Reaction Optimization Using a Microwave Autosampler

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Introduction

Upon discovery of a novel chemical transformation, the time-consuming and often-tedious process of reaction optimization begins (with substrate screening to follow). Though microscale reactions may be performed in parallel using a heating block, some reaction parameters cannot be adjusted easily in this format, consuming precious time for manually-performed, sequential reactions. The Autosampler 12 and 48 (developed in conjunction with the CEM Discover® 2.0 microwave reactor), however, provides researchers a more efficient means to optimize and screen their chemistry. The Hantzsch dihydropyridine synthesis.
Scheme 1: The Hantzsch dihydropyridine synthesis.

To demonstrate the improved simplicity and efficiency offered by the Autosampler, a general microwave-assisted Hantzsch dihydropyridine synthesis (Scheme 1) was optimized and then applied in the synthesis of a small chemical library. In the Hantzsch dihydropyridine synthesis, ammonia, an aldehyde, and (most often) a β-keto ester undergo a series of condensations to afford a 1,4-dihydropyridine compound. Though frequently isolated, the dihydropyridine compound can spontaneously oxidize to the corresponding substituted pyridine.