Systematic Stereochemical Nomenclature & Vladimir Prelog
To the Student: Sections 1 and 2 are the most substantive portion of this page for a course in organic chemistry. The other sections may help to make this topic memorable and should contribute insight on the character and personalities of several leading organic chemists of the 20th Century
1) Stereochemistry ~1950
2) Cahn, Ingold, Prelog
3) Buergenstock Declaration
4) Remembering Prelog
5) Prelog Stories
- - - Robinson & Woodward
- - - Ruzicka as Administrator
- - - The Montenegran Peasant
The first was signaled by Derek H.R. Barton's paper "The Conformation of the Steroid Nucleus" (1950), which brought serious consideration of conformation of organic molecules to centerstage and ultimately led to Barton's Nobel Prize.
The figure at the right, from Barton's 1950 paper, shows the chair conformation of the "A" ring of a steroid molecule. A change since 1950 is that we now call one set of substituents "axial" instead of "polar" (p), though we still use Barton's "equatorial" for the other set. A more significant change is our understanding of the correct directions for the bonds. What is wrong with Barton's figure? (click for answer)
(Bijvoet's Tartaric Acid)
The second important development was a 1951 paper (announced in 1949) by Johannes Martin Bijvoet (pronounced "buy foot" 1892-1980) a Dutch crystallographer. In "Determination of the Absolute Configuration of Optically Active Compounds by Means of X-Rays" Bijvoet reported that using the sodium/rubidium salt of (wouldn't you know) tartaric acid and a special property of the heavy Rb atom (called "anomalous dispersion") he was able to do what no one had been able to do before - prove which enantiomer of a chiral compound was which. He showed that, given a 50:50 chance, Emil Fischer had guessed right when he drew the Fischer projection of tartaric acid 58 years earlier. From this time forward it would be possible to draw and name compounds according to their actual, or "absolute", configuration, rather than their configuration relative to an arbitrary standard (like Fischer's D-glyceraldehyde).
As Bijvoet wrote in 1951,
The question of nomenclature is beyond the scope of our investigation... The problem of nomenclature now concerns given configurations, and requires a notation which denotes these configurations in an unambiguous and if possible self-explanatory way.
Although conventions existed for drawing unambiguous diagrams of chiral molecules, there was no simple, systematic, unambiguous nomenclature for them. This need was addressed in a 1950 paper by two Englishmen, R. S. Cahn (1899-1981), editor of the Journal of the Chemical Society (of London), and Christopher Ingold (1893-1970) of University College London, who was a leader in discovering how reactions occur (in fact he studied, and named, the SN1 and SN2 substitution processes, which we will soon discuss). Their paper, "Specification of Configuration about Quadricovalent Asymmetric Atoms", proposed a scheme based on a sequence rule of atom priorities. As Lavoisier would have predicted, the availability of an appropriate nomenclature has made working, thinking, and communicating in this field much more efficient and productive.
In 1955 the scheme of Cahn and Ingold was expanded and generalized in collaboration with Vladimir Prelog of the Swiss Federal Institute of Technology (ETH), Zurich. Prelog had impressive credentials from accomplishments in synthesizing antibiotics and other natural products and would receive the Nobel Prize in 1975 "for his research into the stereochemistry of organic molecules and reactions." His logical insights improved the R/S nomenclature scheme, which is now known as CIP (Cahn, Ingold, Prelog). Just as importantly Prelog's sense of humor and personal magnetism facilitated quick acceptance of the scheme.
Every spring since 1966 a conference on stereochemistry has taken place at Bürgenstock, a Swiss resort overlooking the Lake of Lucerne. The photograph at the right shows Cahn, Ingold, and Prelog (l to r) at the first conference.
(thanks to Jeffrey Seeman for this photo)
The "Buergenstock Declaration," generated at the 1966 session of the Bürgenstock conference, was signed by C, I, and P. (reproduced by permission of the scribe and coauthor, J. D. Dunitz)
Problem: interpret Prelog's signature on this document
If you give up on deciphering his (Cyrillic?) signature, click here.
Prelog's capsule Nobel autobiography and his book "My 132 Semesters of Chemistry Studies" (J. Seeman, ed., American Chemical Society, 1991, from which two stories and the figures were taken) reveal a person of keen intelligence, irresistible charm, and deep wisdom. The title of the book refers to his ruse for staying on at the ETH after reaching the compulsory retirement age. He enrolled as a student. In these accounts:
• You meet a citizen of the world who, as an 8-year old in Sarajevo, was waiting to scatter his little basket of flowers in front of the carriage carrying Archduke Franz Ferdinand and his duchess, when a few hundred meters away they were assassinated, triggering World War I.
Robinson and Woodward after a As I already mentioned, Robinson disliked
system for the specification of
molecular chirality. When we once met at Zurich airport on
the way to Israel to celebrate the 25th anniversary of the
Weizmann Institute, the first words we exchanged were the
following: Woodward and Sir Robert Robinson held
each other in high esteem, but they did not always get along
well. One day, probably in the late 1950s, when Woodward
visited us in Zurich he said to me, I suspecting something wrong, asked,
"What did he say?" And Woodward triumphantly replied,
"Prelog is a lousy chemist, but he is a
rather nice guy." How true!
1951 MIT seminar by Robinson
on the Robinson annelation
in Steroid Synthesis
(photo J.D. Roberts, by permission)
Katchalsky. What are you doing here in Zurich?"
I: "Excuse me, Sir Robert, I am only Prelog, and I live here."
Robinson: "You know, Prelog, your and Ingold's configurational notation is all wrong."
I: "Sir Robert, it can't be wrong. It is just a convention. You either accept it or not."
Robinson: "Well then, if it is not wrong, it is absolutely unnecessary."
