Cope reaction

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Cope reaction
Named after Arthur C. Cope
Reaction type Elimination reaction
Identifiers
Organic Chemistry Portal cope-elimination
RSC ontology ID RXNO:0000539

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] [2] [3] [4]

Contents

Mechanism and applications

The reaction mechanism involves an intramolecular 5-membered cyclic transition state, leading to a syn elimination product, an Ei pathway. This organic reaction is closely related to the Hofmann elimination, 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 meta-chloroperoxybenzoic acid (mCPBA). The actual elimination just requires heat.

Cope reaction CopeReaction.png
Cope reaction

Illustrative of the Cope reaction is a synthesis of methylenecyclohexane: [5]

MethyleneCyclohexaneByCopeReaction.svg

Piperidines are resistant to an intramolecular Cope reaction [6] [7] [8] 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.

CopeReactionJACS82-4656.svg

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]

Sulfoxides can undergo an essentially identical reaction to produce sulfenic acids which is important in the antioxidant chemistry of garlic and other plants of the genus Allium . Selenoxides likewise undergo selenoxide eliminations. Other Ei reactions proceed similarly.

Related Research Articles

Hydroboration–oxidation reaction is a two-step hydration reaction that converts an alkene into an alcohol. The process results in the syn addition of a hydrogen and a hydroxyl group where the double bond had been. Hydroboration–oxidation is an anti-Markovnikov reaction, with the hydroxyl group attaching to the less-substituted carbon. The reaction thus provides a more stereospecific and complementary regiochemical alternative to other hydration reactions such as acid-catalyzed addition and the oxymercuration–reduction process. The reaction was first reported by Herbert C. Brown in the late 1950s and it was recognized in his receiving the Nobel Prize in Chemistry in 1979.

<span class="mw-page-title-main">Epoxide</span> Organic compounds with a carbon-carbon-oxygen ring

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<span class="mw-page-title-main">2,3-sigmatropic rearrangement</span> Class of chemical reaction

2,3-Sigmatropic rearrangements are a type of sigmatropic rearrangements and can be classified into two types. Rearrangements of allylic sulfoxides, amine oxides, selenoxides are neutral. Rearrangements of carbanions of allyl ethers are anionic. The general scheme for this kind of rearrangement is:

<span class="mw-page-title-main">Amine oxide</span> Chemical compound containing the functional group R3N→O

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<span class="mw-page-title-main">Aziridines</span> Functional group made of a carbon-carbon-nitrogen heterocycle

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<span class="mw-page-title-main">Hydroamination</span> Addition of an N–H group across a C=C or C≡C bond

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Selenoxide elimination is a method for the chemical synthesis of alkenes from selenoxides. It is most commonly used to synthesize α,β-unsaturated carbonyl compounds from the corresponding saturated analogues. It is mechanistically related to the Cope reaction.

Amide reduction is a reaction in organic synthesis where an amide is reduced to either an amine or an aldehyde functional group.

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<span class="mw-page-title-main">White catalyst</span> Chemical compound

The White catalyst is a transition metal coordination complex named after the chemist by whom it was first synthesized, M. Christina White, a professor at the University of Illinois. The catalyst has been used in a variety of allylic C-H functionalization reactions of α-olefins. In addition, it has been shown to catalyze oxidative Heck reactions.

<span class="mw-page-title-main">Photoredox catalysis</span>

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A nitroalkene, or nitro olefin, is a functional group combining the functionality of its constituent parts, an alkene and nitro group, while displaying its own chemical properties through alkene activation, making the functional group useful in specialty reactions such as the Michael reaction or Diels-Alder additions.

The Riley oxidation is a selenium dioxide-mediated oxidation of methylene groups adjacent to carbonyls. It was first reported by Riley and co-workers in 1932. In the decade that ensued, selenium-mediated oxidation rapidly expanded in use, and in 1939, Guillemonat and co-workers disclosed the selenium dioxide-mediated oxidation of olefins at the allylic position. Today, selenium-dioxide-mediated oxidation of methylene groups to alpha ketones and at the allylic position of olefins is known as the Riley Oxidation.

