History2

This paper has been published in journal "Chemical Education". Volume 71, Number 2, February 1994

The University of Kazan-Provincial Cradle of Russian Organic Chemistry. Part II: Aleksandr Zaitsev and his Students. David E. Lewis South Dakota State University, Box 2202, Brookings, SD 57007

With the departure of Markovnikov the chair of organic chemistry and the direction of the chemistry school at the University of Kazan passed to Aleksandr Mikhailovich Zaitsev, of whom Butlerov had written to the dean of the faculty in 1869, "Based on the results of his work, A.M. Zaitsev occupies one of the first places among young Russian chemists who do not yet have an academic position."

Like his mentor, Butlerov, and his contemporary, Markovnikov, Zaitsev was the mentor of several important organic chemists, including Reformatsky, Wagner, and Arbuzov. But, unlike many of his contemporaries (e. g., Markovnikov and Demyanov), Zaitsev did not receive early recognition for his work (even as recently as the 1960's, few textbooks in organic chemistry bothered to put his name on Zaytsev's rule, and his contributions to the development of chemistry in Russia were overshadowed, perhaps unfairly so, by those of Markovnikov). In part, this may be due to the fact that he spent his entire career at Kazan, rather than moving to Moscow or St. Petersburg.

Figure 1. A.M. Zaitsev (1841-1910).

A.M. Zaitsev.
Zaitsev was born in a mercantile family, and his father wanted him to follow in his footsteps. However, Zaitsev's maternal uncle, the astronomer Mikhail Lyapnbov, convinced his brother-in-law that Zaitsev should enter the university, and personally taught his nephew the Latin required to enter the study of law. Zaitsev graduated from the University of Kazan in 1862 with a degree in law, although the two years of chemistry required (taught by Butlerov) so captivated him that he decided upon chemistry rather than law as a career. Immediately following his graduation, he broke with tradition by going abroad to study chemistry before completing his dissertation for the degree of kandidat. His first stop abroad was at the University of Marburg, where he studied under Hermann Kolbe. In 1863 he also submitted his kandidat's dissertation (on Kolbe's structural theory) to the University of Kazan. The degree was not awarded.

At Marburg, he began work with the chemistry of organic sulfides that led to his discovery of the sulfoxides (1). In August 1864, he travelled to Paris, where he spent nine months in the laboratories of Aldolphe Wurtz, studying the nitration of aromatics and the chemistry of cyanoacetic ester (2). He returned to Marburg in May 1865, where he continued his work with organic sulfides. However, when Kolbe accepted the chair of chemistry at Leipzig, Zaitsev chose to return to Kazan. In 1866 he did send his published papers to the University of Leipzig in the form of a dissertation and, thanks to Kolbe's support, he was awarded his PhD by that university.

On his return to Kazan, Zaitsev first worked as an unpaid laboratory assistant for Butlerov. As soon as he had obtained his kandidat degree, Butlerov secured a junior position for him on the faculty as a laboratory technologist in agronomic chemistry, although it was fairly obvious that he would assume a position in the chemistry department as soon as one became available. His Kandidat's and Master's dissertations at Kazan were presented in 1865 and 1867. Both clearly showed the influence of his time with Kolbe. They described chemistry of thioethers and their reactions with nitric acid (the first report of the preparation of sulfoxides, (1) and methyl iodide (3). He presented his doctoral dissertation on the transformations of alcohols in 1870.

(Zatsev. 1866) As a student of Kolbe and Butlerov, Zaitsev had been exposed to modern chemical theory, so that he should have found in Markovnikov a kindred spirit. Scientifically, he did so, but this was not the case socially. Initially, Markovnikov had little regard for his fellow student, possibly because of his break with tradition by studying in Germany before submitting his candidate’s dissertation, possibly because of his obtaining a foreign PhD degree, or possibly because of Zaitsev's social and scientific conservatism. Where Markovnikov was progressive 'in his social views, Zaitsev was equally conservative. Indeed, it may well have been his conservative views that gained for him the strong support of the dean of the faculty when Zaitsev was first proposed for a chair in chemistry.

Zaitsev's independent research program after his return to Russia reflected the influence of Butlerov on Russian chemistry at this time. Zaitsev remained true to the course set by his mentor (Russian sources speak of the "Butlerov-Zaitsev school"), and he attracted many of the finest young chemists in Russia. Thus, many of Zaitsev's papers concerned the development of synthetic methods based upon the reactions of zinc alkyls with carbonyl compounds. The synthesis of tertiary alcohols had been one of Butlerov's early triumphs. With his student Egor Egorevich Vagner, Zaitsev developed a general method for the synthesis of secondary alcohols from aldehydes and zinc alkyls (4).

