- Title
- Synthesis of L-menthyl glyoxylate, an important intermediate in the manufacture of ARVS, using flow chemistry technology
- Creator
- Moyo, McQuillan
- Subject
- Chemistry
- Subject
- Pharmaceutical chemistry
- Subject
- Organic compounds -- Synthesis
- Date Issued
- 2017
- Date
- 2017
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/12019
- Identifier
- vital:27018
- Description
- Herein an alternative approach to the conventional batch synthesis of L-menthyl glyoxylate hydrate (MGH), an important intermediate in the synthesis of drugs of importance is reported, through flow chemistry technology. MGH was initially synthesized in batch and various reaction parameters optimized. It was found to proceed to completion after 6 hours of esterifying glyoxylic acid with excess alcohol (L-menthol) in the presence of a catalyst, ideally amberlyst-15 (an ion exchange resin) at 105 °C giving a yield of 72 %. The batch reaction conditions were adopted in a continuous flow synthesis setup, using the Labtrix Start system, in which reaction conditions were optimized. The optimization of glyoxylic acid conversion (92 %) in the Labtrix Start system gave reaction conditions that resulted in low MGH selectivity (25 %) whereas the optimization for MGH selectivity (100 %) gave a conversion a poor glyoxylic acid conversion (15 %). The FlowSyn system fitted with a column reactor gave the best results, in which the optimum conditions were an excess of L-menthol (1.5 M, 6.0 equiv.), temperature (80 °C) and a residence time of 2.5 minutes with a high selectivity (77 %) and average conversion (50 %). The optimized reaction conditions for conversion and selectivity on the different flow systems did not vary significantly and similar trends were observed for the systems. It was shown that an increase in temperature, mole equivalents and residence time led to an increase in MGH conversion in all flow systems. The scale up of the esterification reaction from the Labtrix Start system (19 μL microreactor) to the FlowSyn system fitted with a 2 mL reactor chip, showed that the reaction proceeds with a slight drop in selectivity from 100 % to 92 % while conversion dropped from 15 to 12 %. On the contrary, a significant drop in conversion and selectivity were observed when the FlowSyn column reactor was up-scaled to the Elite-tubular furnace, owing to the poor mixing in the larger channel size reactor.
- Format
- x, 146 leaves
- Format
- Publisher
- Nelson Mandela Metropolitan University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela Metropolitan University
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NMMU School of BioMolecular and Chemical Sciences
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