Polycyclic Thiophenes Research Articles

Cross-linked conjugated polymers based on triazine and poly-branched polycyclic thiophene for improved photocatalytic hydrogen evolution

Conjugated porous polymers (CPPs) incorporating donor-acceptor (D-A) structures are gaining significant interest for their potential in photocatalytic hydrogen evolution reaction (HER). The microstructure and electronic properties of the polymer frameworks...

Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis-Dihydroxylation and Epoxidation.

Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while cis-dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, cis/trans epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine.

A metal-free cascade reaction of β-halo-α,β-unsaturated aldehydes and 1,4-dithiane-2,5-diols: synthesis of polycyclic 2-formylthiophenes.

A metal-free cascade reaction strategy has been developed for the synthesis of novel polycyclic 2-formylthiophenes from β-halo-α,β-unsaturated aldehydes and 1,4-dithiane-2,5-diols. A recyclable polymer supported organic base was used to perform the reaction process. This synthetic protocol was applied to synthesize several novel polycyclic thiophenes including steroidal D-ring annelated thiophene. Our synthetic strategy provides a high yield of thiophenes, avoids a tedious work-up procedure and minimizes the formation of waste.

Site-Selective Polycyclic Thiophenes From Alkynes via C–H Activation

Site-Selective Polycyclic Thiophenes From Alkynes via C–H Activation

QSAR Study on a Series of Protein Tyrosine Phosphatase 1B Inhibitors

As a therapeutic target, protein tyrosine phosphatase 1B (PTP1B) has received considerable attention for the treatment of diabetes mellitus. A QSAR study using substituted monocyclic and polycyclic thiophene derivatives, recently reported as potent PTP1B inhibitors, was carried out. More than 60 physicochemical descriptors were calculated which underwent rational selection before their use in derivation of QSAR models. Statistically significant equations were generated using multiple linear regression analysis. External validation of the derived models with test set compounds proved good predictability of the models. Interpretation of the results revealed lipophilicity as a key regulatory feature which affects PTP1B inhibition along with several electronic and steric parameters. The study provides an important platform upon which novel rationally designed molecules can be synthesized with cautious optimism.

A Palladium-Catalyzed Approach to Polycyclic Sulfur Heterocycles

The synthesis of a variety of polycyclic thiophenes and benzothiophenes is accomplished via a palladium-catalyzed domino ortho-alkylation/direct arylation reaction. An examination of the intramolecular direct arylation of thiophenes suggests that an electrophilic metalation mechanism may be present. This method was further extended to include the synthesis of a (thieno)benzoxepine.

Synthesis of Polycyclic Heterocycles via a One-Pot Ortho Alkylation/Direct Heteroarylation Sequence

[reaction: see text] Polycyclic thiophenes and furans were synthesized using a one-pot ortho alkylation/direct heteroarylation reaction sequence. Under the optimized reaction conditions, aryl iodides were coupled with 3-(bromoalkyl)thiophenes or -furans, affording six- and seven-membered annulated ring products via formation of two C-C bonds from two aryl C-H bonds.

Unexpected conversion of a polycyclic thiophene to a macrocyclic anhydride

Oxygenation of 2,5,9,12-tetra( tert-butyl)diacenaphtho[1,2- b:1′,2′- d]-thiophene ( 1 , C 40H 44S) by peracids gave the cyclic sulfonic ester 4 (2,7,10,13-tetra( tert-butyl)diacenaphtho[1,2- c:1′,2′- e]oxathiin 5,5-dioxide, C 40H 44O 3S) which, when heated in nitrobenzene, is converted into a complex, macrocyclic anhydride 3 (C 80H 88O 3), which is derived from two molecules of 4 . Further investigation found a likely intermediate in this reaction, 4,4′,7,7′-tetra( tert-butyl)-1,1′-biacenaphthylenylidene-2,2′-dione ( 5 , C 40H 44O 2), apparently formed from 4 by additional oxidation. Anhydride 3 plausibly arises by Diels–Alder reaction of 4 and 5 followed by several ring fragmentations. The structures of 3 , 4 , and 5 were unambiguously established by X-ray crystallography.

