And formation of sulfones

Introduction of the sulfonic acid group by replacement of hydrogen is much less important in the aliphatic than in the aromatic series. On direct sulfonation of alkanes by sulfuric acid, oleum, or sulfur trioxide side reactions (isomerization, dehydrogenation, oxidation, and formation of sulfone bonds) occur to such an extent that this process has found hardly any practical applications. 

Without additional reagents Partial replacement of sulfhydryl by chlorine with replacement by hydroxyl and formation of sulfonic acids... 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

An example of cleavage ol the sulfur-oxygen bond in trifluoromethane-sulfonic ester has been reported Tnfluororaethyl triflate reacts with neutral or anionic nucleophiles with elimination of carbonyl difluoride and formation of trifluoromethanesulfonyl fluoride [57] (equation 32) The mechanism of this reaction involves elimination of fluoride ion, which is a chain carrier in the substitution of fluorine for the trifluoromethoxy group... 

Thus, simple ketones or aliphatic aldehydes may be successfully used as starting materials in the CSIC (Carbanion mediated Sulfonate Intramolecular Cyclization) reaction. Ai-alkylsulfonamides could be also cyclized under CSIC conditions (99T(55)7625) affording the spiroisothiazoline 79. By treatment with TMSCl, Nal in acetonitrile at r.t., hydrolysis of the enamine and formation of the corresponding keto derivative 80 was obtained. 

The antiarrhythmic activity of local anesthetics has been noted several times previously. Another such agent is prepared by first alkylating isopropylamine with sulfone 199. Reaction of the ])ioduct (200) with diethylethylenediamine and carbonyldiimidazole results in transfer of the CDI carbonyl group and formation of the urea suricainide (201) [52]. The transform in all likelihood involves stepwise replacement of the imidazole groups by the basic groups in the other reactants. 

In connection with route A, the formation of sulfones from sulfinates and a-haloketones on the one hand, and of isomeric enol sulfonates on the other (cf. Section III. A.4), should be pointed out. 

Since the ratio of the two sulfones 2 and 3 increases with the polarity of the solvent (from 1 4 in benzene to 16 1 in formamide) a possible concerted [2,3]sigmatropic rearrangement for the formation of sulfone 3 was first considered. However, other evidence such as the effects of solvent and added salts seem to support an ionization mechanism, with the formation of the two sulfones by recombination from two different ion-pair species40. 

The formation of sulfone is assisted in particular by high reaction temperatures, whereas the formation of anhydride is influenced by the S03/LAB ratio and the residence time [152]. Usually an S03/LAB ratio between 1-1.1 to 1 is chosen and the residence time kept as short as possible [153-155]. 

Sulfur trioxide reacts with MesSiCl 14 to give the trimethylsilyl ester of chloro-sulfonic acid 1334 [96], which on treatment vvdth iodosobenzene forms iodosoben-zenedichloride 1335, HMDSO 7, and regenerated SO3 [97]. Addition of olefins such as cyclohexene leads to the formation of sulfones such as 1336 [97]. With... 

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

The symmetric diarylthiirene oxides (18) are much more thermally stable than the corresponding saturated thiiranes and unsaturated thiirene dioxides. Thus, the thiirene oxide 18a shows only slight decomposition after 24 hours of reflux in benzene, whereas the analogous sulfone 19b fragments completely to SO2 and diphenylacetylene after less than six hours under the same conditions Irradiation of the oxide 18a, however, does result in the elimination of sulfur monoxide and formation of diphenylacetylene. Its thermolysis at 130 °C afforded benzil as the only isolable product, implying that SO is not being eliminated in this thermolytic process. 

In contrast with the relatively facile thermal rearrangement of sulfinates to sulfones discussed in the preceding section, the reverse process is relatively, rarely encountered and is usually observed only at elevated temperatures. One of the first thermal sulfone to sulfinate isomerizations has been invoked by Fields and Meyerson to occur during the pyrolysis of dibenzothiophene S, S-dioxide (26) to dibenzofuran, through elimination of sulfur monoxide from the sultine intermediate 27 (equation 27). More recently, the flash vapor-phase pyrolysis of various 2,5-dialkyl and diaryl thiophene-S, S-dioxides has also been shown to involve SO extrusion and formation of the corresponding furans in good yields . 

Directed lithiation of aromatic compounds is a reaction of broad scope and considerable synthetic utility. The metalation of arenesulfonyl systems was first observed by Gilman and Webb and by Truce and Amos who reported that diphenyl sulfone is easily metalated at an orf/io-position by butyllithium. Subsequently, in 1958, Truce and coworkers discovered that metalation of mesityl phenyl sulfone (110) occurred entirely at an orf/io-methyl group and not at a ring carbon, as expected. Furthermore, refluxing an ether solution of the lithiated species resulted in a novel and unusual variation of the Smiles rearrangement and formation of 2-benzyl-4,6-dimethyl-benzenesulfinic acid (111) in almost quatitative yield (equation 78). Several other o-methyl diaryl sulfones have also been shown to rearrange to o-benzylbenzenesulfinic acids when heated in ether solution with... 

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