Thienothiophenes oxidation

Unsubstituted thieno[3,4-6]thiophene (3) (see Litvinov and Fraenkel ), was prepared by Cava and Pollack s method for benzo[c]-thiophene i.e., thermal decomposition of H, 3 -benzo[c]thiophene sulfoxide. By refluxing 4/f,6/f-thieno[3,4-ft]thiophene-2-carboxylic acid 5-oxide (91) with acetic anhydride (the synthesis of dihydrothieno-thiophenes will be described below), Wynberg et a/." obtained the mixed anhydride 92 in 95% yield. Hydrolysis gave thieno[3,4-6]-thiophene-2-carboxylic acid (93) (88%). Decarboxylation of the acid (93) gave thienothiophene 3, unstable at room temperature [Eq. (29)]. 

Zwanenburg and Wynberg also proposed another route to the thienothiophene (112). 2,5-Dibromo-3,4-bisbromomethylthiophene (116) was cyclized with sodium sulfide to give 4,6-dibromo-l f,3/f-thieno[3,4-c]thiophene (117) in 60% yield 117 was then reduced to thienothiophene (112). l,3,7,9-Tetrabromo-4i/,67f,10.H, 12ff-dithieno-[3,4 C 3, 4 -/i][l,6]dithiecin (118) (18%) was also formed during the ring closure. Oxidation of thienothiophene (117) followed by reduction by zinc in acetic acid gave l/f,3H-thieno[3,4-c]thiophene 2,2-dioxide (119). ... 

Dihydrothieno[3,4-Z ]thiophene (131) was prepared by two methods. In the first (Scheme 8), chloromethylation of methyl thiophene-2-carboxylate (132) forms methyl 2,3-bischloromethyl-thiophene-5-carboxylate (133) (85%) cyclization of 133 with sodium sulfide in methanol yields (66%) methyl 4,6-dihydrothieno[3,4-i]-thiophene-2-carboxylate (134). Peroxide oxidation of 134 gives 2-methoxycarbonyl-4,6-dihydrothieno[3,4-h]thiophene 5,5-dioxide (135) and hydrolysis of 134 followed by metaperiodate oxidation furnishes the sulfoxide (91). Thienothiophene (131) was produced by hydrolysis and decarboxylation of 134. As indicated above, the sulfoxide (91) was used for the synthesis of thieno[3,4-6]thiophene (3). 

In 1967 Cava and Pollack obtained derivatives of the fourth, so-called nonclassical , thienothiophene— thieno[3,4-c]thiophene (4), a condensed heterocycle with formdly tetracovalent sulfur (42)j. The reaction of 3,4-bischloromethyl-2,5-dimethylthiophene (141) with sodium sulfide afforded 4,6-dimethyl-lif,3ff-thieno[3,4-c]thiophene (142) periodate oxidation of 142 gave die corresponding sulfoxide (143) in 91% yield. Attempts to convert the sulfoxide (143) into the thieno-[3,4-c]thiophene by the method used for S3mthesizing benzo[c]-thiophene led only to polymer. However, 24% of adduct 144 and 10% of 145 were obtained by refluxing sulfoxide (143) with N-phenylmaleimide in acetic anhydride, indicating that the thieno[3,4-c]-thiophene was formed as an intermediate. 

The presence of benzo[6]thiophene in commercial naphthalene, its possible contamination with isomeric thienothiophenes 1 and 2, and their ability to poison aromatic hydrogenation catalysts led Maxted and Walker to develop detoxification by a preliminary short hydrogenation, in which thienothiophenes 1 and 2, and benzo[6]-thiophene are adsorbed on the catalyst. This is followed by their hydrogenation products that can easUy be oxidized with hydrogen peroxide or permolybdic acid to nontoxic sulfones subsequent hydrogenation of the aromatic hydrocarbons is then performed as usual. 

It was also shown, by Challenger and Gibson, that the carboxylic acids formed on oxidation of 2-acetylthieno[2,3-6]thiophene and on metalation of thienothiophene 1 followed by carbonation, were identical. 