Pattern Change of Several Polycyclic Aromatic Furans and Analogous Thiophenes on Oxidative Pyrolysis of Pitches in Flue Gases, and the Relevance to their Quantitative Analysis

Coal tars, coal-tar pitches, and ring-furnace flue gases have been analyzed by GC–MS for several classes of polycyclic aromatic furans and thiophenes and concentration patterns were obtained for benzonaphthofurans, benzonaphthothiophenes, benzobisbenzofurans, and their isomers. During formation of tar in a coke oven battery non-peripheral and alternating polycyclic thiophenes are formed preferentially. Peripheral polycyclic furans were not found in any of the materials. During tar processing the concentrations of minor fractions of peripheral benzonaphthothiophene isomers are reduced substantially. A further reduction occurs during pitch carbonization under oxidative conditions in an annular baking furnace. This largely facilitates quantification of the non-peripheral compounds.

ChemInform Abstract: Regioselective Alkylation of Polycyclic Thiophene Derivatives by Butyllithium and Alkyl Halide.

Abstract Polycyclic thiophene derivatives including the bisthiophene have been regioselectively alkylated by n-BuLi, and methyl iodide/ and allyl bromide.

Regioselective Alkylation Of Polycyclic Thiophene Derivatives By Butyllithium And Alkyl Halide

Polycyclic thiophene derivatives including the bisthiophene have been regioselectively alkylated by n-BuLi, and methyl iodide/ and allyl bromide.

(–)-(M,7S)-Colchicine and (–)-(M,7S)-10-Ethylthiocolchicide/Alkyne Cycloaddition Reactions: Synthesis of Novel Colchicine Derivatives by Consecutive [4+2] and [3+2] Cycloadditions

Cycloaddition reactions of the facially dissymmetric diene moiety of (–)-(M,7S)-colchicine (5) and (–)-(M,7S)-10-ethylthiocolchicide (9) to various alkynes have been studied. With 5 and the dienophilic benzyne (3), dimethyl acetylenedicarboxylate (DMAD) (4) and cyclooctyne (6) as starting materials all cycloadditions could be realized with high regioselectivity at the 8,12-positions of the alkaloid. The approach of the dienophiles preferentially occurred toward the syn π-face of the diene. In contrast to the cycloaddition mode of 5 the ethylthiocolchicide 9 surprisingly reacted in a different manner. With benzyne as starting material a novel [3+2] cycloaddition of the thioenol ether moiety of 9 towards the dipolarophilic benzyne is supposed, affording the unexpected colchicide 10 after [1,5]H shift of the primarily formed cycloadduct followed by cleavage of the C–S linkage. With DMAD (4) and cyclooctyne (6) the reaction course is more complex. In a consecutive [4+2]/[3+2] cycloaddition (or vice versa) followed by a thermally induced cycloreversion of a not identified intermediate DMAD (4) gives rise to the polycyclic thiophene derivative 13 and the novel allocolchicinoid 14. In a similar way cyclooctyne (6) yielded three products, the thiophene-annulated homobarrelenones 18 and 19 and the tetracyclic allocolchicinoid 21. The structures of the novel colchicine derivatives were assigned on the basis of spectral data, those of the cycloadducts 1 and 19 were verified by X-ray crystallography. For the unprecedented formation of the various allocolchicinoids by consecutive [4+2]/[3+2] cycloadditions plausible reaction pathways are suggested, as far as possible. In addition the inhibitory effects on the tubulin polymerization reaction in vitro of 10, 14, and 21 are reported.

Studies on polycyclic thiaarenes: Part II. An improved synthesis of phenanthro[1,2‐b]thiophene and a synthesis of acenaphtho[1,2‐b]naphtho‐[2,3‐d]thiophene, a novel polynuclear thiaarene

AbstractAn improved synthesis of phenanthro[1,2‐b]thiophene (6) from 1‐chloro‐3,4‐dihydrophenanthrene‐2‐aldehyde (2) by condensation with thioglycolate followed by hydrolysis, decarboxylation and dehydrogenation is described. A new polycyclic thiophene derivative 14 has also been prepared from acenaphthothiophene (7) by Friedel‐Craft's reaction with phthalic anhydride followed by lactonisation of the keto carboxylic acid 9 and then reduction and finally cyclisation of the resultant aldehyde 13.

Formation of polycyclic thiophenes from reaction of selected polycyclic aromatic hydrocarbons with elemental sulfur and/or pyrite under mild conditions

Formation of polycyclic thiophenes from reaction of selected polycyclic aromatic hydrocarbons with elemental sulfur and/or pyrite under mild conditions

The synthesis of polycyclic thiophenes derived from phenanthrene intermediates

AbstractThe synthesis of benzo[b]triphenyleno[2,1‐d]thiophene (9), benzo[b]triphenyleno[1,2‐d]thiophene (13), 5‐methylbenz[7,8]anthra[2,1‐b]thiophene (17), l‐methylchryseno[3,4‐b]thiophene (18), triphenyleno[1,2‐c]dibenzothiophene (22), triphenyleno[2,1‐a]dibenzothiophene (26), triphenyleno[1,2‐a]dibenzothiophene (29), and triphenyleno[2,1‐b]dibenzothiophene (30) is described.

