[rpatasu]

Hi!
Is it possible to see the spot of DCU (by product from DCC coupling) on normal silica TLC plates? I think it is not UV-active, can sombody help me with a staining reagent that I can use to observe DCU spots on TLC?
Thanks. 

[Captain Sci]

Hello RPatasu

The removal of dicyclohexylurea, DCU, from any reaction mixture can be a serious pain for the synthetic chemist! I remember as a PhD student having to deal with large quantities of this substance, which was the by-product of my dicyclohexylcarbodiimide (DCC) mediated coupling reactions.

If you are desperate to see a DCU spot on your TLC plate, I would suggest one of the following stains:

1) 2,4-Dinitrophenyl hydrazine (gives red and yellow spots against an orange background). Prepare by dissolving 2,4-Dinitrophenyl hydrazine (12 g) in a mixture of concentrated sulfuric acid (60 ml), deionised water (80 ml) and ethanol (200 ml).
2) Potassium Permanganate (gives yellow spots against a violet background, but may require gentle heating to visualise spots). Prepare from potassium permanganate (3 g) and potassium carbonate (20 g) in 5% aqueous sodium hydroxide (5 ml) and deionised water (300 ml).

In some of my reactions, separation of DCU from my reaction mixture was quite literally impossible. I found two ways in which separation could be achieved by alternative means, however, and I would be happy to share these with you.

First, instead of using silica gel as a purification sorbent try Florisil(R). This magnesia-silica gel is much less polar than standard silica and your DCU should be eluted from it without streaking and without the requirement of a polar solvent.

If your supervisor is feeling generous why not try silica-bound carbodiimide instead of DCC? This reagent is basically silica gel whose hydroxyl (OH) functional groups have been converted to carbodiimide (N=C=N) groups. It is completely insoluble in all reaction media, since it is fully end-capped, so at the end of your reaction the notorious urea by-product would be bound to the silica and removed by filtration.

If you need more help or information drop me an email. I would be happy to send you experimental conditions or tips on catch-and-release techniques.

Best wishes

Athan

[vladimir]

Dear Athan,

I also have DCU separation problems. I make amides and use DCC and HOBT. Can you give me advice about the use of column chromatography in solving this problem? What mobile phase should i use? I usually use combination of chloroform and methanol to extract my amide but the side product of this coupling show up in my product after purification.Should i use gradient, for example to start with chloroform only and to continue with increasing percent of methanol (1-10%)?

Thank you,

Vladimir

[OC pro]

That´s why in industry and medchem no one is using DCC 

Try staining with ninhydrin. Use different solvent mixtures for TLC. Petrol ether/ethyl acetate; petrol ether/ tert-butyl methyl ether and so on. Chloroform and dichloromethane/methanol mixtures are always bad when having a difficult separation.

Instead one could also do the acid chloride out of the acid and then react it with the amine using base. This works always best when the acid part survives the conditions necessary for making the acid chloride (e.g. thionyl chlorid, cat. DMF, heating, evaporation with toluene).