To return to coal-tar pharmaceutical preparations. At the present time seven distinct derivatives of quinoline, all formed by pyridising the amido-group in aniline, amido-phenols, &c., are known in medicine under such names as kairine, kairoline, thalline, and thermifugine. The mode of preparation of these compounds cannot be entered into here, Kairine, the first of the artificial alkaloïds, is a derivative of hydroxy-quinoline, which was discovered in 1881 by Otto Fischer. All these quinoline derivatives have the property of lowering the temperature of the body in certain kinds of fevers, and may therefore be considered as the first artificial products coming into competition with the natural alkaloïd, quinine. There is reason for believing that the latter alkaloïd, the most valuable of all febrifuges, is related to the quinoline bases, so that if its synthesis is accomplished—as may certainly be anticipated—we shall have to look to coal-tar as a source of the raw materials.
Another valuable artificial alkaloïd, discovered in 1883 by Ludwig Knorr, claims aniline as a point of departure. When aniline and analogous bases are diazotised, and the diazo-salts reduced in the cold with a very gentle reducing agent, such as stannous chloride, there are formed certain basic compounds, containing one atom of nitrogen and one atom of hydrogen more than the original base. These bases were discovered in 1876 by Emil Fischer, and they are known as hydrazines, the particular compound thus obtained from aniline being phenylhydrazine. By the action of this base on a certain compound ether derived from acetic acid, which is known as aceto-acetic ether, there is formed a product termed “pyrazole,” and this on methylation gives the alkaloïd in question, which is now well known in pharmacy under the name of “antipyrine.”
While dealing with this first industrial application of a hydrazine, it must be mentioned that the original process by which Fischer prepared these bases was improved upon by Victor Meyer and Lecco in 1883, who discovered the use of a cold solution of stannous chloride for reducing the diazo-chloride to the hydrazine. By this method the manufacture of phenylhydrazine and other hydrazines is effected on a large scale—all kinds of amido-compounds and their sulpho-acids can be diazotised and reduced to their hydrazines. Out of this discovery has arisen the manufacture of a new class of colouring-matters related to the azo-dyes. The hydrazines combine with quinones and analogous compounds with the elimination of water, the oxygen coming from the quinone, and the hydrogen from the hydrazine. The resulting products are coloured compounds very similar in properties to the azo-dyes, and one of these was introduced in 1885 by Ziegler, under the name of “tartrazine.” The latter is obtained by the action of a sulpho-acid of phenylhydrazine on dioxytartaric acid, and is a yellow dye, which is of special interest on account of its extraordinary fastness towards light.
Another direction in which coal-tar products have been utilized is in the formation of certain aromatic compounds which occur in the vegetable kingdom. Thus the artificial production of bitter-almond oil from toluene has already been explained. By heating phenol with caustic alkali and chloroform, the aldehyde of salicylic acid, i.e. salicylic aldehyde, is formed, and this, on heating with dry sodium acetate and acetic anhydride, passes into coumarin, the fragrant crystalline substance which is contained in the Tonka bean and the sweet-scented woodruff. Furthermore, the familiar flavour and scent of the vanilla bean, which is due to a crystalline substance known as vanillin, can be obtained from coal-tar without the use of the plant. The researches of Tiemann and Haarman having shown that vanillin is a derivative of benzene containing the aldehyde group, one hydroxyl- and one methoxy-group, the synthesis of this compound soon followed (Ulrich, 1884). The starting-point in this synthesis is nitrobenzoic aldehyde, so that here again we begin with toluene as a raw material. A mixture of vanillin and benzoic aldehyde when attenuated to a state of extreme dilution in a spirituous solvent, gives the perfume known as “heliotrope.”
Not the least romantic chapter of coal-tar chemistry is this production of fragrant perfumes from the evil-smelling tar. Be it remembered that these products—which Nature elaborates by obscure physiological processes in the living plant—are no more contained in the tar than are the hundreds of colouring-matters which have been prepared from this same source. It is by chemical skill that these compounds have been built up from their elemental groups; and the artificial products, as in the case of indigo and alizarin, are chemically identical with those obtained from the plant. Among the late achievements in the synthesis of vegetable products from coal-tar compounds is that of juglone, a crystalline substance found in walnut-shell. It was shown by Bernthsen in 1884 that this compound was hydroxy-naphthaquinone, and in 1887 its synthesis from naphthalene was accomplished by this same chemist in conjunction with Dr. Semper.
