Solvolysis of esters

[gilden]

How can the solvolysis of esters be avoided? We are actually performing reactions in DMF at room temperature with functionalized carboxylic acid esters. The ester function has to stay intact. However, some of the ester is hydrolyzed. We know that DMF (polar solvent) enhances the formation of the carbocation, which is the rate limiting step in the SN1 type hydrolysis reaction. Furthermore, the substituents (phenyl-groups)on the the carbocation are strong electron donors and therefore strongly stabilize the carbocation. Does somebody have an idea how this hydrolysis can be inhibited? Decreasing the temperature is not really an option because not practical at large scale.

 

[moltenmetal]

In the absense of water, acid or base, shouldn't your ester be safe regardless of the polarity of the solvent? An ester can't come apart to re-form the acid and the alcohol without finding water from somewhere. Perhaps pre-purification of your solvent is in order.

 

[gilden]

There is always some small amount of water present in the DMF (due to water that is formed during reactions performed on the other functions on the esters).

 

[moltenmetal]

What about sopping up the water in-situ as fast as it's produced by using an adsorbent or dessicant? Something like anhydrous copper sulphate which you can filter from the solution afterward?

 

[gilden]

Yes, this could be a solution. I was rather thinking of adding a molecular sieve.

 

[25362]

Gilden, although water could contribute to hydrolysis of the esters depending on their molecular mass, as well a of DMF itself, water quantities appear to be originally small.

Water, if generated by esterification, should be eliminated. However, not all esters are prepared by reacting a carboxylic acid with an alcohol (a reversible equilibrium reaction), some use aldehydes. Could you specify what reactions are taking place ? How much ester is suffering hydrolysis ? What are these esters ?

Is there a reason to discard your original suspicion ? The presence of minute quantities of formic acid (about 50 ppm) in commercial DMF or the acidity used to catalyse the formation of the esters, could act as catalyst for the nucleophilic reactions you are mentioning by polarizing the electron deficient carbonyl group of the ester increasing its susceptibility to nucleophilic attack.
DMF contains also traces of DMA, a known nucleophile.

DMF's polarity appears precisely because electrons from the -N(CH₃)₂ moiety move to the oxygen of the carbonyl in the amide. Could this nucleophilic lending of electrons happen to the carbonyl of the esters ?

Anyway, if your assumptions are right, it appears one should try to eliminate residual acidity besides unwanted water.

 

[Velterop]

Water generated by esterification can be removed as it is formed by way of pervaporation. We obtained some pretty good results with a ceramic pervaporation membrane, even under acidic environment. You can contact me at:
maurice.velterop@pervatech.nl