Elimination of oxidative degradation during the per-O-methylation of carbohydrates

J Am Chem Soc. 2003 Dec 31;125(52):16213-9. doi: 10.1021/ja035660t.


The possible oxidative degradation mechanism occurring during the per-O-methylation of carbohydrates in dimethyl sulfoxide with methyl iodide in the presence of base is described. Evidence is presented that this process occurs only under anhydrous conditions when there is a long reaction time between the carbohydrate dissolved in dimethyl sulfoxide and methyl iodide, followed by reaction with the base. Under these specific conditions, the oxidative degradation of alditols, and cyclic carbohydrates, with and without a free hemiacetal group, is observed. The reaction between carbohydrate and methyl iodide in dimethyl sulfoxide can result in a complete oxidative degradation depending on the type of carbohydrate and the time of reaction. The oxidative degradation can be accelerated by replacing methyl iodide with dimethyl sulfate. Mass spectrometric identification of the degradation products of d-glucitol indicates simultaneous oxidation processes at all the hydroxyl groups, with site dependent rates of their reactivity. This oxidative process is not a characteristic of the methylation of carbohydrates in dimethyl sulfoxide with methyl iodide in the presence of solid sodium hydroxide and can be totally avoided by treating the carbohydrate with powdered sodium hydroxide before introduction of methyl iodide under nonanhydrous conditions, or by adding a trace of water in dimethyl sulfoxide before methyl iodide, or by using N,N-dimethylacetamide as the solvent. The degradation of the per-O-methylated carbohydrates in the liquid-liquid extraction process is also taken into account, and it is found that the degradation process can be avoid by neutralization of the base before extraction, by using benzene or tetrachloromethane as extraction solvent, and by drying the final organic extract.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrates / chemistry*
  • Dimethyl Sulfoxide / chemistry
  • Fructose / chemistry
  • Gas Chromatography-Mass Spectrometry
  • Glucose / chemistry
  • Hydrocarbons, Iodinated / chemistry
  • Methylation
  • Oxidation-Reduction
  • Sodium Hydroxide / chemistry
  • Sorbitol / chemistry


  • Carbohydrates
  • Hydrocarbons, Iodinated
  • Fructose
  • Sorbitol
  • Sodium Hydroxide
  • methyl iodide
  • Glucose
  • Dimethyl Sulfoxide