HOFMANN ELIMINATION, in alkenes

In the procedure of Hofmann elimination, the amine is first completely methylated with excess iodomethane (exhaustive methylation) and then treated with wet silver oxide (a source of HO ) to produce the ammonium hydroxide. Heating degrades this salt to the alkene. When more than one regioisomer is possible, Hofmann elimination, in contrast to most E2 processes, tends to give less substituted alkenes as the major products. Recall that this result adheres to Hofmann s rule (Section 11-6) and appears to be caused by the bulk of the ammonium group, which directs the base to the less hindered protons in the molecule. 

Similarly, in the reaction of 2-substituted pentanes (Figure 10.21), as the size of the leaving group is increased, the proportion of 1-alkene produced also increases where steric hindrance is a problem, the base abstracts the more accessible, terminal hydrogen atom. The reaction features that favor Zaitsev or Hofmann elimination in E2 processes are summarized in Table 10.1. 

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became established as a synthetic method Similarly most of the analytical applications of Hofmann elimination have been replaced by spectroscopic methods... 

Hofmann elimination (Section 22 14) Conversion of a quater nary ammonium hydroxide especially an alkyltnmethyl ammonium hydroxide to an alkene on heating Elimination occurs in the direction that gives the less substituted double bond... 

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 least sterically hindered p hydrogen is removed by the base in Hofmann elimination reactions. Methyl groups are deprotonated in preference to methylene groups, and methylene groups are deprotonated in preference to methines. The regioselectivity of Hofmann elimination is opposite to that predicted by the Zaitsev rule (Section 5.10). Elimination reactions of alkyltrimethylammonium hydroxides are said to obey the Hofmann rule they yield the less substituted alkene. 

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. 

Many of the reactions of amines are familiar from past chapters. Thus, amines react with alkyl halides in S 2 reactions and with acid chlorides in nucleophilic acyl substitution reactions. Amines also undergo E2 elimination to yield alkenes if they are first qualernized by treatment with iodomethane and then heated with silver oxide, a process called the Hofmann 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-... 

The primary products obtained from 2-butanol are of mechanistic. significance and may be compared with other eliminations in the sec-butyl system 87). The direction of elimination does not follow the Hofmann rule 88) nor is it governed by statistical factors. The latter would predict 60% 1-butene and 40% 2-butene. The greater amount of 2-alkene and especially the unusual predominance of the cis-olefin over the trans isomer rules out a concerted cis elimination, in which steric factors invariably hinder the formation of cis-olefin. For example, the following ratios oicisjtrans 2-butene are obtained on pyrolysis of 2-butyl compounds acetate, 0.53 89, 90) xanthate, 0.45 (S7) and amine oxide, 0.57 86) whereas dehydration of 2-butanol over the alkali-free alumina (P) gave a cisjtrans ratio of 4.3 (Fig. 3). 

The Hofmann elimination converts an amine into an alkene. The process begins by converting an amine to a quaternciry cimmonium salt (that is, it has a nitrogen atom with four bonds). The general mechanism for the elimination step is in Figure 13-40. Figure 13-41 illustrates a sample reaction scheme for the Hofmann elimination. 

Heating the quarternary ammonium hydroxide results in the Hofmann elimination to form an alkene. 

Notice that the LEAST stable alkene is the major product in the Hofmann elimination, called the Hofmann product. 

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