[supRS]

I have conducted my synthesis experiment with only 2 reactants, no catalyst.  The amount of both reactants are very small, 184 mg for the first one and 134 mg for the other.  After checking the completion of the reaction with TLC, I have found that I have got pretty low yield of my product.  My colleague who is really in organic synthesis field suggested me not to do any aftertreatment for my reaction mixture.  The reason is that it would be very difficult to purify or to separate my product from reactants. Actually, I plan to use TLC plates to purify my product, since I don't have any column chromatography at this moment. 

If you have any suggestions about how to get my product, Please kindly let me know.  Thank you.

I'd like to tell you one more thing.  I am just a material scientist.  This is my first time to run an experiment in organic synthesis.

[Dan]

You will have to tell us what you want to make. We are chemists, not psychics.

[supRS]

Thank you Dan.  You are correct.  Sorry for that.  My reaction is an esterification between curcumin and an amino acid chloride.  I used dichloromethane mixed with dry pyridine as my solvent.  What else do I need to tell ?  Thanks.

[Dan]

What is the structure of the amino acid chloride?

After checking the completion of the reaction with TLC, I have found that I have got pretty low yield of my product.

What did TLC show, unreacted starting material or did the reaction go to completion? If the reaction did reach completion, how many products can you see by TLC - what is it that indicated that the yield is low?

My colleague who is really in organic synthesis field suggested me not to do any aftertreatment for my reaction mixture.

What was the aftertreatment (workup)? Can you post your full experimental procedure with details of what your TLC analysis is showing?

[fledarmus]

I think you're going to need to show your reaction scheme for this one. Curcumin is a diol, so it can react at both ends. There is also a potential reacting group in the center. Which amino acid chloride did you use? I'm assuming the amine was protected - was it an acid sensitive protecting group? Did you use a base to absorb the acid generated by the reaction? How many products do you expect, what are they, which one are you trying to isolate, how many spots did you see on the TLC, did you use a solvent, how did you remove the solvent, did you do any analysis besides TLC on your crude product that leads you to believe you got a low yield...

There is a lot of thinking that goes into a purification procedure. Without a little more detail, it's hard to tell how much you've done.

[supRS]

Which amino acid chloride did you use? I'm assuming the amine was protected - was it an acid sensitive protecting group?

Thank you very much for paying attention to my problem.  I used N-phthaloyl glycyl chloride.  It is correct that the amino group is protected.  This protecting group is sensitive to base, isn't it?

Did you use a base to absorb the acid generated by the reaction?

I added pyridine into my reaction mixture.  Can it serve this function? I mean neutralizing hydrochloric acid from the reaction.

How many products do you expect

Actually, I expect to get one product as a major component.  It can be either 1,7-Bis(4-o-glycinoyl-3-methoxyphenyl)-1,6-heptadiene-3,5-dione or the product from the reaction of the amino acid with only one phenolic group of curcumin.

how many spots did you see on the TLC

I saw 5 spots, 3 spots are at the same height as curcumin reactant.  2 more spots are above.  The highest spot shows fluorescence property. 

did you use a solvent, how did you remove the solvent

Yes, I used dichlromethane.  At this moment, I have not removed it yet?

did you do any analysis besides TLC on your crude product that leads you to believe you got a low yield

No, I did not.  I did my analysis only with TLC.  Any instrument I can use for this purpose?

[discodermolide]

If three spots have the same Rf as curcumin how do you know there are three spots?

[fledarmus]

One of your spots should also be pyridine. Did you co-spot against that?

I suspect your other starting material will also show as a spot at the origin.

What was the ratio in moles of your two starting materials?

[supRS]

Thanks to all of you.  For TLC analysis, I did it twice.  First, I spotted 3 dots on one plate after 6 hours of reaction time. Two dots were from my reactants, curcumin and amino acid. One dot was from the solution mixture.  After it developed, I took it to observe under short and long wavelength UV light. 
For the second time, I did it again but only 2 dots, after the reaction was run overnight.  One was from the solution mixture.  The other was from curcumin.  I spotted them side by side. 
For curcumin itself, it shows three spots of curcumin, desmethoxy curcumin, and bis desmethoxy curcumin.
Compared to all spots from curcumin, the reaction mixture has 2 more dots which have higher Rf.
I think my reaction was complete by observing the color intensity of two spots.  First spot is the one having similar Rf to curcumin.  The second is from the spot that I think it should be my product.  It has higher Rf compared to curcumin.   I approximately compared the intensity difference to that of the first analysis.  I could not find any obvious differences.  I think there was no further reaction because of this.  Is it correct for what I have done so far?   

