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Applications

The Ritter reaction is most useful in the formation of new carbon-nitrogen bonds, especially in the formation of amides in which the nitrogen has a tertiary alkyl group. It is also used in industrial processes as it can be effectively scaled up from laboratory experiments to large-scale applications while maintaining high yield. Commercial applications include Merck’s industrial-scale synthesis of anti-HIV drug Crixivan (indinavir)^[1]; the production of the falcipain-2 inhibitor PK 11195; the synthesis of the alkaloid aristotelone^[4]; and synthesis of Amantadine, an antiviral and antiparkinsonian drug ^[6]. Other applications of the Ritter reaction include synthesis of dopamine receptor ligands^[4] and production of amphetamine from allylbenzene^[5].

A problem with the Ritter reaction is the necessity of an extremely strong acid catalyst in order to produce the carbocation. This poses an environmental risk, as the acids are extremely corrosive and also cannot be reused. However, other methods have been proposed in order promote carbocation formation, including photosensitized electron transfer^[2] or direct photolysis^[3].

1. Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford Press: New York, 2001.
2. Mattes, S. L.; Farid, S. J. Chem. Soc., Chem. Commun., 1980, 126–129 doi:10.1039/C39800000126
3. Kropp, P. J.; Poindexter, G. S.; Pienta, N. J.; Hamilton, D. C. J. Am. Chem. Soc., 1976, 98, 8135–8144. doi:10.1021/ja00441a043
4. Kurti, L.; Czako, B. (2005). Strategic Applications of Named in Organic Synthesis. Burlington, MA Elsevier Academic Press.
5. Fujisawa and Deguchi, Chemical Abstracts, 52, 11965 (1958)
6. Vardanyan, R.; Hruby, V.J. Synthesis of Essential Drugs, 1st Ed. Amsterdam: Elsevier, 2006; pp. 137