Quaternary ammonium salts hydroxides, Hofmann elimination

Thermal decomposition of quaternary ammonium salts and bases is most valuable in structural investigations of amines, particularly heterocyclic secondary amines (Hofmann exhaustive methylation). The course of the elimination (A or B) is determined by the nature of the four alkyl groups on the nitrogen atom. The reaction has found little use in the synthesis of pure olefins. The yields are low even when three of the alkyl groups are methyl radicals. Carbon-skeleton rearrangement does not occur. Thus, the only olefin obtained by pyrolysis of pinacolyltri-methylammonium hydroxide, (CHj),CCH(CHj)N(CHj)j OH, is /-butylethylene (50%). ... 

Apart from the reactions of diazonium salts, a number of other reactions are known in which the C-N bond is broken. The best known of these is the Hofmann elimination of quaternary ammonium hydroxides (Scheme 2.37). An amine is converted by methylation with methyl iodide to the quaternary ammonium salt ( exhaustive methylation ). The iodide, on treatment with moist silver oxide, forms the quaternary ammonium hydroxide which undergoes a bimolecular elimination to form an alkene. The bimolecular elimination of onium salts yields the least alkylated alkene. This substitution pattern is determined by the ease with which a hydrogen atom can be attacked by the base. 

Sulfonium salts (20) have a non-planar tetrahedral configuration, and consequently the structure is chiral when all the attached groups, namely R, R and R", are different. Such sulfonium salts can generally be resolved into quite stable optical isomers (see Chapter 6, p. 83). Sulfonium salts are analogous to quaternary ammonium salts and the hydroxides are strong bases which behave similarly on heating (cf. the Hofmann elimination of quaternary ammonium hydroxides). 

Hofmann rule The principal alkene formed in the decomposition of quaternary ammonium hydroxides that contain different primary alkyl groups is always ethylene, if an ethyl group is present. Originally given in this limited form by A.W. Hofmann, the rule has since been extended and modified as follows When two or more alkenes can be produced in a P-elimination reaction, the alkene having the smallest number of alkyl groups attached to the double bond carbon atoms will be the predominant product. This orientation described by the Hofmann rule is observed in elimination reactions of quaternary ammonium salts and tertiary sulfonium salts, and in certain other cases. 

Another interesting comparison was reported by von Braun 150> in which various quaternary ammonium hydroxides were decomposed under Hofmann conditions and in the presence of glycerol. These results also show that the displacement reaction is favored in the presence of a hydroxylic solvent. It was also noted by Hanhart and Ingold 57> that displacement reactions are favored over elimination reactions in thermal decompositions of quaternary ammonium salts as the nucleophilicity of the anion is increased from chloride to acetate. 

We shall discuss later how to make ammonium hydroxide salts such as R4N+ OH, which are known as quaternary ammonium salts because N has four alkyl groups attached to it, and which undergo Hofmann elimination reactions on heating. 

Methylation now proceeds further to fomti GGG, another quaternary ammonium salt. GGG in turn reacts with AgaO to form a quaternary ammonium hydroxide, which undergoes the Hofmann elimination. The amino group is finally... 

Sodium hydroxide Elimination of N-heterocycles via Hofmann degradation of quaternary ammonium salts with opening of O-heterocycles Aromatization by ring elimination... 

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. 

Displacement of a tertiary amine by the attack of a nucleophile on the a-carbon of a quaternary salt is a reaction that competes with the Hofmann elimination and is found to take place preferably with weak bases (carbonate, acetate, etc.) . In some cases steric influences rather than basicity may promote the substitution reaction in favor of elimination. For example, the reaction of propyltrimethyl-ammonium ion with hydroxide ion yields 19% methanol and 81% propylene, whereas the reaction with phenoxide ion yields 65% anisole and 15% propylene (equation 13) . Phenyl groups attached... 

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