Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and benzo[b]furans: synthesis of benzo[b]thiophene 2,3-oxide

Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several methyl substituted derivatives was found to occur in both the carbocyclic and heterocyclic rings. Relative and absolute configurations and enantiopurities of the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.     

Preparation of Nitrogen Heterocycles of Spiro[Furo[2,3‐d]‐Pyrimidine]Pyrimidine Derivatives

Abstract

The NMR evaluation of the reaction progression of the bromination of heterocyclic dibarbiturates was used to develop an efficient synthetic procedure for the preparation of heterocyclic spiro[furo]pyrimidines. The structure of one of these compounds was confirmed by X‐ray analysis.     

Compressing a Non-Planar Aromatic Heterocyclic [7]Helicene to a Planar Hetero[8]Circulene

This work describes a synthetic approach where a non-planar aromatic heterocyclic [7]helicene is compressed to yield a hetero[8]circulene containing an inner antiaromatic cyclooctatetraene (COT) core. This [8]circulene consists of four benzene rings and four heterocyclic rings, and it is the first heterocyclic [8]circulene containing three different heteroatoms. The synthetic pathway proceeds via a the flattened dehydro-hetero[7]helicene, which is partially a helicene and partially a circulene: it is non-planar and helically chiral as helicenes, and contains a COT motif like [8]circulenes. The antiaromaticity of the COT core is confirmed by nucleus independent chemical shift (NICS) calculations. The planarization from a helically π-conjugated [7]helicene to a fully planar heterocyclic [8]circulene significantly alters the spectroscopic properties of the molecules. Post-functionalization of the [7]helicenes and the [8]circulenes by oxygenation of the thiophene rings to the corresponding thiophene-sulfones allows an almost complete fluorescence emission coverage of the visible region of the optical spectrum (400–700 nm).     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 16. [1]benzothieno[2′,3′:4,5]thieno[2,3-c]quinoline and [1]benzothieno[2′,3′:4,5]thieno[2,3-c]naphtho[1,2-f]quinoline

The synthesis of two previously unknown polycyclic heterocyclic ring systems via photocyclization is described. The unequivocal assignment of their proton and carbon spectra was achieved by utilizing two-dimensional nmr techniques.     

Electrophilically Activated Nitroalkanes in Double Annulation of [1,2,4]Triazolo[4,3-a]quinolines and 1,3,4-Oxadiazole Rings

Nitroalkanes activated with polyphosphoric acid could serve as efficient electrophiles in reactions with amines and hydrazines, enabling various cascade transformations toward heterocyclic systems. This strategy was developed for an innovative synthetic protocol employing simultaneous or sequential annulation of two different heterocyclic cores, affording [1,2,4]triazolo[4,3-a]quinolines with 1,3,4-oxadiazole substituents.     

Heterocycles from amino acids. A novel synthetic approach for imidazo[1,5-a]pyridines and imidazo[1,5-a]quinolines

From the corresponding heterocyclic amino acids 2 and 9a the heterocyclic systems imidazo[1,5-a]pyridine ( 3 ) and imidazo[1,5-a]quinoline ( 10 ) are easily accessible. From compound 7 the tricyclic system 11 was prepared and from compound 17a a pyridyl-1,2,4-triazinone ( 18 ) could be obtained.     

A synthesis of 5-oxo-1,2,3,4-tetrahydro[1,4]azepino-[6,7,1 -kl]phenothiazine

A synthesis of a new heterocyclic system (5) is described starting from 1-carbomethoxyphenothiazine.     

A Facile Synthesis of Benzo[4,5]Imidazo[2,1-b]-Pyrimido[5,4-f][1,3,4]Thiadiazepines

Benzo[4,5]imidazo[2,1-b]pyrimido[5,4-f][1,3,4]thiadiazepines representing a new heterocyclic system were prepared by cyclocondensation reaction of l-aminobenzimidazol-2-thione with 6-chloropyrimidine-5-carbaldehydes. 4-Dimethylamino derivative of this tetraheterocyclic system possessed anti-HIV activity.     

Synthesis of regioisomeric 6,9-(chlorofluoro)-substituted benzo[g]quinoline-5,10-diones,benzo[g] isoquinoline-5,10-diones and 6-chloro-9-fluorobenzo[g]quinoxaline-5,10-dione

Treatment of difluoro or chloro fluoro-substituted benzyl bromides 5a-c with zinc dust in tetrahydro-furan leads to the corresponding benzylic zinc bromides 6a-c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa-c and 7Ba-c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo-substituted heterocyclic quinones 2.     

Spirane—X : 2,2′,3,3′-tetrahydro-3,3′-spirobi[4H-[1,5]-benzo-oxathiepin] und 2,3,4,5-tetrahydrospiro[1H-benzo-[f]-[1,5]-diazepin-3,1′-cyclopropan]; schnelles gleichgewicht zwischen diastereokonformeren

The synthesis of two unknown spiran systems has been described. The conformation of the first system determined by NMR spectroscopy contains two heterocyclic rings in the chair form and can be represented by three diastereomeric structures. Two of the structures possess C₂-symmetry one C₁-symmetry. They are topologically equivalent. The second system has the heterocyclic ring in chair form.     

