Thieno furan

Thieno[3,4-c]furan dipole moment, 4, 1049 (74JA1817) Thieno[2,3-d]pyridazine... 

Thieno[3,4-d][l,3]dithiol-2-one, 1-nitro-synthesis, 6, 1013 Thieno[3,4-c]furan, 4,6-dichloro-synthesis, 6, 1013 Thieno[3,4-c]furan, tetraphenyl-formation, 4, 1060 synthesis, 4, 1060 UV spectra, 4, 1044 Thieno[3,2-6]furans structure, 4, 1039 synthesis, 6, 1020 Thieno[3,4-c]furans... 

N. A-Diethyl-2.3-dihydro-8//-thieno[2,3-r/]azcpin-7-amine (20), which is obtained in 49 % yield by photolysis of 6-azido-2,3-dihydrothiophene in a mixture of diethylamine and tetrahydro-furan. on treatment with bromine yields the fully unsaturated derivative 21.1,4... 

Gol dfarb and Kondakova obtained, by hydrolysis of 2,5-di-r-butyl-3,4-bischloromethylthiophene (125), a product with m.p. 220°-221°, first thought to be 4,6-di-r-butyl-li/,3ff-thieno[3,4-c]furan. However, NMR and IR spectra and molecular weight measurements demonstrated later l,3,7,9-tetra-l-butyl-4i/,6//,10i/,12i/-dithieno[3,4-c 3, 4 -/i](l,6]-dioxecin (126) structure [Eq. (39)]. 

Novitskii, Khachaturova and Yur ev obtained 4i/,6/f-thieno[3,4-c]-furan (128) from 3,4-bischloromethylfuran (127) and sodium sulfide. The thienofuran (128) was converted into an adduct (129) with maleic anhydride and into 3,4-dimethylfuran (130) by desulfurization with Raney nickel [Eq. (40)]. 

Reduction of the furan (152) with sodium borohydride gave diol 154 and its cyclization (P2SJ/CS2) formed 19% of sulfide (155). Periodate oxidation of 155 gave (92%) the corresponding sulfoxide (156). The latter reacted with dimethyl acetylenedicarboxylate forming the adduct 157 (70%) the formation of 157 is evidence of the presence of the thieno[3,4-c]furan system (158) as an intermediate. Cyclization of diketone 153 in the presence of phosphorus pentasulfide proceeds M. P. Cava and M. A. Sprecker, J. Amer. Chem. Soc. 94, 6214 (1972). 

The lability of thieno[3,4-6]thiophene (3) and other iso-annelated systems, such as benzo[c]thiophene and benzole] furan, may be due to the strain effect (Mills-Nixon effect see also Zwanenburg et alP and references therein) in the condensed five-membered ring. The stability of the iso-annelated dithienothiophenes 7—9 is noteworthy. Simple LCAO MO method calculations on benzo[c]thiophene indicate that its instability is due to low specific delocalization energy and high free valence index at position 1. 

Svoboda and co-workers studied substitution reactivity of thieno[3,2- ][l]benzofuran 61 <1997CCG1468> in comparison with the isomeric [l]benzothieno[3,2-. ]furan 60, which was already described <1993CCC2983>. They discovered that under electrophilic substitution conditions, the system 61 is more stable than 60. 

The furo[3,4- ]pyrroles 132, 133 <2002TL6983>, thieno[2,3-f]furan 134, <1996JOC6166>, and furo[2,3-f]pyrrole 135 <1995T193>, which are mostly less stable than the benzo-fused analogues, were trapped by Diels-Alder reactions with dienophiles followed by elimination of water to give the corresponding indoles 136-139, 140, 141, and benzothiephenes 142, 143, and 144 with good to excellent yields (Scheme 13). 

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>. 

Annelation of a furan ring onto a thiophene is also possible by flash vacuum pyrolysis at 650 °C of the acrylate 368 and malonate 369, which gave 2-(methylthio)thieno[3,2-/ ]furan 370 and methyl-5-(methylthio)thieno[3,2- ]furan-2-carboxylate 371, respectively, in yields of 21% and 22% <1997J(P1)2483>. 

Dichloro-5-methoxyphenyl)amino]thieno[3,2- ]pyridine-6-carbonitriles substituted with heteroaryl groups at position C-2, 160, have been found to inhibit Src kinase activity. The highest activity in Src and cell assays has been found with a 2,5-furan or 2,5-pyridine substituent at C-2 <2005BML4681, 2005JME3891>. 

Other rings have been fused onto thieno[2,3-f]pyridazines. The reaction of 48 with ethyl chloroacetate provides a fused furan derivative 49 (Equation 19) <1999M1117>. 

Fusion of thiophene to a furan nucleus gives rise (inter alia) to the two positional isomers" 345 (thieno[2,3-c]furan) and 346 (thieno[3,4-c]furan). 

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 method has been extended to o-hydroxyaryl ketones for the synthesis of naphtho[l,2-6]furanes,656 thieno[3,2-e]benzofurans,657 furo-flavones,658 furoxanthones,659 furoquinolines,611,660 phenanthrofur-ans,660 and other complex benzofurans.661... 

Thieno[3,2- >]furan Thieno[3,2- >]pyrrole Selenolo[3,2-6]thiophene... 

Thieno[3,4-6]furan Thieno[2,3-c]pyrrole SeIenoIo[2,3-c]thiophene... 

Thieno[3,4-c]thiophene Selenolo[3,4-c]thiophene Thieno[3,4-c]furan... 

The diols (266) upon treatment with P4S10 gave the cyclic sulfides (267). Conversion to the sulfoxide, followed by Pummerer dehydration with acetic anhydride, produced the unstable thieno[3,4-c]furan (127), isolated as its N- phenylmaleimide adduct (268) while the thienopyrroles (12) and (13) were sufficiently stable to permit isolation (Scheme 92) (75ACR139). The thienofuran (127) was also generated under base-catalyzed Pummerer... 

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