On the Density of Racemic and Homochiral Crystals: Wallach, Liebisch and Sommerfeld in Göttingen

CHIRALITY – SYmmeTRIeS And ASYmmeTRIeS CHIMIA 2018, 72, No. 6 399

doi:10.2533/chimia.2018.399 Chimia 72 (2018) 399–403 © Swiss Chemical Society On the Density of Racemic and Homochiral Crystals: Wallach, Liebisch and Sommerfeld in Göttingen

Karl-Heinz Ernst*ab

Dedicated to Prof. Jack Dunitz on the occasion of his 95th birthday. In memoriam of Howard Flack

Abstract: The first comparison of heterochiral crystals with their homochiral counterparts was given by Otto Wallach in an account on carvone bromide crystals in 1895 in Liebigs Annalen der Chemie. Although the well- known mineralogist Theodor Liebisch, professor in Göttingen from 1887 to 1908, performed the analyses and wrote the last four pages of that Annalen paper, his colleague from chemistry, Wallach served as sole author. We discuss whether Wallach or Liebisch had the idea of a comparative study of crystal densities of racemates and their homochiral analogues and who of the two should be credited. Keywords: Arnold Sommerfeld · Chiral crystallization · History of science · Otto Wallach · Theodor Liebisch

the Swiss Federal Laboratories for an essay about this small episode of the Materials Science and Technology. In history of science,[9] it was Wallach’s col- 1995 he founded the Molecular Surface league Theodor Liebisch, professor of Science Group, specializing in chirality of mineralogy in Göttingen, who performed two-dimensional molecular crystals, func- and reported on the density of crystals tional surfaces and single molecule surface of chiral compounds in the Wallach- dynamics. He was visiting researcher at authored Annalen paper. In the same pa- the Physics Department of UC Berkeley, per, which even contains measurements at the Department of Bioengineering at the performed by Arnold Sommerfeld, both University of Washington in Seattle and at Wallach and Liebisch claimed to be the IBM Almaden Research Center, San José, father of the idea of such comparative Born in Northeim near Göttingen in CA. Currently he holds an adjunct faculty studies. Although it was common at that Lower Saxony, Germany, Karl-Heinz position at the Department of Chemistry at time not to have students and assistants Ernst was originally trained as Chemical the University of Zurich and was recently listed as coauthors, it is quite interesting Technical Assistant (CTA). He studied promoted at Empa to Distinguished Senior to speculate why Wallach did not include Chemical Engineering and Chemistry at Scientist. his colleague as a coauthor. the TFH Berlin and the Freie Universität Berlin, respectively. His PhD studies were conducted at the Berlin Electron Storage 1. Introduction 2. Otto Wallach (1847–1931) Ring for Synchrotron Radiation (BESSY I) and the Freie Universität Berlin. After a In 1895 Otto Wallach published as Otto Wallach was born (27.3.1847) postdoctoral research stay at the University sole author a paper entitled ‘Zur Kenntnis in Königsberg, East Prussia, and grew of Washington in Seattle he joined Empa, der Terpene und der ätherischen Oele; up in Potsdam near Berlin (Fig. 1). Due No. 34: Ueber gebromte Derivate der to health problems, he had a bad start in Carvonreihe’,[1] in Justus Liebigs Annalen school,[10] but became a good student later. der Chemie 286, pp. 119–143.[2] One im- His friend Georg Borsche introduced him portant result of the paper is the evalua- to chemistry and Wallach followed him tion of the density of racemate crystals in 1867 to Göttingen to study chemistry with respect to their homochiral counter- under Friedrich Wöhler. He spent one se- parts. For eight of the nine tested samples, mester inbetween in Berlin with August *Correspondence: Prof. Dr. K.-H. Ernstab E-mail: [email protected] higher densities (up to 4%) were reported Wilhelm von Hofmann (1818–1892), who aEmpa – Swiss Federal Laboratories for Materials for the racemate crystals. The empirical had just come from London as Eilhard Science and Technology finding, namely, that racemic crystals Mitscherlich’s (1794–1863) successor. Laboratory for Nanoscale Materials Science Überlandstrasse 125 tend to have a higher density than their Wallach completed his PhD after only CH-8600 Dübendorf homochiral analogues, was coined later five semesters! In his doctorate work bDepartment of Chemistry ‘Wallach’s rule’,[3] an expression which (‘Über von Toluol abgeleitete neue iso- University of Zurich Winterthurerstrasse 190 has subsequently often been used in the mere Verbindungen’) under the direction CH-8057 Zürich literature.[4–8] As published previously in of Hans Hübner, he isolated an unknown 400 CHIMIA 2018, 72, No. 6 CHIRALITY – SYmmeTRIeS And ASYmmeTRIeS

