Synthesis of some novel 3,7‐dimethyl‐4H‐pyrazolo[5,1‐c][1,2,4]triazin‐4‐ones

Abstract

Some novel 3,7-dimethyl-6H-pyrazolo [5,1-c][1,2,4]triazin-4-ones were prepared (3a-g). Compounds 3a,b were treated with hydrazines to afford various products 7a,b, 8a,b, 9 and 11a,b depending on the type of hydrazine derivative and reaction conditions. The benzoyloxyimino-pyrazolo [5,1-c][1,2,4]triazines (13a,b) were synthesized by refluxing of compounds 3a,b with hydroxylamine hydrochloride to afford the corresponding oxime derivatives followed by treatment with benzoyl chloride.J. Heterocyclic Chem., 38, 711 (2001).For few years, we have been occupied with the chemistry of 1,2,4-triazines[1-3] due to their importance and wide application in biological fields. A number of this class of compounds were found to act as antimicrobial [4], antiviral [5], anti-inflammatory [6][7][8] and antimalarial [9] agents. 4-Amino-1,2,4-triazin-5(4H)-one derivatives have attracted considerable interest, because of their herbicidal activities and important intermediates for the preparation of the fused 1,2,4-triazinone heterocycles [10].In an attempt to synthesize fused 1,2,4-thiadiazine ring with 1,2,4-triazines, we studied the reaction of 4-amino-6-methyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine (1) with brominated 1,3-dicarbonyl active methylene compounds. The reaction was carried out by stirring of 1,3-dicarbonyl active methylene compounds (2a-e) with N-bromosuccinimide (NBS) in the presence of benzoyl peroxide in ethanol at room temperature for 1 / 2 hour followed by addition of compound 1 and refluxing for 2 hours. The products from this reaction were shown to be 3,7-dimethyl-6H-pyrazolo[5,1-c][1,2,4]triazin-4-ones (3a-e) rather than the expected 3,7-dimethyl-6H-[1,2,4]thiadiazino[2,3-c][1,2,4]triazin-4-ones (4a-e) (cf. Scheme 1). In the ir, 1 H nmr and 13 C nmr spectra no observable differences are found capable of differentiating between compounds 3a-e and 4a-e. The only differences capable of differentiating between them were observed in their mass spectra and elemental analyses. Mass spectra showed the existence of the molecular ion peaks M + at m/z 206, 268 and 207 corresponding to 3a, 3b, and 3c respectively and the elemental microanalysis of these compounds for S gave zero %. The proof for formation of elemental sulfur came from its mass spectrum corresponding to M + = 256 (S 8 ). The above results confirm that pyrazolo [5,1-c] The mechanism for the formation of compounds 3a-e is postulated as shown in scheme 2. It proceeds by nucleophilic attack of the amino group of 1 on the carbonyl group of 6a to give 6b, followed by elimination of water from 6b to gave 6c which subsequently undergoes internal nucleophilic attack accompanied by the elimination of hydrogen sulfide to give the 8-bromopyrazolo[5,1-c]-[1,2,4]triazines derivative (6d). Compound 6d undgoes a redox reaction with the eliminated hydrogen sulfide to afford the 8-bromo-6,7,8-trihydropyrazolo[5,1-c]-[1,2,4]triazines (6e) and elemental sulfur. Elimination of hydrogen bromide from 6e afforded the 6,7-dimethyl-6H-

Stereoselective synthesis of dihydrothiadiazinoazines and dihydrothiadiazinoazoles and their pyrolytic desulfurization ring contraction

“…Similar phenomenon has been reported for [1,2,4]triazolo[3,4-b]thiadiazinium bromides where the crystalline trans derivatives equilibrate to 60:40 mixtures of trans and cis isomers in CDCl 3 solution. 5b Similar syntheses of the dihydrothiadiazino-1,2,4-triazine derivatives 8 had not yet been reported prior to this study. Therefore, the reaction of 4-arylideneamino-2,3-dihydro-3-thioxo-1,2-4-triazin-5(4H)-ones 6 (obtained from 5 and ArCHO) with ubromoacetophenone derivatives or ethyl bromoacetate has been studied under different conditions and the best condition was achieved by stirring for 2 h in acetonitrile at room temperature in the presence of anhydrous K 2 CO 3 (Scheme 3).…”

“…Alternatively, compounds 19a and 19j have been readily obtained by heating the starting 4-amino-1,2,4-triazine derivatives 5a with dibenzoylbromomethane and ethyl a-bromoacetoacetate, respectively, in ethanol following reported procedures. 8 Moreover, compounds 20 were prepared by pyrolysis of the corresponding 24 at 230 C as described previously. 2 The new derivatives 24 were synthesized from 5 as shown in Scheme 7 by reacting with bromoacetophenone derivatives 22 to yield the corresponding 3-arolylmethylsulfanyltriazines 23, which were then cyclized to 24 upon refluxing in ethanol in the presence of p-toluenesulfonic acid.…”

Synthesis of 8-R-7-amino-3-tert-butylpyrazolo- [5,1-c][1,2,4]triazin-4(6H)-ones derivatives

“…In particular, pyrazolo- [5,1-c][1,2,4]triazin-4-ones derivatives exhibit antimicrobial activity [1,2]. The synthesis of pyrazolo[5,1-c]-[1,2,4]triazin-4-ones by the action of CH acids such as 3-oxopropanethioamides [3], arylsulfonylacetonitriles [4], and 1,3-dicarbonyl compounds [5] on 6-R-4-amino-3-methylsulfanyl-4,5-dihydro-1,2,4-triazin-5-ones has been described.…”

Advances in the domain of 4-amino-3-mercapto-1,2,4-triazine-5-ones

“…73 Cyclocondensation reaction of aminotriazinethiones 7 [R ¼ methyl, phenyl] with substituted benzaldehydes gave 65 In addition compound 7 was reacted with brominated 1,3-dicarbonyl 166 to furnish 3,7-dimethyl-6H-pyrazolo[5,1-c]-1,2,4-triazin-4-ones 167 (Scheme 57). 93 The mechanism for the formation of compounds 167 is postulated as shown in (Fig. 5).…”

“…While, the reaction of 167, contaminated with elemental sulfur, with phenyl hydrazine in reuxing 2-propanol furnished bis(3,7-dimethyl-4oxo-4,6-dihydropyrazolo[5,1-c]-1,2,4-triazin-8-yl)disulde (171) (Scheme 58). 93 Treatment of 167 with hydrazine hydrate in 2-propanol at room temperature afforded the hydrazinium salts 172 which by reuxing in 2-propanol in the presence of a few drops of acetic acid furnished N,N 0 -bis[(3,7-dimethyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-1,2,4-triazin-8-yl)-ethylidene(and/or benzylidene)]hydrazine (173). Compound 173 was prepared directly by the reaction of 167 with hydrazine hydrate in reuxing 2propanol in the presence of a few drops of acetic acid (Scheme 59).…”