Synthesis of substituted 2,3-dihydro-1H-boroles by transmetalation of aluminacyclopent-2-enes with BF3·Et2O

A procedure was developed for selective synthesis of 4,5-dialkyl-1-fluoro-2,3-dihydro-1H-boroles via transmetalation of the corresponding aluminacyclopent-2-enes with BF₃·Et₂O. 4,5-Dialkyl-1-fluoro-2,3-dihydro-1H-boroles were isolated as complexes with BEtF₂. 4-Alkyl-5-dimethylaminomethyl-1-fluoro-2,3-dihydro-1H-boroles were synthesized for the first time.     

Preparation of novel heterocyclic systems from isatoic anhydrides

Isatoic anhydride ( 1a ) and 5-chloroisatoic anhydride ( 1b ) were treated with 2-(1-methylhydrazino)ethanol ( 2 ) to produce 2-aminobenzoic acid 2-(2-hydroxyethyl)-2-methylhydrazide ( 3a ) and its 5-chloro analog 3b , respectively. Treatment of 3a and 3b with carbon disulfide gave, respectively, 2,3-dihydro-3-[(2-hydroxyethyl)methylamino]-2-thioxo-4-(1H)quinazolinone ( 4a ) and its 6-chloro analog 4b . Compounds 4a and 4b afforded 5,6-dihydro-5-methyl-2-thioxo-4H,8H-[1,3,5,6]oxathiadiazocino[4,5-b]quinazolin-8-one ( 5a ) and its 10-chloro analog 5b , respectively, upon treatment with thiophosgene. Compound 5a could be produced directly from 3a and thiophosgene. Treatment of 4a and 4b with trifluoroacetic anhydride followed by potassium carbonate gave 3,4-dihydro-4-methyl-2H,6H-[1,3,4]thiadiazino[2,3-b]quinazolin-6-one ( 7a ) and its 8-chloro analog 7b , respectively. Treatment of 4a with thionyl chloride also gave 7a , but 4b and thionyl chloride afforded a mixture of 7b and 8-chloro-3,4-dihydro-4-methyl-2H,6H-[1,3,4]oxadiazino[2,3-b]quinazolin-6-one ( 10 ). The dimethyl analogs of 4a and 4b ( 13a and 13b ) upon treatment with thiophosgene afforded 3,4-dihydro-2,2,4-trimethyl-2H,6H-[1,3,4]oxadiazino[2,3-b]quinazolin-6-one ( 14a ) and its 8-chloro analog 14b , respectively.     

Chemoenzymatic synthesis of both enantiomers of 3-hydroxy-2,3-dihydro-4H-chromen-4-one

4-Oxo-3,4-dihydro-2-chromen-3-yl acetate is synthesized using manganese(III)acetate starting from 2,3-dihydro-4H-chromen-4-one. K₂CO₃ mediated hydrolysis of 4-oxo-3,4-dihdro-2-chromen-3-yl acetate furnished 3-hydroxy-2,3-dihydro-4H-chromen-4-one in high yield.The enantioselective hydrolysis of (±)-4-oxo-3,4-dihydro-2-chromen-3-yl acetate in various organic solvent-phosphate buffer (pH7) systems and enantioselective transesterification of (±)-3-hydroxy-2,3-dihydro-4H-chromen-4-one in organic solvents was investigated by screening a range of lipases. The lipase Amano PS, PPL, PLE and CCL-catalyzed asymmetric ester hydrolysis and transesterification afforded the enantiomers of 3-hydroxy-2,3-dihydro-4H-chromen-4-one and 4-oxo-3,4-dihydro-2-chromen-3-yl acetate with high enantiomeric excess (up to 97% ee) and in good yields.     

Synthesis of 2,3-dihydro-1H-inden-1-one derivatives via Ni-catalyzed intramolecular hydroacylation

An efficient synthetic method for the formation of 2,3-dihydro-1H-inden-1-one derivatives through a Ni-catalyzed intramolecular hydroacylation of 2-(prop-2-ynyl)benzaldehydes has been developed. Examination of various nickel and other transition metal catalysts and phosphine ligands showed that the use of Ni(COD)₂ catalyst combined with P(i-Pr)₃ ligand was the best choice to the success of the present intramolecular hydroacylation. A wide range of functional groups were tolerated, affording the corresponding substituted α-lidene-2,3-dihydro-1H-inden-1-ones in good to high yields with a sole E-selectivity under present reaction conditions.     

