On the amination of 3-nitro-1,8-naphthyridines

A number of 3-nitro-2-X-1,8-naphthyridines (X = H,Cl,NH₂,OE_t) were successfully aminated into the corresponding 4-amino-3-nitro-2-X-naphthyridines, using liquid ammonia and potassium permanganate as reagents. 4-Amino-1,4-dihydro-3-nitro-2-X-1,8-naphthyridines are the actual species being oxidized by the potassium permanganate; their existence has been by ¹H nmr spectroscopy.     

Imination of N-methylpyridinium salts by liquid ammonia-potassium permanganate. A new synthesis of nudiflorine

Reaction of substituted 1-methyl(benzyl)pyridinium salts ( 1 ) with liquid ammonia/potassium permanganate leads to introduction of the imino group at the carbon adjacent to the nitrogen. The regiospecificity of the reaction strongly depends on substituent X: at C-6 for X = H, CONH₂, C₆H₅ and at C-2 for X = CH₃. 3-Aminocarbonyl-1-t-butylpyridinium iodide ( 5 ) on treatment with liquid ammonia/potassium permanganate exclusively gives the 4-imino compound 8 ; ¹H nmr spectroscopy shows that 5 in liquid ammonia gives a mixture of the σ-adducts 4-amino-1,4-dihydro- and 6-amino-1,6-dihydro-3-pyridinecarbonamide ( 6 and 7 ). Surprisingly, an oxodemethylation reaction is observed on treatment of 3-aminocarbonyl-1,6-dimethylpyridinium iodide ( 13 ) with liquid ammonia/potassium permanganate, 1,6-dihydro-1-methyl-6-oxo-3-pyridinecarboxamide ( 14 ) being obtained. This compound can easily be converted by phosphorus oxychloride into the alkaloid nudiflorine ( 15 ).     

On the chichibabin amination of quinoline and some nitroquinolines

Quinoline is aminated into 2-aminoquinoline (55-60%) when treated with potassium amide/liquid ammonia/potassium permanganate at ?65°. When the amination is carried out by allowing the solution of quinoline in potassium amide/liquid ammonia to raise from ?60° to + 15° before addition of potassium permanganate, the main product is 4-aminoquinoline. Using as reagent liquid ammonia/potassium permanganate (thus without the presence of potassium amide) 3-nitroquinoline is exclusively aminated at ?40° into 4-amino-3-nitroquinoline. Using the same conditions, from 4-nitroquinoline 3-amino-4-nitroquinoline is obtained. The mechanism of these amination reactions is discussed.     

Synthesis of 6-Amino-5-R2-7-(6-R1-4-oxo-3,4-dihydro-2-quinazolyl)-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

It has been found that malonodinitrile and 2-(6-R¹-oxo-3,4-dihydro-2-quinazolyl)acetonitrile in the presence of triethylamine undergo hetarylation by 5,6-dichloro-2,3-pyrazinedicarbonitrile at the active methylene group to give the triethylammonium salt of 2-(3-chloro-5,6-dicyano-2-pyrazinyl)malononitrile or 5-chloro-6-cyano(6-R¹-4-oxo-1,2,3,4-tetrahydro-2-quinazolylidene)methyl-2,3-pyrazinedicarbonitriles. Reaction of these with primary amines leads to annelation of the pyrrole ring at the pyrazine [b] edge to give 6-amino-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3,7-tricarbonitriles and 6-amino-5-R²-7-(6-R¹-4-oxo-3,4-dihydro-2-quinazolyl)-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles respectively.     

On the chichibabin amination of pyrimidine and N-alkylpyrimidinium salts using liquid ammonia/potassium permanganate

