S. N. REFORMATSKII AND HIS REACTION' A. SEMENTSOV Lafayette College, Easton, Pennsylvania
P a o m s s o a Sergei Nikolayevich Reformatskil was born in the family of a country minister in 1860. At that time it was customary that sons of priests should also choose the priesthood, and he was sent to a preparatory school for the theological seminary. Instead of theological education, however, he preferred a scientific one and entered the University of Kazan. He chose this university because Kazan was a small city in which the living conditions were cheaper than in a large university city, but if he had intended to choose a university best suited to prepare a good chemist he could not have made a better choice. The chemical laboratory of the university, founded by Klaus, was a real nursery for professors and researchers in chemistry for all Russia. Other directors
were A. M. Butlerov and A. M. Zaltsev. The role of this laboratory for Russia can he compared to the role of the Liebig laboratory in Giessen for Germany. 1 I n this laboratory, as a young student, Reformatskil found not only the competent guidance of a distinguished chemist, Z a i t ~ e v ,but ~ also a real spirit of scientific research which he himself later realized in his own laboratory in Kiev. The deep interest in chemistry was combined in him with experimental ability, and he became one of the best and beloved pupils of . . Zaltsev. In the year 1882, Reformatski? was graduated from the universitv and his thesis on the hvdrocarbons C10H18 was awarded the gold medal. After graduation he worked a t his Alma Mater in succession as custodian
' Presented before the Division of History of Chemistry at the
%ALEXANDER MIKHMLOVICH ZA~TSEV (1841-1910) published many important works in the field of organic chemistry. Mostly known is his rule for the direction of dehydration and dehydrohalogenation when two routes are open.
130th Meeting of the American Chemical Society, Atlantic City, September, 1956.
JOURNAL O F CHEMICAL EDUCATION
of a chemical museum, assistant professor, and in the year 1886 he was elected private-dozent. Three years later he received a stipend for work abroad. Two semesters were spent in the lahoratory of the famous organic chemist, V. Meyer. In this laboratory he observed the important fact that trimethylacetic acid cannot be brominated by the HellVolhardt,Zeliniskii method (brornination in presence of red phosphorus), and in this way provided evidence that only an a hydrogen atom can be substituted by halogens under these conditions. The third semester he devoted to the just-created physical chemistry in the laboratory of Wilhelm Ostwald. In Germany he wrote his book on his synthesis of hydroxy acids. PROFESSOR OF ORGANIC CHEMISTRY AT KIEV
In the next year he became professor of organic chemistry a t the University of Kiev, where he taught until his death in 1934. The greatest concern of his life-and his beloved child-was his laboratory. The present author remembers always with pleasure the two years he spent in this lahoratory. There was a really scientific atmosphere. All the people working there worked in the same branch of organic chemistry; all were inspired by a lively interest in the science, and there was friendly collaboration. For students who performed research work, the laboratory was open day and night including Sundays and holidays. The chief of gendarmes (political police), General Xovitskii, waa so suspicious of this that he wrote to the superintendent of schools to ask what was going on in this lahoratory during the nights. When the pupils of Reformatski1 presented him on his silver jubilee with a collective volume of the works of his lahoratory (about 1000 pages), he said proudly, "That is our answer to General Novitskil." He was a very good lecturer-zoncise, but understandable. He demonstrated many experiments in his classes. I have never seen so many. Often he gave popular lectures. The author of this paper was present at such lectures when he was only sixteen years old, and probably these lectures decided his choice of career. He was an exacting teacher but always helpful and friendly. He was helpful to his pupils, not only when they were students of the university, but also after graduation. He aided in finding a job and in case they were in any trouble. He always gave way to the young researchers, his students. Every time one of them had an interesting idea, he was allowed to give the themes for theses to a graduate student in spite of the professor's own interests. Iteformatskii published a concise textbook of organic chemistry. One of my university mates had the patience to discover that on 700 pages over 700 substances and 1500 preparation methods were described. However, it was very clearly written and understandable. This book was organized in an original manner. The substances were classified, not by their carbon skeletons as was usually done in big university courses, hut by their functional groups. This method allowed great economy of time and permitted an easy emphasis on the difference and likeness of substances with the same function but different radicals. The book was popular and was published in seventeen editions and 200,000 copies. VOLUME 34, NO. 11, NOVEMBER, 1957
Professor Reformatskii organized the Physical Chemical Society in Kiev and was its chairman for many years. He was very sociable and readily participated in parties organized by his chemical colleagues and by his pupils. He had a pleasant baritone and willingly sang folk and student songs with the participants of the party. The singing was always started with the traditional "Gaudeamus."
