Reaction of N-substituted 2-oxochromen-3-carboxamides with bromoderivatives of zinc enolates prepared from alkyl 2,2-dialkyl-4,4-dibromo-3-oxoalkanoates and zinc

Zinc enolates obtained from ethyl 2,2-dialkyl-4,4-dibromo-3-oxobutanoates and zinc react with N-substituted 2-oxochromen-3-carboxamides forming ethyl 3-{1a-(R³-carbamoyl)-2-oxo-1a,7b-dihydrocyclopropa[c]chromen-1-yl}-2,2-dialkyl-3-oxopropanoate isomer with a Z-position of methine hydrogens. Zinc enolates prepared from alkyl 2,2-dialkyl-4,4-dibromo-3-oxopentanoates and-hexanoates and zinc react with N-substituted 2-oxochromen-3-carboxamides to give rise to esters of 3-{1-alkyl-1a-(R³-carbamoyl)-2-oxo-1a,7b-dihydrocyclopropa-[c]chromen-1-yl}-2,2-dialkyl-3-oxopropanoic acid as isomers with the E-position of the methine proton and the alkyl substituent. The reaction carried out in the presence of small quantities of THF and HMPA leads to the formation of 9c-alkyl-2-R³-9b,9c-dihydro-5-oxa-2-azacyclopenta[2,3]-cyclopropa[1,2-a]naphthalene-1,3,4-triones. Zinc enolates from alkyl 2,2-dialkyl-4,4-dibromo-3-oxopentanoates and-hexanoates and zinc with the secondary amides of 2-oxochromen-3-carboxylic acid form alkyl 3-{2-oxo-1a-(piperidinocarbonyl)-and 3-{6-R¹-1a-(morpholinocarbonyl)-2-oxo-1a,7b-dihydrocyclopropa[c]chromen-1-yl}-2,2-R²,R²-3-oxopropanoates as single geometrical isomers.     

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.     

Synthesis of 8-R-9c-alkyl-1-aryl-2-benzyl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-aza-cyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones and reaction thereof with acetic anhydride

The reaction of zinc enolates synthesized from 1-aryl-2,2-dibromoalkanones and zinc with 6-R-2-oxochromene-3-carboxylic acid N-benzylamide affords 8-R-9c-alkyl-1-aryl-2-benzyl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-aza-cyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones. Acylation of these compounds is accompanied by an unexpected rearrangement producing a sole geometrical isomer of 4′-alkyl-5′-aryl-1′-benzyl-3,4,2′,3′-tetrahydro-2,2′-dioxospiro[chroman-3,3′-pyrrol]-4-yl acetates.     

Cyclopropanation of N-Substituted 2-Oxochromene- and 6-Bromo-2-oxochromene-3-carboxamides with Zinc Enolates Derived from 1-Aryl-2,2-dibromoalkanones

Zinc enolates derived from 1-aryl-2,2-dibromoalkanones react with N-cyclohexyl-2-oxochromene-3-carboxamides to give N-cyclohexyl-1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides mainly as cis isomers with respect to the substituents in positions 1 and 1a. Reactions of the same zinc enolates with N-benzyl-2-oxochromene-3-carboxamide and N-benzyl-6-bromo-2-oxochromene-3-carboxamide lead to formation of 1-aryl-2-benzyl- and 1-aryl-2-benzyl-6-bromo-1-hydroxy-9c-alkyl-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones. The reaction of zinc enolates with N-aryl-2-oxochromene-3-carboxamides in a weakly polar solvent (diethyl ether or ethyl acetate) affords mixtures of cis-N-aryl-1-aroyl-1-alkyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides and their cyclic isomers, 9c-alkyl-1,2-diaryl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-azacyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones, the latter prevailing. N-Substituted 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxamides in which the aroyl group on C¹ and the carboxamide group on C^1a are arranged trans are formed by reactions of zinc enolates with the corresponding 2-oxochromene-3-carboxamides in the presence of hexamethylphosphoric triamide.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 4, 2005, pp. 539–546.Original Russian Text Copyright © 2005 by V. Shchepin, Silaichev, R. Shchepin, Ezhikova, Kodess.     