Treatment of the 2-R-pyrimidines ( 1 , R = methyl, ethyl, i-propyl and t-butyl) with potassium amide/liquid ammonia/potassium permanganate leads to amination at C-4(6). The yields of the 4(6)-amino compounds 3 in-crease in the order 2-methyl (10%), 2-ethyl (30%), 2-i-propyl (45%) and 2-t-butyl (60%). Treatment of the 2-R-N-methylpyrimidinium salts ( 4 , R = hydrogen, methyl) with liquid ammonia/potassium permanganate leads to a regiospecific imination at C-6, the corresponding 2-R-1,6-dihydro-6-imino-1-methylpyrimidines 6 being obtained in 80-85% yield. It is proved by ¹⁵N-labelling that no ring opening is involved in these imination reactions. Treatment of the imino compounds with base leads to the corresponding 2.R-6-methylamino-pyrimidines 8 , involving, as proved by ¹⁵N-labelling, an ANRORC-mechanism. 2-t-Butyl-1-ethylpyrimidinium tetrafluoroborate ( 9b ) when treated with liquid ammonia/potassium permanganate undergoes N-deethylation, 2-t-butylpyrimidine being exclusively formed.     

On the mechanism of the conversion of 6-chloropyrido[2,3-B]pyrazine into 1h-lmidazo[4,5-b] pyridine by potassium amide in liquid ammonia

The synthesis of a number of 2-R₁, 3-R₂-6-X-pyrido[2,3-b]pyrazines (1) is reported and their reaction with potassium amide in liquid ammonia investigated. Ring contraction into a 2-R-1H-imidazo[4,5-b]pyridine was found to occur with X = Cl, R₁ = H, R₂ = C₆H₅ (1b); X = Cl, R₁ = R₂ = C₆H₅ ( 1c ); X = Cl, R₁ = H, R₂ = t-C₄H₉ ( 1d ). Besides ring contraction, an increasing amount of dechlorination of 1 was found: 1a , 20%; 1b , 30%; 1d , 40%; 1c , 60%; 1g , 95%. 1e (X = Cl, R₁ = t-C₄H₉, R₂ = H) yields the unreactive anionic σ-adduct at C-3 i.e., 3-amino-2-t-butyl-6-chloro-3,4-dihydropyrido[2,3-b]pyrazine. The ring contraction only proceeds with X = Cl. 1b (X = F) gives an amino-defluorination, 1b (X = Br) exclusively undergoes reductive debromination. The ring contraction of 1a (X = Cl, R₁ = R₂ = H) is investigated by ¹⁵N- and ¹³C-labelling. It is concluded that the conversion into 1H-imidazo[4,5-b]pyridine proceeds via the reactive anionic σ-adduct at C-2, under exclusive elimination of C-2.     

4-氧代-3（4H）-喹唑啉-5-羧酸的合成

以2-氨基-6-甲基苯甲酸为起始原料,通过合环反应生成两种4-氧代-3(4H)-喹唑啉-5-羧酸衍生物(1a, 1b), 1a, 1b分别经高锰酸钾氧化合成了4-氧代-3(4H)-喹唑啉-5-羧酸（2a, 2b）,其结构经¹H NMR, ¹³C NMR和MS表征。研究了投料比｛r［n(高锰酸钾) :n(5-甲基-3(4H)-喹唑啉-4-酮)］｝和反应温度等对收率的影响。结果表明：在最佳反应条件（r=7:1,中性高锰酸钾氧化,于90 ℃反应）下合成2总收率可达66%。     

Cyclocondensation of N-aryl-3-oxobutanethioamides with 5-amino-3-R-4-R1-pyrazoles

The cyclocondensation products of N-aryl-3-oxobutanethioamides with 5-amino-3-R-4-R¹-pyrazoles are 4-(arylamino)-2-methyl-7-R-8-R¹-pyrazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine-4-thione derivatives, the ratio of which depends on the nucleophilicity of the starting 5-amino-3-R-4-R¹-pyrazoles and the presence of a proton donor solvent. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1550-1555, October, 2008.     

Synthesis of new imidazo[4,5-d][1,3]diazepine derivatives from 5-amino-4-(cyanoformimidoyl)imidazoles

N¹-[(Z) -2- Amino-1,2-dicyanovinyl]formamidines 1a-d react readily with tosyl isocyanate to form novel 8-amino-3-substituted-5-oxo-7-tosylaminoimidazo[4,5-d][1,3]diazepines 6a-d rather than the 6-cyano-2-oxopurine derivatives 5a-d expected. Compound 5a has been synthesized from 1a by reaction with ethyl chloroformate and base-catalyzed cyclization of the resultant 5-ethoxycarbonylamino-4-(cyanoformimidoyl)imidazole. Treatment of the 5-amino-4-cyanoimidazoles 7a and b with tosyl isocyanate under similar conditions gives the 4-cyano-5-(3′-tosylureido)imidazoles 8a and b , which on treatment with ethanolic ammonia cyclizes to the corresponding isoguanines 10a and b .     

