N-methylethanolamine and an OTC HMPA substitute from sarcosine?
It is well-known that sarcosine can react with formaldehyde to generate the azomethine ylide methylaminodimethylene, typically written as one
resonance isomer [SMILES: C=N+(C)C-], which undergoes 3+2 cycloaddition reactions with aldehydes to give oxazolidines, see e.g.:
https://www.sciencedirect.com/science/article/pii/S004040391...
It is also known that in some cases formaldehyde can react with azomethine ylides to give an oxazolidine, as seen in a number examples in this review:
https://mdpi-res.com/d_attachment/molecules/molecules-21-009...
Unfortunately, I have not seen any case where sarcosine itself reacts with two equivalents of formaldehyde to give the simplest possible product,
3-methyl-2H-oxazolidine. This would constitute a very simple preparation of mono-N-methylethanolamine by reaction of sarcosine with formaldehyde
followed by hydrolysis.
Now, this is the same as the product of reducing sarcosine with e.g. LAH, but (para)formaldehyde is much cheaper than LAH or any comparable reducing
agent.
So what does this have to do with HMPA? HMPA is a high-polarity aprotic solvent with resonance isomers that put a negative charge (delta-minus) on the
carbonyl oxygen atom. That negative charge allows it to solvate cations. It's also carcinogenic, which has motivated the use of expensive substitutes
like dimethylimidazolidinone (DMI) and DMPU.
If N-methylethanolamine is subjected to carbonyl substitution with urea and ZnO, analogous to the synthesis of cyclic carbonate esters, the expected
product is 3-methyl-2-oxazolidinone (3MOx). This is halfway in-between ethylene carbonate and DMI, with a very high dipole moment (5) and the desired
resonance structure.
For contrast, propylene carbonate, which also has a high dipole moment (though not as high as 3MOx or HMPA), has less negative charge on the carbonyl
oxygen because the ether oxygens don't give up their electrons as easily as an amide nitrogen. In fact, DMF often dissolves cations better than
propylene carbonate, even though the latter is more polar on paper. 3MOx, however, should offer the best of both DMF/PC.
It's also pretty expensive in and of itself, but unlike HMPA, DMI, or DMPU, it might be prepared from just three cheap commodity chemicals: sarcosine,
paraformaldehyde and urea.
[Edited on 04-20-1969 by clearly_not_atara]
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