Benzo thiophenes, preparation from

Some Benzo[6]thiophenes Prepared from the 2- or 3-Lithio Derivative... 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of S02 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide122. When 1,3-dihydro-l-(4-pentenyl)benzo[c]thiophene 2,2-dioxide (201) prepared from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and 4-pentenyl bromide is heated in di-n-butyl... 

The formation of l-lithio-.io so. si.ssi 2.iithio-, and 3-lithiodibenzothiophene has been achieved by translithiation of the appropriate bromodibenzothiophene (Section VI, C, 3) with butyllithium. Higher yields of derivatives are obtained from 2-lithiodibenzothiophene by conducting the reactions at 0° rather than at room temperature. The comparatively low yield of compounds derived from 3-lithiodibenzothiophene at 0° may indicate that even lower reaction temperatures are required for this particular isomer, reduced yields probably being due to ortho-translithiation to the thermally stable 4-lithiodibenzothiophene (cf. the instability of 3-lithio-benzo[6]thiophene at 0° ). Both 2-lithio- and 3-lithio-4-methyldibenzo-thiophene have been prepared from the respective bromo compound, and a similar synthesis of 1 -lithio-4-methoxydibenzothiophene has been described. ... 

Silica gel is an effective catalyst for the t-butylation of thiophene and benzo[/ ]thiophene using t-butyl bromide. 2,5-Di-r-butylthiophene and 3-f-butylbenzo[b]thiophene can be prepared easily by this procedure (84JOC4161). Alkylation of thiophene with f-butyl chloride, isopropyl chloride or ethyl chloride at - 70°C in the presence of A1C13 produced a-complexes under kinetic control. On thermal equilibration, migration of alkyl from position 3 to position 2, as well as disproportionation to dialkyl-and trialkyl thiophenes can occur (86T759). 

Alternative methods of preparing the starting acids can be used, but are generally less convenient. Benzo[6 ]thiophene derivatives were prepared from 2-methyl-3-(2 -thenoyl)propionic acid, which was obtained either by reacting 2-thienylmagnesium iodide with methylsuccinic anhydride, or by coupling 2-bromoacetylthiophene with the sodium salt of diethyl methylmalonate (45JA1645). 

The 3-acylbenzo[6]thiophenes, separated from the mixture obtained on acylation of benzo[6]thiophene (Section 3.14.2.4), are readily reduced to 3-alkylbenzo[6]thiophenes. 3-Benzo[6 ]thienyllithium can be prepared from 3-bromobenzo[6]thiophene at -70 °C (68JCS2733) and this may serve as a source of 3-acylbenzo[Z>]thiophenes. In certain instances, Friedel-Crafts alkylation gives the 3-substituted benzo[6]thiophenes nearly exclusively. For example, 3-t-amylbenzo[6]thiophene was the exclusive product of alkylation of benzo[6 Jthiophene with t-amyl alcohol in the presence of tin(IV) chloride <70AHC(11)177). 

Robba and coworkers succeeded in preparing the o-quinonoid thieno[3,4-with hydrazine (equation 35) (67BSF2495). Compound (314) is obtained as yellow crystals with m.p. 135-136 °C. Compared with benzo[c ]thiophene the stability of (314) is considerably increased. Thieno[3,4-prepared from the corresponding aldehydic acids of thiophene and hydrazines. 

The synthesis of benzo[6]thiophenes by the PPA-promoted cyclization of (arylthio)acetaldehyde dimethyl or diethyl acetals [Eq. (4)] was introduced by Tilak287, 288 in 1950 and improved in 1951.289 The acetals are readily prepared from aryl mercaptans and bromo-acetaldehyde dimethyl (or diethyl) acetal in the presence of sodium ethoxide, or by reaction of an aryllithium compound with [(MeO)2CHCH2S]2.290 Diethyl acetal as starting material sometimes gives better yields of product than the corresponding dimethyl acetal.291 Optimum yields of benzo[6]thiophenes are obtained when cyclization of the acetals is carried out under reduced pressure so that the lower boiling benzo[6]thiophenes distill as soon as they are formed. Experimental conditions for obtaining optimum yields vary from case... 

