P. V. Kazakov
Nov 1, 2003
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Journal
Pharmaceutical Chemistry Journal
Abstract
N-substituted (naphth-1-yl)methylamines serve as precursors in the synthesis of some biologically active substances [1] including drugs (e.g., terbinafine) [2]. At present, there are two known pathways for the synthesis of N-alkyl(naphth-1-yl)methylamines. Reductive amination of 1-naphthaldehyde in hydrogen in the presence of Raney nickel allows N-methyl-(naphth-1-yl)methylamine to be obtained with a yield as high as 88% [3]. The reaction proceeds practically without formation of any side products and the target compound is readily isolated. The initial 1-naphthaldehyde can be obtained with a 60% yield via a modified Sommelet reaction proceeding from 1-(chloromethyl)naphthalene and urotropin [4]. Thus, the overall yield of N-methyl(naphth-1-yl)methylamine recalculated for 1-(chloromethyl)naphthalene does not exceed 53%. Originally, N-methylor ethyl-(naphth-1-yl)methylamine were obtained by alkylating the corresponding alkylamines with 1-(chloromethyl)naphthalene (I). The reaction in benzene with a fourfold excess of alkylamine yields the target product (II) in a mixture with the corresponding tertiary amine (III) [5]. Taking anhydrous alkylamines in a sixfold excess, it is possible to obtain amine II with a yield of 65 – 69% [1]. The only available method for the synthesis of 1-(chloromethyl)naphthalene (I) is based on the Blanc reaction.