Reductive alkylation of methylamine

Reductive alkylation of methylamine by 2,3-dimethoxybenzaldehyde, 59 Replacement, bromine by a thiol group, 35... 

Figure 7.19 Two-step synthesis of fatty acid glucamides by reductive alkylation of methylamine with glucose using Raney nickel as the hydrogenation catalyst to obtain Al-methyl glucamine, which is acylated by a base-catalyzed reaction with fatty acid methyl ester in a second step.

Other starting materials to make f, aside from nitriles, are fatty alcohols. F. are obtained by reductive alkylation of ammonia or methylamine with fatty alcohols at 90-190 °C under low hydrogen pressure in the presence of Raney nickel. If water is removed continuously from the reaction mixture, only secondary or tertiary amines are obtained. This reaction is mainly used when starting from synthetic fatty alcohols and focuses on the manufacture of textile softeners. It is, however, also used for making medium-chain (Cg-Cio) trialkylamines... 

Reduction of phenylacetone in the presence of methylamine rather than ammonia gives methamphetamine (53), an agent similar in action to the primary amine. Alkylation of 53 with benzyl chloride affords the analog, benzphetamine (54). ... 

Most of the widely used antidepressants are tricyclics related to imipramine. A 1-phenyltetrahy-droisoquinoline analogue, nomifensine (60), departs from this structural pattern. Hiarmacologi-cally it inhibits the reuptake of catecholamines such as dopamine at neurons. It can be synthesized by alkylation of 2-nitrobenzyl-methylamine with phenacyl bromide followed by catalytic reduction of the nitro group (Pd-C) and then hydride reduction of the keto moiety to give 59. Strong acid treatment leads to cyclodehydration to nomifensine (60) [17]. 

Methoxyphenylurea, 31,10,13 Methyl -acetylbenzoate, 32, 81 Methyl acrylate, 30, 65 32, 86 y-Methylallophanate, 32, 62 Methylamine, 30, 60 4 -Methyl-2-aminobenzophenone, 32,12 N-Methylaniline, 30, 62 31,110 N-Methylarylamines, preparation by reductive alkylation, 30, 59, 60 Methylation, of e-caprolactam, 31, 72 of quinacetophenone, with dimethyl sulfate, 31, 91 with methyl iodide, 31, 90 2-Methyl-3,l,4-benzoxaz-4-one, 32, 12 N-Methyl-a-bromo-n-butyranilide, 30, 63... 

In the second method (Scheme 26) a 3-oxo ester is synthesized from an acid chloride and 2,2-dimethyl-l,3-dioxane-4,6-dione. Then, reductive amination of the 3-oxo ester with a-methyl(phenyl)methylamine provides a 3-amino- 3-alkyl propionic acid ester. This compound is then converted into the corresponding aldehyde, which is condensed with an eno-late to afford the final product. A representative synthetic procedure of this method is given in detail. 

Aromatic hydrocarbons can be reduced to cycloalkenes by calcium dissolved in a mixture of methylamine and ethylenediamine. For example, calcium reduction of p-xylene (57) and anthracene (59) gives 1,4-dimethyl-l-cyclohexene (58) or decahydroanthracene (60) in 84% and 85% yield, respectively (Scheme 4.16). Calcium-amine combinations are different from lithium-amine systems in that they have little or no propensity to reduce internal double bonds despite the large excess of calcium employed. A grayish white precipitate, seemingly calcium alkyl amide. 

This variation on the activated aluminum method of reductive alkylation has the advantage of using methylamine hydrochloride directly in the reaction soup. Since methylamine is now very dangerous or impossible to obtain commercially, and also since the best method for making methylamine yields methylamine hydrochloride, the usefulness of this variation is obvious. 

Methylamine, 30, 60 Methylaniline, 30, 62 31, 110 N-Methylarylamines, preparation by reductive alkylation, 30, 59, 60 Methylation, of e-caprolactam, 31, 72 of quinacetophenone with dimethyl sulfate, 31, 91... 

N-Alkylation of amides. Benzotriazol-l-ylmethylation on the nitrogen atom of an amide is accomplished in refluxing acetic acid. Benzotriazole can then be displaced by reaction with an organometallic reagent (R2Zn, etc.). On LiAlH4 reduction A -methylamines are obtained. 

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