Thiophene ring disulfides

This linear polysulflde obviously formed according to the sequence 2,5-di(thiocyano) thiophene potassium 2-mercaptido-5-thiacyanonothiophene —> (tristhio)maleic anhydride thiophene-2,5-disulfenyl biradical (the diradical valence tautomer) —> the depicted linear polymer in which the thiophene rings are connected through disulfide bridges (Scheme 8.17). 

The thiophene ring of 3-benzoylthiocoumarone opens and gives o-mercaptophenylpyrazole together with the corresponding disulfide.384 Similarly, 3-acylpyrroles are converted to pyrazoles.359 414... 

A thiophene ring synthesis has been achieved by reactions of 1,3-dicarbonyl compounds with carbon disulfide, followed by annulation with ethyl bromoacetate, giving for instance the system 13 <07T2724>. 

Aminothiophenes can also be obtained from carbon disulfide-derived intermediates. For example, one of the methylthio groups of ketene dithioacetal 57, obtained from pentane-2,4-dione as shown, can be displaced with a secondary amine and the thiophene ring constructed by reaction with, for example, ethyl thioglycolate for final ring closure (Scheme 79) [127]. 

Examples of reactions involving replacement and cyclization are the long-known preparation of thiophenes (89) from 1,4-diketones, and the formation of l,2-dithiole-3-thione (90) from the salicylate ester analog (91).120 In the latter instance, oxidative cyclization with formation of an S—S bond has occurred this is a common feature of these reactions, particularly if such a link is needed to complete a five-membered ring. Another example of this aspect is afforded by the reaction of the propane-1,3-dione derivatives (92) which yield 3,5-diaryl-1,2-dithiolylium salts (93) when heated with phosphorus pentasulfide in carbon disulfide, followed by perchloric acid.121... 

In the previous examples, the sulfur atom acted as a nucleophile. Electron-deficient sulfur species such as sulfenyl ion and its equivalents (e.g. disulfide/Lewis acid complexes, sulfenic acids, sulfenyl halides, sulfonium ions, sulfines, etc.), can also serve as an electrophile. Oxidative ring closure of enethiols (a-thioketocarboxylic acid) (124), which proceeds via disulfides, produces thiophenes (125) in good yields (86EUP158380, 88JHC367). 

Disulfides were shown to be intermediates in the iodine oxidation of 1,3-butadiene-l-thiols and related compounds to form thiophenes (56JOC39). Several simple disulfides were converted to thiophene derivatives under these same conditions (64JOC2372). For example, bis(2-biphenyl) disulfide (13) produced dibenzothiophene (14) in 64% yield when heated with iodine in ethylene glycol for one hour. Treatment of (13) in benzene with aluminum bromide gave (14) in 76% theoretical yield, with an equivalent amount of the thiol, 2-biphenylthiol (62JOC4111). Thus the iodine reagent is more efficient, since it oxidizes the mercaptan, formed by the Friedel-Crafts reaction of disulfide on the adjacent aromatic ring, to disulfide for further reaction, and also serves as a catalyst for the initial reaction. 

Both the 2-thiahex-5-enyl and the 2-sulfonylhex-5-enyl radicals exhibit a significant preference for 5-exo cyclisa-tion to the thiophene over formation of tetrahydrothiopyran by 6-endo ring closure (Equation 144) <2000TL7987> and only at higher I2 concentration does the formation of tetrahydrothiopyrans compete successfully with thietane and tetrahydrothiophene production when methylene-intermpted dienoates 455 react with dimethyl disulfide (Equation 145) <1994TL5575>. 

Octahydro- (we have used this nomenclature throughout) or perhydrobenzo[c]thiophene (35) exists as the cis and trans isomers and is more commonly named 2-thiahydrindane or 8-thiabicyclo-[4.3.0]nonane. Each stereoisomer may be prepared by treating the corresponding isomer of l,2-di(bromomethyl)cyclohexane with sodium sulfide (details of the products are given in Table IV).45 Cyclization of the cis isomer may be effected partially with thiourea via the formation of cis-hexahydro-o-xylylenebis(isothiouronium bromide) with sodium disulfide it gives a mixture of cis-octahydro-benzo[c]thiophene and cis-2,3-dithiadecalin.46 Optically pure ( —)-(8 R,9I )-lran -octahydrobenzo[c]thiophene has been prepared from (+ )-dicarboxylic acid via reduction of the diacid to the diol, tosylation, and ring closure of the bistosylate with sodium sulfide.47... 

Oxidative ring closure of enethiols (a-thioketocarboxylic acid) (46), which proceeds via disulfides, produces thiophenes (47) in good yields (Equation (5)) <86EUPI58380,88JHC367). 

The reaction of diethyl 3,4-dimethylthieno[2,3-Z ]thiophene-2,5-dicarboxylate (117, R = Me, EWG = C02Et) with hydrazine hydrate afforded dihydrazide 231, which was subjected to various transformations. For example, the reactions with acetylacetone, ethyl acetoacetate or malononitrile (93BCJ2011) are accompanied by the closure of the exocyclic pyrazole ring to form the corresponding derivatives 232-234. The reaction of dihydrazide 231 with carbon disulfide in the presence of KOH followed by decomposition with dilute HCl or concentrated H2SO4 produces di(oxadiazole) (235) or di(thiadiazole) derivative (236). Condensation of di(oxadia-zolyl)thienothiophene 235 with hydrazine hydrate affords di(triazolyl)thienothio-phene 237. 

Hydrodesulfurization [HDS, Eq. (1)] is the process by which sulfur is removed from fossil materials upon treatment with a high pressure of H2 (3.5-17 MPa) at high temperature (300-425 °C) in the presence of heterogenexius catalysts, generally transition metal sulfides (Mo, W, Co, Ni) supported on alumina [1]. About 90% of the sulfur in fossil materials is contained in thiophenic molecules, which comprise an enormous variety of substituted thiophenes, and benzo[b]thiophenes, di-benzo[b,d]thiophenes as well as other fused-ring thiophenes, most of which are generally less easily desulfurized over heterogeneous catalysts than any other sulfur compound in petroleum feedstocks (e.g., thiols, sulfide, and disulfides). 

The mechanism of oxidative ring closure of compounds of the 1,3-butadiene-1-thiol type with halogens to give thiophen derivatives has been studied by Chapman.A polar mechanism has been assumed, although a free radical mechanism is not completely ruled out and, indeed, is proposed for the cycliza-tion under other conditions. Thus, photolysis of the disulfide 124 in boiling xylene gives the thiophen 125 in 40% yield the proposed mechanism is depicted in Scheme 59. Such a mechanism involves efficient cyclization toward the (Cy5) compound in a Cy5/Cy4 case and the conversion of the (Cy 5) radical into a thiophene. 

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