Thieno thiophenes formation

The thermolysis of 2-(propargylthio)thiophene (350) and the 3-isomer (351) in the presence of diisopropylamine in a polar solvent such as DMSO led to the formation of the thienothiophenes (56) and (356) in yields of 53% and 65%, respectively. The by-products of these reactions were the thienothiopyrans (354) and (355), which could be conveniently eliminated by treatment with potassium f-butoxide prior to workup. A thio-Claisen rearrangement of (350) and (351) could lead to the presumed allenic thione intermediates (352) and (353), which then rearrange to the observed products (Schemes 121 and 122). In the absence of the amine catalyst, only thienothiopyrans were formed. The ratio of thieno-thiophene to thienothiopyran in the reaction mixture was dependent on the nature of the amine and the solvent used. Diisopropylamine favored the formation of thienothiophenes in... 

An extremely interesting example of electrocyclic thiophene formation is the intramolecular closure of a tropolone to form a thieno-fused bicyclic derivative this compound may be induced to undergo photochemical isomerization to produce a novel thienopyridine derivative (Scheme 6)... 

Electrooxidation of l,3,4,6-tetraaryl-2k482-thieno[3,4-c]thiophenes85 causes a thiophene ring to open with formation of y-keto thioketones. 

A thiophene ring can also be produced from two methylene groups. Here 2,5-dicarbethoxy-3,4-dicyanomethylthiophene 19 reacted with sulfur mono-chloride to give tetrasubstituted thieno[3,4-c]thiophene 20 in moderate yield (2002JCX72453). A mechanism for the thiophene 20 formation was proposed and 1,2-dithiine derivative 21 was likely to be an intermediate (Scheme 10) because sulfur monochloride gave higher yields of 20 than SCl2. At the next step (21 20), sulfur monochloride apparently acted as an oxidant. 

The formation of thieno[3,2-6]thiophene (2) together with thieno[2,3-6]-thiophene (1) in reactions of citric acid with PjSj or of acetylene with sulfur was first suggested by Anschutz and Blhc us. ... 

Challenger and Harrison found both thienothiophene 1 and its isomer 2 in the products of the reaction between acetylene and sulfur. To identify these compounds, Challenger et developed syntheses of unsubstituted and 2-alkyl-substituted thieno[3,2-f>]thiophene (2) from thiophene derivatives. Cyclization of (3-thienylthio)acetic acid in the presence of sulfuric acid gave 2,3-dihydrothieno[3,2-6]thiophen-3-one (22) (R = H) in 14% yield reducing the latter with lithium aluminum hydride resulted in thienothiophene (2) formation in 80% yield [Eq. (9)]. Similarly 2-methyl- and 2-ethyl-2,3-dihydrothieno[3,2-/>]thiophen-3-one were obtained from a-(3-thienylthio)propionic and a-(3-tWenylthio)-butyric acids in 30% and 27% yields, respectively their reduction yielded 2-methyl (32%) and 2-ethylthieno[3,2-6]thiophenes (52%). The parent acids were prepared from 3-mercaptothiophene. ... 

Continuing their search for ways to synthesize this system. Cava and Husbands " allowed tetrabenzoylethane (146) to react with phosphorus pentasulfide in refluxing xylene to obtain 46% of 1,3,4,6-tetraphenyl-li/,3if-thieno[3,4-c]thiophene (147) oxidized with periodate the latter yielded the sulfoxide (148), which was dehydrated with acetic anhydride to produce the stable l,3,4,6-tetraphenylthieno[3,4-c]thiophene (149) (87%). The latter is obtained in one step, in about 3% yield, by the reaction of tetrabenzoylethane (146) with phosphorus pentasulfide in refluxing xylene, along with the formation of 147 (30%). A mixture of two ad-... 

Finally, in this section of syntheses from thiophenes, a catalytic one-step meftod for the preparation of thieno[3,2-2>]thiophene (2) should be mentioned. Reaction of 2-ethylthiophene with SOj over CrjOj/AljOj at 450° afforded a 13% yield of thienothiophene 2, together with thiophene, 2-methylthiophene, 2-vinylthiophene, and 2-aceto-thienone [Eq. (45)]. Under these conditions formation of the isomeric thieno[2,3-6]thiophene (1) was not observed. 