isomer of bromotoluene by crystallization. Although a true finding, it was disputed by ab Wöhler’s assistant Fittig, who offered his head if Wallach were right. (“Der Wallach will ein neues Bromtoluol gefunden haben! Ich lege meinen Kopf auf diesen Tisch und Sie können ihn abhauen, wenn das richtig ist.”[11] “Wallach claims discovery of a new bromotoluene! I will lay down my head onto this table and you may decollate it, if this is correct.”). Wallach was happy to leave Göttingen in 1869, “with the quiet and genuine desire: never to be seen there again.”[11] As Fig. 1 Fig. 1. a) Otto Wallach, Nobel Laureate in Chemistry 1910. b) Wallach is buried at the shows, it turned out differently. Wallach Stadtfriedhof in Göttingen among seven other Nobel laureates and many famous scientists and became assistant of Hermann Wichelhaus mathematicians. in Berlin and worked with August Kekulé in Bonn. After voluntary service in the German-French war, he went to Agfa in on terpenes until his retirement in 1915. bromides and aims at elucidation of their Berlin, but returned to Bonn again to work Wallach was very active even after his molecular structure by analyzing chemical with Kekulé and achieved his Habilitation. retirement and remained a bachelor his and physical properties. Besides the puz- As professor for pharmacy in Bonn, entire life. He was appointed already in zling role Liebisch plays in that paper, it Wallach began his seminal terpene work. 1885 fellow of the Deutsche Akademie contains several other remarkable com- Wallach described later as cause for his in- der Naturforscher Leopoldina, which ponents (Fig. 2). Concerning conglomer- terest in ethereal oils, flasks on a cupboard awarded him – long before Emil Fischer – ate versus racemate crystallization, the in Kekulé’s private laboratory containing with its prestigious Cothenius Medal. most important part is described in the such substances, but being untouched for As fellow of the Prussian Academy of chapter ‘Ueber racemie’ (About race- fifteen years. Wallach’s request to perform Sciences, Wallach became decorated with mism). Wallach repeatedly emphasizes research on their content were granted by more medals by Prussia. His colleagues in the importance of studies on racemism, Kekulé with ironical laughter: “Yes, if you England elected him as Honorary Fellow “because complete darkness prevails can make anything out of them!”