Oxidation of Sulfides to Sulfoxides an Anti-ulcer Medication

4 Oxidation of Sulfides to Sulfoxides an Anti-ulcer Medication 

Astra-Zeneca commercialized esomeprazole (the S enantiomer of omeprazole) obtained by asymmetric oxidation of pyrmetazole (Equation 28) in 2000, using a modified version of the Kagan-Modena protocol. Esomeprazole is an anti-ulcer medicine and one of the largest selling drugs worldwide. It is produced under very mild conditions in a multi tonne per year scale. 

The transformation of the laboratory protocol into this successful industrial process was facilitated by i) the addition of an organic base (diisopropylethyla-mine), which substantially increased both the ee and the productivity ii) the addition of the appropriate amount of water (0.5/1 with respect to Ti) which directly influenced the stereochemical outcome Hi) the use of a 1 2 ratio of [Ti(0- -Pr)4] and diethyl tartrate iv) the use of cumene hydroperoxide as the oxidant v) the replacement of chlorinated solvents with more environmentally friendly ones (toluene, ethyl acetate) and vi) carrying out the oxidation at higher and technically more convenient temperatures than before ( 0-30°C vx. -20°C). 

Discussion Point DPS The Sharpless enantioselective catalyst system has some substantial disadvantages with respect to other enantioselective systems name at least two. Enantioselective oxidation is to some extent underdeveloped with respect to e.g. hydrogenation can you establish logical connections with i) the stability of catalysts in the reaction medium ii) the nature of the oxidants used and their environmental impact Hi) the number of reactions that can successfully be accomplished. 

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