Benzo thiophenes halogenation

Halogens react with benzo[ ]furan by an addition-elimination mechanism to give 2- and 3-substituted products (76JCS(P2)266). Treatment of benzo[ ]thiophene with chlorine or bromine in acetic acid gives predominantly 3-substituted products (71JCS(B)79). 2,2,3,3,4,5,6,7-Octachloro-2,3-dihydrobenzothiophene is obtained when benzo[ ]thiophene is treated with chlorine in the presence of 1 equivalent of iodine (80JOC2151). 

Italian authors227 found the following order of decreasing reactivity in halogenation and acylation a-position in thiophene > /3-position in benzo[ ]thiophene > a-position in benzo[6]thiophene > /3-position in thiophene. 

A halogen attached to position 2 of benzo[ > ]thiophene can be selectively removed in the presence of a 3-halogen atom by H2/Pd or Zn/HOAc. Dehalogenation of a 3-halo derivative can be accomplished using Na/Hg or HI (70AHC(11)177). 

Benzo(6]thiophene halogenation, 57, 294 iodination, 59, 254 resonance energy, 56, 352 Ru, Ir complexes, 58, 150 Benzo[6]thiophene, 3-benzoyl-, reaction with hydrazine, 56, 128 Benzo[l)]thiophene, 3-bromo-, chlorination, 57, 293 Benzo[6]thiophene, 4-fluoro-, 60, 17 Benzo[/>)thiophene, 4,5,6,7-tetrafluoro-2,3-dihydro-2-methyl-, 60, 28 Benzo(e]thiophenes, resonance energy,... 

In a competitive halogen-Li exchange reaction, it has been found that 4-bromo-3-methyl-benzo[(>]thiophene exchanges much faster than 6-bromo-3-methylbenzo[Z>]thiophene this has been attributed to the relief of steric strain in the former <85H(23)2391 >. In 2,4- or 2,6-dibromo-benzo[(>]thiophene, selective removal of the 2-bromo substituent is possible. Treatment with one equivalent of Bu"Li followed by hydrolysis gives 4- or 6-bromobenzo[Z>]thiophene <85H(23)239l>. 

Metalation and Halogen-Metal Exchange.—Metalation of benzo[ >]thiophen with organolithium compounds occurs in the a-position and is therefore of great synthetic importance, as electrophilic substitution predominantly occurs in the j8-position. 

By introducing reasonable values (about 2 for nitrogen, 4 for oxygen) for the electron affinity parameter relative to carbon, 8, and for the induced electron affinity for adjacent atoms (32/8i = Vio), we have shown that the calculated permanent charge distributions for pyridine, toluene, phenyltrimethylammonium ion, nitrobenzene, benzoic acid, benzaldehyde, acetophenone, benzo-nitrile, furan, thiophene, pyrrole, aniline, and phenol can be satisfactorily correlated qualitatively with the observed positions and rates of substitution. For naphthalene and the halogen benzenes this calculation does not lead to results... 

Controlled chlorination of benzo[6]thiophene gives 3-chlorobenzo[6]thiophene similarly, the 3-bromo derivative can also be obtained (70AHC(ll)l77). Excess halogen leads to the 2,3-dihalo derivative. Iodination in the presence of HgO gives 3-iodobenzo[6]thiophene. 

Reaction of 5-bromobenzo[6]thiophene with one mole of n -butyllithium leads to 5-bromo-2-benzo[6]thienyllithium with two moles of n-butyllithium, the 2,5-dilithio derivative is formed (70AHC( 11)177). Monolithio derivatives of dibenzothiophene have been prepared by halogen-metal exchange from the 1-, 2- and 3-bromo compounds. Dilithio-dibenzothiophenes have also been prepared by the same procedure (74AHC(i6)l8i). 

Halogen-metal exchange can also be conveniently used to prepare lithium derivatives of benzo[7 ]thiophene. Some examples are shown in Scheme 168 <70AHC(ll)l77. ... 

Halogen Derivatives of Thiophenes and Benzo[6]thiophenes 3.15.9.6.1 Fluorine derivatives... 

The use of modern physical methods (NMR, UV, and IR spectroscopy, mass spectrometry, and gas-liquid (GLC) and thin-layer (TLC) chromatography is becoming increasingly noticeable. By 19522 few systematic studies of the preparation of derivatives of benzo [6]thiophene had been undertaken, no attempt had been made to alkylate benzo[6]thiophene by means of the Friedel-Crafts reaction, and Friedel-Crafts acylation had been little studied. Halogenation of benzo[6]thiophene had only been superficially investigated and... 

The halogenation of substituted benzo[6]thiophenes containing other functional groups is discussed in the relevant sections. 

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