Recently I had done this reaction with a phenyl derivative of phenylacetic acid with CDI(1,1 Carbonyl diimidazole) but the reaction never seems to go to completion no matter how long one keeps it. After work up as provided in the references for preparation of these class of compounds there are always two spots and the NMR reveals a mixture of product and unreacted starting material (acid). Yet none of the literature procedures for preparation of these class of compounds which I have gone through states that column chromatography was done (I wonder why) . Some have stated about recrystallization but I have significant amount of starting material (about 20%). I just can't seem to purify it.
Mr. Biswas,
Try with https://www.reaxys.com/, using the chemical diagrams of the reagents and/or products. There is obtained all possible synthetic roads, refs., conditions, and more.
And my desired organic compound is unstable in basic medium as workup with Sodium bicarbonate solution led to decomposition of my desired compound the first time I tried it to remove unreacted carboxylic acid.
Are you trying to isolate an amide coupling product or the activated imidazolide? Also, do you see recovered starting material due to low reactivity, or is your product hydrolyzing on work-up? In other words, have you checked your reaction by TLC to ensure it is complete before you work it up?
If you're product is unstable on workup, you can try cooling your reaction mixture and your washing solutions in an ice-bath before working it up.
Hope this helps.
I am interested in the activated imidazolide. I see the starting material (unreacted carboxylic acid) even if it is stirred for a pretty long time. The starting material is never fully consumed, perhaps because of low reactivity. The product decomposes if work-up is done with NaHCO3 solution. Hence I am doing work-up with simple water. Strangely none of the procedures I have gone through mentions about column chromatography though I see two spots.
In my experience working with active imidazolides, they are stable to neutral workup. I usually use a slight excess (1.1 or 1.2 equiv.) of CDI in THF, stir at room temperature overnight, then cool in ice bath and quench with saturated ammonium chloride, extract aqueous with ethyl acetate (x3), wash combined organic with brine, dry over sodium sulfate and filter/concentrate. The crude can be used directly, or the imidazolides are stable to column chromatography. See the following reference:
B.S. Gerstenberger, et al. Org. Lett., 2008, 10 (3), pp 369–372.
Are you certain the second spot you see is unreacted starting material? The imidazole byproduct might be running at the same Rf as your starting material...
Hope this helps!
Phenylacetic acids have a peculiar nature in TLC. They move little from the base even when TLC plate is eluted in pure Ethyl Acetate (looks like a trailing spot no matter how little I spot it). If present in small amounts in a mixture it can move as a rounded spot. While doing column it may start coming even after the lower spot started coming. And many test tubes come as a mixture even with large difference in polarity. Probably that's why I didn't come across any procedure which reported elution with Column Chromatography as a purification protocol.Its giving me a hard time to purify it from unreacted acid. I am doing the reaction in DCM solvent.
Why should I cool my reaction mixture before working up?Are the imidazolides unstable at higher temperature
Yes, in my experience, the imidazolides can hydrolize back to their respective starting acids, even when quenched at room temperature. Cooling on ice when quenching will prevent hydrolysis of the imidazolides during workup.
I quenched with cold saturated aqueous ammonium chloride today but NMR reveals the carboxylic acid is intact with not a trace of the product in it.
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