Acetals of lactams and acid amides

The reaction of dimethylformamide diethylacetal with -cyano--dimethylaminoacrylamide proceeds at the NH₂ amide group to give the corresponding acylformamidine, from which 3-cyano-4-dimethylamino-2-pyridone was obtained by thermal cyclization. Pyrrolo-, pyrido-, and azepino-[3,2-c]pyridine derivatives were similarly synthesized from 1-methyl-2-(2-cyano-2-carbamido)-methylenepyrrolidine and the homologous six- and seven-membered enaminoamides.See [1] for communication XVII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1509–1512, November, 1976.     

Synthesis and reactions of pyrrolo[2,3-c]azepine derivatives

The construction of the pyrrolo[2,3-c]azepine system by the reaction of 2-oxo-3-hydroxy-4-cyano-2H, 1,5,6,7-tetrahydroazepine with glycine ester and subsequent cyclization of the resulting N-substituted amino nitrile in an alcohol solution of sodium ethoxide was studied. The pyrrolo[2,3-c]azepine system was converted to the three-ring pyrimido[4,54,5]pyrrolo[2,3-c]azepine system, the alkylation of which gave N,N-dialkyl and N,N,N-trialkyl derivatives. Cyclization of 3-benzyl-4, 6-dioxo-5-(N,N-dimethyl)aminoethyl-6H,3,4,7,8,9,10-hexahydropyrimido[4,54,5]pyrrolo[2,3-c] azepine hydrochloride under the influence of phosphorus oxychloride gave the four-ring pyrazino[3,2,1-b,c]azepino[3,4-b]pyrrolo[3,2-d]-pyrimidine system. The structures of the compounds obtained were confirmed by their IR, UV, and PMR spectra.Communication 34 from the series Research on Lactams. See [1] for communication 33.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1097–1100, August, 1980.     

Study of nitrogen- and sulfur-containing heterocycles. 46. New heterocyclic systems — Derivatives of pyrido[3′,2′∶5,6][1,4]thiazino[3,4-c]- and pyrimido-[5′,4′∶5,6][1,4]thiazino[3,4-c][1,2,4]triazines. Synthesis,properties

Representatives of new heterocyclic systems were obtained — pyrido[3,25,6][1,4]thiazino[3,4-c]- and pyrimido[5,45,6][1,4]thiazino[3,4-c][1,2, 4]triazines. Hydrazides of N-(pyrid-3-yl)- and N-(pyrimid-5-yl)oxamic acids were isolated and characterized. Their acylation products were investigated.For communication 45, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 559–562, April, 1993.     

Cyclization reactions of nitriles. 28. Synthesis and reactions of 3β-acetoxy-2′-methyl-5′-cyanoandrost-5-eno[17,16-c]pyridine-6′ (1′H)-thione

3-Acetoxy-2-methyl-5-cyanoandrost-5-eno[17,16-c]pyridine-6(1H)-thione was obtained by thiylation of 16-dicyanomethyl-3-hydroxypregn-5-en-20-one acetate, and its alkylation by chloroacetonitrile and phenacyl bromide was studied. The same thione was also synthesized by treating the corresponding 6-bromo-2-methyl-5-cyanoandrost-5-eno[17,16-c]pyridine with urea.Communication 27, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 943–946, July, 1988.     

(9-(Pyridazinyl-4)-4-azafluorenes and spiro compounds with 4-azafluorene and indeno[1,2-c]pyridazine (4h-5,6-dihydro-1,2-diazepine) fragments

9-(3,6-Diphenylpyridazinyl-4)-4-azafluorene has been synthesized, and its conversions at the C⁹ position have been studied. From its C⁹-hydroxy derivative, 3-phenylspiro-[4-azafluorene-9,5-indeno[1,2-c]pyridazine] has been obtained. From 9-(1,2-dibenzoylethylidene-4-azafluorene, 3,7-diphenylspiro-[4H-5,6-dihydro-1,2-diazepine-5,9-4-azafluorene] has been synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1357–1360, October, 1992.     

Synthesis of 3-Cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine 1-riboside

3-Cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine was synthesized by cyclization of 3,4-dicyano-5-aminopyrazole with CS₂ in pyridine with subsequent Dimroth rearrangement and methylation of the resulting 3-cyano-4,6-dimercaptopyrazolo[3,4-d]-pyrimidine with methyl iodide. Glycosylation of the product by fusion with 1,2,3,5-tetra-O-acetyl--D-ribofuranose in the presence of iodine gave 1-(2,3,5-tri-O-acetyl--D-ribofuranosyl)-3-cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine, the deacetylation of which with a 1% solution of hydrogen chloride in methanol led to 3-cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine 1-fiboside. The structures of the compounds were established by IR, UV, circular dichroism, PMR, and ¹³NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1687–1692, December, 1979.Original article submitted March 29, 1979.     

