Mono-C-methylation

Another way in which to gain structural information concerning the N-terminal residue of glycophorins A" and A is to study the N-terminal, mono[ C]methyl derivatives these are produced by using limited amounts of [ C]formaldehyde. There are distinct differences between the N, N -di[ C]methylamino and N -mono[ C]methylamino species (i) a significant, chemical-shift difference exists between the N-terminal dimethyl and monomethyl species (43 and 34 p.p.m.) (li) all of the C resonances of the N-terminal dimethyl species move upheld as the pH is increased (if they move at all), whereas all of the C resonances of the N-terminal, monomethyl species move downfield as the pH is increased and (in) A for the N-terminal monomethyl species tends to be much larger than that for the N-terminal dimethyl species. Point (in) would tend to indicate that it may be more advantageous to study the N-terminal monomethyl species. However, because of allowable protein concentrations, detection limits on available instruments, and technical difficulties, it has thus far... 

Table III gives the titration parameters for the C resonances of the N-terminal mono[ C]methyl labels of a variety of peptides and glycopep-tides related to the N-terminus of glycophorins and A. The titration...

Data of Figure 1 show that at low temperature the prevailing product was 3-MA, while the formation of C-methylated compounds was considerably lower. On increasing the reaction temperature, and hence the conversion of m-cresol, the selectivity to 3-MA rapidly decreased, while that to C-methylated compounds correspondingly increased. Amongst the latter, products of ortho C-methylation (2,3- and 2,5-DMP) were clearly favored with respect to that of para methylation (3,4-DMP). However, the formation of mono-C-methylated compounds was accompanied by consecutive polyalkylations, and the corresponding products became soon the prevailing ones, when the reaction temperature was raised above 350°C. 

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

Similarly, in the presence of weak inorganic bases (K2CO3), the reactions of DMC with sulfones bearing a-methylenic groups (RCH2SO2R R = AUcyl, Aryl R = Aryl) afford the respective mono-C-methylated compounds [RCH(CH3)S02R ] with >99% selectivity at complete conversions (Scheme 4.7). ... 

Figure 4.4 The mono-C-methylation of o-tolylacetonitrile with DMC. Gaschromatograms refer to different reaction times, (a) 0CH3C6H4CH2CN (b) o-CH3CgH4CH(CH3)CN (c) o-CH3C6H4CH(C02Me)CN (d) o-CH3C6H4C(Me)(C02Me)CN.

Scheme 4.10 Mechanism of the mono-C-methylation of CH2-active compounds (X = CN, CO2CH3) with DMC.

Dimethylcarbonate, in presence of K2CO3, has been found to react with benzyl aryl and alkyl aryl sulfones RCH2S02Ar at 180-210 °C to form the corresponding mono-C-methyl derivative selectively and in high yield. The monomethylation has been attributed to a methoxycarbonylation-methylation-demethoxycarbonylation sequence via ArS02C(Me)(C02Me)R. 

Mono-C-Methylation of Arylacetonitriles and Methyl Arylacetates by Dimethylcarbonate A General Method for the Synthesis of Pure 2-Arylpropionic Acids. 

Methylations. Phenols are converted to their methyl ethers on reaction with CsjCOj and COCOMe). At a relatively high temperature (180°) alkyl aryl sulfones undergo mono-C-methylation. Primary arylamines also give monomethyl derivatives when a zeolite catalyst is present. ... 

Tundo, P. Selva, M. Bomben, A., Mono-C-methylation of Aryacetonitriles and Methyl Arylac-etates by Dimethyl Carbonate A General Method for the Synthesis of Pure 2-Arylpropionic Acids. 2-Phenylpropionic Acid. Org. Syn. 1998,16,169. 

Figure 1.12 summarizes the result of this comparative evaluation of DMC as green methylating agent. The assessment was based on atom economy (AE) and mass index (MI) for three model transformations O-methylation of phenol, the mono-C-methylation of phenylacetonitrile and the mono-N-methylation of aniline. 

MONO-C-METHYLATION OF ARYLACETONITRILES AND METHYL ARYLACETATES BY DIMETHYL CARBONATE, 76, 169... 

FLUORO-2-PHENYLPROPANE, represents another route to a number of monofluorinated compounds. The mono-C-methylation of arylacetonitriles and methyl arylacetates by dimethyl carbonate as a route to 2-arylpropionic acids is exemplified by the synthesis of 2-PHENYLPROPIONIC ACID, the simplest member of an important class of anti-inflammatory agents. 

Pietro Tundo, Maurizio Selva, and Andrea Bomben 169 MONO-C-METHYLATION OF ARYLACETONITRILES AND METHYL ARYLACETATES BY DIMETHYL CARBONATE A GENERAL METHOD FOR THE SYNTHESIS OF PURE 2-ARYLPROPIONIC ACIDS. 2-PHENYLPROPIONIC ACID... 

Pietro Tundo, Maurizio Selva, 169 MONO-C-METHYLATION OF... 

Sulfones bearing a-methylene groups (benzylaryl- and alkylaryl-sulfones ArCH2S02Ar and RCH2S02Ar ) can be effectively mono-C-methylated (selectivity >99%) by DMC, even when a mild base (K2CO3) is used (9) (Eq. 5). 

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