Chalcones in the synthesis of heterocyclic compounds: pyrazoles, flavans and pyrimidines

This study was aimed at the synthesis of a library of heterocyclic compounds. The initial

reactions involved the condensation of substituted acetophenones with benzaldehyde

derivatives in either ethanolic solution of sodium hydroxide or by grinding method to yield

chalcones. The percentage yield of the products was substantially higher by grinding method

compared to that of ethanolic NaOH conventional method. It is noteworthy that the grinding

technique is an environmentally friendly method that avoids the organic solvents pollution

problem in organic synthesis. Thin layer chromatography was used to follow the reactions.

The structures of all compounds were characterized by spectroscopic techniques and verified

by comparison of their data with literature of similar compounds. In total eight chalcones

were synthesized being (E)-3-(2-hydoxyphenyl)-1-phenylprop-2-en-1-one 39, (E)-3-(4-

fluoro-2-hydoxyphenyl)-1-phenylprop-2-en-1-one 40, (E)-1-(4-aminophenyl)-3-(2-

hydoxyphenyl)prop-2-en-1-one 41, (E)-3-(4-fluorophenyl)-1-(4-nitrophenyl)prop-2-en-1-one

42, (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one 43, (E)-1-(4-fluorophenyl)-3-phenylprop 2-en-1-one 45, (E)-1,3-bis(4-fluorophenyl)prop-2-en-1-one 46, and (E)-1-(4-ethylphenyl)-3-

(4-fluorophenyl)prop-2-en-1-one 47 in yields of 65-79%. Methanolic 2'-hydroxychalcones

39-41, were reduced on subsequent addition of sodium borohydride to afford alcohols, 51-53,

which in the presence of glacial acetic acid cyclized to the corresponding flavans. Three

flavans were obtained namely 2-phenylchromane 54, 5-fluoro-2-phenylchromane 55, and 4-

(chroman-2-yl) aniline 56 in 80-82% yields. The chalcones employed to make flavans were

also used in the attempted synthesis of benzo[c]chromen-6-one using Et3N as the base with

just a 15% conversion. Reaction of chalcones with hydrazine hydrate in the presence of acetic

acid produced seven pyrazolines: 2(3-phenyl-4,5-dihydro-1H-pyrazol-5-yl)phenol 60, 5-(4-

fluorophenyl)-3-(4-nitrophenyl)-4,5-dihydro-1H-pyrazole 61, 1-(5-(4-nitrophenyl)-3-phenyl-

iii

4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one 62, 1-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-

yl)ethan-1-one 63, 1-(3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one

64, 1-(3,5-bis(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one 65 and 1-(3-(4-

ethylphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one 66, in 69-77%

yields. The chalcones were further reacted with thiourea in the presence of a base in ethanol,

which led to the formation of pyrimidine derivatives. The pyrimidines were described as

mixture made of three compounds in 67-69% yields. The pyrimidines synthesized were 2-(2-

mercapto-6-phenyl-1,2-dihydropyrimidin-4-yl) phenol 67a, 4-(2-hydroxyphenyl)-6-

phenylpyrimidine-2(1H)-thione 67b and 2-(2-mercapto-6-phenylpyrimidin-4-yl) phenol 67c,

4-(4-fluorophenyl)-6-(4-nitrophenyl)-1,2-dihydropyrimidine-2-thiol 68a, 4-(4-fluorophenyl)-

6-(4-nitrophenyl)pyrimidine-2(1H)-thione 68b, 4-(4-fluorophenyl)-6-(4-

nitrophenyl)pyrimidine-2-thiol 68c, 4,6-diphenyl-1,2-dihydropyrimidine-2-thiol 69 and 6-(4-

fluorophenyl)-4-phenyl-1,2-dihydropyrimidine-2-thiol 70. The reported synthetic method for

compound 58-59, is an alternative to hazardous methods reported in literature.