Azide-tetrazole tautomerism of diazidodiazines and their benzo analogs

It has been discovered with the aid of IR and NMR spectroscopy that 5-azidotetrazolo [1,5-a]quinazoline exists in solutions in a tautomeric equilibrium with ditetrazolo [1,5-a:1,5-c]quinazoline, and the thermodynamic and kinetic characteristics of the equilibrium have been determined. Azide-tetrazole tautomerism is not observed under these conditions for ditetrazolo[1,5-a:5,1-c]pyrazine, 6-azidotetrazolo [1,5-b]pyridazine, and their benzo analogs.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2002–2007, September, 1989.     

Synthesis of derivatives of pyrazolo[3,4-d]pyrimidin-3-ylacetic acid and their nucleosides

3-Cyanomethyl-4,6-dimethylmercaptopyrazolo[3,4-d]pyrimidine was synthesized on the basis of 3-cyanomethyl-4-cyano-5-aminopyrazole. Ribosylation of this product gave 1-(2,3,5-tri-O-acetyl--D-ribofuranosyl)-3-cyanomethyl-4,6-dimethylmercaptopyrazolo[3,4-d]pyrimidine in 63% yield and small amounts of the 1- and 2- isomers. A number of derivatives of 6-methylmercaptopyrazolo[3,4-d]pyrimidin-3-ylacetic acid and their 1-ribosides were synthesized. The 4-methylmercapto group was replaced by amino, hydrazino, oxo, N-piperidino, and N-morpholino groups. The nitrile group was saponified in an alkaline medium to carbamoyl and carboxy groups. The corresponding 4-morpholino and 4-piperidino derivatives were obtained by the reaction of 3-cyano-4,6-dimethylmercaptopyrazolo[3,4-d]pyrimidine per-O-acetylated 1--D-ribofuranoside with secondary cyclic amines. The high resistance of the 6-methylmercapto group to the action of nucleophilic agents and the higher reactivity of the 4-methylmercapto group as compared with the nitrile group are discussed. Data on the cytotoxic activity of the synthesized compounds were obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 536–545, April, 1981.     

Synthesis of derivatives of the new heterocyclic system pyrimido[4′,5′:4,5]pyrimido[1,2-a]benzimidazole

3-Phenyl-5-methyl(phenyl)-1H,3H-pyrimido[4,5:4,5]pyrimido[1,2-a]benzimi-dazole-2,4-diones were obtained by the cyclization of N-phenyl-N-[3-ethoxycar-bonyl-4-methyl(phenyl)pyrimido [1,2-a]benzimidazol-2-yl]ureas by the action of potassium carbonate. 2-Methyl-5-phenyl-1H-pyrimido[4,5:4,5]pyrimido[1,2-a]benzimidazol-4-one was obtained by the reaction of N-3-ethoxycarbonyl-4-phenylpyrimido[1,2-a]benzimidazol-2-yl]-N,N-dimethylacetamidine with ammonium acetate in ethanol. The synthesized compounds are members of a new heterocyclic system. The molecular and crystal structure of the solvate of 3-phenyl-5-methyl-1H,3H-pyrimido[4,5:4,5] pyrimido[1,2-a]benzimidazole-2,4-dione with two molecules of DMF was studied by x-ray crystallographic analysis.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2587–2592, November, 1991.     

Preparation and stereochemical characterization of some N-acyl-[1]benzopyrano[3,4-c]pyrazole derivatives from rotenoids

Summary Several new N-acyl derivatives of 1-(4-hydroxy-2,3-dihydrobenzofuran-5-yl)-7,8-di methoxy-1,9 b,2,3,3 a,4-hexahydro-[1]benzopyrano[3,4-c]pyrazole-1-ene have been prepared by appropriate chemical transformation of isohydrazones of rotenone and amorphigenin. A study of their¹H- and¹³C-NMR spectra confirmed the presence of the twocis 3a, 9b, 2 and 3a, 9b, 2 diastereomers in the parent isohydrazones and revealed the strong predominance of the conformers withendo orientation of the 3-NAc group. The conformations due to rotation about the 1,5-bond between rings C and D in the 4-OH and 4-O-substituted compounds were also determined by taking into account the anisotropic effect of aromatic rings A and D, and the hydrogen bond between 4-OH and the 2-N atom, as well as by inspecting the Dreiding models.

