Benzo thiophenes, hydroxy

A general route to both benzo[/)]furans and benzo[/>]thiophenes depends upon the cyclodehydration of either 2-hydroxy- or 2-sulfanylbenzyl ketones or aldehydes (Scheme 7.23a). 2-Acetylbenzo[6]furan can be obtained by reacting the sodium salt of 2-formylphenol with chloroace-tone (chloropropanone) (Scheme 7.23b). A similar reaction using sodium 2-formylbenzenethiolate yields 2-acetylbenzo[Z)]thiophene. 

Apart from a single claim to the contrary, most workers have shown spectroscopically (Section III,B) that 2- and 3-hydroxy -benzo[6]thiophene exist exclusively as their oxo tautomers. They are therefore more correctly called benzo[ ]thiophen-2(3 )-one (Chemical Abstracts uses this terminology) or 2,3-dihydrobenzo[6]thiophen-2-one and benzo[6]tbiophen-3(2/f)-one or 2,3-dihydrobenzo[6]thiophen-3-one, respectively. To avoid confusion, especially for derivatives of these compounds for which little is known of their spectroscopic behavior, we shall use the simpler nomenclature, thiooxindole and thioindoxyl, respectively. 

Nitro-, 5-hydroxy-, and 6-bromo-2,3-dihydro-benzo[ ]thiophene-... 

Unlike the hydroxy derivatives, no tautomerism tends to exist in the simple 2- and 3-thiophenethiols <1977ACB198>, nor in benzo[. ]thiophene-3-thiol <1970JC2431>. 

The drugs were dissolved in saline and stored in a concentration of 100 pmol/ml for subcutaneous (s.c.) and 50 pmol/ml for per oral (p.o.) administration and diluted, if necessary, with saline before administration. A volume of 1 ml/kg was administered for s.c. administration and 2 ml/kg for p.o. administration. The drugs that were used were 6-(N,N-di- -propylamino)tetrahydrobenzo[A]thiophene (34), 5-(N,N-di- -propylamino)tetrahydro-benzo[/)]thiophene (35), 5-hydroxy-2-(N,N-di- -propylamino)tetralin (5-OH-DPAT, 9), trans-2,3,4a,5,6,10b-hexahydro-4//-thianaphth[4,5e][l,4]oxazine (38) and /raws-N-w-propyl-... 

Reactions of the Side-chain of Benzothiophens.—The C n.m.r. chemical shifts in 2-benzo[ j]thenyl carbenium ions have been investigated.The thermal decomposition of 2-azidophenyl 2-(3-methylbenzo[ >]thienyl) sulphide and of 2-azidophenyl 3-(2-methylbenzo[ ]thienyl) sulphide proceeded efficiently through spiro-benzothiazolines to give (161) and (162). 5-Hydroxy-3-methyl-benzo[ ]thiophen-2-carboxylic acid is most conveniently decarboxylated by refluxing with 48% hydrobromic acid. The decomposition of benzo[/)]thiophen-2(3//)-one and of 3-diazobenzo[/ ]thiophen-2-one at high temperatures provided convenient syntheses of benzothiet and the transient benzothiet keten. The decomposition reactions were carried out in the reactor of a photoelectron spectrometer.Heterotriptycenes have been obtained from... 

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[6]thiophene, 2-acetyl-3-hydroxy-synthesis, 4, 892 Benzo[6]thiophene, 2-acyl-synthesis, 4, 918 Benzo[6]thiophene, 3-acyl-synthesis, 4, 918- 19 Benzo[6]thiophene, acylamino-synthesis, 4, 815 Benzo[6]thiophene, alkenyl-synthesis, 4, 917 Benzo[6]thiophene, 2-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 3-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 4-alkoxy-synthesis, 4, 930 Benzo[6]thiophene, 2-alkyl-synthesis, 4, 877-878 Benzo[6]thiophene, 2-alkylthio-synthesis, 4, 931 Benzo[6]thiophene, 2-amino-diazotization, 4, 810 reactivity, 4, 797 stability, 4, 810 synthesis, 4, 869, 924-925 tautomerism, 4, 38 Benzo[6]thiophene, 3-amino-cycloaddition reactions, 4, 68 synthesis, 4, 109, 881, 925 Benzo[6]thiophene, 4-amino-synthesis, 4, 925 Benzo[6]thiophene, 5-amino-synthesis, 4, 925 Benzo[6]thiophene, 7-amino-synthesis, 4, 925 Benzo[6]thiophene, 3-t-amyl-synthesis, 4, 915 Benzo[6]thiophene, 2-aryl-synthesis, 4, 881... 