(Vagner, Zaitsev. 1875)

Zaitsev was a productive worker. In addition to his discovery of the sulfoxides, he reported the first preparation of butyrolactone (5). However, it was his paper (published under the German spelling of his name, Saytzeff) in Justus Liebigs Annalen der Chemie in 1875 (6) that has led to his enduring fame in sophomore organic chemistry textbooks. In 1885, he became a corresponding member of the Academy of Science, and in 1903 he was appointed an honorary member of the faculty of Kiev University, possibly at the urging of his student Aleksandr Nikolaevich Reformatsky, who was professor of chemistry at Moscow University and who probably influenced his more famous brother, Sergei Nikolaevich, to support the nomination.

Although Markovnikov's departure had left a large gap in the chemistry research program at Kazan Zaitsev's research group continued the Kazan tradition of attracting some of the finest minds of the next generation. Among these were Sergei Nikolayevich Reformatskii (or Reformatsky), Egor Egorevich Vagner (better known under the German spelling of his name, Wagner), and Aleksandr Erminingeldovich Arbuzov.

E.E. Vagner.
Egor Egorevich Vagner (1849-1903) was one of the founders of the field of terpene chemistry. Like his mentor before him, Vagner began his studies at the University of Kazan as a student in law (1867-1868), where he heard chemistry lectures by both Markovnikov and Zaitsev. After two years in the study of law, he transferred to the Physics-Mathematics Department, where he carried out research under Zaitsev (4b). Among his papers was a method for the synthesis of secondary alcohols by the reaction between aldehydes and zinc alkyls.

Figure 2. E.E. Vagner (1849-1903). Vagner graduated from Kazan in 1874, and he became an instructor there. In 1875 he was sent to St. Petersburg, where he continued his synthesis of secondary alcohols under the direction of Butlerov. In 1876, he became a laboratory assistant in analytical chemistry under Menshutkin, and in 1882 he moved to Novo-Aleksandr Agricultural Institute in Poland as professor of chemistry. Here he began work on his master's dissertation, which he submitted to the University of St. Petersburg in 1885. In 1886, he moved to the University of Warsaw, where he spent the remainder of his career. He submitted his doctoral dissertation to the University of Warsaw in 1888. During his first independent position, Vagner developed permanganate oxidation of olefins to glycols (7) as a means for locating the position of double bonds in terpenoid hydrocarbons. This work rendered tractable the problems in structure determination of many terpenoid compounds whose structures would otherwise have remained unknown.

(Vagner, 1988) Vagner's lasting fame, however, couples his name with that of German chemist Hans Meerwein, in the form of the Wagner-Meerwein rearrangement. Vagner's elucidation of the structures of the cyclic monoterpene hydrocarbons led him to propose relationships between them where there was a shift of bonding from one site to another. The camphene-bomene rearrangement was first elucidated by him (8, 9), although the details of the mechanism were proposed by Meerwein (10). As part of his work in bicyclic terpenes, Vagner also first proposed the correct structure for pinene (11), whose four-membered ring had been a serious stumbling block for more tradition-minded chemists. Vagner's work was held in great esteem in Germany. One of the first tasks set for a young Vladimir Ipatieff when he joined Adolf von Baeyer's research group was to translate Vagner's work from Russian into German (12). Vagner was quite a bon vivant, as is revealed by one anecdote told by Ipatieff in his autobiography. At the end of the scientific convention at St. Vladimir University in Kiev in 1898, Vagner led a group of chemists in a dinner at a restaurant/cabaret on Trukhanov Island on the Dnieper River. The dinner was accompanied by copious quantities of vodka, tea, and cognac. "Vagner was the life of the party and I must note that few can achieve the happy and pleasant state of mind that he could. We returned to our hotel at four o'clock in the morning..." (12).

