Title:Recent Advances in the Multistep Continuous Preparation of APIs and Fine Chemicals
Volume: 23
Issue: 11
Author(s): Pedro P. de Castro*, Gabriel M.F. Batista, Giovanni W. Amarante, Timothy J. Brocksom and Kleber T. de Oliveira*
Affiliation:
- Department of Chemistry, Federal University of São Carlos, São Carlos, 13565-905, SP, Brazil
- Department of Chemistry, Federal University of São Carlos, São Carlos, 13565-905, SP, Brazil;
Keywords:
Continuous flow, Telescoped syntheses, End-to-end, APIs, Agrochemicals, Fragrances, Fine chemicals.
Abstract: Over the last two decades, with the advent of continuous flow technologies, continuous
processes have emerged as a major area in organic synthesis. In this context, continuous flow processes
have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine
chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development
of multi-step protocols has attracted special interest from the academic and industrial chemistry
communities. In addition to the beneficial aspects intrinsically associated with continuous
processes (e.g., waste reduction, optimal heat transfer, improved safety, and the possibility to work
under harsh reaction conditions and with more dangerous reagents), these protocols also allow a rapid
increase in molecular complexity. Moreover, in telescoped multi-step processes, isolation and
purification steps are generally avoided or, if necessary, carried out in-line, presenting an important
economy of time, solvents, reagents, and labor. Last, important synthetic strategies such as photochemical
and electrochemical reactions are compatible with flow processes and are delivering relevant
advances to the synthetic approaches. In this review, a general overview of the fundamentals of
continuous flow processes is presented. Recent examples of multi-step continuous processes for the
preparation of fine chemicals, including telescoped and end-to-end processes, are discussed, pointing
out the possible advantages and/or limitations of each of these methodologies.
