F. Kóródi
1994
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Journal
Heterocyclic Communications
Abstract
Synthesis of 4-(1H-1,2,4-triazol-1-yl)quinolines by the reaction of 4-chloroquinolines with 1,2,4-triazole was studied under neutral, acidic and basic reaction conditions. Significant role of the acid and base catalysis as well as substituent effects on the reactivity of 4-chloroquinolines in these reactions are reported. As a result of this study one can choose the best reaction conditions for the preparation of the title compounds according to the substituents on the quinoline ring. INTRODUCTION A lot of work concerning both synthetic and mechanistic aspects of the reactions of 2and 4-chloroquinolines with various nucleophilic reagents have been published (1). Differences in behaviour of 2and 4-chloro group in these reactions, furthermore, solvent and substituent effects in case of both charged anionic nucleophilic agents (alkoxide ions) and uncharged reagents (amines, thiols) have been thoroughly investigated, and the existence of acid catalysis caused by the protonation of quinoline ring nitrogen atom in the latter case is well documented (2). Since aminoquinolines are of special interest due to their different kinds of biological activity, reactions of chloroquinolines with a wide variety of aliphatic, aromatic and heteroaromatic amines have been investigated (1). However, nitrogen-heterocycles containing -NHmoiety have been given little attention as nucleophilic agents in these reactions. As the sole example we have found in the literature, 4-chloroquinolines are reported to give 4-imidazolylquinolines when heated with imidazole or its derivatives at 200 °C for 24 hrs (3). Our interest in the synthesis of new 2or 4-(1H-1,2,4-triazol-1-yl)quinolines possessing antiinflammatory and fungicidal activity (4) prompted us to investigate the reaction of 2and 4-chloroquinolines with 1H-1,2,4-triazole in detail. The primary aim of our work was to find the best reaction conditions for the preparation of the products. On the other hand, we hoped to get further contributions to the present knowledge on the nucleophilic displacement reactions of chloroquinolines using such an N-nucleophilic agent which can react depending on the reaction conditions both as a neutral reagent and as an anion, since its -NHmoiety can readily be deprotonated by means of a strong base. Comparative study on the reactivity of chloroquinolines toward N-nucleophilic reagents under neutral, acidic and basic reaction conditions has not been reported so far. RESULTS AND DISCUSSION In this paper we report on the results related to the nucleophilic substitution reaction of 4-chloroquinolines with 1,2,4-triazole. The substituents of the quinoline ring were selected from both electron-releasing (alkyl) and mild (CI) or strong (N02, CCI3, CF3) electron-withdrawing groups. With respect to the known characteristic features of the nucleophilic displacement reactions of 4-chloroquinolines (1, 2) three general methods were used in our