Synthesis of new heteroaromatic systems: Naphth[2,1-e]imidazo[5,1-c]-1,2,4-triazines and benz[e]imidazo-[5,1-c]-1,2,4-triazines

Cyclization of azo compounds, synthesized from 5-diazoimidazoles and 2-naphthol or p-substituted phenols, into naphth[2,1-e]imidazo[5,1-c]-1,2,4-triazines and benz[e]imidazo[5,1-c]-1,2,4-triazines occurs only in the presence of p-toluenesulfonic acid. Imidazo[4,5-d]-1,2,3-triazines are also formed in this reaction when an amide substituent is present in the imidazole ring.Ural State Technical University, Ekaterinburg 620002, Russia: e-mail: mokr@htf.ustu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 540–546, April, 2000.     

6- and 7-aryl-1,2,4-triazolo[4,3-b]-1,2,4-triazines. Synthesis and characterization

Synthetic methods for the preparation of 6-aryl-1,2,4-triazolo[4,3-b]-1,2,4-triazines ( 1 ) and the 7-aryl isomers ( 2 ) are described. Compounds 1 were prepared from aryl glyoxaldoximes 76 via 6-aryl-1,2,4-triazin-3(2H)ones ( 75 ). A simple procedure for the preparation of the 7-aryl isomers was effected using arylglyoxals 11 and the triazoles ( 4, 12a and 12b ). However, complete regioselectivity was not realized in all cases, especially when the triazoles were substituted at the C-5 position. A regiospecific synthesis of the 7-aryl isomers 2 was developed via the 3-methylthio-5-aryl-1,2,4-triazines ( 61 ). The structure of the parent 6-phenyl derivative 5 was confirmed by x-ray crystallography.     

Synthesis of 1,4-dihydroimidazo[5,1-c]-1,2,4-triazin-4-ones and imidazo[5,1-c]-1,2,4-triazoles

Azo compounds obtained by the coupling of 5-diazoimidazoles with diethyl esters of nitro-, chloro-, bromo-, and acetylaminomalonic acids under conditions of base catalysis are cyclized to give 1,4-dihydroimidazo[5,1-c]-1,2,4-triazin-4-ones or imidazo[5,1-c]-1,2,4-triazoles. The chloro, bromo, and nitro groups in the bicyclic products are readily replaced by action of nucleophiles. The imidazotriazinones are converted to chloroimidazotriazines by reaction with thionyl chloride or phosphorus oxychlorideUrals State Technical University-UPI, 620002 Yekaterinburg, Russia Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1544–1553, November, 1999.     

Nitroazines. 7. Alkylation of 6-nitro-7-oxo-4,7-dihydroazolo[5,1-c][1,2,4]-triazines and identification of the products

Reaction of 6-nitro-7-oxo-4,7-dihydroazolo[5,1-c][1,2,4]triazines with methyl iodide or dimethyl sulfate affords the N-methyl derivatives, no O-alkylation products being found. The effect of the alkylating agent, solvent, and the azole moiety on the course of the reaction has been examined.For Communication 6, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1543–1550, November, 1987.     

Synthesis and nmr study of 7-aryl-1,2,4-triazolo-[1,5-a]-1, 3,5-triazines

The reactionof N-(1,2,4)-triazol-5-yl)amidines with ethyl orthoformate is a convenient method for the fusion of a triazine ring to the triazole ring. An NMR study showed that the heterocyclic compounds obtained are 7-aryl-1,2,4-triazolo-[1,5- a]-1,3,5-triazines.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2386–2388, October, 1989.     

Synthesis of 6,8-substituted derivatives of imidazo[5,1-c][1,2,4]triazines and 1,4-dihydroimidazo[5,1-c][1,2,4]triazin-4-ones

The cyclization of imidazolylhydrazines, synthesized from 5-diazoimidazoles and cyanoacetic acid derivatives, to 4-aminoimidazo[5,1-c][1,2,4]triazines and imidazo[5,1-c][1,2,4]triazin-4-ones has been studied. It was established that electron-withdrawing substituents at position 4 of the imidazole ring had a weak effect on the cyclization process. On the other hand, electron-donating substituents at positions 4 or 2 of this ring inhibited and in some cases completely prevented the formation of bicyclic products.Urals State Technical University (UPI), Ekaterinburg 620002, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 805–815, June, 1998.     