[12] of the Chemical Society and awarded him about the principles in which such trans- In the 1880s research on terpenes the Honorary Doctor of the University of formations occur”; and “a solution to this had been lacking a systematic approach. Manchester. He received honorary doctor- question is only expected when numerous Wallach: “...if one casts a glance over the ates from the University of Leipzig and suitable examples are studied”. Wallach old literature of the terpenes, it does not the Institute of Technology Braunschweig. compares physical properties, like melt- appear a particularly enticing subject for (Even a crater on the moon was named ing and boiling points as well as crystal investigation. There were isolated obser- after him in 1979). Wallach was awarded shape, of optically active bromocarvones vations in almost incomprehensible abun- with the Nobel Prize in Chemistry 1910 with their inactive modifications (Fig. 2). dance.”[13] Or in the words of Leopold and learned about it from a newspaper on He particularly points out that he, in con- Ružicˇka (1887–1976, Chemistry Nobel the train from Hannover to Göttingen.[15] trast to others, believes in the importance laureate 1939): “…Wallach had plunged of synthesizing optically active as well as into work in a neglected garden so over- inactive crystalline counterparts. Wallach run with weeds that the useful plants could 3. Wallach’s Annalen from 1895 also made a side blow at Emil Fischer, not thrive. Any good gardeners had al- who ignored[16] Wallach’s discussion on ready attempted to improve its condition, The work reported in the Annalen pa- racemism ([My work has] “... not received but each had soon damaged his hands and per from 1895 serves as a good example the slightest attention” Wallach writes in a the weeds had begun to flourish again with for Wallach’s approach.[1] He describes the footnote of ref. [1]). renewed vigor. […] After about the begin- bromination of carvone and dihydrocar- Wallach clearly points out that there ning of 1890, the garden was well weeded vone, reports their tri-, tetra-, and penta- are exceptions from the tendency that ra- and it soon enticed other gardeners to investigate the conditions of life and the Fig. 2. Collection of properties of the plants, and to determine melting points and [12] their species.” crystal forms of race- Wallach reported in 1888 that dipentene mic and enantiopure is nothing but the racemic mixture of limo- carvone bromides. nene enantiomers,[14] and managed to iso- late (–)-limonene from spruce needle oil. As already had been applied in his doctoral work, Wallach brominated the compounds and achieved thus products that could be readily crystallized. As with Liebisch later in Göttingen, he involved a mineralogist (Carl Adolf Ferdinand Hintze, 1851–1916) in his analyses. When Victor Meyer went to Heidelberg in 1889 to replace Bunsen, Wallach succeeded him and went back to Göttingen, where he continued his work CHIRALITY – SYmmeTRIeS And ASYmmeTRIeS CHIMIA 2018, 72, No. 6 401

