Thieno furans, preparation

Thieno[3,2- ][l]benzofuran 61 was synthesized on a preparative scale starting with benzo[/ ]furan-2-carbaldehyde 344. Condensation of aldehyde 344 with 2-thioxothiazolidin-4-one in the presence of sodium acetate in acetic acid afforded 345, which by base-catalyzed hydrolysis gave 346 in good yield. Upon treatment with bromine, acid 346 was cyclized to give acid 347, which on standard decarboxylation by treatment with copper in quinoline afforded 61 in high yield (Scheme 35) <1997CCC1468>. 

Thieno[2,3-c]furans have also been prepared in situ by the Pummerer-rearrangement cyclization reaction (96JOC6166). For transient generation of thieno[2,3-c]furans see also Kuroda et al. [91JCS(CC)1635]. These compounds proved to be reactive intermediates for inter- and intramolecular Diels-Alder reactions (see Section IV). 

The parent thieno[3,4-6]furan (21) is known <86TL3045> and some of its more stable derivatives have been prepared and their reactions studied <86JCS(Pl)2223>. 

The thieno[2,3-Z ]furan-2-sulfonamides (346) (Scheme 28) have been prepared and evaluated as topical carbonic anhydrase inhibitors <91JMC1805>. 

A total synthesis of the mold metabolite ethisolide <86TL445> (404) has been described. Two reduced thieno[3,4-/>]furan systems have been prepared to test their value as food flavorings (405) <70GEP(0)1964803> and as antiinflammatory agents (406) <73GEP(O)2238204>. 

The thieno[2,3-6]furan-2-sulfonamides (11), thieno[2,3-6]thiophene-2-sulfonamides, and thieno-[3,2-6]thiophene-2-sulfonamides were prepared and found to be a new class of topically active ocular hypotensive carbonic anhydrase inhibitors (91JMC1805,92JMC3027). 

Treatment of 2-(l,2-dibromoethenyl)quinoxalines 57 with Na2CS3 affords thieno[2,3- ]quinoxalines 59. Addition of the thiocarbonate to the side chain generates 58. Intramolecular cyclization of 58 with loss of CS2 and NaBr leads to 59 (Scheme 14) <2001J(P1)154>. Azulenothiophenes 61 are prepared from azulene derivatives 60 by the reaction with thioacetamide (Scheme 15) <2002H(58)405>. Similar reactions of furyl ketones 62 afford thieno[3,4-3]furans 63 <1998JHC71>. 

Condensation of benzo[fr]furan-3(2H)-one with 1 in acetic acid in the presence of triethylamine afforded 2-(3-benzo[fr]furyl)dimedone 481, which upon acylation with acid anhydrides in the presence of 70% perchloric acid led to the corresponding tetrahydrobenzo[t>]furo[2,3-cJ-pyrylium perchlorate 482 (94CHE283). Similarly, benzo[fr]thieno[2,3-c]-pyrylium perchlorate 484 (94CHE283) and benzo[t>]seleno[2,3-cJpyrylium salt 485 were prepared (94CHE283). 

Banks M.R., Barker J.M. and Huddleston P.R. (1986) Preparation and some reactions of substitued thieno[3,4-b]furans. J. Chem. Soc, Perkin Trans. 2223-32. 

Acid catalysed cyclisation of the substituted furans 20 led to formation of the spiro-systems 21 and 22, the latter being formed preferably <97TL7641>. Other syntheses involving the intermediacy of an oxonium ion include the preparation of thieno[2]azepines <97JHC1494>, l,2,3,4-tetrahydro-5//-l-benzazepine-6,9-quinones <97H(45)1703> and a new synthesis of ( )-cis- and ( )-/ra 8-clavicipitic acid <97T51 >. 

Extrusion of sulfur dioxide from oxidized thiophene derivatives is an exceptional method to prepare cis-dienes as components for Diels-Alder reactions. An example of this approach utilizes the Diels-Alder reactivity of the furan ring in substituted 4//,6ff-thieno[3,4-c]furan-3,S-dioxides to react with a variety of dienophiles such as DMAD, dimethyl maleate and dimethyl fumarate which then lose SO2 to form another reactive diene (Eq. 17) <94H961>. A review of the preparation and use of 4i/,6f/-thieno[3,4-c]furan-S,5-dioxides as well as other heteroaromatic-fused 3-suIfolenes is report <94H1417>. The preparation of dihydrothienooxazole 80 requires the careful control of the reaction time and temperature as well as the reactants molar ratio <94JOC2241>. Specific control of the alkylation conditions for 81 (X = COCH3) allows for the preparation of either 1,4-disubstituted or 1,6-disubstituted 4, 6//-thieno[3,4-c]furan-S,S-dioxides. These molecules could be used as intermediates for the preparation of novel pentacyclic compounds <94JCS(P1)1371>. 

Thieno[3,4-c]furans.— Tetraphenylthieno[3,4-c]furan (68), the first reported member of this system, has been prepared in solution by heating the sulphoxide (67) in acetic anhydride. A violet compound, it could not be isolated, but when generated in the presence of dimethyl acetylenedicarbox-ylate it formed the adduct (69). 

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