SYNTHESIS OF ISOMERIC ALKYL DERIVATIVES IN THE 2-METHYL-5-CHLOROBENZIMIDAZOLE SERIES
Authors
B.B. Zhuraev, E.O. Rakhmatov, T.M. Muminova, D.A. Ziyodov, I.S. Ortikov
Share
Annotation
Origin of the problem. Currently, benzimidazoles and their derivatives are of great importance from theoretical and practical points of view among heterocyclic compounds. The presence in their molecule of a benzene and imidazole ring and an ambifunctional fragment containing a secondary nitrogen atom leads to their existence in various tautomeric forms and allows regioselective reactions of alkylation, acylation, arylsulfonylation and chlorosulfonylation at one or another center.
It should be noted that among benzimidazoles and their derivatives there are quite highly effective drugs that are successfully used in agriculture, medicine, pharmaceuticals and other industries. For example, Veliparib (ABT-888) is a potential anticancer drug that acts as a PARP (poly(ADP-ribose) polymerase) inhibitor. Veliparib during radiation therapy causes the whole brain to work effectively against brain metastases from non-small cell lung cancer (NSCLC - Non-small-cell lung cancer). Additionally, Lerisetron (F-0930-RS) is a drug that acts as an antagonist (namely, it kills the virus) at the 5-HT3 receptor, which is a potent antiemetic and is being used in clinical trials to treat nausea associated with cancer chemotherapy.
Thanks to scientific research, the synthesis and introduction into practice of various pharmacologically active drugs is becoming important for restoring the health of many patients. The synthesis of new derivatives of heterocyclic compounds, the study of possible reaction mechanisms, and the implementation of targeted synthesis of biologically active substances are also important.
Therefore, the study of alkylation reactions of benzimidazoles and their derivatives, identification of the main factors influencing the course and direction of reactions, and the search for biologically active substances among synthesized compounds is an urgent task.
Purpose of the work. Synthesis of Nendo-protected 2-methyl-5-chlorobenzimidazoles (N-alkyl derivatives), determination of the type and ratio of isomers, determination of factors influencing the course of the reaction and study of the structure of the resulting compounds (IR, 1H and 13C NMR spectroscopy).
Methodology. Carrying out reactions of introducing an alkyl group into the 2-methyl-5-chlorobenzimidazole molecule with alkyl halides in a protic solvent (alcohol) in the presence of alkalis and studying the proposed mechanism. Studying the structure of substances using IR, 1H and 13C NMR spectroscopy methods.
Scientific novelty. Taking into account the main factors influencing the course of reactions, new isomeric 1,2-dialkyl derivatives were synthesized under various conditions and an optimal method for obtaining the target products was developed.
Results obtained. The synthesis of new dialkyl isomers in the series of benzimidazoles containing various alkyl groups has been carried out. The structure of the substances was analyzed based on IR, 1H and 13C NMR spectroscopy data and their correspondence to the proposed structures was proven.
Keywords
Authors
B.B. Zhuraev, E.O. Rakhmatov, T.M. Muminova, D.A. Ziyodov, I.S. Ortikov
Share
References:
Tahlan S., Kumar S., Narasimhan B. Pharmacological significance of heterocyclic 1 H-benzimidazole scaffolds: a review // BMC chemistry. – 2019. – Vol.12-13. –№1. – С.1-21.
Tahlan S. et al. Design, synthesis and therapeutic potential of 3-(2-(1H-benzo [d] imidazol-2-ylthio) acetamido)-N-(substituted phenyl) benzamide analogues // Chemistry Central Journal. – 2019. – Vol. 12. – №1. – P.1-12.
Tahlan S., Ramasamy K., Lim S.M., Shah S.A.A., Mani V., Narasimhan B. (2-(1H-Benzo[d]imidazol-2-ylthio)acetamido)-N-(substituted phenyl) benzamides: design, synthesis and biological evaluation // BMC Chemistry. -2019. – Vol.3. - №12. -P.1–16.
Alpan A. S. et al. Synthesis, biological activity and molecular modeling studies on 1H-benzimidazole derivatives as acetylcholinesterase inhibitors // Bioorganic & medicinal chemistry. – 2013. –Vol.21. – №17. –P.4928-4937.
Andrzejewska M. et al. Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4, 6-dibromo-and 4, 6-dichloro-2-mercaptobenzimidazoles // European journal of pharmaceutical sciences. – 2004. – Vol.21. – №2-3. –С.323-329.
Shaharyar M. et al. Benzimidazoles: A biologically active compounds //Arabian Journal of Chemistry. – 2017. –Vol. 10. – P.S157-S173.
Yoon Y. K. et al. Synthesis and evaluation of antimycobacterial activity of new benzimidazole aminoesters // European journal of medicinal chemistry. – 2015. – Т. 93. – С. 614-624.
Tahlan S. et al. 2-Mercaptobenzimidazole Schiff bases: design, synthesis, antimicrobial studies and anticancer activity on HCT-116 cell line // Mini reviews in medicinal chemistry. –2019. – Vol.19. –№13. – P.1080-1092.
Kakkar S. et al. Benzoxazole derivatives: design, synthesis and biological evaluation // Chemistry Central Journal. – 2018. –Т.12. – №1. – С.1-16.
Tahlan S., Kumar S., Narasimhan B. Pharmacological significance of heterocyclic 1 H-benzimidazole scaffolds: a review // BMC chemistry. –2019. – Vol.13. – P.101-122.
Prajapat P. Importance of Benzothiazole Motif in Modern Drug Discovery: Introduction // Modern Approaches in Drug Designing (MADD). -2018. – Vol.1. -№4. –P.1-2.
Jurayev B.B., Ortikov I.S., Elmuradov B.J., Tadjimukhamedov Kh.S. // Improved methods of synthesis of 2-alkyl-5-chlorobenzimidazoles // “Zamonaviy kimyoning dolzarb muammolari” mavzusidagi respublika miqyosidagi xorijiy olimlar ishtirokidagi onlayn ilmiy-amaliy anjumani, Buxoro, 2020, 4-5-dekabr, 254-256-betlar.
Juraev B., Oxunxo’jayeva Z., Tojiboev A., Bobakulov Kh., Turgunov K., Elmuradov B., Zokhidov K. Synthesis, crystal structure and Hirshfeld surface analysis of isomeric 1-butyl-5/6-chloro-2-methyl-1H-benzo[d]imidazoles hydrochloride monohydrate. Journal of Molecular Structure, 2023, 1289, Article ID. 135844 (7 pages). DOI: 10.1016/j.molstruc.2023.135844
Other articles of the issue
