There are, of course, many ways to go about this reaction. Hydrogen peroxide in the presence of a Lewis acid (1), Caro’s acid (2), and NaIO4 (3) are a few examples. At industrial scale DMSO is manufactured using a catalytic NO2 / O2 system, but this is difficult to manage in the lab. Although many of these reaction conditions are high- yielding and selective, most published procedures have drawbacks. These may include:

  •  long reaction times (NaIO4)
  • cost (Magnesium Monoperoxyphthalate)
  •  and safety (Potassium Peroxymonosulfate, sodium percarbonate, vanadium (V) oxide)  (4,5).

The selective oxidation of sulfides to sulfoxides is commercially relevant in the case of

 

Large scale sulfide oxidation: Prevacid ® (Lansoprazole)

Takeda’s proton pump inhibitor Prevacid® (Lansoprazole). The final step requires the oxidation of Lansoprazole sulfide, and a thoughtful analysis of oxidants appropriate for use on a manufacturing scale was recently published (5).

In our case, we decided to evaluate three options, all of which used a form of ‘activated’ hydrogen peroxide. The reagents were prepared to test:

  •  a variation of the Payne reaction (acetonitrile / H2O2)  (4)
  • A TMSCl-promoted oxidation (6)
  • an interesting PVP-supported hydroperoxide oxidation reagent (7)

 

 

Artie McKim.

(1) Watanabe, Y.; Numata, T.; Oae, S. Synthesis (1981) 204

(2) Lakouraj, M.M.; Movassagh, B.; Ghodrati, K. Synth. Commun. 32, (2002) 847 (3)

(3) Leonard, N.J.; Johnson, C.R. J. Org. Chem. 27 (1962), 282

(4) Page, P.C.B.; Graham, A.E.; Bethell, D.; Park, B.K. Synthetic Communications 23, 11  (1993) 1507-1514. The authors make the interesting comment that MCPBA ‘will soon be withdrawn from sale’. This paper was somewhat dated by the time I came across it, but has MCPBA supply been constrained?

(5)  Harrington, P. J. Pharmaceutical Process Chemistry for Synthesis: Rethinking the Routes to Scale-Up  John Wiley and Sons, Pubs. Hoboken, NJ (2011) p. 228-237

(6) Bahrami, K.; Khodaei, M.M.; Yousefi, B.; Arabi, M.S. Tetrahedron Letters 51 (2010) 6939-6941

(7) Lakouraj, M.M.; Aghajani, B.; Mokhtary, M. Phosphorus, Sulfur, and Silicon 185 (2010) 2393-2401