Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions.

Nicole C Neyt,Darren L Riley

doi:10.3762/bjoc.14.129

Abstract

We recently reported a novel hybrid batch–flow synthesis of the antipsychotic drug clozapine in which the reduction of a nitroaryl group is described under flow conditions using sodium dithionite. We now report the expansion of this method to include the reduction of aldehydes. The method developed affords yields which are comparable to those under batch conditions, has a reduced reaction time and improved space-time productivity. Furthermore, the approach allows the selective reduction of aldehydes in the presence of ketones and has been demonstrated as a continuous process.

Highlights

Flow chemistry and continuous processing has been acknowledged by the American Chemical Society (ACS), the Green Chemistry Institute (GCI) and several global pharmaceutical companies as one of the primary areas for research and development for chemical manufacturing [1-4]
We recently published a batch–flow hybrid synthesis of the antipsychotic drug clozapine in which we demonstrated a flowbased reduction of a nitro group utilising sodium dithionite as a reductant [14]
In this publication we report the efficient reduction of aldehydes under flow conditions utilising sodium dithionite under basic conditions and the expansion of the approach to allow the selective reduction of aldehydes in the presence of ketones

Summary

Introduction

In this publication we report the efficient reduction of aldehydes under flow conditions utilising sodium dithionite under basic conditions and the expansion of the approach to allow the selective reduction of aldehydes in the presence of ketones. The process required 4.5 equivalents of sodium dithionite and was optimised in terms of flow rate and temperature using the reactor set-up shown in dence time of 64 minutes in the mixing chip and heated coil reactor (Table 2, Figure 3).

Results

Conclusion