cemates have higher melting points. He Fig. 3. a) Photograph states that repeated re-crystallization ac- a of Liebisch. companied with decreasing melting points (© Wissenschaftliche to conglomerate crystallization (“come Sammlungen an der apart into the components”). In a footnote Humboldt-Universität Berlin). Wallach mentions that Emil Fischer had b) Sommerfeld as doubts that lower-melting racemates are post-doc in mineral- actually true racemates although Wallach ogy in Göttingen. had clearly identified such for terpenes.[17] From ref. [30]. As the discussions of Fischer, Wallach and others at that time show, the problem of racemate versus conglomerate was a hot topic. Although 50 years had passed since Pasteur’s optical resolution of tartaric enantiomers, Alfred Werner (1866–1919), for example, only realized in 1899 that conglomerate crystallization could prove his coordination theory.[18,19]

4. Theodor Liebisch (1852–1922) and Arnold Sommerfeld (1868– b 1951)

In ref. [1], Wallach lets his colleague Theodore Liebisch finish the paper. Born in Breslau (polish Wroclaw), Liebisch (Fig. 3) received his PhD in geology.[20] In Berlin he worked at the Mineralogisches Museum der Friedrich-Wilhelms-Universität, and became lecturer (Privatdozent) and professor for mineralogy and petrography. During the course of his career he occupied professor positions in Breslau, Greifswald, Königsberg, Göttingen and finally again in Berlin.LiebischwasfellowoftheGöttinger and Prussian Academy of Sciences, author of textbooks and monographs and publish- er of different mineralogy journals.[21–25] His work was very much oriented to- Sommerfeld accepted the offer and went alogy and Sommerfeld’s strong desire for wards physics and optics, in particular, to Göttingen in 1893 (Fig. 3). mathematics led finally to the break-up af- polarization microscopy. Expressions like Although now assistant to Liebisch, ter few months. Liebisch-twin and Liebisch-law connect who requested his full commitment to min- his name to different phenomena in mineralogy, Sommerfeld had the hope that he eralogy.[26] With the exception of some de- would find extra time to pursue mathemat- 5. Density of Racemate Crystals tailed obituaries,[27–29] not much is known ics.[30] Page 141 of the Annalen paper actu- and their Pure Counterparts: about Liebisch’s personality. However, ally lists crystallographic characterizations Wallach or Liebisch? thanks to Arnold Sommerfeld, assistant performed by Sommerfeld. of Liebisch in 1893, we have a somewhat In Göttingen Sommerfeld found a fa- Wallach states in the Annalen paper closer view on Liebisch. During his time therly friend in Wallach. Not only both that crystal form and density of racemic in Göttingen, Sommerfeld was writing al- being from Königsberg, they were also mixtures may differ with respect to their most daily letters to his mother, which are distantly related. Sommerfeld reported components and the need for evaluation still available.[30] about Wallach: “Always authentic, hard- of many samples.[1] The most important Arnold Sommerfeld, one of the working, utterly incisive, engaging, help- statement in this respect is then: “I am founders of modern theoretical physics, ful.” and: “He has an awful lot to do, and is especially grateful to my highly esteemed also came from Königsberg, where he very diligent.” Interestingly, Sommerfeld colleague professor dr. Th. Liebisch that he studied mathematics under Hilbert and cites Wallach commenting on Liebisch: allowed the relevant evaluation of material Lindemann.[30] It was actually his affec- “Professor Wallach advised me rather obtained in our laboratory in his miner- tion for mathematics that brought him to against a career such as Professor Liebisch alogy institute, and that he notably was Göttingen. Initial contacts to Liebisch, has in mind; Liebisch-style mineralogy in personally involved. Professor Liebisch however, were established by the spouses Germanyisnot,inhisopinion,anitemmuch discloses the following about the previous of former Königsberg professors and their in demand.”[30b] (If Wallach was so dismis- results: …” (Fig. 4). network. Sommerfeld’s mother learned sive about Liebisch-style mineralogy, why By taking then over for the last four indirectly from Adelheid Liebisch that her did he ask then his colleague for help in the pages of the Annalen paper, Liebisch husband was looking for an assistant. So evaluation of his compounds?) Liebisch’s makes clear that he is the father of the idea Sommerfeld was proposed as the candidate disappointment that Sommerfeld was as of comparing the densities of homochiral to Liebisch. After his positive response, not committed as he had hoped to miner- crystals with the corresponding racemate 402 CHIMIA 2018, 72, No. 6 CHIRALITY – SYmmeTRIeS And ASYmmeTRIeS

