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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: endophytic on July 02, 2013, 06:22:26 AM

Title: Role of TEA in amide coupling ?
Post by: endophytic on July 02, 2013, 06:22:26 AM

Let's say I want to form an amide from a carboxylic fatty acid and aniline.
I dissolve one eq. of acide and one eq. of the amine in DCM and add 1.3 eq of a coupling agent like EDAC or DCC and 1.3 eq of a coupling additive like HOBt.

Many times I can see in various paper that triethylamine is also added. What is the point ? What is the exact role of TEA here ? Is it necessary ?


Thanks for your insights  ;)

E.

Title: Re: Role of TEA in amide coupling ?
Post by: magician4 on July 02, 2013, 11:42:10 AM

TEA is a strong base which catches the protons , even better than aniline
as a result, aniline is liberated from salt-forming with the organic acid, hence is in effect of higher "active" concentration

... which supports a fast reaction with good yields


regards

Ingo

Title: Re: Role of TEA in amide coupling ?
Post by: endophytic on July 02, 2013, 12:24:07 PM

Thanks Ingo.

Wich work up would you suggest knowing the amine is 4bromo-aniline and the acid is a diacid (suberic acid) so I should have a product with an amide, a saturated carbon chain and a terminal carboxylic acid ... I am in DCM an used TEA.

Should I dry the rxn mixture then dilute with aq. KOH filter then acidify the filtrate with HCl and filter my product ?? Does this seems like a correct work up or would you suggest a better alternative ??

Thanks,

E.

Title: Re: Role of TEA in amide coupling ?
Post by: magician4 on July 02, 2013, 12:52:39 PM

problem seems to me, that you will have a statistical distribution of amide, diamide and non-reacted aniline by the end of you process.


hence:

I would start by removing all voilatile material, i.e. "drying"

the residue I would wash with slightly HCl - acidified water ./. DEE (removal of TEA as hydrochloride, removal of excess aniline ) . higher amounts of suberic acid might be insoluble in both layers, so filtration might be necessary / a good idea

the etheric layer then should consist of amide, diamide and suberic acid in etheric solution

as I expect the solubility of the suberic acid to be significantly higher ( 2,5 g/L , 20°C) than the respective solubility of the monoamide, I would wash with water once or twice

by now, it depends: KOH/water ? might form a soap and spoil the party, or might work and allow for separation from the diamide -  you'll have to test for that

anyway, recrystallisation or chromatographic workup looks like the final step to me


regards

Ingo