Announcement about the defense of Berdiev Abdugani's Doctor of Philosophy (PhD) dissertation

Announcement

about the defense of Berdiev Abdugani's Doctor of Philosophy (PhD) dissertation

I. General information.

Dissertation topic, specialization code (name of the field of study for which the degree is awarded): “Synthesis and chemical transformations of 5,6-Disubstituted-4-chlorothieno[2,3-d]pyrimidines”, 02.00.03 – Organic chemistry (chemical sciences).

Dissertation topic registered number: B2023.2.PhD/K620

Supervisor: Elmuradov Burkhon Zhurayevich

Dissertation prepared institution: Institute of the Chemistry of Plant Substances named after Acad. S.Y. Yunusov. AS RUz.

Institution where Scientific Council operates, Scientific Council number: Institute of the Chemistry of Plant Substances named after Acad. S.Y. Yunusov. AS RUz., DSc. 02/30.01.2020.K/T.104.01.

Opponents: doctor of chemical sciences, professor Abdushukurov Anvar Kabirovich, doctor of chemical sciences, professor Bozorov Khurshed Abdulloyevich.

Lead organization: Tashkent Institute of chemical technology.

Dissertation direction: theoretical and practical.

II. The aim of the study is to develop improved methods for the synthesis of esters of disubstituted 2-aminothiophenes, thieno[2,3-d]pyrimidin-4-ones and 4-chloro(hydrazinyl)thieno[2,3-d]pyrimidines, carrying out reactions of their nucleophilic substitution and electrophilic additions with amines (diamines) and carbonyl compounds, determination of the structure, physicochemical and biological properties of the synthesized compounds.

III. Scientific novelty of the study is as follows:

it was revealed that as a result of an increase in the electrophilicity of the carbon atom of the imidoyl chloride (Cl-C⁴=N) fragment of the 4-chloro-TP, a nucleophilic attack of amines occurs in these center and new amino compounds containing C-N bonds are formed and a reaction mechanism is proposed;

it was discovered for the first time that the reaction of nucleophilic substitution of 5,6-disubstituted 4-chloro-TP with tryptamine (a natural alkaloid) in an equimolar ratio of reagents is carried out by a nucleophilic attack of the exocyclic amino group and the formation of “NH-bridged” new “tryptamine-TP” hybrid molecules with high yields;

it was established for the first time that the reaction of secondary heterocyclic amines with 5,6-disubstituted 4-chloro-TP leads to the formation of mono- and disubstituted symmetrical products depending on the structure of the amino component; the reactivity of the starting substances and the yield of products increase in the series of (CH₂)₅→( CH₂)₃→(CH₂)₄ polymethylene chain;

for the first time, reactions of nucleophilic substitution of the natural alkaloid cytisine and 5,6-disubstituted 4-chloro-TP in various solvents (EtOH, CCl₄, C₆H₆) were carried out, and it was revealed that the most suitable solvent is CCl₄ and new “cytisine-TP” hybrid molecules are formed in high yields;

as a result of the nucleophilic addition-elimination reaction of 5,6-disubstituted 4-hydrazinyl-TP with aromatic aldehydes in the presence of acid catalysts, E-isomeric benzylidene-hydrazinyl-TP was synthesized in good and high yields, the structure of the products was confirmed by modern spectral methods;

for the first time, reactions of TP containing a hydrazine (binucleophilic) fragment with a dicarbonyl compound (acetylacetone) under “green chemistry” conditions were carried out, and it was established that as a result of mono- and bis-heterocyclization, new hybrid molecules containing a pyrazole ring are formed;

for the first time, Suzuki-Miyaura cross-coupling reactions of TP, containing C-Cl bonds and phenylboronic acid under the influence of a Pd catalyst were carried out and the main factors influencing the yield of products were identified.

IV. Implementation of research results.

Based on scientific results obtained on the improved synthesis of 2-aminothiophene esters, 5,6-disubstituted TP-4-ones, 4-chloro-TP, 4-hydrazinyl-TP, preparation of targeted amino compounds, hybrid molecules and cross-coupling products, definitions structure and biological properties of the obtained compounds:

X-ray diffraction results of 3-(5,6,7-trihydrocyclopenta[4,5]thieno[2,3-d]pyrimidin-4-yl)-1,2,3,4,5,6-hexahydro-8H-1, 5-methanopyrido[1,2-a][1,5]diazocin-8-one, 3-(5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, 3-(5,6-dimethylthieno [2,3-d]pyrimidin-4-yl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5] diazocine-8-one, 5-methyl-4-(8-oxo-1,5,6,8-tetrahydro-2H-1,5-methanopyrido [1,2a][1,5]diazocin-3(4H)-yl) thieno[2,3-d]pyrimidine-6-ethylcarboxylate are included into Cambridge Crystallographic Database (The Cambridge Structural Database, https://www.ccdc.cam, CCDC: 2279685, 2279686, 2279687, 2279688). The results of including new compounds into the database made it possible to synthesize similar compounds and describe their structure;

the results of the synthesis and chemical transformations of 5,6-disubstituted-4-chloro(hydrazinyl)thieno[2,3-d]pyrimidines were used in the fundamental project No. VA-FA-F-7-006 “Fundamental principles of the synthesis of new generation selective pesticides in the series of sulfonylureas, triazines and their heterocyclic analogues” in the synthesis of promising hydrazines by the reaction of 5,6-disubstituted-4-chlorothieno[2,3-d]pyrimidines with hydrazine hydrate and their successful interaction with carbonyl compounds to form the corresponding potentially active arylhydrazines in E-isomeric forms (Certificate 4/1255-697 of the Academy of Sciences of the Republic of Uzbekistan dated March 28, 2024). As a result, it was established that the reaction of 2,3-trimethylene-3,4-dihydroquinazoline-4-thione with hydrazine hydrate makes it possible to synthesize promising hydrazines and successfully use of them in reactions with carbonyl compounds.

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