2.5- Dibromo-3-substituted thiophenes

The electrochemical conversion of 2,5-dibromo-3-substituted thiophenes to the corresponding thienylzinc species has been achieved by a similar method in an undivided cell fitted with a zinc sacrificial anode using catalytic amounts of NiBr2(bpy) as the catalyst43. The overall reaction giving (11) and (12) is presented in equation 35. The results are reported in Table 3. 

Analysis of the above methods for the synthesis of thienothiophenes and their analogues based on thiophene derivatives demonstrates that mono- and dibromo-substituted thiophenes are most often successfully used as the starting compounds. It should be noted that intramolecular cyclization of compounds derived from the above-mentioned thiophenes serves as the key step. In this step, vicinal carbonyl functions (generally, formyl or acyl) interact with fragments containing an activated methylene group. 

The synthesis of 4-substituted products from 2-acylfurans and 2-acylselenophenes is difficult. Their predominant formation was observed on bromination of aluminum chloride complexes of furfural and to a lesser extent of 2-acetylfuran (731ZV2733). Bromination of complexes of selenophene-2-carbaldehyde and 2-acetylselenophene with AICI3 leads mainly to 4-substituted derivative (exceeded 70%) (95JHC53). In all cases a significant amount of 4,5-dibromo-substituted products was obtained (Scheme 21). Competing reactions show that the complex of selenophene-2-carbaldehyde with aluminum chloride is brominated more rapidly than its thiophene analogue (95JHC53). 

Bromo-5-methyl-3-fluoromethylthieno[2,3-Z ]thiophene-2-carboxylic acid (24) was synthesized by the reaction of dibromo-substituted thienyl ketone 25 with ethyl thioglicolate 12 in ethanolic sodium ethoxide. 

A different approach to oligothiophenes has been reported by Van Keuren et al. [200], who coupled 2,5-bis(trimethylstannyl)thiophene (and other stannyl-thiophenes) with 5,7-dibromo-2,3-didecylthieno[3,4]bipyrazine under controlled conditions. Hicks and Nodwell [201] prepared a series of oligothiophenes with 2-mesitylthio substituents by coupling 2-stannylthiophenes with 2-bromo-5-mesitylthio-thiophenes. 3,4-Ethylenedioxy-substituted thiophene rings were also... 

Several monomers (thiophene and substituted thiophenes, dihalobenzenes, 4,4 -dibromobiphenyl and 2,7-dibromo-9,10-dihydrophenanthrene) were polymerized and the corresponding conjugated aromatic polymers obtained in high yield. As the dehalogenating Ni(0) complex, a mixture of bis(l,5-cyclooctadiene) nickel and a neutral ligand L was employed. Table 6.1 shows the principal results reported. 

The first example of alkylthiophene bromination was also demonstrated at that time. Methylthiophene which was obtained from coal tar as a mixture with toluene was reacted with bromine, and dibromo(methyl)thiophene separated from toluene. Its further bromination led to the synthesis of fully substituted tribromo(methyl) thiophene. 2-Iodo-5-methylthiophene was obtained by the same iodination procedure as iodothiophene. Deiodination with sodium allowed for the isolation of pure methylthiophene [80]. 

Cross-coupling reactions between organoboranes and heteroaryl halides are effectively catalyzed by Pd(0) in the presence of a base. Couplings in simple pyrimidines are illustrated by the reaction between 2-chloropyrimidine and 2- or 3-thiophene- and selenophene-boronic acids which give the corresponding 2-substituted pyrimidines (921) (Scheme 72). In 2,4-dichloro- or 2,4-dibromo-pyrimidine it is the 4-halo substituent which is the more reactive. 

Bromination under strongly acidic conditions using bromine and silver sulfate in concentrated sulfuric acid leads to substitution in the thiophene ring. With one equivalent of bromine, mixtures of 3-bromo and 2,3-dibromo derivatives are obtained (equation 51) whereas two equivalents of bromine results in high yields of 2,3-dibromo derivatives. Under neutral conditions, using bromine in carbon tetrachloride-pyridine, substitution occurs selectively in the borazaropyridine ring. 

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-... 

Halogens react with benzo[A]furan by an additionelimination mechanism to give 2- and 3-substituted products. Treatment of benzo[A]thiophene with chlorine or bromine in acetic acid gives predominantly 3-substituted products and bromination of a 3-bromobenzo[A]furan gives the 2,3-dibromo derivative <2003S925>. 2,2,3,3,4,5,6,7-Octachloro-2,3-dihydrobenzothiophene is obtained when benzo[A]thiophene is treated with chlorine in the presence of one equivalent of iodine. 

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