Similarly, acetylation of thieno[3,2-6]thiophene (2) afforded 2-acetyl-thieno[3,2-6]thiophene, which was converted into methyl n-hexyl ketone by desulfurization with Raney nickel. Oxidation of 2-acetylthieno-[3,2-i]thiophene followed by nitration gave 5-nitrothieno[3,2-6]-thiophene-2-carboxylic acid. Decarboxylation of the latter furnished 2-nitrothieno[3,2-ft]thiophene identical with the compound obtained by direct nitration of thienothiophene 2 [Eq. (60)]. 

Gol dfarb and Litvinov first formylated a thienothiophene. In Vilsmeier formylation of 2-ethylthieno[2,3- ]thiophene (20) the formyl group enters the vacant a-position, producing 5-ethyl-2-formylthieno-[2,3- ]thiophene 16%). Oxidation of the latter with silver oxide gives 5-ethylthieno[2,3-6]thiophene-2-carboxylic acid (55) identical with that formed by cydizing the ester of (5-ethyl-3-formyl-2-thienylthio)acetic... 

Unsubstituted thienothiophenes 1 and 2 are smoothly formylated in the 2-positions by DMF-phosphorus oxychloride in dchloro-ethane. The site of substitution in thienothiophene 2 was confirmed by preparing the corresponding formyl derivative from 2-lithiothieno-[3,2-6]thiophene and DMF, and in the case of 1, by oxidizing the formyl derivative to thieno[2,3-h]thiophene-2-carboxylic acid, as well as the NMR spectra [Eqs. (66) and (67)]. 

Oxidation of acetyl- and acetylnitro-substituted thienothiophenes 1 and 2 with ferricyanide or hypoiodite to the corresponding acids was used primarily to confirm the site of electrophilic substitution at position 2 in the thienothiophenes. " Permanganate degrades the thieno[3,2-A]-thiophene (2) ring system, while potassium hypobromite produced bromo derivatives of thieno[2,3-6]thiophene-2-carboxylic acid. ... 

In 1948 Maxted and Walker studied the detoxification of catalyst poisons in the hydrogenation of aromatic hydrocarbons and found that the isomeric thienothiophenes 1 and 2 could be converted into the sul-fones of fully hydrogenated thienothiophenes 1 and 2, which do not poison the catalysts. This conversion is performed by brief preliminary hydrogenation and subsequent oxidation by hydrogen peroxide or per-molybdic acid. However, no data on the isolation or foe properties of these disulfones are available. It has been reported that direct oxidation of thienothiophenes 1 and 2 does not produce sulfones. 

The reduction of thienothiophene 2 with Na-K alloy produced a radical-anion (see Section III,D), and a radical-cation resulted from oxidation with AlCl, in nitromethane or SbCl, in methylene chloride (see Section IV,B 5). No such conversion was observed in the case of thienothiophene 1 this is explained by the extended conjugation throughout the thienothiophene 2 molecide, impossible in thienothiophene 1. 

Iodination and chlorination have been considerably less studied. Data on iodination are limited to those of Challenger and co-workers, who showed that thienothiophenes 119 and 220 with iodine and mercuric oxide give rather unstable 2-iodo derivatives, the structures of which were confirmed by their conversion into the corresponding 2-carboxylic acids.20 The formation of 2,5-diiodothieno[3,2-6]thiophene by iodination of 2 was also observed.22... 

Thienothiophenes 1 and 2 with ethylmagnesium bromide afford organometallic derivatives that can be carbonated to form the 2-carboxylic acids identical with those prepared by oxidation of the 2-acetyl derivatives.19-21,26,218 Thieno[3,2-i]thiophene-2,5-dicarboxylic acid was obtained analogously in the reaction of thienothiophene 2, using an excess of ethylmagnesium bromide.218... 

To construct additional heterocycles fused to the thienothiophene system, a number of approaches other than the above-mentioned photocyclizations were used. For example, heating 2-acetylamino-3-hydroxythieno[3,2-Z>]thiophene (206) in the presence of P2S5 afforded 2-methylthieno[3,2-fe]thieno[3,2-[Pg.158]

We have recently shown that 3,6-dimethoxythieno[3,2-h]thiophene 21 leads to a polymer presenting low oxidation potential and moderate bandgap (1.7 eV) [74]. The advantage of thienothiophene unit compared to bithiophene one resides in the planar structure and absence of positional isomers. Furthermore, the crystallographic structure of the dimer 22 (Figure 13.1), shows a hilly planar conjugated system stabilized by noncovalent intramolecular sulhir-oxygen interactions. 

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