Y. V. Grigoriev, S. V. Voitekhovich, O. Ivashkevich
May 5, 2012
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Russian Journal of Organic Chemistry
Abstract
Nitro derivatives of 1,2,4-triazoles possess a combination of unique properties, such as high energy capacity but considerable heat resistance, biological activity, and complexing ability. Therefore, these compounds are promising from the viewpoint of their application in various fields of human activity, specialty devices, industry, agriculture (as fungicides and herbicides), biochemistry, and pharmacology [1]. Elaboration of methods for the synthesis of nitro-substituted 1,2,4-triazoles seems to be important for the development of the reactivity theory of heterocycles and procedures for regioselective functionalization of ambident compounds. Up to now, alkylation of relatively accessible 5-substituted 3-nitro-1,2,4-triazoles has been studied in sufficient detail. The presence in their molecules of three potential reactions centers for attack by electrophilic reagents, one pyrroleand two pyridine-type nitrogen atoms, implies that the alkylation may involve either of them. In fact, treatment of these compounds with alkyl halides, dialkyl sulfates [2–7], halocarboxylic acid esters [8, 9], chloroethanol, and oxirane [10] in basic or neutral medium often leads to formation of three isomeric N-substituted 3-nitro-1,2,4-triazoles. Some advances were achieved in the alkylation of 5-R-3-nitro-1,2,4-triazoles with alcohols in acid medium. In particular, Saraev et al. [11] reported on their selective alkylation at N with adamantan-1-ol and tert-butyl alcohol in sulfuric acid, whereas the alkylation with isopropyl alcohol afforded exclusively the corresponding N-derivative [12]. The observed regioselectivity may be interpreted in terms of weakly basic properties of triazoles which undergo protonation at the most basic nitrogen atom. Obviously, the nature of alkylating agent is also an important factor responsible for the reaction selectivity. Taking the above stated into account, it seemed reasonable to examine the behavior of nitro-substituted 1,2,4-triazoles in reactions with other alkylating agents, specifically with allyl bromide and cyclohexa-1,3-diene which were successfully used by us previously for N-functionalization of tetrazole ring [13, 14]. We found that the alkylation of 3-nitro-1H-1,2,4-triazole (I) with allyl bromide under conditions analogous to the alkylation of 5-R-tetrazoles (concentrated sulfuric acid, 7 days) [13] gave 65% of a mixture of isomeric N-alkyl derivatives with appreciable prevalence of 1-(1-bromopropan-2-yl)-5-nitro-1H-1,2,4-triazole (IIa). The ratio of regioisomers IIa, IIb, and IIc was estimated at 1 : 0.3 : 0.2 by the intensities of NMR signals from the CH proton in the triazole ring. Predominant formation of isomer IIa is likely to be determined by protonation of initial triazole I in sulfuric acid with formation of 3-nitro-1H-1,2,4-triazol-4ium cation where only the N atom is accessible to attack by the cation generated from allyl bromide. This mechanism was recently proposed to rationalize selective alkylation of triazole (I) with tert-butyl alcohol [12] and was based on the data for selective acidcatalyzed N-alkylation of tetrazoles as structural analogs of I [15]. Isomeric products IIb and IIc may be formed as a result of electrophilic attack on unprotonated 3-nitro-1,2,4-triazole species present in the reaction mixture at a small concentration. Concentrated phosphoric acid turned out to be the most efficient medium for the alkylation of triazole I with cyclohexa-1,3-diene. Such acids as sulfuric and perchloric could not be used because of oligoand ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 610–612. © Pleiades Publishing, Ltd., 2012. Original Russian Text © Yu.V. Grigoriev, S.V. Voitekhovich, O.A. Ivashkevich, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4, pp. 611–613.