A rapid access to indolo[2,1-a]pyrrolo[4′,3′:4,5]pyrano[5,6-c]coumarin/[6,5-c]chromone derivatives by domino Knoevenagal intramolecular hetero Diels-Alder reactions

Knoevenagal condensation of indole-2-carbaldehyde containing an internal dienophile with coumarins, followed by domino intramolecular hetero Diels-Alder reaction, provides polycyclic heterocycles. Different approaches for stereo- and chemoselective synthesis of indolo[2,1-a]pyrrolo[4′,3′:4,5]pyrano[5,6-c]coumarin and indolo[2,1-a]pyrrolo[4′,3′:4,5]pyrano[6,5-c]chromone derivatives are described.     

Enantiospecific synthesis of 5-phenylpyrrolo[2,1-c][1,4]benzodiazepines

Enantiomerically pure 5-phenylpyrrolo[2,1-c][1,4]benzodiazepines were synthesized starting from 2-aminobenzophenones and 2-amino-4-methoxyxanthone, using l-proline as a chiral building block.     

A new route to pyrazolo[3,4-c] and [4,3-c]pyridinones via heterocyclization of vic-substituted hydroxamic acids of acetylenylpyrazoles

We report in this paper the synthesis of 6-substituted pyrazolo[4,3-c]pyridin-4-ones, 6-substituted 5-hydroxypyrazolo[4,3-c]pyridin-6-ones, 5-substituted pyrazolo[3,4-c]pyridin-7-ones and 5-substituted 6-hydroxypyrazolo[3,4-c]pyridin-7-ones by heterocyclization of vic-acetylenylpyrazol-hydroxamic acids under the influence of copper(I) salt in dimethylformamide or with organic bases in butanol or methanol.     

Selective construction of indeno[1,2-b]phenothiazine and indeno[2,1-c]phenothiazine via tandem annulation reaction

AcOH promoted annulation reaction of 2-arylideneindane-1,3-diones with methyl 2-(benzo[b][1,4]thiazin-3-ylidene)acetate in refluxing ethanol afforded pentacyclic tetrahydroindeno [1,2-b]phenothiazine in satisfactory yields and with high diastereoselectivity according to the unexpected tandem annulation process. When the above reaction was carried out in refluxing acetic acid, isomeric dihydroindeno [1,2-b]phenothiazines and dihydroindeno [2,1-c]phenothiazines were obtained in comparable yields according to alternate tandem annulation process.     

Five-membered 2,3-dioxo heterocycles: CI. Reaction of 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with arylhydrazines. Crystal and molecular structure of substituted 2-hydrazonopyrrolo[2,1-c][1,4]benzoxazine

A new direction of nucleophilic attack was revealed in the reactions of 3-aroylpyrrolo[2,1-c][1,4]-benzoxazine-1,2,4-triones with o-tolylhydrazine and 2-hydrazinylbenzoic acid hydrochloride, which afforded the corresponding hydrazones at the C²=O carbonyl group, substituted 2-(2-o-tolylhydrazono)pyrrolo[2,1-c]-[1,4]benzoxazine-1,4(2H)-diones and pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidenehydrazinylbenzoic acids. The structure of (Z)-2-{2-[3-benzoyl-1,4-dioxo-1H-pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidene]hydrazinyl}-benzoic acid was determined by X-ray analysis.     

Novel synthesis of the pyrrolo[2,1-c][1,4]benzodiazocine ring system via a Dieckmann condensation

A novel four-step synthesis to the pyrrolo[2,1-c][1,4]benzodiazocine ring system is described. 1H-Pyrrole-2-carbaldehyde was alkylated with ethyl or methyl bromoacetate and the resulting ethyl or methyl (2-formyl-1H-pyrrol-1-yl)acetates oxidised with potassium permanganate to the corresponding 1-[(2-ethoxy or methoxy)-2-oxoethyl]-1H-pyrrole-2-carboxylic acids. The latter was converted into their acid chlorides by reaction with thionyl chloride and without isolation transformed into the respective methyl 2-({[1-(2-ethoxy or methoxy-2-oxoethyl)-1H-pyrrol-2-yl]carbonyl}amino)benzoates by reaction with methyl anthranilate. Dieckmann condensation of methyl 2-({[1-(2-methoxy-2-oxoethyl)-1H-pyrrol-2-yl]carbonyl}amino)benzoate provided the pyrrolo[2,1-c][1,4]benzodiazocine.     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

Microwave enhanced reduction of nitro and azido arenes to N-arylformamides employing Zn-HCOONH4: synthesis of 4(3H)-quinazolinones and pyrrolo[2,1-c][1,4]benzodiazepines

Microwave mediated reduction of nitro and azido arenes to N-arylformamides using Zn-HCOONH₄ is described. In the absence of microwave conditions, this methodology affords amines. This protocol has been extended to the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines and 4(3H)-quinazolinones.     

Synthesis of 1,4,6,7-tetrahydroimidazo[2,1-c] [1,2,4] triazines

From 2-methylthioimidazoline and phenaeylbromides in DMF there were obtained the 2-(2-methylthio-2-imidazolin-1-yl)aeetopht'nones 3a-3f . From these the substituted 3-phenyl-1,4,6,7-tetrahytlroimidazo[2,1-c][1,2,4]triazines 4a-4n were prepared upon reaction with hydrazine and methylhydrazine respectively. Compound 4a was degraded to the triazine 6. From the (2-methylthio-2-imidazolin-l-yl)-acetie acid ester 10, the imidazo[2,1-c] [1,2,4]triazines 11a-11c were prepared. Selective ethylation on the oxygen was achieved with 11b in the presence of Meerwein' salt.     

