Three-Component Spiro Heterocyclization of Pyrrolediones,Indane-1,3-dione,and Heterocyclic Enamines

Russian Journal of Organic Chemistry - 3-Methyl-2′,5-dioxo-5′-phenyl-1′,2′,5,10-tetrahydrospiro(indeno[1,2-b]isoxazolo[4,3-e]pyridine-4,3′-pyrroles) and...     

Three-Component Spiro Heterocyclization of Pyrrolediones with Indan-1,3-dione and Acyclic Enamines

Ethyl 4,5-dioxo-2-phenyl-4,5-dihydro-1H-pynole-3-carboxylates reacted with indan-1,3-dione and 3-amino-1-phenylbut-2-en-1-one or 3-aminobut-2-enenitrile to give 3-benzoyl-2-methyl-2′,5-dioxo-5′-prienyl-1,1′,2′,5-tetrahydrospiro[indeno[1,2-b]pyridine-4,3′-pyrroles] and 2-methyl-2′,5-dioxo-5′-phenyl-1,1′,2′,5-tetrahydrospiro[indeno[1,2-b]pyridine-4,3′-pyrrole]-3-carbonitriles, respectively.

     

Three-Component Spiro Heterocyclization of Pyrrolediones with Malononitrile and Cyclic Enols

Ethyl 4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates reacted with malononitrile and five-membered cyclic enols, indan-1,3-dione and cyclopentane-1,3-dione to give 1-substituted ethyl 2-amino-3- cyano-2′,5-dioxo-5′-phenyl-1′,2′-dihydro-5H-spiro[indeno[1,2-b]pyran-4,3′-pyrrole]-4′-carboxylates and ethyl 2-amino-3-cyano-2′,5-dioxo-5′-phenyl-1′,2′,6,7-tetrahydro-5H-spiro[cyclopenta[b]pyran-4,3′-pyrrole]-4′-carboxylates, respectively.     

Acetals of lactams and acid amides. 35. Synthesis of condensed two- and three-ring pyridine systems on the basis of enamino amides

The synthesis of 2,3,5,6-tetrahydropyrrolo[3,2-c]pyrid-6-one was accomplished by rearrangement of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1, 2-c]pyrimidine. Pyrrolo[3,2-c]pyrimidine, 1,6-naphthyridine, and pyrimido[4,3-b]-azepine derivatives were synthesized on the basis of enamino dinitriles. The hydrolysis of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1,2-c]-pyrimidine in 50% CH₃COOH leads to a pyrrolo[1,2-c]pyrido[4,3-d]pyrimidine derivative. A similar dipyrido[4,3-d-1,2-c]pyrimidine derivative was obtained from 1-cyano-9-dimethylaminomethylene-2,5,6,7,8,9-hexahydropyrido[1,2-c]pyrimidine under these conditions, and 3,4-dioxo-3,4,7,8,9,10-hexahydropyrido[1,2-c]pyrano[4,3-d]-pyrimidine was synthesized bytreatment with a 1 N solution of HCl.See [1] for Communication 34.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 518–522, April, 1982.     

Polyfunctional macroheterocycles

The reaction of 1-[1,2-bis(carbomethoxy)ethyl]aziridine with ethane-1,2-dithiol leads to 1.8-bis[1,2-bis(carbomethoxy)ethylamino]-3,6-dithiaoctane. Condensation with phthalic and terephthalic acid dichloride gives 9,10-benzo-8, 11-dioxo-7,12-bis[1,2-bis(carbomethoxy)ethyl]-1,4-dithia-7,12-diazacyclotetradec-9-ene and 9,12-benzo-8,13-dioxo-7,14-bis[1,2-bis(carbomethoxy)ethyl]-1,4-dithia-7,14-diazacyclohexadeca-9,12-diene, respectively, while condensation with formaldehyde gives 7,9,18,20-tetrakis[1,2-bis(carbomethoxy)ethyl]-1,4,12,15-tetrathia-7,9,18.29-tetraazacyclodocosane. The corresponding disulfone is formed in the oxidation of 9,10-benzo-8,11-dioxo-7,12-bis[1,2-bis(carbomethoxy) ethyl]-1,4-dithia-7,12-diazacyclotetradec-9-ene with 30% hydrogen peroxide.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1563–1565, November, 1988.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.     

First nucleophilic aromatic substitution of annelated pyrazole.

