Benzothiophene halogenation

Thiophene-2-carbaldehyde, 3-bromo-synthesis, 4, 81 Thiophenecarbaldehydes benzothiophene synthesis from, 4, 906 reactions, 4, 807 synthesis, 4, 148 Wittig reactions, 4, 807 Thiophene-2-carb aldehydes bromination, 4, 753 conformation, 4, 33 halogenation, 4, 753 reactions, 4, 72-73 reactivity, 4, 72-73 reduction, 4, 776 Thiophene-3-carb aldehydes conformation, 4, 33 reactivity, 4, 72... 

F, Furan T, thiophene BF, benzofuran BT, benzothiophene DCE, dichloroethane ATFA, acetyl trifluoroacetate. c Relative rate of halogenation of the 2-methoxycarbonyl derivatives. 

Similar elimination reactions are employed in the synthesis of the benzologs of five-membered heterocyclic compounds. For example, /3-phenylethyl alcohols having hydroxyl, sulfhydryl, and amino groups in the ortbo position ate cyclized to the dihydro derivatives of benzofuran, benzothiophene, and benzopyrrole, respectively. Likewise, dehydro-halogenation of /3-(o-hydroxyphenyl)-ethyl bromide gives dihydtobenzo-furan in 72% yield. ... 

Benzothiophene, like thiophene, is a n-electron rich heterocycle. Unlike thiophene, electrophilic attack occurs selectively at the P-position (or 3-position) [10a, Ila] however, substitution at the a-center (2-position) can also be achieved [11b]. The order of positional reactivity, based on nitration, is 3 > 2 > 6 > 5 > 4 > 7 [1 la, 12a]. Also, halogenation under acidic conditions affords the 3-halobenzothiophene [11c, 13a]. In terms of metalation chemistiy, deprotonation occurs preferentially at the 2-position (a) [lid, 13b] metal-halogen exchange is also favored at the a-center over the P-center [12b]. 

To summarize, electrophilic substitutions and metalations of thiophenes take place preferably at the a-positions due to the electronegativity of the sulfur atom. This is the consequence of the more effective incorporation of lone pair electrons on the sulfur into the aromatic system. In contrast, electrophilic substitution of benzo[fe]thiophenes occurs at the P-position however, the preference is not strong and substitution can result in other positions. Like thiophene, metalation and metal-halogen exchange are favored at the a-position. Also, oxidative couplings of thiophenes and benzothiophenes are not very... 

Halogen at a benzothiophene 2-position is subject to displacement with amine nucleophiles, and, more easily than halogen at the 3-position. 

Lithio-benzothiophenes can be generated, and reacted with electrophiles, if the temperature is kept low. ° Direct deprotonation of benzothiophenes follows the usual pattern for flve-membered heterocycles and takes place adjacent to the heteroatom,"" and in concord with this pattern, metal-halogen exchange processes favour a 2- over a 3-halogen the sequence below shows how this can be utilised to develop substituted benzothiophenes. 2-Lithiated reagents react with electrophiles for example with p-toluenesulfonyl cyanide, 2-cyano derivatives are produced and similarly, 2-trimethylstannylbenzofuran and -benzothiophene and benzofuran-2- and benzothiophene-2-boronic acids can be prepared. 

Audi Benzo-[b]-thiophen, welches sieh offenbar nieht photochemisch dimerisieren laBt addiert Halogen-olefine nach der sensibilisierten Lichtanregung2. Damit verwandt sind Photocyeloadditionen mit Benzothiophen-dioxiden3 und N-acylierten Tndolen4. 

Acylation and metallation studies on monomers, dimers, trimers, and tetramers containing linked thiophen, pyridine, pyrimidine, furan, benzofuran, benzothiophen, and indole moieties have been published/ Deuteriation, halogenation, and diazo-coupling reactions of 2-oxo- and 2-thioxo-l,2-dihy-dropyrimidinium salts have been studied and compared with results for 2,2-dialkyl-1,2-dihydropyrimidinium and 2,3-dihydro-1,4-diazepinium salts in order to demonstrate the effect of an adjacent 0x0- or thioxo-group on the properties of a 1,5-diazopentadienium system/ Vilsmeier formylation of, and tautomerism in, 2-hydroxypyrazolo[5,l-h]quinazolone and l-phenylpyrazolo[5,l-A]-quinazoline-2,9-dione have been studied/ The pyrazolo[3,4-c]pyrazole (71) has been methylated and acetylated, the major products being (72)/ ... 

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