JOHN H. WOTlZ Southern Illinois University Carboodale, Illinois 82901
Adolf von Baeyer and the Naming of Barbituric Acid George B. Kauffman' California Stat? Uniuersity, Fresno Fresno, CA 93740 Hnrhiturates, "the most verintileoiall depr&sant dr119," ran produrean entire rsnrct:ofrt'frcts from m~lda d ~ t i m flhey were the "tranquilizersn;f an earlier era) through deep anesthesia to death (1, 2). In 1958 American physicians prescribed about three to four billion doses of harbiturates, which are still the most widely used drugs for inducing sleep (sop'-rifics). Although barbituric acid (2,4,6-trioxohexahydropyrimidine) was discovered by Adolf von Baeyer (1835-1917) and although he and many dher (3-9) in prepared a great variety of its derivatives, the medicinal value of barbiturates went unrecognized until 1903 when Emil Fischer (1852-1919). Baever's most illustrious student. and Joseph "on ~ e r i n g(18i9-1908), the German physician, nhvsioloeist. and nharmacolo~ist.discovered that diethvlbaihitur; acid ( ~ e r o n aor l bariitalj could be used to put dogs to sleep. Within the next half-century more than 2,500 barbiturates were synthesized, and by 1955 U S . production amounted to 864,000 nounds-enourh to ~ t million . u ten adults to sleep every ni'ght of the year'(l). Baeyer was the first student of Friedrich August Kekul6 (1829-18961, the founder of structural organic chemistry, and in 1858, the year that Baeyer received his doctorate, he followed Kekul6 from Heidelberg to Ghent. On this journey he met Adolf Schlieper (1825-871, a textile printer and industrialist a t Elherfeld who had worked on uric acid under Justus Leibig (1803-73) and who gave Baeyer a box of preparations that led him to begin his own researches on this compound and its derivatives. Baeyer's first work in this field-on uramil (amidobarhituric acid)-was carried out with Schlieper (10). A study of uric acid provided the basis for Baeyer's Habilitationsschrift, by which he qualified as a Priuatdozent in 1860, the same year in which he became a lecturer a t the Gewerheinstitut (Trade Institute) in Berlin. It was here that he prepared harbituric acid from hydrurilic acid, which Schlieper had prepared by the action of dilute nitric acid on uric acid (11). Baeyer established its constitution as malonyl urea H
(I
I 111
8 7i c)' \&;I
\H
I 011
H
by its hydrolysis to form urea and malonicacid (12,13). The basic structure of harbiturates is thus a rine com~osedof four
' The author gratefully acknowledgesthe assistance of the National
Science Foundation (Grant SOC 7fi-112fi7). 222 / Journal of Chemical Education
almost any combination of alkyl, alkenyl, aryl, or cycloalkyl groups or certain modifications of these groups leads to the various central nervous system depressants on the market. Baeyer never gave reasons in print for his choice of the name barbituric acid. In his first mention of the compound, in the article "Untersuchungen uber die Harnsa0regruppe:Erste Abhandlung," he merely writes: (14) According to this, violuric aeid [5-isonitrosabarbiturieacid] appears which I have to be anitrosa substitution product of an acid N2C4O3H4, named barbituric acid [Rnrbitursriure],a view which is completely confirmed by the further action of nitric acid on violuric acid. Nevertheless, conflicting stories attributed to B~~~~~concerning the source of the name have circulated in the chemical
literature for years.
Probably the most authoritative account is that of Richard Willstitter (1872-1942), Baeyer's student, Priuatassistent, of organic chemistry and successor as head of the ~~~~i~~~~ at the Munich Technische Hochschule (8, p, 119), When he first obtained the ureide of malanie aeid, which, later on, Emil Fischer was destined to make a focal point in the industrial svnthesis of sooorifics.. Baever . soueht - a name for the beautiful substance. Nowadavs manufacturers make millions a "ear easilv on h.~rl,it~w.~ttj n d IIU\.V II.I idea .,I the si"t>itlca~u d'thr w t n t In hiIICIIIIF., H x w r uitd t u s d ) , "A1 the time I w a i i n lu\.e \ \ i l l > d hli-i t i d ~ r a.
