Sulfones, thiomethyl

A wide variety of products can be obtained by thioalkylation (42). The reactants ate usually an aldehyde, a thiol, and either a phenol, a sulfone, an amine, or a heterocychc compound. Phenols primarily react with formaldehyde in a process known as thiomethylation (eq. 26). Other types of reactions are depicted in equations 27 and 28. 

A similar Knoevenagel-type condensation takes place between methyl methyl-thiomethyl sulfone and aromatic aldehydes. In this reaction, use of K2C03 (2 mol equiv) as base and refluxing in isopropanol gave the best result178. 

Other miscelleanous oxidation reactions involve S-oxidation of thioethers to sulfoxides and sulfones as observed with pergohde (33), the thiomethyl derivative of spironolactone (47), and suHndac (48). 

Oxidation of a thiomethyl group in indolo azepines to a sulfoxide and a sulfone has been reported (2004AP486). Thione 415 with a variety of hydrazides 416 under thermal conditions (n-butanol, reflux) gives fused triazoles 417 in moderate to good yields as the products of a substitution/cyclization sequence (Scheme 87, Section 5.2.1.3 (1993LA1141)). 

Sulfur has been used in linkers such as thioethers, sulfoxides, sulfones, sulfonic acids and their corresponding derivatives. A safety-catch linker for amines is based on 2-(thiobenzyl)ethylcarbamates [44]. Linkage is performed with preformed handles containing ethenyloxycarbonyl-protected amines 37. Attachment to thiomethyl-ated polystyrene 38 is performed under conditions involving radicals. Cleavage was performed with an oxidizing agent, which forms the retro Michael substrate (Scheme 6.1.11). 

Reductive desulfurization of 9-(phenylsulfonyl)furo[2,3- ]quinoline and its 2-methyl derivative can be effected by treatment with LAH in THF solution at reflux, but proceeded poorly with aluminum amalgam, the reagent of choice for the reductive cleavage of vinyl sulfones <83JOC774>. Raney nickel was used to remove a thiomethyl substituent from the central ring of a furochromone direct precursor to visnagan <89JOC448l>. 

A report of Backer and Blaas6 is responsible for evolution of the present procedure these workers were first to conduct a Diels-Alder synthesis utilizing a 3-sulfolene in place of the free diene (by heating the cyclic adduct of sulfur dioxide and 2-methyl-3-thiomethyl-1,3-butadiene with maleic anhydride). The generality of the method as a variant of the conventional diene synthesis is limited largely by the availability of the appropriate 3-sulfolene its greatest utility, perhaps, will be presently realized in those diene reactions normally requiring 1,3-butadiene, since 3-sulfolene itself is now the least expensive and most widely available diene cyclic sulfone. 

In a similar vein, the adducts derived from the anion of methoxymethyl phenyl sulfone and cyclic ketones rearrange on Lewis acid catalysis (Scheme 13). This rearrangement is quite stereospecific, in that a single diastereoisomer is formed and it is the most substituted group which migrates. Similar results were obtained with adducts derived from phenyl thiomethyl phenyl sulfone (Scheme 14). ... 

This pathway accounts for the thiomethyl metabolites formed from several classes of xenobiotics. Thiomethyl metabolites can be further oxidized by the microsomal flavin-containing monooxygenases to their corresponding sulfoxide and sulfone derivatives. 

Krut ko prepared [2-(thiomethyl)ethyl]tetrameth-ylcyclopentadienes 468 by treatment of 2-lithio-2-butenes 466, obtained by lithiation of 465, with ethyl 3-(thiomethyl)propanoate via dienol 467, which underwent ring closure in the presence of />toluene-sulfonic acid in moderate yield (Scheme 87). Treat-... 

Methyl Methylthiomethyl Sulfone. Methyl methyl-thiomethyl sulfone is the 5-methyl analog of MT-sulfone and it is conveniently synthesized by oxidation of methyl methylthiomethyl sulfoxide (FAMSO) with potassium permanganate or H202-Na0H. It is useful for synthetic methods similar to those using MT-sulfone synthesis of carboxylic esters, ketones, and a-aLkoxy- -arylacetates. In the reaction of this reagent with allylic bromides, a-methylthio- /,5-unsaturated sulfones are obtained by stirring the bromide with potassium carbonate and potassium iodide in hexamethylphosphoric triamide (eq 14), which does not occur with MT-sulfone. 

Conversion of the 3-thiomethyl ether (180) to the sulfone (181) was accomplished by oxidation with 2 equiv of m-chloroperbenzoic acid. Reduction of the sulfoxide group in 181 with phosphorous trichloride in DMF gave the methylsulfonyl derivative (182). Removal of the protective groups by a known procedure yielded the acid (183) which was devoid of biological activity. 

The primary ozonation products of organophosphorous pesticides in water such as diazinone, phenthione (MPP) and ediphenphos (EDDP) [39], are identifled by means of GC-MS analysis. The massspectra of the ozonation products of 17 organophosphorous pesticides point oxones as the primary reaction products. This fact is also confirmed by the SO generation resulting from the ozonation of their thiophosphoryl bonds. Oxones are relatively stable towards ozone attack but they are further hydrolyzed to trialkylphosphate and other hydrolysis products. However, with MPP the thiomethyl radicals are first oxidized to thiophosphoryl bonds giving MPP-sulfoxide, MPP-sulfone, MPP-sulfoxide-oxone are also obtained. Two main oxidation products have been identified at the oxidation of bis-dithio-type ethiones. Phosphate type EDDP is stable towards ozonolysis but its oxidation products are identified after hydrolysis [39]. 

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