This paper has been published in journal "Chemical Education". Volume 71, Number 1, February 1994
The University of Kazan-Provincial Cradle of Russian Organic Chemistry.
Part I: Nikolai Zinin and the Butlerov School.
David E. Lewis
South Dakota State University. Box 2202. Brookings. 3D 57007

Most organic chemistry instructors and the authors of most organic chemistry textbooks make quite clear (and justifiably so) the contributions of the great German masters of the science to modern organic chemistry. Organic chemistry 1.5 full of German names and German name reactions, many of which we expect our students to learn. In part, this may stem from the fact that most English-speaking chemists trace their "professional genealogy" to the German schools of Liebig, Bunsen. Erienmeyer, Kolbe, von Baeyer, Kekule, or Hofmann (who was brought to London to introduce the German way of teaching organic chemistry), so that their mentors were much more aware of the German schools and their contributions. However, we tend to overlook the importance of the contributions of the Russian contemporaries of these chemists, despite their names-Saytzeff, Markovnikov. Favorskii and Zelinsky, to name just a few - appearing widely in most undergraduate organic chemistry textbooks. Moreover, relatively few English-speaking organic chemists realize that some chemists who are almost universally considered German (Beilstein, Kishner, and Wagner of Wagner-Meerwein rearrangement fame) were, in fact, Russian. It is the purpose of this article to remedy some of this oversight on the part of English-speaking chemists, and to focus on the contributions of the University of Kazan, in particular.

Before beginning the history of the Kazan school of chemistry, the reader will be well served by some pertinent information about the Russian educational system of the 19th century. Each department was headed by a professor, who occupied a chair. In order to occupy a chair of chemistry, one had to obtain the degree of doctor of chemistry by writing and defending a dissertation. However, the scope of the oral examination was not restricted to demonstration of only one subject as the most modern oral presentation and the candidate was required to demonstrate a knowledge of chemistry in all its sub-disciplines. Prior to obtaining the doctoral degree, a student wrote dissertations for the degree of "kandidat" and for the degree of master of chemistry. The degree of kandidat was somewhere between a modern master's and doctoral degree in level. The master of chemistry was a higher qualification (the master's dissertation had to be defended orally), and it was a necessary pre-requisite for obtaining the rank of professor at a Russian university. Until the end of the 19th century, by which time there were many eminent Russian chemists, it was tradition for students to write their kandidat dissertation and to leave Russia for a period of study abroad, after which they would return to write their master's and doctoral dissertations.

The University of Kazan: Some Background
The University of Kazan was founded in 1804. The courses of study were divided into four faculties Physics-Mathematics, Law, Medicine and History-Philosophy. Despite its provincial status, it has numbered among its chemistry graduates and faculty some of the finest minds of Russian organic chemistry. What may be surprising to the reader is the fact that at many of these chemists (Vladimir Vasilevich Markovnikov, Aleksandr Mikhailovich Zaitsev, and Egor Egorevich Vagner to name just three) actually began their undergraduate studies as law or economics students in the faculty of law. At the University of Kazan, any student studying law or finance was required to take two years of chemistry as part of the course of study.

The professor of chemistry held his chair in the Physics-Mathematics Academy of the university, and much of the notable research carried out by the chemists at Kazan appeared first in the Bulletin of the Physics-Mathematics Academy. There was no separate Chemistry Department until after the turn of the 20th century. Despite the high caliber of the research carried out by the chemists at Kazan, the university remained small, and its reputation remained overshadowed by those of the Universities of St. Petersburg and Moscow. Consequently, most of the eminent Russian chemists of the 19th century became so only after they moved from Kazan: Butlerov to St. Petersburg, Markovnikov to Moscow, Vagner to Warsaw, and Reformatsky to Kiev.

