Thiophene series. Note IX . The absence of secondary steric effects in nucleophilic substitutions of thiophene derivatives: Kinetics of the reactions of 2-bromo-3,5-dinitrothiophene and 2-bromo-3,5-dinitro-4-methylthiophene with piperidine

The kinetics of the reactions of piperidine with 2-bromo-3,5-dinitrothiophcne (IV) and 2-bromo-3,5-dinitro-4-methylthiophene (III) have been measured in methanol, ethanol and benzene. Molecular model predictions were confirmed when the kinetic results (k_IV/k_III ? 2) demonstrated, for the first time, the absence of secondary steric effects for nucleophilic substitutions in thiophene compounds.     

TFAA/H3PO4‐Mediated C‐2 Acylation of Thiophene: A Direct Synthesis of Known and Novel Thiophene Derivatives of Pharmacological Interest

A number of aliphatic and aromatic carboxylic acids were reacted with thiophene in the presence of trifluoroacetic anhydride and H₃PO₄ to give a variety of acylated thiophenes in good to excellent yields. The methodology was used to prepare known nonsteroidal anti‐inflammatory drug‐based novel compounds of potential pharmacological significances. Molecular modeling studies were carried out by using nonsteroidal anti‐inflammatory drug‐based thiophene derivatives to assess their cyclooxygenase inhibiting potential in silico. On the basis of docking studies followed by subsequent in vitro assay, indomethacin‐based thiophene derivative was identified as a novel cyclooxygenase‐2 inhibitor with balanced selectivity.     

Synthesis of Some Novel 2‐Anilinothiophene, 2,3′‐Bithienyl and Thienylthiopyridine Derivatives Resistance to Penicillium Digitatum Effect the Fruit

Reaction of benzotriazol‐1‐yl acetone 1 with phenyl isothiocyanate followed with α‐chloroacetone or ethyl‐α‐chloroacetate afforded 2‐anilinothiophenes 3 or 4 , respectively. Treatment of 3 with malononitrile at different reaction conditions afforded 6 or 7 . Reaction of 1 with CS₂ in DMF and phenacylbromide afforded S‐alkylated thiophene 10 . Reactions of the latter compound with different active methylene nitriles afforded thienylthiopyridine derivatives 14 and 15 . Condensation of 10 with hydrazine hydrate afforded hydrazon derivative 16 . Reaction of thiophene 17 with formamide in DMF afforded 19 which converted to N‐thienylpyrimidine 20 when treated with malononitrile. The structure of the newly synthesized compounds has been established on the basis of their analytical and spectral data. The compounds were also investigated for antibacterial and antifungal activities.     

Kinetic behavior of benzene hydrogenation and thiophene hydrogenolysis on sulfide Ni-Mo/Al2O3 catalyst

Summary An unsteady-state kinetic model of both benzene hydrogenation (HDA) and thiophene hydrogenolysis (HDS) on a sulfide hydrotreating catalyst Ni-Mo/Al₂O₃ has been developed. The model adequately describes experimental data obtained at the pressure 2 MPa, temperature 573 K and at various contact times and ratios of benzene/thiophene. The model is based on the assumption that the catalyst surface contains only one type of active sites, i.e., Ni atoms in the sulfide bimetallic species, which are responsible for both hydrogenolysis and hydrogenation reactions.     

Synthesis and Reactions of Some Heterocyclic Candidates Based on 2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene Moiety as Anti‐Arrhythmic Agents

In continuation of our previous work, a series of novel thiophene derivatives 4 , 5 , 6 , 8 , 9 , 9a , 9b , 9c , 9d , 9e , 10 , 10a , 10b , 10c , 10d , 10e , 11 , 12 , 13 , 14 , 15 , 16 were synthesized by the reaction of ethyl 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylate ( 1 ) or 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carbonitrile ( 2 ) with different organic reagents. Fusion of 1 with ethylcyanoacetate or maleic anhydride afforded the corresponding thienooxazinone derivative 4 and N‐thienylmalimide derivative 5 , respectively. Acylation of 1 with chloroacetylchloride afforded the amide 6 , which was cyclized with ammonium thiocyanate to give the corresponding N‐theinylthiazole derivative 8 . On the other hand, reaction of 1 with substituted aroylisothiocyanate derivatives gave the corresponding thiourea derivatives 9a , 9b , 9c , 9d , 9e , which were cyclized by the action of sodium ethoxide to afford the corresponding N‐substituted thiopyrimidine derivatives 10a , 10b , 10c , 10d , 10e . Condensation of 2 with acid anhydrides in refluxing acetic acid afforded the corresponding imide carbonitrile derivatives 11 , 12 , 13 . Similarly, condensation of 1 with the previous acid anhydride yielded the corresponding imide ethyl ester derivatives 14 , 15 , 16 , respectively. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, MS spectral data, and elemental analysis. The detailed synthesis, spectroscopic data, LD₅₀, and pharmacological activities of the synthesized compounds are reported.     