"You know, Sir Robert is a bad
I: "How can you say something like that about the greatest living organic chemist?"
Woodward: "Yesterday, I spent the whole day with him in Oxford. He doesn't communicate much with me any more about chemistry, but he does talk about individuals. He didn't find a single good word for any chemist in the whole world."
I: "Perhaps he was in a bad mood; that doesn't mean that he is evil."
Woodward, irritated by my contradicting, replied, "Indeed, I didn't tell the truth. He said something nice about you."
[the "How true" is Prelog's and
part of the story. Prelog painstakingly reworked these
two stories to make sure they were just right for his
published autobiography. He decided on a bowdlerized
punch line "Prelog is not a good chemist, but he is a
nice person." On the advice of his friends I have
retained a version quoted by Heilbronner in A
Philatelic Ramble through
Robinson and Woodward after a
As I already mentioned, Robinson disliked the CIP system for the specification of molecular chirality. When we once met at Zurich airport on the way to Israel to celebrate the 25th anniversary of the Weizmann Institute, the first words we exchanged were the following:
Woodward and Sir Robert Robinson held each other in high esteem, but they did not always get along well. One day, probably in the late 1950s, when Woodward visited us in Zurich he said to me,
I suspecting something wrong, asked, "What did he say?"
And Woodward triumphantly replied, "Prelog is a lousy chemist, but he is a rather nice guy."
A resident of many countries, including Croatia, Czechoslovakia, and Switzerland, and a frequent visitor to Britain and the U.S., Prelog was skilled in his use of foreign languages, but self-deprecating about it. He loved telling stories, and how he told them was part of his charm and humor.
Prelog with his mentor Ruzicka
in Zurich, 1953
(photo J. D. Roberts, used by permission)
Click to hear Prelog tell
Leopold Ruzicka as an Administrator
(recorded in 1992, and transcribed below):
(When you click above in a properly configured browser, a small sound control window
should appear. It may be hidden behind this window, and you may also need to
adjust the volume elsewhere. There are pedantic notes for the words in italics.)
I think chemical research costs now about 10 to 100 times as much as it did in '45.
You know, we bought Perkin-Elmer. Thompson was here and so on, so Ruzicka said, "We must have Perkin-Elmer" - infrared.
Perkin-Elmer was 60,000 Francs. It was unheard. Nobody was able to give so much money. So the school gave 20,000 Francs, and then industry gave 20,000 Francs, and still 20,000 Francs were lacking.
But there is a foundation here, of our school, which from time to time can spend some money. So at the sitting of this foundation they decided to give Ruzicka the last 20,000 Francs.
And he had many people - the people didn't like him. The chair was Professor Frey-Wyssling, and he was president of the school and so forth, or expert and so. So this Frey-Wyssling told Ruzicka, "Ruzicka, hier bekennen Sie. (You have to confess.) You ordered this machine before we decided to give you this 20,000 Francs."
And Ruzicka said, "You don't know me at all. The machine is already half a year working."
And then the President took Ruzicka and said, "Professor Ruzicka, you shouldn't say such things before the public. Your financial activity is not a solid one."
And he said, "Oh, I did it for 60 years, and I was always very glücklich (happy)"
And the President said, "Ruzicka, you don't still speak well German. You were not happy; you were lucky." (He said, "You were not glücklich, you were glückhaft.")
Here is a final Prelog story about his attitude toward the Nazis, who occupied Zagreb when he was a lecturer there in 1941, forcing him and his wife to flee to Switzerland:
Montenegro is the poorest part of the Balkans. Early this century there was a Montenegran peasant who had nothing but a sickly goat. One day a wolf came out of the forest and ate the goat.
The peasant had no choice but to emigrate to Italy, where by menial jobs he earned passage to Canada. Finally he arrived in the United States, where he found a job stocking shelves in a grocery store. When by hard work and frugal living he had saved a little money, he bought part interest in the store. Eventually he was able to buy the grocery store outright, and finally to acquire a whole chain of grocery stores.
Although he had become very successful, he never forgot his roots. Faithfully each year on his name day he went to the Orthodox church to light two candles - one for his patron saint, and one for the wolf.
Perkin-Elmer: An instrument company founded in 1937 in Norwalk, Connecticut, as an American source of precision optics. Perkin-Elmer entered the emerging field of analytical instrumentation in the 1940s. For many organic chemists Perkin-Elmer was synonymous with recording IR spectrometer.
Thompson: Harold W. (Tommy) Thompson (1908-1983), of Oxford, pioneered the application of IR spectroscopy for organic chemical analysis. In his 1944 Tilden Lecture "The Scope and Limitations of Infra-red Measurements in Chemistry", he modestly wrote,
It seems probably that infra-red analysis will soon rank highly for routine and research work in organic chemistry, where its usefulness may at least equal that of ultra-violet spectroscopy.
[Thompson was using IR to analyze German high-performance aviation fuel. This fine lecture was published in 1944 on pages 183-192 of the thin 723-page wartime volume of Journal of the Chemical Society (London). In 1938 this journal had 2200 pages; in 1948, 2375. ]
After the war Thompson gave a series of lectures on IR in Zurich. He was obviously a good ambassador and salesman for this technique. (For an obituary notice, pointing out that Sir Harold also had a "major impact on association football" see Rex Richards, Chemistry in Britain, 1985, 21, 941)
Frey-Wyssling: Professor Albert Frey-Wyssling (1900-1990) a distinguished botanist with an interest in structure was a foreign member of the U.S. National Academy of Science. He made some of the first x-ray diffraction studies of cellulose.
The chair was: This is filler. No one has yet made out the few words in here.
60 years: This was Ruzicka's age at the time, i.e. he has been doing this for his whole life. Prelog seems to toy with the alternative of 50 years (as a very young child Ruzicka may have been better behaved).