3-Chloropyrazolo[3,4-c]quinoline 5, 3-chloropyrazolo[3,4-c]isoquinoline 6, 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]quinolin-3-one 8, and 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]isoquinolin-3-one 10 were obtained by acid-induced nucleophilic aromatic substitution (S(N)H) of H-3 in N-hydroxypyrazolo[3,4-c]quinoline 1b and in N-hydroxy pyrazolo[3,4-c]isoquinoline 3b. In the acid-induced chlorination, 3b was far more reactive than 1b, whereas the related N-hydroxypyrazolo[4,3-c]quinoline 2b and N-hydroxypyrazolo[4,3-c]isoquinoline 4b were completely unreactive toward S(N)H under identical conditions.     

5,6-Dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetic acid diethyl ester,an useful synthon for the synthesis of new polycyclic nitrogen systems of pharmacological interest

This report describes the synthesis of derivatives of two nitrogen tetracyclic ring systems, respectively 9H,11H-pyrimido[4,3-c]pyrrolo[1,2-a][1,4]benzodiazepine and spiro[piperidine-4,4′-[4H]pyrrolo[1,2-a][1,4]-benzodiazepine], by the use of the diethyl ester of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetic acid as a synthon. This compound was obtained by condensation of 1-(2-aminomethylphenyl)-1H-pyrrole with diethyl 1,3-acetonedicarboxylate in acid medium. Pyrimidopyrrolobenzodiazepine derivatives were obtained by treating either the pyrrolobenzodiazepine 4,4-diacetate or the related 4-methyl-4-acetate with phenylisocyanate in boiling diethyl ether in the presence of sodium metal. The structure of 12,13-dihydro-11,13-dioxo-12-phenyl-9H,11H-pyrimido[4,3-c]pyrrolo[1,2-a][1,4]benzodiazepine, a product formed by loss of an acetate unit when 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetate, sodium metal and phenyl-isocyanate reacted in boiling xylene, was proved by catalytic reduction to 11,13-dioxo-12-phenyl-12,13,14,14a-tetrahydro-9H,11H-pyrimido[4,3-c]pyrrolo[1,2-a][1,4]benzodiazepine, which was synthesized by unambiguous pathway via 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4-acetate. The 2,6-dioxospiro[piperidine-4,4′-[4H]pyrrolo[1,2-a][1,4]benzodiazepine] derivatives were synthesized from the N-BOC derivative of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepine-4,4-diacetic acid diethyl ester, by hydrolysis followed by treatment with 2 equivalents of 1,1′-carbonyldiimidazole (CDI) and then with aniline or benzylamine. Removal of BOC from the N-phenyl-2,6-dioxopiperidine derivative was obtained by heating the related spiroderivative in toluene in the presence of p-toluenesulphonic acid. Similar reaction failed when the N-benzyl-2,6-dioxopiperidine analog was used as substrate.     

Synthesis of alkyl hexahydropyrazino-[1,2-<Emphasis Type="Italic">c</Emphasis>]pyrimidine-9-carboxylates

Cyclocondensation of 3-alkoxycarbonylmethylidenepiperazin-2-ones with α-chlorobenzyl isocyanates gave alkyl 8-aryl-1,6-dioxo-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidine-9-carboxylates. The use of 1-aryl-2,2,2-trifluoroethyl isocyanates in an analogous cyclization gave 6-aryl-1,8-dioxo-6-trifluoromethyl-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidine-9-carboxylates.     

Synthese von imidazo[1,5-a]- und pyrazino[1,2-a]benzimidazolen

1,2-Dihydro-3H-imidazo[1,5-a]benzimidazoles (6), 1-oxo-1,2-dihydro-3H-imidazo[ 1,5-a] benzimidazoles (8), 3H-imidazo[1,5-a]benzimidazoles (7), 3-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a] benzimidazoles (12), and 3,4-dioxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]benzinudazoles (13) were synthesized from 2-α-aminobenzyl (benzhydryl)-benzimidazoles (2).     

Synthesis of new imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-one derivatives by iodocyclization of 6-alkenyl(alkynyl)-aminopyrazolo[3,4-d]pyrimidin-4(5H)-ones

6-Allyl(diallyl, prop-2-yn-1-yl)amino-1-R-pyrazolo[3,4-d]pyrimidin-4(5H)-ones reacted with iodine to give angularly fused 8-iodomethyl-7,8-dihydro-1-R-imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-ones which were treated with sodium acetate to obtain 8-methylidene-1-R-7,8-dihydroimidazo[1,2-a]pyrazolo-[4,3-e]pyrimidin-4(6H)-ones as a result of elimination of hydrogen iodide. 8-Methylidene-1-R-7,8-dihydroimidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-ones were converted into 8-methyl-1-R-imidazo[1,2-a]pyrazolo-[4,3-e]pyrimidin-4(5H)-ones on heating to the melting point. 8-Methylidene-1-phenyl-7,8-dihydroimidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6H)-one underwent isomerization into linearly fused 6-methyl-1-phenyl-1,8-dihydro-4H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-4-one on heating in sulfuric acid.     