离子液体催化剂用于煤焦化苯深度脱硫制无硫苯

从扩大有机合成用苯的需求出发,采用研制的离子液体催化剂考察了煤焦化苯深度脱硫制无硫苯的过程。结果表明：N-甲基咪唑硫酸氢盐[Hmim][HSO₄]离子液体催化剂脱噻吩效果与其酸函数值有关。本文采用Hammett指示剂测定离子液体的酸函数H₀,并得出：在-4至-12的范围,离子液体催化剂可以使煤焦化苯噻吩脱至0. 5mg/L以下。与固体酸催化机理相似,酸量和酸强度一定的离子液体催化剂通过Friedel-Crafts反应形成烷基噻吩等,与苯的物性拉开距离,对苯的分离精制是必不可少的,但是过多、过强的[Hmim][HSO₄]酸值也更有利于苯-噻吩-烯烃共聚合等副反应的发生,从而影响离子液体催化剂重复使用的寿命。本研究利用煤焦化苯脱硫反应形成的噻吩衍生物作为提供电荷流通的聚合物,将反复使用后性能不佳的离子液体成分等作为“受电子型”和“给电子型”的掺杂剂,进行导电（抗静电）材料的制备。结果显示：对煤焦化苯脱硫形成的噻吩衍生物等可以用于掺杂导电材料的试制。     

The Intramolecular Interaction of Thiophene and Furan with Aromatic and Fluoroaromatic Systems in Some [3.3]Meta(heterocyclo)paracyclophanes: A Combined Computational and NMR Spectroscopic Study

Four thiophene‐ and furan‐containing [3.3]meta(heterocyclo)paracyclophanes were designed and synthesized to study the intramolecular interaction between standard heteroaromatic rings and tetra‐H‐ or tetra‐F‐substituted benzenes. A complete conformational analysis, carried out by DFT calculations and variable‐temperature NMR techniques, showed that, despite their structural similarity, these adducts have different conformational preferences and undergo different types of isomerizations depending on the nature of the heterocycle. The thiophene‐derived adducts adopted a parallel stacked arrangement of the aromatic systems in the ground‐state conformations. Their isomerization pathways involved a thiophene ring‐flip process passing through an edge‐to‐face arranged transition state in which the heterocycle is perpendicular to the benzene platform and its sulfur atom points toward the center of that ring. The threshold energy barrier to the ring‐flip process was higher by 10 kJ mol^?1 in the case of the adduct featuring the perfluorinated benzene. This difference was rationalized by assuming that the ground‐state conformations of the H‐ and F‐substituted compounds have different stability. On the contrary, the furan‐derived adducts were shown by calculations and NMR spectroscopy to adopt, in their ground‐state conformations, a perpendicular edge‐to‐face disposition of the rings with the oxygen atom pointing toward the benzene platform. The adoption of this arrangement was confirmed by X‐ray crystallography. In the case of these compounds, the isomerization process involved distortion of the CH₂SCH₂ bridges connecting the aromatic systems and the adoption of transition‐state geometries for which the rings were arranged in a parallel‐stacked orientation. Once again a very nice agreement was observed between the predicted and the experimentally determined geometries and pathways. In the case of the furan‐containing compounds, the threshold barriers were found to be much lower in energy that those observed for the thiophene derivatives. Remarkably, they were virtually independent of the presence of fluorine atoms on the platform benzene ring.     

Photochromic dihetarylethenes. 14. Synthesis of symmetrical and unsymmetrical dihetarylcyclobutene-1,2-diones

A procedure was developed for the synthesis of symmetrical and unsymmetrical cyclobutene-1,2-dione derivatives bearing thiophene and thieno[3,2-b]thiophene substituents by the Friedel—Crafts reaction of the corresponding heterocyclic compounds with squaric acid dichloride in the presence of AlCl₃. In addition to the target dihetarylcyclobutenediones, monoacylation products of methyl (2,5-dimethylthiophen-3-yl)acetate and methyl 5-methylthieno[3,2-b]thiophene-2-carboxylate with squaric acid dichloride were isolated and characterized.     