In organic chemistry, the Davis oxidation or Davis' oxaziridine oxidation refers to oxidations involving the use of the Davis reagent or other similar oxaziridine reagents. This reaction mainly refers to the generation of α-hydroxy carbonyl compounds (acyloins) from ketones or esters. The reaction is carried out in a basic environment to generate the corresponding enolate from the ketone or ester. This reaction has been shown to work for amides.

<span class="mw-page-title-main">Hydrocupration</span> Chemical reaction

A hydrocupration is a chemical reaction whereby a ligated copper hydride species, reacts with a carbon-carbon or carbon-oxygen pi-system; this insertion is typically thought to occur via a four-membered ring transition state, producing a new copper-carbon or copper-oxygen sigma-bond and a stable (generally) carbon-hydrogen sigma-bond. In the latter instance (copper-oxygen), protonation (protodemetalation) is typical – the former (copper-carbon) has broad utility. The generated copper-carbon bond (organocuprate) has been employed in various nucleophilic additions to polar conjugated and non-conjugated systems and has also been used to forge new carbon-heteroatom bonds.

References

  1. Cope, Arthur C.; Foster, Theodore T.; Towle, Philip H. (1949). "Thermal Decomposition of Amine Oxides to Olefins and Dialkylhydroxylamines". Journal of the American Chemical Society . 71 (12): 3932–3935. doi:10.1021/ja01180a014.
  2. Cope, Arthur C.; Towle, Philip H. (1949). "Rearrangement of Allyldialkylamine Oxides and Benzyldimethylamine Oxide". Journal of the American Chemical Society . 71 (10): 3423–3428. doi:10.1021/ja01178a048.
  3. Cope, Arthur C.; Pike, Roscoe A.; Spencer, Claude F. (1953). "Cyclic Polyolefins. XXVII. cis- and trans-Cycloöctene from N,N-Dimethylcycloöctylamine". Journal of the American Chemical Society . 75 (13): 3212–3215. doi:10.1021/ja01109a049.
  4. Peter C. Astles; Simon V. Mortlock; Eric J. Thomas (1991). "The Cope Elimination, Sulfoxide Elimination and Related Thermal Reactions". Comprehensive Organic Synthesis. Vol. 6. pp. 1011–1039. doi:10.1016/B978-0-08-052349-1.00178-5. ISBN   978-0-08-052349-1.
  5. Cope, Arthur C.; Ciganek, Engelbert (1963). "Methylenecyclohexane and N,N-Dimethylhydroxylamine Hydrochloride". Organic Syntheses . 4: 612. doi:10.15227/orgsyn.039.0040.
  6. March, Jerry; Smith, Michael B. (2007). March's advanced organic chemistry: reactions, mechanisms, and structure (6th. ed.). Wiley-Interscience. p.  1525. ISBN   978-0-471-72091-1.
  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 doi : 10.1021/ja01502a053
  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. doi : 10.1021/ja01502a052
  9. Ciganek, Engelbert; Read, John M.; Calabrese, Joseph C. (September 1995). "Reverse Cope elimination reactions. 1. Mechanism and scope". The Journal of Organic Chemistry. 60 (18): 5795–5802. doi:10.1021/jo00123a013.
  10. Ciganek, Engelbert (September 1995). "Reverse Cope elimination reactions. 2. Application to synthesis". The Journal of Organic Chemistry. 60 (18): 5803–5807. doi:10.1021/jo00123a014.
  11. Beauchemin, André M.; Moran, Joseph; Lebrun, Marie-Eve; Séguin, Catherine; Dimitrijevic, Elena; Zhang, Lili; Gorelsky, Serge I. (8 February 2008). "Intermolecular Cope-Type Hydroamination of Alkenes and Alkynes". Angewandte Chemie. 120 (8): 1432–1435. Bibcode:2008AngCh.120.1432B. doi:10.1002/ange.200703495.