3-Acetylbenzo thiophene

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. 

Sulfonation of benzo[6 ]thiophene with concentrated sulfuric acid in acetic anhydride at 20 °C gives a mixture which is chiefly the 3-sulfonic acid, with some 2-isomer and 3-acetylbenzo[6 Jthiophene (70AHC(i)l77). Chlorosulfonation of 2- or 3-methyl-benzo[6 Jthiophene gives the corresponding 3- or 2-sulfonyl chloride in satisfactory yield. The various available 4-, 5-, 6- and 7-mercaptobenzothiophenes or sulfides (Section 3.15.9.5.2) can be oxidized to sulfonic acids or sulfones by conventional means. 

Acetylbenzo[6]tellurophene is also formed in isolable quantities. Benzo[6]selenophene is converted into 2-acyl derivatives by reaction with acid chlorides in the presence of aluminum chloride, whereas similar Friedel-Crafts acylation of benzo[6]thiophene yields 3-substituted products. When the 2-position is blocked, formylation can be directed into the 3-position. Thus treatment of 2-bromobenzo[6]selenophene with dichloromethyl butyl ether (Cl2CHOBu) and titanium tetrachloride yields the 3-formyl derivative (72BSF3955). If the 2- and 3-positions of benzo[6]selenophene are blocked with methyl groups, acylation under Friedel-Crafts conditions occurs in the 6-position (78CR(C)(287)333>. 

When a cyclization reaction leads to mixtures of two isomeric benzo[6]thiophenes, their relative proportions are readily estimated by examination of the 1H NMR spectrum of the mixture.96 104-106 Mixtures obtained by acetylation98 and bromination 76,90 reactions and by Baeyer-Villiger oxidation of acetylbenzo[6]thiophenes107 have been similarly analyzed. The 19F NMR spectra of several polyfluoro-benzo[6]thiophenes have been examined,103,108-m and used to study the reaction of 4,5,6,7-tetrafluorobenzo[6]thiophene with nucleophiles.108 The tautomerism of 2-amino-,112-114 3-N-phenylamino-,116 and 3-hydroxybenzo[6]thiophene109,116-117 derivatives has been studied by 7H NMR spectroscopy. 

There is surprisingly little reliable information on the sulfonation of benzo[6]thiophene or its derivatives. Benzo[6]thiophene is more readily sulfonated than naphthalene.699 Reaction with concentrated sulfuric acid at 80° gives a mixture of mono-, di-, and trisulfonic acids, reaction with 70% sulfuric acid at 80° gives a monosulfonic acid,699 and reaction with 18% oleum gives a disulfonic acid 86 in each case the orientation of the products is unknown. Treatment of benzo[6]thiophene with concentrated sulfuric acid in acetic anhydride at 20° gives 3-acetylbenzo[6]thiophene (ca. 10%) and a sulfonation product (isolated as the potassium salt), which was believed to be the 3-sulfonic acid.660 Recently, the sulfonation product has been shown to contain the 2- (8%) and 3-isomer (92%), by conversion into the sulfonyl chlorides and reduction to a separable mixture of 2- and 3-mercaptobenzo[6]thiophene.84... 

The formation of naphtho[6c]thiophene-3-ones 106 takes place on acylation of 2-substituted benzo[b]thiophenes 103 with cinnamoyl chloride (78AP710, 78LA627 79LA965). Interestingly, the aromatization of the intermediate 105 occurs with elimination of benzene. Chalcone 104 also may be obtained on acetylation of benzo[fe]thiophene 103, followed by condensation of benzaldehyde with the methyl group of the 3-acetylbenzo[b]thiophene intermediate (79LA965). 

Structures such as 8.18 and 8.19 must have real significance, as shown by the positional yields in nitration of 3-nitrobenzo[b]thiophene (8.25) (68MI5) and of 3-acetylbenzo[6]thiophene (8.26) [70JCS(C)933], though it... 

Benzo[ 7]thiophen-3-yl)pyrrole (37) and 2-(benzo[ 7]thiophen-3-yl)-N-vinylpyrrole (38) were synthesized directly from 3-acetylbenzo[ 7] thiophene oxime (39) and acetylene in 68% yield (Scheme 7) (09CEJ5823). Devinylation of pyrrole 38 led to the corresponding IH-pyrrole 37 in 63% yield. 

The UV absorption of isomeric acetylbenzo[b]thiophenes has been discussed as a means of complementing the NMR method72 for locating the position of an acetyl substituent.110 The spectra of 2,3-dihydrobenzo[h] thiophene 1-oxide111 and 1,1-dioxide112 have been investigated. 

Theoretical aspects of UV-PE spectra have been discussed in Section II,A. Photoelectronic spectroscopy can give information on molecular conformation, as well as on electronic structures. Thus, it has been deduced that 2- and 3-acetylbenzo[fr]thiophenes are planar, whereas the 2-phenyl derivative is not.33... 

A green one-step protocol for the preparation of substituted 2-acetylbenzo[fc] thiophenes from 2-acetylbenzo[l)]thiophenes and 2-ace-tyl-3-aminobenzo [It] thiophenes was described by cyclocondensation of... 

SCHEME 1.61 Synthesis of 2-(benzo[f>]thiophen-3-yl)-N-vinylpyrrole from 3-acetylbenzo[h]thiophene oxime and acetylene. 

SCHEME 1.62 Two-step synthesis of 2-(benzo[b]thiophen-3-yl)pyrrole via O-vinyl oxime of 3-acetylbenzo[b]thiophene. 

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