Amines as Leaving Groups The Hofmann Elimination

Elimination of the quaternary ammonium salt generally takes place by the E2 mechanism, which requires a strong base. To provide the base, the quaternary ammonium iodide is converted to the hydroxide salt by treatment with silver oxide. Heating of the quatanary ammonium hydroxide results in E2 elimination and formation of an alkene. This elimination of a quaternary ammonium hydroxide is called the Hofinann elimination. Conversion to the hydroxide salt 

The Hofmann elimination is a one-step, concerted E2 reaction using an amine as the leaving group. 

For example, when 2-butanamine is exhaustively methylated, converted to the hydroxide salt, and heated, elimination takes place to form a mixture of 1-butene and 2-butene. 

In Chapter 7, we saw that eliminations of alkyl halides usually follow the Zaitsev s rule that is, the most substituted product predominates. This rule applies because the most-substituted alkene is usually the most stable. In the Hofmann elimination, however, the product is commonly the leort-substituted alkene. We often classify an elimination as giving mostly the Zaitsev pmduct (the most-substituted alkene) or the Hofmann product (the least-substituted alkene). 

Some of the stereochemical features of the Hofmann elimination are best studied using your models. Models are essential for working problems involving this elimination, such as Problem 19-20. 

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

Hofmann elimination (Section 25.12) An E2 elimination reaction that converts an amine into a quaternary ammonium salt as the leaving group. The Hofmann elimination gives the less substituted alkene as the major product. 

A variation of the Hofmann elimination, where a tertiary amine oxide eliminates to an alkene with a hydroxylamine serving as the leaving group, (p. 907)... 

Alkenes may be obtained by elimination reactions from alkyl haUdes, alcohols, sulfonates or amines. The substitution pattern of the alkene and the stereospecificity of these methods depend quite subtly on the structure of the individual substrate. If the leaving group occupies an unsymmetrical position in a compound, one of two isomeric alkenes can be formed (Scheme 3.1). Elimination to give an alkene bearing the greatest number of alkyl groups is known as the Saytzeff elimination and is commonly found with alkyl halides. When the elimination gives preferentially the less-substituted alkene, it is known as the Hofmann elimination This substitution pattern is commonly foimd with the elimination of alkylammonium salts. In practice, mixtures of alkenes are often obtained. 

The choice of the Hofmann elimination is somewhat more involved. This classic reaction, discovered by Hofmann (1851), shows that quatemized amines on treatment with base (or simply heated in solution if the anion is OH) will eliminate the smallest alkyl group (larger than methyl) that is sterically least hindered, as an olefin, leaving a tertiary amine (Eq. 8.10). 

A typical synthetic transformation using the Hofmann elimination also illustrates an alternative synthetic approach to this reaction. Reaction of iodomethane with the dimethylamino moiety in 215 leads to the trimethylammonium salt. This ammonium leaving group allows the usual Hofmann elimination sequence, with thermal syn-elimination giving the vinyl derivative, 216.203 204 j is variation is important since using an amine as a Hofmann precursor is often more convenient than relying on an Sn2 reaction of an amine and a halide to produce the requisite ammonium salt (sec. 2.1.A). 

A quaternary ammonium ion can undergo an elimination reaction with a strong base such as hydroxide ion. The reaction is known as a Hofinann elimination reaction. The leaving group in a Hofmann elimination reaction is a tertiary amine. Because a tertiary amine is a relatively poor leaving group, the reaction requires heat. 

As in the case of substitution reactions, the basicity of the leaving group is important in P-elimination reactions. Consequently, amines do not undergo P-elimination reactions because both NH2 and NH3 are poor leaving groups. However, one specialized reaction in which an amine is converted into a quaternary ammonium ion is an E2 elimination. We will discuss this process, known as the Hofmann elimination, in Section 23.15. 

Hofmann elimination occurs in quaternary amines where one of the attached alkyl groups leaves the nitrogen in the form of an alkene. The reaction happens in an alkaline medium, usually with the aid of heating and vacuum. With unsymmetrical amines, the major alkene product is derived from the least substituted and generally the least stable alkyl group, an observation known as the Hofmann rule. This is in direct contrast to normal elimination reactions where the more substituted, stable product is dominant. 

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