Another recent development in the present branch of chemistry brings a coal-tar product into competition with sugar. In 1879 Dr. Fahlberg discovered a certain derivative of toluene which possessed an intensely sweet taste. By 1884 the manufacture of this product had been improved to a sufficient extent to enable it to be introduced into commerce as a flavouring material in cases where sweetness is wanted without the use of sugar, such as in the food of diabetic patients. Under the name of “saccharin,” Fahlberg thus gave to commerce a substance having more than three hundred times the sweetening power of cane-sugar—a substance not only possessed of an intense taste, but not acted upon by ferments, and possessing distinctly antiseptic properties. The future of coal-tar saccharin has yet to be developed; but its advantages are so numerous that it cannot fail to become sooner or later one of the most important of coal-tar products. In cases where sweetening is required without the possibility of the subsequent formation of alcohol by fermentation, saccharin has been used with great success, especially in the manufacture of aërated waters. Its value in medicine has been recognized by its recent admission into the Pharmacopœia.
The remarkable achievements of modern chemistry in connection with coal-tar products do not end with the formation of colouring-matters, medicines, and perfumes. The introduction of the beautiful dyes has had an influence in other directions, and has led to results quite unsuspected until the restless spirit of investigation opened out new fields for their application. A few of these secondary uses are sufficiently important to be chronicled here. In sanitary engineering, for example, the intense colouring power of fluoresceïn is frequently made use of to test the soundness of drains, or to find out whether a well receives drainage from insanitary sources. In photography also coal-tar colouring-matters are playing an important part by virtue of a certain property which some of these compounds possess.
The ordinary photographic plate is, as is well known, much more sensitive to blue and violet than to yellow or red, so that in photographing coloured objects the picture gives a false impression of colour intensity, the violets and blues impressing themselves too strongly, and the yellows and reds too feebly. It was discovered by Dr. H. W. Vogel in 1873 that if the sensitive film is slightly tinted with certain colouring-matters, the sensitiveness for yellow and red can be much increased, so that the picture is a more natural representation of the object. Plates thus dyed are said to be “isochromatic” or “orthochromatic,” and by their use paintings or other coloured objects can be photographed with much better results than by the use of ordinary plates. The boon thus conferred upon photographic art is therefore to be attributed to coal-tar chemistry. Among the numerous colouring-matters which have been experimented with, the most effective special sensitizers are erythrosin, one of the phthaleïns, quinoline red, a compound related to the same group, and cyanin, a fugitive blue colouring-matter obtained from quinoline in 1860 by Greville Williams.
In yet another way has photography become indebted to the tar chemist. Two important developers now in common use are coal-tar products, viz. hydroquinone and eikonogen. The history of these compounds is worthy of narration as showing how a product when once given by chemistry to the world may become applicable in quite unexpected directions. Chloroform is a case in point. This compound was discovered by Liebig in 1831, but its use as an anæsthetic did not come about till seventeen years after its discovery. It was Sir James Simpson who in 1848 first showed the value of chloroform in surgical operations. A similar story can be told with respect to these photographic developers.
Towards the middle of the last century a French chemist, the Count de la Garaye, noticed a crystalline substance deposited from the extract of Peruvian bark, then, as now, used in medicine. This substance was the lime salt of an acid to which Vauquelin in 1806 gave the name of quinic acid (acide quinique). In 1838 Woskresensky, by oxidizing quinic acid with sulphuric acid and oxide of manganese, obtained a crystalline substance which he called quinoyl. The name was changed to quinone by Wöhler, and, as we have already seen (p. [172]), the term has now become generic, indicating a group of similarly constituted oxygen derivatives of hydrocarbons. Hydroquinone was obtained by Caventou and Pelletier by heating quinic acid, but these chemists did not recognize its true nature. It was the illustrious Wöhler who in 1844 first prepared the compound in a state of purity, and established its relationship to quinone. This relationship, as the name given by Wöhler indicates, is that of the nature of a hydrogenised quinone. The compound is readily prepared by the action of sulphurous acid or any other reducing agent on the quinone.