Anisole succinimide

A(-(Arylthiomethyl)amines, which are easily prepared and reportedly have better shelf stability than the corresponding )V-(alkoxymethyl)amines, have also been utilized to prepare tertiary amines. Alkenyl cuprate addition to )V,A -diethylphenylthiomethylamine produces allylic amines in high yield (entry 1, Table 6). Both alkenyl groups of the cuprate react. 5-(Dialkylaminomethyl) dithiocarbamates (entry 2, Table 6), sulfonates (entry 3, Table 6) and amides also generate iminium salts in situ. Of a variety of amides examined, imides such as dialkylaminomethyl-succinimides (entry 4, Table 6) and -phthali-mides provide the best overall yields. Organolithium reagents are rarely utilized in aminomethylation reactions. However, )V-chloromethylamines condense readily with lithiated anisole derivatives (entry S, Table 6). ... 

This side reaction is relatively innocuous because the by-product is irreversibly bound to the polymer and only the yield is affected not the purity of the synthetic peptide. More disturbing is the succinimide ring formation at aspartyl residues exposed to HF. Alkylation of the indole ring in tryptophan, the phenolic side chain in tyrosine and the sulfur atom in methionine must be suppressed by the addition of scavengers. The often appUed anisole is less than unequivocal in this role it can be the source of methyl groups which convert the methionine thioether to a tertiary sulfonium derivative. The acid stable thioanisole seems to be a better scavenger. 

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See also in sourсe #XX -- [ ]

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