Cope reaction

- Dec 04, 2018-

The Cope reaction or Cope elimination, developed by Arthur C. Cope, is an elimination reaction of the N-oxide to form an alkene and a hydroxylamine.[1]

Mechanism and applications

The reaction mechanism involves an intramolecular 5-membered cyclic transition state,[1] leading to a syn elimination product, an Ei pathway. This organic reaction is closely related to the Hofmann elimination,[2] but the base is a part of the leaving group. The amine oxide is prepared by oxidation of the corresponding amine with an oxidant such as mCPBA. The actual elimination just requires heat.

Cope reaction

Illustrative of the Cope reaction is a synthesis of methylenecyclohexane:[2]

  • synthesis of methylenecyclohexane

Piperidines are resistant to an intramolecular Cope reaction[3][4][5] but with pyrrolidine and with rings of size 7 and larger, the reaction product is an unsaturated hydroxyl amine. This result is consistent with the 5-membered cyclic transition state.

  • intramolecular Cope reaction

References

  1. ^ Peter C. Astles, Simon V. Mortlock, Eric J. Thomas (1991). "The Cope Elimination, Sulfoxide Elimination and Related Thermal Reactions". Comprehensive Organic Synthesis6. pp. 1011–1039. doi:10.1016/B978-0-08-052349-1.00178-5.

  2. ^ Cope, Arthur C.; Ciganek, Engelbert (1963). "Methylenecyclohexane and N,N-Dimethylhydroxylamine Hydrochloride". Organic Syntheses4: 612. doi:10.15227/orgsyn.039.0040.

  3. ^ March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.), New York: Wiley, ISBN 0-471-85472-7

  4. ^ 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 doi:10.1021/ja01502a053

  5. ^ 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. doi:10.1021/ja01502a052