5- thieno thiophenes

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... 

A similar method (Scheme 3) was used s for the third isomeric thieno-thiophene (3). 3,4-Dibromothiophene, obtained by detn-omination of 2,3,4,S-tetrabromothiophene, was converted by the method of Gronowitz et al. into 4-bromo-3-thiophenealdehyde and the corresponding acetal. 

In 1962 Gompper, Kutter, and Topfl prepared substituted thieno-thiophenes (1) from dithiocarboxylate s ts. With haloacetic acid derivatives these give ketenemercaptals (104), which are easily converted by base into 3-amino- and 3-hydroxythiophenes (105). Further cyclization of 105 results in substituted thienotMophenes 106, which may also be obtained directly by heating the dithiocarboxylates with haloacetic acid derivatives in alcoholic sodium alkoxide (Scheme 7). 

Substituting a formyl, carboxy, or carbalkoxy group into a thieno-thiophene or selenophenothiophene molecule has no substantial effect on Ae coupling constants but considerably affects the chemical shifts (see Litvinov and Fraenkel and Michael and Gronowitz ). The chemical shifts of the protons in the selenophene ring are characteristic of different t rpes of condensation of the thiophene and selenophene rings and increase in the order 15 > 14 > 16 irrespective of the solvent used (acetone, CCIJ. A similar sequence is observed in the carbonyl derivatives of the isomeric selenophenothiophenes. 

Calculations of the UV spectra of the isomeric thieno-thiophenes " indicate that, as in the case of thiophene,3d and higher sulfur orbitals hardly affect the electronic spectra of sulfur-containing condensed heteroaromatics. In the case of sulfones of thienothiophene 2 and dithienothiophenes 5-10 in which the sulfur... 

In a search for routes to periannelated systems containing a thieno-thiophene fragment, the reactions of 239 with primary amines (ethylamine, aniline, -nitroaniline, and cyclohexylamine) were studied. The ratio of dichloromethyl thienothiophene to amine varied from 1 1 to 1 4, but only diamines 242 were found, and no periannelated compounds of type 243 [Eq. (83)]. 

Systems outside the scope of this review are, for example (a) those in which no N-doublets contribute to the -system these include thieno-thiophenes 18 and 21 (cf. CKL Section III,H,4 and ref. 34) (b) compounds with sulfur or oxygen at the ring junction, such as trithiapentalenes (22)35 and 6a-thia-l,6-diazapentalenes (23),36 and (c) systems with a third fused heterocyclic ring, e.g., thiazolo 3,2-c]purines (24).37... 

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... 

The experimental data on the isomeric thienothiophenes 1-3 support these predictions. Electrophilic attack on thienothiophenes 1 and 2 results in 2-substituted compounds (see refs. 20, 21, 25, 28, 41, 218, 219). The second electrophilic substituent enters position 5. Thieno-thiophene 3 is attacked at positions 6 and 4 to give, for example, 4- and 6-formylthieno[3,4-6]thiophenes on formylation.167... 

Anilides and quinolones with nitrogen-bearing substituents and thieno-thiophene from benzo[ ]thiophenes and thieno[2,3-c]thiophenes have been prepared (14EJM267). Benzo[ ]thieno[2,3c]- and thieno[3, 2 4,5]thieno[2,3-c] quinolones were prepared by the reaction of photochemical dehydrogenation from corresponding anilides. The compounds were tested for anti-cancer activity as well as DNA-binding propensities topoisomerases inhibition. 

B. S. Lee, V. Seshadri, H. Palko, G. A. Sotzing, Ring-sulfonated poly(thieno-thiophene), Advanced Materials 2005, 17, 1792. 

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. 

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