At which pH imine formation reaction between water soluble aldehydes and primary amines is the highest? Can protonated amines take part in the reaction?
A pH of around 5 is optimal for imine formation. At higher pH there is insufficient acid present and at lower pH the amine will be protonated rendering it unable to do a nucleophilic attack at the carbonyl carbon.
could you please provide any reference in this regard @ Phillip Leigh Van der Peet
What, if we have a very strong base amine, pKb = 4, so it is protonated from pH 10?
You need toprotonate the oxygen in order to actívate the system towards nucleophilic atack by the nitrogen. There is some sort of balance here. Too low the pH, gives an efficient protonation of the oxygen, but also of the nitrogen of the amine, so the production of the imine results inefficient. On the other hand, at higher pH values, the oxygen does not get protonated enough to trigger the reaction. So there is an optimum, between pH 4.5 and 6, for this reactionto take place.
Influence of the pH on imine formation in a water solution is that at highly acidic PH conditions the imine may get hydrolysed to form keto compound with the liberation of the ammonia.
With a base of pKb 4, at pH 5, the ratio of protonated base to deprotonated base would be 100 000:1. Though you might think that would be sufficient to bring the reaction to a halt, with such a low pKb it is likely that the amine in question would also be a strong neucleophile and the reaction would still proceed at an appreciable rate.
In acidic pH strong amines are completely protonated, probability of finding nonprotonated amine at pH1 is around zero. Probably in acidic condition mechanism of the reaction is different (?). May be aldehyde group is directly attacked by protonated amine (?).
Patrick,
Aryl amines (those bonded to a phenyl ring) are significantly less basic than their alkyl counterparts. The pKa of methylamine is 11, whereas aniline is around 4.5. This is due to delocalization of the nitrogen lone pair into the aromatic ring. While this reduces anilines basicity the phenyl ring may also donate electron density to the nitrogen, improving its nucleophilicity. Couple this with the ramped up acidic catalyses you'd see at pH 0 and I'm sure your detection reagent works an absolute treat. (The pKa of indole is around -2). Does your diagnostic test involve reducing the imine and isolating the amine as a salt?
Tomasz,
An aldehyde group could never be attacked directly by a protonated amine. Any such reaction would have to involve transfer of the proton from the amine to the aldehyde first in order to free up a lone pair on nitrogen, which might then attack the carbonyl carbon. I suspect such a proton transfer would be very unlikely. I'm not convinced the aldehyde necessarily be protonated prior to attack by the amine either. As long as there are protons available in the reaction media attack and protonation may occur as a concerted process.
We also conduct reaction between aliphatic amine and aldehyde group and observe a color product. Due to our observation reaction doesn’t go at the pH when amine is protonated, we have to get to very high pH, sometimes about 8... Theory is great, but practice is real...
Dear Patric, I believe You. May be the reaction path at acidic and basic pH are different. Sometimes we observe that reaction goes a bit different way. Sometimes it is a different reaction, but practical results are the final argument. Ultima ratio regis….
Patric, Phillip, Friends
I've dug deeper in the literature. There are two good pH for imine formation. One is 4-5, and second one is at pH 8-9. This second one (basic pH) reaction is quicker and equilibrium is more shifted towards imine (Schiff base) formation, at basic pH imine is more stable than in acidic.
[Bioconigate techniques, Greg Hermanson]
If one book says something – check another, if three books says the same – it means it is probable, but to be sure do experiment by yourself, and ask Your friend to repeat…and keep in mind that You may still be wrong…
Well put Tomasz, I never claim to be certain of anything but my name! Cordes and Jencks put it nicely in JACS way back when:
"N-p-chlorobenzylideneaniline formation, like that of oximes and semicarbazones,
undergoes a transition in rate-determining step from rate-determining dehydration of the carbinolamine addition product at neutral pH to rate-determining amine attack under acidic conditions"
In between you will have a trough. The exact pH ranges in which these two mechanisms function at a maximum rate will rely on the substrates.
Please check this reference. Hope it helps
Scheller et al. ChemCatChem 2015, 7, 3239 – 3242
Hi,
I want to synthsize imine crossloinked microgel and want to test the degradability, I read some papers. They said 1% (v/v) acetic acid solution is the media to conduct the synthesis. What about the exact pH of synthesis then and how to cleave that iminine functional group?
Dear Pabitra
What are the other componnents are You using, what type of microgell? Acidic condution speads up imine formation but also imine hydrolysis.
TC
It is consisting of PGMA and PVCL. It is expected to be a soft microgel with thermo and pH responsiveness. imine functionalised cross-linked point will behave as pH responsive part of the microgel. Do you have any suggestion how to test the degradibility of the microgel in presence of varying pH as imine is very labile to pH treatment!
The best is the book:
Bioconjugate techniques, Greg, Hermanson,
Check also our papers:
Dextran nanoparticle synthesis and properties, Plos One, v11,1, 2016, ss. 1-17.
Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett’s esophageal adenocarcinoma, International Journal of Nanomedicine, v10, 2015, ss. 6811-6823.
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