Thieno thiophene synthesis

Thieno[3,4-6]benzofuran, aryl-reduction, 4, 1074 Thieno[3,4-6]benzofurans synthesis, 4, 1074 Thienobenzo thiophenes synthesis, 4, 758... 

The authors of this review have developed a straightforward procedure for the synthesis of unsubstituted and alkyl-substituted thieno-thiophenes 1, 2, and 3 the method involves intramolecular condensation of ortho-bifunctional thiophene derivatives. Vilsmeier formylation of an alkyl (5-ethyl-2-thienylthio)acetate (53) furnishes the (5-ethyl-3-formyl-. 2-thienylthio)acetate (54) which when heated with alcoholic sodium... 

Rutherford, D.R., et al. 1992. Poly(2,5-ethynylenethiophenediylethynylenes), related heteroaromatic analogs, and poly(thieno[3,2-l ]thiophenes) Synthesis and thermal and electrical properties. Macromolecules 25 2294. 

S. Yoneda, K. Ozaki, A. Tsubouchi, H. Kojima and K. Yanagi, Tetrakis(alkylthio)thieno[3,4-c]thiophene-synthesis, stability and reactivity, J. Heterocycl. Chem., 25, 559-563 (1988). 

The thienothiophens, like thiophen, are smoothly metalated by ethereal butyl-lithium in the a-positions. By means of competitive metalation experiments, both thieno[2,3-Z>]thiophen and thieno[3,2-Z>]thiophen were found to be about six times more reactive. The unsymmetrical thieno-thiophen (296) gives the 4-lithio- and 2-lithio-derivatives in a 1 4 ratio. Also, (293) and (294) are smoothly metalated in the a-positions. Halogen-metal exchange between 2,3,5-tribromothieno[3,2-6]thiophen and butyl-lithium at — 70 °C followed by hydrolysis could be used for the synthesis of the 2,6-dibromo-compound. However, the same reaction with 2,3,5-tribromothieno[2,3-6]thiophen led to ring-opening. 

Hu S, Huang Y, Poss MA, Gentles RG (2005) A novel route to the 5,6-dihydio-4H-thieno[3,2-b]pyrrol-5-one ring system involving an intermediate substituted-thiophene synthesis. J Heterocyclic Chem 42 661-667... 

Thieno[3,2-h]thiinium perchlorates synthesis, 4, 1028 Thieno[3,2-c]thiinium perchlorates synthesis, 4, 1028 Thienothiinium salts, 4, 1027 synthesis, 4, 1028 UV spectra, 4, 1029 Thienothiins synthesis, 6, 1011 Thieno[2,3-h]thiophene, 2-acetyl-nitration, 4, 1054 Thieno[2,3-h]thiophene, 2-amino-synthesis, 4, 1070... 

Thieno[3,2-h]thiophene, 3-methyl-synthesis, 4, 1066 Thieno[3,2-h]thiophene, 2-phenyl-synthesis, 4, 1070 Thieno[3,2-h]thiophene, 3-phenyl-synthesis, 4, 1066... 

Thieno[3,4-h]thiophene, 2-methoxycarbonyl-formylation, 4, 1052 Thieno[3,4-c]thiophene, 1,3-dimethyl-synthesis, 4, 1058... 

The 2-(2-pheriylvinyl) derivative 18 and the thienyl compound 20 cyclize exclusively at the alkene carbon, and at the thiophene ring, to give 3,4-diphenyl-l//-2-benzazepine (19) and 4-phenyl-6-//-thieno[3,2-e]-2-benzazepine (21), respectively.48 A mechanistic rationale for these results has been offered. This method has been extended to the synthesis of 7Z7-pyrido[3,4-t/]-, 7//-pyrido[2,3-t/]- and 77/-pyrido[4,3-r/]benzazepincs and to other thieno- and furo-fused 2-benzazepines.244... 

E. Lim, B. Jung, and H. Shim, Synthesis and characterization of a new light-emitting fluorene-thieno[3,2-6]thiophene-based conjugated copolymer, Macromolecules, 36 4288-4293, 2003. 

This method has a general character, and was successfully applied to the synthesis of photochrome 166 containing fused thieno[3,2-b]thiophene... 

The synthesis of alkylated thieno[3,2-h]thiophenes (2) via a similar procedure was also studied. As stated above, existing methods for the preparation of a-alkyl-substituted thienothiophene 2 derivatives and thienothiophene 2 itself are inefficient. The reduction of 4-bromo-2-acetothienone (56) (prepared by bromination of 2-acetothienone )... 

Ortho-bi functional thiophenes provide the most convenient route to unsubstituted thieno[2,3-6]thiophene (1). 3-Bromothiophene yielded 3-thiophenealdehyde. The corresponding diethyl acetal, using the procedure for thienothiophene 2, led to thieno[2,3-6]thiophene (l) in about 40% yield based on 3-bromothiophene [Eq. (24)]. This method was also used by Gronowitz and Persson for the synthesis of thienothiophene 1. 

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)]. 

In 1972 Wright prepared 3-chlorothieno[3,2-6]thiophene-2-carbonyl chloride (94) in 11-13% yield by heating 3-(2-thienyl)acrylic acid, thionyl chloride, and pyridine, a method of synthesis of benzo[6]-thiophene-2-carbonyl chloride derivatives. " Methyl 3,5-dichloro-thieno[3,2-6]thiophene-2-carboxylate (95) and methyl 2-chloro-3-(5-chloro-2-thienyl)acrylate were also isolated. When fte reaction was carried out in refluxing toluene or chlorobenzene, the acid chloride (94)... 

Substituted 3-hydroxythiophenes are convenient starting-points for the synthesis of the thieno[3,2-Mthiophene system. Shvedov et obtained 50% of 3-chloro-3-ethoxycarbonyl-5-methylthiophene-2-aldehyde (110) from 3-ethoxycarbonyl-4-hydroxy-2-methylthiophene (109) by Vilsmeier formylation at 100°. Reaction with thioglycolic ter formed 3-ethoxycarbonyl-5-methoxycarbonyl-2-methylthieno[3,2-6]-thiophene (111) [. (36)]. 

To study the effect of ring strain (Mills-Nixon effect) on the properties of five-membered heteroaromatics, Wynberg and Zwanenburg developed a new synthesis of l/f,3H-thieno[3,4-c]thiophene (112) [Eq. (37)]. They obtained 3,4-dimethylthiophene-2,5-dicarboxylate (113) by... 

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 1973 Cava et al. reported the synthesis of 4,6-dimethyl-l/f,3if-thieno[3,4-c]thiophene (142) and l,3,4,6-tetraphenylthieno[3,4-cl-thiophene (149) ° as well as data on some chemicaJ conversions of the latter and the dehydration of 4,6-dimethoxycarbonyl-l/f,3H-thieno-[3,4-c]thiophene sulfoxide. Thienothiophene (149) was also obtained (42%) by Potts and McKeough by condensation of anhydro-4-hydroxy-2,3,5-triphenylthiazolium hydroxide with dibenzoylacetylene followed by reaction of the product with P S,. 

Alkyl aryl ketones are convenient intermediates for preparing other substituted aromatic and heteroaromatic compounds. Challenger and co-workers " acetylated thieno[2,3-h]thiophene (1) with acetyl chloride and stannic chloride [Eq. (59)]. The 2-acetylthieno[2,3-A]-thiophene obtained by this method was reduced to the 2-ethyl derivative (20) identical with the product of an independent synthesis. ... 

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