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School of Education, Box U-33 :!;;& The University of Connecticut g?&!~

Storrh, CT 06268

Julius Bredt and the Structure of Camphor: On the Threshold of Modern Stereochemistry

George B. Kauffman Californ~a State University, Fresno Fresno. CA 93740

I)espite hi- vi~lu.d,le colirril~utioni I,, urgani~. ~.h(,mistry. .luliun Ilrtvlt I 18% 1!1:C1 hni IWCII 3lmust t<,rgtrttcll n) KII . gliah-qwnkttty chemi.ri. Fur enattlplr, ht: hits I K I ~ heen in- d11~1ed in the reven! t d i t i m d'Scrihncr'~ "1)1cli~>11nry Svi- entific H i w r a t ~ l ~ ~ . " Yet rhis ~i l iwcl~c sterewhtmist l1el011g9

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in the first rank of researchers oncamphor and its derivatives, alone with such scientists as Adolf Ossian Aschan (1860-1939), .. . h I , , l i ~ , m Hatyr I lA:i%lYl;~, and Ott,, Wallach (1847 l!J:ll I . On the <r.<a.;ion ui l3redt' ~ t , m r ~ l c l i ~ ~ d 2: \ears at lhe .Adchef1 Technische Hochschule, the entire ~ o v e m b e r 1922 issue of the Journal fur ~raht ische Chemie (of which he was a co- editor since i91f) was entitled "J. Bredt zum fiinfundzwan- zigjihrigen Lehrjuhilaum an der Technischen Hochschule zu Aachen" and consisted of articles on inorganic and technical chemistry by his colleagues and former students. In the words of one of his former students, Bredt "had the good fortune to sit as a student at the feet of the great classic figures of organic chemistry and himself became classic figure of structural theory" ( la) .

Before 1893, when Bredt proposed his formula for camphor, the one that is universally accepted today, more than thirty incorrect formulas had been proposed by various chemists in attempts to represent the structure of the familiar, pleas- ant-smelling substance that has heen used for medicinal purposes since earliest times (2). Camphor, CI0H160, is a hi- cyclic ketone occurring naturally in the wood of the camphor tree (Cinnamomum camphors), which is native to Taiwan, China. J a ~ a n , and the Malay Archipelago (3). Its chief in- du3rri;ll use ha; heen ns ;I plastici,er ror th(, ~n.~nuf'ocrurr c r f I I I I I I n r i iiln I . The w ~ i w r ~ i m i,f . ~

~.itmphur, a terlr.tat. to 11 cymtw, an ,trc~maria c.nnla)und, by di>ttlldtim wit h p11oiphur.1~ pvntc,xide ( JI ahcw(:d that I I I ~ I I ~

twpe11es tnwt be ring c m ~ ~ h ~ u n d + , I h t r tht, : ~ I J I K I I ~ C narur(, ut tt.rl,ew redvti,,ni indicated rhn~ ~ht.yitre mure highly silt- urated than IYIMW :irtmcttics ! i t . In I A X K~kul6 161, whu . . heheved p-cymene to be p-n-propyltoluene.' proposed the following structural formula for camphor (8):

C J b I

Stepwise oxidation, however, showed that the carbon atoms of the methyl and isopropyl groups were not freely attached to the hydrocarbon ring hut formed a second ring within it. In 1893 Bredt made his most important contribution to ste- reochemistry. Largely based on studies of the oxidation products of camphor, he proposed his own constitutional

Julius Bredt (1855.1938) Coultesy, Dr. P. Muiler, Technische Hochschule Aachen.

formula for camphor, which involved the transfer of the iso- propyl group as a mesomethylene bridge member in the ring and the recognition of a new type of bicyclic ring system (9):

Bredt's formula was fullv confirmed hv svnthesis of the oxi- . . dati,,n l ~ r t d ~ ~ c t i 01 ca~npln,r ( lo) , comphurunit .avid I 1 1 1. ;mil wrnrhr ic acid ,121. nnd IIY I ht: >vn~he-ii oi . a m l h ~ r f r o n t cambhoric acid (13). ~ r e d t s p e n t a number of years experi-

"Profiles in Chemistry" is a biographical feature, highlighting the contributions of distinguished chemists in the context of their lives. The column is designed for curriculum enrichment, allowing the secondary schooi teacher to enhance the vitality of chemistry with the sense of scholarship and adventure shared by chemists throughout history.

