Global Warming Causes

Batch Methylation Reactions with DMC

Under batch conditions, methylations with DMC must necessarily be run in sealed autoclaves, given its boiling point (90°C) and the reaction temperature (>160°C). Batch methylations with DMC can be performed on a number of different substrates and, under such conditions, the reaction mechanism can be conveniently investigated: in fact, the sampling of the reaction mixture at different conversions, and the identification of possible intermediates (see later) is easier with respect to CF-processes. For compounds that are susceptible to multiple methylation, the results are of special interest, since methylation with DMC totally inhibits multiple substitution in both N- and C-alkylation, for primary aromatic amines and for CH2-active compounds, respectively.

The most interesting and best-studied reaction, particularly in view of its selectivity, is the mono-C-methylation of arylacetonitriles (Scheme 4.6).

In the presence of a weak base (usually K2CO3), these compounds can be

Scheme 4.6 Mono-C-methylation of arylacetonitriles (X = CN).

Scheme 4.6 Mono-C-methylation of arylacetonitriles (X = CN).

effectively mono-C-methylated with an unprecedented selectivity—greater than 99%—at complete conversions. For instance, when a mixture of PhCH2CN, DMC, and K2CO3 in a 1:20:2 molar ratio, respectively, was allowed to react at 180°C for 3.75 h, 2-phenylpropionitrile was obtained in a 95% yield with a purity >99%.19 For comparison, in the same reaction run under PTC conditions and using CH3I, the mono- to dimethyl-derivative ratio never exceeded 2.4.20 The very high monomethyl selectivity has turned out to be much interesting for the synthesis of precursors for anti-inflammatory drugs: some examples are listed in Table 4.5.

Similarly, in the presence of weak inorganic bases (K2CO3), the reactions of DMC with sulfones bearing a-methylenic groups (RCH2SO2R'; R = Alkyl, Aryl; R' = Aryl) afford the respective mono-C-methylated compounds [RCH(CH3)SO2R'] with >99% selectivity at complete conversions (Scheme 4.7).21

Conditions: Autoclave, substrate:DMC:K2CO3 = 1:18:2 molar ratio, T = 180-220°C.

Conditions: Autoclave, substrate:DMC:K2CO3 = 1:18:2 molar ratio, T = 180-220°C.

Was this article helpful?

Growing Soilless

This is an easy-to-follow, step-by-step guide to growing organic, healthy vegetable, herbs and house plants without soil. Clearly illustrated with black and white line drawings, the book covers every aspect of home hydroponic gardening.

Get My Free Ebook