Omeprazole Mechanism (I)

From WikidChem

slide 21 This slide shows a mechanism for creating omeprazole, which is chiral because of the non-planar structure of its sulfoxide group. Starting out with a sulfide group (two 'R' groups and two lone pairs on the Sulfur atom) and a peroxy acid, one notices that the lone pairs on sulfur in the sulfide group are both unusually high homos, and that the O-O* antibonding orbital of the peroxy acid is an unusually low lumo. Since oxygens are low in energy to begin with, an O-O* antibonding orbital will be unusually low due to poor overlap and energy splitting.

(I think that the O-O* bond is unusually low just because O has such low energy to begin with and that poor overlap and energy splitting is what makes any LUMO a LUMO, but not necessarily a low LUMO.) (O has a higher nuclear charge than carbon, and is thus located below the "normal" dotted line on energy diagrams! This makes it a low LUMO because it starts out lower-AB)

In the resulting reaction between the sulfide group and the peroxy acid, sulfur donates a lone pair to the antibonding orbital between the two oxygens, breaking the bond. The O-H group from peroxy acid thus forms a bond with the sulfur atom, which is now positively charged, and the oxygen that remains with the product acid will receive two electrons and become negatively charged (after this it no longer affects the reaction).

Now, there is a low lumo on the sulfur atom because of its vacant d-orbital. Its positive charge also makes it likely to react (A positive charge suggests an absence of electrons, which would make for a lower LUMO -AB). There is a high homo on the oxygen atom of the hydroxyl group(a lone pair occupying a p-orbital). This will cause a double bond to form between sulfur and oxygen(which will now have a positive charge). (Note that there is a double headed arrow between the molecule with the vacant d-orbital and the one with a double bond between the S and the O. This means that these two are resonant structures and that the real way that the two interact is inbetween the way our Lewis structures show them as. It is not an equillibrium between two different molecules as the next one is.-KJA)

The product cation is acidic, thus the hydrogen bonded to its oxygen can be lost to any old molecule with an unshared pair of electrons. Finally, a sulfoxide has been created- in essence omeprazole (if the two R groups are the proper constituents substituents). When this entire reaction takes place, a racemate is created as the product, since either lone pair from the sulfur of the sulfide group could have been the high homo. last modified by J Michael McBride (mcbride) on Dec 5, 2006 8:41:25 AM