Zinin and the Rise of the Chemistry School
The rise of the chemistry school at Kazan may be attributed to one man, Nikolai Nikolaevich Zinin (1812-1880) (1), who graduated from Kazan in 1836, and who was appointed professor of technical chemistry there in 1841 after spending three years studying abroad in western Europe (including a year spent in the laboratories of Justus Liebig In Glessen. His colleague at Kazan was prof. Klaus, the discoverer of ruthenium. However, the two men were of completely different mind when it came to chemistry. Klaus was a conservative, and he held strongly to the views of Berzelius. On the other hand, Zinin had been introduced to the ideas of Gerhardt and Laurent while in Europe, and he imparted them to his own students. His vitality was in stark contrast to Klaus' stodginess, and it was Zinin who was largely responsible for the growth of the chemistry school at Kazan.

While in Liebig's laboratories Zinin studied the reactions of benzoyl compounds. His first paper there concerned the benzilic acid from benzil (2), whose synthesis from benzoin he also described. In fact, it was while in Liebig's laboratories that Zinin wrote his doctoral dissertation on the benzoin condensation, which he defended at the University of St. Petersburg in 1841. In 1848, Zinin was appointed to a professorship at the Academy of Medicine and Surgery of the University of St. Petersburg, where he continued to attract bright young students, among them the renowned chemist-composer Aleksandr Porfirevich Borodin (1833-1887), discoverer of the aldol (3) and Hunsdiecker-Borodin (4) reactions.
 

Figure 1. N. N. Zinin (1812-1880).
 
(Zinin, 1840)
 
Zinin studied the reduction of benzoin to hydrobenzoin, and of benzil to benzoin in the presence of a dissolving metal (a reactior attributed to "patient" hydrogen as late as the 1940's). His discovery of a method tor tlie synthesis of a wide variety of aromatic amines by ammonium sulfide reduction of the corresponding aromatic nitro compounds led to a long series of papers published in the journals of the St. Petersburg academies (5); these papers were all translated into German by the abstractors of Liebig's Annalen (6). This work, which included the first synthesis of aniline, was pivotal to the later development of the aniline dye industry, and its importance was recognized and commented upon by no less an amine chemist than A.W. von Hofmann himself, who said of this work, "If Zinin had done nothing more than to convert nitrobenzene into aniline, even then his name should be inscribed in golden letters in the history of chemistry" (7).
 
(Zinin, 1842)

Butlerov and His Influence at Kazan
While at Kazan, Zinin and Klaus educated one of the most influential chemists of the next generation, Aleksandr Mikhailovich Butlerov (1828-1886) (8). Butlerov was a student at the University of Kazan from 1844 to 1849, where Zinin persuaded him to study chemistry. However, after Zinin left for St. Petersburg, Butlerov lost interest in chemistry in large part because he was not inspired by the extremely traditional Berzelian views held by Klaus. In fact, Butlerov wrote his kandidat thesis in entomology ("Diurnal Butterflies of Volga-Ural Fauna," based on the results of an excursion to the Volga-Ural region of Russia). One of his life-long interests was apiculture, and his articles on the subject were published after his death (9). However, following his graduation from Kazan in 1849, Butlerov began to teach chemistry there. His master's thesis, which he defended in 1851, gave little indication of the highly creative and original individual responsible for it, although it did give the first report of his work on osmic acid oxidation of organic compounds (10). His doctoral thesis, likewise, was mainly a historical summary of essential oils; however, it was sufficient for him to obtain his doctor of chemistry from the University of Moscow in 1854 (although not after a fight it had originally been submitted to the University of Kazan, but one of the three examiners did not feel that it was of sufficient merit to warrant the award of the degree). Following his graduation, he was promoted to professor. From 1852, when Klaus moved to Dorpat, Butlerov taught all the chemistry courses at the University of Kazan. On two occasions during his last three years at Kazan, Butlerov was Rector of the University.