Fig. 4. Crystal analy- cussed the possibility of such experiments. sis: Liebisch reports We suggest therefore to turn ‘Wallach’s his results for densi- Rule’ into Liebisch-Wallach rule (LWR). ties and specifc a In Wallach’s elaborate memoirs Liebisch’s volumes for tartaric name appears only once in a plain list of acid (a), Wallach’s samples (b) and the professors in Göttingen at the time samples Liebisch b when he arrived. Otherwise, he does not received from Miers mention Liebisch at all. and Pope (c).[1] The Liebisch-Wallach rule (LWR) de- scribing the tendency that racemates pack denser than their homochiral analogues is purely empirical. LWR has statistically been verified for 65 pairs of resolvable compounds.[3] However, as the authors noted, there is a statistical bias, because compounds with the racemate profoundly less stable will not be covered. Mandelic acid is a typical example not obeying LWR, the pure enantiomer crystals are denser than those of the racemate.[7] As Dunitz and Gavezzotti found for 20 chiral- racemic pairs of proteogenic amino acids, LWR does not apply for these compounds either.[34] Interestingly, a helical intermo- lecular packing motif, mediated by hydro- crystals of a particular compound: “When of racemic compounds and their compo- gen bonds in the homochiral crystal, brings I was occupied during summer of 1894 nents’.[28] However, such a subtitle does more stability than the centrosymmetric with the production of water-free paratar- not exist in the Annalen paper. enantiomer packing of the racemate. taric acid (traubensäure) according to the Wallach seemed clearly annoyed by A promising approach towards better specifications of A. Scacchi,[31] I was led Emil Fischer’s neglect of his earlier work. understanding might be studying well- to compare the specific volume of these It seems unlikely that he would allow defined model systems like the two-di- crystals with that of right-handed tartaric Liebisch to make the claim of being the mensional (2D) crystallization of chiral acid (Rechts-Weinsäure). It resulted: …” initiator of such studies, if Wallach was the molecules at surfaces.[35] Based on the (Fig. 4a). “It shows that the aggregation of initiator himself. Maybe he felt generous fact that certain symmetry operations are right-handed tartaric acid and left-handed by being the sole author? One expects that not available, Lahav and Leiserovitz con- tartaric acid occurs under reduction of Wallach and Liebisch must have agreed on jectured that 2D conglomerate crystalliza- volume. The contraction amounts to al- the way Liebisch’s results went public. In tion should be favored.[36] Early studies most one percent.” “Due to the kindness conclusion, we are not able to clearly as- seemed to confirm this picture, but were of Prof. Wallach, I was in the position to sign who deserves the credit for the idea likely biased by the choices of surface perform similar studies on seven racemic of comparative studies of densities. Being scientists, who at first focused on amino compounds and their components synthe- at the same university, both probably dis- acids and other polar species.[37] A newer sized by him. The result is compiled in the following table[28]:”[38] (Fig. 4b). “It shows that only for the last listed body can no Fig. 5. a) The list of change of volume be noted. In all other the presentations cases the combination of the optical iso- in the Nachrichten meric bodies into a crystallized racemic showed that Liebisch compound occurs under contraction. The talked on Dec. 8th investigation of Sobrerol (pinolhydrate), 1894 about ‘On that I owe to the gentlemen H. A. Miers crystallographic properties of race- and W. J. Pope in London, led to the same mates’. It states also: result.” (Fig. 4c). ‘Will appear in the Liebisch also refers (ref. [28] in ref. Nachrichten.’ At the [1]) to his presentation of these results same meeting Klein at the meeting of the Royal Academy of presented results Science in Göttingen on December 8th of Sommerfeld. b) 1894,[32] which is confirmed by a list of Sommerfeld pub- contributions for the year 1894 (Fig. 5).[33] lished then in the pro- Although announced to appear as a report ceedings: ‘About the in the proceedings (Nachrichten) of the mathematical theory of diffraction’. Royal Academy of Science in Göttingen later, these results were exclusively published in the Annalen paper the following year. Remarkably, Liebisch’s own list of publications has the last four pages of the Annalen paper as his own separate work with the title ‘On density and crystal form CHIRALITY – SYmmeTRIeS And ASYmmeTRIeS CHIMIA 2018, 72, No. 6 403

