3-Bromobenzo thiophene

Bromobenzo [ ] thiophene 1,1-dioxide 117 and 3-bromo-2-phenylbenzo-[b]thiophene 1,1-dioxide 119 reacted with ammonia and primary and secondary amines to give the corresponding 3-aminobenzothiophene dioxides, 118 and 120, in good yields (Scheme 68) [17, 192-194]. 2-Benzoyl-3-chloro-benzo[ ]thiophene 1,1-dioxide 121 also reacted with a series of nitrogen nucleophiles to give substitution products 122 in good yields (Scheme 69) [195]. 

Through direct trifluoromethylation, 7-methyl-3-trifluoromethyl-benzo[f>]thio-phene 179 was prepared in 54 % yield from 7-methyl-3-bromobenzo[( ]thiophene 59. The reaction took place with sodium trifluoroacetate and copper(I) iodide in N-methylpyrrolidone at 180 °C [35]. 

There has been surprisingly little interest in this area. Spectra of the following have been recorded aryloxy, arylthio, arylsulfonyl, and dialkylamino derivatives of 2,3-dimethylbenzo[ ]thiophene92 2-bromobenzo[ ]thiophene-3-carboxaldehyde and 2-bromo-3-(dibromomethyl)benzo[Z>]thio-phene93 several chloro- and phenylbenzo[b]thiophenes and their... 

During nitration of several amino derivatives, diazotisation and oxidation occurred to produce internal diazonium phenoxide compounds. 5-Acetylamino-3-bromobenzo[h ]thiophene unexpectedly underwent hydrolysis, diazotisation and oxidation to the explosive compound below. 

Electrophilic halogenation processes can involve conventional mechanisms with a carbocation intermediate, or pathways that are of the addition-elimination type. Sometimes the process does not go beyond the addition stage there are also examples of halodehalogenation in which the displaced halogen attaches elsewhere in the ring, as in the chlorination of 3-bromobenzo[fe]thiophene to give 2-bromo-3-chlorobenzo[6]thiophene as one of the products (73IJS233). 

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). 

JOC4257). In the reaction of monobromo compounds (486) and (487) with piperidine, the major products are normal ones with 3-bromobenzo[6]thiophene (487) a small amount of the cine substituted product (489) is formed (Scheme 166). 2,3-Dibromobenzo[f>]thio-phene (488) initially gives the 2-piperidino-3-bromo derivative (490) at 106 °C, which is debrominated to (489) at 180 °C. This result suggests that the small amount of (489) from (487) might arise through a transbromination-debromination sequence (73JOC1365). 

Thiophene is known to be oxidized to 2,2 - and 2,3 -dithienyls in the presence of palladium salts (78DOK(241)148). The coupling may proceed through the 7r,o--intermediate (507). Finally, the PdCl2-assisted conversion of 3-bromobenzo[6]thiophene to 3-deuteriobenzo[6]thio-phene by NaBD4 has been reported (73TL4699). 

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... 

The addition of hydrogen bromide and sulfur dioxide to phenylpropiolic acid (210) in diethyl ether at -50 °C is reported to give 3-bromobenzo[6]thiophene-2-carboxylic acid (211) (75ZOR1776). If hydrogen bromide and sulfur dioxide can react under these conditions to give thionyl bromide, the reaction is similar to the reaction of thionyl chloride with unsaturated acids, reported in the previous section. 

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). 

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>. 

Prominent bands in the vapor phase UV spectra of 3-chloro-,179 5-chloro-,180,181 and 7-bromobenzo[6]thiophene181 have been tentatively assigned. Spectra of substituted benzo [6]thiophenes in various solvents have been recorded but not examined in detail data for a number of monosubstituted derivatives have been collected in Table I. 

This hetaryne may have been handled in 1933 by Komppa and Weckman 405 when 3-bromobenzo[6]thiophene was heated with ethanolic potassium hydroxide at 200° to give a mixture of starting material (4%), benzo[6]thiophene (65%), and thiooxindole (15%). In 1954, Brower and Amstutz406 treated 3-bromobenzo[6]thiophene with piperidine at 255° and obtained a mixture of benzo[6]thiophene and 2-piperidinobenzo[6]thiophene. It is possible that these reactions involve the formation of benzo[6]thiophyne (123) as an intermediate they have not been reinvestigated so far as we are aware. However, it is more probable that they proceed via an AEa mechanism.4068... 

