Dimethyl sulfide, protonation

In the alcohol oxidations, the sulfonium intermediate (2, nucleophile = R2C(OH)) loses a proton and dimethyl sulfide to give the carbonyl compound (42). The most common mechanism for the decomposition of (2) is attack by a mild base to remove a proton from one of the methyl groups. Subsequent cycHc coUapse leads to the carbonyl compound and dimethyl sulfide (eq. 9) ... 

When DMSO is mixed with concentrated hydrochloric acid, protonated DMSO is in equiUbtium with the chlorodimethylsiilfonium ion. Pummerer reactions and subsequent reaction of the initial products give a complex mixture of products including formaldehyde, bis(methylthio)methane, methanethiol, dimethyl disulfide, dimethyl sulfide, and others. 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

The order of decreasing Lewis basicity toward trimethylaluminum is thiane, thiolane, diethyl (or dimethyl) sulfide, thietane and 2-methylthiirane (67IC1461). Thietane can be protonated at -60 °C with fluorosulfonic acid in antimony pentafluoride-liquid sulfur dioxide the NMR spectrum shows bands at 8 7.40 (S—H) and 3.20-4.40 p.p.m. (C—H) (71JOC1121). 

The final stage of this reaction involves an E2 elimination. In this step, illustrated below, a proton adjacent to the oxygen is removed by a base such as triethylamine. The negative charge then forms a double bond with the oxygen and dimethyl-sulfide is eliminated. The overall oxidation process converts an alcohol into an aldehyde. 

Base removes a benzylic proton, and dimethyl sulfide is eliminated in an E2 reaction. 

A base (the trifluoroacetate ion) abstracts a proton from one of the methyl groups of the oxysulfonium ion, and a bond shift through a five-membered transition state gives the ketone and dimethyl sulfide [1016 (equation 261). 

The mechanism of the Swem oxidation has been studied in depth and the formation of an initial adduct 7 from the reaction between dimethyl sulfoxide and oxalyl chloride which then collapses to give a dimethylchlorosulfonium species 8 is clearly indicated by mechanistic studies.3,8 Reaction of 8 with an alcohol then produces the alkyoxysulfonium ion 9 which upon treatment with an amine base gives the ylide 10. Subsequent proton extraction gives the carbonyl product 2 with the release of dimethyl sulfide. 

The breath of a test person was analyzed over a time period of about 30 hours by means of proton-transfer-reaction mass spectrometry [55]. After ingestion of cut raw garlic, tiie components allyl metfiyl sulfide, allyl methyl disulfide, diallyl sulfide, diallyl disulfide, diallyl trisulfide, dimethyl sulfide, and acetone were detected. While the concentrations of allyl mediyl disulfide, diallyl sulfide, diallyl disulfide, and diallyl trisulfide reached maximum concentration shortly after ingestion of garlic and declined to baseline values within the next 2-3 h, concentrations of allyl methyl sulfide, dimethyl sulfide, and acetone increased much more slowly... 

The alcohol has been a spectator in these events so far but the chlorosulfonium ion now formed can react with it to give a new sulfonium salt. This is the sole purpose of all the reactions up to this point. This sulfonium salt is deprotonated by the base (Et3N) to form an ylid. The final step completes the redox reaction the transfer of a proton to the anionic carbon gives an aldehyde, with overall reduction of dimethylsulfoxide (DMSO) to dimethyl-sulfide (DMS). 

Step 4 Intramolecular proton abstraction from the H—C—O unit by the negatively charged carbon triggers dissociation of the ylide to an aldehyde or ketone and dimethyl sulfide. 

The original Pfittner-Moffatt procedure for alcohol oxidation by activated dimethyl sulfoxide utilized dicyclohexylcarbodiimide (DCC) and a source of protons such as polyphosphoric acid or pyridinium tri-fluoroacetate. The use of strong acids such as the common mineral acids must be avoided since, although acidic conditions are initially required, the reaction must readily become basic in the later stages of the process. Mechanistically it is reasonable to suggest that the activation follows the pattern whereby initial attack of the nucleophilic sulfinyl oxygen of dimethyl sulfoxide, with the protonated carbodiimide, forms a sulfonium isourea. This is followed by displacement of dicyclohexylurea by the alcohol to form an alkoxysulfonium salt. Base treatment of this salt forms an ylide, which collapses via the proven cyclic mechanism to the carbonyl compound and dimethyl sulfide (Scheme 4). 

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