Amongst other compounds chlorphydroxybenzoic acid is used in the preparation of the materials employed in the synthesis of depsides; the free phenolic group, however, exerts a disturbing influence when aromatic acids are acted upon by phosphorus chloride, and another group, which can subsequently be easily removed, must therefore be introduced to cover the disturbing influence referred to. For this purpose, Fischer [Footnote: Ber., 1908, 41, 2860.] chose the carbomethoxy group, and this investigator succeeded, by the action of chlorocarbonic alkyl ester and alkali upon hydroxybenzoic acid in cold aqueous solution, in obtaining substances with the properties required. [Footnote: Ber., 1908, 41, 2875.] In such substances (e.g., salicylic acid) where the hydroxyl occupies the ortho-position to the carboxyl, complete carbomethoxylation does not take place, whereas the m- or p- positions offer no hindrance. In the case of the o-position, however, the action of chlorocarbonic alkyl ester is successfully assisted by the presence of dimethylaniline in an inert solvent, e.g., benzene.[Footnote: U.S. Pat, 1,639,174, 12, xii., 1899.] The difficulty encountered by the o-position is eliminated when the carboxyl is not directly linked to the benzene nucleus, e.g., o-cumaric acid. Many hydroxybenzoic acids require an excess of chlorocarbonic methyl ester, which then also, to some extent, attacks the carboxyl group; but on dissolving the product in acetone and treating it with bicarbonate the carboxyl group as such is again restored without splitting off the carbomethoxy group.[Footnote: Ber., 1913, 46, 2400.] In this way all hydroxybenzoic acids may be carbomethoxylated. [Footnote: Ibid., 1908, 41, 2877, 2881, 2882; 1909, 42, 226, 218, 223, 225; Liebig's Ann., 1912, 391, 357, 366; Ber., 1913, 46, 1145, 2390, 2400.] The carbomethoxy group is easily removed by excess of aqueous alkali in the cold, and is also partially removed when insufficient alkali is present; the latter fact is of importance in the synthesis of didepsides.
Chlorides of Carbomethoxyhydroxybenzoic Acids
The chlorides of these compounds are obtained when phosphorus pentachloride is allowed to act upon the acids, and are as a rule crystalline. For the purpose of synthesis they may be employed as follows:
1. They readily form esters with alcohols, which on subsequent saponification with alkali are converted into the esters of the free hydroxybenzoic acids.
2. The chlorides interact energetically with esters of amino-acids, and may be coupled with amino-acids in aqueous alkaline solution. On subsequently removing the carbo-methoxy group derivatives of hydroxybenzoic acids are obtained, e.g.,
CH_3.CO_2.O.C_6H_4.CO.Cl + 2NH_2CH_2.CO.C_2H_5
= NH_2.CH_2.CO_2.C_2H_5 + HCl + CH_3.CO_2.O.C_6H_4 CO.NH.CH_2CO_2C_2H_5.
CH_3.CO_2.O.C_6H_4.CO.NH.CH_2.CO_2.C_2H_5 + 3NaOH
= Na_2CO_3 + C_2H_5OH + CH_3OH + HO.C_6H_4.CO.NH.CH_2.COONa.
3. In the presence of AlCl_3 the chlorides easily combine with benzene, and on removing the carbomethoxy group unsymmetrical hydroxy derivatives of benzophenone are formed:—
CH_3.CO_2.O.C_6H_4.CO.Cl + C_6H_6 = CH_3.CO_2.O.C_6H_4.CO.C_6H_5 + HCl
CH_3.CO_2.O.C_6H_4.CO.C_6H_5 + 3NaOH
= NaO.C_6H_4.CO.C_6H_5 + Na_3CO_3 + CH_3OH + H_2O
4. The chlorides may be coupled with free hydroxybenzoic acids, and on removing the carbomethoxy group didepsides are obtained. Repetition of these operations yields tri- and tetradepsides.
Preparation of Didepsides