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Darstellung und stereochemische Charakterisierung einiger N-Acyl-[1]benzopyrano[3,4-c]pyrazol-Derivate von Rotenoiden

Zusammenfassung Mittels geeigneter chemischer Transformationen von Isohydrazonen von Rotenon und Amorphigenin wurden einige neue N-Acyl-Derivate von 1-(4-Hydroxy-2,3-dihydrobenzofuran-5-yl)-7,8-dimethoxy-1,9 b,2,3,3 a,4-hexahydro-[1]benzopyrano[3,4-c]pyrazol-1-en hergestellt. Eine Untersuchung ihrer¹H und¹³C-NMR-Spektren zeigt die Gegenwart von zweicis 3a, 9b, 2- und 3a, 9b, 2-Diastereomeren in den Ausgangs-Isohydrazonen und eine starke Bevorzugung der Konformeren mitendo-Orientierung der 3-NAc-Gruppe. Die Konformationen bezüglich der Rotation um die 1,5-Bindung zwischen Ring C und D werden für die 4-OH und 4-O-substituierten Verbindungen unter Berücksichtigung von Anisotropie-Effekten der aromatischen A- und D-Ringe, der Wasserstoffbrücken zwischen 4-OH und dem 2-N Atom und auch der Betrachtung der entspechenden Dreiding-Modelle diskutiert.

     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions. 16. Synthesis and properties of benzo[b]-1,4-diazabicyclo[2.2.2]octene and dibenzo[b,e]-1,4-diazabicyclo[2.2.2]octadiene,containing primary aromatic amino acids

4-Aminobenzo[1,2-b]-1,4-diazabicyclo[2.2.2]octene and 4-aminodibenzo[1,2-b, e]-1,4-diazabicyclo[2.2.2]octadiene have been prepared by cyclization reactions of N--chloroethyl derivatives of 1,2,4-triaminobenzene and aminophenazine, and subsequent catalytic hydrogenation of the corresponding 4-nitrobenzo[1,2-b]-1,4-diazabicyclo[2.2.2]octene and 4-benzylaminodibenzo[1,2-b,e]-1,4-diazabicyclo[2.2.2]-octadiene. Using the conversion of these compounds to azides as an example, we have demonstrated the feasibility of applying these primary aromatic amines for the synthesis of derivatives of these heterocycles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 831–837, June, 1988.     

Synthesen in der Pyridazin-Reihe, 31. Mitt.: Über einige neue polycyclische Azolo- und Azinopyridazine

Zusammenfassung Synthesen von verschiedenen neuen polyazaheterocyclischen Systemen, wie 11H-Imidazo[1,22,3]pyridazino[6,1-b]-chinazolin-11-on (3), 11H-s-Triazolo[4,32,3]pyridazino[6,1-b]chinazolin-11-on (4), der Isomeren 4H-Pyrido[2,34,5]-pyridazino[6,1-c]-as-triazin (6) und 4H-Pyrido[3,24,5]-pyridazino[6,1-c]-as-triazin (9), Pyrido[3,24,5]pyridazino[1,6-b]benzimidazol (14) sowie Pyrido[3,24,5]-s-triazolo[4,32,3]pyridazino[1,6-a]benzimidazol (15) werden beschrieben.

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Syntheses of pyridazines, XXXI: Some new polycyclic azolo and azino-pyridazines

Syntheses of several new polyazaheterocyclic systems are described, i.e. 11H-Imidazo[1,22,3]pyridazino[6,1-b]quinazolin-11-one (3), 11H-s-Triazolo[4,32,3]pyridazino[6,1-b]quinazolin-11-one (4), the isomeric 4H-Pyrido[2,34,5]pyridazino[6,1-c]-as-triazine (6) and 4H-Pyrido[3,24,5]pyridazino[6,1-c]-as-triazine (9), Pyrido[3,24,5]pyridazino[1,6-b]-benzimidazole (14) and Pyrido[3,24,5]-s-triazolo[4,32,3]pyridazino[1,6-a]benzimidazole (15).

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Heterocyclen, 69. Mitt.     

