I've been finding a ton of conflicting information on this topic regarding monomethylations and dimethylations.
Some people have insisted that the formaldehyde imine is not easily reversible in water and tolerates a wide range of PH's, allowing for an indirect
monomethylation without the risk of dimethylation caused by reverse-formation of the imine. A sign for this being the noticeably exothermic reaction
that happens when aq. formaldehyde is added to alkyl amines.
Alternatively there was a study(attached below) involving the mono- and di- methylation of carboxylic acids using zinc/formaldehyde, that stated a
mildly acidic phosphate buffer was needed to control monomethylation. Though some have suggested this is due to the resonance effects of the
carboxylic acid that destabilizes the formaldehyde-imine.
The only papers on this topic I could find are the one attached below. There were many people on this forum throughout many threads claiming the aq.
formaldehyde imine formation of alkyl amines is not easily reversible, often citing the Rhodium archives entry as a source, which doesn't help seeing
as those entries are not notoriously detailed or accurate most of the time.
Can anyone provide insight into the stability dynamics of this formaldehyde imine in aq. solutions? What is it about the formaldehyde imine in aq.
solutions that seems to lie to the right of the imine equilibrium?
Usually a cosolvent is used when forming imines with aqueous formaldehyde. Methanol is best for stabilizing imines. If you are asking about the
stability of an isolated imine in pure water, the answer will depend entirely upon the specific system being studied, rather than any general
assumptions about 'imines'.
[Edited on 5-5-2014 by forgottenpassword]FireLion3 - 5-5-2014 at 07:52
Does this happen due to the imines general solubility in organic solvents, causing it to be mostly separated from the aq. layer when the aldehyde
attaches to the amine?
I have noticed there seems to be time given to allow for formaldehyde to react with the amine in the solution before, ~15-30 minutes, before
attempting to reduce the imine.Nicodem - 6-5-2014 at 06:19
Ammonia and amines do not form imines with formaldehyde. The product with ammonia is hexamine, which is stable toward hydrolysis in basic, neutral and
up to fairly acidic media. The primary amines give the corresponding 1,3,5-trialkylhexahydro-s-triazines. Secondary amines initially get
N-hydroxymethylated and yield 1,1-bis(dialkylamino)methanes as the final products.
All these do form trough transient imines and iminiums which are nevertheless not the reaction products. You would better review the literature
instead of asking such a wide and undefined questions. Like forgottenpassword said, the answer depends on the specific reaction system and conditions.FireLion3 - 6-5-2014 at 19:13
See, that is a very interesting piece of information. Out of all the pages I looked at regarding the reaction of formaldehyde with primary amines
there was not any mention of any formed triazines. All of them seem to declare it as simple as:
No sources I have encountered have made any sort of statement regarding intermediate triazines in this process. And these are stable in aqueous
solutions?
Nicodem, what would be the structure of something like that, "1,3,5-trialkylhexahydro-s-triazines"? Cross reference searching formaldehyde, primary
amines, and/or triazines does not yield any results other than unrelated excerpts from various sources. I hope I can get a visual idea of how this
structure is formed, and then hydrogenated to the secondary amine.
Edited:
Been looking into these triazines, interesting. Was taking a look at how ammonia forms to hexamine..... is the formaldehyde-triazine molecule formed
between 3 molecules of the amine? If so, this sounds like it could pretty badly distort chirality, yet, for instance in the Eschweiler–Clarke
reaction amines do not racemize during this sort of interaction/reduction with formaldehyde.
