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Sulfuric acid-promoted DMSO oxidation of benzylic alcohols

29 Mar 18
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DMSO is a useful reagent for selective oxidation of primary alcohols to aldehydes.  These oxidations generally involve DMSO activation by another species such as dicyclohexylcarbodiimide [Pfitzner-Moffatt oxidation], oxalyl chloride [Swern oxidation] or pyridine sulfur trioxide [Parikh-Doering].  While these reactions have been widely used, they have some disadvantages in terms of atom economy, cost, difficult reaction conditions (low temperature, anhydrous atmosphere), toxicity, and unwanted byproducts.  The newly reported procedure by Sheikhi’s group, however, eliminates many of these disadvantages and provides a low cost alternative procedure to convert benzylic alcohols to benzaldehydes using only sulfuric acid and DMSO (Figure 1).1

Figure 1: Oxidation of a benzylic alcohol in DMSO and sulfuric acid.

These researchers found that the best yields were achieved under reflux and excellent yields were achieved with 0.5 equivalents of sulfuric acid in approximately 2-2.5 hours. (The yields with one equivalent of sulfuric acid were only marginally better in all cases; however, they were accomplished in approximately one half of the time.)

The reaction was successful with a variety of substituents on the aromatic ring.  (Figure 2 shows a few examples.) Even the benzyl alcohol with a strongly electron withdrawing group (4-NO2) still gave a very good isolated yield (78%) with 0.5 equivalents of sulfuric acid.

Of note, the authors state that in all cases there was no need for purification after the reaction.  The workup for the reaction simply required the addition of brine and extraction of the product into dichloromethane.  After drying of the organic layer and removal of the solvent, the authors state that only high purity product remained.

Figure 2: Isolated yields with 0.5 equivalents of sulfuric acid

While these researchers did not undertake mechanistic studies, they did offer a proposed mechanism given the reaction conditions (Figure 3).  They proposed that the reaction proceeds through carbocation formation at the benzylic position.  This is followed by the attack of DMSO, deprotonation of the resulting intermediate, and an intramolecular proton exchange leading to creation of the aldehyde and dimethylsulfide.

Figure 3:  Proposed mechanism

In conclusion, this work shows an alternate method to use DMSO as an efficient and high yielding oxidant to convert benzylic alcohols into aldehydes.  This method only requires inexpensive and readily-available sulfuric acid and DMSO.  In addition, this method does not result in the generation of difficult-to-handle unwanted byproducts.

 

Debra Dolliver, Ph.D.

 

References

  1. Sheikhi, E.; Adib, M.; Karajabad, M. A.; Gohari, S. J. A. Synlett 2018, 29, A-E.
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