Stereochemical specificity of the palladium-catalyzed hydrogenation of cyclohexa[b]thiopyrans and their derivatives

Conformationally and configurationally homogeneous 2-R¹-4-R²-cis-1-thiadecalins with an equatorial orientation of the substituents attached to the C(₂) and C(₄) atoms were isolated as the final reduction products in the catalytic hydrogenation on palladium of 2-R¹-4-R²-4H(6H)-cyclohexa[b]thiopyrans, cis-3-R¹-5-R²-2-thiabicyclo[4.4.0]-^1,6-decenes, and 2-R¹-4-R²-cyclohexa[b]thiopyrylium tetrafluoroborates and trifluoroacetates. cis-3-R¹-5-R²-2-Thiabicyclo[4.4.0]-^1,6-decenes were obtained as intermediates in the incomplete reduction of 2-phenyl- and 2,4-diphenyl-4H-cyclohexa[b]thiopyrans and 2-(4-methoxyphenyl)-4-R²-cyclohexa[b]thiopyrylium salts; 2-R¹-4-R²-6H-cyclohexa[b]thiopyrans undergo complete reduction of the double bonds of the heteroring. The hydrogenation products were oxidized to sulfoxides and sulfones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 614–619, May, 1987.     

Amination of 4-nitropyridazine 1-oxides by liquid ammonia/potassium permanganate

Treatment of 4-nitropyridazine 1-oxide ( 1a ) 3-methoxy-6-chloro-4-nitropyridazine 1-oxide ( 1b ) or 3,6-dimethoxy-4-nitropyridazine 1-oxide ( 1c ) with a solution of potassium permanganate in liquid ammonia gives in reasonable-to-good yields the corresponding 5-amino-4-nitropyridazine 1-oxides (75%, 54% and 62%, respectively). 3,6-Dimethoxypyridazine ( 4a ) and 3-methoxypyridazine ( 4b ) are converted into the corresponding 4-aminopyridazines 6a,6b on treatment with potassium amide/liquid ammonia/potassium permanganate (yield 50 and 22% respectively). In the last-mentioned reaction besides 6b 3,3′-dimethoxy 4,4′-bipyridazine (7, 23%) was obtained. It is suggested that the neutral 1:1 σ-adducts formed between ( 1a–1c ) and liquid ammonia and the anionic σ-adducts, formed between ( 5a–5b ) and potassium amide are intermediates in this amino-oxidation reaction.     

Features of the reaction of unsymmetrical 2-mercapto-imidazoles with aromatic and aliphatic ketones

The cyclization of unsymmetrical 2-mercaptoimidazoles with aliphatic and aromatic ketones has been studied. Using ¹H NMR and X-ray analysis it has been shown that 4-R¹-1H-2-mercaptoimidazoles undergo selective oxidative cyclization to the corresponding 3-R³-2-R²-6-R¹-imidazo[2,1-b][1,3]thiazoles while 6-R⁴-1H-2-mercaptobenzo[d]imidazoles give a mixture of 6-R⁴-3-R²-2-R³-benzo[4,5]imidazo[2,1-b][1,3]thiazole and 7-R⁴-3-R²-2-R₃-benzo[4,5]imidazo[2,1-b][1,3]thiazole in the ratio 1: 1. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 115–122, January, 2007.     

Aromatic derivatives of 2H-pyrimidino[5,6-b]-1,4-thiazine

5-R¹3-(4-R-Phenyl)-2H-pyrimidino[5,6-b]-1,4-thiazines [R¹=N(CH₃)₂ or OCH₃], which exist primarily in the 2H form, were synthesized by the reaction of -bromoacetophenones with 4-R¹-5-amino-6-thiopyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 275–277, February, 1987     

On triazoles. V. Synthesis of 1- and 2-R1-3-R2,R3-amino-5-amino-1,2,4-triazoles

The correct isomeric and tautomeric structure of different 1- and 2-R¹-3-R²,R³-amino-5-amino-1,2,4-triazole derivatives prepared from the corresponding N-cyano-N'-R²,R³-S-methyl-isothioureas and the corresponding hydrazines was proved with the help of their ir, uv, ¹H-nmr and ¹³C-nmr spectra as well as the uv spectra of the Schiff bases of an isomeric pair.     

