Preparation of 1,1´-(alkyldiyl)-bis-(2-alkylimidazole-4,5-dicarboxylic) acids

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Abstract

BACKGROUND: Alkyl-bis-imidazole-4,5-dicarboxylic acids can be used both in the production of polymers with pronounced fluorescent properties and as potential antiviral agents. However, there is currently no simple method for the synthesis of alkyl-bis-imidazole-4,5-dicarboxylic acids with a wide range of substituents at both 1, 1ʹ and 2, 2ʹ positions. Therefore, the search for alternative, easier ways to synthesize compounds of this series remains relevant.

AIM: To develop a method for obtaining 2-substituted bis-imidazole-4,5-dicarboxylic acids connected at positions 1, 1ʹ by an alkyl chain of various lengths containing substituents of various lengths and nature at positions 2, 2ʹ (alkyl substituents of various lengths and heteroaryl substituents).

MATERIALS AND METHODS: Compounds of a number of bis-imidazole-4,5-dicarboxylic acids were obtained using methods of fine organic synthesis.

RESULTS: It has been shown that the oxidation of 1,1ʹ-(alkyldiyl)-bis-(2-alkylbenzimidazoles) with hydrogen peroxide in concentrated sulfuric acid leads to the production of targeted 1,1ʹ-(alkyldiyl)-bis-(2-alkylimidazole-4,5-dicarboxylic acids) in preparative quantities.

CONCLUSIONS: A new preparative method has been proposed for the preparation of 1,1ʹ-(alkyldiyl)-bis-(2-alkylimidazole-4,5-dicarboxylic acids).

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About the authors

Maxim A. Menshikov

Saint Petersburg State Institute of Technology (Technical University); Institute of Experimental Medicine

Author for correspondence.
Email: max.menshikov32@gmail.com
ORCID iD: 0009-0006-5651-7502

