An unexpected 1,2-hydride shift in phosphoric acid-promoted cyclodimerization of styrene oxides under solvent-free conditions. A synthetic route towards 2,4-disubstituted 1,3-dioxolanes

A 1,2-hydride shift in the phosphoric acid-promoted cyclodimerization of styrene oxide and its chloro derivatives under solvent-free conditions leading to 2,4-disubstituted 1,3-dioxolanes is described. Methoxy substituents on the aromatic ring of the styrene oxide prevent the 1,2-hydride shift reaction leading to substituted 1,4-dioxanes. A possible mechanism for the formation of the 1,3-dioxolanes is proposed.     

2-氨基-4-羰基噻吩的Knoevenagel反应

在碳酸钾等无机碱的存在下,异硫氰酸酯和4-氯乙酰乙酸乙酯反应生成2-氨基-4-羰基-4,5-二氢噻吩-3-甲酸乙酯。该化合物显示了与醛基的反应活性,即Knoevenagel反应,本文对该噻吩化合物的Knoevenagel反应位点选择性进行了研究。运用Gaussian03程序对化合物进行了几何全优化和相应的电荷、轨道能量分析研究。     

Synthesis, docking studies and biological evaluation of benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives on 5-HT1A serotonin receptors

A series of novel benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives 6a-f, 7a-f and their corresponding alcohols 8a-f were synthesized and evaluated for their affinity towards 5-HT(1A) receptors. The influence of arylpiperazine moiety and benzo[b]thiophene ring substitutions on binding affinity was studied. The most promising analogue, 1-(benzo[b]thiophen-2-yl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan-1-one (7e) displayed micromolar affinity (K(i) = 2.30 μM) toward 5-HT(1A) sites. Docking studies shed light on the relevant electrostatic interactions which could explain the observed affinity for this compound.     

Unexpected solid-state photochemistry of an alpha-thiophenyl-alpha'-thiophenyl-S,S-dioxo-substituted ketone

Samples of 2,4-dimethyl-2-(thiophen-3-yl)-4-(thiophen-3-yl-S,S-dioxo)pentan-3-one 2 were obtained by controlled MCPBA oxidation of 2,4-dimethyl-2,4-di(thiophen-3-yl)pentan-3-one 1. Rather than the expected photodecarbonylation, UV--vis irradiation of 2 led to the intramolecular 2 + 2 photocycloaddition product 5 in quantitative yields (by GC and NMR) both in solution and in crystalline solid state. Detailed X-ray powder diffraction analyses revealed that the solid-state reaction of sulfone 2 occurs with a loss of long-range order despite retaining some birefringence under polarized microscopy.     

Synthesis of aryl-containing terpenoids based on 1,4-dihydronaphthalene

Successive transformations including oxidation of 1,4-dihydronaphthalene into 1,2,3,4-tetrahydronaphthalen-2-one, Reformatskii reaction of the latter with methyl bromoacetate, ozonolysis of the Reformatsky reaction product, and Emmons olefination of the aldehyde group in methyl 3-oxo-5-(2-formylphenyl)pentanate thus formed gave analogs of highly active dienoate juvenoids having an aromatic ring in their molecules.     

Synthesis and some transformations of 1-methyl-2-(thiophen-3-yl)-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

1-Methyl-2-(thiophen-3-yl)-1H-benzimidazole was synthesized by the Weidenhagen reaction, followed by N-methylation. Electrophilic substitution reactions of the title compound, in particular nitration, bromination, sulfonation, formylation, and acylation, were studied. The formylation and acylation in polyphosphoric acid afforded mixtures of 2- and 5-substituted isomers at the thiophene ring. The nitration of 1-methyl-2-(thiophen-3-yl)-1H-benzimidazole involved the thiophene ring or both thiophene and benzene fragments, depending on the conditions. Steric arrangement of the heterocycles in the 1-methyl-2-(thiophen-3-yl)-1H-benzimidazole molecule was analyzed by quantum chemical calculations.     

Studies in sulphur heterocycles. Part 7 . Tricyclic compounds related to 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene

Synthesis of a number of tricyclic compounds with a fused thiophene ring starting from 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-4-one and benzosuberone is described. Biological testing of these compounds for their antiparasitic activities has been carried out.     

