Which is the preferred substrate in an esterification reaction: acid; acid halide; or anhydride?

1 Answer
Nov 11, 2017

The preferred substrate is the one that works with the least pfaff....

Explanation:

And of course, whether they work is the province of experiment.

To use an acid halide, we have to take the starting carboxylic acid, heat it to reflux in thionyl chloride, and THEN add the alcohol, sometimes along with the one equiv of the non-nucleophilic base #Et_3N# to take out the #HCl#...

#RCO_2H(l)stackrel(SOCl_2, Delta)rarrRCOCl(l) + HCl(g) + SO_2(g)#

And the acid halide is then treated with the carboxylic acid with one equiv of non-nucleophilic base....

#RCOCl(l) + HOR'stackrel(Et_3N)rarrRC(=O)OR'(l) + Et_3N*HCl(s)#

The use of an acid anhydride MAY be more convenient in that you take the anhydride and heat it to reflux in the presence of the desired alcohol...with maybe a little acid catalysis.....

#RC(=O)O(O=)CRstackrel(H^+, R'OH)rarr2RC(=O)OR'#

It has been a long time since I had to these sorts of reactions....but when I wanted to make an ester, I would ALWAYS go by the acid halide route....in that acyl halides are reactive intermediates - of course, this means you have to take special measures to store them and protect them.....