student, student assistant

Russian Federation, Saint Petersburg; Saint Petersburg

Maria A. Brusina

Institute of Experimental Medicine

Email: mashasemen@gmail.com
ORCID iD: 0000-0001-8433-120X

Cand. Sci. (Chemistry), Research Associate

Russian Federation, Saint Petersburg

References

  1. Liu J, Chen L, Cui H, et al. Applications of metal-organic frameworks in heterogeneous supramolecular catalysis. Chem Soc Rev. 2002;43:6011–6061. doi: 10.1039/C4CS00094C
  2. Babu KS, Reddy MS, Tagore AR, et al. Efficient synthesis of olmesartan medoxomil, an antihypertensive drug. Synth Commun. 2009;39:291–298. doi: 10.1080/00397910802372558
  3. Efremov OM, Alexandrova IYa, Kulikov SV, et al. The effect of a number of imidazole-4,5-dicarboxylic acid derivatives on the activity of N-methyl-D-aspartic acid (NMDA) receptors. Experimental and Clinical Pharmacology. 2005;68(1):7–9. EDN: SZWZVD doi: 10.30906/0869-2092-2005-68-1-7-9
  4. Dergachev VD, Yakovleva EE, Brusina MA, et al. Antiparkinsonian activity of new N-methyl-D-aspartate receptor ligands in arecoline hyperkinesis test. Medical Council. 2021;12:406–412. EDN: YKVVXC doi: 10.21518/2079-701X-2021-12-406-412
  5. Yakovleva EE, Focsha SP, Brusina MA, et al. Studying the anticonvulsive activity of new ligands of NDMA-receptor complex – imidazole-4,5-dicarbonic acid derivatives. Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(2):149–154. EDN: XKEHDC doi: 10.17816/RCF182149-154
  6. Yuan G, Zhang C, Shao K, et al. Syntheses, crystal structures and fluorescent properties of three coordination polymers assembled from flexible bis-(imidazole-4,5-dicarboxylate) ligand and d10/s2 metal ions. Inorganic Chemistry Communications. 2019;100:16–20. EDN: BJALPU doi: 10.1016/j.inoche.2018.12.011
  7. Piotrovsky LB, Lishko PV, Maksimyuk AP, et al. A new class of agonists and antagonists of N-methyl-D-aspartic acid receptors are derivatives of imidazole-4,5- and pyrazole-3,4-dicarboxylic acids. Russ J Physiol. 1999;85(4):523–530.
  8. Lishko PV, Piotrovsky LB, Maksimyuk AP, et al. Dependence of pharmacological activity of new NMDA agonists and antagonists on their chemical structure. Neurophysiology. 1999;31:147–149. doi: 10.1007/BF02515058
  9. Mohan P, Singh R, Baba M. Potential anti-AIDS agents. Synthesis and antiviral activity of naphthalenesulfonic acid derivatives against HIV-1 and HIV-2. J Med Chem. 1991;34(1):212–217. doi: 10.1021/jm00105a033
  10. Mohan P, Wong MF, Verma S, et al. Structure-activity relationship studies with symmetric naphthalenesulfonic acid derivatives. Synthesis and Influence of spacer and naphthalenesulfonic acid moiety on anti-HIV-1 activity. J Med Chem. 1993;36(14):1996–2003. doi: 10.1021/jm00066a008
  11. Mohan P, Loya S, Avidan O, et al. Synthesis of naphthalenesulfonic acid small molecules as selective inhibitors of the DNA polymerase and ribonuclease H activities of HIV-1 reverse transcriptase. J Med Chem. 1994;37(16):2513–2519. doi: 10.1021/jm00042a004
  12. O’Connell JF, Parquette J, Yelle WE, et al. Convenient synthesis of methyl 1-methyl-2,4-dibromo-5-imidazolecarboxylate. Synthesis. 1988;10:767–771. doi: 10.1055/S-1988-27702
  13. Collman JP, Yan Y, Lei J, et al. Efficient synthesis of trisimidazole and glutaric acid bearing porphyrins: ligands for active-site models of bacterial nitric oxide reductase. Org Lett. 2006;8:923–926. doi: 10.1021/ol053118z
  14. Ohtsuka Y. Chemistry of diaminomaleonitrile. II. Preparation of the open-chain adduct with ketone in phosphorus pentoxide-ethanol system. J Org Chem. 1976;41:629–633. doi: 10.1021/jo00866a010
  15. Al-Azmi A, Elassara A, Booth BL. The chemistry of diaminomaleonitrile and its utility in heterocyclic synthesis. Tetrahedron. 2003;59:2749–2763. doi: 10.1016/S0040-4020(03)00153-4
  16. Al-Azmi A, George P, El-Dusouqui O, et al. Alkylation of azoles: synthesis of new heterocyclic-based AT1-nonpeptide angiotensin (II) receptor antagonists. J Heterocycl Chem. 2007;44:515–520. doi: 10.1002/jhet.5570440302
  17. Brusina MA, Piotrovskii LB, Gubina YuA, et al. Influence of oxidation conditions on the yield of 2-substituted imidazole-4,5-dicarboxylic acids. Russian Journal of General Chemistry. 2018;88(5):729–733. EDN: UOVPMW
  18. Patent RUS No. 2665712/04.09.2018. Byul. No. 25. Piotrovsky LB, Brusina MA, Nikolaev DN, et al. Method for obtaining 1- and 1,2-dialkyl(aryl)-imidazole-4,5-dicarbonic acids. Available from: https://patentimages.storage.googleapis.com/a8/c8/36/bdc3a168e0c8ea/RU2665712C1.pdf (In Russ.)
  19. Porai-Koshits BA, Kharkharova GM. Synthesis and properties of some benzimidazole derivatives. Interaction of o-phenylenediamine with some carboxylic acids. Russian Journal of General Chemistry. 1955;25:2138–2185. (In Russ.)
  20. Phillips MA. The formation of 2-substitued benzimidazoles. J Chem Soc. 1928:2393–2399.
  21. Pool WO, Harwood HJ, Ralston AW. 2-Alkylbenzimidazoles as derivatives for the identification of aliphatic acids. JACS. 1937;59:178–179.
  22. Kanaoka Y, Yonemitsu O, Tanizawa K, Ban Y. Polyphosphate esters as synthetic reagents. I. Synthesis of 2-substituted benzimidazoles. Chem Pharm Bull (Tokyo). 1964;12:773–778. doi: 10.1248/cpb.12.773
  23. Aksenov AV, Smirnov AN, Aksenov NA. Benzimidazoles and benzoxazoles via the nucleophilic addition of anilines to nitroalkanes. Org Biomol Chem. 2015;13(14):4289–4295. doi: 10.1039/c5ob00131e
  24. Childers WE, Baudy RB. N-Methyl-D-aspartate antagonists and neuropathic pain: the search for relief. J Med Chem. 2007;50(11):2557–2562. doi: 10.1021/jm060728b
  25. Porai-Koshits BA, Ginzburg OF, Efros LS. Research in the field of imidazole derivatives. I. On the mechanism of formation of benzimidazole derivatives and the role of hydrochloric acid in this reaction. Russian Journal of General Chemistry. 1947;17:1768–1773. (In Russ.)
  26. Porai-Koshits BA, Kharkharova GM. Synthesis and properties of some benzimidazole derivatives. Russian Journal of General Chemistry. 1954;24:1651–1659. (In Russ.)
  27. Brusina MA, Nikolaev DN, Piotrovskii LB, Ramsh SM. Unexpected formation of imidazole-4,5-dicarboxylic acid during oxidation of 2-substituted benzimidazoles with hydrogen peroxide. Russian Journal of Organic Chemistry. 2016;52(10):1533–1535. EDN: XWTVXV

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2. Fig. 1. Structure of 1,1ʹ-(alkyldiyl)-bis-(imidazole-4,5-dicarboxylic acids)

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3. Fig. 2. Obtaining 1,1ʹ-(alkyldiyl)-bis-(imidazole-4,5-dicarboxylic acids) (11–16)

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