Synthesis of novel fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives

New fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives are obtained in moderate to good yields, through a one-pot aldolization-intramolecular S_NAr process, from the tetrakis(dimethylamino)ethylene (TDAE) mediated reductive cleavage of two N,N-dimethylamino-bis-chlorodifluoroacetyl substrates in the presence of heteroaryl aldehydes.     

Diastereodivergent Synthesis of Hexahydro-6H-benzo[c]chromen-6-one Derivatives Catalyzed by Modularly Designed Organocatalysts

The diastereodivergent synthesis of hexahydro-6H-benzo[c]chromen-6-one derivatives with good to high diastereoselectivities (up to 98:2 d.r.) and enantioselectivities (up to >99 % ee) has been achieved by using a domino Michael/Michael/hemiacetalization reaction between trans-2-hydroxy-β-nitrostyrenes and trans-7-oxo-5-heptenals followed by oxidation. With use of appropriate modularly designed organocatalysts (MDOs) that are self-assembled in situ from amino acid derivatives and cinchona alkaloid derivatives, two different diastereomers of the desired hexahydro-6H-benzo[c]chromen-6-ones are obtained from the same substrates.     

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.     

Synthesis of 6H-benzo[c]chromen-6-ones by cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-formylcoumarin

6H-benzo[c]chromen-6-ones were prepared by base mediated cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-formylcoumarin.     

Synthesis of 7-hydroxy-6H-benzo[c]chromen-6-ones based on a ‘[3+3] cyclization/domino retro-Michael-aldol-lactonization’ strategy

The TiCl₄-mediated [3+3] cyclization of 2,4-bis(trimethylsilyloxy)penta-1,3-diene with 3-silyloxyalk-2-en-1-ones afforded 2-acetylphenols, which were transformed into functionalized chromones. The Me₃SiOTf-mediated condensation of the latter with 1,3-bis(silyl enol ethers) and subsequent domino ‘retro-Michael-aldol-lactonization’ reaction afforded 7-hydroxy-6H-benzo[c]chromen-6-ones.     

Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.     

A facile route to phenyl, phenylsulfanyl and phenylselanyl substituted pyrano[3,2-c]chromenes

The synthesis of phenyl, phenylsulfanyl and phenylselanyl substituted pyrano[3,2-c]chromenes 4 is accomplished via cyclocondensation of 4-oxo-4H-chromen-3-carbaldehydes 1 with appropriately substituted acetic acids 2 under mild conditions. Further treatment of 4 with alcohol or water led to 5-alkoxy- and 5-hydroxy-2H,5H-pyrano[3,2-c]chromen-2-ones 5 and 6, respectively. Acid and thermal catalysed rearrangement of 4-6 gave 5-hydroxypyrano[2,3-b]chromen-2(10aH)-ones 7 and their subsequent substitution led to 5-alkoxyderivatives 8. Reaction of 4 with amides led to 5-acylamino or 5-phenylsulfonamino substituted 2H,5H-pyrano[3,2-c]chromen-2-ones 9. Reactions were performed under heating or microwave irradiation.     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

Photochemical reactions of 6-alkylamino- and 6-alkylanilino-5H-benzo[a]phenothiazin-5-ones

Photochemical reactions of 6-alkylamino- and 6-alkylanilino-5H-benzo[a]phenothiazin-5-ones have been investigated. 6-Ethylamino- and 6-isopropylamino-5H-benzo[a]phenothiazin-5-ones and 6-methylanilino- and 6-ethylanilino-5H-benzo[a]phenothiazin-5-ones gave 6-amino-5H-benzo[a]phenothiazin-5-one and 6-anilino-5H-benzo[a]phenothiazin-5-one, respectively, on irradiation.     

