HOFMANN ELIMINATION, in alkenes preparation

With a regioselectivity opposite to that of the Zaitsev rule the Hofmann ehmma tion IS sometimes used in synthesis to prepare alkenes not accessible by dehydrohalo genation of alkyl halides This application decreased in importance once the Wittig reac tion (Section 17 12) became established as a synthetic method Similarly most of the analytical applications of Hofmann elimination have been replaced by spectroscopic methods... 

This reaction is known as the Hofmann elimination it was developed by August W. Hofmann in the middle of the nineteenth century and is both a synthetic method to prepare alkenes and an analytical tool for structure detennination. 

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. 

The Hofmann elimination is useful synthetically for preparing alkenes since it gives the least substituted alkene. The reaction involves thermal elimination of a tertiary amine from a quaternary ammonium hydroxide these are often formed by alkylation of a primary amine with methyl iodide followed by reaction with silver oxide. The mechanism of the elimination is shown in Scheme 1.13 in this synthesis of 1-methyl-1-... 

In this reaction two different procedures have been used. The first is the classical Hofmann degradation, which prepares the alkene by thermal decomposition of the quaternary ammonium hydroxide. Hofmann orientation is generally observed in acyclic and Zaitsev orientation in cyclohexyl substrates. The second is the treatment of quaternary ammonium halides with very strong bases, e.g. PhLi, KNH2 in liquid NH3. The formation of the alkene proceeds via an 1 mechanism, which means a syn elimination in contrast to the anti elimination which is observed in most of the classical Hofmann degradations. In some cases this type of elimination can also be accomplished by heating the salt with KOH in polyethylene glycol monomethyl ether. 

Exocyclic alkenes can also be prepared using dimethylaminomethylcycloalkanes, e.g. pyrolysis of the trisamine oxide (24) gave trimethylenecyclobutane (25 equation 11). In this case the analogous Hofmann elimination was accompanied by double bond migration and gave dimethylene-1-methylcyclo-butene (26). Terminal double bonds can also be introduced using Cope eliminations. An example is found in the synthesis of the vinyl steroid (27 equation 12). ... 

However, it was suggested that if the residual anions could be completely removed from the organoclays, the primary degradation pathway would switch to an elimination-type mechanism [16]. The Hofmann elimination of ammonium compounds was most probably the source of additional amounts of vinyl-type unsaturation found in melt-processed OMMT-PE relative to both the polymer control and the Na+MMT-PE samples [28]. On the other hand, the presence of alkenes was also explained by three possible routes of decomposition (i) pyrolysis of alkanes derived from the major component of the organic part, i.e., hydrogenated tallow (HT) (ii) pyrolysis of the tallow (unsaturated fatty acids used for the preparation of the quaternary ammonium salt) and (iii) decarboxylation of RCOO and RCO radicals [17, 29]. 

With a regioselectivity opposite to that of the Zaitsev rule, the Hofmann elimination is sometimes used in synthesis to prepare alkenes not accessible by dehydrohalogenation... 

In a mild alternative to the Hofmann elimination, acrydinium salts (20), prepared from the corresponding pentacyclic pyrilium salt and primary amines, are converted into terminal olefins (21) on heating with the non-nucleo-philic base triphenylpyridine. Small quantities of 2-alkenes are formed as by-products. 

The reaction has been extensively used for the determination of the structure of naturally occurring bases (e.g. the alkaloids). However it has rather limited preparative value, even though the elimination reaction occurs without any rearrangement of the carbon skeleton, and the regioisomer which predominates in the product is the less highly substituted alkene (Hofmann rule contrast the Saytzeff rule). Such alkenes are now more usually prepared by other procedures noted below. 

Rearrangement of N-nitrosoamides. N-Nitrosamides (1), prepared by acetylation of primary amines followed by nitrosation, are known to decompose in nonpolar solvents at 80-100° to form alkyl acetates with elimination of nitrogen.9 The presumed diazoalkane intermediate (a) can be trapped as a rhodium carbene (b), which undergoes rearrangement to an alkene (equation I). The overall result is a mild, nonbasic version of the classical Hofmann degradation of amines. 

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