Indolobenzo[b] furans. 2. Some indolo[5,6-d]- and indolo[5,4-d] benzo[b]furans

The reactivities of new heterocyclic systems, viz., indolo [5,6-d]- and indolo[5,4-d]benzo[b]furans, in several electrophilic-substitution reactions (the Mannich and Vilsmeier reactions and acylation) were studied. It was established that the indicated heterocycles, like indole, are readily formylated and aminomethylated; some anomalies are observed only in the case of acylation.See [1] for Communication 1.Translated from Kihimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 355–358, March, 1985.     

A novel practical synthesis of pyrrolo[1,2-a]thieno[2,3-e][1,4]diazepines

In an investigation of new heterocyclic systems, a novel way to obtain pyrrolo[1,2-a]thieno[2,3-e][1,4]diazepine 8 was effected by ring closure to the appropriate nitroaldehyde compound which was synthesized in five steps from 3-bromomethyl-2-nitrothiophene 1 .     

New reaction of benzo[b]thieno[3,2-b]benzo[b]thiophene disulfone

A new reaction of benzo[b]thieno[3,2-b]benzo[b]thiophene disulfone with amines that takes place with opening of one of the thiophene rings and nucleophilic substitution in the heteroaromatic ring at the site of cleavage of the S-C bond was observed. The molecular structures of the products of amination of the disulfone were determined by x-ray diffraction analysis. Hydrolysis and dehydration of the amination products gave derivatives of a new heterocyclic system, viz., benzo[b]-thieno[3,2-e]benzo[c]-1,2-oxathiin. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 320–323, March, 1980.     

Synthesis of imidazo[1,2-a]pyridine-6-carbohydrazides and 1H-pyrido[1,2-a]pyrimidine-7-carbohydrazides

The one-pot, multicomponent synthesis of imidazopyridine and pyridopyrimidine fused heterocyclic systems from readily available diamines, l,l-bis(methylthio)-2-nitroethene, cyanoacetohydrazide and aromatic aldehydes in good to high yields is described. This protocol has the advantages of simple work-up, mild reaction conditions, absence of catalyst and provides an entry point to fused heterocyclic structures.     

Synthesis of Benzo[d]Benzo[2,3][1,4]Diazepino[1,7-b]Isothiazole,a New Heterocyclic Ring System

A facile synthesis of benzo[d]benzo[2,3][1,4]diazepino[1,7-b] isothiazole, a new heterocyclic ring system is reported.     

Synthesen von basisch substituierten ([1]Benzo-)Thieno-[2,3—d]pyrimidin-Derivaten und von ([1]Benzo-)Thieno-[2,3-d]-1,2,4-triazolo[4,3-a]pyrimidin-Derivaten

Reaction of 2-methylthio-thieno[2.3-d]pyrimidin-4(3H)-ones with heterocyclic secondary amines, ethanolamine and hydrazine, resp., gave the corresponding derivatives with a basic substituent in position 2. Cyclization of the hydrazino compounds with formic acid gave derivatives of thieno[2.3-d]-1.2.4-triazolo[4.3-a]pyrimidine and [1]benzothieno[2.3-d]-1.2.4-triazolo[4.3-a]pyrimidine, two new heterocyclic systems.     

Synthesis of 2-methylthie no [3,2-b]thieno-[2,3-d]thiazole

A new heterocyclic base — 2-methylthieno[3,2-b]thieno[2,3-d]thiazole — was synthesized by heating 2-acetamido-3-hydroxythieno[3,2-b]thiophene with phosphorus pentasulfide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1039–1041, August, 1976.     

Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocycles by cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to high yields. Catalysis by scandium triflate was used in the reactions that implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b. Cyclic voltammetry of selected examples showed irreversible processes that were influenced by the electrochemical activity of peripheral groups bonded to the heterocyclic system.     

Spirane—III 3,3′-spirobi[benzo-[2H.4H]-[1.5]-dioxepin]

The conformation of the mentioned new spiran system has been determined by NMR spectroscopy. It contains two heterocyclic rings in the chair form, is chiral and shows a twofold axis of symmetry.     

Multicomponent Synthesis of 2,3-Dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones: A Novel Heterocyclic Scaffold with Antibacterial Activity

A multicomponent reaction of 3-aminopyrazol-5-ones with substituted salicylic aldehydes and acetylacetic ester leading to the formation of novel 2,3-dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones was discovered. The elucidation of the reaction scope revealed that 5-aminopyrazoles, 3-amino-1,2,4-triazoles and 6-aminouracil could be used as the heterocyclic amine component. Selected heterocyclic products were found to possess notable antibacterial activities.