Figure 4.4 The mono-C-methylation of o-tolylacetonitrile with DMC. Gaschromatograms refer to different reaction times. (a) o-CH3C6H4CH2CN; (b) o-CH3C6H4CH(CH3)CN; (c) o-CH3C6H4CH(CO2Me)CN; (d) o-CH3C6H4C(Me)(CO2Me)CN.
ArC'-'HX + (CH30)2C0 , - ArCH(COOCH3)X + CH30" (2)
ArCH(COOCH3)X + B - ArC<->(COOCH3)X + BH+ (4)
ArC'-)(COOCH3)X + (CH30)2C0 —Ar-C—X +C02+CH30" (5)
H3COOC 4 | *6 _ Ar-Ç—X +CH30" - ArC<-)(CH3)X + (CH30)2C0 (6)
Scheme 4.10 Mechanism of the mono-C-methylation of CH2-active compounds (X = CN, CO2CH3) with DMC.
DMC proceed through the corresponding methoxycarbonylated and methyl methoxy carbonylated intermediates [WCH(CO2Me)X and WC(Me)(CO2Me)X; W = ArO, X = CN, CO2Me; W = Ar, X = SO2R].
In the particular case of methyl sulfones (ArSO2Me), the pathway of Scheme 4.10 also accounts for the previously mentioned homologation of the methyl to ¿-propyl group. In fact, once the methoxycarbonylated compound ArSO2CH2CO2Me is formed, only two protons remain available for the next methylation step.
In order to investigate in more depth the mechanism of Scheme 4.10, a detailed kinetic analysis has been performed by choosing the methylation of phe-nylacetonitrile (2a) and methyl phenylacetate (2b) with DMC as model reactions.25 Some general considerations are the following.
In the case of compound 2a, the rate-determining step of the overall transformation is the methoxycarbonylation reaction (step 2). The similarity of k_2 and k6
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