5- Arylation benzo thiophene

Intramolecular palladium catalyzed thio-enolate S-arylation has been used in a route to a set of fused benzo[ ]thiophenes, as illustrated by the conversion of the substrate 10 into the product 11 <06T11513>. 

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). 

Ring-closure techniques are more commonly used to obtain 3-alkylbenzo[6]thiophenes. Thus, acid-catalyzed cyclization of arylthio methyl ketones gives the 3-alkylbenzo[6]thio-phenes in good yield, with little rearrangement (equation 3). Formation of the 3-aryl-benzo[6]thiophenes by this approach is complicated, however, by rearrangement to the 2-isomer (Section 3.15.2.3.2). 3-Methylbenzo[f> Jthiophene is also obtained by decarboxylation of the corresponding 2-carboxylic acid (equation 4), readily available from ar-mer-captocinnamic acids (Section 3.15.2.1.1). 

The possibility of optical isomerism arising from restricted rotation (atropisomerism) about the 2,2 -bond in 3-substituted 2-(2-naphthyl)-benzo[6]thiophenes has been recognized by Lamberton and McGrail.54 Schuetz and Ciporin164 have interpreted the UV spectra of six 3-aryl-benzo[6]thiophenes according to a theory of steric hindrance to free rotation about the pivot bond of the two aromatic rings, but the results are now invalid, since some of the 3-arylbenzo[6]thiophenes used in this study have been shown to be the corresponding 2-isomers (see Section IV, C). No attempt appears to have been made to resolve compounds of this type. 

Ab initio MO calculations have been carried out on benzo[. ]thiophene (BT), 2-methylbenzo[/ ]thiophene (2-MeBT), 3-methylbenzo[ ]thiophene (3-MeBT), and a number of organometallic complexes containing these thiophenic moieties in an attempt to understand the usual preference for insertion of metal fragments into the sulfur-carbon(vinyl) bond of BT and the recent observations of insertion into the sulfur-carbon(aryl) bond <19980M3798>. 

At present the most robust photochromic molecules are diarylethenes with benzo-thiophene aryl groups [13]. They undergo more than 1.3 x 10" photochromic cycles in the presence of oxygen without destruction. Recently crystalline photochromic diarylethenes have been developed [57, 58] which could repeat the cycles more than 10 times. 

Examples of the former two reaction types are illustrated. An early Heck cyclization of 2-carboxy-2 -iododiphenylamine to 1-carbazolecarboxylic acid (73% yield) [346] has been generally overlooked by subsequent investigators. A microwave method is useful for the synthesis of azaindoles from aminopyridines and ketones [347], and a variety of cyclopent[/ ]indolones and carbazolones are available using this Heck chemistry [348, 349]. The requisite enamines can also be generated in situ by the addition of 2-haloani-lines to alkynes with TiC [350]. The aryl Heck variation affords carbazoles [351-353] including novel indolo[3,2-/ ]benzo[/ ]thiophenes [353]. 

Pharmacologically Active Compounds. - 2-Aryl-3-alkoxybenzo[Z)]thiophens have been shown to possess hypolipidemic activity. Alkyl and poly-halophenyl esters of benzo[ ] thiophen-3-carbamic acid show antibacterial and antifungal activities. Benzo[Z ]thiophen-3-sulphonamides show herbicidal activity. Derivatives of 2-cyano-3-hydroxybenzo[Z>] thiophen show sympatholytic activity. ... 

Ohta and co-workers carried out extensive studies on intermolecular arylation of various heterocycles (furan, thiophene, pyrrole, oxazole, thiazole, A-methylimi-dazole, benz[fe]oxazole, benzo[i>]furan, and benzo[ ]thiophene) with mainly chlo-ropyrazines as heteroaryl halides using Pd(PPh3)4 and AcOK [3]. 

Benzo[ ] thiophene (18) is arylated with the aryl bromide 17 as expected at C-2 to afford 19 [3b], Intramolecular 3-arylation of the thiophene in 20 gave the tetracyclic /S-lactam 21 containing thiophene in the presence of TI2CO3 as a base [6],... 

Reactions and Reactivity.— Thiophens can be induced to behave as dienes in Diels-Alder reactions at high pressure, as in the reaction between thiophen itself and maleic anhydride in dichloromethane at 100 and IS kbar, which gives the adduct (27). Aromatic hydrocarbons (ArH) can be added across the 2,3-bond of benzo[6]thiophens under Friedel-Crafts conditions at low temperatures, giving the adducts (28) and (29) at higher temperatures the main product is a 2-aryl-benzo[6]thiophen. ... 

Reaction at Sulphur.—The oxidation of benzo[6]thiophens to sulphoxides by t-butyl hypochlorite has been studied. In the presence of a ruthenium catalyst, dibenzothiophen was oxidized by oxygen to the sulphone. The reactions of benzo[ >]thiophen 1,1-dioxides with various reagents such as amines, amino-alcohols,3-aminopropylsilanes, and aromatic sulphonyl chlorides have been studied. Four detailed papers on the reaction of dibenzophenonium salts with aryl-lithiums have appeared in which the mechanism of ligand exchange was elucidated. " ... 

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

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... 

Benzo[6]thiophene, 3-aryl-2-methyl-1,1-dioxide synthesis, 4, 930... 

Diacyl-3,4-dihydroxythiophenes have been formulated as dienol tautomers (77T191). The same holds for 2,5-diaryl- and 5-aryl-2-carboxy derivatives (91JHC1449). ESR investigations of 6-halogeno-benzo[h] thiophene-2,3-semidiones (Scheme 13) have been reported (81JOC751). 

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