Sciencemadness Discussion Board

A few esterification questions

Sciocrat - 31-3-2011 at 00:31

I am interested in the following esterification reaction:

C2H5OH + ClCH2COOH <-> ClCH2COOC2H5 + H2O

(ethanol + chloroacetic acid <-> ethyl chloroacetate + water)

I have been reading about the synthesis of ethyl bromoacetate in Vogel and in several other sources and I assume the synthesis of ethyl chloroacetate would be similar. However, most of the preparation methods that I encountered, require some way of water removal from the reaction, in order to shift the equilibrium in favor of the product. In case one didn't have the necessary equipment to facilitate the removal of water, would simply adding a surplus of ethanol be enough to achieve a reasonable yield?

Also, after the reaction solution has been refluxed for some time in order to achieve equilibrium, could the ester simply be obtained by dumping the mixture in cold water? Chloroacetic acid and ethanol are miscible/soluble in water. However, ethyl chloroacetate doesn't dissolve in water, so it would thereby separate and could be collected and dried?

Sorry if this seems banal, but I just wanted to check if I understand things correctly.

Random - 31-3-2011 at 07:41

ethyl chloroacetate is very toxic like http://en.wikipedia.org/wiki/Ethyl_bromoacetate

check, I wouldn't suggest you making it, though, if there was a safe way to make it I am interested too

It can be used for strawberry aroma synthesis.

Nicodem - 31-3-2011 at 10:05

Quote: Originally posted by Sciocrat  
Also, after the reaction solution has been refluxed for some time in order to achieve equilibrium, could the ester simply be obtained by dumping the mixture in cold water? Chloroacetic acid and ethanol are miscible/soluble in water. However, ethyl chloroacetate doesn't dissolve in water, so it would thereby separate and could be collected and dried?

An excess of ethanol will improve the conversion at the equilibrium point, but it will also reduce the recovery from the extraction. First of all, by the rule of thumb you add the reaction mixture in water soluble solvents (EtOH, MeOH, THF, DMSO, DMF, etc.) to at least 4-times the volume of water and depending on the logP of your desired product you apply from one to several extractions with the most appropriate solvent, combine the extract and then you can continue with washings, rotavaping and fractionation. If you will not dilute with enough water your recovery will suffer.
But in any case it is better to use more sulfuric acid for the esterification if you suspect your ester is a hard to form one - not only you reach the equilibrium faster, you also move the equilibrium to the right by binding water by protonation. It is not unusual to use 100 mol% H2SO4 or more for esterifications (instead of "catalytic amounts" only).

chemoleo - 31-3-2011 at 14:08

Under what conditions would you get the ether then (by loss of HCl)?

Strong base, i.e. 5M KOH?

i.e.
C2H5OH + ClCH2COOH <-> C2H5O-CH2COOH+ HCl

smuv - 31-3-2011 at 18:52

I would be more worried about getting diethyl ether by dehydration of ethanol. Also, chloroacetic acid is acidic enough that it needs no additional acid catalyst (though it might be desirable to mop up some water). I recall the preparation of the chloro-acetate esters (methyl/ethyl) as being common in older lab manuals; sciocrat, maybe you should look through the forum library to see what you find?

UnintentionalChaos - 31-3-2011 at 19:33

Quote: Originally posted by smuv  
I would be more worried about getting diethyl ether by dehydration of ethanol. Also, chloroacetic acid is acidic enough that it needs no additional acid catalyst (though it might be desirable to mop up some water). I recall the preparation of the chloro-acetate esters (methyl/ethyl) as being common in older lab manuals; sciocrat, maybe you should look through the forum library to see what you find?


Apparently however, a strong acid catalyst speeds the reaction and improves yield. See note 8: http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3...

I don't know how toxic the stuff is, but it does note that it is very lachrymatory.

smuv - 1-4-2011 at 06:49

YES, it is extremely lachrymatory, so much so that the toxicity is kinda irrelevant. I wouldn't use this stuff outside of a hood.

Wow, that really isn't much sulfuric acid, definitely not enough to offset the equilibrium due to soaking up some water; I guess chloroacetic acid is really just borderline acidic enough to catalyze its own esterification.