An innovative approach to the synthesis of annelated [a]diaza-anthracenones through tandem cyclization

An innovative route for the synthesis of a novel class of 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a-diazacyclopenta[a]anthracene-6-carbonitriles 5a-h and 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a-diazabenzo[a]anthracene-7-carbonitriles 5i-k has been developed by ring transformation of suitably functionalized 2H-pyran-2-ones 1 with α-oxoketene cyclic aminals 2 to give compounds 4 followed by photo-induced cyclization.     

A one-pot synthesis of an annelated [a]aza-thieno[3,2-g]naphthalenone through ring transformation followed by photocyclization

A concise synthesis of 4-aryl-10-oxo-1,2,3,10-tetrahydro-9-thia-1,3a-diazadicyclopenta[a,g]naphthalene-6-carbonitriles 5a-f and 5-aryl-11-oxo-1,3,4,11-tetrahydro-2H-10-thia-1,4a-diaza-cyclopenta[b]phenanthrene-7-carbonitriles 5g-i has been delineated through ring transformations of the 2H-pyran-2-one 1, followed by photocyclization of product 4.     

Intramolecular amidation: synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of 2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde and 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.     

A convenient synthesis of partially reduced benzo[c]phenanthrenes, its ketals and ketones

A concise and convenient synthesis of various partially reduced 6-sec-amino-1,2,3,4,7,8-hexahydro-, 6-sec-amino-1,2,7,8-tetrahydrobenzo[c]phenanthrene-5-carbonitriles, 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-2-one-5-carbonitrile cycloalkene ketals, pendant with electron donor and acceptor substituents has been described through base catalyzed ring transformation of 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by cyclohexanone, 2-cyclohexen-1-one, 1,4-cyclohexanedione monocycloalkene ketals. The acid catalyzed deketalation of 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-2-one-carbonitrile ketals led to yield 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-3-carbonitrile-2-ones in excellent yield. We also performed the X-ray studies of the molecules 3d and 6a to know the degree of non-planarity.     

Versatility of 2-oxobenzo[h]chromene for the synthesis of oxabenzo[c]chrysenes

An innovative and concise synthesis of (7,8-dihydro-5-oxabenzo[c]chrysene-6-ylidene)acetonitriles is described through base catalyzed ring transformation of 2-oxo-4-piperidin-1-yl-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 1-tetralone in very good yields.     

A novel synthesis of aryl tethered imidazo[4,5-b]pyrazin-2-ones through in situ ring construction and contraction

An innovative synthesis of aryl tethered 1,3-dimethylimidazo[4,5-b]pyrazin-2-ones 4 and 6 has been delineated through base catalyzed ring transformation of 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles 1 and methyl 6-aryl-4-methylsulfanyl-2H-pyran-2-one-3-carboxylates 5 with 7-acetyl-1,3-dimethyllumazine 2 with subsequent ring contraction of the fused pyrimidine to an imidazole ring. An additional product, methyl [6-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)-4-thiophen-2-ylpyran-2-ylidene]acetate 8b, was also isolated from the reaction of 5 and 2, as a minor constituent.     

Five-membered 2,3-dioxoheterocycles: XCVI. Reactions of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5h)-triones with substituted 1,3,3-trimethyl-2-azaspiro[4.5]dec-1-enes

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones react with 1,3,3,7,9-pentamethyl-2-azaspiro-[4.5] deca-1,6,9-trien-8-one and 2′,5′,5′-trimethyl-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-4-one providing 3-aroyl-2-hydroxy-3a-{(3,3,7,9-tetramethyl-8-oxo-2-azaspiro[4.5]deca-1,6,9-trien-1-yl)methyl}pyrrolo[1,2-a-quinoxaline-1,4(3a H,5H)-diones and 3-aroyl-2-hydroxy-3a-{(5′,5′-dimethyl-4-oxo-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-2′-yl)methyl}pyrrolo[1,2-a]-quinoxaline-1,4(3aH,5H)-diones.     

Convenient synthesis of 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]- and [2,3-b]-1,5-oxazocine-6-ones

A convenient and diversity-oriented method for synthesis of the novel 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,5-b]-1,5-oxazocine-6-one skeleton 1 and the very rarely described 7-aryl-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocine-6-one skeleton 2, featuring cyclization using nucleophilic aromatic substitution (S_NAr) and Suzuki coupling, is described.     

