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Issue 15, 2017
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Reaction screening and optimization of continuous-flow atropine synthesis by preparative electrospray mass spectrometry

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Abstract

Preparative electrospray (ES) exploits the acceleration of reactions in charged microdroplets to perform a small scale chemical synthesis. In combination with on-line mass spectrometric (MS) analysis, it constitutes a rapid screening tool to select reagents to generate specific products. A successful reaction in preparative ES triggers a refined microfluidic reaction screening procedure which includes the optimization for stoichiometry, temperature and residence time. We apply this combined approach for refining a flow synthesis of atropine. A successful preparative ES pathway for the synthesis of the phenylacetyl ester intermediate, using tropine/HCl/phenylacetyl chloride, was optimized for solvent in both the preparative ES and microfluidics flow systems and a base screening was conducted by both methods to increase atropine yield, increase percentage conversion and reduce byproducts. In preparative ES, the first step yielded 55% conversion (judged using MS) to intermediate and the second step yielded 47% conversion to atropine. When combined in two discrete steps in continuous-flow microfluidics, a 44% conversion of the starting material and a 30% actual yield of atropine were achieved. When the reactions were continuously telescoped in a new form of preparative reactive extractive electrospray (EES), atropine was synthesized with a 24% conversion. The corresponding continuous-flow microfluidics experiment gave a 55% conversion with an average of 34% yield in 8 min residence time. This is the first in depth study to utilize telescoped preparative ES and the first use of dual ESI emitters for multistep synthesis.

Graphical abstract: Reaction screening and optimization of continuous-flow atropine synthesis by preparative electrospray mass spectrometry

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Publication details

The article was received on 13 Apr 2017, accepted on 20 Jun 2017 and first published on 21 Jun 2017


Article type: Paper
DOI: 10.1039/C7AN00622E
Citation: Analyst, 2017,142, 2836-2845
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    Reaction screening and optimization of continuous-flow atropine synthesis by preparative electrospray mass spectrometry

    C. E. Falcone, Z. Jaman, M. Wleklinski, A. Koswara, D. H. Thompson and R. G. Cooks, Analyst, 2017, 142, 2836
    DOI: 10.1039/C7AN00622E

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