Of thioethers

Figure 3-17. Consecutive application of two reaction schemes to model the oxidation of thioethers to sulfoxides.

Clearly, for symmetry reasons, the reverse process should also be considered. In fact, early versions of our reaction prediction and synthesis design system EROS [21] contained the reaction schemes of Figures 3-13, 3-15, and 3-16 and the reverse of the scheme shown in Figure 3-16. These four reaction schemes and their combined application include the majority of reactions observed in organic chemistry. Figure 3-17 shows a consecutive application of the reaction schemes of Figures 3-16 and 3-13 to model the oxidation of thioethers to sulfoxides. 

Since the exocyclic sulfur is more reactive in the ambident anion than in A-4-thiazoIine-2-thione. greater nucleophilic reactivity is to be expected. Thus a large variety of thioethers were prepared in good yields starting from alkylhalides (e.g.. Scheme 38 (54, 91, 111, 166-179). lactones (54, 160), aryl halides (54, 152. 180, 181), acyl chlorides (54. 149, 182-184). halothiazoles (54, 185-190), a-haloesters (149. 152. 177. 191-194), cyanuric chloride (151). fV.N-dimethylthiocarbamoyl chloride (151, 152. 195. 196), /3-chloroethyl ester of acrylic acid (197), (3-dimethylaminoethyl chloride (152). l,4-dichloro-2-butyne (152), 1,4-dichloro-2-butene (152), and 2-chloro-propionitrile (152). A general... 

The reaction of thioethers with ethyleneimine in the presence of acid yields sulfonium compounds. The reaction is reversible under alkaline conditions (125). Compounds in which double-bonded sulfur can exist in tautomerism with a form having a free SH group, such as thiourea (126,127), thiocarboxyhc acids (128), and thiophosphates (129), react to give aminoaLkylated products. The P-aminoethyl thiocarboxylate rearranges to give the amide. 

Sulfur Substituents. Acetylation and alkylation of pyridinethiones usually take place on sulfur (39). An exception to this is 4-pyridinethione [19829-29-9] which is acetylated on nitrogen. Displacement of thioethers can be achieved with hydroxide or amines (eq. 13) (40). Thioether functional groups can also be removed by reduction (39). 

Yields of thioethers, formed under nonacidic conditions (Ph2CHCl or PhjCCl, DMF, 80-90°, 2 h, N2) are not as high (RSCHPh2, 50% yield RSCPh3, 75% yield) as the yields obtained under the acidic conditions described above. 

Pd(Ph3P)4, dimedone, THF, 88-95% yield. The catalyst is not poisoned by the presence of thioethers such as methionine. Diethyl malonate has also been used as a nucleophile to trap the 7r-allylpaladium intermediate and regenerate Pd(0). ... 

In two patents,the preparation of thioether-substituted selena-zoles of the general formula (6) have been described. These are stated to be formed by reaction of halogenoketothioethers with selenoamide components selenoacetamide, selenobenzamide, and A -ethylseleno-urea are given as examples. The resulting selenazoles were not further characterized. They are stated to be starting materials for the preparation of cyanine dyestuffs which are useful photographically. 

Using thiophenol instead of phenol, Michel et al. [49] found a new selective reaction that takes place exclusively with allylic chlorines and not with tertiary chlorines. A single product of thioether structure is formed [Eq. (11)]. 

RuCl3(DMSO)3 reacts with sulphides to form mixed sulphide/sulphoxide complexes that are catalysts for oxidation of thioethers to sulphoxides [114a] ... 

Coordination chemistry of thioethers, selenoethers and telluroethers in transition metal complexes. S. G. Murray and F. R. Hartley, Chem. Rev., 1981, 81, 365-414 (748). 

Two-component methods represent the most widely applied principles in sulfone syntheses, including C—S bond formation between carbon and RSOz species of nucleophilic, radical or electrophilic character as well as oxidations of thioethers or sulfoxides, and cheletropic reactions of sulfur dioxide. Three-component methods use sulfur dioxide as a binding link in order to connect two carbons by a radical or polar route, or use sulfur trioxide as an electrophilic condensation agent to combine two hydrocarbon moieties by a sulfonyl bridge with elimination of water. 

The most widely applied method to prepare sulfones is the oxidation of thioethers. In the course of these oxidations sulfoxides must occur as intermediates. However, since oxidation mechanisms for thioethers and sulfoxides are partly different, these oxidations will be discussed separately. A recently published method337,338 allows oxidation of a... 

The usual oxidizing agents transfer oxygen (or halogens and related species with subsequent hydrolysis) stepwise to the sulfur of thioethers Rates of step A compared with those of step B are faster with electrophilic oxidation agents (peroxy acids) inversely, rates of step B compared with those of step A are faster with nucleophilic oxidation agents (peroxy anions)339-341. 

Table 11 affords a survey on oxidation methods of thioethers and sulfoxides. 

TABLE 11. Oxidation of thioethers and sulfoxides by various methods... 

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