Fully Automated Flow-Through Synthesis of Secondary Sulfonamides in a Binary Reactor System

Abstract

A fully automated flow-through process for the production of secondary sulfonamides is presented. Primary sulfonamides were monoalkylated using a two-step "catch and release" protocol to generate library products of high purity. The automated flow synthesis platform incorporates four independent reactor columns and is able to perform automated column regeneration. A 48-member sulfonamide library was prepared as two 24-member sublibraries, affording library compounds in good yields and high purities without the need for further column chromatographic purification.

9.03 Organic Synthesis in Small Scale Continuous Flow: Flow Chemistry

“…The researchers were able to screen 48 combinations of sulfonamides (common medicinal functionalities) using the system outlined in Figure 37. 114 In many cases, the products were pure enough for direct biological application without further purification. Purity was determined by offline ultra performance liquid chromatography.…”

Continuous flow based catch and release protocol for the synthesis of α-ketoesters

“…Finally, after flow-washing (step 3), the solid supported species is hydrolysed, liberating α-ketoester product 4 by flowing aqueous acetic acid (step 4) through the in-line column. The overall route constitutes a new flow chemistry example of the catch - react - and - release concept that we have used successfully in other synthesis programmes [101–103]. …”

Polymer‐Supported Organosuperbases

“…Due to the strong basicity, high steric hindrance and low quaternizability of polymersupported superbase reagents, several types of O-and N-alkylation reactions have been reported, with the goal of contributing to combinatorial chemistry [45][46][47][48][49][50][51][52][53][54][55][56][57][58] The role of PS-TBD can be easily understood if it is considered that it works not only as a base to deprotonate phenols, but also as a scavenger to trap unreacted excess starting phenols. In addition, also established was a convenient strategy for performing multi-step conversions in one-pot operation as represented by Scheme 6.12 [47].…”