STRUCTURAL NMR ANALYSIS OF TRIAZOLIC COMPOUNDS DERIVED FROM ISONICOTINIC ACID

Headnote

SUMMARY

The present article is aimed towards the structural NMR analysis of 4H-4-amino- 3-mercapto-5-(4-pyridil)-1,2,4-triazole (3) and its product of alkylation (via sodium salt) with ethyl chloroacetate in absolute ethanol. 4H-4-amino-3-mercapto-5-(4-pyridil)-1,2,4- triazole and 4H-4-amino-5-ethoxycarbonyl-methylsulfanyl-3-(4-pyridil)-1,2,4-triazole (4) were characterized by IR, ^sup 1^H-NMR, ^sup 13^C-NMR spectroscopy and structures were elucidated by 2D-^sup 1^H-^sup 13^C-HMBC spectroscopy.

Keywords: isonicotinic acid derivatives; S-alkylation; mercapto-1,2,4-triazole; NMR analysis; 2D-^sup 1^H-^sup 13^C-HMBC.

INTRODUCTION

Pyridinecarboxylic acids exist as three isomers with different position of carboxylic acid relative to nitrogen in pyridine. Isonicotinic acid (4-pyridinecarboxylic acid) is a heterocyclic acid used in manufacturing pharmaceuticals and agrochemicals. It is chiefly used in antituberculosis drugs, such as Isoniazid (isonicotinic acid hydrazide) - which is the most effective one, and Ethionamide (2-ethylthioisonicotinamide) [1], in antidepressant and anxyolitic medication as Iproniazid (N'-isopropylisonicotinohydrazide) [2] or Nialamide (N-benzyl-3-(N'-(pyridine-4-carbonyl)hydrazino)propanamide).

A large number of 1,2,4-triazole-containing rings were incorporated into a wide variety of therapeutically drug candidates, including NSAIDs, CNS stimulants, antianxiety and antimicrobial agents and antimycotic "conazoles" [3]. 1,2,4-triazole groups are already used as pharmacophores in certain drugs like Triazolam, Alprazolam, Etizolam and Furacylin [3]. Sulfur-containing heterocycles such as mercapto- and/or thione-substituted 1,2,4-triazole ring systems (1) have been well studied and so far a variety of pharmacological activities were achieved[3].

The present article is aimed towards the structural NMR analysis of 4H-4-amino-3- mercapto-5-(4-pyridil)-1,2,4-triazole (3) and its product of alkylation (via sodium salt) with ethyl chloroacetate in absolute ethanol, namely 4H-4-amino-5-ethoxycarbonylmethylsulfanyl- 3-(4-pyridil)-1,2,4-triazole (4). The synthesized compounds were characterized by IR, ^sup 1^H-NMR and ^sup 13^C-NMR spectroscopy.

MATERIALS AND METHODS

The reagents were commercial products (Merck, Fluka, Aldrich) and used without further purification. Melting points were determined on a Böetius PHMK (Veb Analytik Dresden) instrument, and thin-layer chromatography was carried out on silica gel-coated plates 60 F254 Merck using benzene:methanol 7:3, benzene:methanol 3:7...