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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: Moz29386 on March 29, 2012, 04:12:24 PM

Title: How to maximise yields for this reaction
Post by: Moz29386 on March 29, 2012, 04:12:24 PM

Evening folks,

Basically I am coupling a carboxyl group to an amine using HBTU to activate the carboxy group. The first reactant containing the carboxy group is dissolved in dichloromethane. Diisopropylethylamine is added followed by HBTU and left to stir for 10 minutes. The second reagent (benzylamine) is then added to the mixture and left overnight.

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Fi44.tinypic.com%2F25oxend.jpg&hash=5f334d2eac024bb5fd80dc41d22c7ba756f5c39b)

At the moment my yield is approx 20% which is quiet poor.

I have devised several strategies of my own:

1) After re-crystallisation when I filter the product I will evaporate the liquid filtrate (as it may contain some of the product) and recrystallise that again.
2) Change of coupling agents: Try different coupling agents such as DCC, HATU, CDI etc...

If anybody could give me some possible ideas that would be great!

Thanks.

Title: Re: How to maximise yields for this reaction
Post by: Babcock_Hall on March 29, 2012, 05:03:51 PM

Can you follow the reaction by TLC?  If you have been following with TLC already, does it look mostly complete or not?  If the crude yield is high, then it sounds as if strategy 1 is reasonable.

Title: Re: How to maximise yields for this reaction
Post by: sjb on March 29, 2012, 05:36:05 PM

Is there a reason that you're doing this via HBTU and that style of activating agent? Seems to me that acid chloride formation with e.g. thionyl chloride or similar would be relatively high yielding and quick too?

Title: Re: How to maximise yields for this reaction
Post by: Doc Oc on March 29, 2012, 05:41:26 PM

Agree with sjb, although another nearly fail-proof coupling agent I used was EDC.

Also, your product could be lost in the recrystallization, you may need to choose another purification method.  That one should come off of a flash column cleanly and fairly easily.

Title: Re: How to maximise yields for this reaction
Post by: 408 on March 30, 2012, 06:25:28 AM

use an isocynanate instead of a carboxylic acid.

Title: Re: How to maximise yields for this reaction
Post by: OC pro on March 30, 2012, 07:00:09 AM

SOCl2 --> acid chloride, then amine + Et3N in dichloromethane, will give at least >75% yield.