' In 1891 p-cymene was found to be p-isopropyltoluene (7)

Volume 60 Number 4 April 1983 341

mentally clarifying some of the contradictions resulting from his camphor formula.

From his studies of dehydrocamphoric acids, Bredt pro- posed his famous rule on the strain relationships in polycyclic systems with bridges, viz., that in bridged rings the bridgehead cannot participate in double bonding (Bredt's role) (14) This rule proved its heuristic value in Angeli's investigation of the constitution of camphenone. From his work on hornylcar- boxylic acid, Bredt discovered hornylenecarhoxylic acid by the hitherto unsuccessful reduction of camphorcarboxylic acid. a B-ketonic acid. which he accomnlished hv electrolvtic reduction a t a mercury cathode. In a;ery elegant series of reactions, the bornylenecarboxylic acid led to the isolation of epicamphor or P-camphor, a structural isomer of camphor, in which the keto eroup is in the 3-wosition. Bredt also isolated . . bornylene, perivyc I.~..~mph.m.,n(., :and 11-ilikvl~~ciirnl~hane. \Ve are aliu indvlrtt { I I ,him iur t h ~ n o r p h ~ , l ~ x \ c r i the caml~hane skeleton (146); the concept of endo-ex i'omerism, which he developed from the isomer pair of borne01 and isoborneol; the conceit of meso-trans position, which he developed from the dehydrocamphoric acids; the first clear recognition of the significance of the Nametkin rearrangement in many race- mizations of camphor derivatives; application of the Grignard reaction to fenchone. camwhenilone. and nolvketones of . . camphane; a study of the ~ & r d reaction with camphene; the elucidation of the structure of tricyclene acid; and the reac- tions of chloryl- and bromylphthalimide. Furthermore, in his work he developed manv useful devices and techniaues, ~ a r -

half a century earlier (15) Konrad Julius Bredt was horn in Berlin on March 29,1855

(1, 16, 17). The son of August Wilhelm and Amalie (n6e Leyen) Bredt, he was originally expected to study jurispru- dence, even though he showed a strong inclination for natural science at the Gymnasium. He studied at the University of Leipzig where he was attracted to the lectures of chemist Hermann Kolhe 11818-1884) and uhvsioloeist Carl Ludwie . " (1816-1895). ~ f t e ; a year's study at the agri&ltural instituc of Carl Remieius Fresenius (1818-1897) in Wiesbaden. in 1877 he hegan stuby under Rudolf Fittig (1835-1910) a t the Uni- versitv of Strasboura (then Germanv. now France), where he received his doctorate in 1880. He rkmained there as Unter- richtsassistent (teachine assistant) until 1882. After several years of study with ~&i!io Noelting (1851-1922) a t the Chemieschnle (now the Ecole Supgrieure de Chimie) in Mulhausen (then Germany, now Mulhouse, France) and with Carl Hermann Wichelhaus (1842-1927) in Berlin, Bredt worked in a silk dye works in Crefeld and in the aniline dye firm of Kalle & Co. in Biebrich am Rhein. He thus worked in the German dye industry during its years of rapid develop- ment, and he followed this practical experience in the manu- facture and awolication of coal tar dvestuffs with vears of

in organic chemistry a t the University of Bonn, where he also was first Unterrichtsassistent to the supreme patriarch of structural organic chemistry, August Kekul6 (1829-1896). In the Fall of 1897 he was named Ludwig Claisen's (1851-1930) successor as Ordentlicher Professor (Full Professor) and Di-

rector of the Organic Chemistry Laboratory at the Technische Hochschnle at Aachen. A modest and reserved nerson. he was

professor of Chemistry at ~ a i h e n (1923-1947). Bredt retired in 1923 and died in Aachen on September 21.1937.

