Benzo thiophene, hydrogenation

Biocatalytic asymmetric oxidation of 2,3-dihydrobenzo[. ]thiophene to (—)-(lJ)-sulfoxide in excellent yield has been reported. The enzyme used is a chloroperoxidase from the marine fungus Caldariomycesfumago. This enzyme is relatively stable and does not require any cofactor. Hydrogen peroxide was the oxygen source. Using this system, 2,3-dihydro-benzo[. ]thiophene was converted to the (—)-(i )-sulfoxide in 99.5% yield, with an ee of 99%. Similarly, 1,3-dihydro-benzo[f]thiophene could be oxidized to the corresponding sulfoxide in 80% yield <1998CH246>. 

Of the three possible substrates, thiophene, benzo[ ]thiophene, and dibenzo[, thiophene, benzo[ ]thiophene is the most easily hydrogenated to the dihydro derivative this is ascribable to the more pronounced olefinic character of the C(2)-C(3) double bond in benzo[, ]thiophene as compared to that in thiophene. There is no example in the literature of the hydrogenation of dibenzothiophene either to the tetrahydro or the hexahydro stage. The hydrogenation of benzol ]thiophene is catalyzed by transition metals such as Ru, Os, Rh, and Ir. An excellent overview of homogeneous catalytic hydrogenation of thiophenic substrates has been presented recently <2004JOM (689)4277>. 

Benzo[ ]thiophene 1,1-dioxide 38 and its derivatives act as typical a, ft-unsaturated sulfones, and a variety of nucleophiles add to the carbon atom at the 3-position. Thus, amines and the conjugated bases of water, alcohols, thiophenol, and diethyl malonate all add to 38 to give the corresponding adducts 110 in excellent yields (Scheme 65) [189]. Even hydrogen bromide can add to 38. When 2-bromobenzo[b]thiophene 1,1-dioxide 111 was treated with piperidine and morpholine under appropriate conditions, excellent yields of adducts 112 were isolated without being accompanied by dehydrobromination (Scheme 66) [190]. 

Benzo[fr]thiophene 1,1-dioxide and its derivatives are reduced to the corresponding 2,3-dihydro derivatives by catalytic hydrogenation in good yields (Scheme 94). In this reduction, the sulfonyl moiety remains unchanged [13,189, 238, 239]. However, reduction of benzo[ ]thiophene 1,1-dioxide with LiAlH4 affords deoxygenated 2,3-dihydrobenzo[ ]thiophene in 79% yield [233]. Benzo[fr]thiophene 1,1-dioxide was also reduced to the 2,3-dihydro derivative by an electrochemical method (Scheme 95) [240]. 

Ionic hydrogenation has been referred to in CHEC-I <84CHEC-I(4)741>. Logically, this has to find a place in this section, since it represents reaction of a thiophenium ion with a hydride ion derived from triethylsilane. This has been reviewed <85HC(44/i)457>. Reduction of 5-hydroxy-benzo[ >]thiophene with triethylsilane in TEA has given the 2,3-dihydroderivative <91SC959>. 

Benzo[h]thiophene itself reacts slowly under ionic hydrogenation conditions to give 2,3-dihydrobenzo[h]thiophene, whereas 2-alkyl or 3-alkyl benzo[( ]thiophenes are readily reduced. As shown in Table 3, the ionic hydrogenation of... 

As might be anticipated from the behaviour of the parent heterocycles, C-2 of indole, benzo[i]furan and benzo[i]thiophene (Table 13) is shifted to lower field than C-3. However, the shifts for C-2 (O, 144.8 Se, 128.8 S, 126.1 NH, 124.7 Te, 120.8) and C-7a (O, 155.0 Se, 141.3 S, 139.6 NH, 135.7 Te, 133.0) in the benzo[i] heterocycles vary irregularly (80OMR(l3)3l9), and the sequence is different to that observed for C-2 in the parent heterocycles, namely 0>Se>Te>S>NH. Also noteworthy is the upheld position of C-7, especially in indole and benzofuran, relative to the other benzenoid carbons at positions 4, 5 and 6. A similar situation pertains in the dibenzo heterocycles (Table 14), where not only are C-1 and C-8 shifted upheld in carbazole and dibenzofuran relative to the corresponding carbons in dibenzothiophene and fluorene, but similar, though smaller, shifts can be discerned for C-3 and C-6 in the former compounds. These carbon atoms are of course ortho and para to the heteroatom and the shifts reflect its mesomeric properties. Little variation in the carbon-hydrogen coupling constants is observed for these dibenzo compounds with V(qh) = 158-165 and V(c,h) = 6-8 Hz. 

Smirnov-Zamkov et al. have shown that sulfur dioxide and hydrogen bromide react with alkynes with phenylacetylene derivatives, such as the sulfonamide (42), a benzo[b]thiophene (43) is formed.50 The mixture of sulfur dioxide and hydrogen bromide appears to behave like thionyl bromide, cf. thionyl chloride (see Section V,B). 

Meyer et a/. obtained in low yields thiophene, 2-methylthiophene, benzo[6]thiophene, traces of thienothiophene 1, and some other products on passing a mixture of acetylene, hydrogen (or methane), and hydrogen sulfide at 640°-670° through a tube filled wth FeSj. 

The presence of benzo[6]thiophene in commercial naphthalene, its possible contamination with isomeric thienothiophenes 1 and 2, and their ability to poison aromatic hydrogenation catalysts led Maxted and Walker to develop detoxification by a preliminary short hydrogenation, in which thienothiophenes 1 and 2, and benzo[6]-thiophene are adsorbed on the catalyst. This is followed by their hydrogenation products that can easUy be oxidized with hydrogen peroxide or permolybdic acid to nontoxic sulfones subsequent hydrogenation of the aromatic hydrocarbons is then performed as usual. 

For benzo[Z ]thiophene the heterocycle is rather more resistant to ring opening and oxidation with hydrogen peroxide in acetic acid at 95 C, for example, gives the 1,1-dioxide (Scheme 7.22) reduction with either sodium and ethanol or triethylsilane in trifluoroacetic acid affords 2,3-dihydrobenzo[Z)]thiophene. Electrophiles give mainly 3-substituted benzo[Z ]thiophenes, although these products are often accompanied by smaller amounts of the 2-isomers. 

Electron-withdrawing substituents seem to stabilize the benzo[cjfuran system as they do in the analogous benzo[c]thiophene and benzo [c]indole series. l-Cyano-3-phenylbenzo[c]furan (128) was obtained from the aldehyde 127 as stable yellow needles hydrolysis with base yields the carboxylic acid (129). Catalyzed hydrogenation of these cornpounds leads to 1,3-dihydrobenzo[c]furans (130, R = CH2NH2, COOH = Ph). Increased... 

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