Announcement about the defense of the doctoral (DSc) thesis of Kodirov Abduakhad Abdurakhimovich

 

Announcement about the defense of the doctoral (DSc) thesis of Kodirov Abduakhad Abdurakhimovich

I. General information.

The topic of the dissertation, specialty code (the name of the branch where the academic degree is awarded): «Synthesis, quantum chemical classification, modification, biological activity of aliphatic and heterocyclic nitriles and amides», 02.00.03 – Organic chemistry.

Dissertation topic registered number: B2022.3.DSc/K136.

Scientific advisors: Elmuradov Burkhon Jurayevich, doctor of chemical sciences, professor.

Name of the institution where the dissertation was completed: Karshi State University and Institute of the Chemistry of Plant Substances.

Name of the institution where the scientific council works, Number of the scientific council: Institute of the Chemistry of Plant Substances, DSc.02/30.01.2020.K/T.104.01.

Official opponents: Abdushukurov Anvar Kabirovich Doctor of Chemical Sciences, Professor; Bozorov Khurshed Abdulloevich Doctor of Chemical Sciences, Professor; Zhurakulov Sherzod Niyatkabulovich Doctor of Chemical Sciences, senior researcher.

Leading organization: Tashkent Pharmaceutical Institute

Dissertation direction: theoretical and practical.

II. The aim of the research work is development of improved one-pot methods for the synthesis of aminonitriles in a series of aliphatic, aromatic and heterocyclic amines using the Strecker reaction, carrying out their targeted chemical transformations, comparative analysis of the results, determining the structures, physicochemical and biological properties of the resulting compounds.

The scientific novelty of the dissertation research is as follows:

for the first time, the condensation of aliphatic, aromatic, heterocyclic amines and aliphatic diamines with acetone cyanohydrin was systematically studied and it was found that, depending on the structure of the substrate, the ratio of reagents, temperature and duration of reactions, mono- and bis-aminonitriles of various structures are formed;

it has been established that the cyanation reactions of amines and diamines in the presence of certain organic (acetone cyanohydrin, ACH) and a mixture of inorganic cyanides (NaCN, KCN, NH₄CN) with acetone proceeds according to the mechanism of one-pot synthesis and are recommended as an alternative cyanation agents;

the synthesis of aminonitriles is a reversible process, and it has been established that reactions are carried out with water-attracting agents (dry Na₂SO₄, K₂CO₃, CaCl₂) or by distillation of water, and the products are formed in a relatively short time and in high yield;

it has been established that nucleophilic substitution reactions involving diamines and ACH in a reagent ratio of 1:1 selectively form mono-aminonitriles in high yields at a significantly lower temperature (-15^оС); a decrease or increase in temperature leads to a decrease in the yield of the product or the formation of a mixture of mono- and bis-aminonitriles;

it has been established that reactions of nucleophilic substitution of diamines in the presence of acetone cyanohydrin and alternative cyanating agents [(cyanides + acetone)] in a reagent ratio of 1:2 under mild conditions (20-25^оС) lead only to bis-aminonitriles;

it was found that the formation reactions of monoaminonitriles of substituted anilines with an electron-donating group in the para-position (methods A, B, C, D) are more effective compared to aniline, which is associated with the low basicity of aniline, spatial factors, the increased basicity of amines is explained due to the electron-donating effect methyl and methoxy groups, the ease of nucleophilic substitution reactions, and the reaction mechanism was proposed;

nucleophilic substitution reactions of cyanohydrins synthesized on the basis of ketones (methyl ethyl ketone, cyclohexanone), benzaldehyde and p-substituted benzaldehydes with aliphatic, heterocyclic and aromatic amines were carried out, and methods for multicomponent one-pot synthesis of mono- and bis-aminonitriles and reaction mechanisms were proposed;

for the first time, as a result of the reaction of the natural alkaloid cytisine with acetone cyanohydrin and some aromatic aldehydes in the presence of an alkaline catalyst (K₂CO₃), aminonitriles with an additional asymmetric carbon atom in the molecule were synthesized, and their diastereomers were proven using X-ray diffraction analysis and physical research methods;

as a result of quantum chemical studies (Gaussian98 program, methods B3LYP/6-311G, DFT-B3LYP) of the structure and reactivity of (amino)nitriles, synthesized or comparatively selected in the course of research, products of their modification, it is theoretically substantiated that electron-withdrawing groups (nitrile , amide, thioamide) in the molecule have a significant effect on the charge distribution and direction of reactions with electrophilic agents (ipso-substitution and electrophilic addition);

complete hydrolysis of some synthesized bis-aminonitriles under various conditions occurs non-selectively; it has been established that as a result of the hydrolysis of both nitrile groups, a new bis-amino acid - 2,2'-(butane-1,4-diylbis(azandiyl))bis(2-methylpropane acid) is formed in high yield, which serves as an important building-block for organic synthesis and the reaction mechanism has been proposed;

hydrolysis of some of the obtained mono- and bis-aminonitriles was carried out, the synthesis of mono- and di-substituted derivatives under the influence of electrophilic reagents (acid anhydrides and acid chlorides) was carried out, and factors (temperature, catalyst) influencing the course of reactions were determined and the reaction mechanism was recommended.

IV. Implementation of the research results. Based on scientific results of research on the synthesis of α-aminonitriles and their various new derivatives, determination of the structure and biological activity of compounds obtained as a result of their chemical transformations:

on N,N-bis-(α-cyanoisopropyl)ethylenediamine, which has growth properties, a patent for an invention was received from the Center for Intellectual Property under the Ministry of Justice of the Republic of Uzbekistan (№IAP 07542, 2023). As a result, a highly water-soluble, low-toxic and highly effective synthetic stimulant was created for widespread use in agriculture;

the textbook “For laboratory training in organic chemistry” was published, approved by order of the Ministry of Higher Education, Science and Innovations of the Republic of Uzbekistan No. 314 dated July 17, 2023 (permission No. 314-207, 2023). As a result, students studying in this area have the opportunity to use a textbook that reflects modern chemical experiments;

methods for the synthesis of nitriles with an asymmetric carbon atom of heterocyclic amines and aromatic aldehydes in the presence of acetocyanohydrin 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”, carried out in 2012-2016 (Certificate 4/1255-2483 of the Academy of Sciences of the Republic of Uzbekistan dated November 8, 2023). As a result, the project succeeded in creating effective methods for the production of natural (alkaloid cytisine) and synthetic (piperidine, morpholine) nitriles of secondary amines with an asymmetric carbon atom;

there is a certificate No. 04/30-04/8646 dated November 21, 2022 from the Ministry of Agriculture of the Republic of Uzbekistan, confirming the results of using the preparation to increase cotton-tree harvest. As a result, it was found that cotton-tree treated with the preparation increases resistance to various diseases and, as a result of early harvest, the prolificness is 40 c/ha, profitableness is 11.8%;

based on the results of using the drug in experimental testing practice in a number of farms, Certificate №01/03-3392 of the “Council of farmers, farms and landowners of Uzbekistan” dated December 23, 2022 was received. As a result, the drug is recommended for use in order to increase the economic efficiency of cluster enterprises and farms, and the possibility of obtaining additional harvest has been created;

the preparation “Oltin Kuz”, which exhibits growth-stimulating properties, has received a Certificate as a trademark of the Center for Intellectual Property under the Ministry of Justice of the Republic of Uzbekistan (MGU 47964, 2023).

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