Tetrahydrobenzo[6]thiophen-4-one (103) may be prepared from y-(2-thienyl)butyric acid by cyclization with phosphoric acid854 or by Friedel-Crafts cyclization of the corresponding acid chloride.194, 355.358 j s 5-methyl,357 2-ethyl,194 2-isopropyl,358 2- and 3-tert-butyl,359 2,3-dimethyl,360 2-ethyl-3-methyl,360 and 2-bromo 354 derivatives and diethyl 4,5,6,7-tetrahydrobenzo[6]thiophene-4,5-di-carboxylate861 may be prepared similarly. 4,5,6,7-Tetrahydrobenzo-[6]thiophen-7-one (104)357 362,863 and its 5- and 6-methyl 357 and 2-chloro 362 derivatives are obtained from the appropriately substituted y-(3-thienyl)butyric acid, A recent patent 364 describes the vapor phase cyclization of y-(2-thienyl)butyric acid to 103. Ketones (103 and 104) are useful intermediates for the synthesis of 4- and 7-substituted benzo[6]thiophenes, respectively their reactions are discussed in Section VI, B, 4. 

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... 

Hydroxybenzo[6]thiophene has been isolated from coal tar.42 It may be prepared from 6-aminobenzo[fr]thiophene by standard procedures.241 6-Methoxybenzo[h]thiophene may be prepared by decarboxylation of the corresponding 2-carboxylic acid,341 and 6-ethoxybenzo[6]thiophene is obtained by reduction of 6-(ethoxy)-thioindoxyl (Section VI, 1,2). 6-Methoxy-5-methylbenzo[6]thiophene is obtained by cyclization of (3-methoxy-4-methylphenylthio)-acetaldehyde dimethyl acetal (Section IV,B).617 The product previously described542 as 6-hydroxy-3-phenylbenzo[6]thiophene has now been shown to be the 2-phenyl isomer.307 6-Methoxy-818 and 6-methoxy-5-methyl-benzo[6]thiophene617 are demethylated by pyridine hydrochloride. 

Hydroxy benzo[6]thiophene-4-carboxaldehyde, which is prepared from 5-hydroxybenzo[6]thiophene by the Duff reaction 338 or, better, by a modified Gattermann reaction,340 reacts with diethyl bromo-malonate to give the thienobenzofuran (282), and undergoes the Perkin reaction to give the thienobenzo-a-pyrone (283).338... 

Aminobenzo[6]thiophene-2-carhoxylic acids are conveniently obtained by reduction of the corresponding nitro compound.152,185,333, 334,33c, 338,497 Djazotization of these, followed by the usual replacement reactions of the diazonium group, provides many substituted benzo[6]thiophene-2-carboxylic acids, decarboxylation of which leads to some otherwise rather inaccessible benzo[6]thiophenes. 5-Hydroxy-benzo[6]thiophene-2-carboxylic acid is most conveniently prepared from the corresponding amino compound by means of the Bucherer reaction,338,497 in which the dicarboxylic acid (303) is formed as a by-product.152... 

The sulfones of 4-benzo[6]thienyl-ZV-methylcarbamate and its 2,3-dihydro derivative possess insecticidal activity.610 Several mero-cyanine dyes have been prepared from thioindoxyl-1,1-dioxide,735 736 and a number of 2-arylbenzo[6]thiophene-l, 1-dioxides are fluorescent and are useful commercially (e.g., as dyes 737 and in photographic films738). 2-(p-Isocyanatophenyl)benzo[6]thiophene-l, 1-dioxide has been incorporated in copolymers of use in the printing industry-302... 

Diiodobenzo[f ]thiophene is prepared by treating the bis(mercuric chloride) derivative with iodine. Benzo[ >]thiophenes having an iodine atom at the 4-, 5-, 6- and 7-positions are obtained in high yield from the appropriate diazonium salt by the usual replacement reactions. 

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