Microwave assisted synthesis of 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones using Mn(OAc)3

2-Hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one 2a and 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one 2b, were obtained in high yields under mild conditions from the cyclization reactions of bis-(2,4,6-trichlorophenyl) malonate and 2-aminobenzothiazole or 2-aminothiazole, respectively. A new class of compounds, 2,3-dihydro-4H-benzo[4,5]thiazolo[3,2-a]furo[2,3-d]pyrimidin-4-ones and 6,7-dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones, were synthesized via the microwave assisted radical addition of compounds 2a and 2b to various alkenes using manganese(III) acetate. A preliminary acetylcholine esterase (AchE) inhibition test of compound 4e showed excellent (92%) inhibitory potential, comparable with the standard drug Donapezil®.     

Reactions of zinc enolates derived from 1-aryl-2,2-di-bromoalkanones with 2-acyl-3H-benzo[f]chromen-3-ones, 6-bromo-2-oxochromene-3-carboxamides, and 3-oxo-3H-benzo-[f]chromene-2-carboxamides

Zinc enolates derived from substituted 1-aryl-2,2-dibromoalkanones reacted with 2-acyl-3H-benzo-[f]chromen-3-ones to give 1-alkyl-1-aroyl-1a-acyl-1a, 9c-dihydro-1H-3-oxacyclopropa[c]phenanthren-2-ones which were formed as a single stereoisomer. Reactions of the same zinc enolates with 6-bromo-2-oxo-chromene-3-carboxamides (piperidides and morpholides) afforded 1-aroyl-6-bromo-1-alkyl-1a-piperidino-(morpholino)carbonyl-1a,7b-dihydrocyclopropa[c]chromen-2-ones with high stereoselectivity. Likewise, 1-benzoyl-1-methyl-1a-morpholinocarbonyl-1a, 9c-dihydro-1H-3-oxacyclopropa[c]phenanthren-2-one was obtained by reac-tion with 3-oxo-3H-benzo[f]chromene-2-carboxylic acid morpholide.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004, pp. 1399–1404.Original Russian Text Copyright © 2004 by V. Shchepin, Kalyuzhnyi, Silaichev, Russkikh, R. Shchepin, Ezhikova, Kodess.This study was performed under financial support by the Russian Foundation for Basic Research (project no. 04-03-96 036).     

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.     

Facile synthetic route to benzo[c]chromenones and thieno[2,3-c]chromenones

Convenient two-step procedure for the synthesis of fused chromenone derivatives was developed. Reduction of the obtained in the Meerwein arylation reaction aryl- and thienylquinones allowed to construct 6H-benzo[c]chromene-6-ones and 4H-thieno[2,3-c]chromen-4-one in a more cost- and time-effective manner in comparison with already known methods. The obtained products have provided a new entry to chromenone derivatives.     

Synthesis of 1-benzyl-8,9-dihydroimidazo[4,5-c]pyrrolo[3,2-g]quinolin-4(5H)-one via palladium-catalyzed intramolecular arylation

The synthesis of a novel tetracyclic structure, 8,9-dihydroimidazo[4,5-c]pyrrolo[3,2-g]quinolin-4(5H)-one, has been achieved by a convergent pathway. Coupling of the weakly nucleophilic hindered aromatic amine with 1-benzylimidazole-4-carboxylic acid, 7, afforded the corresponding amide 9 using a DCP/DMF complex; subsequent Heck-type arylation leading to desired tetracyclic molecule imidazo[4,5-c]-pyrrolo[3,2-g]quinolin-4(5H)-one.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Reactions of zinc enolates derived from α,α-dibromo carbonyl compounds with 3-(2-oxo-4a,8a-dihydro-2H-chromene-3-carbonyl)chromen-2-one