Synthesis of new halo-substituted pyrazolo[5,1-c][1,2,4]triazines

Ethyl 3-tert-butyl-4-oxo-7-X-4,6-dihydropyrazolo[5,1-c][1,2,4]triazine-8-carboxylates (X = H, Cl, Br) were synthesized for the first time by diazotization of 7-amino-3-tert-butyl-4oxo-8-ethoxycarbonyl-6H-pyrazolo[5,1-c][1,2,4]triazines with tert-butyl nitrite in the presence of trimethylsilyl halides. A new method was developed: a reaction between 7-amino-3-tert-butyl-4-oxo-6H-pyrazolo[5,1-c][1,2,4]triazine-8-carboxylic acid and I₂/TEA followed by treatment with NaBH₄ led to a mild decarboxylation. The acid reacts with N-halosuccinimides to give novel 8-halo-substituted derivatives. The amino groups of the latter were acylated by treatment with trifluoroacetic anhydride to give monoacylation products.

     

Synthesis of 4-arylcarbamoyl-5-(2-hydroxynaphthylazo)imidazoles and 1-substituted naphtho[2,1-e]imidazo[5,1-c][1,2,4]triazines

The reactions of β-naphthol with 5-diazoimidazoles and imidazolyl-5-diazonium salts containing chemically different carboxamide groups in position 4 were studied. Heterocyclization of 4-arylcarbamoyl-5-(2-hydroxynaphthylazo)imidazoles formed in these reactions was investigated. The presence of the NH fragment in the amide group prevents this process, the reaction giving instead 3-substituted 3,7-dihydroimidazo[4,5-d][1,2,3]triazin-4-ones, which is due to reversibility of C-azo coupling. Methods for modification of 1-ethoxycarbonyl group in the naphtho[2,1-e]imidazo[5,1-c][1,2,4]triazine system were developed and used to prepare substituted carboxamides inaccessible by other routes. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1208–1213, July, 2006.     

THE SYNTHESIS OF 15N LABELED 6-NITRO-1,2,4-TRIAZOLO- [5,1-c][1,2,4]TRIAZIN-7-ONE

A general method for inclusion of the ¹⁵N label into the position 1 of 6-nitro-1,2,4-triazolo[5,1-c][1,2,4]triazin-7-one by using K¹⁵NO₃ has been developed.     

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 some hydroxy and methoxymethyl derivations of 1H-pyrazolo[5,1-c]-1,2,4-triazoles

Electrophilic hydroxylation of a pyrazolotriazole with a mixture of trifuoroacetic attack of methanolic hydroxide ion on a dichloropyrazolotriazole gave a 6-methoxymethylpyrazolotriazole by a mechanism involveing a cyclopropane intermediate.     

NH acidities of 7-oxo-4,7-dihydropyrazolo- and 1,2,4-triazolo[5,1-c][1,2,4]triazines

The pK_a values of a number of 7-oxo-4,7-dihydropyrazolo- and 1,2,4-triazolo[5,1-c]-[1,2,4]triazines, which range from 0.33 to 6.50 and correlate with the meta constants of substituents in the 6 position, were determined by spectrophotometric and potentiometric methods.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 697–699, May, 1984.     

A novel synthesis of fused imidazo[5,1-c]-1,2,4-triazoles

The new fused imidazo[5,1-c]-1,2,4-triazoles 4 were obtained by cyclization of the corresponding 2-imidazolidinone 4-phenylhydrazones 2 which were obtained by the action of phenylhydrazine on the arylmethylene derivatives of 4-thioxo-2-imidazolidinone 1 . The benzylimino derivatives 6 were obtained by the reaction of benzylamine with 1 . Alkylation of 1 with phenacyl bromide and/or ethyl bromoacetate afforded the S-alkyl derivatives 7.     

Synthesis of thieno[2,3-e]-1,2,4-triazines

3-Methylmercapto-5-oxo-6-vinyl- and 2-methyl-3-mercapto-5-oxo-6-vinyl-2,5-dihydro-1,2,4-triazines were readily converted into the corresponding thieno[2,3-e]-1,2,4-triazine in one step by the action of phosphorus pentasulfide in pyridine. 4-Methyl-3-mercapto-5-oxo-4,5-dihydro-1,2,4-triazine is only converted into the 5-thioxo analog and no thiophene ring product was obtained under the same conditions. Thieno[2,3-e]-1,2,4-triazines were also more efficiently obtained by the action of phosphorus petnasulfide in pyridine on the appropriate 6-acylmethyl-3-mercapto-5-oxo-2,5-dihydro-1,2,4-triazine.     

Synthesis of 2-aryl-6-carbethoxythiazolo[4,5-c]pyridine and 7-chloro-2-phenylthiazolo[5,4-c]pyridine

Starting from readily available 2-aryl-5-formyl-4-mehtylthiazole, 2-aryl-6-carbethoxythiazolo[4,5-c]pyridine was prepared. β-(2-Phenylthiazol-4-yl)acrylic acid was converted to the corresponding azide (VI). Cyclization of compound VI afforded 2-phenylthiazolo[5,4-c]pyridin-7(6H)one. Reaction of the latter with phosphorous oxychloride gave 7-chloro-2-phenylthiazolo[5,4-c]pyridine.