Carl Julius Fritzsche and the Discovery of Anthranilic Acid, 1841 FRED E. SHEIBLEY
'1
The Carborundum Company, Niagara Falls, New York
NDIGO . was known to the ancients and its valuable dyelng properties made it one of the most important of the natural dyestuffs. The interest of the early chemists in this substance, therefore, is not surprising, and their labors together with the millions of dollars spent in its study, culminating in the first commercial synthesis in 1880, all contributed to make indigo one of the most important of the synthetic dyestuffs. Carl Julius Fritzsche became interested in indigo sometime before 1839 (1). Fritzsche is an excellent example of the hard-working early chemist who combined high experimental skill with strong powers of observation. He was born a t Neustadt in Saxony in 1808 and had gained some experience in pharmacy before he became an assistant to Mitscherlich who later (1834) discovered nitrobenzene. He afterward attributed his chemical stock in trade to Mitscherlicb, for the doctor of philosophy degree which he took a t the University of Berlin in 1833 was in botany. Fritzsche emigrated to Russia in 1834 where his scientific services were retained by the government for many years. His chemical work, most of which appeared initially in the publications of the Academy at St. Petersburg, touched on uric acid, indigo, the harmala alkaloids, osmium, and oxides of nitrogen. He discovered the isomeric ortho (I) and para nitrophenols, demonstrated the identity of murexide with the ammonium salt of purpuric acid, and studied the double compounds which picric acid and 2,7-dinitro-. anthraquinone f o m with aromatic hydrocarbons (2). In 1840 Fritzsche published his first paper (3) on the action of caustic alkalies on indigo. By distilling the red-brown crystalline mass which results when heated mixtures of these substances are allowed to cool he obtained a basic oil which he purified and analyzed correctly. He studied the oxalate and hy-
drochloride of the base and called i t Anilin after the Spanish name for indigo, anil.. Erdmann, then editor of the Journal fiir praktische Chemie, immediately recognized the identity of aniline with Krystallin, a base which Unverdorben had prepared from indigo in 1826, and called attention to this fact in a note (4) following Fritzsche's paper. While experimenting with aniline (3), Fritzsche had observed that the red-brown crystalline mass contained a salt of a singular acid which he proposed to investigate further. The promised study (5) resulted in the discovery of two new acids and was published in 1841. Wben the filtered, aqueous, greenish-yellow solution of the material prepared by adding indigo to a very highly concentrated solution of caustic potash a t 150°C. is acidified, a dark red-brown precipitate separates. This product appeared to be homogeneous and was named Chrysanilsaure in reference to its source and the golden-yellow color of its solutions. But chrysanilic acid is a complicated substance with a relatively high molecular weight and properties tending to make its study difficult, and it is not surprising that Fritzsche was unable definitely to determine its composition. He analyzed specimens of the acid isolated in the course of several varying attempts at pnrification, and also examined the lead salt; but chrysanilic acid does not crystallize well, and consistent results were not obtained. This uncertainty persisted almost sixty years later in a paper by Hentschel (6),and was only clarified in 1910 by the synthetic work of Friedlander and his collaborators (7),(8). Having failed to learn the exact composition of his singular acid Fritzsche turned to an interesting degradative reaction. On warming chrysanilic acid with mineral acids he obtained a bluish-black precipitate, presumably an indigoid dyestuff, which to date has not been thoroughly investigated, and an aqueous
solution of another acid which he precipitated as the zinc salt. This acid was also prepared directly by allowing an alcoholic solution of the indigo-caustic potash reaction mixture to stand in air until the initial green color changed to brown, after which the liquid was saturated with carbon dioxide and concentrated, when the 'potassium salt of the new acid crystallized. The free acid, isolated by treating a suspension of the zinc salt in alcohol with sulfuric acid or by adding acetic acid to a solution of the potassium salt, was appropriately designated Anthranilsiiure, a beautiful name which rolls harmoniously off the tongue and indicates the origin of the acid in indigo as well as the bluish fluorescence of its solutions. Anthranilic acid crystallizes easily from hot water or alcohol in long needles and plates. Fritzsche obtained it colorless, and from a number of excellent analyses of the acid and its silver salt he was able to describe its composition accurately. He mentions its sweet taste and states that it melts and sublimes a t +135OC. This observation was possibly made with a large amount of material, perhaps during a decarboxylation experiment, since the accepted melting point (9) is 144-145'C. and few chemists a t that time attached much importance to melting points. When anthranilic acid is heated above the melting point it decomposes into carbon dioxide and aniline. Fritzsche observed this reaction for the first time and recognized the products; and that its importance was not lost is indicated by the italics (10) which are used to describe it. He effected the change quantitatively and collected 99.6 per cent of the theoretical amount of carbon dioxide (5). A nicely crystalline product like anthranilic acid and its relation to the composition of indigo did not fail to attract the attention of other chemists. Liebig was so interested that he a t once repeated parts of Fritzsche's experiments, with modiiications, and described his results in a paper (11) in his Annulen der Chemie und Pharllzacie immediately following the published account (5) of Fritzsche's work in that journal. He confirmed the decomposition of anthranilic acid into carbon dioxide and aniline, and even checked the compositions of the acid and its silver salt. Fritzsche returned to the subject in 1843 (12). but his most important observation was the recognition of the identity of Zmin's Benzidam with aniline. Zinin prepared Benzidam by reducing nitrobenzene with ammonium sulfide, and Fritzsche showed its identity with aniline in a note (13) which follows Z i s classic paper (14). The constitution of chrysanilic add was finally elucidated through the experiments of Friedlander and his co-workers in 1910 (7), (8). By carefully acidifying a dilute aqueous solution of the indigocaustic potash reaction products in the presence of a large volume of ether they succeeded in isolating indoxyl-2-aldehyde and anthranilic acid, and represented the action of hot caustic alkalies on indigo (I) as follows:
.