Zinc enolates derived from 1-R-2,2-dibromoethanone reacted with 3-(2-oxo-4a,8a-dihydro-2H-chromene-3-carbonyl)chromen-2-one to give the corresponding 1-R-1a-{(1-R-2-oxo-1,7b-dihydrocyclopropa[c]chromen-1(2H)-yl)carbonyl}-1a,7b-dihydrocyclopropa[c]chromen-2(1H]-ones as a single diastereoisomer with cis arrangement of the hydrogen atoms with respect to the cyclopropane ring plane. Reactions of the same electrophilic substrate with zinc enolates obtained from 1-aryl-2,2-dibromoalkanones led to the formation of 1-alkyl-1a-{(1-alkyl-1-aroyl-2-oxo-1,7b-dihydrocyclopropa[c]chromen-1(2H)-yl)carbonyl}-1-aroyl-1a,7b-dihydrocyclopropa[c]chromen-2(1H)-ones as a single diastereoisomer with trans arrangement of the alkyl group and hydrogen atom with respect to the cyclopropane ring plane.     

Synthesis of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones and 2-(trifluoromethyl)-4H-thieno[2,3-c]chromen-4-ones from 2-trifluoromethylchromones and ethyl mercaptoacetate

The redox reaction of 2-trifluoromethylchromones with ethyl mercaptoacetate in the presence of triethylamine results in the formation of 1,2-dihydrothieno[2,3-c]chromen-4-ones and diethyl 3,4-dithiadipate in high yields. Oxidation of the first compounds with nitrogen dioxide gave 1,2-dihydrothieno[2,3-c]chromen-3,4-diones which were converted into thieno[2,3-c]chromen-4-ones.     

New iminophosphorane-mediated synthesis of thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones and 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes

Mono(iminophosphorane) 4 was selectively prepared from the reaction of 3,4-diaminothieno[2,3-b]thiophene 3 with excess triphenylphosphine, C₂Cl₆, and Et₃N due to intramolecular double hydrogen bond formation. Mono(iminophosphorane) 4 reacted with aromatic isocyanates to give stable carbodiimides 8, which were further treated with aliphatic secondary or primary amines to give 2-amino substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 10 or 12 in the presence of a catalytic amounts of EtO⁻Na⁺. However, in the presence of a catalytic amounts of potassium carbonate, the carbodiimides 8 were transformed into previously unreported 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes 13 via direct cyclization in high yields. The reaction of carbodiimides 8 with phenols in the presence of a catalytic amounts of potassium carbonate gave a mixture of 2-aryloxy substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 14 and 13. X-ray structure analysis of 10m supported the structure and the proposed reactivity of amino group.     

Synthesis, reactions and antineoplastic activity of 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromene derivatives

The key 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromen-5-yl acetates 3 were synthesized in high yields by cyclocondensation of 4-oxo-4H-chromen-3-carbaldehydes 1 with coumarin-3-acetic acids 2 under mild conditions. The reaction pathway involves aldol condensation and subsequent intramolecular lactonization to afford 2-oxo-2H,5H-pyrano[3,2-c]chromene skeleton 3. Further treatment of acetates 3 with alcohols, water or nitrogen containing compounds led to 5-alkoxy-, 5-hydroxy- or 5-acylamino-2H,5H-pyrano[3,2-c]chromen-2-ones 4-6 via nucleophilic substitution of acetyloxy group at C-5. Acetates and hydroxyl derivatives 3 and 5 undergo facile rearrangement in an acid medium yielding 5-hydroxypyrano[2,3-b]chromen-2(10aH)-ones 7. Twelve prepared compounds were evaluated on their antineoplastic activities on 60 human tumour cell line panels in NCI USA. The obtained biological results confirmed that 3-(2-oxo-2H-chromen-3-yl)-2H,5H-pyrano[3,2-c]chromen-2-one represents a new leading skeleton suitable for further antitumour activity study.     

The photochemical reactions of 5H-benzo[a]phenoxazin-5-one with alkylthiols and thiophenol

6-Alkylthio- and 6-phenylthio-5H-benzo[a]phenoxazin-5-ones have been synthesized by the photochemical reaction of 5H-benzo[a]phenoxazin-5-one with alkylthiols and thiophenol.