Pyrimidines. 24. Analogues and derivatives of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP)

Preparation of a number of derivatives of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) including the 2-dialkylaminoalkylamino-, 2-hydroxyalkylamino-, 2-ethoxycarbonylamino- and 2-alkylaminocarbonyl-amino- groups substituted on the pyrimidine ring as well as preparation of 1-(alkylaminoalkyl)-4,6-dioxo-8-phenyl-2,3,4,6-tetrahydro-1H-pyrimido[1,2-α]pyrimidines and 3,5-dioxo-7-phenyl-1,2,3,5-tetrahydroimidazo-[1,2-α]pyrimidines with or without the bromo-substitution are reported.     

The synthesis of 1,2-diazabicyclo[3,3,1]nonane and 1,9-diazabicyclo-[4,3,0]nonane. iv

The new bicyclic systems 1,2-diazabicyclo[3,3,1]nonane and 1,9- diazabicyclo [4,3,0]nonane have been synthesized from 2- (and 3-) piperidineacetic acid via their nitroso-derivatives, and 3-oxo-1,2 diazabicyclo [3,3,1]nonane and 8-oxo-1,9-diazabicyclo[4,3, 0]nonane.For Part III, see [3].     

Pyrano[4,3-d]pyrimidinium salts 3. Reactions of 1,3-dimethyl-2,4-dioxo-1H,3H-pyrano[4,3-d]pyrimidinium salts with azomethines

Reactions of 1,3-dimethyl-2,4-dioxo-1H,3H-pyrano[4,3-d]pyrimidinium salts with azomethines have been studied. The reactions lead to 1,3-dimethyl-2,4-dioxo-1H,3H-pyrido-[4,3-d]pyrimidinium salts and aromatic aldehydes.     

Recherches en série triazépine-1,2,4: II — Etude de la réaction de l'acétylacétate d'éthyle avec les diamino-3,4 oxo-5 dihydro-4,5 triazines-1,2,4

The reaction of 3,4-diamino-5-oxo-4,5-dihydro-l,2,4-triazine or its 6-methyl or 6-phenyl substituted derivatives and ethyl acetoacetate gave three compounds: 4,7-dioxo-9-methyl-1,4,6,7-tetrahydro-as-triazino[4,3-b]-1,2,4-triazepine in poor yield, isomeric 4,9-dioxo-7-methyl-1,4,8,9-tetrahydro-as -triazino[4,3-b]-1,2,4-triazepine and by competitive cyclisation, 2-methyl-7-oxo-3,7-dihydro-s-triazolo[3,2-c]-1,2,4-triazine. By condensation of 3-methylamino-4-amino-5-oxo-4,5-dihydro-1,2,4-triazine with ethyl acetoacetate, the formation of 4,9-dioxo-7,10-dimethyl-4,8,9,10-tetrahydro-as-triazino[4,3-b]-1,2,4-triazepine was strongly favored.     

The synthesis and properties of pyridazino[4,3-e] -as-triazines and pyridazino[4,5-e] -as-triazines,two novel condensed pyridazine ring systems

The compounds prepared in the novel pyridazino[4,3-e]-as-triazine ring system are: 8-chloro-4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 21 ), 8-chloro-2,4-dimethyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 23 ), 8-chloro-2-ethyl-4-methyl-3,4-dihydropyridazino[4,3-e]-as- triazine ( 24 ), 4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine-8-thione ( 25 ), 4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 26 ), 2,4-dimethyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 27 ), and 2-ethyl-4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 28 ). In the novel pyridazino[4,5-e]-as-triazine ring system the following compounds were prepared: 1,2-dihydropyridazino[4,5-e]-as-triazine ( 31 ), 3-methyl-1,2-dihydropyridazino[4,5-e]-as-triazine ( 32 ), 3-ethyl-1,2-dihydropyridazino[4,5-e]-as-triazine ( 33 ), and 1-methyl-1,2-dihydropyridazino[4,5-e]-as-triazine ( 35 ). The preparation of a number of previously unreported intermediates and compounds for structure proof are also described.     

