Download (4Mb) - Etheses - Saurashtra University

Chapter – 4 Studies on different types of reactions…..
hydrochloric acid at reflux temperature (Fig. 4.26). The product of this novel
one-pot, three-component synthesis that precipitated on cooling of the
reaction mixture was identified correctly by Biginelli as 3, 4-dihydropyrimidine-
2(1H)-one. Apart from a series of publications by the late Karl Folkers in the
mid 1930s, the “Biginelli reaction” or “Biginelli condensation” as it was
henceforth called was largely ignored in the early part of the 20 th century. The
synthetic potential of this new heterocycle synthesis therefore remained
unexplored for quite some time. In the 1970s and 1980s, interest slowly
increased and the scope of the original cyclocondensation reaction was
gradually extended by variation of all three building blocks, allowing access to
a large number of multifunctionalized dihydropyrimidines. 297-299
Dihydropyrimidinone derivatives are of considerable interest in industry
as well as in academia because of their promising biological activities as
calcium channel blockers, antihypertensive agents, and anticancer drugs. 298,
299 300 300
They also show anti fungal activity, antibacterial activity, antiviral
activity 301 and antitumor 301 activity. They are also known as analgesics 302
and antidepressants. 303 Thus, synthesis of this heterocyclic nucleus is of
much importance, and quite a number of synthetic procedures based on the
modifications of the century-old Biginelli’s reaction involving acid-catalyzed
three-component condensation of 1,3-dicarbonyl compound, aldehyde, and
urea, have been developed during past few years. 298, 299 Basically, these
methods are all similar, using different Lewis acid catalysts such as BF3, 304a
FeCl3, 304b InCl3, 304c BiCl3, 304d LaCl3, 304e LiClO4, 304f Mn-(OAc)3, 304g CAN,
304h
and VCl3 304i in a solvent such as CH3CN, CH2Cl2, or THF. Recently, a
number of procedures under solvent-free conditions using Yb(OTf)3, 304j
montmorillonite 304k and ionic liquid 304l as catalysts have also been reported.
Biginelli reaction consists three components i.e. aldehyde functional
group, urea or thiourea and β-keto ester. Many reactions have been reported
using differently substituted aromatic as well as aliphatic aldehydes.
Substituted ureas and thioureas have also been used in the synthesis of Nsubstituted
dihydropyrimidine derivatives as well. Simple β-keto esters viz.
ethylacetoacetate, methylacetoacetate and acetylacetone have been widely
Department of Chemistry, Saurashtra University, Rajkot – 360 005 214