A simple application of these syntheses is offered by p-hydroxybenzoic acid. When the chloride of its carbomethoxy derivative is allowed to interact with p-hydroxybenzoic acid in aqueous alkaline solution, in the cold, the alkali salt of carbomethoxy-p-hydroxybenzoic acid is formed:—[Footnote 1: Ber., 1909, 42, 216.]
CH_3.CO_2.O.C_6H_4.CO.Cl + NaO.C_6H_4.COONa
= CH_3.CO_2.O.C_6H_4.CO_2.C_6H_4.CO_2.Na + NaCl.
Being sparingly soluble, the salt in this case is readily deposited as crystals, but is readily converted into the free acid by hydrochloric acid. In most other cases, however, the alkali salts are easily soluble and the aqueous solution is then directly acidified with a mineral acid. The chlorides, being for the most part solids, the mode of procedure is as follows:—the hydroxybenzoic acid required for coupling is dissolved in normal or double-normal alkali (the volume calculated per molecule acid), a little acetone added, and the mixture well cooled; a further molecule of 2N caustic soda and the chloride (I molecule) dissolved in dry acetone are added in small portions, whilst stirring, to the mixture. In spite of the low temperature the coupling proceeds quickly and the sparingly soluble product can in most cases be precipitated from the solution by acidifying and diluting with water. In case of more easily soluble coupling products the acetone is driven off under reduced pressure or the liquid acidified and diluted, and the substance extracted with ether. Instead of alkali, dimethylaniline may be employed, with the exclusion of water as a solvent for the purpose of coupling.
Another suitable method of obtaining o-didepsides is that of treating o-hydroxybenzoic acids with phosphorus trichloride and dimethylaniline (e.g., synthesis of disalicylic acid, Boehringer & Sons).[Footnote: Ger. Pat., 211,403.]
The carbomethoxy derivatives of the depsides are as a rule crystalline substances of distinct acidic character, and decompose alkaline carbonates.
The elimination of the carbomethoxy group may be brought about by dilute alkaline solutions in the cold, or by aqueous ammonia. If the depside formed is so stable as to resist the action of alkali for several hours, the use of the latter is very convenient for the purpose required. The substance is dissolved directly in sufficient normal alkali to neutralise the carboxyl group and a further 2 molecules of caustic soda for each carbomethoxy group to be eliminated are added. The temperature should be about 20° C., when the reaction as a rule is completed after one-half to three-quarters of an hour. It is usual, however, to use an aqueous ammonia solution in considerable excess, whereby the temperature should again be about 20° C., and the solution of ammonia normal or half normal.
The didepsides so far investigated are crystalline bodies, sparingly soluble in cold water; they—as a rule—decompose when fused, possess acid reaction, and are dissolved by bicarbonates. On account of the presence of a free phenolic group they give a coloration with ferric chloride; if the phenolic group occupies the o-position to carboxyl, the coloration with ferric chloride is red or bluish-violet Excess of dilute alkali resolved all didepsides into their components at ordinary temperatures. The didepsides of gallic, proto-catechuic, gentisinic, and [Greek: b]-resorcylic acids precipitate gelatine and quinine acetate, and in this respect approach the natural tannins.
The following summary gives an account of depsides which have been prepared synthetically or which occur naturally:—[Footnote 1: Ber., 1908, 41, 2888; 1909, 42, 217; 1913, 45, 2718; 1913, 46, 1130, 2396, 1141, 1143; Liebig's Ann., 384, 230, 233, 238; 391, 356, 362.]
Di-p-hydroxybenzoic acid.
Di-m-hydroxybenzoic acid.
Disalicylic acid.
Diprotocatechuic acid.
Digentisinic acid.
Di-[Greek: b]-resorcylic acid.
p-Diorsellic acid.
o-Diorsellic acid.
m-Digallic acid.
Disyringic acid.
Di-o-cumaric acid.
Diferulic acid.
Di-[Greek: b]-hydroxynaphthoic acid.
p-Hydroxybenzoyl-m-hydroxybenzoic acid.
m-Hydroxybenzoyl-p-hydroxybenzoic acid.
Salicyl-p-hydroxybenzoic acid,
Vanilloyl-p-hydroxybenzoic acid.
Feruloyl-p-hydroxybenzoic acid.
[Greek: a]-Hydroxynaphthoyl-p-hydroxybenzoic acid.
Orsellinoyl-p-hydroxybenzoic acid.
Protocatechuyl-p-hydroxybenzoic acid.
Galloyl-p-hydroxybenzoic acid.
Pyrogallolcarboy p-hydroxybenzoic acid.
Syringoyl-p-hydroxybenzoic acid.
p-Hydroxybenzoyl-syringic acid.
Pentamethyl-m-digallic acid.
Pentamethyl-p-digallic acid.
Vanilloyl vanillin.
Preparation of Tridepsides