Benzo thiophenes nitration

The fact that the a > p reactivity order parallels that in thiophene rather than benzo[ ]thiophene has also been observed in nitration and bromination [77CS( 12)97], and was regarded as being explicable only by sophisticated MO methods. However this is not necessary. Reference to Scheme 8.1 shows that in benzo[ ]thiophene, 3-substitution is favored over 2-substitution because both canonicals for the former are benzenoid, whereas only one is for the latter. If, however, a second thiophene ring is fused to the benzene ring, then because of the bond fixation in thiophene, the nonbenzenoid canonicals for 2-substitution become much... 

Nitration of benzo[6]thiophene (HNOs/AcOH) yields mainly the 3-nitro derivative. Under these conditions the /3 to a ratio of substitution is approximately 5 1, which is... 

Benzo[6]thiophene, 1,2-dimethyl-cycloaddition reactions with dichloroethene, 4, 793 Benzo[6]thiophene, 2,3-dimethyl-nitration, 4, 763... 

FIGURE 2.2 Transformation of (a) 5-aminonaphthalene-2-sulfonate, (b) benzo[fc]thiophene, (c) 4-chloro-biphenyl, (d) 4-nitrotoluene, (e) 3,5-dichlor-4-methoxybenzyl alcohol, (f) 2,3-diaminonaphthalene in presence of nitrate, and (g) 3,4-dichloroaniline presence of nitrate. 

There are examples of ipso attack during the nitration of pyrroles, furans and thiophenes and in the corresponding benzo-fused systems. Reactions resulting in nitro-dealkylation, nitrodeacylation, nitro-decarboxylation and nitro-dehalogenation are to be found in the monograph reactivity chapters of CHEC. Treatment of the 3-azophenylindole (64) with nitric acid in acetic acid at room temperature gives 80% of the 3-nitroindole (65) (81JCS(P2)628). 

The normal reactions of benzo[6]thiophene 1,1-dioxides have been reviewed (70AHC(11)177). Electrophilic substitution (nitration, bromination) takes place at position 6. 3-Halo derivatives undergo normal nucleophilic displacement reactions, but 2-bromobenzo[6]thiophene dioxide gives the 3-ethoxy derivative in ethanolic NaOH. The reaction of 3-methoxy derivatives with secondary amines can give rise either to enamines... 

Mononitration of benzo[6]thiophene gives a complex mixture in which the 3-isomer predominates (73% in acetic anhydride at 25 °C) and can be separated from other isomers, which may include 4-, 5-, 6- and 7-nitro derivatives. However, benzo[6]thiophenes with electron-donating groups at the 3-position, e.g. 3-methyl-, 3-acetamido- or 3-bromo-benzo[6]thiophene, are nitrated almost exclusively in the 2-position. 2-Nitro-benzo[6] thiophene may be prepared by debromination of 3-bromo-2-nitro-benzo[6 ]thiophene, or by decarboxylation of 2-nitrobenzo[6]thiophene-3-carboxylic acid (70AHC(11)177). 

Benzo[6 jthiophenes with nitro groups at the 4-, 5-, 6- or 7-positions may be synthesized by ring closure reactions of appropriately substituted benzene derivatives. Nitration of 5-acetaminobenzo[6]thiophene gives the 4-nitro derivative, which can be hydrolyzed and deaminated to yield 4-nitrobenzo[6]thiophene (equation 44). 5-Nitrobenzo[6]thiophene is conveniently available by decarboxylation of 5-nitrobenzo[6]thiophene-2-carboxylic acid, which in turn is available by a Perkin reaction of 4-nitro-2-formylphenylthioglycoIic ester (equation 45 Section 3.15.2.3). The 7-nitro isomer may be obtained similarly. 

Disubstituted Benzo[b]thiophenes 2,3-I)ibromobenzo[6]thiophene undergoes Friedel-Crafts acylation in the 6-position,77 but gives a mixture of the 4- and 6-nitro isomer on nitration.101 Similarly, 2,3-dimethylbenzo[b]thiophene undergoes Friedel-Crafts acetylation82,136,418 and bromination81 mainly in... 

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-... 

On heating a solution of 3,4-dibromo-4-nitro-4,5-dihydrobenzo[6]-thiophen-5-one (Section VI, 1,4) in benzene, 3-bromobenzo[6]thio-phene-4,5-quinone is obtained.497 The unstable product readily condenses with ethyl cyanoacetate in the presence of base to give 3-bromo-7-(carbethoxy cyanomethyl)benzo[6]thiophene-4,5-quinone. The 4-bromo-4-nitro-4,5-dihydrobenzo[6]thiophen-5-ones prepared by nitration of 3,4-dibromo-,152,421 4,6-dibromo-,152 3,4,6-tri-bromo-,421 and 2,3,4,6-tetrabromo-5-hydroxybenzo[6]thiophene421 decompose similarly to the corresponding 4,5-quinones on being boiled in benzene. 

Nitration of the sulfonation product of benzo[6]thiophene, followed by desulfonation of the resulting products, gives a mixture of nitro-benzo[6]thiophenes, the composition of which depends on the nitration conditions (Section VI, E, l).84... 

Hydrodesulfurization of the mixture of isomers obtained by the nitration of benzo[6]thiophene gives a mixture of amines, the identification of which indicates the possible orientations of the nitro groups.84,412 It should be noted, however, that 5- and 7-nitrobenzo[6]-thiophene both give m-ethylaniline in this reaction. 

Benzo[c]thiophene readily forms adducts with maleic anhydride (m.p. 153°-154°,5 6 148°-152°52), dimethyl acetylenedicarboxylate (see above),61 and A-phenylmaleimide (to give 62).52,61 In the last case the exo and endo isomers of the adduct may be separated by fractional crystallization.52 Benzo[c]thiophene reacts with acetyl nitrate by 1,3-addition in preference to substitution.6 It exhibits halochromy with concentrated sulfuric acid, trichloroacetic acid, and stannic chloride.62... 

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