From 1857 to 1858, Butlerov travelled abroad. During his travels he met Kekule, whom he much admired from the beginning of their friendship, and Erlenmeyer. For six months (December 1857-May 1858) he worked in the laboratories of Charles Adolphe Wurtz in Paris, where he may have had the opportunity to interact with Wurtz' student, Archibald Scott Couper. At this time, Paris was a vibrant center of organic chemistry research, and it was during this trip that Butlerov was exposed to the new ideas of structure in organic chemistry. He embraced them avidly (11). By 1860, Butlerov had developed his own structural theory of organic chemistry, which, according to Markovnikov, he had begun expounding in his lectures by 1860. It was Butlerov who first used the term chemical structure with its modem meaning. In addition to his theoretical work, Butlerov also carried out research in organic synthesis. The reaction between acid chlorides and dialkylzincs to give tertiary alcohols, the Butlerov reaction, was discovered in 1864 (12), and was the first reaction to permit the synthesis of a tertiary alcohol, whose existence had been predicted by Hermann Kolbe in 1860 based on the type theory of Dumas.
 

(Butlerov, 1864)
 
Until the discovery of the Grignard reaction over three decades later (13), the Butlerov synthesis was the only reliable method for the synthesis of these compounds. One gathers from biographies of Butlerov and his students that Butlerov's lectures and laboratory courses were nothing short of electrifying. He rapidly drew some of the finest young minds in Russia to him, including two leaders of the next generation. Among the leaders of the "Butlerov School" were Aleksandr Mikhailovich Zaitsev (1841-1910). who is better known by the German spelling of his name (Saytzeff), and Vladimir Vasilevich Markovnikov (1837-1904), both of whom succeeded Butlerov to the chair of organic chemistry at Kazan.
 
Figure 2. A. M. Butlerov (1828-1886).
 
In order to disseminate his theory of structure more widely, Butlerov wrote a textbook of organic chemistry (14) which was edited by his colleague and personal assistant Mikhail Dmitrievich Lvov (1846-1899). This book, which subsequently appeared in German (13), was the first textbook to be based entirely on structural theory. It was one of the most influential textbooks of its day and had much to do with the general acceptance of structural theory. For 10 months during 1867 and 1868, Butlerov again went abroad, ostensibly to promote the German edition of his textbook, but also to defend his claims to priority in the development of structural theory. At that time, Kekule alone was receiving the credit for the development of this milestone in organic chemistry (Couper's claims were ignored until quite recently). Butlerov's claims of priority led to a long dispute over just who did first develop structural theory (15). While he was absent, his lectures in organic chemistry were delivered by Markovnikov, who substituted for his mentor.

In May 1868, Butlerov was appointed as Professor of Chemistry at the University of St. Petersburg, although, at the request of the board of governors of the University of Kazan, he did not actually leave until January of the following year. At St. Petersburg, he continued to attract "disciples" of the highest caliber, among them Alexei Evgrafovich Favorskii (1860-1945). A man ahead of his times in many ways, Butlerov promoted the higher education of women and knew the importance of maintaining a good rapport with the general public. He organized university courses for women and regularly gave public lectures on chemical topics. He also relished a fight: in 1874. and again in 1880, he and Zinin jointly proposed Mendeleev for membership in the Russian Academy of Sciences. When Mendeleev was denied membership on both occasions. Butlerov did not hesitate to use public opinion to block the candidacy of the opposing faction's nominee, Beilstein, and he wrote an open letter in the public newspapers to gain popular support for his point of view. In later life, Butlerov became a devotee of spiritualism (16}.

Markovnikov: Butlerov's Successor
Butlerov's senior student at Kazan was Vladimir Vasilevich Markovnikov. Markovnikov (27) began his studies at the University of Kazan as a student in law, but he was captivated by the lectures of Butlerov, and immediately after his graduation in 1860 with a degree in economics he became Butlerov's assistant. In 1865, Markovnikov took his master's degree and then left Russia on a fellowship for foreign study, where he years, two years in Germany, mainly in the laboratories of Richard Erienmeyer, in Heidelberg, and Hermann Kolbe, in Leipzig. He was, therefore, in Kolbe's laboratories immediately after his fellow student Zaitsev. In 1867, Markovnikov returned to Kazan as a junior faculty member in chemistry, and he immediately began work on his doctoral dissertation. His degree of doctor of chemistry was awarded in 1869 with Butlerov as the formal opponent (chief examiner).

