Selective Mono-C-methylations of Arylacetonitriles and Arylacetates with Dimethylcarbonate:  A Mechanistic Investigation

Abstract

The very high mono-C-methylation selectivity (>99%) of arylacetic acid derivatives (ArCH 2 X; X ) CN, CO 2 Me) with dimethyl carbonate (DMC) is due to a mechanism that involves consecutive methoxycarbonylation, methylation, and demethoxycarbonylation steps. Important aspects of this mechanism are clarified herein by a kinetic investigation. In the case of arylacetonitriles, at 140°C, the comparison of the rate constants of model reactions involving 2-phenyl propionitrile, phenylacetonitrile, 2-methoxycarbonylphenylacetonitrile, and 2-methyl-2-methoxy carbonylphenyl acetonitrile (compounds 1a-4a, respectively) with DMC indicates that the methylation process is the fastest and the irreversible step, which drives the overall reaction to completion. The situation is reversed for arylacetic esters, where the methylation is more difficult than the demethoxycarbonylation reaction; therefore, a higher reaction temperature is required.

Sulfur and Nitrogen Mustard Carbonate Analogues

“…[10] In this work, we account for the first time on the synthesis and chemical behaviour of nitrogen and sulfur half-mus- Figure 2. Sulfur and nitrogen half-mustard carbonate analogues 2-7 and the carbonate 1 used as reference compound for this study.…”

“…We already reported some examples where substituting chlorine chemistry with DMC and taking advantage of the related B Ac 2/B Al 2 reaction mechanism resulted in quite unexpected outcomes, i.e., the selective mono-C-methylation of CH 2 -acidic compounds such as arylacetonitriles, intermediates for the synthesis of anti-inflammatory drugs. [10] In this work, we account for the first time on the synthesis and chemical behaviour of nitrogen and sulfur half-mus- Figure 2. Sulfur and nitrogen half-mustard carbonate analogues 2-7 and the carbonate 1 used as reference compound for this study.…”

Direct synthesis of N-methylurethanes from primary amines with dimethyl carbonate

“…(1) (2) In some cases, such discrimination was shown to be complete: more than 99 % selectivity was obtained for the O-methylation of phenols and the mono-methylation of CH 2 acidic compounds like *Paper based on a presentation at the 4 th International Conference of the Chemical Societies of the South-Eastern European Countries 3 3 3 2 arylacetonitriles, arylacetates, aryloxyacetic esters, sulfones, sulfoxides, and lactones [5]. Actually, in the latter cases, the mono-methyl derivative is the final outcome of a series of reactions that proceed selectively.…”

Upgrading of Biobased Lactones with Dialkylcarbonates

“…K 2 CO 3 in the presence of DMC at T > 200°C. 44 Although this possibility is plausible, it should be noted that the nucleophilic activation of phenylacetonitrile by K 2 CO 3 was observed previously at temperatures as low as 140°C, 59 where the formation of methoxide is likely to be disfavored. It was readily apparent that the reactions of GBL with DMC and DEC (products 1c and 2c of Table 8) suffered from the formation of byproducts.…”