Hofmann exhaustive

Hofmann exhaustive methyiation reaction org chem The thermal decomposition of quaternary ammonium hydroxide compounds to yield an olefin and water an exception is tetramethyiammonium hydroxide, which decomposes to give an alcohol. haf-mon ig z6s-tiv. meth-o la-shon re,ak-sh3n )... 

The Hofmann exhaustive N-methylation procedure, often used in classical structure determinations of alkaloids containing the piperidine nucleus, depends upon the formation of quaternary methyl salts. 

The above example was selected because the penta-1,4-diene cannot isomerize to a more conjugated isomer however, in many other examples this is not the case and, for example, a Hofmann exhaustive methylation reaction upon piperidine itself eventually leads to penta-2,4-diene (Scheme 2.33). 

A compound could be either 4-methoxycarbonyl-2,5-diphenylpiperi-dine or 4-methoxycarbonyl-3,5-diphenylpiperidine. How could you determine which formulation is correct, using the Hofmann exhaustive methylation procedure followed by reductive ozonolysis ... 

Assuming isomerism occurs to give the mosl stable (most conjugated and most highly substituted) dienes during the reactions, the two piperidines would undergo Hofmann exhaustive methyl-ation and subsequent ozonolysis as shown below. The diflerent orientation patterns are then reflected in the constitutions of the aldehydes and ketones that are formed. 

The present preparation of methylenecyclohexane is an example of an amine oxide pyrolysis. This route from amines to olefins in many cases yields pure olefins where the alternative method, the Hofmann exhaustive methylation reaction, is accompanied by some rearrangement to more stable isomeric olefins. 

An alternative bimolecular elimination process involves the thermal decomposition in an atmosphere of nitrogen of a quaternary ammonium hydroxide (Hofmann exhaustive methylation procedure). 

In analogy to piperidines, some 3-piperideines were subjected to the Hofmann exhaustive methylation. 5-Dimethylamino-l,3-pentadiene... 

Formations of 6-dimethylamino-2,4-hexadiene (163) from 1,6-dimethyl-3-piperideine,87 5-dimethylamino-4-methyl-1,3-pen tadiene (164) from l,3-dimethyl-3-piperideine,82 5-dimethylamino-3-methyl-1,3-pentadiene (165) from l,4-dimethyl-3-piperideine,83 and 6-di-methylamino-2,4-heptadiene (166) from l,2,6-trimethyl-3-piperi-deine94 may serve as further examples of the Hofmann exhaustive methylation in the 3-piperideine series. 

Hofmann exhaustive methylation, 43 Hydantoins, hydrolysis, 437 preparation, 437... 

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%). ... 

An example of a reaction that shows this latter regiochemistry is the Hofmann exhaustive methylation, which is sometimes called, rather ambiguously, the Hofmann degradation (this is a term best avoided, because it is sometimes also used to describe the Hofmann rearrangement). In this reaction, an amine is methylated with methyl iodide until the quaternary ammonium iodide is formed. This is then treated with moist silver oxide to convert the iodide to the hydroxide. Write out the final elimination step that occurs on heating. 

When we looked at anti-E2 bimolecular eliminations, we saw that the Hofmann exhaustive methylation followed that pathway. There are occasions, however, when it proceeds via different route. Normally, the hydroxide anion removes the (P-hydrogen, which then initiates the E2 mechanism. If, however, the quaternary ammonium derivative is so highly hindered that this is not possible, then the hydroxide anion removes a proton from one of the methyl... 

Hofmann degradation, but this causes confusion with the Hofmann exhaustive methylation, in which a quaternary ammonium hydroxide is... 

Hofmann degradation See Hofmann exhaustive methylation and Hofmann rearrangement. A term best avoided, because it is ambiguous. 

Hofmann exhaustive methylation The treatment of an amine with excess methyl iodide to form the quaternary ammonium iodide, which is then converted into the hydroxide by treatment with moist silver oxide on heating in an aqueous or alcoholic solution, it decomposes to give an alkene. Also called the Hofmann degradation. 

The synthesis has been carried out by Kamal et al. (1962) through an Hofmann exhaustive methylation of the Mannich product obtained by reaction of methylpyrazine with formaldehyde and dimethylamine hydrochloride. Goldman (1963) prepared vinylpyrazine by pyrolysis of pyrazine-ethanol. 

Hofmann exhaustive methylation of diol VII gave first the non-styrenoid product XIII in contrast to similar degradation of rhoeadine. 

The modified Hofmann exhaustive methylation of another reduction product of cytisine was useful in confirming the tertiary and bridge-head... 

Ethyl and methyl esters of aphyllic acid were prepared ethyl aphyllate,C17H30N2O2(monohydrate,m.p.76-77°, [a]o 25.3° (methanol)) methyl aphyllate, C16H28N2O2 (monohydrate, m.p. 82-83°). Hydrolysis of either ester yielded aphyllic acid, C16H26N2O2, m.p. 218-221°. On repeated distillation of the acid, the lactam, C18H24N2O ([a]J, 10.1° (methanol)), was reformed and was found to be identical with aphylline. The Hofmann exhaustive methylation of aphylline proceeded normally... 

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