A new synthetic route to 7H-imidazo[1,2-b][1,2,4]triazoles

The reaction of benzil 1-ureidoethylidene hydrazones 8 with a mixture of triphenylphosphine, carbon tetrachloride, and triethylamine provides a general route to 7H-imidazo[1,2-b][1,2,4]triazoles 18 via the thermal reaction of the expected keto azine carbodiimide intermediates 13, and the structure of 18 was confirmed by X-ray crystallographic analysis.     

A novel synthetic route to 1,2-dimethyl-5-phenyl-1H-imidazo[4,5-b]pyridin-7-ol

Heating a mixture of 4-amino-1,2-dimethyl-1H-imidazole-5-carboxylic acid ethyl ester with ethyl benzoyl acetate resulted in the formation of 8-ethoxycarbonyl-6,7-dimethyl-4-oxo-2-phenylimidazo[1,5-a]pyrimidin-5-ium, hydroxide, inner salt. This compound was then transformed into 1,2-dimethyl-5-phenyl-1H-imidazo-[4,5-b]pyridin-7-ol via several intermediates. A number of structurally interesting compounds were also isolated during the course of this work. Thus, the target ring system was formed by a circuitous series of ring-chain tautomerizations/rearrangements.     

New synthesis of 5,6-dihydrothiazolo[3,2-b][1,2,4]triazoles

Russian Journal of Organic Chemistry -     

Synthesis of 7-Amino-3-tert-butyl-2-alkylthiopyrrolo[1,2-b][1,2,4]triazine-6-carboxylates

Russian Journal of General Chemistry - Alkylation of tert-butyl-7-amino-3-tert-butyl-8-R1-2-oxo-1,2-dihydropyrrolo[1,2-b][1,2,4]triazin-6-carboxylates with alkyl halides R2Br (R1 = CN, CO2Et; R2 =...     

Condensed imidazo-1,2,4-azines 22. Alkylation of 5H-imidazo[1,2-b]-1,2,4-triazepin-4-ones

Substituted 5H-imidazo[1,2-b]-1,2,4-triazepin-4-ones react with alkyl (alkenyl) halides, 2-chloroethanol, glycerin dichlorohydrin, haloacetic acids, the methyl ester and amide of monochloroacetic acid in a methanol-sodium methylate system to form N₍₅₎-alkylation products, and with hydroxylamino-O-sulfonic acid to form 5-aminoimidazo[1,2-b]-1,2,4-triazepin-4-one.For Communication 21, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 234–236, February, 1990.     

A new route to benzo[4,5]cyclohepta[1,2-b]naphthalenes: synthesis of radermachol

[formula: see text] Condensation of 3-phenylsulfonyl-1,3-isobenzofuranone (3) with benzocyclohept-6,7-en-5-ones such as 4 and 15 provides a straightforward, general method for synthesis of functionalized benzo[4,5]cyclohepta[1,2-b]naphthalenes (e.g., 5 and 16). This finding was used to achieve a brief and efficient preparation of 6,7-benzo-3,4-(1,4-dimethoxy-2,3-naphtho)-1,5-dioxosuberane (2), an established intermediate to the naturally occurring red pigment radermachol (1).     

A new site‐selective route for synthesis of functionalized imidazo[2,1‐c][1,2,4]triazoles

Reactions of 4‐arylhydrazono‐2‐methylthio‐imidazolin‐5(1H)‐one 3 with various hydrazonoyl halides 1 proved to be site‐selective and yielded the respective imidazo[2,1‐c][1,2,4]triazole derivatives 8 . The structure of the latter was elucidated by X‐ray analysis and the mechanism of the studied reactions was discussed.     

From thiourea to bicyclic structures: an original route to imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines,and 2H,6H-pyrimido[2,1-b][1,3]thiazines

We report an example of an efficient regioselective synthesis of biheterocyclic compounds using thiourea as starting material. In fact, N,N'-bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3) diazadienes, respectively, themselves undergoing cyclization reactions to yield imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any regioisomeric ambiguity. This straightforward route represents an original and unambiguously regioselective pathway to these valuable heterocycles.     

Microwave Assisted Synthesis of 6-Aryl-3-substituted-5H-[1,2,4]-triazolo[4,3-b][1,2,4]triazoles: A Case for a Comparative Study

A simple and fast synthesis of 6-aryl-3-substituted-5H-[1,2,4]-triazolo[4,3-b][1,2,4]triazoles 4 in high yields has been developed by microwave assisted heterocyclization of N-(3-methylthio-5-substituted-4H-1,2,4-triazol-4-yl)benzenecarboximidamides 3 . The effectiveness of the microwave irradiation and conventional heating for the formation of compounds 4 has been investigated.     

Synthesis of 2,3-dihydro-1H-imidazo[1,2-b]pyrazoles

Two novel 2,3-dihydro-1H-imidazo[1,2-b]pyrazole derivatives 7 and 8 have been prepared by hydrazinolysis with 2,4-dinitrophenylhydrazine of 1-(benzylideneamino)-2-(2-ethoxycarbonyl-2-nitromethylidene)-imidazolidine 4 . The precursor 4 was conveniently prepared from ethyl nitroacetate and 1-(benzylidene-amino)-2-(methylthio)imidazoline 3 . Two examples are presented in which ethyl aceto(and trifluoroaceto)acetate 2-nitrophenyl-hyrazone, 9 and 10 , both of which also feature the β-hydrazinoacrylate arrangement, are refluxed in ethanol containing hydrochloric acid and thereby converted into pyrazolones 11 and 12 , pyrazoles 13 and 14 , and ketone 2-nitrophenylhydrazones 15 and 16 , respectively.     

