Amines Cope elimination

Cope Elimination- elimination of R2NOH from an amine oxide... 

Elimination. Ahphatic amine oxides having an ahphatic hydrogen P to the nitrogen form olefins and diaLkyl hydroxylamines when heated. This reaction is known as the Cope elimination (17)... 

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. 

Certain amine oxides, especially those derived from six-membered heterocyclic amines e.g. N-methylpiperidine oxide, that cannot go through a planar, five-membered transition state, do not undergo the Cope elimination reaction. 

The preparation of an alkene 3 from an amine 1 by application of a /3-elimination reaction is an important method in organic chemistry. A common procedure is the Hofmann elimination where the amine is first converted into a quaternary ammonium salt by exhaustive methylation. Another route for the conversion of amines to alkenes is offered by the Cope elimination. 

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]. 

Oxidations of a range of p-cyanoethyl tertiary amines (44) with m-CPBA in CH2CI2 give the corresponding A-oxides (45), which can be isolated or undergo Cope elimination affording hydroxylamines (46) in high yields (Scheme 2.16) (Table 2.1) (96). Hydroxylamines (46) can be easily oxidated into nitrones (see Section 2.2.1.3). 

Cope Elimination oxidize 3° amine to tertiary ammonium oxide (R N -< V I. heat produces RHC=CH2... 

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 . ... 

C-4 -amine via Cope elimination) or a C-4 -hydroxy via Martin s sulfurane dehydration or Burgess dehydration), followed by dihydroxylation, would provide (+)-MLR-52 (320) (Schemes 5.232 and 5.233). 

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. 

When 3-phenyl-l,2,4-triazine (411) reacts with the enamine (406), orientation B is followed. In this case the 3,4-dihydropyridine (412) is formed and is isolated. Elimination of the amine directly is unfavourable, because of the cis orientation, and transfer of the proton to the pyridine nitrogen is impossible. Oxidation to the (V-oxide (413) and Cope elimination affords the condensed pyridine (414) (78UP21900). 

The second step involves a syi elimination similar to the Cope elimination of amine oxides. 

Cope elimination reactions of threo- and entf/zro-A, Ai-dimethyl-3-phenyl-2-butyl-amine oxide have been investigated using QM/MM calculations in water, THF, and DMSO.8 The aprotic solvents provided rate accelerations of up to 106-fold. It has been found that the amine oxide oxygen is the acceptor of three hydrogen bonds from water molecules for the reactant but only one or two weaker ones at the transition state. 

In the first synthesis [50] phenol (150) prepared from dehydroabietic acid as starting material [51] and this was converted to trifluoroacetate (151). The azide (152) prepared from (151), underwent Curtis rearrangement yielding isocyanate (153). Reduction of (153) followed by heating the resulting material with formic acid and formaldehyde provided the tertiary amine (154). Its conversion to ketone (155) was accomplished in three steps (a) oxidation with m-cloroperbenzoic acid, (b) Cope elimination and (c) oxidative cleavage. 

Amines as Leaving Groups The Hofmann Elimination 904 Mechanism 19-4 Hofmann Elimination 904 19-15 Oxidation of Amines The Cope Elimination 907... 

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

The Cope elimination is a one-step, concerted internal elimination 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. 

Sinee the Cope elimination reaetion of amine oxides proeeeds with intramoleeular proton abstraction by the A -oxide group aeeording to Eq. (5-122), it is not surprising that with dimethyl sulfoxide as solvent the reaetion oeeurs at room temperature [328, 331]. Pro tie solvents require temperatures of 120 to 150 °C beeause hydrogen bonding of the oxygen terminal makes the reaetion more diffieult. 

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