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1.2.1.2 Third Component 1,3-Dicarbonyl Compound (with Ammonia or Amines: Hantzsch Pyridine Synthesis)

DOI: 10.1055/sos-SD-210-00051

Vanden Eynde, J. J.; Mayence, A.Science of Synthesis: Multicomponent Reactions, (2014167.

General Introduction

Derivatives of the 1,4-dihydropyridine-3,5-dicarboxylic acid skeleton and structurally related analogues are widely known under the name of Hantzsch 1,4-dihydropyridines or the 1,4-DHP abbreviation. It was at the end of the 19th century that Arthur Hantzsch had the idea to heat a mixture of acetaldehyde, ammonia, and ethyl 3-oxobutanoate in the absence of solvent. The compound so-obtained was identified as diethyl 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) (Scheme 1). A first report on the experiment appeared in 1881[‌1‌] and it was followed, 1 year later, by the habilitation thesis of Hantzsch published in Justus Liebigs Annalen der Chemie.[‌2‌] The reaction is now named the “Hantzsch pyridine synthesis”, although the products are in fact dihydropyridines.

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References