Thioethers groups

Anions of allylic thioethers may also be alkylated with alkyl bromides in high yield. The thioether groups can subsequently be removed by hydrogenolysis (F.W. Sum, 1979). 

Much of the current work is based on the fact that the side chain can be replaced by an alternative functionality, which contains sulfur. Metabolic destruction presumably involves the readily oxidized thioether groups. 

A remarkable case of a Meerwein reaction of phenylacetylene was reported by Leardini et al. (1985) in a new synthetic route to benzothiophene derivatives. Aryldi-azonium salts with a thioether group in the 2-position add phenylacetylene and substituted phenylacetylenes in the presence of metallic copper or iodide ion in acetone, or of FeS04 in DMSO (Scheme 10-60). The radical 10.21 formed initially is attacked intramolecularly by the sulfur atom of the thioether group to give the benzothiophene 10.22 in high yields (55-95%) as shown in (Scheme 10-60). Lear-... 

Similar reactions have been carried out with other thioacetals, as well as with compounds containing three thioether groups on a carbon. ... 

Since the pioneering work on the 3-bromo-2-butanol system similar observations have been made, not only with neighboring ether, ester, and thioether groups, but also with neighboring carbon. 

Synthesis. The first example of a stable, soluble pz peripherally substituted with a heteroatomic moiety involved appended thioether groups, M[pz(.V-Mc)8, as reported in 1980 by Schramm and Hoffman (2) (Scheme 9, 45-48). Mg[pz(5 -Me)s], 46, was prepared in a 60% yield by a magnesium templated macrocyclization of dinitrile, 45. Demetalation with sulfuric acid gave H2[pz(5 -Me)8], 47 (65%) and remetalation with the anhydrous acetate salts of copper and nickel gave 48 (80%) and 49 (65%). 

The many sulphur dyes synthesised via quinonimine intermediates are polymeric products containing numerous disulphide crosslinkages that can be broken by reduction in aqueous sodium sulphide thioether groups survive the reduction process. The smaller thiolate-containing molecules formed are substantive to cellulose. Although the actual structures of such dyes are complex, their essential features can be illustrated in an idealised model (Scheme 6.23), in which X = S, NH or O, and R indicates substituents or annelated rings. 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

Another new catalyst was described by Leardini and coworkers158, namely FeSC>4 in DMSO. It was applied to a Meerwein reaction of phenylethyne and substituted phenylethynes with arenediazonium salts containing a thioether group in the 2-position. 

A series of hexadiendioic acid derivatives such as (17) (of uncertain stereochemistry) inhibited cRBL and rat ISN (2 /rM in both), and also inhibited AAE (10 /rg/ear topically, 20 mg/kg p.o.) [57].The thioether group in (17) was required for activity, but the nature of the alkyl group was unimportant. Benzoyl groups or preferably esters were required at each end of the molecule. In vivo activity did not correlate with 5-LO inhibition. 

Cimetidine contains an imidazole ring comparable to histamine, a sulfur atom (thioether group) in the side-chain, and a terminal functional group based upon a guanidine (see Section 4.5.4). Ranitidine bears considerable similarity to cimetidine, but there are some important differences. The heterocycle is now furan rather than imidazole, and the guanidine has been modified to an amidine (see Section 4.5.4). A newer drug, nizatidine, is a variant on ranitidine with a thiazole heterocyclic ring system. 

By prior substitution at the a-carbon centre (deprotonation, followed by sUylation), also asymmetrically functionalized bis(lithiomethyl)silanes like compound 161 are accessible from their substituted parent compounds (e.g. compound 160). This selective reaction sequence is based on the possibility of deprotonating bis(phenylthiomethyl)silane 155f with w-butyllithium without attacking the thioether groups (Scheme 58). ... 

Reductive removal of a thioether group can be effected by a variety of reducing agents, e.g. Scheme 124 (60CB1590). 

Thieno[2,3-r]pyridinium salt 48 displays strong fluorescence, in agreement with a high /3-value that was determined by PM3 calculations <1998J(P2)437>. UV spectroscopy of compounds 38, 48, and analogous thieno[2,3-r]-and thieno[3,4-r]-pyridine derivatives confirms that the thioether group serves as a superior electron donor <1996J(P2)1377>. 

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