2,3-Dihydro-1H-1,3-diazepin-2-ones: synthesis and novel rearrangements into pyrrole derivatives

A novel synthesis of 2,3-dihydro-1H-1,3-diazepin-2-ones based on thermal elimination of methanol from 4-methoxy-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones has been developed. The prepared dihydrodiazepinones underwent two new rearrangements under basic or acidic conditions to give the pyrrole derivatives, 3-(aminomethylene)-2,3-dihydro-1H-pyrrol-2-ones and 1-carbamoyl-1H-pyrroles, respectively. Plausible mechanisms for the rearrangements are proposed.     

Stable carbenes. Synthesis and properties of benzimidazol-2-ylidenes

A new stable crystalline carbene, 1,3-bis(1-adamantyl)benzimidazol-2-ylidene, was synthesized by decomposition of 1,3-bis(1-adamantyl)-2,3-dihydro-1H-benzimidazol-2-ylacetonitrile on heating under reduced pressure. Heteroaromatic 1,3-R₂-disubstituted benzimidazol-2-ylidenes, both stable (R = 1-Ad) and generated in situ (R = Me, Bzl), as well as 1,3,4,5-tetraphenylimidazol-2-ylidene (generated in situ), reacted with acetonitrile to give the corresponding insertion products, 1,3-disubstituted 2-cyanomethyl-2,3-dihidro-1H-(benz)-imidazoles. The geometric parameters of 1,3-bis(1-adamantyl)benzimidazol-2-ylidene, determined by X-ray analysis, suggest its lower aromaticity as compared to imidazol-2-ylidenes and 1,2,4-triazol-5-ylidenes. The structures of 2-cyanomethyl-2,3-dihydro-1H-benzimidazoles, 2-cyanomethyl-1,3,4,5-tetraphenyl-2,3-dihydro-1H-imidazole, and 1-(1-adamantyl)-5-cyanomethyl-3,4-diphenyl-4,5-dihydro-1H-1,2,4-triazole are characterized by partial conjugation in the heteroring; some compounds exhibit luminescence under UV irradiation. 1,3-Bis(1-adamantyl)benzimidazol-2-ylidene reacted with molecular sulfur in benzene to give 1,3-bis-(1-adamantyl)-2,3-dihydro-1H-benzimidazole-2-thione, but it failed to react with selenium under analogous conditions.     

Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines

The eudesmane-type methylene lactones (isoalantolactone, alantolactone, 4,15-epoxyisoalantolactone, 2′,2′-dichloro-4H-spiro[cyclopropane-1′,4-eudesma-11(13)-en-8β,12-olide], and alantolactone) react with 8-bromoxanthines (8-bromocaffeine, 8-bromotheobromine, 8-bromo-3-butyltheobromine, 8-bromotheophylline, 8-bromo-9-butyltheophylline) under Heck reaction conditions to produce the target (E)-13-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)eudesma-4(15),11(13)-dien-8β,12-olides and the subsequent endocyclic isomers - 11-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)-13-normethyleudecma-4(15)-7(11)-dien-8α,12-olides. It was revealed that the yield and product ratio depends on the reaction conditions and the structure of methylene lactone. The effectiveness of Pd(OAc)₂–caffeine catalytic system has been demonstrated in this reaction. The electric eel acetylcholinesterase inhibitory activity of the eudecmanolide-xanthine hybrids was evaluated. Among the new type bisheterocycles compound 27 with butyl and 2-oxodecahydronaphtho[2,3-b]furan-3(2H)-ylidene)methyl substituents at C-7 and C-8 of the xanthine core showed moderate activity with IC₅₀ value of 40 μM.     

