Weygand/Hilgetag Preparative Organic Chemistry

372 Formation of carbon-oxygen bonds
/>-Aminophenylacetic acid hydrochloride 806 is converted into its ethyl
ester merely on recrystallization from ethanol.
A method of esterification introduced by Meyer 807 is to dissolve the carboxylic
acid in an excess of concentrated sulfuric acid (if necessary with warming)
and to treat the solution cautiously with a small excess of the requisite alcohol;
when the reaction, which is often violent, ceases—if the mixture does not
become warm, it must be heated—the solution is poured on solid sodium
carbonate and worked up. This method has been used for esterification of
sterically hindered acids and for carboxy derivatives of nitrogenous heterocycles,
also for preparation of acetonedicarboxylic esters from citric acid and
alcohols. 808
Anhydrous salts 809 can often be used with advantage in place of the catalysts
discussed above, e.g., copper, iron, nickel, zinc, cobalt, or manganese
sulfate. Hydroxy acids such as lactic, 2-hydroxybutyric, and hydroxyvaleric
acid are smoothly esterified in the presence of anhydrous copper sulfate. 810
Acid chlorides such as thionyl chloride, acetyl chloride, stearoyl chloride,
and chloroformic esters have also proved to be very effective esterification
catalysts, being superior to mineral acids for, in particular, heat-sensitive
substances. 811 Even acids that react sluggishly, such as 2-phenyl-4-quinolinecarboxylic
acid, can be esterified in good yield by using chlorosulfonic
acid, of which only small quantities are required (0.01-0.05 equivalent). 812
Dimethyl sulfite, 813 boron trifluoride, 148 * 814 * 815 aromatic sulfonyl chlorides,
816 and phosphoryl chloride 817 have also proved their value for catalysing
esterifications.
Esterification in the presence of phosphoryl chloride is carried out as follows: The carboxylic
acid is dissolved or suspended in three to fives times its weight of the alcohol; then phosphoryl
chloride (3-5 % calculated on the amount of acid used) is dropped into this solution with
stirring and cooling during 20-30 min at such a rate that the temperature does not rise above
30-40°.
The phosphoryl chloride may also be added in larger portions with shaking; the mixture
must then be either boiled for 2-3 h or set aside at room temperature for 1-3 days.
For the synthesis of esters that cannot be obtained by the usual methods,
Staab 818 recommends the use of l,r-carbonyldiimidazole; this process is
useful for preparing esters of acid-sensitive alcohols or acids.
806 H. Salkowski, Ber. Deut. Chem. Ges., 28, 1917 (1895); B. Flursheim, /. Prakt. Chem.,
[ii], 68, 347 (1903).
807 H. Meyer, Monatsh. Chem., 25, 1202 (1904).
808 G. Schroeter, Ber. Deut. Chem. Ges., 49, 2710 (1916).
809 A. Bogojawlensky and J. Narbutt, Ber. Deut. Chem. Ges., 38, 3344 (1905).
810 E. Clemmensen and A. H. C. Heitman, /. Amer. Chem. Soc, 42, 319 (1909).
811 K. Freudenberg and W. Jakob, Ber. Deut. Chem. Ges., 74, 1001 (1941).
812 J. Erdos, Angew. Chem., 63, 329 (1951).
813 J. C. Sheehan and R. C. O'Neill, /. Amer. Chem. Soc, 72, 4614 (1950).
814 H. D. Hinton and J. A. Nieuwland, /. Amer. Chem. Soc, 54, 2017 (1932).
815 F.J. Sowa and J. A. Nieuwland, /. Amer. Chem. Soc, 58, 271 (1936); T.B.Dorris
and F. J. Sowa, /. Amer. Chem. Soc, 60, 358 (1938).
816 J. H. Brewster and C. J. Ciotti Jr., /. Amer. Chem. Soc, 11, 6214 (1955).
817 J. Klosa, Arch. Pharm., 289, 125 (1956).
818 H. A. Staab, Angew. Chem., 71, 194 (1959).