Issue in Honor of Prof. Keith Smith ARKIVOC 2012 (vii) 282-293
Mesoporous Structured Silica – An improved catalyst for direct amide synthesis and its application to continuous flow processing
James W. Comerford, Thomas J. Farmer, Duncan J. Macquarrie,* Simon W. Breeden, and James H. Clark
Green Chemistry Centre of Excellence, Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK E-mail:
[email protected]
This paper is dedicated to Professor Keith Smith, for the occasion of his 65th birthday
Abstract
We recently published details of an effective, reusable and benign heterogeneous amidation catalyst based on thermal treatment of amorphous K60 silica, however the loading of catalyst required was high for some reactions. We report herein our further development of a series of heterogeneous catalysts based on structured silica (SBA) that retain all the green credentials of the previously described amorphous silica, but with increased efficiency. These catalysts were then utilised in continuous flow systems, achieving excellent conversions with dramatically reduced reaction times.
Keywords: SBA-15, silica, amide, continuous process
Introduction
The formation of amides is one of the most important reactions in the pharmaceutical industry, though typically suffers from poor atom economy, with stoichiometric activating agents being required to achieve amide formation.1 In addition, many bio-derived platform molecules are acids, and there is great need to develop clean synthetic routes to form derivatives of these molecules, thus broadening the range of natural and sustainably derived pharmaceutical products.2-4 Ishihara and Whiting have both recently published catalytic routes to amides using boronic acids as catalysts, but the syntheses and recovery of these materials were problematic and the E-factor for amide synthesis when including the synthesis of the catalyst, but assuming no recovery, was high.5-6 We recently published research on a new route to amides using thermally-treated chromatographic silica as a clean and reusable catalyst, giving excellent yields (>70%) for a range of amides.7 More recently, Akamanchi et al. have demonstrated that sulfated
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