JOHN H. WOTlZ SouIhwn llllnol~Unlv.nly Carbondal., 62901
tetrachloroethane. The cycloadduct was therefore either 1-phenyl-3,3-difluoro-4,4-dichlorocyclobutene or the 3,3dichloro-4,4-difluoro isomer.
A Case History of Unplanned Development of New Chemistry J o h n D. Roberts California Institute of Technology Pasadena, 91125
\
A considerable part of the new chemistry of cyclohutane derivatives which has been developed over the last 30 years, including that of cyclohutenones, cyclohntadienoquinones, hydroxycyclohutadienoquinones (the strongest known neutral C,H,O acids), squaric acid, and so on,',2 depended on the discovery that the structural unit =C-CFin cyclobutene derivatives could he hydrolyzed in concentrated sulfuric acid solution to =C-C(=O)-. The development of this reaction as a synthetic procedure owes much t o a fortunate accident and provides an amusing illustration of why one should not ignore what fate is determined to thrust upon you. Too often the scientific papers describing discoveries omit the story of what really happened. The real object of the research a t that time was to prepare a cyclohutadiene derivative, any one, by the shortest and quickest possible route. Among the sequences considered was one based on the low-temperature, high-yield (2 2) cycloaddition discovered by Coffman and coworkers3 of tetrafluoroethene to l-huten-3-yne to give l-ethenyl3,3,4,4-tetrafluorocyclobutene.This in itself was a hreathtaking discovery although not highlighted in the Coffman paper. CH
+
cF,=cFI
+ Hc=c-cH=cH1
-c i
\\C-cH=cH,
\ /
CF, The proposal for synthesizing a cyclohutadiene derivative was t o add 1.2-dichloro-1.2-difluoroethene to phenylethyne and treat the resulting adduct with zinc to get a cyclohutadiene derivative in two quick steps
'cPc1 However, the requisite dichlorodifluoroethene was not availahle, hut the Du Pont Company said they could supply 1,2-difluorotetrachloroethane,which was known to give the right ethene on treatment with zinc. The starting material was purchased and the synthesis proceeded according to plan, except that the reaction of zinc with the cycloadduct did not give a cyclohutadiene derivative. This and the infrared spectrum of the ethene indicated that it was not the desired isomer but was 1.1-dichloro-2,2-difluoroethene. The material supplied by Du Pont was in fact 1,l-difluoro708 / Journal of Chemical Education
/
CF, When the originally desired CFCl=CFCl was synthesized and tried in the cycloaddition, the reaction failed and this approach was suspended. After failures in many other appro ache^,^ it was decided to reinvestigate the undesired adduct, although the inertness of -CF2groups was well documented. Hydrolysis in water or in base was unsuccessful, but there was a current paper suggesting that hydrolysis of the -CC13 of phenyltrichloromethane was acid catalyzed. Sure enough, hydrogen halide fumed off a mixture of the cycloadduct and concentrated HzSOc A full-scale reaction gave a beautiful crystalline product--hut with the wrong analysis (gloom). However, recalculation showed that the hydrolysis reaction had converted the -CFto -C(=O)and left the -CC12intact! Subsequent studies showed that the product was 2,2-dichloro-3-phenylcyclohutenone. .CH .CH
'
C ' F,
c,H,-c
\CCl, /
-+
c,H,-c
The happy accidents were not over. Some preparations gave a ketone of different melting point. This was traced to an amine-catalyzed allylic rearrangement from a trace of triethylamine which was added to react with small amounts of hydrogen halide formed during the cycloaddition reaction and which seemed to induce polymer formation. CH \
/
CCl,
This ketone with a hydrogen on the carbon next to the carhonyl group is just an enolization away from a cyclobutadiene derivative. Roberb, J. D.,Rec. Chem. Progr., 17,95 (1956). Cohen, S., Lacher, J. R., and Park, J. D., J. Amer. Chem. Soe.,
81.3480 (1959). Coffman, D. D., Barrick, P. L., Cramer, R. D., and Raasch, M. S., J. Amer. Chem. Sac., 71,490 (1949).
'Kline, G. B., PhD Thesis, Massachusetts Institute of Technol-
ogy. 1952.
Jenny, E. F., and Roberts, J. U.,J. Amer. Chem. Sac., 78,2005 (1956).
'
cc1
C=O
/ CC1
c6H5-C\
+
C&-C
b
H
NCd The sto+ of how this ketone, when made optically active, racemizes on heating without enolizing is too long to repeat here, but is another example of the fascinating cbemistry uncovered as the result of the chain of accidental events which seemed to bless this research program. Perhaps the frosting on the cake was the response of the supplier who sent the wrong material to hegin with, "We knew i t was not the right isomer, but we thought you were going to use it as a solvent!"