A novel hydrogen peroxide-dependent oxidation pathway of dopamine via 6-hydroxydopamine

In the presence of excess H₂O₂, oxidation of dopamine was diverted from the usual pigment-forming pathway to afford 6-hydroxydopamine and then a colorless reaction mixture comprising a polar non-extractable product. The latter was obtained in 20% yield by oxidation of 6-hydroxydopamine and was tentatively formulated as the novel 5-(2-aminoethyl)-2-hydroxy-5-(3-hydroxy-2-oxotetrahydro-1aH-oxireno[2,3]cyclopenta[1,2-b]pyrrol-3a(4H)-yl)cyclohex-2-ene-1,4-dione by extensive spectral analysis and conversion to a tetraacetyl derivative. Mechanistic experiments suggested that formation of the product proceeds via 6-hydroxydopamine by H₂O₂-dependent epoxidation and cyclization steps followed by dimerization and ring contraction with decarboxylation.     

Oxidation of Methyl Function of 3,3-(3-Fluorobenzyl)-2-Propanone by Thionyl Chloride

In the presence of a catalytic amount of a tertiary amine, thionyl chloride generally oxidizes carboxylic acids^1,2 and ketones¹ at α carbon atoms to form α-chloro-α-chlorosulfenyl derivatives and their subsequent reaction products. Examination of reaction mixtures of thionyl chloride with a number of variously substituted 4-aryl-2-butanones revealed that in the case of the 3-methoxy or 3-hydroxy derivatives, cyclization onto the aromatic ring to form a benzo[b] thiophene competes quite favorably with cyclization onto enol to form a thietanone.⁴ The results were consistent only with thionyl chloride oxidation proceeding exclusively at the methylene position.     

Synthesis and Characterization of a New Series of Hydroxy Pyrazolines

3-Phenyl-1-(thiophen-2-yl)prop-2-en-1-one obtained by Claisen–Schmidt condensation of 2-acetyl thiophene with benzaldehyde was converted into 2,3-dibromo-3-phenyl-1-(thiophen-2-yl)propan-1-one, which on treatment with various thiosemicarbazides in the presence of triethylamine in absolute ethanol, yielded the corresponding hydroxy pyrazolines 3a–h. All the compounds were characterized by IR, ¹H NMR, and ¹³C NMR spectra.     

1,1,2,2-Tetrahydroperoxy-1,2-Diphenylethane: An efficient and high oxygen content oxidant in various oxidative reactions

Several oxidative approaches namely thiocyanation of aromatic compounds, epoxidation of alkenes, amidation of aromatic aldehydes, epoxidation of α, β-unsaturated ketones, oxidation of sulfides to sulfoxides and sulfones, bayer-villeger reaction, bromination and iodation of aniline and phenol derivatives oxidative esterification, oxidation of pyridines and oxidation of secondary, allylic and benzyllic alcohols were carried out using 1,1,2,2-Tetrahydroperoxy-1,2-Diphenylethane as the potential solid oxidant which can be stored for several months without any loss in its activity. All of the procedures were accomplished via mild reaction conditions and the products were afforded in high yields and short reaction times.     

A facile synthesis of benzo[b]thiophene derivatives

Lithiation of S-(2-methylphenyl) N,N,N',N'-tetramethylphosphorodiamidothioate with sec-BuLi at -105° gave the corresponding benzylic anion which was acylated with various aromatic esters to give various deoxybenzoin derivatives in moderate to high yields. Acidic treatment of these products in refluxing formic acid gave 2-arylbenzo[b]thiophene derivatives. 2-Methylbenzo[b]thiophene and benzo[b]thiophen-2(3H)-one were also prepared using the similar procedure.     

Condensation Reactions of Sulfur-Containing Chalcone Analogs

Three-component condensation of heterocyclic chalcone analogs containing a thiophene ring with 5,5-dimethylcyclohexane-1,3-dione (dimedone) and ammonia at 140–145°C under pressure afforded functionalized 1,4,5,6,7,8-hexahydroquinoline derivatives; the corresponding triketones were formed under milder conditions (100–105°C). The condensation of 1,3-di(thiophen-2-yl)prop-2-en-1-one with dimedone and ammonia under harsh conditions unexpectedly produced functional 1,2,3,4,5,6,7,8,9,10-decahydroacridine derivative. Heterocyclic chalcone analogs reacted with ethyl acetoacetate in the presence of ammonia to give cyclocondensation products, ethyl 2-oxocyclohex-3-ene-1-carboxylates.     

Synthesis of nitrogen heterocycles underlain by application of 3-(4-Acetyl[phenyl)-2H-coumarin

3-(4-Acetylphenyl)-2H-chromen-2-one was obtained from 4-acetylphenyldiazonium chloride in the conditions of Meerwein reaction. Reactions of 3-[4-(2-bromoacetyl)phenyl]-2H-chromen-2-one with pyridine, 4-methylpyridine, quinoline, benzo[f]quinoline, and triphenylphosphine afforded quaternary salts, and with thioacetamide, thiourea, 2-aminopyridine, 2-aminopyrimidine, and 6-aminopurine provided the corresponding derivatives of thiazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, imidazo[2,1-i]purine. In the reaction of the same bromo derivative with thiosemicarbazide and aromatic aldehydes a thiazole ring is built and the corresponding hydrazones are formed.     