Tin(IV) and organotin(IV) derivatives of novel β-diketones: Part IV. Triorganotin(IV) complexes of fluorinated 4-acyl-5-pyrazolones. Crystal structure of (1-(4-trifluoromethylphenyl)-3-methyl-4-acetylpyrazolon-5-ato)triphenyltin(IV)

The synthesis of three 1-(4-trifluoromethylphenyl)-3-methyl-4-R¹(C=O)-5-pyrazolone proligands LH (L¹H; R¹=C₆H₅: L²H; R¹=CH₃: L³H; R¹=CF₃) and their interaction with R₃Sn(IV) acceptors (R=Me, Buⁿ, Ph) are reported. When R=Me or Buⁿ, aquo (4-acylpyrazolonate)SnR₃(H₂O) derivatives are obtained and the anionic donors 4-acylpyrazolonate (L⁻) act in the O–monodentate form. These triorganotin complexes are not stable in chlorohydrocarbon solvents and decompose to R₄Sn and bis(4-acyl-5-pyrazolonate)₂SnR₂. When R=Ph, stable (4-acyl-5-pyrazolonate)SnPh₃ derivatives, both in solution and in the solid state, are obtained. The crystal structure of (1-(4-trifluoromethylphenyl)-3-methyl-4-acetylpyrazolon-5-ato)triphenyltin(IV) shows a five-coordinate tin atom in a strongly distorted cis-bipyramidal trigonal environment (axial angle=161.2(2)°) with the acylpyrazolonate donor acting as an asymmetric O₂–bidentate species (Sn–O(1)=2.081(6) Å: Sn–O(2)=2.424(5) Å). Electronic effects are responsible for the different behavior shown by these trialkyl and triphenyl derivatives.     

Investigation of the reactions of fluorine containing 3-hydrazino-5H-1, 2, 4-triazino[5, 6-b]indoles with ethyl acetoacetate. Synthesis of some novel tetracyclic ring systems

Novel tetracyclic ring systems viz. 3-methyl-1-oxo-12H-1, 2, 4-triazepino[3′,4′:3, 4][1, 2, 4]triazino[5, 6-b]indole ( 4a ) and 3-methyl-5-oxo-12H-1, 2, 4-triazepino[4′,3′:2, 3][1, 2, 4]triazino[5, 6-b]indole ( 5a ), having angular and linear structures respectively, were synthesized by the cyclization of 3-oxobutanoic acid [5H-1, 2, 4-triazino-[5, 6-b]indole-3-yl]hydrazone ( 3a ). However, cyclization of 3b (R = CH_a, R¹ = R² = H) afforded the angular product 4b exclusively. Moreover, cyclization of 3c (R = R³ = H, R¹ = F) yielded 7-fluoro-1-0xo-10H-1, 3-imidazo[2′,3′:3, 4][1, 2, 4]triazino[5, 6-b]indole ( 6c ) and 7-fluoro-3-oxo-10H-1, 3-imidazo[3′,2′:2, 3][1, 2, 4]triazino-[5, 6-b]indole ( 7c ) instead of the expected triazepinone derivatives. Compound 3d (R = R¹ = H, R² = CF₃) also gave an imidazole derivative but only one angular product was obtained. In all these reactions, formation of the angular product involving cyclization at N-4 is favoured. Characterization of these products have been done by elemental analyses, ir, pmr, ¹⁹F nmr and mass spectral studies.     