Cyclopropanation of 2-arylmethylidenemalononitriles,alkyl 3-aryl-2-cyanoprop-2-enoates,and N-substituted 3-aryl-2-cyanoprop-2-enamides with bromine-containing zinc enolates

Zinc enolates derived from 2,2-dibromoindan-1-one and 2,2-dibromo-1,2,3,4-tetrahydronaphthalen-1-one reacted with 2-arylmethylidenemalononitriles, alkyl 3-aryl-2-cyanoprop-2-enoates, and N-substituted 3-aryl-2-cyanoprop-2-enamides to give, respectively, 3-aryl-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-2-dicarbonitriles, 3-aryl-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2,2-dicarbonitriles, alkyl 3-aryl-2-cyano-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-carboxylates, alkyl 3-aryl-2-cyano-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxylates, and N-substituted 3-aryl-2-cyanol-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxamides as a single diastereoisomer. The stereoconfiguration of the products was determined by ¹H and ¹³C NMR spectroscopy.     

Fused 1,2,4-triazole heterocycles. IV. Synthesis of four new heterocyclic ring systems of [1,2,4]triazolo[1,3]thiazinoquinolines

Syntheses of 5H-[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,4-c]quinolines 8, 5H-[1,2,4]triazolo[3′,4′:2)3][1,3]thiazino[5,4-c]quinolines 9, 5H-[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,6-c]quinolines 14 and 5H-[1,2,4]triazolo[3′,4′:2,3][1,3]thiazino[5,6-c]quinolines 15 are described starting from 4-chloro-3-chloromethylquinaldine (4) and 1,2,4-triazole-5-thiols 5 taking advantage of different reactivity of the chlorine atoms of 4 under different reaction conditions. The structures of products 8, 9, 14 and 15 and the intermediates leading to them were confirmed by desulfurization, unequivocal syntheses and nmr spectroscopy as well.     

Reaction of methyl 1-bromocyclopentane- and -cyclohexanecarboxylates with zinc and 2-arylmethylideneindan-1,3-diones

Methyl 1-bromocyclopentanecarboxylate and methyl 1-bromocyclohexanecarboxylate reacted with zinc and 2-arylmethylideneindan-1,3-diones to give methyl-1-[(aryl)(1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-methyl]cyclopentane(or cyclohexane)carboxylates and 4′-aryl-2′H-spiro[cyclopentane(or cyclohexane)-1,3′-indeno[ 1,2-b]pyran]-2′,5′(4′H)-diones.     

Five-membered 2,3-dioxo heterocycles: CII. Spiro heterocyclization of 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones by the action of tetrahydroquinoline

3-Aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with 1,2,3,4-tetrahydroquinoline to give 3-aroyl-4-hydroxy-1-(2-hydroxyphenyl)-5′,6′-dihydrospiro[pyrrole-2,1′-pyrrolo[3,2,1-ij]quinoline]-2′,5(1H,4′H)-diones.     

Reformatsky reaction of methyl 1-bromocyclohexane-1-carboxylate with N-aryl-2-oxochromene-3-carboxamides

Reformatsky reagent generated from methyl 1-bromocyclohexane-1-carboxylate reacted with N-aryl-2-oxochromene-3-carboxamides and N-aryl-6-bromo-2-oxochromene-3-carboxamides to give, depending on the conditions, the corresponding N-aryl-(6-bromo)-4-(1-methoxycarbonylcyclohexyl)-2-oxochroman-3-carboxamides or 3-aryl-(9-bromo)-1,1-pentamethylene-2,3,4,4a,5,10b-hexahydro-1H-chromeno[3,4-c]pyridine-2,4,5-triones. The products were isolated as a single diastereoisomer.     

Synthesis of condensed tetrahydroimidazo[1,2-a]quinazoline-1,5-dione derivatives

Heating of N-{2-[(R-amino)carbonyl]phenyl}prolinamides in triethyl orthoformate solution was found to give 6-R-5,6,6a,8,9,10,10a,11-octahydropyrrolo[1′,2′:3,4]imidazo[1,2-a]quinazoline-5,11-diones. Similar reaction of N-{2-[(R-amino)carbonyl]phenyl}thiazolidine-4-carboxamides afforded 6-R-5,6,6a,10,10a,11-hexahydrothiazolo[3′,4′:3,4]imidazo[1,2-a]quinazoline-5,11-diones. The relative configuration of C-6a and C-10a centres of the tetracyclic compounds obtained was assigned as trans on the basis of X-ray crystallographic study.     

