check this out DOI: 10.1002/anie.197805221 http://onlinelibrary.wiley.com/doi/10.1002/anie.197805221/abstract;jsessionid=7D5AC02222C8D9518C68D3A02D418EC0.d04t02

check this out DOI: 10.1002/anie.197805221 http://onlinelibrary.wiley.com/doi/10.1002/anie.197805221/abstract;jsessionid=7D5AC02222C8D9518C68D3A02D418EC0.d04t02

Thank you for the link.

Everywhere it seems esterification reaction as an easy process. But to attain high conversion is difficult. if we use anhydride or acid chlorides instead of corresponding acid, the reaction is fast and generally 100%. But problem is with the direct acid-alcohol esterification. Also in case of unsaturation in alcohol also creates problems during esterification. These are my observations. I am more concerned about the reaction set up. How we can remove the by-product water from reaction mixture? I tried with Dean&stark like apparatus and PTSA catalyst in toluene. But couldn't attain >50% conversions. That too with very high reaction time. Everybody go for toughest and rare catalysts and they will be applicable in milligram scales. I am more interested in simple systems and how they can give maximum yields.

If an acid and alcohol (both anhydrous) are used water is formed as one of the products...if there is a provision to remove as and when water is formed ( continuous extraction appapratus ) or azeotropic separation apparatus to separate water nearly cent percent conversion can be effected.

Try using concentrated H2SO4. It will remove water if you apply heat. It works for small scale reactions. Also try to use very dry staring material. I would sublime benzoic acid under low pressure before start the reaction.

I like 1,1'-carbonyldiimidazole - treat your acid with this reagent in dry THF or CH2Cl2, monitor formation of imidazyl intermediate, when complete add the alcohol. Driven by formation of CO2 which you can watch as a sign of reaction in the first step if on a big enough scale, two equivalents of imidazole base are formed in situ; how good is that, nothing more to add. When complete, wash with dilute acid to remove imidazole, dry and conc for ester. I don't recall if there are any carboxylic acids which won't react so I assume it'll work for aromatic ones. Just read up on side reactions.

DCC, DMAP etc are costlier ones. I would prefer a low cost catalyst with high conversions and yield. Also these forms many side reactions and decomposition of alcohol and acid.

DCC-DMAP route is costly only if you do the reaction on a molar scale - but if you need only few grams of product and high yield I'd try that (note that the Steglich esterification is done on room temperature - that means mild conditions when compared to most other methods that require reflux).

The cheapest method I can think of is in in situ acid chloride formation with SOCl2 and DMF followed by the addition of the alcohol.

Have you considered using lipase to catalyze the reaction? I would conduct the reaction in the alcohol with incremental addition of the acid in the presence of immobilized lipase and with gentle heating.

This might help:

http://dx.doi.org/10.1016/j.procbio.2011.10.037

Can you just add molecular sieves to help remove the h20? I always used a dean stark trap or distillation. I never tried this. Just a simple idea.

If you are doing the reaction in reflux condition, use the still apparatus (filled 1/4th with the molecular seives) set in between the reaction bottle and the reflux condenser. I tried this upto 100 g scale. Works well.

Thanks Pratap. I thought it could be done. I think we also may have used some kind of white powder that absorbed h2O. Maybe it was magnesium sulfate. I don't remember.

I just want to say that adding the lipase is a very creative answer. But enymes normally don't survive acidic conditions or heat. And enzymes will do things sterospecifically.

Reaction of benzoylchloride with alcohol in some non-mixing with water solvent (dichloromethane). Another way is boiling of reagents with sulphuric acid and Dean-Stark apparatus rectification. I think boiling point of your ester will be lower than alcohol's one.