Hofmann elimination reaction mechanism

It has been noticed that the reverse reaction of Eq. (5) is a particular type of the Hofmann elimination reaction (26) via either an E2 or an ElcB mechanism. An E2 mechanism seems to be more obvious for this reaction than an ElcB mechanism, however. 

Eubanks, J. R. I., Sims, L. B., Fry, A. Carbon isotope effect studies of the mechanism of the Hofmann elimination reaction of para-substituted (2-phenylethyl-1- C)- and (2-phenylethyl-2- C)-trimethylammonium bromides. J. Am. Chem. Soc. 1991, 113, 8821-8829. 

It is noted that a nitrogen ylid has been invoked in the Hofmann elimination reaction (sec. 2.9.C.i). 4 This ylid mechanism is highly questionable for many substrates that proceed via 3-elimination with a coordinated hydroxide.In those cases, removal of the hydrogen directly by hydroxide appears more likely. The ylid mechanism probably operates when PhLi is used as a base and when there is steric inhibition of the usual (3-elimination process. 

Cope, A.C., Mehta, A.S. (1%3) Mechanism of the Hofmann elimination reaction an yUde intermediate in the pyrolysis of a highly branched quaternary hydroxide. Journal of the American Chemical Society, 85, 1949-1952. 

Sulfonium compounds (—C— SR2) undergo elimination similar to that of their ammonium counterparts (17-6 and 17-7) in scope and mechanism but this reaction is not of great synthetic importance. These syn-elimination reactions are related to the Cope elimination (17-8) and the Hofmann elimination (17-6). ... 

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 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. 

For the reaction mechanism it was suggested that the hydrochloride salts of 540 suffered Hofmann elimination to give pyrimidines 544. The 4-chloro-5-[(2-benzylamino)ethyl] pyrimidines 544 then underwent cycliza-tion to pyrrolo[2,3-[Pg.166]

The leaving groups commonly employed in E2 reactions are listed in Table 2.1. As you can see, they are essentially the same as those displaced in nucleophilic substitution reactions (see Part 2), with two exceptions. First, protonated alcohols are not listed as substrates RX in Table 2.1, because they usually react by the El mechanism (as we shall see later) rather than the E2 mechanism. Secondly, the trimethylammonium and dimethylsulfonium groups have limited importance as leaving groups in substitution reactions, although they are particularly important in elimination reactions. In fact, the reaction involving trimethylammonium is known, after its discoverer, as the Hofmann elimination... 

The duality of stereochemical mechanism persists in the Hofmann elimination from the beta deuterium-labelled derivatives of the threo and erythro isomers of the compound (99). under a variety of reaction conditions. ... 

The intramolecular elimination just illustrated is under kinetic control, rather than thermodynamic control, and the transition state leading to removal of a P-proton from the less substituted P-carbon is lower in energy, so reaction occurs faster. This is the fiindamental difference between E2 reactions and intramolecular elimination reactions. The transformation of amine 42 to alkene 43 is called Hofmann elimination, named after August Hofmann (Germany 1818-1892). Other elimination reactions proceed by an intramolecular elimination mechanism, but Hofmann ehmination is the only one that will be discussed. 

The mechanism of the Hofmann elimination has received considerable attention in the last two decades and a number of reviews on the mechanism of this and other elimination reactions have appeared . Two facets of the reaction have been studied in particular, the degree of concertedness of the reaction and the orientation of the elimination. 

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