Friedel-crafts copolymerization of thiophene and p-di(chloromethyl)benzene. I. Products,kinetics, and mechanism of the early stages of the reaction

The rate of polymerization of thiophene, at concentrations of catalyst (SnCl₄), and thiophene of the same order as was subsequently used in studying the reaction between thiophene and di(chloromethyl)benzene, is of the order of 10^-2%/hr at 30°C. There is no significant self-condensation of DCMB under the same conditions. Since the reaction between thiophene and DCMB is complete at 30°C in minutes rather than hours, it is assumed that self-condensation of thiophene or DCMB during the reaction between them will be negligible and should not influence the course of the reaction or the structure of the resulting polymer. Reaction at 30°C is much too fast for convenient study. A temperature of 0°C is more appropriate and was used in subsequent kinetic work. The first two products of the condensation of p-di(chloromethyl)benzene (DCMB) with thiophene have been identified by a combination of mass, infrared, and nuclear magnetic resonance spectroscopy as thenylchloromethylbenzene (TCMB) and dithenylbenzene (DTB). DCMB, TCMB, and DTB have been estimated quantitatively during the course of the reaction by gas-liquid chromatography (GLC), and it has been established that the rates of each of the two reaction steps is first-order with respect to the chloro compound (DCMB and TCMB respectively), thiophene, and SnCl₄. Rate constants for these two consecutive reactions were calculated to be k₁ = 2.79 × 10^-4l.²/mole²-sec, k₂ = 6.37 × 10^-3l.²/mole²-sec; the corresponding energies of activation are E₁ = 7.93 kcal/mole, E₂ = 7°67 kcal/mole. These rate constants are appreciably higher than values previously obtained for the corresponding DCMB–benzene reactions.     

Potassium tert‐Butoxide Catalyzed Synthesis and Characterization of Novel 3‐Aryl‐3‐(phenylthio)‐1‐(thiophen‐3‐yl)propan‐1‐one Derivatives

A series of thiophenyl‐containing 3‐thiophene derivatives ( 4a – 4i ) were prepared via the reaction of chalcone‐analogua compounds ( 3a – 3i ) and thiophenol in the presence of catalytic amount of KOBu‐t in CH₂Cl₂ with moderate to high yields. The mechanistic pathway of the reaction was explained by the Michael‐type addition of thiophenol to chalcone derivatives ( 3a – 3i ).     

Benzo[b] thiophene derivatives. XIV. Derivatives of naphtho[1,8-c] thiophene

In the course of our efforts to synthesize the sulfur isostere of lysergic acid, we have prepared a number of derivatives of the little known naphtho[1,8-bc]thiophene ring system. Two previously reported compounds, 2-bromo-3,4-dihydro-5-oxo-5H-naphtho[1,8-bc]thiophene and 2-bromo-5-hydroxy-3,4-dihydro-5H-naphtho[1,8-bc] thiophene have been obtained pure for the first time, and the syntheses and spectral data of eighteen new compounds are presented. The new compounds include alcohols, ketones, and halogen derivatives of partially reduced naphtho-[1,8-bc] thiophene, as well as the sulfones of several of these compounds.     

Reaction of piperidine and morpholine with 2H-pyran-2-ones, 2H-thiopyran-2-ones, 2H-pyran-2-thiones,and 2H-thiopyran-2-thiones. A novel route to thiophene derivatives

The reaction of piperidine or morpholine with 2H-pyran-2-ones was found to give open chain δ-oxoamides, while with 2H-thiopyran-2-ones, thiophene derivatives were formed. For 2H-pyran-2-thiones, either open chain δ-oxothioamides or thiophene derivatives were obtained. From the ¹ H nmr data of the pyran derivatives, the effect of the replacement of ring and carbonyl oxygens with sulphur on the chemical shift of the H-3 proton could be studied.     