Markovnikov's status as Butlerov's assistant, and the fact that he had substituted for him in the lecture courses in organic chemistry while Butlerov was abroad, made Markovnikov the logical choice to succeed his mentor at Kazan. However, his irascible nature and his progressive ideas were some cause for concern to the university administration (to the extent that they decided to appoint two professors to replace Butlerov instead of one). His biographers all point out his willingness to participate in scientific arguments with his conservative mentor, Kolbe. Anyone who would venture to argue with the European dean of organic chemistry was likely to prove to be a formidable opponent, indeed. Despite their misgivings, the University Council appointed Markovnikov as extraordinary professor of chemistry in 1868 and promoted him to ordinary professor in 1870. They had planned to appoint a fellow Butlerov student, Aleksandr Nikolaevich Popov (d. 1881), as his colleague, even before he had written his master's thesis. In 1869 Popov wrote a brilliant master's thesis on structural theory, but he was not of robust health, and the thought of acting as a buffer between the forceful Markovnikov and the university administration may have daunted him. Despite Markovnikov's strong support for him. He accepted the chair of chemistry at the University of Warsaw, instead (18). In many ways, this may have been fortunate for the University of Kazan because Popov accomplished nothing further of note after his arrival in Warsaw (although he did begin the long and fruitful association between the University of Kazan and universities in Poland).

During his time as professor at Kazan, Markovnikov began the research into orientation effects in addition reactions that led to his formulation of what we call Markovnikov's Rule (19). Interestingly, much of Markovnikov's work, especially his theoretical papers, appeared only in Russian. He was intensely nationalistic, and although he frequently bemoaned the backwater conditions under which Russian scientists worked, he never considered taking an appointment in any other country. By publishing his best work only in Russian journals he believed that he was helping the cause of Russian chemistry.
 

Figure 3. V. V. Markovnikov (1837-1904).
 
