Regioselectivity of Hofmann elimination

The least sterically hindered p hydrogen is removed by the base m Hofmann elim matron reactions Methyl groups are deprotonated m preference to methylene groups and methylene groups are deprotonated m preference to methmes The regioselectivity of Hofmann elimination is opposite to that predicted by the Zaitsev rule (Section 5 10) Elimination reactions of alkyltrimethylammonmm hydroxides are said to obey the Hofmann rule, they yield the less substituted alkene... 

Quaternary ammonium hydroxides undergo Hofmann elimination when they are heated. A point to be considered here concerns the regioselectivity of Hofmann eliminations it is the less hindered / proton that is removed by the base giving the less substituted alkene. 

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became established as a synthetic method Similarly most of the analytical applications of Hofmann elimination have been replaced by spectroscopic methods... 

Fig. 4.7. Regioselectivity of the elimination of H/Het from Rsec—Het. When C/5 has fewer alkyl substituents than CI3 the constitutionally isomeric products are Hofmann product (A) and Saytzeff product (B).

A novel aspect of the Hofmann elimination is its regioselectivity Elimination m alkyltrimethylammonmm hydroxides proceeds m the direction that gives the less substi tuted alkene... 

Quaternary ammonium hydroxides un dergo elimination on being heated It is an anti elimination of the E2 type The regioselectivity of the Hofmann elimina tion IS opposite to that of the Zaitsev rule and leads to the less highly substi tuted alkene... 

This regioselectivity distinguishes a Hofmann elimination from other E2 eliminations, which form the more substituted double bond by the Zaitsev rule (Section 8.5). This result is sometimes explained by the size of the leaving group, N(CH3)3. In a Hofmann elimination, the base removes a proton from the less substituted, more accessible carbon atom, because the bulky leaving group on the nearby a carbon. 

We can understand the regioselectivity of the Hofmann elimination by comparing steric effects in the E2 transition states for formation of 1-butene and trans-2-... 

FIGURE 7.88 The regioselectivity of the E2 reaction depends on the identity of the leaving group. Leaving groups such as fluoride, ammonium (R3N ), and sulfonium (RjS ) lead to predominant Hofmann elimination, in which the less stable isomer is the major product. 

We can understand the regioselectivity of the Hofmann elimination by comparing steric... 

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 the above example, only one elimination product can form. The Hofmann elimination of quaternary ammonium salts is regioselective. This E2 ehmination occurs to give the less substituted alkene by removal of the less sterically hindered P hydrogen atom by base. Hence, methyl groups lose a proton in the ehmination reaction in preference to loss of a proton from a methylene group. The less substituted alkene, which forms preferentially, is termed the Hofrnann product. 

The same six center-type process may provide an explanation for the peculiar regioselectivity of organometal-promoted eliminations. In violation of Saytzeff s rule and conformal with Hofmann s rule, 2-methoxyoctane produces with organoalkalis almost exclusively 1-octene. Only traces (4%) of cis- and trans-2-octene are detected. ... 

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