The Cope Elimination of an Amine Oxide

The Cope elimination is a one-step, concerted E2 reaction using an amine oxide as both the base and the leaving group. Syn stereochemistry is required for the Cope elimination. 

Cope elimination occurs under milder conditions than Hofmann elimination. It is particularly useful when a sensitive or reactive alkene must be synthesized by the elimination of an amine. Because the Cope elimination involves a cyclic transition state, it occurs with syn stereochemistry. 

Predict the products expected when the following compound is treated with H2O2 and heated. 

Oxidation converts the tertiary amine to an amine oxide. Cope elimination ean give either of two alkenes. We expeet the less-hitxlered elimination to be favored, giving the Hofmann produet. 

Give the products expected when the foiiowing tertiary amines are treated with a peroxyacid and heated. 

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Mechanism 19-5 The Cope Elimination of an Amine Oxide 908 19-16 Reactions of Amines with Nitrous Acid 910... 

This conclusion was supported by the observation that pyrolysis of 3-butenol has a AS of —8.8 eu, which is similar to the activation entropy values reported for pyrolysis of ethyl formate and for 3-butenoic acid, and the activation energies for all three pyrolyses are also similar (about 40 kcal/mol). Another well-known concerted syn elimination is the Cope elimination, which involves the thermal elimination of an alkene from an amine oxide (Figure 10.53). Unlike the reactions discussed above, all of which have... 

When an amine oxide with at least one j8-hydrogen is heated, it undergoes thermal decomposition to form an alkene and an N,N-dialkylhydroxylamine. Thermal decomposition of an amine oxide to an alkene is known as a Cope elimination after its discoverer Arthur C. Cope of the Massachusetts Institute of Technology. 

The a ,P-mode is a p-elimination unleashed by an electron-rich carbon center that is intramolecularly located at an a -position. Such a process is frequently met with ylides. It is related to the Cope elimination of amine oxides, which also implies a syn-periplanar scission but occurs at much higher temperatures. Organolithiums deprotonate an alkyltrimethylammonium salt preferentially or exclusively at a methyl group. Subsequently, the electron-rich carbon in the ylide 243 acts as a base and accomplishes an... 

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

Preparation of 3-vinylindole (84) via Cope elimination of N,N-diethyltrypt-amine-N-oxide has been reported [87], An alternate approach based on the Wittig reaction of the readily accessible N-phenylsulfonylindole-3-carbalde-hyde failed because cleavage of the sulfonyl protecting group easily produced an anion whose neutralization led to polymerization [86]. 

Oxidation of organonitrogen compounds is an important process from both industrial and synthetic viewpoints . N-oxides are obtained by oxidation of tertiary amines (equation 52), which in some cases may undergo further reactions like Cope elimination and Meisenheimer rearrangement . The oxygenation products of secondary amines are generally hydroxylamines, nitroxides and nitrones (equation 53), while oxidation of primary amines usually afforded oxime, nitro, nitroso derivatives and azo and azoxy compounds through coupling, as shown in Scheme 17. Product composition depends on the oxidant, catalyst and reaction conditions employed. 

In the Cope elimination, thirty percent hydrogen peroxide, H202, is used to produce an amine oxide, which upon heating undergoes elimination. This is a syn-elimination process. Figure 13-45 illustrates the general reaction, while Figure 13-46 shows the mechanism of the syn-elimination step. 

As an alternative to an olefination method, the Cope elimination can be used as a preparative method for unsymmetrical hydroxylamines. Addition of unsymmetrical secondary amine 41 to a,p-unsaturated compounds gave access to compound 42, which underwent oxidation and Cope elimination to yield the unsymmetrical hydroxylamine product 44.16... 

In an analogous way, secondary amines can be protected through attachment of / -cyanoethyl or a similar function. The cyanoethyl group undergoes facile Cope elimination from initially formed A-oxide (e.g. 137, equation 91) thus giving the corresponding hydroxylamine 138 in a good yield . ... 

Cleavage of amine oxides to produce an alkene and a hydroxylamine is called the Cope reaction or Cope elimination (not to be confused with the Cope rearrangement, 18-32). It is an alternative to 17-7 and 17-8. The reaction is usually... 

The tertiary amine A-oxides with a (3-hydrogen in the alkyl substituted group may also undergo Cope elimination to give a hydroxylamine and an olefin. The A-oxide metabolite of SC-57461 was found to be unstable in organic... 

Cope elimination A variation of the Hofmann elimination, where a tertiary amine oxide eliminates to an alkene with a hydroxylamine serving as the leaving group, (p. 900) diazo coupling The use of a diazonium salt as an electrophile in electrophilic aromatic substitution. (p. 907)... 

The [2,3]-rearrangement of amine iV-oxides was utilized in an efficient S5mthesis of 2,6-dimethyl-l,5-heptadien-3-ol acetate 61, a pheromone of the insect Pseudococcus comstocki tScheme lS.12id Dimethylpyridine 55 was converted in two steps into silylated piperidine 56, which was oxidized with m-CPBA to generate cyclic amine A-oxide 57. Sila-Cope elimination furnished O-silylhydroxylamine 58, which was methylated and desilylated in the presence of Mel and CsF to yield acyclic amine A-oxide 59. Heating this ammonium zwitterion facilitated the [2,3]-Meisenheimer rearrangement to O-allylhydroxylamine 60, which was transformed to the desired pheromone 61 in three steps. 

The pyrolysis of amine oxides is called Cope elimination and typically takes place at 120 °C (Scheme 6.21). The reaction is a syn periplanar elimination in which six electrons move in a five-membered ring according to a concerted, thermally induced mechanism to yield an alkene and a hydroxylamine. 

Oxidation of a tertiary amine with a peroxide (mCPBA) forms an A-oxide that undergoes an intramolecular deprotonation with syn stereoselectivity upon heating. This reaction is known as a Cope elimination. If given a choice, this deprotonation will occur on a less hindered P-carbon, giving rise to a less substituted alkene product (this regioselectivity, known as the Hofmann rule, is the opposite predicted by Zaitsev s rule). 

It turned out that 25 was an impractical 1,3-dipole for implementation of the plan, but ketal 30 served admirably. This 1,3-dipole was prepared by conversion of 27 to the corresponding ketal 28. Oxidation of 28 to the amine oxide, followed by a Cope elimination, gave hydroxylamine derivative 29. 

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