Photoinduzierte 1, 3-dipolare Cycloaddition von 3-Phenyl-2H-azirinen an Azodicarbonsäure-diäthylester. 32. Mitteilung über Photoreaktionen

Irradiation of 2, 2-dimethyl-3-phenyl- ( 1a ), 2, 3-diphenyl-2H-azirine ( 1b ) or the azirine-precursors 1-azido-1-phenyl-propene ( 2a ) and 1-azido-1-phenyl-ethylene ( 2b ), respectively, in benzene in the presence of azodicarboxylic acid diethylester, yields the corresponding 1, 2-carbethoxy-3-phenyl-Δ³-1, 2, 4-triazolines 4a–d (Scheme 1). Refluxing 4 ( a, c or d ) in 0, 2–0, 4M aqueous ethanolic potassium hydroxide leads to the formation of the 1-carbethoxy-3-phenyl-Δ²-1, 2, 4-triazolines 6 ( a, c or d ). Under the same conditions 4b is converted to 3, 5-diphenyl-1, 2, 4-triazole ( 7b , Scheme 2). In 10M aqueous potassium hydroxide solution heating of either 4 ( c or d ) or 6 ( c or d ) yields the 3-phenyl-1, 2, 4-triazoles 7 ( c or d ). Photolysis of 1-carbethoxy-5, 5-dimethyl-3-phenyl-Δ²-1, 2, 4-triazoline ( 6a ) in benzene in the presence of oxygen and trifluoroacetic acid methylester gives the 5-methoxy-2, 2-dimethyl-4-phenyl-5-trifluoromethyl-3-oxazoline ( 13 , Scheme 5). 5, 5-Dimethyl-3-phenyl-1, 2, 4-triazole seems to be the intermediate, which on losing nitrogen gives the benzonitrile-isopropylide ( 3a ).     

Cycloaddition reactions of cyclic ketene-N,S-acetals with 1,2,4,5-tetrazines

Reaction of 3,6-diphenyl-, 3,6-bis(2-pyridyl)- and the unsubstituted 1,2,4,5-tetrazine with 4,5-dihydro-1-methyl-2-(methylthio)pyrrole ( 2 ) and 1-raethyl-2-(methylthio)-4.5,6,7-tetrahydroazepine ( 3 ) gives 4,7-di-R-2,3-dihydro-1-methylpyrrolo[2,3-d]pyridazine ( 4 , R = phenyl, 2-pyridyl, hydrogen) and 6,9-di-R-1-methyl-2,3,4,5-tetrahydropyridazino[4,5-6]azepine ( 5 ), R = phenyl, 2-pyridyl, hydrogen), respectively, in reasonable to good yields. The compounds 4 (R = phenyl, hydrogen) are converted into their corresponding 1-methylpyrrolo-[2,3-d]pyridazines 6 by reaction with potassium permanganate in butanone. Reaction of 3-phenyl-1,2,4,5-te-trazine with 2 and 3 leads to the exclusive formation of the 7-phenyl isomer 4d and 9-phenyl isomer 5d , respectively, indicating that the cycloaddition is regiospecific. The mechanism is discussed.     

Simple synthesis of alkyl 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-7-carboxylates from 5-acetyl-4-aminopyrimidines

A method for the synthesis of methyl and ethyl 2-R¹-4-R²-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-7-carboxylates was proposed. The method is based on condensation of 2-R¹-6-R²-5-acetyl-4-aminopyrimidines with ethyl oxalate in the presence of MeONa or EtONa. Products of the Friedländer self-condensation of the starting pyrimidines were also obtained.     

Synthesis of 2H-1,4-thiazin-3(4H)-one 1-oxide and 2H-1,4-thiazin-3-(4H)-one 1,1-dioxide,structural analogs of uracil

The synthesis of 1,4-thiazine 1-oxide and 1,1-dioxide analogs of the antibiotic emimycin is described. Reaction of methylthioglycolate with 1-bromo-2,2-diethoxyethane gave methyl (2,2-diethoxyethylthio)acetate ( 2 ). Treatment of 2 with methanolic ammonia followed by cyclization furnished 2H-1,4-thiazin-3(4H)-one ( 5 ). Oxidation of 5 with m-chloroperoxybenzoic acid converted it to 2H-1,4-thiazin-3(4H)-one 1-oxide ( 6 ). Oxidation of 2 with potassium permanganate, followed by treatment with methanolic ammonia, and cyclization gave 2H-1,4-thiazin-3(4H)-one 1,1-dioxide.