Amine Hofmann elimination reaction

The reactions of (174) with various amines has been studied." " Hydrolysis of the hexamine salt of (174) gave not the symmetric diamine but (184) via a cyclic intermediate. The pyrolysis of 5-methyl-2-thenyltrimethyl ammonium hydroxide (185) is claimed to give (186) through a 1,6 Hofmann elimination reaction. The Bischler-Napieralski cyclization has been applied to acetyl derivatives of 2-(2-thienyl) ethylamine and 2-(3-thienyl) ethylamine for the preparation of sulfur analogs of isoquinoline. ... 

Hofmann elimination reactions from hi- and tri-cyclic systems can, however, be used to create internal unsaturation without loss of a trialkyl amine as shown in Scheme 1.14 for the synthesis of the hexahydrothieno [ZjJazecine. 

A. C. Cope and E. R. Trumbull, Olefins from amines the Hofmann elimination reaction and amine... 

Here, we envisage building the benzimidazole scaffold directly onto the linker and, by analogy with a regular tertiary amine synthesis on the REM linker, we can quaternize the resin-bound benzimidazole compounds by reaction with reactive bromides. The quaternary salt can then be liberated by a Hofmann elimination reaction upon treatment with base. 

J. K. Crandall, M. Apparu, Base-Promoted Isomerizations of Epoxides, Org. React. 1983, 29, 345—443. A. C. Cope, E. R. Trumbull, Olefins from Amines The Hofmann Elimination Reaction and Amine Oxide Pyrolysis, Org. React. 1960, 11, 317-493. 

Hofmann elimination reaction id iintwrtant primarily becautc of its historical use as a degradativc tool in the structure detennirution of man> complex naturally occurring amines. The reaction is not often used today because the product alkcnes can he made more easily in other ways... 

Amines are converted into alkenes by a two-step process called the Hofmann elimination. Reaction of the amine with excess CHjI in the first step yields an intermediate that undergoes E2 reaction when treated with basic silver oxide. Pentyl-amine, for example, yields 1-pentene. Propose a structure for the intermediate, and explain why it undergoes ready elimination. (See Section 24.7.)... 

The classical Hofmann elimination reaction (which dates back to 1851) has been adapted to the solid phase in combination with the Michael addition. The REM resin, called this way because the resin tinker is REgenerated after product cleavage and functionalized by means of a Michael addition, has been developed to prepare arrays of tertiary amines. The procedure involves acylation of hydroxy-methylpolystyrene with acrylic chloride to furnish the acrylate on resin. Then, a secondary amine, whose substituents offer two potential sites of diversity, is bound by Michael addition. Quaternization of the amine with an alkyl halide (or reductive animation) introduces another site of diversity and activates the tinker to release the amine by a Hofmann elimination with DIEA (Figure 15.14) [127-129]. Additionally, the use of a second basic resin has been described as a source reagent to promote the elimination [130, 131]. 

Figure 15.14 Preparation of tertiary amines with the REM linker, based on the Hofmann elimination reaction.

Olefins from Amines The Hofmann Elimination Reaction and Amine Oxide... 

A Hofmann elimination reaction is an E2 reaction. Recall that an E2 reaction is a concerted, one-step reaction—the proton and the tertiary amine are removed in the same step (Section 11.1). Very little substitution product is formed. 

The Hofmann elimination reaction was used by early organic chemists as the last step of a process known as a Hofmaim degradation—a method used to identify amines. In a Hofmann degradation, an amine is exhaustively methylated with methyl iodide, treated with silver oxide to convert the quaternary ammonium iodide to a quaternary ammonium hydroxide, and then heated to allow it to undergo a Hofmann elimination. Once the alkene is identified, working backwards gives the stmcture of the amine. 

Amine oxides undergo a reaction similar to the Hofmann elimination reaction, called a Cope elimination reaction. In a Cope elimination reaction, a tertiary amine oxide rather than a quaternary anunonium ion undergoes elimination. The Cope elimination reaction occurs under milder conditions than does a Hofmann elimination reaction. 

Quaternary ammonium hydroxides and amine oxides undergo E2 elimination reactions known as Hofmann elimination reactions and Cope elimination reactions, respectively. In both reactions, the proton from the j8-carbon bonded to the greater number of hydrogens is removed. 

PROBLEM 6.38 There are three products formed in the Hofmann elimination reaction. They can be seen moving off the screen at the end at the reaction. Stop the animation while all three are stUl on the screen. You should be able to see water, an alkene, and an amine. Which do you suppose is the best nucleophile Select the HOMO representation for the animation. Remember that the HOMO represents the most available electrons, in other words, the most nucleophihc electrons. Based on the calculated HOMO, which of the three products is the most nucleophilic ... 

The Hofmann elimination reaction, on the other hand, is a process where a quaternary ammonium salt is decomposed into an olefin and a tertiary amine via exposure to basic conditions e.g., silver oxide and water) (Scheme 2.2). 

Bellucci et al. have proposed that in the Hofmann elimination reaction amine, the corresponding olefin and acidic sites in the aluminosilicate are formed during OLS decomposition... 

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. 

Hofmann elimination reaction elimination of a proton and a tratiary amine from a quatranary ammonium hydroxide (11.10). 

Exhaustive methylation of an amine, followed hy a Hofmann elimination reaction (11.10). 

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