As the university administration had feared, Markovnikov's progressive views led to conflict, and his tenure at Kazan was short-lived. In 1871 he resigned his position along with six colleagues to protest the actions of the University Rector. He was immediately offered the chair of chemistry at the University of Odessa, which he accepted, and then, in 1873, he was asked to assume the chair of chemistry at the University of Moscow, where he spent the remainder of his professional career, becoming mentor to several well-known organic chemists, among them Nikolai Yakovlevich Demyanov (1861-1938), Alexei Yevgenievich Chichibabin (1871-1945), and Nikolai Matveyevich Kizhner (1867-1935). At Moscow, Markovnikov turned his attention to the chemistry of petroleum and alicyclic compounds, in spite of protests from his colleagues who urged him not to leave the path of "pure chemistry". In 1881, his report of the synthesis of a cyclobutane derivative (20) helped to dispel the extant belief that carbocyclic rings other than six-membered could not be formed, while his synthesis of a cycloheptane derivative (27) from suberone in 1890 (the same year (22) that William Henry Perkin, Jr. synthesized a cycloheptane derivative from 2,8-nonanedione) helped to dispel the belief that rings larger than six-membered could not exist.
       (Markovnikov, 1881)        (Markovnikov, 1890)        (Markovnikov, 1891)
Literature Cited
[1] For biographics of Zinin see (a) Leicester H. M. Chem. Eiliir. 1940. 17. 303-306. (b) Butlerov. A. M.; Borodin. A. P. Ber. Deul. chem. Ges. 1881, 14, 2887-2908.
[2] Zinin. N. Ann. Chem. Pharm. 1839, 31. 329-332; 1840. 34. 186-192.
[3] Borodin, A. Ber. Deut. chem. Ges.1873, 6. 982-985. His earlier reports to the Chemical Society of St. Petersburg were reported as correspondence: Richter. V. von Ber. Deut. chem. Ges. 1869, 2, 552-554; 1870, 3, 421-428; 1872. 5. 477-482.
[4] (a) Borodine, A. Ann. Chem. Pharm. 1861. 119. 121-123. (b) Hunsdieckcr. H.; Hunsdiecker, C. Chem. Ber. 1942, 75, 291-297. (c) Hunsdiecker. C.; Hunsdiecker. H.; Vogt, E. U.S. Pat. 2,176,181(1939); Chem. Ahslr. 1940. 34. 1685.
[5] Early papers: Zinin. N. Bull. Sci. Acad. St. Petersburg 1842. 18: Bull. Phys. Math. Acad. St. Petersburg 1852. 348.
[6] Early papers: Zinin. N. Ann. Chem. Pharm. 1842. 44. 283-287; 1844, 52, 361-362: 1853, 85,328-329.
[7] Hofmann. A. W. von Ber. Deut. chem. Ges. 1880. 13,. 449-450.
[8] For biographies of Butlerov, see: (a) Leicester, H. M. J. Chem. Educ. 1940. 17. 203-209. (b) J. Russ. Phys. Chem. Soc. 1887. 19, is a supplement to the journal containing the text of speeches in memorial of Butlerov by N. A- Menshutkin. A. M. Zaitsev, V. V. Markovnikov, among others.
[9] Butlerov, A. Articles on Apiculture ( Kazan. 1891).
[10] Butlerov. A. Bull. Phys. Math. Acad. St. Petersburg 1852, 177; Ann. Chrm. Pharm., 1853, 84, 278-280.
[11] Couper's theory of structure and Butlerov's commentary of it were published together in 1859; (a)Couper, A.S.Ann. Chem. Pharm. 1859, 110, 4651. Ibl Butlerov, A. Ann. Chem. Pharm. 1859. 110. 5166.
[12] Butlerov. A. Jahresb. 1863, 475; 1864, 496: Ann. Cnem. Pharm. 1867. 144. 132.
[13] (a) Grignard. V. Compt. rend. 1900, 130. 1322-1324; 1901. 133. 336-338; 558-561; 1902, 134. 849-851; Chem. Zentr. 1901, II ,622-625. (b) Grignard. V: Tissier. L. Compt. rend. 1901, 133, 835-837: 1902, 134. 107-108. (c) Tissier. L.: Grignard. V. Compt. rend. 1901. 683-685.
[14] (a) Butlerov. A. Introduction to the Study of Organic Chemistry  Kazan. 18641. (b) Butlerov, A. Lehrbuch der organischen Chemie zur Einfuhrung in dan specieile Studium derselben (Leipzig, 1867).
[15] For more complete accounts of Butlerov's contributions to modern structural theory and the attendant controversies, see: (a) Bykov. G. V, J. Chem. Educ. 1962. 39. 220-224. (b) Jacques, J. Bull. Soc. Chim. France 1953, 528-530, (c) Leicester. H. M. J. Chem. Educ. 1953, 36, 328-329.
[16] Butlerov, A. Articles on Mediumism. (St. Petersburg, 1889).
[17] For biographies of Markovnikov, see: (a) Leicester, H. M. J. Chem. Educ., 1941. 18, 53-57. (b) Decker, H. Ber. Deut. chem. Ges. 1906, 38. 4249-4262.
[18] (a) Arbuzov. A.E.A Brief Sketch of the Development of Organic Chemistry-in Russia:
(Academy of Science USSR, Leningrad, 19481, pp 187-188 lln Russian],  Alexander Mikhailovich Zaitsev. Moscow. 1980 p 20 [In Russian].
[19] Markovnikov, V. Ann. Chem. Pharm. 1870, 153. 228-259; Compt. rend. 1875. 82. 668-671,728-730,776-779.
[20] Markovnikov, V.: Krestovnikov, A. Ann. Pharm. Chem. 1881, 208. 333-349.
[21] Markovnikov, V. Compt. rend. 1890. 110. 466-468: 1892. 115. 462-464
[22] Kipping, F. S.; Perkin, W. H.. Jr. J. Chem. Soc. 1891. 59. 214-229.