Synthetic Tannins, Their Synthesis, Industrial Production and Application Part 3

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.c.o.o.na.

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. Repet.i.tion of these operations yields tri- and tetradepsides.

Preparation of Didepsides

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.c.o.o.na = 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_-c.u.maric 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

Monohydroxybenzoic acids allow theoretically of tri-depsides of the type HO.C_6H_4COO.C_6H_4.COO.C_6H_4.COOH only; if, on the other hand, di- or trihydroxybenzoic acids are dealt with, two formulae are possible, viz.:--

HO.C_6H_4.COO } C_6H_3.COOH HO.C_6H_4.COO

Of the former type, two compounds are known, _i.e._, di-_p_-hydroxybenzoyl-_p_-hydroxybenzoic acid and vanilloyl-_p_-hydroxybenzoyl-_p_-hydroxybenzoic acid--

HO } C_6H_3.COO.C_6H_4.COO.C_6H_4.COOH CH_3O

The first named of these two compounds was obtained by Klepl, in addition to the didepside, by heating _p_-hydroxybenzoic acid. Fischer and Freudenberg obtained a beautifully crystalline form in the following way: carbethoxyhydroxy-benzoyl chloride was coupled with _p_-hydroxybenzoyl-_p_-hydroxybenzoic acid in alkaline solution, the compound dissolved in a mixture of pyridine and acetone, and ammonia added for the purpose of removing the carbethoxy group. The tridepside was then obtained as long needles by re-dissolving in acetone.

Both tridepsides melt well above 200 C., are practically insoluble in water, and are but sparingly soluble in practically all organic solvents. In alcoholic solution they give colour reaction with ferric chloride similar to those given by _p_-hydroxybenzoic acids.

Preparation of Tetradepsides [Footnote: Fischer and Freudenberg, Liebig's _Ann._, 1910, 372, 32.]

Here, again, two forms are known, _e.g._, tri-_p_-hydroxybenzoyl-_p_-hydroxybenzoic acid--

HO.C_5H_4.COO.C_6H_4.COO.C_6H_4COO.C_6H_4 COOH

and vanilloyl-di-_p_-hydroxybenzoyl-_p_-hydroxybenzoic acid--

HO } C_6H_3.COO.C_6H_4.COO.C_6H_4.COO.C_6H_4.COOH CH_3O

The former has been prepared from carbethoxyhydroxy-benzoyl-_p_-hydroxybenzoyl chloride and _p_-hydroxybenzoyl-_p_-hydroxybenzoic acid in alkaline solution; the second tetradepside was prepared from carbomethoxyvanilloyl-_p_-hydroxybenzoyl chloride and _p_-hydroxybenzoyl-_p_-hydroxy-benzoic acid.

The preparation of these compounds is rendered difficult by the slight solubility of the substances and their slight affinities for entering into reaction. Both tetradepsides were obtained in crystalline form, and are but very little soluble in most organic solvents. They decompose on being fused.

Tannoid Substances of the Tannin Type

The preparation of pentagalloyl glucose has proved this compound to be nearly identical with tannin obtained from galls (_tannin_); a few other natural tannins belong to this type which Fischer terms acyl compounds of sugar with hydroxybenzoic acids. The method of preparation employed in the synthesis of pentagalloyl glucose may be easily applied to other hydroxybenzoic acids, _e.g._ penta[_p_-hydroxybenzoyl] glucose [Footnote: Fischer and Freudenberg, _Ber._, 1912, 45, 933.] was prepared in this way. Similar characteristics are exhibited by pentasalicylo glucose. Mention must also be made of the corresponding derivative of pyruvic acid and the compound with pyrogallolcarboxylic acid, penta-[pyrogallolcarboyl]glucose. [Footnote: Fischer and Rapoport, _Ber._, 1913, 46, 2397.] The latter is isomeric with pentagalloyl glucose and possesses similar properties; there is, however, a vast difference in the solubility of the two. Whereas the galloyl compound is easily soluble in cold water, its isomer is hardly soluble in hot, and completely insoluble in cold water. Considering the very similar structure of these two tannins, such differences appear surprising, but an a.n.a.logy may be readily found in the existence of colloidal solutions of tannin and the (nearly) identical pentagalloyl glucose. These properties clearly show how dependent is the colloidal state on small differences in the structure of two substances. On the other hand, the formation of hydrosols is of the greatest importance relatively to the part played by these substances in Nature as well as relating to their chemical characteristics; thus it is extremely difficult to make a solution of penta-[pyrogallolcarboyl]-glucose, at the same time ascertaining its astringent taste and its property of precipitating gelatine.

The experience gained by the methyl glucosides makes it exceedingly probable that the simpler polyhydric alcohols also are suitable substances to employ in these syntheses; as a matter of fact, glycerol has been condensed with gallic acid. [Footnote: Fischer and Freudenberg, _Ber., 1912, 45, 935.]

One of the chief characteristics of synthetic tannins is their high molecular weight; for instance, the molecular weight of penta-[tricarbomethoxygalloyl]-glucose is 1,810, that of penta-[pentamethyl-_m_-digalloyl]-glucose 2,051. Employing gallic acid derivatives, especially the tribenzoyl compounds, coupled with glucose, _e.g._, mannite, yielded a neutral ester of molecular weight 2,967.

The determination of the elementary composition of compounds of high molecular weight is greatly facilitated by employing their halogen derivatives; so, for instance, is _p_ iodophenyl maltosazone very suitable. Coupling the latter with tribenzoylgalloyl chloride yielded hepta-[tribenzoyl-galloyl]-_p_-iodophenyl maltosazone, the structure of which is represented by--

CH:N_2H.C_6H_4I | C:N_2H.C_6H_4I | CH.O.R R = CO.C_6H_2(O.CO.C_6H_6)_2 | CH.O.R | CH.O.R R R R R | O O O O | | | | | CH_2.O.CH.CH.CH.CH.CH.CH_2 | | ---O---