Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

Abstract

Microreactor technology and flow chemistry could play an important role in the development of green and sustainable synthetic processes. In this review, some recent relevant examples in the field of flash chemistry, catalysis, hazardous chemistry and continuous flow processing are described. Selected examples highlight the role that flow chemistry could play in the near future for a sustainable development.

Continuous‐Flow Synthesis of (R)‐Propylene Carbonate: An Important Intermediate in the Synthesis of Tenofovir

“…It also induces obligate chain termination when incorporated into DNA due to the lack of a 3′-hydroxy group. [3][4][5][6][7][8] Additionally, the synthesis of the enantiomerically pure 6 by the use of enantiomerically pure templates such as lactic acid or (R)glycidol (10) has been reported, as depicted in Scheme 1. The incorporation of this chiral group into the structures of TAF (1), TDF (2) or PMPA (3) can be achieved by the substitution reaction between the corresponding (R)-propylene carbonate [(R)-PC, 6] and adenine (5), which yields adenine 4 bearing a chiral secondary hydroxy group (Scheme 1).…”

“…The incorporation of this chiral group into the structures of TAF (1), TDF (2) or PMPA (3) can be achieved by the substitution reaction between the corresponding (R)-propylene carbonate [(R)-PC, 6] and adenine (5), which yields adenine 4 bearing a chiral secondary hydroxy group (Scheme 1). On the other hand, when starting from (R)-glycidol (10), hydrogenolysis of the epoxide leads to the corresponding (R)-1,2-propanediol (11) and subsequent reaction with dimethyl carbonate (12) will lead to the desired (R)-PC (6) in good yield and selectivity. When Scheme 1.…”

“…[9][10][11][12][13][14][15][16] Additionally, continuous-flow processes present advantages over batch procedures, such as improved mass and heat transfer, better safety profile, easier work-up, facilitated automation and scale-up, as well as a precise control of temperature, pressure and reaction time leading to higher reproducibility. [9][10][11][12][13][14][15][16] Additionally, continuous-flow processes present advantages over batch procedures, such as improved mass and heat transfer, better safety profile, easier work-up, facilitated automation and scale-up, as well as a precise control of temperature, pressure and reaction time leading to higher reproducibility.…”

“…In the approach presented in Scheme 2, (R)-6 is obtained from (R)-1,2-propanediol (11), which is available from racemic glycidol (10). The continuous-flow lipase-mediated kinetic resolution of 10 or 11 is the key step in the delivery of enantiomerically pure 6.…”

Continuous flow (micro-)reactors for heterogeneously catalyzed reactions: Main design and modelling issues

“…Several examples of continuous flow multistep reactions, often catalytically mediated, have been recently reviewed [8,51]. Very versatile configurations of micromixers, microreactors, heaters, pumps, membrane separators, etc.…”