Cope reaction explained

Cope reaction should not be confused with Cope rearrangement.

The Cope reaction or Cope elimination, developed by Arthur C. Cope, is the elimination reaction of an N-oxide to an alkene and a hydroxylamine.^{[1] [2] [3] [4]} Typically, the amine oxide is prepared from the corresponding amine with a peroxy acid or comparable oxidant. The actual elimination requires just heat. Illustrative is a synthesis of methylenecyclohexane:^[5]

Mechanism and related eliminations

The reaction proceeds through the E_i pathway, with an intramolecular, cyclic 5-membered transition state. Consequently, the elimination product is always syn and rarely occurs with 6-membered rings. (Rings with 5 or 7 or more members undergo the reaction just fine.)^{[6] [7] [8]} This organic reaction is closely related to the Hofmann elimination, but the base is a part of the leaving group. Sulfoxides can undergo an essentially identical reaction to produce sulfenic acids, which is important in the antioxidant chemistry of garlic and other alliums. Selenoxides likewise undergo selenoxide eliminations.

Reverse reaction

The reverse or retro-Cope elimination has been reported, in which an N,N-disubstituted hydroxylamine reacts with an alkene to form a tertiary N-oxide.^{[9] [10]} The reaction is a form of hydroamination and can be extended to the use of unsubstituted hydroxylamine, in which case oximes are produced.^[11]

Notes and References

1. Cope . Arthur C. . Foster . Theodore T. . Towle . Philip H. . Arthur C. Cope . Thermal Decomposition of Amine Oxides to Olefins and Dialkylhydroxylamines . . 1949 . 71 . 12 . 3932–3935 . 10.1021/ja01180a014.
2. Cope . Arthur C. . Towle . Philip H. . Arthur C. Cope . Rearrangement of Allyldialkylamine Oxides and Benzyldimethylamine Oxide . . 1949 . 71 . 10 . 3423–3428 . 10.1021/ja01178a048.
3. Cope . Arthur C. . Pike . Roscoe A. . Spencer . Claude F. . Arthur C. Cope . Cyclic Polyolefins. XXVII. cis- and trans-Cycloöctene from N,N-Dimethylcycloöctylamine . . 1953 . 75 . 13 . 3212–3215 . 10.1021/ja01109a049.
4. Encyclopedia: 6. 1991. 1011–1039. Comprehensive Organic Synthesis. The Cope Elimination, Sulfoxide Elimination and Related Thermal Reactions . Peter C. Astles . Simon V. Mortlock . Eric J. Thomas. 10.1016/B978-0-08-052349-1.00178-5. 978-0-08-052349-1.
5. Cope . Arthur C. . Arthur C. Cope . Ciganek . Engelbert . 1963 . Methylenecyclohexane and N,N-Dimethylhydroxylamine Hydrochloride . . 4 . 612 . 10.15227/orgsyn.039.0040.
6. Book: March . Jerry . March's advanced organic chemistry: reactions, mechanisms, and structure. . Smith . Michael B. . Wiley-Interscience . 2007 . 978-0-471-72091-1 . 6th. . 1525 . limited.
7. Amine Oxides. VIII. Medium-sized Cyclic Olefins from Amine Oxides and Quaternary Ammonium Hydroxides Arthur C. Cope, Engelbert Ciganek, Charles F. Howell, Edward E. Schweizer J. Am. Chem. Soc., 1960, 82 (17), pp 4663–4669
8. Amine Oxides. VII. The Thermal Decomposition of the N-Oxides of N-Methylazacycloalkanes Arthur C. Cope, Norman A. LeBel; J. Am. Chem. Soc.; 1960; 82(17); 4656-4662.
9. Ciganek . Engelbert . Read . John M. . Calabrese . Joseph C. . Reverse Cope elimination reactions. 1. Mechanism and scope . The Journal of Organic Chemistry . September 1995 . 60 . 18 . 5795–5802 . 10.1021/jo00123a013.
10. Ciganek . Engelbert . Reverse Cope elimination reactions. 2. Application to synthesis . The Journal of Organic Chemistry . September 1995 . 60 . 18 . 5803–5807 . 10.1021/jo00123a014.
11. Beauchemin . André M. . Moran . Joseph . Lebrun . Marie-Eve . Séguin . Catherine . Dimitrijevic . Elena . Zhang . Lili . Gorelsky . Serge I. . Intermolecular Cope-Type Hydroamination of Alkenes and Alkynes . Angewandte Chemie . 8 February 2008 . 120 . 8 . 1432–1435 . 10.1002/ange.200703495. 2008AngCh.120.1432B .