aliphatic compounds, particularly fatty acids, began early in his career. He was particularly concerned with the charac- terization of simple aliphatic lactones. His first scientific success was his discoverv and structure-wroof of isocavro- lactone, the first aliphatic"lactone, which he synthesized from isocawronic acid. Since at that time camwhoronic acid (18) was he1ie;ed to he a lactonic acid, Bredt turhed to this compound, for which he corrected the errors of his predecessors and de- termined its constitution to he a,a,P-trimethylcarballylic acid (19), a structure later confirmed by Perkin and Thorpe's synthesis (11 ). Thus hegan Bredt's lifelong preoccupation with camphor derivatives and other alicyclic compounds, leading to the contributions already mentioned.

Today, thanks to Bredt's pioneering work on camphor and its derivatives, this area is one of the most thoroughly inves- tigated and understood fields of organic chemistry. Yet the significance of Bredt's research is not limited to the specific area of terpene chemistry. I t has resulted in important con- cepts and data of value not only for the structural chemistry of hicyclic systems hut also for stereochemistry in general.

Acknowledgment The author wishes to acknowledge the assistance of Dr. P.

Miiller of the Bibliothek der Rheinisch-Westfalischen Technische Hochschule Aachen and Prof. Dr. F. Dallacker of the Rheinisch-Westfalischen Technische Hochschnle Aachen.

Literature Cited (1) Lipp,P.. (a) J. prokt. Chem.,213,1(1922): (b) Re,., 70A. 150(1937). (2) Lapworth A,, Brit. Assor. Reports, 299 (19W). For 28 alternative formulas ivith ref-

erence citations see Walden. P.. '"Geschichta der organischen Chemie seit 1880: Julius Springer, Bedin, 1941, pp. 552-555.

(3) Naller, C. R., '"Chomistxy of Organic Compounds,). 3rdEd.. W.B. SaundeaCo.,Phil~ adelphisand London. 1965. pp. 961-962.

(4) ~ u m a s , J. B. A,, e n d ~ e ~ a t s n d e , z . , ~ n n . chim., 60, 225 (1832):6~,400 (1833). ( 5 ) 1hde.A.. "TheDevelopment of Modern Chemi3try"Harper sndRow. NewYork, 1964,

" PC" -. (6) Kekuli ,A. ,Bri ,6 ,931 (1873). (7) Widman,O.,Eer..24,439 (1391). (8) Farber, E.,"TheEvolutionofChemistry,).2ndEd.. The RonaldPressCo.,NorYork,

1969. on. 37S380.

"., ,"" x.m"",.

(13) Haller,A.,Compt. rend., 122,448 (1896). (14) Bredt, J., (8) Ann.. 395, 26 (1913): (b) 437, l (1924); (c) J . prokt. Chem., 121 95, 134

(1917): (dl Wittig, G.,"Stereochemie,). Akadunische Verlagsgesellrchaft M. B. H., Leipig, 1930, pp. 15L156: (4 Ebel, F., in heudenbeigJ K. (Editor), "Stereoehemie,). Fmne Deuticke, Leipig, Vienna, 1933. pp. 849450.

(15) Bredt. J.,andDemeure,F., J .p iok t . Chem., 149,153 (1937). (16) Anft, B. P., "Neue Drutsche Biographie,' Dunekei & Humblot, Berlilin, 1953, Voi. 2,

p. 568. (17) G a t , P. (Editor),"Die Technische Hochschule xu Aaehen 1870-1920: Eine Gedmk-

schnfft,). La Ruelle'schz Aecidenldruckerei und Lith Anstalt, Aachen, 1921, pp. 316-317.

(13) Kachler, J., Ann., 159,281 11871). (19) Bredt, J .Ann .226 .249 (1885):Bar. 18,2989 (1888).

342 Journal of Chemical Education