Some transformations of 1-(1,2,3,4-tetrahydronaphthylidene)-malononitrile or cyanoacetate

Summary Syntheses of 11-amino-5,6-dihydronaphtho[1,2:4,5]thieno[2,3-d]pyrimidine (8) and its 10-oxide 7 from 2-amino-1-cyano-4,5-dihydronaphtho[2,1-b]thiophene and its derivatives are described. Several open chain tetrahydronaphthylidene derivatives and a substituted pyrimidine derivative9 were also prepared.Dedicated to Professor Dr. K. Gewald on the occasion of his 60th birthday     

New monomers for the synthesis of heat-stable polyheterocycles

To obtain benzodioxazole analogs of the polypyromellitimides and polymers with alternating pyromellitimide and benzodioxazole links, we have synthesized 2,6-di(paminophyl)benzo[1,2-d5,4-d]dioxazole (I), 2,6-di[p-(p-aminophenoxy)phenyl]benzo-[1,2-d5,4-d]dioxazole (II), N,N-di(p-chloroformylphenyl)pyromellitdiimide (III) and N,N-di(p-chloroformylphenyl)-2,5-dimethoxycarbonyl terephthalamide (IV). Derivatives modelling the polymers mentioned above have been synthesized from the diamines mentioned, and also from 4,6-diaminoresorcinol.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 6, pp. 739–743, June, 1970.     

9-(2′,5′-Dimethyl-4′-pyridyl)fluorene in syntheses of fluorospirodihydrofuropyridine and pyridofluoranthene

1,2,5-Trimethyl-4-(9-fluorenylidene)piperidine, which is formed by condensation of fluorene with 1,2,5-trimethyl-4-piperidone, is converted catalytically to 9(2,5-dimethyl-4-pyridyl)fluorene, from which 2-methylpyrido[4,5-a]fluoranthene and its demethylated analog were obtained by catalytic dehydrocyclization. Oxidation of 9-(2,5-dimethy1-4-pyridyl)fluorene gave 9-(2,5-dimethyl-4-pyridyl)9-fluorenol and fluorene-9-spiro-4-(6-oxo-2-carboxypyrido[4,5-c]-4-6-dihydrofuran). 6-Methyl-2-phenyl-7-(9-fluorenyl)indolizine was synthesized by the Chichibabin method.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1087–1090, August, 1978.     

Pyrimidines

It is shown that the reaction of benzalbisurea with 3-amino-5-hydroxy-1-R-pyrazoles gives 1-R-dipyrazolo[3,4-b:4,3-e]pyridine (R=CH₃) or a spiro(pyrazole-4,5-pyrimidine) derivative (R=C₆H₅). Similar reactions of benzalbisurea with 3-hydroxy-5-amino-1-methylpyrazole give 2-methyldipyrazole[3,4-b:4,3-e]pyridine or substituted tetrahydropyrazolo[3,4-d] pyrimidine. Only the corresponding dipyrazolo[3,4-b:4,3-e]pyridines are formed in the reaction of 1-methylhydroxyaminopyrazoles with methylenebisurea.See [1] for communication XXXIX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 823–827, June, 1974.     

Synthesis of isomeric benzodipyrrolenines and their derivatives

The Fischer reaction was used to synthesize 2,3,3,5,5,6-hexamethyl-3H,5H-benzo[1,2-b5,4-b]dipyrrole and 2,3,3,7,8,8-hexamethyl-3H,8H-benzo[1,2-b3,4-b]dipyrrole from the dihydrazone obtained by the action of methyl isopropyl ketone on m-phenylenedihydrazine. Centrosymmetrical 2,3,3,6,7,7-hexamethyl-3H,7H-benzo[1,2-b4,5-b]dipyrrole was synthesized from p-phenylenediamine and methyl bromoisopropyl ketone. Mono- and diquaternary salts were obtained from the new bases. The diquaternary salts were converted to bismethylene bases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 614–617, May, 1971.     