Bromination of 2-methyl-,447, 481 7-methyl-,78,478 5-bromo-,76 2-fluoro-,482 or 2-phenylbenzo[6]thiophene483 in either chloroform or carbon tetrachloride gives the 3-bromo compound in each case. 2-(2-Naphthyl )benzo[6]thiophene is brominated,54 chlorinated, and iodinated484 in the 3-position. In the cases of 3-methyl-485 and 3-bromobenzo[6]thiophene,107 bromination takes place in the 2-position. Bromination of 2,3-dimethylbenzo[6]thiophene in dilute chloroform solution at 0° gives mainly nuclear substitution in the 6-position,81 but chlorination in acetic acid causes substitution in the 2-methyl group, to give 2-chloromethyl-3-methvlbenzo[6]thiophene.419... 

The Hunsdiecker reaction has been used only twice as a potential source of bromobenzo[6]thiophenes with 3-bromo-5-nitrobenzo[6]-thiophene-2-carboxylic acid it proceeds normally to give 2,3-dibromo-5-nitrobenzo[6]thiophene,152 but with 5-nitrobenzo[6]thiophene-2-carboxylic acid the main product is 3-bromo-5-nitrobenzo[6]thio-phene-2-carboxylic acid, accompanied by smaller amounts of 2,3-dibromo-5-nitrobenzo[6]thiophene.152 497... 

Bromo-,54,81,294,302,337,483,512,513 and less frequently, chloro-benzo[6]thiophenes81 are readily converted into the corresponding nitriles by heating them with cuprous cyanide in a suitable solvent. 2-Bromobenzo[6]thiophene may be smoothly converted into 2-methoxybenzo[6]thiophene183 or 2-piperidinobenzo[6]thiophene406 by heating it with sodium methoxide in the presence of cupric oxide... 

V-Substituted 3-aminobenzo[6]thiophenes are readily obtained by heating thioindoxyl with the appropriate primary or secondary aromatic amine,539 541,553,554 or primary aliphatic amine541 (Section VI, 1,2). 3-A7,jV-I)ialkylaminobemo[ ]thiophenes are best obtained by reaction of 3-bromobenzo[6]thiophene-1,1 -dioxide with a secondary aliphatic amine, followed by reduction of the product with lithium aluminum hydride (Section VI,P,2,/).541 3-Amino-2-nitrobenzo[6]-thiophene and its A-substituted derivatives are conveniently obtained... 

Bromination and nitration of 5-acetamidobenzo[6]thiophene422 and its 2-carboxylic acid,497 and bromination of 5-aminobenzo[6]-thiophene,422 its 2-carboxylic acid,497 and its 3-bromo derivative,152 take place in the 4-position. 5-Amino-4-bromobenzo[6]thiophene is brominated in the 6-position, whereas 5-acetamido-4-bromobenzo[6]-thiophene is brominated in the 3-position.152 Treatment of 5-acet-amido-3-bromobenzo[6]thiophene with an excess of nitric acid in hot... 

Catalytic cyclodehydrogenation of 5-amino-2-ethylthiophenol affords 6-aminobenzo[6]thiophene.239,241 6-Acetamido-2,3-di-bromo-,77 6-acetamido-2-bromo-3-methyl-,102 6-acetamido-3-bromo-2-methyl-,102 and 6-acetamido-3-bromobenzo[f>]thiophene107 may be obtained from the corresponding 6-acetyl compound by means of the Schmidt reaction. In some cases the 6-acetamido compound is accompanied by a smaller amount of the amine sulfate.102,107 6-Aminobenzo[6]thiophene may be converted into 6-chloro- or 6-cyanobenzo[6]thiophene by means of the Sandmeyer reaction.241... 

Methoxybenzo[ >]thiophene may be prepared by treating 2-bromobenzo[6]thiophene with sodium methoxide it is metallated by n-butyllithium, and undergoes electrophilic substitution in the 3-position.183... 

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. 

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