Reactions with Thiophene and Benzothiophene

The reactions of a series of arynes from aromatic anhydrides with thiophene and benzothiophene at 690° revealed some processes not as clearly evident with other reagents. 

In a typical experiment, a solution of 2-96 g (0-02 mole) of phthalic anhydride in 31-46 ml (0-4 mole) of thiophene was pyrolyzed in dry, high-purity nitrogen flowing at 2-7 1/hr. The contact time was 19 sec. The products were distilled to recover 27-4 ml of thiophene. The distillation residue, 2-5 g, was analyzed by gas chromatography, by comparison of retention times with authentic samples  

Yields were calculated as in Section E on the basis of aromatic anhydride. 

Several products in minor amounts were formed in the reaction of phthalic anhydride with thiophene in addition to those listed. These 

Insertion and Addition Products of Arynes with Thiophene and Benzothiophene 

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Scheme 1.55 Test reaction with thiophene- and benzothiophene-oxazoline/ phosphine-containing ligands.

Ohta s group investigated the heteroaryl Heck reaction of thiophenes and benzothiophenes with aryl halides [127] and chloropyrazines [128]. Addition of the electrophiles invariably took place at C(2) as exemplified by the formation of arylbenzothiophene 156 from the reaction of benzothiophene and p-bromobenzaldehyde [127]. As expected, the heteroaryl Heck reaction of 2-thienylnitrile, an activated thiophene, with iodobenzene afforded the arylation product 157 [129],... 

The major products from the reaction of arynes with thiophene and benzothiophene by addition and insertion are shown in Table 11. Benzyne from phthalic anhydride reacted with thiophene at 690° to give naphthalene and benzothiophene by 1,4-addition and loss of sulfur, and by 1,2-addition and loss of acetylene, respectively, as well as phenyl-thiophene by insertion (Fields and Meyerson, 1966d, 1967e) (Scheme 19). The ratio of naphthalene to benzothiophene was about 9 1, nearly the same preference for 1,4-over 1,2-addition as was inferred from the reaction of benzyne with dichlorobenzenes and pyridine at the same temperature, and again reflects the strong tendency of benzyne to act as a dienophile. 

Thiophenes continue to play a major role in commercial applications as well as basic research. In addition to its aromatic properties that make it a useful replacement for benzene in small molecule syntheses, thiophene is a key element in superconductors, photochemical switches and polymers. The presence of sulfur-containing components (especially thiophene and benzothiophene) in crude petroleum requires development of new catalysts to promote their removal (hydrodesulfurization, HDS) at refineries. Interspersed with these commercial applications, basic research on thiophene has continued to study its role in electrocyclic reactions, newer routes for its formation and substitution and new derivatives of therapeutic potential. New reports of selenophenes and tellurophenes continue to be modest in number. 

As discussed in Section III, when the sulfur content is lowered from 0.20 to 0.05%, the chemistry of HDS of gas oils is essentially the chemistry of alkyl-substituted dibenzothiophenes. Though gas oils initially contain mostly alkyl-substituted benzothiophenes, these are completely removed by the time 0.20% S is achieved. Thus, this review will deal predominantly with the reaction pathways involved in the HDS of alkyl-substituted dibenzothiophenes. There are many excellent reviews on reaction pathways of the more reactive sulfur species such as thiophenes and benzothiophenes (2, 5, 8, 23, 24), and the reader is referred to those reviews for information on the reaction pathways and mechanisms of HDS for the more reactive... 

Diels-Alder reactivity of thiophene and benzothiophene remains poorly understood. AMI semiempirical studies examining the activation of thiophene for this thermally allowed [4+2] cycloaddition process have shown that the usual synthesis approaches (use of highly reactive dienophiles, substitution on thiophene, increased reaction pressures) have only small effects on rate enhancement. However, use of the corresponding S-methylthiophenium salts, which have little aromaticity, should provide excellent activation for Diels-Alder reactions of thiophenes even with poor dienophiles such as ethylene <95JHC483>. This AMI approach has been applied to examine Diels-Alder reactions of benzo[6] and benzo[c]thiophenes the theoretical data agree with experimental results <95JCS(P1)1217>. 