Reactions of vinyl 2,3-epoxypropyl ethers with 4,5-dihydro-1H-pyrazoles

Reactions of vinyl 2,3-epoxypropyl ether and 2-(vinyloxy)ethyl 2,3-epoxypropyl ether with 4,5-dihydro-1H-pyrazoles give, respectively, 3-vinyloxy-1-(4,5-dihydro-1H-pyrazol-1-yl)propan-2-ols and 3-(2-vinyloxyethoxy)-1-(4,5-dihydro-1H-pyrazol-1-yl)propan-2-ols in 70–91% yield.     

Synthesis of novel 1-(2,3-dihydro-5H-4,1-benzoxathiepin-3-yl)-uracil and -thymine, and their corresponding S-oxidized derivatives

On the basis of molecular variations on isosteric replacements from the prototype 1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil a series of 3-(2,3-dihydro-5H-4,1-benzoxathiepin-3-yl)-uracil or -thymine O,N-acetals was prepared. The nature of the cis- and trans-sulfoxide isomers was established by means of their conformational analyses carried out with Sybyl and after comparing the theoretical results with the ¹H NMR responses of the target molecules. (RS)-3-(1,1-Dioxo-2,3-dihydro-5H-4,1-benzoxathiepin-3-yl)thymine and (1S*,3S*)-1-(1-oxo-3,5-dihydro-2H-4,1-benzoxathiepin-3-yl)thymine were found to be inhibitors of the MCF-7 cell growth.     

Meso-trans-diaryldihexadecyltetrabenzoporphyrins and their zinc complexes: Synthesis and spectra

3-[(1-Oxo-1H-isoindol-3-yl)(phenyl)methylidene]-2,3-dihydro-1H-isoindol-1-one, 3-[(1-oxo-1H-isoindol-3-yl)(1-naphthyl)methylidene]-2,3-dihydro-1H-isoindol-1-one, and 3-[(1-oxo-1H-isoindol-3-yl)(9-anthryl)methylidene]-2,3-dihydro-1H-isoindol-1-one were prepared by the reactions of phthalimide with phenylacetic, 1-naphthylacetic, and 9-anthrylacetic acids, respectively. Heating of these precursors with stearic acid in the presence of zinc oxide yielded zinc complexes of meso-trans-diphenyldihexadecyltetrabenzoporphyrin, meso-trans-di(1-naphthyl)dihexadecyltetrabenzoporphyrin, and meso-trans-di(9-anthryl)dihexadecyltetrabenzoporphyrin, respectively. Treatment of the metal complexes with HCl yielded the porphyrin bases. The spectral properties of the compounds were studied.     

Reaction of azolethiones with diacetylene

Reactions of 2,3-dihydro-1H-benzimidazole-2-thione, 2,3-dihydro-1H-1,2,4-triazole-3-thione, 4-amino-5-phenyl-3,4-dihydro-2H-1,2,4-triazole, and 6-aminopurine-2-thiol with diacetylene in DMSO gave the corresponding 1-(azolylsulfanyl)but-1-en-3-ynes having Z configuration of the double bond.     

Synthesis and spectral properties of unsymmetrical benzoporphyrins containing phenoxy groups or quinoxaline fragments

Condensation of phthalimide and 4-tert-butylphthalimide with zinc(II) acetate gave 3-(3-oxo-2,3-dihydro-1H-isoindol-1-ylidenemethyl)-1H-isoindol-1-one and 5-tert-butyl-3-(5-tert-butyl-3-oxo-2,3-dihydro-1H-isoindol-1-ylidenemethyl)-1H-isoindol-1-one, respectively. Their reactions with 4-phenoxyphthalimide and quinoxaline-2,3-dicarboximide in the presence of Zn(OAc)₂ led to the formation of zinc complexes of cis-4,4′-diphenoxytetrabenzoporphyrin and cis-di(4-tert-butylbenzo)diquinoxalinoporphyrin. The complexes were converted into the free bases by treatment with sulfuric acid. Spectral properties of the obtained porphyrin derivatives were studied.     

Synthesis, stereochemical and conformational properties of trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one oxime ethers

A convenient synthesis and structural characterization of (Z)- and (E)-trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one oxime ethers has been achieved. By analysis of vicinal interproton coupling constants, it is believed that trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-ones which exist predominantly in the diequatorial half-chair or sofa conformation was found to exist predominantly in the diaxial orientation upon conversion to the corresponding oxime ether derivatives.     

