Fischer esterification reaction limitations

Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction. Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 

Normal Fischer esterification of tertiary alcohols is unsatisfactory because the acid catalyst required causes dehydration or rearrangement of the tertiary substrate. Moreover, reactions with acid chlorides or anhydrides are also of limited value for similar reasons. However, treatment of acetic anhydride with calcium carbide (or calcium hydride) followed by addition of the dry tertiary alcohol gives the desired acetate in good yield. 

First law of thermodynamics, 24 645-648 First limiting amino acid, 2 601 First-order irreversible chemical kinetics, 25 286-287, 292-293 First-principle approach, in particle size measurement, 13 153 First sale doctrine, 7 793 Fischer, Emil, 16 768 Fischer carbene reaction, 24 35-36 Fischer esterification, 10 499 Fischer formula, 4 697 Fischer-Indole synthesis, 9 288 Fischer lock and key hypothesis, 24 38 Fischer-Tropsch (FT) synthesis, 6 791, 827 12 431... 

Both methods are successful since the formation of a tetrahedral intermediate about the ester carbonyl carbon, which is rate limiting in classical Fischer esterification , is avoided in the HERON reaction of hydrazines and 1-acyl-l-alkoxydiazenes. 

Fischer esterifications proceed very slowly in the absence of strong acids, but they reach equilibrium within a matter of a few hours when an acid and an alcohol are refluxed with a small amount of concentrated sulfuric acid or hydro n chloride. Since the position of equilibrium controls the amount of the ester formed, the use of an excess of either the carboxylic add or the alcohol increases the yield based on the limiting reagent. Just which component we choose to use in excess will depend on its availability and cost. The yield of an esterification reaction can also be ino-eased by removing water from the reaction mixture as it is formed. 

---