The Study On O And N-Methylation Reactions Using Dimethyl Sulfoxide As Carbon Source

Dimethyl sulfoxide has been widely used as solvent in chemical reactions due to its low toxicity, low cost, great dissolving capacity and relative stability. Meanwhile, it can be also used as a mild oxidant and an oxygen source. In recent years, DMSO is considered as a safe, green, practical carbon source and attracted more and more attention in organic synthesis. Many chemists have reported that DMSO can partici-pate in reactions by acting as a methyl, formyl, methylthiol, methyl sulfone or cyano source. Although, DMSO served as carbon source has been well studied, to the best of our knowledge, only few examples were reported that DMSO was used as methyl source. In this paper, oxygen and nitrogen methylation were systematically studied by using DMSO as a methyl source.（1）The O-methylation with DMSO as methyl source was studied. At first, benzoic acid was chosen as the model substrate for the optimization of the reaction conditions. After a tedious reaction parameters screening, such as reaction temperature, type of catalyst and so on, we got the optimized conditions:benzoic acid 0.5 mmol, CaCl₂ （1.0 equiv.）, K₂CO₃（1.0 equiv.）, CuCl₂-2H₂O （10%）,30% H₂O₂（3.0 equiv.）, DMSO （2.0 mL）,80℃, O2,15 h. With this optimized conditions in hand, we discussed the substrates scope of carboxylic acids and sulfoxide compounds. Then, on the basis of optimised reaction conditions above, we used phenol as the model substrate and got the best reaction conditions, the substrate scope of phenol was also studied. In addition, alcohols, aldehydes and ketones were tested under these optimized reaction conditions and they were found unsuitable in this reaction system. Finally, control experiments and isotope labeling experiments were conducted to get more information of the reaction mechanism, and a possible reaction mechanism was given at last.（2）The N-methylation reaction of amines using DMSO as methyl source was studied. Initially, Aniline was treated as model substrate to get the optimal reaction conditions:aniline:0.5 mmol, CaCl₂ （1.0 equiv.）, CuCl₂-2H₂O （10%）, K₂CO₃ （2.0 equiv.）,30% H₂O₂（3.0 equiv.）, DMSO （2.0 mL）,70℃, Air,15 h. Then, the substrate scope of primary and secondary amines were explored under the optimized conditions. In addition, the mesylation of primary amines and formylation of secondary amines with DMSO were also studied.（3）The selectivity of methylation reaction of oxygen and nitrogen was discussed. Firstly,2-aminobenzoic acid was chosen to be model substrate, and some factors, such as base, reaction temperature, catalyst and the amount of hydrogen peroxide were found have little effect to selectivity. Then some multisubstituted substrates （-OH,-COOH or -NH₂） were employed to study the selectivity of methylation.