Reinvestigating Raney nickel mediated selective alkylation of amines with alcohols via hydrogen autotransfer methodology

•New application of Raney nickel (R-Ni) for N-alkylation of amines using alcohol.•R-Ni prepared and characterized as autohydrogen transfer agents.•Scope of reaction explored with different amines and alcohols.•Optimized conditions applied to synthesis of pharmaceutical actives.

An efficient, cost-effective use of Raney nickel (R-Ni) a widely used industrial catalyst for N-alkylation using alcohols is highlighted here. The work describes the scope and capability of R-Ni in hydrogen autotransfer reactions enabling its widespread use in the Chemical and Pharmaceutical industry. R-Ni of W4, T4, and W7 grades were prepared and evaluated for alkylation of amines. The best activity and selectivity for mono alkylation of amines were obtained using W4 R-Ni at 1:4 moles of amine to alcohol in xylene at reflux. T4 R-Ni also showed ability to form stable imines. The prepared R-Ni was also recycled and reused for N-alkylation reaction. The optimized methodology was applied for synthesis of Active Pharmaceutical ingredients Piribedil and Mepyramine. The simplicity and wide substrate scope makes this method a preferred Hydrogen Auto-transfer protocol for the alkylation of amines.

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