5,15-dialkyl-substituted tetrabenzoporphyrins and their zinc complexes. Synthesis and spectral properties

Reactions of phthalimide with capric and stearic acids gave 1-[1-(1-oxo-1H-isoindol-3-yl)nonylidene]-2,3-dihydro-1H-isoindol-3-one and 1-[1-oxo-1H-isoindol-3-yl)heptadecylidene]-2,3-dihydro-1H-isoindol-3-one, respectively. The latter were heated with zinc(II) acetate to obtain zinc complexes of 5,15-dioctyl-and 5,15-dihexadecyltetrabenzoporphyrins. The same complexes were synthesized by reaction of 1-(1-oxo-1H-isoindol-3-ylmethylidene)-2,3-dihydro-1H-isoindol-3-one with capric or stearic acid in the presence of zinc(II) oxide. The corresponding free porphyrin ligands were obtained by treatment of the metal complexes with sulfuric acid.     

A one-pot three-component reaction in aqueous micellar medium: an easy route to chromeno[2,3-b]quinolinedione

An efficient and green synthesis of hitherto unreported 5-aryl-3,3-dimethyl-2,3-dihydro-5aH-chromeno[2,3-b]quinoline-1,11(4H,5H)dione has been accomplished by a three-component reaction involving chromone-3-carbaldehyde, an aromatic amine, and 5,5-dimethyl-1,3-cyclohexanedione (dimedone) in 1.8 M aqueous TBAB solution. It is noteworthy that the TBAB/H₂O system can be recovered and reused for seven cycles directly.     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

Five-membered 2,3-Dioxoheterocycles: LIX. Reaction of 3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with Acyclic β-Enaminoesters. Crystal and Molecular Structure of Ethyl 3-Benzoyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,3-dihydro-1H-pyrrolo-2-spiro-3′-(5-methyl-2-oxo-2,3-dihydro-1H-pyrrolo-4-carboxylate)

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with substituted alkyl 3-amino-2-propenoates to form substituted alkyl 3-aroyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,5-dihydro-1H-pyrrole-2-spiro-3′-(2-oxo-2,3-dihydro-1H-pyrrole-4-carboxylates). Crystal and molecular structure of ethyl 3-benzoyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,5-dihydro-1H-pyrrole-2-spiro-3′-(5-methyl-2-oxo-2,3-dihydro-1H-pyrrole-4-carboxylate) was investigated.     

Unprecedented InCl3-catalyzed formation of cis-fused perhydrofuro[2,3-b]oxepines

2-Methylindole and its N-substituted derivatives react smoothly with 2,3-dihydrofuran (DHF) in the presence of a catalytic amount of InCl₃ under mild conditions to afford the corresponding 2-methyl-3-perhydrofuro[2,3-b]oxepin-4-yl-1H-indole derivatives in fairly good yields with high diastereoselectivity, while 3,4-dihydro-2H-pyran (DHP) affords exclusively 5,5-di(1H-3-indolyl)-1-pentanol derivatives in high yields under similar reaction conditions.     

A one-pot synthesis of 2,3-dihydro-1H-pyrrolo[3,2-c]quinolines

A one-pot synthesis of the 2,3-dihydro-1H-pyrrolo[3,2-c]quinoline core from substituted 2-iodoanilines and 2,3-dihydro-1H-pyrrole was achieved using 10 mol % Pd(PPh₃)₄, and K₂CO₃ in 1,4-dioxane at 170 °C for 1 h in a microwave oven. This reaction can be carried out on a gram scale. The proposed mechanism involves a Heck-coupling reaction followed by intra-molecular Schiff base formation and double bond migration.     

Reaction of 2-(2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indol-3-ylidene)acetic acid esters with benzene-1,2-diamine and 2-aminobenzenethiol

2-(2-Oxo-2,3-dihydro-1H-indol-3-ylidene)acetic acid esters reacted with benzene-1,2-diamine or 2-aminobenzenethiol to give (2-oxo-2,3-dihydro-1H-indol-3-yl)-substituted 3,4-dihydroquinoxalin-2(1H)-ones or 2H-1,4-benzothiazin-3(4H)-ones.