2-Oxobenzo[h]chromene: a novel entry for the concise and efficient synthesis of indeno[1,2-c]phenanthrenes

An efficient and concise synthesis of 7-sec-amino-5,13-dihydro-6H-indeno[1,2-c]phenanthrene-8-carbonitriles is described through base catalyzed ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 1-indanone in moderate to good yields.     

Synthesis of thiazolo[3,2-a]pyridines via an unusual Mannich-type cyclization

The Mannich-type reaction of N-methylmorpholinium 4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates with 3-(1,3-benzodioxol-5-yl)-2-methylpropanal (ocean propanal) and p-toluidine afforded 7-aryl-2-(1,3-benzodioxol-5-ylmethyl)-2-methyl-3-[(4-methylphenyl)amino]-5-oxo-2,3,6,7-tetrahydro-5H-thiazolo[3,2-a]pyridine-8-carbonitriles in modest (25–46%) yields. The structure of the key compound was confirmed by X-ray crystal structure analysis.     

Design and synthesis of novel tricycles based on 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one

This paper reports our recent efforts to develop novel tricycles based on 4H-benzo[1,4]thiazin-3-one ( 2) and 1,1-dioxo-1,4-dihydro-2H-1lambda(6)-benzo[1,4]thiazin-3-one (3) using 1,5-difluoro-2,4-dinitrobenzene (1). All of these tricycles integrate two privileged structures into one skeleton, including 3,8-dihydro-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (4, 10, 12), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-7-one (5, 11), 3,8-dihydro-5-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (6), 5,5-dioxo-3,5,6,8-tetrahydro-5lambda(6)-thia-1,2,3,8-tetraaza-cyclopenta[b]naphthalene-7-one (7), 3,8-dihydro-1H-5-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (8), and 5,5-dioxo-3,5,6,8-tetrahydro-1H-5lambda(6)-thia-1,3,8-triaza-cyclopenta[b]naphthalene-2,7-dione (9). A typical library of scaffold 5 was synthesized in a parallel solution-phase manner and analyzed by HPLC-UV-MS or HPLC-UV-ELSD method.     

A novel synthesis of new 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile derivatives

New 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitriles are synthesized in good yields, via cyclocondensation of 5-amino-1-(2-oxo-2-arylethyl)-3-(arylamino)-1H-pyrazole-4-carbonitriles, which are prepared by the reaction of 5-amino-3-arylamino-1H-pyrazole-4-carbonitriles and α-bromoacetophenone derivatives in the presence of K₂CO₃ using acetone as the solvent.     

2-Oxobenzo[h]chromene: a novel entry for the synthesis of functionalized angular polycyclic azaarenes

An efficient and short synthesis of (5,6-dihydrobenzo[h]pyrido[2,1-b]quinazolin-2-ylidene)acetonitriles, (5,6-dihydrobenzo[h]pyrazino[2,1-b]quinazolin-2-ylidene)acetonitriles and (5,6-dihydrobenzimidazo[1,2-b]benzo[f]isoquinolin-7-yl)acetonitriles in good yields is delineated through base catalyzed ring transformation of 4-(piperidin-1-yl)-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 2-amino-pyridine, 2-aminopyrazine and (imidazo-2-yl)acetonitrile.     

Reaction of 4-aryl-2-aminobuta-1,3-diene-1,1,3-tricarbonitriles with CH-nucleophiles: I. Synthesis of 5-aryl-2,4-diamino-8,8-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-chromeno[2,3-b]pyridine-3-carbonitriles

5-Aryl-2,4-diamino-8,8-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-chromeno[2,3-b]pyridine-3-carbonitriles were synthesized from 4-aryl-2-aminobuta-1,3-diene-1,1,3-tricarbonitriles and dimedone.     

Cyclopropanation of N-substituted 3-aryl-2-cyanoprop-2-enamides and derivatives of 5,5-Dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic acid and 2-oxochromene-3-carboxylic acid with bromine-containing zinc enolates

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-substituted 3-aryl-2-cyanoprop-2-enamides and 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylic and 2-oxochromene-3-carboxylic acid derivatives to give, respectively, N-substituted 2-alkyl-3-aryl-2-aroyl-1-cyanocyclopropane-1-carboxamides, 6-(4-bromobenzoyl)-4,4,6-trimethyl-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylic acid ethyl ester and morpholide, and 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropla[c]chromene-1a-carboxylic acids as a single geometric isomer. Treatment of 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxylic acids with carboxylic acid anhydrides leads to the formation of the corresponding 9c-alkyl-1-aryl-3,4-dioxo-9b,9c-dihydro-2,5-dioxacyclopenta[2,3]cyclopropa[1,2-a]naphthalen-1-yl carboxylates.     

