Benzothiophene substrates

Recently, several thermophilic organisms have been reported to be capable of sulfur-specific biodesulfurization. These include the Paenibacillus [87,151], Mycobacterium [30,31,85,94,294,295], etc. The ability to desulfurize sulfur compounds other than DBT derivatives, including benzothiophene, naphthothiophene, and benzonaphthothio-phene derivatives has also been demonstrated, thus widening the substrate specificity of the biodesulfurization process. Second, the thermophilic ability of the organisms offers temperature and operational advantages to further improve the commercialization potential of the BDS process. 

Benzothiophene has been shown to be susceptible to microbial metabolism under anaerobic conditions. Kurita et al. (42) observed the release of hydrogen sulfide from this substrate but they did not determine the fate of the carbon atoms. In studies to determine the extent of biodesulfurization of OSC, Kohler et al. (49) added benzothiophene dissolved in paraffin oil to cultures of Desulfovibrio sp. After 6 days of incubation, the amounts of desulfurization ranged from 3.1 to 9.2%. 

This introduces some interesting considerations both the rj S and the T (C=C) forms are actually L-type neutral ligands donating 2 electrons. Thus, in terms of coordinative unsaturation of the active site, the requirements for the desulfurization of thiophenes and for the hydrogenation of olefins or olefin-like substrates such as benzothiophenes, could be identical. The difference in reactivity observed is due to the overall electronic nature of the site, beyond the consideration of the degree of unsaturation alone. Highly electrophilic metal centers will prefer to bind to a C=C bond. 

The above approach of an intermolecular ortho-alkylation followed by an intermolecular Mizoroki-Heck coupling was later extended to heteroaryl iodides by Lautens [48], Using a Pd(OAc)2/triarylphosphine catalyst system, 3-iodothiophene, -benzothiophene, and -indole were transformed to the o/t/zo-alkylation/Mizoroki-Heck coupling products in good to excellent yields (Scheme 17). Unfortunately, 2-iodoheteroaryls were found to be poor substrates for the reaction. 

The employment of aryl 2-chloroprop-2-enyl sulfides (or ethers) as thio-Claisen rearrangement substrates neatly eliminates the necessity for an oxidative step, thus providing a route to 2-methyl-benzothiophenes (-benzofurans). " ... 

Intramolecular aldol/Perkin type condensation of orf/to-formylaryloxyacetic acids and arylthioacetic esters produces benzofuran- and benzothiophene-2-esters respectively, as illustrated below. The synthesis can be performed in one pot, thus ortfto-hydroxyaryl-aldehydes or -ketones, are 0-alkylated with a-halo-ketones, then intramolecular aldol condensation in situ produces 2-acyl or 2-aroyl-benzofurans. ° For benzothiophenes, the ring-closure substrates can also be obtained via methyl thioacetate displacement of fluoride from orf/to-fluoro-araldehydes. ... 

Although method a works well for the conversion of biphenyl to di-benzothiophene, it has generally given poor yields (if any) of the desired bridged products with other substrates.6,7 Notable examples of substrates that produced no isolable bridged product are phenanthrene,7 2,2 -binaph-... 

Reactions of thiol esters with the three most commonly used reagents - tri-butylstannane,tris(trimethylsilyl)silane (TTMSS),and allyltributylstannane -were conducted using AIBN as an initiator. The reaction of 36 with 1.3 equiv of Bu3SnH in refluxing benzene with AIBN for 1 h led to complete consumption of the substrate and clean formation of the cyclization and reduction products (39 and 40, respectively, see Fig. 3) in a ratio of 96 4. As anticipated, dihydro-benzothiophene 41 was also formed in this reaction. It is worth noting that 40... 

HDS catalysts generally consist of (heterogeneous) Mo or W sulfides on alumina supports. However, Bianchini et al. described a two-step procedure for HDS of thiophenes by the hydrogenolysis of thiols, followed by the desulfurization of the thiols by applying their zwitterionic rhodium(I) complex, [Rh(sulphos((cod)] (see previous section) [17]. This complex is soluble in polar solvents, such as methanol and methanol-water mixtures, but not in hydrocarbons. Benzo[b]thiophene was chosen as substrate since it is one of the most difficult thiophene derivatives to degrade. Under the mild reaction conditions of the two-step process, the benzene rings of the (di)benzothiophenes were not affected. In the absence of a base, the double bond of benzo[b]thiophene was hydrogenated, while in the presence of a base (NaOH) 2-ethylthiophenolate was the major product (Scheme 1). 

The arene substrates are not limited to simple benzene derivatives. A variety of het-eroarenes can also participate in alkene arylations to generate the desired coupling products. Stoichiometric oxidative coupling of aromatic heterocycles such as furan, thiophene, selenophene, A-methylpyrrole, benzofiiran and benzothiophene with a variety of alkenes, including acrylonitrile, styrene and methyl acrylate, have been extensively studied by Fu-jiwara and coworkers [8]. Furan, thiophene, selenophene and A-methylpyrrole are easily alkenylated with alkenes to give 2-alkenylated and 2,5-dialkenylated heterocycles in relatively low yields (3 6%) [8a], while the reactions of benzofuran and benzothiophene with alkenes produced a mixture of 2- and 3-alkenylated products [8b]. 

Benzothiophenes can be prepared from the corresponding phenyl ethers in a similar manner. In this case, the yield increased drastically when a more electron-donating amine substituent was present on the substrate. ... 

Clayzic has been used to catalyze various Friedel-Crafts reactions including those of aromatic substrates with alkyl halides, aldehydes and alcohols. Other applications include the preparation of benzothiophenes by cyclisations of... 

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