Abstract. N'-hydroxy-N-alkylpyridinecarboximidamides are new class of N-substituted imidamide derivatives, with diverse potential applications. In this study, the synthesis of novel long-chain N-substituted pyridinecarboximidamides:N '-hydroxy-N-alkylpyridinecar-boximidamides and N'-hydroxy-N,N-dialkylpyridinecarboximidamides is reported. The two methods were proposed and compared: (I) the two-step procedure (synthesis of N-alkylpyri-dinecarboximidamide and next N'-hydroxy-N-alkylpyridinecarboximidamide) and (II) the three-step procedure (synthesis from pyridineamidoxime by pyridinehydroximoyl chloride and finally preparation of N '-hydroxy-N-alkylor -N,N-dialkylpyridinecarboximidamide). It was indicated that only the three-step procedure enabled the efficient synthesis of the N'-hydroxy-N,N-dialkylpyridinecarboximi-damide with the substituent at position 3 and 4 of the pyridine ring.
Keywords: N'-hydroxy-N-alkylpyridinecarboximidamides; synthesis; substitution
IntroductionN-and N'-substituted imidamides, similar to well known simple amidoximes [1-3], possess very important biological activities [4]. They have already been used as antimicrobial [5,6] bactericidal [7] or fungidal agents [8]. N'-substituted pyridinecarboximidamides have been also studied as antihypertensive drugs [9] and in porcine isolated coronary artery [10]. The most important key issues for the preparation of such compounds are their complexing nature mainly towards divalent metals ions [11,12]. Nsubstituted imidamides especially containing both N-hydroxy and N-alkyl groups are amphoteric substances and show tautomeric properties with domination of the oxime form. These properties allow to suppose that the long-chain N'-hydroxy-N-alkylpyridinecarboximidamides and N'-hydroxy-N,N-dialkylpyridinecarboximidamid-es may also demonstrate biological as well as complexing properties. Therefore, the goal of the research was to synthesize N '-hydroxy-N-alkyl-(4a-c -6a-c) and -N,N-dialkylpyridine-2-, -3-, and -4-carboximidamides (7a-c) with hexyl, octyl and 2-ethylhexyl chain. In this work, two methods were proposed and compared, however, only the three-step procedure enabled the synthesis of N '-hydroxy-N-alkylpyridinecarboximidamides and N'-hydroxy-N,N-dialkylpyridine-carboximidamides containing substituent at position 3 and 4 of the pyridine ring.
Results and DiscussionThe N'-hydroxy-N-alkylpyridinecarboximidamides (4a-c, 5a-c) and N'-hydroxy-N,N-dialkylpyridinecarboximidamide (7a-c) were prepared according to a modified procedure of Khalifa et al.[13] (Scheme 1) and Karatas and Tuzun [14] (Scheme 2). However, starting from pyridine-2-, -3-or 4-carbonitrile (1a-c) only N-alkylpyridinecarboximidamides (2a, 3a) were synthesised (Scheme 1) with a yield of 34 and 44%, respectively. 2a and 3a were then converted to the final N'-hydroxy-N-alkylpyridinecarboximidamides (4a, 5a) via nucleophilic substitution by using hydroxylamine hydrochloride at pH = 7 in an ethanolwater mixture (3:1, v/v). All the synthesized compounds were characterized by 1 H-NMR,
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