Monomethylation of arylacetonitriles and

Monomethylation of Arylacetonitriles and Methyl Arylacetates with Dimethyl Carbonate. a Hydrolysis of 2-Arylpropionitriles and Methyl 2-Arylpropionates to 2-Arylpropionic Acids. b... 

Dimethylcarbonate (DMC) is an environmentally friendly substitute for dimethylsulfate (DMS) and methyl halides in methylation reactions. It is also a very selective reagent. The reactions of DMC with methylene-active compounds produce monomethylated derivatives with a selectivity not previously observed. The batchwise monomethylation of arylacetonitriles, arylacetoesters, aroxyacetonitriles, methyl aroxyacetates, ben larylsulfones and alkylarylsulfones with DMC achieve >99% selectivity at 180-220°C in the presence of K2CO3. Mono- -methylation of primary aromatic amines at 120-150 °C in the presence of Y- and X-type zeolites, achieved selectivities up to 97%. At high temperature (200°C) and in the presence of potassium carbonate as the catalyst, DMC splits benzylic and aliphatic ketones into two methyl esters in contrast, DMC converts ketone oximes bearing a methylene group to 3-methyl-4,5-disubstituted-4-oxazolin-2-ones. Dibenzylcarbonate... 

The monomethylation reactions of arylacetonitriles and arylacetoesters start from readily available intermediates and produce 2-arylpropionic acid (antiinflamatory drugs, e.g. ketoprofen, naproxen, etc.). Using a 10-30 molar excess DMC, either under GL-PTC (5) or batch conditions (6), it is possible to synthesize 2-arylpropionic acid derivatives with >99% purity in monomethyl derivatives (Eq. 3). 

Methylation of activated toluenes. Arylacetonitriles and methyl arylacetates are monomethylated at the benzylic position on heating with (MeO)2CO and K2COJ in an autoclave at I80°C. 

The unusually high selectivity observed in the monomethylation of methyl aryloxyacetates and aryloxyacetonitriles may be explained by the mechanism previously described for the reaction of DMC with methyl arylacetates and arylacetonitriles (6) in which ArCH(COOCH3)X and ArC(CH3)(COOCH3)X are the key intermediates. It is likely that this reaction proceeds through the formation of methyl-carboxymethyl intermediates, ArOC(CH3)(COOCH3)X, as these derivatives were actually detected by GC/MS during the course of the reaction. In this case, the attack on the acyl carbon, which produce the possible intermediate PhC(COOCH3)2X, does not affect selectivity, because it is an equilibrium reaction. 

---