Formation of 1,1,4,4-tetramethoxy-2,3,5,6-tetrahydroximinocyclohexane by the interaction of trinitrosophloroglucinol with hydroxylamine hydrochloride in methanol

1,1,4,4-Tetramethoxy-2,3,5,6-tetrahydroximinocyclohexane was obtained by the treatment of trinitrosoploroglucinol with hydroxylamine hydrochloride in methanol. Oxidation of the product with an alkaline solution of potassium hexacyanoferrrate(III) gave a mixture of the isomers 4,4,8,8-tetramethoxy-4H, 8H-benzo[1,2-c:4,5-c']bis[1.2.5]oxadiazole-1,7-dioxide.and 4,4,8,8-tetramethoxy-4H, 8H-benzo[1,2-c:4,5-c']bis-[1.2.5]oxadiazole-1,7-dioxide. Removal of the N-oxide groups from these compounds with triethyl phosphite followed by hydrolysis of the diketal groups gave 4,8-dioxo-4H, 8H-benzo[1,2-c:4,5-c']bis[1.2.5]-dioxazole. Reaction with malonodinitrile gave 4,8-di(dicyanomethylene)-4H, 8H-benzo[1,2-c:4,5-c']bis[1.2.5]-oxadiazole which is an analog of known electron acceptors. Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Acaemy of Sciences, Novosibirsk 630090. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 549–553, April, 1997.     

Electrophilic chemistry of thia-PAHs: stable carbocations (NMR and DFT), S-alkylated onium salts, model electrophilic substitutions (nitration and bromination), and mutagenicity assay

First examples of stable carbocations are reported from several classes of thia-PAHs with four fused rings, namely, benzo[b]naphtho[2,1-d]thiophene (1) and its 3-methoxy derivative (2), phenanthro[4,3-b]thiophene (3) and its 7-methoxy (4), 10-methoxy (5), and 9-methoxy (6) derivatives, phenanthro[3,4-b]thiophene (7) and its 7-methoxy (8) and 9-methoxy (9) derivatives, and 3-methoxybenzo[b]naphtha[1,2-d]thiophene (11). In several cases, the resulting carbocations were also studied by GIAO-DFT. Charge delocalization modes in the resulting carbocations were probed. A series of S-alkylated onium tetrafluoroborates, namely, 1Me+, 1Et+, 2Et+, and 7Me+ (from 1, 2, and 7), 10Me+ and 10Et+ (from benzo[b]naphtha[1,2-d]thiophene 10), 12Me+ and 12Et+ (from phenanthro[3,2-b][1]benzothiophene 12), 13Me+ (from 3-methoxyphenanthro[3,2-b]benzothiophene 13), 14Me+ (from phenanthro[4,3-b][1]benzothiophene 14), and 15Me+ (from 3-methoxyphenanthro[4,3-b][1]benzothiophene 15), were synthesized. PAH-sulfonium salts 1Me+, 1Et+, 10Me+, 10Et+, 12Me+, and 14Me+ proved to be efficient akylating agents toward model nitrogen nucleophile receptors (imidazole and azaindole). Facile transalkylation to model nucleophiles (including guanine) is also supported by favorable reaction energies computed by DFT. Ring opening energies in thia-PAH-epoxides from 1, 3, and 7 and charge delocalization modes in the resulting carbocations were also evaluated. The four-ring-fused thia-PAHs 1, 2, 3, 4, 5, 7, 8, and 11 are effectively nitrated under extremely mild conditions. Nitration regioselectivity corresponds closely to protonation under stable ion conditions. Bromination of 4 and 6 is also reported. Comparative mutagenicity assays (Ames test) were performed on 1 versus 1NO2, 5 versus 5NO2, and 11 versus 11NO2. Compound 5NO2 was found to be a potent direct acting mutagen.     

Synthesis and properties of some derivatives of 2-thionoindeno [1,2-d]-pyrimidine and indeno [1,2-d] [3,1] thiazine

Derivatives of 2-thiono-5-oxo-2,3,4,5-tetrahydroindeno[1,2-d] pyrimidine and 5-oxo-1,2,4,5-tetrahydroindeno [1,2-d] [3,1] thiazine are formed in the cyclocondensation of 2-arylideneindan-1,3-diones with thiourea and N-monomethylthiourea, while only derivatives of indeno [1,2-d]-pyrimidine are formed in the reaction with N,N-di-methylthiourea. S- and N(₃)-Alkylation occur in the alkylation of 2-thiono-4-pheny1-5-oxo-2,3,4,5-tetrahydroindeno[1,2-d]pyrimidine, while only the N-methyl derivative is formed in the alkylation of 2,5-dioxo-4-phenyl-1,2,4,5-tetrahydroindeno [1,2-d] [3,1]thiazine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1136–1141, August, 1988.     

Synthesis of bisarylmethyl-substituted pyrimidines and quinolines

The condensation of 2-chloro-8-methylquinoline-3-carbaldehyde, 2-chloroand 2-chloro-7,8,9,10-tetrahydrobenzo[h]quinoline-3-carbaldehydes, 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde, 6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde, and 2-chloropyrido[1,2-a]pirimidine-3-carbaldehyde with N-substituted anilines gave the corresponding diaryl(hetaryl)methanes.