Angular polycyclic thiophenes containing two thiophene rings. Part II

AbstractThe syntheses of naphtho[1,2–6:7,6‐b′]bisbenzo[b]thiophene (4), naphtho[1,2–6:7,8‐b′]bisbenzo[b]thiophene (5), naphtho[2,1‐b:7,6‐b′]bisbenzo[b]thiophene (8), naphtho[2,1‐b:7,8‐b′]bisbenzo[b]thiophene (9), naphtho‐[1,2–6:5,6‐b′]bisbenzo[b]thiophene (14), naphtho[1,2–6:6,5‐b]bisbenzo[b]thiophene (17) and naphtho[2,1–6:‐6,5‐b′]bisbenzo[b]thiophene (23) are reported.

Angular polycyclic thiophenes containing two thiophene rings. I

AbstractWe describe the synthesis of thieno[2,3‐c]dibenzothiophene (6), thieno[3,2‐c]dibenzothiophene (10), thieno‐[3,2‐a]dibenzothiophene (14), thieno[2,3‐a]dibenzothiophene (16), benzo[1,2‐b:4,3‐b]bisbenzo[b]thiophene (18), benzo[1,2‐‐6:3,4‐b]bisbenzo[b]thiophene (20), benzo[2,1‐‐6:3,4‐b]bisbenzo[b]thiophene (22), benzo[1,2‐b:3,4‐g]bisbenzo[b]thiophene (27), benzo[1,2‐b:4,3‐e]bisbenzo[b]thiophene (29), benzo[2,1‐‐6:3,4‐g]bisbenzo[b]thiophene (36), benzo[2,1‐‐6:4,3‐e]bisbenzo[b]thiophene (38), benzo[1,2‐‐6:4,3‐g]bisbenzo[b]thiophene (41), benzo[1,2‐b:4,5‐g]bisbenzo[b]thiophene (42), benzo[1,2‐b:3,4‐e]bisbenzo[b]thiophene (44) and benzo‐[1,2‐b:5,4‐e]bisbenzo[b]thiophene (45).

ChemInform Abstract: POLYCYCLIC THIOPHENES FROM THE DIRECT INSERTION OF HETEROSULFUR BRIDGES INTO VINYLARENES, BIARYLS, AND ANGULARLY CONDENSED ARENES

AbstractDie Darstellung von Thiophenen und kondensierten Thiophenen (II), (IV), (VI) und (VIII) aus Olefinen (I), Vinylaromaten (III), Biarylen (V) oder angular kondensierten Aromaten wie Phenanthren (VII) durch Umsetzung mit Schwefelwasserstoff an heterogenen Katalysatoren bei Temperaturen von 450 ‐ 630°C wird beschrieben.

POLYCYCLIC THIOPHENES FROM THE DIRECT INSERTION OF HETEROSULFUR BRIDGES INTO VINYLARENES, BIARYLS, AND ANGULARLY CONDENSED ARENES

Abstract There are three synthetic methods for direct introduction of a heterosulfur bridging atom into a vinylarene, biaryl, or angularly condensed arene to form a polycyclic thiophene. Two methods employ elemental sulfur, with or without a catalyst (aluminum chloride). The third method, which uses hydrogen sulfide and a heterogeneous catalyst (usually a metallic oxide) at 450–630°, is reviewed in detail. Thus, results on 20 different substrates (including a number of compounds bearing pyridine rings) are presented. Experimental observations which concern mechanistic aspects of the reaction are summarized and interpreted. For most substrates it is suggested that an ECEC mechanism prevails, whereby an adsorbed sulfide ion attacks a π-electron-deficient, adsorbed substrate to form a dihydro intermediate, which then undergoes aromatization. The substrate is adsorbed onto the catalyst either via the π-electrons or n-electrons (for some pyridine compounds). Type of adsorption and/or relative reactivities of ring positions may control isomeric ratios of products. For 2- and 4-vinylpyridines as substrates it is proposed that 1,2-addition leads to β-pyridylethanethiols and bis-(β-pyridylethyl) sulfides, which undergo thermal cyclization. The sulfur bridging reaction as a laboratory and, also possibly, a natural route to the formation of polycyclic condensed thiophenes found in the environment is discussed.