Biginelli Reaction Lab Report

CHAPTER III
BIGINELLI REACTION
INTRODUCTION

Dihydropyrimidinones (DHPMs), commonly known as Biginelli compounds, have attained unprecedented attention due to its greater biological, pharmaceutical and therapeutic properties. In 1893, Pietro Biginelli reported the first synthesis of 3,4-dihydroprimidin-2(1H)ones (DHPM) by a very simple multi-component one-pot condensation reaction of an aromatic aldehyde, urea and ethyl acetoacetate in ethanolic solution1 (Scheme 1.1). This efficient approach to partly reduced pyrimidines, termed the Biginelli reaction or condensation, was largely ignored in the following years, and therefore, also the synthetic potential of these multi-functionalized dihydropyrimidines remained unexplored. In recent years, however, interest in these compounds has increased rapidly, and the scope of the original cyclocondensation reaction has been widely extended by variation of all three components.

Scheme 1.1. Classical Biginelli

As early as 1930 simple derivatives such as 33 were patented as agents for the protection of wool against moths.52 Later, interest focused on the antiviral activity of Biginelli compounds,53 eventually leading to the development of nitractin (34), which has excellent activity against the viruses of the trachoma group.14,54 The Biginelli compounds also exhibits modest antibacterial activity. 55 Dihydropyrimidinone 1 and some of its analogs were screened as antitumor agents and found to be active against Walker carcinosarcoma in rats and mice.55-57 Pyrimidine 5-carboxamides of type 35 are reported to possess anticarcinogenic58 activity. Antinflammatory,9,59 antioxidant,59b analgesic,9 and blood platelet aggregation inhibitory activity 8 was found in a number of derivatives. 1,4 Dihydropyrimidine 36 is useful as platelet- activating factor antagonist.60 Other Biginelli compounds were shown to inhibit the uptake of adenosine by thrombocytes.