Dimethyl sulfide, reaction with ozonides

When ozonolysis is done in alcoholic solvents, the carbonyl oxide fragmentation product can be trapped as an a-hydroperoxy ether.146 Recombination to the ozonide is then prevented, and the carbonyl compound formed in the fragmentation step can also be isolated. If the reaction mixture is treated with dimethyl sulfide, the hydroperoxide is reduced and the second carbonyl compound is also formed in good yield.147 This procedure prevents oxidation of the aldehyde by the peroxidic compounds present at the conclusion of ozonolysis. 

One of the most common reactions for the complete cleavage of an exocyclic C-C double bond is ozonolysis. The reaction is typically performed at low temperature in dichloromethane, methanol or a mixture of both, followed by the usual reduction of the ozonide with dimethyl sulfide 15 17 80 82 i48,337 or thiourea83 to give excellent yields of the corresponding cyclobu-tanone. 

Dienes react with ozone at one or both double bonds to give carbonyt compounds. When 1,3-cyclohexadiene is dissolved in dichloromethane at -78 °C and treated with 1.5 mol of ozone in dichloromethane solution and the resulting ozonide is stirred overnight at 0 °C with dimethyl sulfide, 2-hexenedial is obtained in 67% yield. If, on the other hand, an excess of ozone is passed through a solution of 1,3-cyclohexadiene at -78 °C until a blue color appears, both double bonds are ozonolyzed, and a 70% yield of 1,4-butanediol is obtained by reducing the reaction mixture with lithium aluminum hydride (equation 138) [92]. More substituted double bonds react with ozone preferentially. 

Another cyclization method towards synthesis of myo- inositols and chiro-inositols resulted from a Sml2-promoted intramolecular pinacol reaction. Treatment of dienes 34 and 35 with ozone produced a dialdehyde after reduction of the ozonide with dimethyl sulfide. Subsequent Sml2-mediated pinacol coupling gave the corresponding protected inositols as a mixture of diastereomers [89]. 

Ozonolysis (Sections 8.16B and 8.19) The oxidative cleavage of a multiple bond using O3 (ozone). The reaction leads to the formation of a cychc compound called an ozonide, which is then reduced to carbonyl compounds by treatment with dimethyl sulfide (M02S) or zinc and acetic acid. 

Reaction of an alkene with ozone leads to a 1,2,3-trioxolane, which rearranges to a 1,2,4-trioxolane (an ozonide). Subsequent treatment with hydrogen peroxide or with dimethyl sulfide leads to an aldehyde, ketone, or carboxylic acid product. When an ozonide contains a C-H unit, oxidation with hydrogen peroxide leads to a carboxylic acid, but reaction with dimethyl sulfide leads to an aldehyde 51, 52, 53, 54, 78,82,83,117. 

The success achieved with phthalimidopenicillin and the knowledge accumulated in these model experiments encouraged Shionogi scientists to examine this reaction sequence with both penicillin V and G. At this point they elected to employ the known thiazoline azetidinone compound 163 which is easily prepared by the method published earlier by Cooper and Jose (1970). They reasoned that the terminal double bond in 163 was suitable for the removal of a one-carbon unit to afford the expected ozonized product. And indeed, when the bicyclic derivative (163) was ozonized in methylene chloride-methanol at -78°C followed by reduction of the ozonide with an excess of dimethyl sulfide, the desired enol ester (164) was isolated in 70% yield (see also Volume 1, Chapter 1). 

Ozone, O3, is produced in the laboratory in an instrument called an ozonator, in which an arc discharge generates 3 % ozone in a dry oxygen stream. The gas mixture is passed through a solution of the alkene in methanol or dichloromethane. The first isolable intermediate is a species called an ozonide, which is reduced directly in a subsequent step by exposure to zinc in acetic acid or by reaction with dimethyl sulfide. The net result of the ozonolysis-reduction sequence is the cleavage of the molecule at the carbon-carbon double bond oxygen becomes attached to each of the carbons that had originally been doubly bonded. 

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