An efficient one-pot synthesis of tetrahydrobenzo[a]xanthene-11-one and diazabenzo[a]anthracene-9,11-dione derivatives under solvent free condition

Indium(III) chloride catalyzed one-pot synthesis of 12-aryl/alkyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-one and 8,10-dimethyl-12-aryl-8,12-dihydro-7-oxa-8,10-diazabenzo[a]anthracene-9,11-dione derivatives have been achieved by three component cyclocondensation of aldehydes, β-naphthol and cyclic 1,3-dicarbonyl compounds under solvent free condition in high yields. P₂O₅ too has been found as an effective catalyst towards this transformation.     

Synthesis of tricyclic isoindoles and thiazolo[3,2-c][1,3]benzoxazines

The thermolysis of (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylic acids in Ac₂O led to novel 3-methylene-2,5-dioxo-3H,9bH-oxazolo[2,3-a]isoindoles and chiral (9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindoles were obtained on FVP. Starting from l-cysteine methyl ester (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo[3,2-c][1,3]benzoxazines were obtained as single stereoisomers. The thermolysis of (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo[3,2-c][1,3]benzoxazine-3-carboxylic acid in Ac₂O gave 5-acetyl-2-phenyl-2,3-dihydrothiazole. The structures of methyl (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylate 1a and methyl (2R,4R)-N-chlorocarbonyl-2-(2-hydroxyphenyl)thiazolidine-4-carboxylate 9 were determined by X-ray crystallography.     

Synthetic potential of 2-oxobenzo[h]chromene for the construction of polycyclic azaheteroaromatics with a steroid-like skeleton

An efficient and concise synthesis of 17-amino-6,15-dihydro-7H-11-oxa-15,16-diazacyclopenta[a]phenanthren-12-ones has been delineated from the reaction of 4-methylsulfanyl/sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles and hydrazine hydrate (98%) at room temperature. Reaction at reflux produced different products, characterized as 1-amino-3b,4,5,11-tetrahydro-3H-2,3,10,11-tetraazanaphtho[2,1-e]azulen-12-ones in moderate yields.     

Synthesis of pyrrolo[2,3-c]2,7-naphthyridine derivatives by cascade heterocyclization reaction of 2-amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles

Alkylation of the title pyridinedicarbonitriles with N-substituted chloroacetamides was found to give 5,6-diamino-8-dialkylamino-2,3-dihydro-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyridine-9-carbonitriles. The structure of obtained compounds was unambiguously confirmed by X-ray crystallographic study. The heterocyclization reaction proceeded regioselectively involving 3-CN group of the starting pyridines without participation of 5-CN. The reasons of the selectivity were discussed. An interaction of prepared naphthyridine derivatives with acetic acid anhydride and cyclohexanone yielded 2-dialkylamino-6,8,9,10-tetrahydro-5-methyl-9-oxopyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridine-1-carbonitriles and 2-dialkylamino-4,5,6,8,9,10-hexahydro-9-oxospiro{pyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridine-5,1′-cyclohexane}-1-carbonitriles, respectively. All fused 2,7-naphthyridines obtained were derivatives of novel heterocyclic systems.     

A non-catalytic approach to the synthesis of 5,6-dihydrobenzo[h]quinolines

A concise synthesis of highly functionalized 5,6-dihydrobenzo[h]quinoline-3-carbonitriles is delineated through base induced ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with S-methylisothiourea sulfate and 1-carboxamidinepyrazole hydrochloride, separately, in DMF. Under analogous reaction conditions the ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by formamidine acetate provided 4-sec-amino-benzo[h]quinoline-3-carbonitriles in moderate yields, while with benzamidine hydrochloride, the reaction followed the same mechanism to yield 2-phenyl-4-sec-amino-5,6-dihydrobenzo[h]quinoline-3-carbonitriles.