account, however, comes to the conclu- [7] J. Marciniak, M. Andrzejewski, W. Cai, A. [21] T. Liebisch, ‘Physikalische Krystallographie’, sion that there is no propensity for either Katrusiak, J. Phys. Chem. C 2014, 118, 4309. Veit & Comp., Leibzig 1891. [38] [8] T. Frišcˇic´, L. Fabian, J. C. Burley, D. G. Reid, [22] T. Liebisch, ‘Grundriss der Physikalische scenario. Chiral surface crystallization M. J. Duer, W. Jones, Chem. Commun. 2008, Krystallographie’, Veit & Comp., Leibzig 1896. is therefore profoundly different to 3D, 1644. [23] T. Liebisch, ‘Die Synthese der Mineralien where racemate crystals clearly outnumber [9] K.-H. Ernst, Isr. J. Chem. 2017, 57, 24. und Gesteine’, Festrede im Namen der conglomerates. [10] W. S. Partridge, E. R. Schierz, J. Chem. Educ. Georg-Augusts-Universität zur akademischen In conclusion, although our knowledge 1947, 24, 106. Preisverleihung am V. Juni MCCCCI. Dieterich, [11] ‘Otto Wallach 1847–1931. Chemiker und Göttingen, 1901. about crystallization has made substan- Nobelpreisträger, Lebenserinnerungen: Pots- [24] T. Liebisch, A. Schönfies, O. Mügge, tial progress during the last two centuries, dam, Berlin, Bonn, Göttingen’, published and ‘Krystallographie, Encyklopädie der math- we realize that – exactly 170 years after annotated by G. Beer, H. Remane, Verlag für ematischen Wissenschaften mit Einschluß ihrer Pasteur’s seminal publication on conglom- Wissenschafts- und Regionalgeschichte, Berlin, Anwendungen’, Teubner, Leipzig, 1905. 2000. [25] T. Liebisch, ‘Geometrische Krystallographie’, erate crystallization of the sodium am- [12] L. Ružicˇka, J. Chem Soc. 1932, 1582. W. Engelmann, Leipzig, 1881. monium salt of acide racemique[39] – not [13] Lecture before the German Chemical Society, [26] G. Gross, Schweiz. Mineral. Petrogr. Mitt. (Bull. much is understood about the mechanisms 1891, from ref. [12]. Suisse Minéral. Pétrogr.) 1972, 52, 523. governing racemate over conglomerate [14] O. Wallach, Justus Liebigs Ann. Chem. 1888, [27] K. Schulz, Centralbl. Mineral. Geol. Paläol. crystallization. 246, 221–239. 1922, 417. [15] “Als ich mir in Hannover eine Abendzeitung [28] O. Mügge, Nachr. Ges. Wiss. Göttingen. gekauft hatte und darin auf dem letzten Weg Geschäftliche Mitt. 1922, 1, 79. Acknowledgements nach Göttingen las, fand ich die mir unglaubli- [29] A. Johnsen, Sitzungsber. Preuss. Akad. Wiss. Continuous support by the Swiss National che Notiz, dass mir der Nobelpreis für 1910 ver- 1923, CXIII–CXV. Science Foundation is gratefully acknowl- liehen sei. Zu Haus empfng mich das bestäti- [30] a) M. Eckert, ‘Arnold Sommerfeld, edged. The author thanks Jack Dunitz for nu- gende Telegramm aus Stockholm. Ein offzieller Atomphysiker und Kulturbote 1868–1951. Eine merous fruitful discussions on chiral crystal- Brief von dem Sekretär der Schwedischen Biografe’, Wallstein, Göttingen, 2013; b) M. lization. Akademie, Aurivillus und ein Privatbrief von Eckert, ‘Arnold Sommerfeld: Science, Life and Arrhenius brachten weitere Bestätigung.” Turbulent Times 1868 – 1951’, Springer, New (“When I bought an evening paper in Hannover York, 2013. Received: April 11, 2018 and read it on the last step of the journey to [31] A. Scacchi, Atti R. Accad. delle Sc. Fis. e Mat., Göttingen I found the unbelievable report that 1869, 4, 4. 24 p. 1 Tav. Napoli. I had been awarded the Nobel Prize for 1910. [32] T. Liebisch, Mitgetheilt in der Sitzung der [1] O. Wallach, Justus Liebigs Ann. Chem. 1895, At home I received the confrmatory telegram [communicated in the meeting of the] Königl. 286, 119. from Stockholm. An offcial letter from the sec- Gesellschaft der Wissenschaften zu Göttingen, [2] Just before this Annalen article Wallach pub- retary of the Swedish Academy, Aurivillus, and 8. December, 1894. lished an account on the chemistry of thujone a private letter from Arrhenius brought further [33] Nachr. 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