N-Substituierte 2-Methyl-3-aminoacetyl-benzo[b]thiophene und 2-Methyl-3-(α-hydroxy-β-amino-äthyl)-benzo[b]thiophene

Zusammenfassung Bromierung von 2-Methyl-3-acetyl-benzo[b]thiophen ergab 2-Methyl-3-bromacetyl-benzo[b]thiophen, das beim Umsetzen mit Dimethylamin, Morpholin und N-Methylpiperazin die entsprechend basisch substituierten 3-Acetylverbindungen lieferte. Diese wurden mit LiAlH₄ zu den -Hydroxyverbindungen reduziert.In ähnlicher Weise wurde auch 3-Diäthylaminoacetyl-benzo[b]thiophen dargestellt.

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Bromination of 2-methyl-3-acetyl-benzo[b]thiophene gave 2-methyl-3-bromacetyl-benzo[b]thiophene, which reacted with dimethylamine, morpholine and N-methylpiperazine to give the corresponding base-substituted 3-acetyl derivatives. These were reduced by LiAlH₄ to the -hydroxy compounds.Similarily 3-diethylaminoacetyl-benzo[b]thiophene was synthesized.

     

3,5-Dilithiated tertiary thiophene 2-carboxamide. Regioselective entries into diversely substituted thiophenes

3,5-Dilithiated N,N-diethyl thiophene 2-carboxamide (3) undergoes reaction with a single electrophile in excess, or two different electrophiles in tandem, to give 2,3- and 2,3,5-substituted thiophene derivatives (4).     

Highly stereo‐efficient synthesis and luminescence properties of novel trans‐regular vinylene– silylene–thiophene polymers

The novel trans‐stereo‐regular silylene–thiophene derivatives ( 4 , 5 ) with perfect consecutive silylene–arylene–silylene–vinylene linkage were synthesized via silylative coupling polycondensation of 2,5‐bis(vinyldimethylsilyl)thiophene ( 2 ) or 5,5′‐bis(vinyldimethylsilyl)‐2,2′‐bithiophene ( 3 ) catalyzed by ruthenium‐hydride complex [RuHCl(CO)(PCy₃)₂] ( 1 ). Their spectroscopic, absorption, and luminescence properties were characterized and compared with those of model compounds containing thiophene or bithiophene chromophores. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 127–137, 2008     

Styryl dyes. Synthesis and study of the solid-state [2+2] autophotocycloaddition by NMR spectroscopy and X-ray diffraction

New styryl dyes of the pyridine and benzothiazole series were synthesized with the aim of investigating the solid-state [2+2] autophotocycloaddition (PCA) reaction. The ¹H NMR spectroscopy showed that for most of the compounds under study, the visible light irradiation of thin polycrystalline films of the dyes affords cyclobutane derivatives. The rate of the photoreaction depends on the structure of the dye and is higher for compounds, which contain a short N-substituent in the heterocyclic moiety and have strong absorption in the visible region. Dyes bearing electron-releasing substituents in the benzene ring undergo the stereospecific PCA in the syn-head-to-tail dimeric pair to give the only rctt isomer of cyclobutane derivatives. Electron-withdrawing and bulky substituents in the benzene fragment of styryl dyes extend the range of the mutual orientations of the molecules in the dimeric pairs, resulting in the formation of two or even four isomeric cyclobutanes in the PCA reactions. The structures of some dyes were established by X-ray diffraction. In the overwhelming majority of the structures, one of two packing modes, either syn-head-to-tail or syn-head-to-head, with extensive stacking interactions is observed. A rare example of the anti-head-to-head stacking mode was found for the dicationic dye containing the bulky N⁺(Et)Me₂ substituent in the benzene ring. The syn-head-to-tail and anti-head-to-head stacking modes can facilitate the PCA reaction due to the close spatial proximity of the ethylenic bonds and their parallel orientation in the dimeric pairs of the dye molecules. Dedicated to Academician G. A. Abakumov on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1797–1819, September, 2007.     

Synthesis and antifungal activity of carvacrol and thymol esters with heteroaromatic carboxylic acids

Aiming to obtain the more effective pathogen inhibitive ingredients and explore the influence of introducing different heterocyclic units to carvacrol and thymol esters, twenty ester derivatives with different heterocyclic units were synthesized. And the in vitro antifungal activity of title compounds against five plant pathogenic fungi was evaluated by mycelium growth rate method. The results showed that some carvacrol and thymol esters showed good to excellent antifungal activity, and compound 9d (4-bromo-5-isopropyl-2-methylphenyl picolinate) exhibited a broad antifungal spectrum. Preliminary study indicated that the introduction of furan, thiophene and pyridine unit could enhance the antifungal activity of carvacrol and thymol esters against Botrytis cinerea and a bromine atom on the para position of benzene moiety could enhance their antifungal activity.     