Über Tetrahydrospiro [cyclohexan-1,4′(1′H)-chinazolin]-2′(3′H)-one

Zusammenfassung Cyclohexanon bzw. Cyclopentanon sowie ihre durch Aldolreaktion entstehenden Dimeren reagieren mit Harnstoff im sauren Medium zu 5,6,7,8-Tetrahydrospiro[cyclohexan-1,4(1H)-chinazolin]-3(2H)-onen (2) bzw. zum Dihydrospiro-(cyclopentan-1,4(1H)-5H-cyclopenta[d]pyrimidin)-2(3H)-on (10). Substituierte Harnsotoffe geben Gemische der isomeren 5,6,7,8-Tetrahydro- und 4a,5,6,7-Tetrahydroverbindungen (2, 3) bzw. 6,7-Dihydro-tH- und 5,6-Dihydro-4aH-verbindungen (10, 11). Charakteristisch für2 (3),10 (11) ist die Reaktivität der Kernstellen 8 bzw. 7 gegenüber elektrophilen Agentien (2f-v, 3f-j, 9 a-i, 10 d-f). Äthylmalonsäurebis-trichlorphenylester bzw. Formaldehyd und prim. Amine führen2 in ein partiell hydriertes 1H-Pyrido[3,2,1-ij]chinazolintrion (6) bzw. 1H-Pyrimido[5,6,1-ij]chinazolinon (7) über. Die 1-Alkylverbindungen (2) geben mit Formaldehyd und primären Aminen Hexahydro-8a-hydroxy-4a,8-propanospiro-(cyclohexan-1,4(1H)-pyrido[4,3-d]pyrimidin)-2(3H)-one (8).

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Heterocycles, XXV: tetrahydrospiro [cyclohexane-1,4(1H)-quinazoline]-2(3H)-ones

Cyclohexanone and cyclopentanone, resp., as well as their dimers (formed by aldol reaction) react with urea in the presence of acids to 5,6,7,8-tetrahydrospiro[cyclohexane-1,4-(1H)-quinazoline]-3(2H)-ones (2) and to the dihydrospiro-(cyclopentane-1,4(2H)-5H-cyclopenta[d]pyrimidine)-2(3H)-one (10), resp. Substituted ureas give the isomeric 5,6,7,8-tetrahydro- and 4a,5,6,7-tetrahydro compounds (2, 3), and 6,7-dihydro-5H- and 5,6-dihydro-4aH-compounds (10, 11), resp. Characteristic for2 (3),10 (11) is the reactivity of the nuclear places 8 and 7 with electrophilic agents (2f-v, 3f-j, 9a-i, 10d-f). Ethylmalonic acid bistrichlorophenylester resp. formaldehyde and primary amines react with2 to the partially-hydrogenated 1H-pyrido[3,2,1-ij]-quinazolinetrione (6) and 1H-pyrimido[5,6,1-ij]-quinazolinone (7), resp. The 1-alkyl compounds (2) give with formaldehyde and primary amines hexahydro-8a-hydroxy-4a, 8-propanospiro(cyclohexane-1,4-(1H)-pyrido[4,3-d]pyrimidine)-2(3H)-ones (8).

     

Synthesis of macrocyclic compounds that are condensed with a pyrazole ring

2-Carbethoxy-[11]--cyclothien-1-one, 2-carbethoxycyclopentadecanone, and 2,15-dicarbethoxy-[9,9]--cyclodithiene-1,14-dione were converted to 2-phenyl-1-methyl-[11]--cyclothieno [1,2-d] pyrazol-3-one, 2-phenyl-1-methyl-4,5-tridecamethylenepyrazol-3-one, and 2,16-diphenyl-1, 15-dimethyl- [9,9]-, -cyclodithienobis [(1,2-d, 14,15-d) pyrazole]-3,17-dione, respectively, by condensation with phenylhydrazine and subsequent methylation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 920–923, July, 1980.     

Study of furan compounds

Research on synthesis of polycyclic spirans of the 1, 6-dioxaspiro-[4, 4]nonane group is continued. Electrolysis of methanol solutions of 2-furylcyclopentanol, 2-(5-methyl-furfuryl)cyclopentanol, and 2-furfuryl-1-indanol, gives, by intramolecular alkoxylation, spiro{perhydrocyclopenta[b]furan-2, 2-(5dihydrofuran)}, spiro{perhydrocyclopenta[b]furan-2, 2-(5-methoxy-5-methyl-2, 5-dihydrofuran)}, and spiro{2, 3, 3a, 8b-tetrahydro-4H-indeno[1, 2-b]furan-2, 2-(5-methoxy-2, 5-dihydrofuran)}, hitherto undescribed in the literature. Depending on the conditions, catalytic hydrogenation of these gives: spiro{perhydiocyclopenta[b]furan-2, 2-(5-methoxytetrahydrofuran)}, spiro{2, 3a, 8b-tetrahydro-4H-indeno[1, 2-b]furan-2, 2-(5-methoxytetrahydrofuran)}, spiro{perhydrocyclopenta[b]furan-2, 2-tetrahydrofuran}, and spiro{2, 3, 3a, 8b-tetrahydro-4H-indeno[1, 2-b]furan-2, 2-tetrahydrofuran}.For Part XXXI see [1].