Polyazasteroids II.. 1,2,4-Triazolol[3′,4′:2,3]pyrimido[4,5-c]quinolin- 11(12H)ones,imidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3] pyrimido[4,5-c]quinolin-11(12H)ones

Starting with 2-substituted quinoline-3,4-dicarboxylic acids, a series of substituted 1,2,3,4-tetrahydropyrimido[4,5-c]quinolinone-3-thiones were obtained. The latter compounds were converted to the three novel polyazasteroid series: 1,2,4-Triazolo[3′,4′:2,3]pyrimido[4,5-c]-quinolin-11(12H)ones, imidazo[2′,1′:2,3]pyrimido[4,5c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones. The intermediate 3-hydrazino-1,2-dihydropyrimido[4,5-c]quinolinones and nitrous acid gave the 3-azido derivatives rather than the tetrazolo compounds.     

Five-membered 2,3-dioxo heterocycles: LXII. Reaction of 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with N,N′-dihydroxycyclohexane-1,2-diamine. Unusual rearrangement in the spiro[quinoxaline-2,2′-pyrrole] system

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with N,N′-dihydroxycyclohexane-1,2-diamine to give 3-aroyl-1′,4,4′-trihydroxy-1-(2-hydroxyphenyl)-4a′,5′,6′,7′,8′,8a′-hexahydro-1′H-spiro[pyrrole-2,2′-quinoxaline]-3′,5(1H,4′H)-diones which underwent rearrangement into 1′-aroyloxy-4,4′-dihydroxy-1-(2-hydroxyphenyl)-4a′,5′,6′,7′,8′,8a′-hexahydro-1′H-spiro[pyrrolidine-2,2′-quinoxaline]3′,4,5(4′H)-triones via [1,4]-migration of the aroyl group. The product structure was proved by X-ray analysis.     

New polyheterocyclic series based on 4,5,6,7-tetrahydrothieno[2,3-c]pyridine

4,8-Dimethyl-6,7,8,9-tetrahydropyrido[4′,3′:4,5]thieno[2,3-e][1,2,4]triazolo[3,4-a]-4H-pyrimidin-5-ones, 7-methyl-2,3,6,7,8,9-hexahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrrolo[1,2-a]-1H, 10H-pyrimidin-10-one, 8-methyl-1,2,3,4,7,8,9,10-octahydropyrido[4′,3′:4,5]thieno[2,3-d]-11H-pyrimidin-11-one, and 9-methyl-2,3,4,5,8,9,10,11-octahydro[4′,3′:4,5]thieno[2,3-d]azepino-[1,2-a]-1H, 12H-pyrimidin-12-one which consist four new heterocyclic ring systems were synthesized from 2-amino-3-carbethoxy-5-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine.     

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.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo[4,3-b]pyridazine (II)

s-Triazolo[4,3-b Jpyridazine (I) photochemically reacted with dihydropyran; 2,3-dihydro-p-dioxin; 2,5-dihydrofuran; 2,5-dimethoxy-2,5-dihydrofuran; and 1,3-dioxep-5-ene to give a new series of substituted pyrrolo[1,2-b]-.s-triazoles (II-IX). In most reactions, two or more products were formed. The following compounds have been prepared from I: 9-methylene-4a,5,6,7,8a,9-hexahydropyrano[2,3 :4,5]pyrrolo[1,2-b]-s-triazole (Ha), the corresponding 9-cyanomethyl product (III), and 9-methylene-4a,7,8,8a-tetrahydro-6H,9H-pyrano[3′,2′:4,5]pyrrolo[1,2-b]-s-triazole (IIb) from dihydropyran; 9-methylene-4a,6,7,8a-tetrahydro-9H-p-dioxino[2′,3′:4,5]-pyrrolo[1,2-6]-s-triazole (IV) from 2,3-dihydro-p-dioxin; 8-methylene-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]pyrrolo[1,2-b]-s-triazole (V) and the corresponding 8-cyanomethyl product (VI) from 2,5-dihydrofuran; 8-cyanomethyl-5,7-dimethoxy-4a,5,7a,8-tetrahydro-7H-furo[3′,4′:4,5]-pyrrolo[1,2-6]-s-lriazole (VII) from 2,5-dimethoxy-2,5-dihydrofuran; and 10-methylene-4a,5,9a,10-tetrahydro-9H-[1,3]dioxepino[5′,6′:4,5]pyrrolo[1,2-b]-s-triazole (VIII) and the corresponding 10-cyanomethyl product (IX) from 1,3-dioxep-5-ene. The addition of several other compounds (1,2,3,6-tetrahydropyridine, 1-acetylimidazole, 3-sulfolene, 2,3-dihydro-p-dithiin, and vinylene carbonate) was attempted, but no reactions were observed.     

