Dimethyl sulfide reaction sequence

Thermal Stability. Dimethyl sulfoxide decomposes slowly at 189°C to a mixture of products that includes methanethiol, formaldehyde, water, bis(methylthio)methane, dimethyl disulfide, dimethyl sulfone, and dimethyl sulfide. The decomposition is accelerated by acids, glycols, or amides (30). This product mixture suggests a sequence in which DMSO initially undergoes a Pummerer reaction to give (methylthio)methano1, which is labile and reacts according to equations 1—3. Disproportionation (eq. 4) also occurs to a small extent ... 

Powerful evidence for the intermediacy of a metaphosphorimidate of type 189 nevertheless comes from the product spectrum obtained on reaction of 202 with KOH in ethanol or propanol. The principal products dimethyl sulfide and potassium O-ethyl (or propyl) phosphoramidate can be readily rationalized in terms of the reaction sequence presented in the Scheme 138). 

Primary amino methylene substituents were introduced by a sequence of cya-nodehalogenation and subsequent reduction of the resulting nitrile with borane dimethyl sulfide. To incorporate tertiary aminomethylene substituents into the 2-pyri-done framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. 

In the first step of this reaction sequence, the primary alcohol 21 is oxidized to the corresponding aldehyde 38 in a Parikh-Doering oxidation which is related to the Swern oxidation. In general, this type of oxidation is conveniently carried out by addition of a solution of pyridine-SOs complex in DMSO to a mixture of the alcohol, DMSO and NEts. It can be assumed that dimethyl sulfoxide and sulfur trioxide react to form 0-dimethylsulfoxonium sulfate 40, which then further reacts with primary alcohol 39 to give 0-alkyl dimethylsulf-oxonium intermediate 41. Then, sulfonium salt 42 is formed and subsequently deprotonated by NEts to give sulfonium ylide 43. Finally, an intramolecular p-elimination occurs to provide the desired aldehyde 44 and dimethyl sulfide. 

Oxidation of methylpyridines to pyridine aldehydes. a-Picolines are oxidized to the corresponding aldehydes by treatment with one equivalent of iodine at room temperature to form a crystalline complex which is then dissolved in DMSO.1 The reaction mixture is then heated to 140-160°, when dimethyl sulfide is evolved. The aldehydes are extracted after neutralization. The oxidation is considered to involve the following sequence ... 

The ring-chain isomerisation of phosphino-substituted triazolo-pyridines was found to depend on the nature of the phosphine substituent. Conversion of the phosphines to their selenides resulted in a complete shift of the equilibrium towards electron-acceptor structure D (Scheme 10). Acenaphthene and acenaphthylene were converted to polycyclic phosphole derivatives via Ti(II)-mediated cyclization of the corresponding dialkynylated arenas. The related phosphole oxides were stable species (Scheme 11). Asymmetric lithiation of dimethyl-tert-butylphosphine sulfide and trimethylsilylation gave an intermediate that was subjected to a five-step reaction sequence including metallation, P-functionalization (in three steps) and removal of the silyl group to yield the precursor of Mini-PHOS (Scheme 12). ... 

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. 

Amides lactams. Dimethyl thioketals of cyclic or acyclic ketones react with iodine azide to form an a-azido sulfide in 75-95% yield. The product rearranges to an amide or a lactam in high yield in the presence of trifluoroacctic acid. This sequence is an attractive alternative to the Beckmann rearrangement or Schmidt reaction. 

In contrast to these results, it has been demonstrated that a-(methylthio)tosylhydrazone monoanions, formed by reaction of an initially formed dianion with dimethyl disulfide, undergo in situ dianion formation rather than elimination, to give vinyl sulfides (Scheme 71 ). Since vinyl sulfides can be hydrolyzed to ketones, this sequence constitutes a very effective 1,2-carbonyl transposition. 

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