(Wagner, Brickner, 1899) S.N. Reformatsky.
Sergei Nikolayevich Reformatsky (1860-1934) was born in Kostroma, northeast of Moscow. He received his early education at the Kostroma Spiritual Seminary, from which he graduated in 1878. He then attended the University of Kazan, where he graduated in 1882 with the degree of kandidat. After his graduation, Reformatsky was made curator of the laboratory museum, a position that paid him a stipend while he completed his research for his master's dissertation under Zaitsev's direction. He submitted his master's dissertation in 1889. From 1889 to 1890, he studied abroad for two years at the Universities of Gottingen, Heidelberg (under Viktor Meyer), and Leipzig (under W. F. Ostwald). His Doctor of Chemistry degree was granted by the University of Warsaw, where Vagner was then professor of chemistry. Just as Butlerov's work with zinc alkyls had led Zaitsev to continue research into the uses of these reagents in organic synthesis, so Zaitsev's work with zinc alkyls led Reformatsky to study these nucleophiles when he began his first independent research. His doctoral thesis contained the first reports of the Reformatsky reaction between aldehydes and ketones and the organozinc ha-lides derived from a-haloesters (13).

Figure 3. S.N. Reformatsky (1860-1934).

(Reformatsky. 1895)

Until the development of strong, non-nucleophnic amide bases in 1970’s rendered the formation of preformed lithium enolates practical, the Reformatsky reaction was the major method for forming b-hydroxycarbonyl compounds, and was one of the few such reactions that did not lead to concomitant dehydration of the product. Although the resurgence of the aldol condensation has somewhat eclipsed the Reformatsky reaction as the method of choice for the synthesis of such compounds, the reaction is still used in appropriate circumstances. On his return to Russia, in 1891, he was appointed professor of chemistry at the University of Kiev, where he continued his research into the reactions of alkylzinc halides (14, 15). In 1891, he wrote a textbook of organic chemistry that went through three editions (16). In 1928, Reformatsky was made a corresponding member of the USSR Academy of Science.

Figure 5. The influence of the University of Kazan chemists over five academic "generations".

A.E. Arbruzov.
One of the last students to study under Zaitsev at Kazan was Aleksandr Erminingeldovich Arbuzov (1877-1968). He graduated from the University of Kazan in 1900, and then followed the path another former Zaitsev student, Egor Egorevich Vagner, as assistant in chemistry (1901), and then Adjunct Professor of Chemistry (1906) at the Novo-Aleksandria Institute of Agriculture and Forestry. In 1911, he succeeded his mentor as professor of chemistry at Kazan, a position he held from 1911 to 1930. In 1922, he was elected Deputy Dean of the physics-mathematics faculty. In 1930, Arbuzov became professor at the Kazan Chemical-Technological Institute, where he remained for the rest of his professional career.

Figure 4. A.E. Arbuzov (1877-1968).

Arbuzov's research work concerned the chemistry of organo-phosphorus compounds, and as part of his master's thesis in 1905 (17) he determined the structure of phosphorous acid and its esters. This work resolved the controversy over the number of hydroxyl groups in the acid and showed the structural differences between phosphorus acid (in which the phosphorus is tetracoordinate and has a PH bond) and the trialkyi phosphites (in which the phosphorus is tricoordinate). He subsequently discovered the rearrangement of phosphite esters to phosphonic acid esters (18), a reaction that has assumed major importance with the development of the Wadsworth-Emmons olefination reaction (19). His name also has become attached to the Michae-lis-Arbuzov reaction, which was discovered by Michaelis and Kaehne in 1898 (20), but much more intensely studied by Arbuzov in the early decades of the 20th century. In collaboration with his son and student, Boris Aleksandrovich Arbuzov (himself a prominent Russian chemist), he developed a new method for the formation of triarylmethyl radicals from triarylmethyl halides and phosphite anions.

During World War II, the members and laboratory equipment of the Moscow and Leningrad (now St. Petersburg) Academies of Science were evacuated to Kazan (21). The rise of the Kazan Institute as a large research institution dates from this time (22). When the 25th anniversary of the Kazan branch of the Soviet Academy of Science was celebrated in 1945, Arbuzov was among a speaker list that included such luminaries as the Joliot-Curies, Robinson, Langmuir, and Svedberg. Arbuzov won numerous awards, including two Stalin Prizes, and he was on several occasions a delegate to the Supreme Soviet (the governing body of the Soviet Union). He was also a historian and wrote a history of chemistry (23) that emphasized the contributions of the Kazan school to the development of Russian chemistry.

(A.E. Arbruzov. 1910)
The influence of the Kazan school went far beyond those individuals in this paper and far beyond the Tatar republic (and yet the first chemist to attain recognition during his own lifetime while remaining at Kazan was Arbuzov). Butlerov was the dominant force of his generation, and through his students he became the dominant force of the next generation too. At Moscow, Markovnikov became a major force in Russian organic chemistry, and he moulded the minds of not only his own students, but also of his colleagues. Similarly, much of the tradition of Polish chemistry at the University of Warsaw can be traced to Butlerov's influence through Popov, and to Zaitsev's influence through Vagner. Reformatsky's students clearly were subject to the influence of Zaitsev (and, through Zaitsev, of Butlerov), and it is clear that Reformatsky held his undergraduate mentor in high esteem.