Synthesis and Characterization of Conducting Copolymers of Thiophene Derivatives

Electrochemical copolymerizations of N¹,N²-bis(thiophen-3-ylmethylene)benzene-1,2-diamine (TMBD), 4-methyl-N¹,N²-bis (thiophen-3-ylmethylene)benzene-1,2-diamine (MTMBD) and 4-nitro-N¹,N²-bis(thiophen-3-ylmethylene)benzene-1,2-diamine (NTMBD) with 3,4-ethylenedioxy thiophene (EDOT) were carried out in CH₃CN/LiClO₄ (0.1 M) solvent–electrolyte couple via potentiodynamic electrolysis. The resulting copolymers were characterized by cyclic voltammetry (CV), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The conductivity measurements of copolymers and PEDOT were carried out by the four-probe technique.     

New easy approach to the synthesis of 2,5-disubstituted and 2,4,5-trisubstituted 1,3-oxazoles. The reaction of 1-(methylthio)acetone with nitriles

The reaction of 1-(methylthio)acetone with different nitriles in the presence of triflic anhydride led to the one-pot formation of 2-substituted 5-methyl-4-methylthio-1,3-oxazoles in good yield. 1,2- and 1,4-Bisozaxolyl-substituted benzenes were obtained when the reaction was carried out using aromatic dinitriles. The methylthio group at the C4 position of the oxazole ring was easily removed with Raney nickel to form 2-substituted 5-methyl-1,3-oxazoles in good yields. 4-Methylsulfonyl derivatives were prepared by the oxidation of the MeS group with m-CPBA. The proposed mechanism for the formation of oxazoles involves an unstable 1-(methylthio)-2-oxopropyl triflate, which was detected from the low-temperature NMR spectra.     

Synthesis of the trans-hydrindane core of dictyoxetane

A concise, stereoselective synthesis of the trans-hydrindane core of the marine natural product dictyoxetane is reported, starting from a Robinson annelation derived bicyclic enone. A phosphorane-mediated, pinacol-like rearrangement of a cis-diol, via a formal 1,2-hydride shift, is used to establish the requisite trans ring junction. (31)P NMR supports the formation of the intermediate phosphorane, generated in situ from the reaction of a diol with Ph(3)PCl(2).     

Reaction of thienocycloalkanones with benzene

Conclusions The reaction of benzene with 4,5,6,7-tetrahydrobenzo[b]thiophen-4-one and 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-4-one under the conditions for acylation in the presence of aluminum chloride and methyl 3-(chloroformyl)propionate forms 3-phenyl-2,3,4,5,6,7-hexahydrobenzo[b]thiophen-4-one and 3-phenyl-2,3,5,6,7,8-hexahydro-4H-cyclohepta[b]thiophen-4-one among other products.Translated from Izvestiya Akademiya Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2534–2536, November, 1976.     

Photochromic Dihetarylethenes: XVI. Synthesis of 1,2-Dihetarylethenes on the Basis of Thieno[3,2-b]pyrrole

The reaction of 3,4-dichlorocyclobutene-1,2-dione with methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate occurs at the thiophene ring of the latter, yielding a product in which the thienopyrrole fragments are linked through a dioxocyclobutene ring. Oxidation of this product with hydrogen peroxide gives previously unknown thermally stable photochromic system containing thienopyrrole groups linked through a 2,5-dioxofuran bridge.     

A convenient procedure for the synthesis of tetrathia-[7]-helicene and the selective α-functionalisation of terminal thiophene ring

This paper describes a convenient preparation of tetrathia-[7]-helicene (TH[7]), the generation of the α-anion on the terminal thiophene ring, and the synthesis of the 2-formyl-tetrathia-[7]-helicene (2-CHO-TH[7]). The key intermediate trans-1,2-dibenzodithiophene-ethene, prepared in 97% yield by McMurry coupling of the 2-formyl-benzo[1,2-b;4,3-b′]dithiophene, was transformed into TH[7] using a known procedure. The described method affords TH[7] in 46% overall yield, which is more than four times the yield previously reported in the literature. The α-anion of TH[7], which is easily generated on the α-position of one of the terminal thiophene rings, reacts with electrophilic reagents such as D₂O and DMF. The latter reaction proved to be the best way to prepare 2-CHO-TH[7], a key intermediate for the preparation of new substituted heterohelicenes.