REFORMAT SKI^ REACTION Butlerov developed in his articles ( I ) , now forgotten but important at that time, the ideas of the structure of organic substances. The word structure was coined by Butlerov ( l a ) . (KekulB used constitution.) With the purpose of confirming his ideas he synthesized trimethylcarbinol (Z), the existence of which was predicted by him (1)and Kolbe (3). He used dimethyl zinc for this synthesis. Butlerov's pupil and Reformatskii's teacher, Zaitsev (4) proposed to replace the unhandy dialkylzincs in the synthesis of alcohols by a mixture of alkyl halides and zinc. This idea was very effective in creating a long series of syntheses. Reformatskii (6) introduced a new idea. He used instead of alkyl halides the halogen esters. The reaction involves three steps: ( 1 ) Formation of organo zinc halide
R'
+ zn
x-~-co.R"'
A,,
-
nr XZ~-~-CO$R"' R" I
(1) ( X represents a halogen, R"' is an alkyl, and R' and Rr'alkyl or hydrogen.) (2) Addition to the carbonyl group R' OZnX R'
(3) Decompositio~.by water
OZnX R' I I
H.0
-
OH R'
I
I
R'-C-C-COnR"'
+ ZnXOH
The final product using aldehydes and ketones is a P hydroxy ester. Starting with esters as carbonyl components 0 keto esters can be prepared but the yields in this case are poor. The hydroxy esters can easily be dehydrated to corresponding unsaturated esters (sometimes dehydration takes place simultaneously). When Grignard introduced organic magnesium compounds, all other syntheses with zinc lost their importance, but the Reformatskii synthesis kept its significance because the halogenated esters do not react normally with magnesium as was shown later by a pupil of Reformatskil(6). The Reformatskii synthesis was used to obtain many
naturally occurring substances or substances related to the natural products by simple reactions. In this way the structure of the substances could he determined. For example, there were synthesized sorhic acid, geranium acid, and terebic acid related to many terpenes. The Reformatskii reaction played a very important role in the determination of structure and synthesis of vitamin A. Karrer (7) used it twice in the synthesis of perhydrovitamin A, and Van Dorp and Arens (8) used the Reformatskii synthesis to prepare an acid corresponding to vitamin h from which the latter could be prepared by hydrogenation. The significance of Reformatskii's reaction is not limited to the synthesis of hydroxy esters and unsaturated esters and corresponding acids. This reaction is one of the general methods for lengthening a carbon chain. Using different carhonyl and halogen ester components it is possible to form straight chain or branched hydroxy and unsaturated compounds. The branching can
take place on the a or 0 carbon atom* or both. Double branching on an a ca~.honatom is also possible. The same goal can be attained by the Perkin reaction and Claisen and Knoevenagel condensations, hut in P branched compounds the yields obtained by these reactions are poor and the a and P branched products can he prepared only by Reformatskii's reaction. Reformatskii's reartion has been used several t,imes in the synthesis of steroids. LITERATURE CITED (1) BWTLEROV, A. \I. (a) Zeil. fur Chem., 1861, 549; (b) 1862, 247. (2) Ibid., 1863, 484. Rd. we. chim., Frniice, 2, 106 (1864). (3) KOLBE, A,, Ann., 118,307 (1861). (4) Z A ~ E V A., M., Ber., 6, 1542 (1873). (5) REFORMATSKI?, S. N., Rer., 20, 1210 (1887). (6) ZELTNER, J., RLP.,41, 580 (1908). (7) KARRER, P., R. \ ~ O R F , A N D I