The influence of Kazan may be best gauged by examining the figure, where the genealogy of Russian chemistry beginning at Kazan is traced. All the chemists whose names appear in boldface earned their undergraduate or graduate degrees from the University of Kazan. Only their more well-known students are listed.

Literature Cited
[1] (a) Saytzeff, A. Ann. Chem. Pharm, 1866. 139, 354-364; 1867. 144. 148-156, (b) Grabowsky.N.: Saytzeff. A. Ann. Chem. Pharm. 1875. 175. 348-351.
[2] Saytzeff. A. Ann. Chem. Pharm. 1865, 133.321-329. 329-335.
[3] Saytzeff, A. Ann. Chem. Pharm. 1867, 114, 145-148.
[4] (a)Kanonnikoff. J.; Saytzeff. A. Ann. Chem. Pharm. 1875, 175. 374-378; 1875. 179. 338. (b) Wagner, G.; Saytzeff. A. Ann. Chem. Pharm. 1875, 175. 351-374; 1875, 179. 302-313, 313-325.
[5] Saytzeff, A. Ann. Chem. Pharm. 1874, 171, 258-290.
[6] Saytzeff, A. Ann. Chem. Pharm. 1875, 179, 296-301.
[7] Wagner, G. Ber. Deut. chem. Ges. 1888, 21, 1230-1240, 3343-3346, 3347-3355, 3356-3360.
[8] Vagner, E. E. J. Russ. Phys. Chem. Soc. 1894, 26, 327-362; 1896, 28, 56-108, 206. 398, 484-501.
[9] Wagner, G.; Brickner. W. Ber. Deut. chem. Ges. 1899, 32, 2302-2325; 1900, 33, 2121-2125.
[10] Meerwein, H.; van Emster. K. Ber. Deut. chem. Ges. 1920, 53B, 1815-1829; 1922, 55B, 2500-2528.
[11] (a) Wagner, G. Ber. Deut. chem. Ges. 1891, 24. 2187-2190. (b) Wagner, G.; Slawinsky, K. Ber. Deut. chem. Ges. 1899, 32. 2064-2083. (c) Wagner, G.; Ginzberg, A. Ber. Deut. chem. Ges. 1896, 29, 886-890.
[12] Ipatieff, V. N. The Life of a Chemist: Memoirs of Vladimir N. Ipatoff, (Stanford University Press: Stanford, CA, 1946).
[13] Reformatsky, S. N. Reaction of the Mixture of Zinc and Ethyl Monochloroacetate with Ketones and Aldehydes (Synthesis of Tertiary b-Hydroxyacids), Dr. Chem. Dissertation, University of Warsaw, 1890 (in Russian).
[14] Reforroatsky, S. Ber. Deut. chem. Ges. 1887. 20, 1210-1211; 1895, 28, 2842-2847, 3262-3265.
[15] Reformatsky, S.; Plesconossoff. B.Ber. Deut. chem. Ges. 1895, 28, 2838-2841.
[16] Reformatsky, S. N. A Beginner's Course of Organic Chemistry (Kiev, 1891).
[17] Arbuzov, A. The Structure of Phosphorous Acid and Us Derivatives (Kazan. 1905).
[18] (a) Arbuzov, A. J. Russ. Phys. Chem. Soc. 1910, 42, 395-420, 549-561; Chem. Zentr. 1910, II, 463-454.
[19] For a review, see: Wadsworth, W. S., Jr. Org. React. 1977, 25, 74.
[20] Michaelis, K.; Kaehne, R. Ber. Deut. chem. Ges. 1898, 37, 1048-1055.
[21] Grechkin, N.P.; Kuznetsov. V. I. Aleksandr Ermininget'dovich Arbuzov 1877-1968;
(Science Publications; Moscow. 1977). [In Russian]
[22] A reviewer has pointed out that Kazan became a major resaerch center lover 1,000 PhD's in phosphorus chemistry I carrying out research into nerve gases, among other work. The author has not been able to verify this, but given Arbuzov's strongly nationalistic feelings for the Soviet Union, it is probably true.
[23] Arbuzov, A. E. A Brief Sketch of the Development of Organic Chemistry in Russia; (Academy of Science USSR, Leningrad. 1948). [In Russian]