Efficient Syntheses of 3-(3-Arylsydnon-4-yl)triazole Derivatives

Abstract

3-Arylsydnone-4-carbohydroximic acid chlorides 1 were reacted with hydrazine hydrate to give hydrazino(3-arylsydnon-4-yl)methanone oximes 2 which are good precursors of 4-triazolyl sydnones. 5-Aryl-3-(3-arylsydnon-4-yl)-1H-[1,2,4]triazoles 4 could be synthesized in excellent yields by reacting hydrazino(3-arylsydnon-4-yl)methanone oximes 2 with aromatic aldehydes 3 under acid catalysis. Compounds 2 were also reacted with 3-aryl-4-formylsydnones 5 and aliphatic aldehydes 7 to produce 3-(3-arylsydnon-4-yl)-5-(3-arylsydnon-4-yl)-1H-[1,2,4]triazoles 6 and 5-alkyl-3-(3-arylsydnon-4-yl)-1H-[1,2,4] triazoles 8, respectively.Many sydnone compounds are associated with pharmacological activities, such as antimicrobial, anti-inflammatory, analgesic and antipyretic properties, 1-6 and various substituted triazoles also exhibit biological properties and behavior. 7-12 Therefore, there exists a continuous interest in the syntheses of triazole derivatives. 13-18 Thus, synthesis of sydnones with a 1,2,4-triazolyl group substituted at a suitable position using a convenient method should be a significant aim for obtaining new biological active compounds. In the previous study, 3-arylsydnone-4-carbohydroximic acid chlorides 1, which were stable at room temperature were easily converted into 3-arylsydnone-4-carbonitrile oxides in polar solvent or basic aqueous solution. 19 The active nitrile oxides generated by this route could undergo cycloaddition with dipolarophiles to produce 4-heterocyclic sydnones. 20-25 3-Arylsydnone-4-carbohydroximic acid chlorides could also be used to react with some nucleophiles to give the precursors which were expected to cyclize with other reagents to yield the desired 4-heterocyclic sydnones. [25][26][27] The present work focuses on the syntheses of 5-aryl-3-(3-arylsydnon-4-yl)-1H-[1,2,4]triazoles 4. The corresponding hydrazino(3-arylsydnon-4-yl)methanone oximes 2 were first obtained through the reaction of starting materials 1 with hydrazine hydrate, and then compounds 2 were cyclized with various aromatic aldehydes 3 to give the desired products 4 under suitable acid catalyzing conditions.Although numerous aspects of 3-arylsydnone-4-carbohydroximic acid chlorides 1 have already been studied, and many 4-heterocyclic sydnones were synthesized, 22-26 the truly stereoisomeric structures of compounds 1 remained unknown until now. Generally, N-hydroxybenzimidomyl chloride contains two stereoisomers, with both E and Z forms existing simultaneously. In this study, compounds 1a-d synthesized as described in the literature 19 (Scheme 1) are exclusively Z-isomers based on the direct X-ray structure analyses of compounds 1a and 1b, and comparison of spectral data. Figures 1 and 2 display the molecular structures of compounds 1a and 1b. Scheme 1 1a: Ar = C 6 H 5 ; 1b: Ar = 4-CH 3 C 6 H 4 ; 1c: Ar = 4-CH 3 OC 6 H 4 ; 1d: Ar = 4-C 2 H 5 OC 6 H 4 Figure 1 Crystal structure of compound 1a Downloaded by: University of Florida. Copyrighted material.

Oxadiazoles

“…The reaction of 3-aryl-4-carbohydroximic acid chlorides with hydrazine hydrate gives hydrazino(3-arylsydnon-4-yl)methanone oximes, which by reaction with aldehydes are good precursors of 4-triazolyl-sydnones (85, Scheme 13.31) [101].…”

The Chemistry of N-Hydroxyamidoximes, N-Aminoamidoximes, and Hydrazidines

“…49 Hydrazine (3-arylsydnon-4-yl) methanone oxime derivatives 28fÀi were reported by Shih et al in good yields (83À96%) from the corresponding carbohydroximic acid chlorides (Scheme 11, Table 12). 50 5.1.2. From Nitrile Oxide and Hydrazines.…”

“…Saikavakali and Irez prepared anti -glyoximehydrazine 28e from the hydrazimic chloride precursor . Hydrazine (3-arylsydnon-4-yl) methanone oxime derivatives 28f – i were reported by Shih et al in good yields (83–96%) from the corresponding carbohydroximic acid chlorides (Scheme , Table ) …”

A Facile Synthesis and Antimicrobial Activity Evaluation of Sydnonyl-Substituted Thiazolidine Derivatives

“…Consequently, chemists still enthusiastically pursue the syntheses and activity evaluation of thiazolidine or thiazolidinone derivatives [ 12 , 13 , 14 , 15 , 16 ]. 3-Aryl-4-formylsydnones 1 have extensively been studied since their discovery [ 17 ] and their applications have been investigated [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Several sydnone derivatives are also associated with a wide range of pharmacological activities, exhibiting antimicrobial, anti-inflammatory, antioxidant, antitumor and anticancer properties [ 25 , 26 , 27 , 28 ].…”