Synthesis of 3-methyl-7-phenylimidazo-[1,2-b]-1,2,4-triazine

The bromocyclization of 3-allylamino-5-phenyl-1,2,4-triazine gives 3-bromomethyl-7-phenyl-2,3-dibromo-1H-imidazo[1,2-b]-1,2,4-triazinium bromide, which is transformed into 3-methyl-7-phenylimidazo-[1,2-b]-1,2,4-triazine.Yekaterinburg Fire-Fighting Technical Institute, Ministry of Internal Affairs, Russian Federation, 620002 Yekaterinburg. Chelyabinsk State University, 454136 Chelyabinsk. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 110–111, January, 1998.     

Synthesis and Tautomeric Structure of 7-Arylhydrazono-7H-[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines

Two synthetic approaches were developed for the title compounds 8a-g via coupling of diazotized anilines with 7-acetyl-6-methyl-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine 7 , and reaction of N-aryl 2-oxopropanehydrazonoyl chlorides 9 with 4-amino-3-mercapto-5-phenyl-1,2,4-triazole 1 . The tautomeric structures of 8 were elucidated by their spectral analyses and correlation of their acid dissociation constants with Hammett equation.     

Synthesis of 1,2,4-triazole, 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives of benzotriazole

A novel series of 1-(1-carbonylmethyl-1H-benzotriazole) thiosemicarbazides 3a-e was synthesized and then cyclized with sodium hydroxide to afford 1-(4-substituted-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazoles 4a-e , which were alkylated with ethyl iodide to l-(3-ethylthio-4-substituted-4H-1,2,4-triazol-5-yl)-methyl-1H-benzotriazoles 5b-e . The reaction of 1H-benzotriazol-1-acetic acid hydrazide ( 2 ) with carbon disulphide and potassium hydroxide followed by hydrazine hydrate gave 1-(4-amino-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazole ( 6 ). Its subsequent condensation with carboxylic acids in the presence of phosphorus oxychloride or with phenacyl bromides afforded two series of fused heterocycles namely; 6-substituted-3-[1-(1H-benzotriazole)methyl]-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 7a-e and 6-substituted phenyl-3-[1-(1H-benzotriazole)methyl]-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 8a-e respectively. The structure of the newly synthesized compounds was elucidated by elemental analyses, ir and nmr spectra.     

Synthesis of 6-phenyl and 6-styrylthiazolo[3,2-b] [1,2,4]triazoles

Thiazole rings have been often encountered in the structure of antibiotic or antitumor drugs. An easy synthesis of them has revealed itself necessary in order to elucidate the mechanism of action of these naturally occurring substances. A method of preparation of conjugated b-ethylenic thiazole[3,2-b] [1,2,4]triazoles by heating a 3-thio substituted [1,2,4]triazole in the presence of polyphosphoric acid is reported here, giving the expected product in a 60% yield.     

New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazo-pyrazolo[5,1-c][1,2,4]triazoles through regioselective alkylation of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles

1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2aa-ad) were obtained by regioselective alkylation of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2a). 1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles 2aa and 2ab were also prepared by coupling phenyldiazonium chloride with 1H-1-alkyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazoles 1aa and 1ab. The new compounds were characterized by IR, UV-VIS, ¹H-NMR, ¹³C-NMR, and ¹⁵N-NMR spectroscopy and their structures and actual tautomeric forms were established unequivocally.      

Synthesis of 3-substituted bicyclic imidazo[1,2-d][1,2,4]thiadiazoles and tricyclic benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazoles

A versatile synthetic route to potentially useful fused-ring [1,2,4]thiadiazole scaffolds (e.g., 7a and 10b) via exchange reactions of the precursor [1,2,4]thiadiazol-3-(2H)one derivatives (e.g., 6 and 9) with appropriately substituted nitriles (e.g., cyanogen bromide or p-toluenesulfonyl cyanide) under mild conditions is described. For example, the tricyclic 3-bromo [1,2,4]THD derivative (7a) underwent S(N)Ar substitution with a variety of nucleophiles, which included amines, malonate esters and alcohols. Likewise, the bicyclic 3-p-tosyl [1,2,4]THD (10b) was employed as a template in reaction with diamines, and the resulting substituted diamines (e.g., 12a or 12e) were further selectively derivatized at the N1 and/or N2 positions in a linear fashion. The X-ray crystal structure of the 3-methyl bicyclic [1,2,4]THD (21) was obtained, and selective methylation at the N1 position via a protection-alkylation-deprotection protocol, as illustrated in Scheme 6, was confirmed. Alternatively, a short convergent synthesis of N1-functionalized derivatives from the reaction of 10b with appropriately substituted secondary amines was also developed. Hence, these synthetic strategies were advantageously exploited to provide access to a variety of diversely derivatized 3-substituted fused-ring [1,2,4]thiadiazole derivatives.