The formation of a radical-anion with a very short lifetime on the surface of a sodium-potassium alloy during the reduction of thieno[3,2- ]-thiophene (2) at —100° was established by ESR (theoretical and experimental spectra are presented). The formation of the thieno[2,3-61-thiophene (1) radical-anion even under such extreme conditions was not observed. The difference in the stability of radical-anions of thienothiophenes 1 and 2 was accounted for by a greater degree of conjugation in thienothiophene 2 molecule as compared to 1. The spectrum of the thienothiophene 2 radical-anion distinctly exhibits two types of hydrogen atoms with coupling constants 4.87 and 0.52 Gauss. The... 

Beckmann rearrangement (SOClj/McjCO) of the oximes of 2-acetyl-thieno[2,3-6] and [3,2-6]thiophene leads to the formation of 2-acetamidothienothiophenes identical with those obtained by reductive acetylation (Hj/Ni/AcjO) of the 2-nitro compound. ... 

As Stated in the previous section, reduction of thieno[3,2-2 ]thiophene (2) with Na-K alloy at —100 results in the formation of a radical-anion. With AlClj in nitromethane at —20°, or SbClj in methylene chloride at —60°, a radical-cation was obtained. The experimental hyperfine splitting constants (HFSC) data are shown in Eq. (73). 

Thieno[2,3- ]pyrrole derivatives 462 were easily synthesized in two different ways using phenyl isothiocyanate and activated methylene compounds (Scheme 55) <2001SL1731>. The relative order of thiophene or pyrrole ring formation was investigated <2003T1557>. 

Thieno[3,4-3]thiophenes 500 were prepared from thiophen-3-yl-substituted [l,3]dithiol-2-ones 496 in good yields <2003JOG7115>. The photochemical irradiation of 496 leads to thieno[3,4-f]dithiines 497 via a unique ring cleavage reaction and subsequent reductive treatment of dithiines 497 proceeds to give 2,3-dihydrothieno[3,4-/ ]thiophenes 498 and 499. Heating of 499 in the presence of further iodomethane leads to the formation of the thieno[3,4-/ ]-thiophenes 500 (Scheme 63). 

The coupling reaction of Fischer carbene complexes, 96, with 3-alkynyl-2-thiophene carboxaldehyde leads to the formation of thieno[2,3-c]pyranones (Scheme 25) <2001TL777, 2002JOC4177>. This reaction is applicable to the oxygenated derivatives. 

Analogs of 457 that possess a sulfur atom at position 2 have also been prepared in a similar way <2002MI717>. The use of thiophene isothiocyanates has also been valuable in the formation of thieno[3,2-t/ pyrimidines. Treatment of 458 with (A)-(- -)-2-amino-l-propanol at reflux in the presence of KOBu produces 459a (Equation 171). 

In one route, tidopidine (1) was assembled via Sn2 displacement of 2-chlorobenzyl chloride (9) with 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (8). " The nucleophile 8 was synthesized by heating 2-thiophen-2-yl-ethylamine (6) with 1,3-dioxolane in the presence of concentrated hydrochloric acid. 1,3-Dioxolone gave better yields than with formaldehyde, paraformaldehyde and 1,3,5-ttioxane. The interesting transformation 6 —> 8 first involved the formation of the corresponding Mannich base 7, which then underwent a Pictet-Spengler type reaction to afford the ring-closure product 8. It was of interest to note that a possible intramolecular aminomethylation did not take place. 

The first example of a [2 + 4] cycloaddition of a thiophene 1-oxide seems to be the formation of a 1 1 mixture of the syn and anti isomers of 3-(2,4,6-trimethylphenyl)-8b-methylbenzo[6]thieno[2,3-mesitonitrile oxide with 3-methyIbenzo[6]thiophene 1-oxide (Scheme 190) (79TL4845). The cycloaddition seems to be regioselective. 

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