Thiol Decomposition. As explained previously, the elimination of sulfur from benzothiophene occurs stepwise after the aromatic thiol (o-thiocresol) has formed and not in a concerted fashion from the thiophenic ring system. Extrapolation of this implies that thio-phenic sulfur in coal is eliminated by conversion to an aromatic thiol that subsequently undergoes desulfurization. Since the aromatic thiol is the apparent organosulfur species that undergoes desulfurization, it is of interest to understand the chemistry involving the elimination of sulfur from aromatic thiols. Thio-phenol was used as a model compound to examine reactions, primarily the thermal decomposition reactions that might lead to sulfur elimination. In the experiments with caustic and benzothiophene, the intermediate (o-thiocresol) most likely exists in the salt... 

As benzothiophene was a product of both the reaction of benzyne with thiophene and the pyrolysis of thiophene alone (Fields and Meyerson, 1966d), we investigated the reaction of benzyne with benzothiophene. Pyrolysis of a mixture of phthalic anhydride and benzothiophene gave the products shown in Table 11. Anthracene and dibenzothiophene probably arose via 1,2-, and phenanthrene via 1,4-addition to the thiophene ring ... 

Homogeneous model complexes shed light on the reactivity of thiophene and benzothiophene. Thiophene is known to coordinate to metals in if- to -fashion, as in (21-XXIV) to (21-XXVII). The rf-S and rf-C,C structures are believed to act as immediate precursors to C—H and C—S addition reactions. This was confirmed spectroscopically for the reaction of (pp3)Ru(N2) with thiophene ... 

The rates of hds of thiophen, benzothiophen, and polyaromatic thiophens were compared over a sulphided commercial C0O-M0O3/AI2O3 catalyst (573 K, 71 atm). Pseudo-first-order kinetics were obeyed. The mechanism of the reaction with thiophen (involving ring hydrogenation) was different from that of other compounds (S extmsion). The reactivity was not governed solely by the size of the ring compound interaction of the ir-electron system with the catalyst surface may be more important than the interaction of S except for thiophen. 

The group of Jones has described the desulfurization of thiophene and benzothiophene using [Ir2(Cp )2(H)2(p-H)] with excess TBE (t-butylethylene) or [lr(Cl)(Cp )(H)]2 in the presence of H2 [53, 106]. The reactions evenmally afford diiridium complexes with sulfide and q q -butadiene bridges and seem to proceed via two consecutive carbon-sulfur bond cleavages that require more than one metal center and the ability to form bridging thiolate intermediates (Scheme 21) [107]. 

Thiophenes and benzothiophenes were used by Ke, Liu, and coworkers to evaluate the efficacy of a group of a-hydroxyimine palladium complexes in direct cross-coupling reactions with aryl and heteroaryl bromides such as 4-bromobenzonitrile (47), 4-bromoanisole (48), and 5-bromopyrimidine (49) (33 examples 50—97% yield) (2015OM4881). In particular, complex 50 operated most efficiently under aerobic conditions and with low catalyst loading (0.55 mol%). This success prompted further exploration of cross-coupling reactions with other heteroaryls such as furans, thiazoles, imidazo[l,2-a]pyridine, and triazoles (19 examples 57—96% yield). 

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]. 

Fagnou and co-workers succeeded to combine Heck cyclization with direct arylation in 2009. This interesting domino palladium-catalyzed Heck-intermolecular direct arylation reaction gave new access to a variety of dihydrobenzofurans, indolines, and oxindoles. A variety of sulfur-containing heterocycles such as thiazoles, thiophenes, and benzothiophene could be employed as the direct arylation coupling partner as well and resulted in yields up to 99% (Scheme 2.35). As the authors demonstrated, in addition to... 

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