The mole ratio for my reactant is 1:1.2( curcumin: amino acid).

As mentioned earlier, this is my first time to do experiment in organic synthesis. If my explanation isn't clear enough, please kindly suggest or ask again.  Thanks to all of you who provided comments or suggestions. 

[discodermolide]

For curcumin itself, it shows three spots of curcumin, desmethoxy curcumin, and bis desmethoxy curcumin.

You need to start with a pure starting material, otherwise you will get a mess. Which you have!
In solution curcumin exists as a mixture of the two enol forms. See http://en.wikipedia.org/wiki/Curcumin
you may be acylating the enol as well as the phenols. What was the ratio of acid chloride to curcumin?

[fledarmus]

Oh boy, this is getting more complicated...

So you started with five known compounds in your reaction mixture - your acid chloride, curcumin, desmethoxy curcumin, bis-desmethoxycurcumin, and pyridine. The ratio of your mixture of curcumins to acid chloride was 1:1.2. If the reaction works at all, you shouldn't expect to see a huge difference in reactivity between any of your phenols (you have now described six different phenols from your three starting materials) and you still have three enols which might also be expected to react. The phenols are far enough away from each other that reacting with one shouldn't change the reactivity of the other. So assuming the acid chloride only reacted with the phenols, you can expect at least four different monoalkylated products and three different dialkylated products. The fact that you only saw two different spots and that the three starting materials are all still present leads me to suspect that the reaction didn't work at all.

If the intensities of your three starting material spots are very different - for instance, if you have say 90% curcumin and only 5% each of the other two - then there is a slight chance that the two new spots are mono- and di-substituted curcumin, and that the products from reactions with the other two starting materials were just too dilute to show. In that case, either spotting them in a more concentrated solution or possibly visualizing your plate (an iodine chamber would probably work well for this) may bring out the additional spots.

If you have easy access to an MS, you might want to throw this mixture on, just to see if you get anything related to product. If you do, it might be worth tracking down; if you don't, I'd worry more about how to set up the next reaction than how to clean this one up.

[Babcock_Hall]

I just have one general comment.  I will assume that the amino acid chloride starting material will or can be hydrolyzed to the carboxylic acid form, and/or to its conjugate base form (carboxylate).  Therefore, it can be removed by passage over Dowex 1, which is an ion-exchange resin, or better still, over Whatman DE-52 which is an ion exchange gel.  As long as your product (which should be an ester if I am following correctly) has no negative charges, it will not bind.  Acid base extraction may or may not work in this case--it depends on the aqueous solubility of the product.

[Babcock_Hall]

Is the starting amino acid chloride protected at the amino group?  If so, then acid base extraction may be a good alternative (relative to ion exchange) to remove the by-product.

[supRS]

Thank you again for all suggestions.

If you have easy access to an MS, you might want to throw this mixture on, just to see if you get anything related to product.

I will try to run MS as being suggested.

Some more questions about pyridine.  Is it strong enough to absorb hydrochloric generated from the reaction?  If I change the mole ratio between curcumin and amino acid chloride to be 1:2.4, there are any textbooks I can study to find a suitable amount of pyridine for the reaction and also how to remove it after the completion of reaction.

[fledarmus]

Some more questions about pyridine.  Is it strong enough to absorb hydrochloric generated from the reaction? 

You should learn to look up some information on the compounds you are using, especially compounds as common and useful as pyridine. Even a wiki search will give you this...

Pyridine is miscible with water and virtually all organic solvents.[7] It is weakly basic, and with hydrochloric acid it forms a crystalline hydrochloride salt which melts at 145–147 °C.

And this...

The nitrogen center of pyridine features a basic lone pair of electrons. Because this lone pair is not part of the aromatic ring, pyridine is a base, having chemical properties similar to those of tertiary amines. The pKa of the conjugate acid is 5.25. Pyridine is protonated by reaction with acids and forms a positively charged aromatic polyatomic ion called pyridinium.