Kolomoitsev O. Chemistry of 5-formylthiazole 2,4-disubstituted derivatives

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

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  • 102 - Хімія


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ДФ 64.051.043

V.N. Karazin Kharkiv National University


The dissertation is devoted to a series of 5-formylthiazole 2,4-disubstituted derivatives. Although to date, the study on the chemistry of thiazole, interest in these compounds is not declining. This is due to their physico-chemical, spectral, biological properties. These compounds have their place in chemistry, biology, pharmacy and materials science as a subject of practical application in many fields of science and technology. Thiazole-containing compounds have been studied since the 19th century, but over time, interest in formylthiazole derivatives has only grown. Thus, many interesting properties of 5-formylthiazole derivatives have been discovered from both scientific and practical points of view. Derivatives such as α,β-unsaturated systems based on 5-formylthiazole, are of interest due to the presence of an enone fragment that is part of them. Approaches to the modification of α,β-unsaturated systems to obtain diazaheterocyclic compounds containing two or more functions in their composition, significantly increase the variability of the functionalization of thiazole-containing compounds. For example, pyrimidines, 1H-imidazoles, 1H-pyrazolines, 1H-benzimidazoles with their interesting physicochemical, spectral, optical and biological properties are obtained, that opens a series of ways for their practical application. The thesis is devoted to the study of the chemical nature of thiazole derivatives, namely the physicochemical and spectral properties of groups of thiazole analogues: 2,4-disubstituted 4-(1,3-thiazol-5-yl)but-3-en-2-ones, 5-aryl-1-(2-dialkylamino-4- chlorothiazol-5-yl)penta-1,4-diene-3-ones, 2-dialkylamino-4-chloro-5-[2-(5-aryl-4,5- dihydro-1H-pyrazol-3-yl)vinyl]thiazoles based on them and diazaheterocyclic compounds ([4-(4-bromophenyl)-6-thiazol-5-yl-pyrimidin-2-yl]methylamines and 5-1H-benzimidazol-2-yl)thiazole). Transformation by the carbonyl group that is a structural fragment of 5-formylthiazoles, by Claisen-Schmidt condensation reactions, as well as modified Horner-Wadsworth-Emmons and Wittig approaches, novel α,β-unsaturated ketones – 4-(1,3-thiazol-5-yl)but-3-ene-2-ones were obtained. Functionalization of positions 2 and 4 of the thiazole cycle allowed to investigate the effect of substituents in these positions on the properties of the obtained compounds. The carbonyl component of 4-(1,3-thiazol-5-yl)but-3-en-2-ones through the Claisen-Schmidt reaction with aromatic aldehydes made it possible to obtain novel asymmetric dienone compounds – 5-aryl-1-(2-dialkylamino-4-chlorothiazol-5- yl)penta-1,4-diene-3-ones. Their properties were investigated by introducing these compounds into cyclocondensation with hydrazine, which also made it possible to obtain one of the two possible isomeric products of this interaction – 2-dialkylamino- 4-chloro-5-[2-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)vinyl]thiazoles. The obtaining of one isomer of 1H-pyrazoline derivatives was confirmed by spectral research methods and quantum chemical calculations. The effect of substituents at positions 2 and 4 of the thiazole cycle was studied for a series of 2,4-disubstituted derivatives of 5-formylthiazole: 4-(1,3-thiazol-5- yl)but-3-en-2-ones, 5-aryl-1-(2-dialkylamino-4-chlorothiazol-5-yl)penta-1,4-diene-3- ones and 2-dialkylamino-4-chloro-5-[2-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)vinyl] thiazoles. A special place in the work is devoted to obtaining of thiazole analogues of chalcone, which was performed by the interaction of 5-formylthiazole with 4-bromoacetophenone. At this stage, a method of bromination of α,β-unsaturated systems containing thiazole nucleus with hydrogen atoms in positions 2 and 4 was developed, in which the formation of halogenation or hydrohalogenation by-products is practically eliminated and the yield of target compounds is close to quantitative. Also, α,β-unsaturated ketone based on 5-formylthiazole has been proposed as an agent for heteroaromatization reactions with various 1,3-binucleophiles. As a result, novel thiazole-containing 1,3-diazaheterocyclic compounds are formed. As such binucleophiles α-aminoamidines were used, for which a convenient synthetic approach has been proposed.


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