was predominant. 

In 1957 Tillmanns and Ritter report that reaction of diol (51) with nitriles led to dihydro-1,3-oxazine products (52) instead of yielding bisamides (Scheme 21). In this process the tertiary alcohol group... 

The enantioselective biomimetic total synthesis of the alkaloid (+)-aristotelone was accomplished by C.H. Heathcock and co-workers." The synthetic sequence commenced with a Hg(N03)2-mediated Ritter reaction between (1S)-(-)-P-pinene and 3-indolylacetonitrile. Upon protonation, the pinene underwent a Wagner-Meerwein rearrangement to generate a tertiary carbocation which reacted with the cyano group. The initially formed imine product was reduced to the corresponding amine by sodium borohydride in methanol. 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

Tertiary butylamine had a world wide production of 1.4 million tons in 1988 [108]. Over 57% was produced using the Ritter reaction. Sterling Chemicals, Nitto Chemical Industry, and Sumitomo Chemicals use the Ritter process [109]. BASF is the only company producing tertiary butylamine with the olefins amination process. 

A variation on the Ritter reaction, suitable for the transformation of primary secondary, and tertiary alcohols to acetamides, involves thionyl chloride in acetonitrile. Reduction of the crude products (Scheme 17) with zinc-acetic acid converts any chloroacetamide product into the acetamide, and overall yields are moderate to good. 

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