Hello guys.
I have faced the problem of being in need of carboxyl-methylated amino acids.
Amino acids I need are not available in the market so I need to synthesize them by myself.
So thus I'm now finding the method for synthesizing.
But what I found was the derivatization of amino acid for GC that can methylate the amine group either, which cannot be used.
And also found the method using acid and dimethylcarbonate but I'm not sure about the amount for that, because the molarity was too small.
So, thanks for reading
The classic way is to buy or make a solution of anhydrous HCl in methanol, approximately 1-4 M, then dissolve the amine in it and reflux it for an hour or so. Following it by TLC helps determine when the methylation is done. This doesn't work for all amino acids, because some will also react. I have successfully done it with serine, alanine, glycine, phenylalanine, phenylglycine and derivatives, valine, leucine, isoleucine, and tyrosine. I have not tried it and would not recommend trying it with tryptophan, glutamine, asparagine, ornithine, citrulline, or cysteine without a literature precedent, in order to give the best conditions. Refluxing any acid with methanol for protracted periods (longer than overnight) will convert methanol to dimethyl ether and water, which decreases the effectiveness of methylation as water accumulates. The lack of methylation of the amine in these circumstances is due to conversion of the free amine group, R-NH2, into an unreactive ammonium salt, R-NH3(+). The hydrochloride salt-methyl ester of many common amino acids are available commercially.
A more risky way to methylate any carboxylic acid with great selectivity over amines is by using diazomethane, which is explosive when concentrated and (of course it follows) in pure form. It can be generated and handled as a yellow solution in ether, but after the reaction is done, any excess must be destroyed by adding an excess of a suitable acid like acetic acid (becomes methyl acetate) or formic acid (becomes methyl formate). In my experience amino acids in zwitterionic form (with a protonated amine and a deprotonated carboxylic acid) do not react unless there is a high concentration at equilibrium of the carboxylic acid. Inorganic acid groups like sulfonic and phosphonic acids are also methylated. Phenols are not readily methylated this way. I've only ever done this on a "much less than a gram scale" of starting acid. Please consult an experience user of diazomethane AND suitable published examples before going this route.
There are other ways but I shouldn't say more unless there's more information about the amino acid being methyl-esterified. Best wishes.
Diazomethane is a reagent known for methylating carboxylic acids and alcohols selectively. It can be used to methylate hydroxyl groups in amino acids without reacting with the amine groups.
Example reaction: Amino acid + Diazomethane → O-methylated amino acid + N2 . As it can Amino acids can be converted to their methyl esters (if not already in ester form) using diazomethane or other esterification methods. The methyl esters can then be hydrolyzed under mild conditions to yield the O-methylated amino acids.
Example reaction: Amino acid ester + Hydrolysis → O-methylated amino acid + Alcohol
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