Novel fluoro-substituted benzo- and benzothieno fused pyrano[2,3-c]pyrazol-4(1H)-ones

A straightforward, two-step synthesis of fluoro substituted chromeno[2,3-c]pyrazol- and [1]benzothieno[2′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones, respectively, is presented. Hence, treatment of 1-substituted or 1,3-disubstituted 2-pyrazolin-5-ones with fluoro substituted 2-fluorobenzoyl chlorides or 3-chloro-6-fluoro-1-benzothiophene-2-carbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-aroylpyrazol-5-ols, which were cyclized into the fused ring systems. 5-Fluorochromeno[2,3-c]pyrazol-4(1H)-one was obtained upon treatment of the 1-(4-methoxybenzyl) protected congener with trifluoroacetic acid. Treatment of 5-fluorochromeno[2,3-c]pyrazol-4(1H)-ones with methylhydrazine afforded novel tetracyclic ring systems such as 2-methyl-7-phenyl-2,7-dihydropyrazolo[4′,3′:5,6]pyrano[4,3,2-cd]indazole. Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N, ¹⁹F) with the obtained compounds were undertaken.     

An efficient catalytic deprotection of thioacetals employing bismuth triflate: synthesis of pyrrolo[2,1-c] [1,4] benzodiazepines

A simple and efficient deprotection of thioacetals has been achieved by employing bismuth triflate. This method has been effectively employed in the preparation of DNA-binding pyrrolo[2,1-c] [1,4]benzodiazepine and its dimers.     

The synthesis of 2-phenyl-5H-imidazo[2,1-a] [2,4]benzodiazepines

A one step synthesis of 2-phenyl-5H-irnidazo[2,1-a][2,4]benzodiazepines ( 4 ) from 2-(2-imidazolyl)benzophenones ( 3 ) is reported. Oximation and reduction of the benzophenone, 3a led to the benzhydrylamine derivative 7 which was cyclized to differently substituted 6,7-di-hydroimidazo[2,1-a][2,4]benzodiazepines depending on the reactant chosen.     

An efficient,three-component synthesis and molecular structure of derivatives of 2-amino-3-R-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine-5,5-dioxide spirocombined with a 2-oxindole nucleus

Spiro[(2-amino-3-R-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine-5,5-dioxide)-4,3′-(1′-R′-5′-R″-indolin-2′-one)] compounds were synthesized based on the three-component interaction of benzo[c][2,1]thiazin-4-on 2,2-dioxide with corresponding isatins and appropriate methylene active nitriles in the presence of a base as a catalyst. The molecular structures of the target compounds were proved uniquely by the X-ray diffraction analysis method.     

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.     

Photochemistry of 3H-furo[3,4-c]pyrazoles and 3H-thieno[3,4-c]pyrazoles

The first examples of 3H-furo[3,4-c]pyrazoles and 3H-thieno[3,4-c]pyrazoles were prepared in an attempt to isolate examples of cyclopropane-fused thiophenes and furans. Adducts of acetylenic ketones and 2-diazopropane were reacted with 10-camphorsulfonic acid or phosphorus pentasulfide to produce the title compounds. Photolysis of these compounds did not give the cyclopropane-fused products rather an unreported photochemical fragmentation was observed.     

A general strategy for the synthesis of oxoisoindolo[2,1-a]quinoline derivatives: the first efficient synthesis of 5,6,6a,11-tetrahydro-11-oxoisoindolo[2,1-a]quinoline-10-carboxylic acids

An efficient two-step synthesis of new isoindolo[2,1-a]quinoline-10-carboxylic acids via [4+2] cycloaddition of the 4-α-furyl-4-N-arylaminobut-1-enes and maleic anhydride is described.     

A facile synthesis and highly atom economic 1,3-dipolar cycloaddition of hexahydropyrido[3,4-c][1,5]benzothiazepines with nitrile oxide: stereoselective formation of hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines

A series of new 2-methyl-11-aryl-4-[(E)-arylmethylidene]-1,2,3,4,11,11a-hexahydropyrido[3,4-c][1,5]benzothiazepines were obtained by the reaction of o-aminothiophenol and (E)-1-methyl-3,5-bis(arylidene)-4-piperidones in the presence of a catalytic amount of acetic acid under solvent-free microwave irradiation. These dipolarophiles undergo a highly atom economic 1,3-dipolar cycloaddition with nitrile oxide to afford a series of novel 6-methyl-1-phenyl-8-aryl-4-[(E)-arylmethylidene]-4,5,6,7,7a,8-hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines stereoselectively.     

Intermolecular cycloaddition of nonstabilized azomethine ylides generated from 1,3-thiazolidine-4-carboxylic acids: synthesis of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.     

A new approach for the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines involving reductive cleavage

A methodology based on reductive cleavage followed by cyclization, for the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines employing DIBAL-H, is described.     

Efficient syntheses of 1,2,3,4,4a,5-hexahydro-pyrazino[2,1-c][1,4]benzothiazine-6,6-dioxide

Expeditious routes to 1,2,3,4,4a,5-hexahydro-pyrazino[2,1-c][1,4]benzothiazine-6,6-dioxide, a methylenesulfone-constrained arylpiperazine, have been developed. The key step forms the tricyclic system in a cascade of reactions via a 1,4-addition, nitrogen alkylation, and aromatic substitution sequence.