Sciencemadness Discussion Board

Problems with Claisen condensation

Hexavalent - 29-10-2012 at 07:58

As some of you know, I recently embarked on a Claisen condensation on ethyl acetate to yield ethyl acetoacetate.

Last night, I ran the reaction on a small scale - using 24.5g of the EtOAc in a 50ml RBF - to test it out before I did it on a larger scale in a 250ml flask. However, I encountered some problems, namely that, during reflux, a large amount of solid formed at the bottom of the flask and a gel-like substance adhered to the walls of the headspace in the flask.

My sodium was bought as 99% pure and was shiny when I cut it and put it into the liquids. The ethyl acetate (and the extra ethanol added) were dried using anhydrous MgSO4 - before anyone suggests this, it was not CaCl2, which would have complexed the ethanol and potentially caused the problem - and all the liquids were tested with CaC2 and anhydrous CuSO4 on a spotplate before using. All tests were negative for water.

My flask and condenser were visually clean - I thoroughly cleanse equipment after each experiment with tap water, soapy water, tap water and then DI water, and I only used the standard minimal amount of grease on the joints. I was also magnetically stirring the flask slowly and the solvent, when heating, was boiling gently. The colour at this point was yellow/tan, and not the red I was expecting.

Any ideas?



[Edited on 29-10-2012 by Hexavalent]

Magpie - 29-10-2012 at 10:28

Quote: Originally posted by Hexavalent  

Any ideas?


Not really. But I can retell from my notes my experience in making this reagent. Although I seemed to have had many surprises and one major faux paux my product was produced in good yield and was used successfully in a later synthesis.

I made a 1/2 scale batch from Brewster, 1960, my old school lab manual. I used 117 mL EtOAc and 9.4g Na in a 250mL RBF. Refluxed on a steam bath for 2 hrs. Mix turned a brown-orange. Then added 2.5mL EtOH and heated for another 30 min. But to get everything dissolved I ended up heating and shaking for another 1 hr. Then added 12.5mL EtOH in 4 portions through the condenser. Everything turned solid again, brown in color. Added 110mL of 50% acetic acid (twice what procedure called for) to get just faint acid color on pH paper.

Now for my major fuck up: I added 200 mL of saturated CaCl2 solution instead of the specified 200mL of sat NaCl soln! This caused an immediate gel formation in the 500mL sep funnel. I salvaged this by adding enough water to get the gel to go into solution, made a phase separation, then added the NaCl soln. Dried the organic over powdered CaCl2. Purified the ethyl acetoacetate by vacuum distillation at ~50mmHg where it boiled at ~100C. My yield was 13mL which according to Brewster was twice what could be expected using distillation at atmospheric pressure. %yield was only 16.7%. Hope this helps.



[Edited on 29-10-2012 by Magpie]

Hexavalent - 29-10-2012 at 10:33

Quote: Originally posted by Magpie  
I used 117 mL EtAc


Do you mean EtOAc?

Either way, lacking a vacuum pump, could one simply distill off, at atmospheric pressure, everything boiling below, e.g. 100*C, and just keep what is left in the stillpot? With a few washes, how pure would the ethyl acetoacetate be now?

Also, is there a substitute for the acetic acid? Could formic acid or a mineral acid be substituted instead?

[Edited on 29-10-2012 by Hexavalent]

UnintentionalChaos - 29-10-2012 at 11:37

Quote: Originally posted by Magpie  


Now for my major fuck up: I added 200 mL of saturated CaCl2 solution instead of the specified 200mL of sat NaCl soln! This caused an immediate gel formation in the 500mL sep funnel. I salvaged this by adding enough water to get the gel to go into solution, made a phase separation, then added the NaCl soln.
[Edited on 29-10-2012 by Magpie]


Sounds like my major issue using the orgsyn prep...
They have you dry the crude organic phase over CaCl2, which contains ethanol, apparently, as it swelled up into glop overnight, entrapping most of the solution...so I added water and proceeded as best I could.

As for you Hexavalent, I expect water is your problem, even though everything seemed to be dry. The orgsyn prep specifies that "If the ester is dry enough to use in this reaction it will not give a gelatinous mass of sodium hydroxide when treated with a little sodium." I got tons of solid with just a few droppers full of the 50% acetic acid at the end. The solution was initially cloudy from a little NaOH, but this dissolved as the reaction proceeded.

[Edited on 10-29-12 by UnintentionalChaos]

Magpie - 29-10-2012 at 11:46

Quote: Originally posted by Hexavalent  
Quote: Originally posted by Magpie  
I used 117 mL EtAc


Do you mean EtOAc?

yes
Quote: Originally posted by Hexavalent  

Either way, lacking a vacuum pump, could one simply distill off, at atmospheric pressure, everything boiling below, e.g. 100*C, and just keep what is left in the stillpot? With a few washes, how pure would the ethyl acetoacetate be now?


Brewster says that cut III (175-185C) is ethyl acetoacetate. Cut II (95-175C) has some ethyl acetoacetate. So keep cut III. Redistill cut II, keeping that boiling in the range 175-185. I can't guess what your purity would be if you merged cuts II & III. Do the redistill of cut II if you want the purity.

Quote: Originally posted by Hexavalent  

Also, is there a substitute for the acetic acid? Could formic acid or a mineral acid be substituted instead?


I think that using acetic acid maintains the ethyl specie. If you add formic you may get some methyl replacing ethyl in your ester product. HCl wouldn't do that but you would not have the mass action of the added ethyl that you get from using acetic acid.

Hexavalent - 29-10-2012 at 11:54

Okay, thanks a lot.

I asked DJF90 earlier and he hypothesised that water was the problem too.

I'll buy some more ethyl acetate at some point and try again, but I'll dry it on its own with CaCl2, dry the ethanol with magnesium sulfate and mix the two. I'll test with sodium before using, and dry further if necessary.

I haven't a thermometer that is graduated past 150*C nor a vacuum pump, so distillation is impossible for me unless I buy a new thermometer or a pump.