-
~ ~ : > c = c < c O KOH ~ NH (1)
OK
I
(p? /' C-C
\NH/
e
OH
1
HOOC,
+ &N/ (11)
(111)
They showed further that under acid conditions indoxyl-2-aldehyde (11) and anthranilic acid (111) react smoothly to give chrysanilic acid (IV) which is therefore, the o-carboxy anil of indoxyl-2-aldehyde:
-.
~ c > HOOx -~~~ OH
I
+.
(11)
+
HEN
(111)
OH
0''\c4HH00 hN I
(IV)
That this reaction occurs upon acidification of the initial greenish-yellow solution of the indigo-caustic potash reaction mixture is indicated by the greenishyellow color of alkaline solutions of indoxyl-2-aldehyde as contrasted with the deep golden yellow of corresponding solutions of chrysanilic acid. In 1840 the organic background of chemical knowledge was insufficient for establishing a systematic nomenclature and chemists were obliged to assign individual names to new substances. Their choices were not always happy ones, and while the desirable practice of designating complicated or little-known natural products by names indicative of their biological sources has persisted, many very classical names amved a t in this manner have entirely disappeared. Fritzsche did not confine himself to Greek roots; the names with which he identified his compounds clearly show the influences of a good taste, and his Anilin has survived the less distinguishing Kristallin, Kyanol (Runge, 1834), and Benzidam. When we consider his disinterested experimenting, his professional services to the Russian government, and his frequent indulgence in foreign travel, i t is not surprising that Fritzsche never engaged in active
teaching. Peter Griess, a brewery chemist, later refused German chemical professorships because he felt that they could interfere with his personal research. How different i t is today when these conditions are reversed, and few opportunities of pursuing satisfactory fundamental investigations are to be found in other than teaching positions a t the larger universities. Fritzsche's laboratory is said to have been of a modest kind but later he shared with Zinin (15) the more ample facilities of the chemical laboratory of the St. Petersburg Academy. What interesting discussions must have passed between these two masters of organic chemistry a t that time! Fritzsche had always enjoyed good health but after 1869 he was bothered with paralysis. He continued working, however, and finished an investigation of the dimorphism of tin b e f o ~ his death in 1871. LITERATURE CITED
(1) , .(a) ,
FRITZSCHE, "Vorliufige Notiz iiber ein neues Zersetzungs-
product des Indigo dumb Salpetersiure," J. prakl. Chem., (1) 16, 507-8 (1839). "Carl Julius Fritzsche," Ber., 5, 1 3 2 4 (1872); J. Chem. Soc., 25, 345-8 (1872).
(3)
FRITZSCHE, "Ueber das Anilin, ein neues Zersetzuugs-
produkt des Indigo," J. @=kt. Chem., (1) 20, 4%-7 (1840); Ann., 36,84-8 (1840). (4) ERDMANN. J. brakt. Chem.. (1)20. 457-9 (1840). FRITZSCHE. " h b e r die prodtkte der ~in&iirk;ng des Kali auf das Indigblau," ibid., (1) 23, 67-83 (1841). "Ueber die Producte der Einwirkung von Kali auf Indigblau," Ann.. 39. 76-91 (1841). HENTSCHEL, " ~ e b e rda; Verhalteu des Indigatins in der Kalischmelze." J. p a k t . Chem,, (2) 60, 577-81 (1899). FRIEDL~NDER AND SC-ENK, "Uber die Zersetzung von Indieoblau und Indinorot durch Alkalien." Ber...43.19713 (iilo). FRIEDL~~NDER AND KIELBASINSKI. ''ijber die Aldehyde des Oxindols, Indoxyls und Oxy-thionaphthens," ibid., 44, 3104-5 (1911). H ~ ~ B N AND E R PETERMANN, "Ueber Isomerieen der aromatischen Siuiuren. 111. Ueberfiihrung der Beuzo@siure in Anthranilsiure und Salicylsiure," Ann., 149, 142 (1869). FR~TZSCHE, J. prakt. Ckcm.. (1) 23, 79 (1841). LIEBIG, "Ueber die Darstellung und Zusammensetzung der Anthranilsiure," Ann., 39, 91+ (1841). FRITZSCHE, "Vorliufige Notiz iiber einige neue K6rper aus der Indigoreihe," J. prak. Chem., (1) 28, 198-204 (1843). Fnr.rzscnE. ibid., (1) 27, !53 (1842). ZININ, "Beschreibung emger neuer organischer Basen, dargestellt durch die einwirkung des Schwefelwasserstoffcs auf Verbindungen der Kohlenwasserstoffe mit Untersalpetersiure," ibid., (1) 27, 140-153,(1842). LEICESTER, 'IN. N. Zinin, an early R u m a n chemist." J. CHEM. EDUC., 17, 3 0 3 4 (1940).
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