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T COMMUNICATIONS

Synthesis of New C-Alkyl-N-pyridoxylmethylbenzimidazoles R. Kh. Bagautdinovaa,*, G. N. Aitbayb, L. K. Kibardinaa, A. G. Strelnika, A. R. Burilova, and M. A. Pudovika a Arbuzov

Institute of Organic and Physical Chemistry, Federal Research Center “Kazan Scientific Center of the Russian Academy of Sciences,” Kazan, 420088 Russia b Kazan National Research Technological University, Kazan, 420015 Russia *e-mail: [email protected] Received March 26, 2020; revised March 26, 2020; accepted April 8, 2020

Abstract—The reactions of pyridoxal monoimine based on ortho-phenylenediamine with aliphatic aldehydes results in the formation of new C-alkyl-N-pyridoxylmethylbenzimidazoles. Keywords: pyridoxal, azomethines, diimines, heterocyclization, benzimidazoles

DOI: 10.1134/S1070363220090261 Benzimidazole derivatives occupy an important place in the search for and creation of new biologically active substances. The benzimidazole fragment is a component of fungicidal drugs [1], as well as drugs used for treatment of arterial hypertension, gastric and duodenal ulcer, erosive gastritis, and some diseases of nervous system [2, 3]. Generally, the above applies to C-alkyl-Nbenzylated derivatives. The synthesis of N,C-dialkylated and C-aryl-N-benzylated derivatives by reacting orthophenylenediamine with aromatic or aliphatic aldehydes in a 1 : 2 ratio has been reported earlier. As a rule, the reactions are carried out in the presence of a catalyst (lactic acid [4], trifluoroacetic acid [5], copper salt [6], zinc chloride [7], indium oxide [8], ionic liquid [9]), as well as under the action of ultrasound [10]. The reactions of pyridoxal with alkylenediamines afforded the corresponding bisazomethines as a sole product regardless of the conditions, ratio and nature of the initial aldehydes [11, 12]. There is only one

example describing the use of aromatic diamines in this reaction: pyridoxal hydrochloride reacts with ortho-phenylenediamine in a methanol solution in the presence of potassium hydroxide to produce monoimine 3 [13]. We assumed that C-alkyl-N-pyridoxal-methylated benzimidazoles, analogs of known drugs, can be obtained through the reaction of monoimine 3 with aliphatic aldehydes. At the first stage, 4-{[(2-aminophenyl)imino]methyl}5-(hydroxymethyl)-2-methylpyridin-3-ol 3 was obtained by the reaction of neutral pyridoxal with orthophenylenediamine in 88% yield (Scheme 1). The presence of a free amino group in compound 3 allows it to react with various aliphatic aldehydes. The reactions of ortho-phenylenediamine with aliphatic aldehydes have been known to afford symmetric diimines, which undergo cyclization to the corresponding benzimidazoles [14]. We assumed that non-symmetrical bisazomethines 4а–4f formed by reacting imine 3

Scheme 1.

1756

SYNTHESIS OF NEW C-ALKYL-N-PYRIDOXYLMETHYLBENZIMIDAZOLES

1757

Scheme 2.

with aliphatic aldehydes can undergo intramolecular heterocyclization involving one of two nonequivalent nitrogen atoms of the azomethine fragments, which is accompanied by 1,3-migration of protons to