Announcement about the defense of the Doctor of Philosophy (Ph.D.) dissertation of Saitkulov Foziljon Ergashevich

General information

The topic of the dissertation, specialization code (name of the industry in which the degree is awarded): “Synthesis of 2Н(substituted)quinazolin-4-ones, some of their thioanalogues and selective methylation under different conditions” 02.00.03 – Organic chemistry (chemical sciences).

Registration number of the dissertation topic: В2022.4.PhD/K558

Scientific supervisor: Elmuradov Burkhon Zhurayevich, Doctor of sciences in chemistry, professor.

Name of the institution where the dissertation was fulfilled: Institute Chemistry of Plant Substances, Tashkent State agrarian university

The institution where Scientific Council operates, Scientific Council number: Institute of the Chemistry of Plant Substances,

DSc. 02/30.01.2020.K/T.104.01.

Official opponents: Khodjaniyazov Khamid Utkirovich, Doctor of sciences in chemistry, Kholikov Tursunali Suyunovich, Doctor of sciences in chemistry.

Leading organization: Tashkent Institute of chemical technology

Direction of the dissertation: theoretical and practical.

II. The purpose of the research is to develop improved methods for the synthesis of 2H (substituted) quinazolin-4-ones and -thiones, to carry out their methylation reactions with “hard” and “soft” methylating agents in an alkaline (KOH) environment, to identify the main factors influencing the direction of reactions and the type of isomers, comparison of the results obtained, determination of the structures, physicochemical and biological properties of the synthesized compounds.

III. Scientific novelty of the research is as follows:

for the first time, the methylation reactions of ambident and polydent anions of quinazolin-4-one were carried out systematically in polar proton (ethanol), aproton (dioxan-1,4), aproton bipolar (DMFA and DMSO) solvents at different temperatures and time durations, as a result, mainly N³-product formation is determined and justified according to Pearson's theory;

when reacting quinazolin-4-one with a "soft" methylating agent in DMFA at 85-90°C (Method B), the difficult-to-synthesize O⁴-methyl isomer (4-methoxyquinazoline) has been shown to be produced in good yield, and this method is recommended for use in target syntheses;

due to the positive inductive effect of the electron-donating (methyl) group, the electron cloud density in the pyrimidine ring of 2-methylquinazolin-4-one increases and as a result of the delocalization of ambient anion electrons, the reactions take place selectively at the N³-nitrogen atom in the presence of "soft" and "hard" methylating agents, in which the conversion is 100 % and it was proved that 2,3-dimethylquinazolin-4-one is formed with high yield;

simple and highly efficient synthesis methods of 2H(methyl, phenyl, 4-nitrophenyl)quinazolin-4-ones and important raw materials for their production - intermediate amides are recommended;

methylation reactions of quinazolin-4-ones with an electron acceptor (phenyl, 4-nitrophenyl) group are relatively difficult and nonselective, unlike analogs with an electron-donating group, but mainly the formation of N³-product and the course of the reaction are significantly dependent on temperature;

for quinazolin-4-one thionation reactions under different conditions, Lavesson's reagent was proved to be the most suitable reagent and a thionation mechanism has been proposed;

the interaction of 2H(methyl, phenyl)quinazolin-4-thiones with "soft" and "hard" methylating agents is carried out under different conditions, and in all methods, the reaction goes to the "soft" sulfur atom in relation to the N³ atom, resulting in the formation of the S⁴-methyl product with high selectivity was determined and this is explained by the easy polarizability of the sulfur atom;

it has been proven that dioxane-1,4 and DMSO are the most suitable solvents for obtaining S⁴-methyl products with high (100%) selectivity from 2H(methyl,phenyl)quinazolin-4-thiones.

IV. Implementation of research results. Based on scientific results obtained on the improved synthesis of 2H (substituted) quinazolin-4-ones and -quinazolin-4-thiones, obtaining selective (N¹-, N³-, O⁴-, S⁴-) methylation products, determining the structure and biological properties of the resulting compounds:

in order to obtain a product with anthelmintic activity, a patent for an invention was obtained from the Center for Intellectual Property of the Republic of Uzbekistan (No. IAP05685, 2018). As a result, it was possible to create a highly effective synthetic anthelmintic agent, easily soluble in water, for use in livestock;

results of X-ray structural analysis of 2,3-dimethylquinazolin-4-one is included to the Cambridge Structural Database (https://www.ccdc.cam, CCDC 1007927). As a result of the introduction of a new compound into the database, it was possible to synthesize similar compounds and describe their structure;

to implement Resolution No. 571 of the Cabinet of Ministers of the Republic of Uzbekistan “On measures to further improve the activities of Samarkand State University” dated July 24, 2018, a textbook “General Chemistry” was published for students (registration number No. 169) (Ministry of Higher and Secondary Special Education of the Republic of Uzbekistan, Decision No. 8 of the Council of SamDU named after Sharof Rashidov, 01/31/2023).

a textbook “Laboratory work in chemistry” was published (registration number No. 500-594) (order No. 500 of the Ministry of Higher and Secondary Special Education of the Republic of Uzbekistan dated November 23, 2021) for students. As a result, it became possible to use the manual in practice as modern generalized laboratory classes in analytical and organic chemistry for 1st-year students studying in the field of agricultural education;

the results of studying the tautomerism of derivatives of  2H(methyl-, methylthio-, phenyl)quinazolin-4-ones, 4-thiones and 4-aminoquinazolines were used in the fundamental project FA-F7-T207 “Theoretical problems of the formation of an asymmetric center in the molecule of biologically active heterocyclic compounds” with study of easy access to electrophilic exchange reactions of the methyl group in position 2 as a result of protonation of the N-1 nitrogen atom in an acidic environment (Certificate 4/1255-679 of the Academy of Sciences of the Republic of Uzbekistan dated March 26, 2024). As a result, a method has been created for the successful application of electrophilic substitution (addition) reactions to analogues of tricyclic quinazolone alkaloids with an activated α-methylene group.

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