Production of pharmaceuticals: Amines from alcohols in a continuous flow fixed bed catalytic reactor

• Published in: Chemical engineering research & design 2010-12, Vol.88 (12), p.1533-1540
• Main Authors: Lamb, Gareth W., Al Badran, Firas A., Williams, Jonathan M.J., Kolaczkowski, Stan T.
• Format: Article
• Language: English
• Subjects: Amines; Applied sciences; Benzyl alcohol; Borrowing hydrogen; Catalysis; Catalysts; Catalytic reactions; Chemical engineering; Chemistry; Continuous flow; Continuous pharmaceutical processing; Exact sciences and technology; General and physical chemistry; Morpholine; N-Alkylation of amines using alcohols; Pharmaceuticals; Production of amines; Reactors; Solvents; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 0263-8762
• DOI: 10.1016/j.cherd.2010.04.005

This paper reports the use of an immobilised ruthenium complex in a continuous flow process for the N-alkylation of morpholine with benzyl alcohol. The ruthenium-based catalyst was supported on a phosphine bound polymer. Screening experiments were first performed in a batch reactor, with a 16 vol% mixture of morpholine and benzyl alcohol (stoichiometric molar ratio of 1:1) in toluene as the solvent. Operating at 110 °C for 24 h, it was shown that high conversions (>99%) into the desired tertiary amine could be achieved. This reaction was then shown to be viable in a continuous flow reactor, where the catalytic polymer beads were retained in the bed. Operating at 150 °C and using p-xylene as a solvent, the conversion into the desired tertiary amine was shown to be as high as 98%. This approach is clearly very promising, as it provides a greener and more atom efficient route for the production of secondary and tertiary amines in the pharmaceutical industry.