Synthesis of New Fused and Spiro Heterocyclic Systems from 3,5‐Pyrazolidinediones

4‐Bromo‐1‐phenyl‐3,5‐pyrazolidinedione 2 reacted with different nucleophilic reagents to give the corresponding 4‐substituted derivatives 3–8 . The cyclized compounds 9–11 were achieved on refluxing compounds 3 , 4 or 6_a in glacial acetic acid or diphenyl ether. 4,4‐Dibromo‐1‐phenyl‐3,5‐pyrazolidinedione 12 reacted with the proper bidentates to give the corresponding spiro 3,5‐pyrazolidinediones 13–15 , respectively. The 4‐aralkylidine derivatives 16_a‐c , were subjected to Mannich reaction to give Mannich bases 17_a‐c‐22_a‐c , respectively. 4‐(p‐Methylphenylaminomethylidine)‐1‐phenyl‐3,5‐pyrazolidinedione 23 or 4‐(p‐methylphenylazo)‐1‐phenyl‐3,5‐pyrazolidinedione 29 were prepared and reacted with active nitriles, cyclic ketones and N,S‐acetals to give pyrano[2,3‐c]pyrazole, pyrazolo[4′,3′:5,6]pyrano[2,3‐c]pyrazole, spiropyrazole‐4,3′‐pyrazole and spiropyrazole‐4,3′‐[1,2,4]triazolane derivatives 24–34 , respectively.     

SYNTHESIS OF FUSED AND SPIRO HETEROCYCLIC COMPOUNDS DERIVED FROM 3,5-PYRAZOLIDINEDIONE DERIVATIVES

Abstract

The reaction of compound 1 with triethyl orthoformate afforded 2, which in turn reacted with CS₂ and active methlyene compounds or malononitrile to give dithiolane and 4-malononitrile methylene derivatives 3,4, respectively. Treatment of compound 4 with active methylene compounds afforded spiro cyclopentene derivatives 5_a-c. Compound 1 was reacted with bromomalononitrile or CS₂ and halocompounds to afford furo-. thieno- and dithiolano-pyrazole derivatives 6–11, respectively. The reaction of compound 12 with phenacyl bromide or benzylidenemalononitrile furnished oxathiol-2-ylidene and pyridinethione derivatives 13,14, respectively. The dibromo derivative 16 was reacted with CS₂ and active methylenes or malononitrile to obtain spiro dithietanes 17a-e and 4-dicyano-methlyene derivative 22, respectively. Compounds 17 underwent a cycloaddition reaction with thioglycolic acid, N-phenylbenzohydrazindoyl bromide, 2,5-dimethylfuran and 1-phenyl-3,5-pyrazolidinedi one to give cycloadducts 18–21, respectively. Treatment of > o-aminothiophenol or o-phenylenediamine with the dicyano compound 22 leads to the formation of spiro thiazepine or spiro diazine derivatives 23_a,b . The arylidene derivatives 24 was reacted with S,S-acetals, N,S-acetals or ammonium dithiocarbamate to afford dithiane, oxazine or pyrazolodithiocarbamate derivatives 25–29, respectively. Chemoselective cyclization of compound 29 with H₂SO₄, NaOH or MeI gave compounds 30–32, respectively. Benzopyrano derivatives 34,36 were obtained through the reaction of compound 1 with a mixture of thiourea, triethyl orthoformate and ethyl cyanoacetate or with cyanoketene S,S diacetals, respectively.     

Development in Synthesis,Electrochemistry, LB Moieties of Phenothiazine Based Units

A convenient and higher yielding synthetic route to N‐alkyl‐bis(thiophene)phenothiazine derivatives is reported and their aggregation, electrochemical properties and polymerization are characterized. The key step in the synthesis of this group of compounds has been the Stille type coupling reaction between the N‐alkyldibromophenothiazine and tin derivatives of thiophene as the best way for preparation of conjugated N‐alkylphenothiazine derivatives. For this group of compounds we also present an electrochemical polymerization effect and widely adopted approach to prepare structurally ordered thin, electroconducting films by Langmuir–Blodgett technique.