Thiophene derivatives desulfuration

An important special case of RSR reduction is desulfurization of thiophene derivatives. This proceeds with concomitant reduction of the double bonds. Many compounds have been made by alkylation of thiophene, followed by reduction ... 

Thiophenes have served as important four-carbon templates for molecular elaboration. Both functionalized cyclic and acyclic chains can be generated by carrying out conventional reactions on the thiophene nucleus and then performing a Raney nickel desulfurization at or near the very end of the scheme. Thus, the major constituent (279) of the Panamanian ant, Atta columbica, was made by Friedel-Crafts acylation of the thiophene derivative (277), followed by Grignard addition to the carbonyl group of (278), dehydration, and reductive desulfurization (Scheme 57) (60JOC1754). 

A new synthetic route to alkyl-substituted quinones has relied on the photochemical reaction of 2,3-dichloro-l,4-naphthoquinone with a thiophene derivative (77CL851). Irradiation of a benzene solution of the quinone and thiophene by a high pressure mercury lamp gave photoadduct (295) in 56% yield. Desulfurization of this compound over Raney nickel (W-7) gave the 2-butyl-1,4-naphthoquinone derivative (296 Scheme 62). Alkyl-substituted quinones such as coenzyme Q and vitamin K, compounds of important biological activity, could possibly be prepared through such methodology. 

Thiophenes are desulfurized to give products with a C4 carbon chain (see eqs. 13.60 and 13.63), and hence the desulfurization of thiophene derivatives has been applied for syntheses of compounds with longer alkyl chains, in particular, for long-chain compounds, which are not easily obtainable by conventional synthetic methods. Examples are shown in eqs. 13.87-13.90. 

The insertion of a metal atom into the C-S bond might constitute the first stage in the ultimate desulfurization of thiophene derivatives. It is therefore of great interest that several reactions have been discovered from which such metallothiacycles could be isolated. 

Badger and Buu-Hoi have made extensive use of nickel desulfurization in synthesis. One general scheme employs thiophene derivatives. For example 7-2-thienylbutyric acid (1, succinoylation of thiophene and reduction) is acetylated (as ester) at the 5-position (2) and converted by Huang-Minlon reduction and... 

S-Containing Compounds. Four thiophene derivatives were identified in the WGH-G, DWGH-G, and AWGH-G systems however two of them were not found in the DWGH and WGH-HQ systems. This is probabfy because of a partial desulfuration reaction and the removal of hydrogen sulfide during either the deamination reaction or during acid hydrolysis. 

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). 

Some substructures of synthetic interest are neither rings nor functional groups but are just hydrocarbon fragments. For example, if the reaction is desulfurization of a 2-substituted thiophene derivative then the product contains a string of four saturated carbons, which are originally part of the thiophene ring, along with the removed sulfur atom. The predominant theme... 

Syntheses by hydrogenolytic desulfuration of S-heterocyclics have found wide application. Long-chain hydroxy carboxylic acids and macrocyclic ketones have been prepared from thiophene derivatives. The thianaphthene ring has also been used with this method G-Labeled compounds have been prepared, and deut-eriated compounds can be obtained by replacing the water in the hydrogenolysis step by D2O... 

H-Labeled compounds by reductive desulfuration of thiophene derivatives and replacement of halogen... 

A reductive Birch desulfurization-hydrolysis of thiophene derivatives using lithium and alcohols in liquid ammonia on a-substituted thiophenes with subsequent hydrolysis of the products led to the conversion of the thiophene fragment of the molecule into a butyryl group [155]. A number of amino ketones of the aliphatic series were obtained from a-(o)-dialkylaminoalkyl)thiophenes. Scheme 139 shows how the yields increased dramatically from 13 to 82% as the length of the aliphatic side-chains increased, which presumably resulted from the remoteness of the functional group from the ring. 

Raney nickel desulfurization (Section 17-8) of thiophene derivatives results in sulfur-free acyclic saturated compounds. 

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