Part 32

ANILINE.

Among the events which gradually led to the production of artificial compounds for which physiological properties and action have been claimed, the discovery of aniline is prominent. The substance, now so well known by that name, was first separated from indigo in 1826 in the course of a dry distillation of that dye by a pharmacist of Erfurt, named Unverdorben. He named his product “crystalline,” from its character. In 1834 the same substance, as it was later known to be, was obtained from coal-tar by Runge, who, observing the violet colour which bleaching powder caused in its aqueous solution, designated the product “kyanol.” Ten years subsequently Hofmann continued the investigations which Runge had pioneered. Meanwhile Fritzsche had obtained anthranilic acid from indigo, and from that he had produced an oily base which he called “aniline.” This term was derived from the specific name of the indigofera anil, which was the Sanskrit designation of the famous blue dye. Hofmann’s researches ultimately proved that Unverdorben’s crystalline, Runge’s kyanol, and Fritzsche’s aniline were all chemically identical. Hofmann would have preferred to retain the first of these names, but the more definite aniline prevailed.

The colour producing power of aniline had been observed (as has been already mentioned) by Runge in 1834, but it was not until 1856 that this property became of practical importance, when W. H. Perkin, at the time a pupil of Hofmann’s, commenced the investigation which resulted in such a complete revolution in the dyeing industry. Perkin’s patent for his “mauve” dye was obtained in 1858. It is an interesting circumstance that he made his discovery as a consequence of experiments he was conducting with the view of manufacturing an artificial quinine. Now we may turn to the

Born, 1818; died, 1892. Was Director of the Royal College of Chemistry, London, 1845–1864; subsequently Professor of Chemistry in Berlin University. Hofmann commenced the researches into coal-tar chemistry and established the chemical characteristics of aniline, and was thus one of the principal founders of modern organic chemistry. ]

IMITATION OF NATURAL ALKALOIDS

(showing how coniine, piperine, atropine, nicotine, caffeine, theobromine, and others, have been synthesised; and that quinine, strychnine, morphine, and codeine await conquest).

Liebig, Gerhardt, and other chemists had been progressing towards this attainment by studying the structural constitution of various alkaloids. In 1842 Gerhardt separated a base which he called quinoline from quinine, cinchonine, and strychnine. This base was subsequently identified by Hofmann with the leucol which Runge had obtained from coal-tar in 1834. In 1846 Runge also produced a substance which he called pyridine from bone oil. Hofmann showed that this was the base of certain other alkaloids, coniine, piperine, nicotine, and atropine among these. Now it will be necessary to illustrate progress by means of a few formulæ diagrams.

Benzene is C{6}H{6}; aniline is a derivative of benzene in which one atom of hydrogen has been replaced by the amino-group, NH{2}. Its formula is C{6}H{5}NH{2}, and it is represented thus:

CH // \\ HC CH | | HC CH \\ // CNH{2}

Aniline is basic; that is, it combines with acids to form salts. Together with aniline in coal-tar there occur other basic nitrogenous substances; of these pyridine and quinoline have already been mentioned, and to them must be added isoquinoline, which is also the parent substance of a series of alkaloids.

In pyridine one of the CH groups of the benzene ring is replaced by a nitrogen atom, the formula of the substance being C{5}H{5}N. In 1886 Ladenburg succeeded in synthesising the alkaloid coniine, starting with pyridine. This was the first occasion on which the artificial preparation of an alkaloid was achieved. The steps of the process were as follows;--

By the action of methyl iodide (CH_{3}I), pyridinium methyl iodide is formed, which is transformed on heating into α-methyl-pyridine hydriodide. The free base, when treated with acetaldehyde (p. 271), yielded a compound known as α-allyl-pyridine, which, in turn, was made to combine with nascent hydrogen. The resulting compound (isoconiine) becomes coniine on heating to 300° C. or boiling with solid potash. The chemical history is shown graphically below:--

CH CH CH CH // \\ // \\ // \\ // \\ HC CH HC CH HC CH H{2}C CH{2} | | | | | | | | HC CH HC CCH{3} HC CC{3}H{5} H{2}C CHC{3}H{7} \\ // \\ // \\ // \\ // N N N NH Pyridine. α-Methyl-pyridine. α-Allyl-pyridine. Coniine.

Pyridine, it may be mentioned, can be built up from its elements.

This coniine triumph of synthetic chemistry has been followed by many others of a similar character, and now all the alkaloids mentioned above in connection with pyridine have been produced artificially. Piperine was synthesised by Ladenburg and Scholtz in 1894; atropine together with other solanaceous alkaloids, and cocaine by Willstätter in 1901–2; and nicotine by Pictet in 1903. The structure of these alkaloids is considerably more complicated than that of coniine; atropine, for example, is represented by the formula

H H{2} H{2}C----C----C CH{2}OH | / \ | | N--CH{3} CH--O--CO--CH | \ / | H{2}C----C----C C{6}H{5} H H{2}

The molecule of quinoline contains a benzene and a pyridine nucleus condensed thus:--

HC CH \ C / // \ / \\ HC || CH HC || CH \\ / \ // \\/ C \// HC N

Among the alkaloids of the quinoline group may be mentioned those of cinchona bark and nux vomica. The constitution of these alkaloids is very complex, and in most cases but little understood. As an example of the cinchona group quinine may be taken. Its structure is probably

CH / | \ / | \ H{2}C CH{2} CH--CH==CH{2} | | | H{2}C HO·C CH{2} \ / | / \/ | / /\ | / / \ | / CH{2} N / HC C // \ C / \\ CH_{3}OC| \ / |CH HC| | | |CH \\ C \ // HC N

the formula being C{20}H{24}N{2}O{2}. Quinine has not been completely synthesised, but it has been prepared from cupreine, another cinchona alkaloid. The strychnos alkaloids likewise have not yet been artificially prepared, and their structure still requires elucidation.

The derivatives of isoquinoline, which was discovered by Hoogewerff and van Dorp in 1885, include some of the opium alkaloids, papaverine and narcotine, for example. Morphine and codeine do not, strictly speaking, fall into either of the three groups mentioned; our knowledge of the chemical nature of these substances has been much advanced recently, and it is probable that their synthesis will be effected before long.

HC CH // \ C / \\ HC| \ / |CH HC| | | |N \\/ C \ // HC CH

Isoquinoline.

One of the most beautiful pieces of work on the synthesis of vital products during recent years was the artificial preparation by Fischer (1895–98) of the bases caffeine and theobromine. The processes employed are too long and complicated to be described here, but the formulas may be given, since they demonstrate the close relationship which exists between the two substances.

(CH{3})N-----CO HN-----CO | | | | | | | | CO C-N(CH{3}) CO C-N(CH{3}) | || \ | || \ | || /CH | || /CH (CH{3})N-----C-N (CH{3})N-----C-N

Caffeine. Theobromine.

OTHER SYNTHETIC PRODUCTS.