Equilibrium and rate constants for the keto-enol tautomerization of 3-hydroxy-indoles and -pyrroles are collected in Table 32 (86TL3275). The pyrroles ketonize substantially (103-104 times) faster than their sulfur or oxygen analogues, and faster still than the benzo-fused systems, indole, benzofuran, and benzothiophene. The rate of ketonization of the hydroxy-thiophenes and -benzothiophenes in acetonitrile-water (9 1) is as follows 2-hydroxybenzo[b]thiophene > 2,5-dihydroxythiophene > 2-hydroxythiophene > 3-hydroxybenzo[/ Jthiophene > 3-hydroxythiophene. 3-Hydroxythiophene does not ketonize readily in the above solvent system, but in 1 1 acetonitrile-water, it ketonizes 6.5 times slower than 2-hydroxythiophene (87PAC1577). 

The method has also proved to be applicable to the synthesis of polycyclic benzofurans naphthofurans from suitable naphthols,215 benzodifurans from Bz-hydroxybenzofurans,219 naphthodifurans from hydroxylated naphthofurans,228 thienobenzofurans from Bz-hydroxy-benzo[6]thiophenes.218,229... 

Thiobenzophenone can also serve as a C3S intermediate in the synthesis of some benzo[c]thiophenes. The carbon source in this case is carbon monoxide. Reaction of various thiobenzophenones with diiron enneacarbonyl in benzene at room temperature produced a complex, Ar2CSFe2(CO)6, which could be oxidized to form 2-hydroxy-5-aryl-benzo[c]thiophenes (226e) in 60-80% yield (73JA4905). 

Oxygen-linked Thiophenes and Benzo[6]thiophenes 3.1S.9.4.1 Hydroxy thiophenes and hydroxybenzo[b]thiophenes... 

The UV spectra of benzo[6]thiophene-4,7-quinone and its 5-hydroxy derivative have been compared with those of their oxygen and selenium analogs.195... 

Reduction of the 2-arylidene-3-hydroxy-2,3-dihydrobenzo[ ]thio-phenes (26 R = R =C1, and R = C1, R = H) with sodium boro-hydride affords mixtures of the cis and Irons alcohols (27).222 The cis-trans isomerism exhibited by a number of 2-arylidene-2,3-dihydro-benzo[6]thiophen-3-ones (e.g., 28) and by two compounds with the... 

Tetrahydrobenzo[6]thiophen-4-one may be converted into 4-hydroxybenzo[6] thiophene by heating it with sulfur,453 or by catalytic dehydrogenation.454,455 5-Methyl- and 5-ethyl-4-hydroxy-benzo[6]thiophene may be prepared similarly.437... 

Hydroxy-,337-342 497 5-methoxy-,341 and 5-hydroxy-3-methyl-benzo[6]thiophene 343 are conveniently prepared by decarboxylation... 

O-Sulfonylation (MeS02Cl or PhCH2S02Cl/C5H5N) of 5-hydroxy-benzo[6]thiophene gives 5-methane- or 5-benzylsulfonyloxybenzo[6]-thiophene, respectively,337 and with epichlorohydrin it affords 5-(3-chloro-2-hydroxypropoxy)benzo[6]thiophene.613 Potential pesticides, analogous to those described in Section VI, 1,3, have been prepared from 5-hydroxybenzo[6]thiophene.610,612... 

Electrophilic substitution reactions of 5-hydroxybenzo[6]thiophene have been investigated in some detail. The 4-position is the most reactive toward nitration,152 nitrosation,497 bromination,422 and formylation (Duff procedure).338 Dibromination in the presence of acetate ion affords 4,6-dibromo-5-hydroxybenzo[6]thiophene,421,422, 497 and not the 3,4-dibromo derivative, as previously believed.542 Dichlorination similarly affords the 4,6-dichloro derivative,421 and not 4,4-dich loro-4,5-dihydrobenzo[6]thiophen-5-one, as reported earlier by Fries d al.542 An interesting comparison can be made between the behavior of 5-hydroxy benzo[6]thiophene and 2-naphthol in electrophilic substitution reactions. It is clear that both positions ortho to the hydroxyl group in 5-hydroxybenzo[6]thiophene are attacked, in contrast to 2-naphthol, where only the 1-position is attacked even in the presence of an excess of the reagent. Disubstitu-... 

Further bromination of 4,6-dibromo-5-hydroxybenzo[6]thiophene affords either of two products, depending on the presence or absence of acetate ion. In the absence of acetate ion, bromination is slow, and 3,4,6-tribromo-5-hydroxybenzo[6]thiophene is obtained.421 It is identical to the product of bromination of 3,4-dibromo-5-hydroxy-benzo[6]thiophene in the presence of acetate ion. In the presence of acetate ion, bromination of 4,6-dibromo-5-hydroxybenzo[6]thiophene is rapid, and 4,4,6-tribromo-4,5-dihydrobenzo[6]thiophen-5-one (244) is obtained. The latter compound is converted into starting material on treatment with sodium hydrosulfite, and into a mixture of 4,6-... 

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