Kekulb's Whirling Snake: Fact or Fict;on Byron VanderblH Green Valley, Arizona 85614 The author recently carried out a search on the knowhow of inventing for his hook, "Inventing: How the Masters Did It." He noted that some, particularly psychologists, consider the dream a part of the creative art. The peculiar thing is that Kekul6's story of "One of the snakes had seized hold of its own tail . . ." '-which has been reported in many organic chemistry textbooks as leading Kekul6 to the structure of benzene-is apparently the only such example in the scientific and technical literature. Furthermore, based on association with R&D personnel for about 40 vears. this author never heard anvone state that a dream ledhim an invention or to the soiution of a problem. In a recent ouestionnaire 15 of mv fellow chemists and chemical engineers, who hold a totaf of about 1,290 US. patents, were asked to check the means by which their patents were conceived and developed. One alternative listed was by dreams. Not a single invention arose from a dream. Friedrich August Kekul6 entered the University of Giessen with the intention of becoming an architect hut after coming under the influence of Justus Von Liebig decided to become a chemist.2 He later studied under Dumas in Paris but returned to Giessen to get his PhD in 1852. He had subsequent appointments in Switzerland, London, a t Heidelberg University, Ghent University, and finally a t Bonn. KekuK accredited a part of his success to the facts that his training and exnerience were not "in one school of ~~~thought" and to his early training in architecture. In 1858 Kekul6 published the results of his experiments which showed that carbon was tetravalent and postulated the self-linking of carbon atoms in compounds. In 1865 he published a paper which postulated that benzene was of cyclic structure. He continued t o publish further evidence of this hexagonal structure based on various chemical derivatives. In 1872 he postulated that the three alternate double honds in benzene were in dynamic equilibrium resulting in the six carbon atoms being equivalent. ~~
~
-
By 1876 KekulB's physical power hegan to fail. He aged nrematurelv and ranidlv. He became verv deaf and ihunned friends. He did Cttle experimental work but spent a ereat deal of time in iustifvinrc his work on constant valence over that of ~ d w & d land and his cyclic structures for aromatic compounds over those of A. S. Couper which had been independently published in 1858. The German Emperor, who during his study a t Bonn was a pupil of Kekul6, revived in 1895 an old Bohemian title of nobility of the Kekule familv. Henceforth, Kekul6 signed his name Kekule Von ~tradonitz,dropping the accent which had been added because of the French influence. I t was not until 1890, a t a "festival" held by the German Chemical Society to honor Kekule on the 25th anniversary of his publicatiin on the benzene ring, that the aged man chose to glamorize his findings in this field? Little did he realize that posterity would grasp his dream story and, as in the case of muchreporting, go far beyond what he said or meant to sav. In this la& Hajor public appearance, Kekule mentioned two instances which helped him to formulate his theories of the structure of carbon compounds. One, which had happenedabout 35 years previously, dealt with a time when "I fell into a reverie . . . ." on a London omnibus while returning from the home of a chemist friend. During this reverie, which is a state of one lost in thought or abstracted musing, Kekul6 dctured chains of atoms in motion, the larger ones dragging the smaller ones. The second instant, iecalled after 25 years, was while dozing before a fireplace fire and seeing a vision of twining and twisting snake-like motion. "One of the snakes had seized hold of its own tail, and the form whirled mockingly before my eyes." Dozing is intermittent light sleep. Since the illusory or hallucinatory experience of true dreams occurs only after about an hour of sound sleeping, Kekul6 was apparently day dreaming in this case. In order that posterity not take his reminiscing too seriously, Kekul6 added the following: "Let us learn to dream, gentlemen, then perhaps we shall find the truth . . . . But let us beware of publishing our dreams till they have been tested by the waking understanding." With Couper abandoning the field after the publication of his paper in 1858, Kekul6 is now generally regarded as . ~ has the primary founder of organic structural t h e ~ r yThis adequately established him as one of the world's great in organic c h e m i ~ t r yhe ; ~ does not need the very questionable distinction of being the only chemist to achieve notoriety via the dream route. 'Benfey, 0. T., J. CHEM. EDUC., 35,21(1958). %Japp,F. R., J. Chem. Soc., 73,97 (1898). 3Keku16-CouperCentennial, J. CHEM. EDUC., 36,319 (1959). 'Benfey, 0.T. (Chairman), "Kekule Centennial,'' Advances in Chemistry, Series No. 61, American Chemical Society, 1966. This column is a series of short articles on the less known events that contributed to important and interesting developments in chemistry. Manuscripts, of about two doublespaced, typewritten pages, and other inquiries should be addressed to the column editor, Dr. John Wotiz, Department of Chemistry snd Biochemistry, Southern Illinois Universitv. Carbondale. Illinois 62901.
Volume 52. Number 11. November 1975 / 709