Reaction of thieno[2,3-b]pyridines with sodium hypochlorite: An unusual and stereoselective one-pot approach to dimeric pyrrolo[2′,3′:4,5]thieno[2,3-b]pyridines

The oxidation of 3-aminothieno[2,3-b]pyridine-2-carboxamides with commercially available bleach leads to the formation of dimeric pyrrolo[2′,3′:4,5]thieno[2,3-b]pyridines (7a,14a-diamino-7,14-bis(aryl)-7,7a,14,14a-tetrahydro-6H,13H-pyrido[3″″,2″″:4?,5?]thieno[2?,3?:4″,5″]pyrrolo-[3″,4″:3′,4′]pyrrolo[2′,3′:4,5]thieno[2,3-b]pyridine-6,13-diones) in moderate yields (37–52%).     

Five-membered 2,3-dioxoheterocycles: XCIV. Recyclization of 4,5-diaroyl-1H-pyrrole-2,3-diones under the action of 3-aminopyrazolo[3,4-b]pyridine. Crystal and molecular structure of substituted pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine

1-Aryl-4,5-diaroyl-1H-pyrrole-2,3-diones react with 3-amino-4,6-dimethyl-2H-pyrazolo[3,4-b]-pyridine affording N-aryl-2,3-diaroyl-8,10-dimethylpyrido [2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-4-carboxamides.     

Some novel heterocyclic systems derived from 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-α]benzimidazole and the corresponding diamine

The preparation of 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-a]benzimidazole from 1,4-diacetamido-2,3-dinitrobenzene is described. Reaction of this compound with 2,5-dimethoxytetrahydrofuran produces 2,3-dihydro-8-nitro-7-N-pyrrolo-1H-pyrrolo[1,2-a]benzimidazole, which can be cyclised to produce two new heterocyclic ring systems, 9,10-dihydro-8H-pyrrolo[1,2-a]pyrrolo(1′,2′:1,2]imidazo[5,4-f]quinoxaline and 9,10-dihydro-8H-pyrrolo[2,1-c]pyrrolo[1′,2′:1,2]imidazo[4,5-h][1,2,4]benzotriazine. The corresponding diamine, 7,8-diamino-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole undergoes a variety of condensation reactions to produce several new heterocyclic systems, for example, with formic acid, 1,7,8,9-tetrahydroimidazo-[4,5-e]pyrrolo[2,1-6]benzimidazole is formed and with diacetyl, 9,10-dihydro-2,3-dimethyl-8H-pyrrolo-[1′,2′:1,2]imidazo[5,4-y]quinoxaline is obtained.     

Reactions of organozinc reagents derived from dialkyl 2,2-dibromomalonates with 3-aryl-2-cyanoprop-2-enamides

Organozinc compounds obtained by treatment of dialkyl 2,2-dibromomalonates with metallic zinc reacted with N-substituted 3-aryl-2-cyanoprop-2-enoic acid amides to give alkyl 3-R-6-aryl-5-cyano-2,4-dioxo-3-azabicyclo[3.1.0]hexane-1-carboxamides as a single stereoisomer.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 6. Naphthothienonaphthyridines

Five novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: naphtho[1′,2′:4,5]thieno[2,3-c][1,8]naphthyridin-6(5H)-one ( 5 ), naphtho-[1′,2′:4,5]thieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 6 ), naphtho[1′,2′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 9 ), naphtho[1′,2′:4,5]thieno[2,3-c][1,2,4]triazolo[4,3-a]-1,5-naphthyridine ( 12 ), and naphtho[2′,1′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 17 ). The direction of photocyclization to produce 9 was established from a zero quantum two-dimensional nmr spectroscopy experiment (ZQCOSY) using 6-chloronaphtho[1′,2′:4,5]thieno[2,3-c]-1,5-naphthyridine ( 8 ) as the model compound.