1876 1976 W
Organic chemistry: the past 1 0 0 years D. S t a n l e y Tarbell, Vanderbilt University
Ira Remsen and his laboratory at Johns Hopkins University, circa 1900
This account will be built around some of the leading figures in organic chemistry in this country during the past 100 years. The choice necessarily will be somewhat arbitrary, and many outstanding figures and some important developments will be omitted. Nevertheless, I hope to present a reasonably comprehensive picture of the development of a major science that has played a basic role in the growth of related fields, such as both naturally occurring and synthetic polymers, biochemistry, molecular biology, medicinal chemistry, organic photochemistry, and several areas of spectroscopy—mass, ultraviolet, infrared, nuclear magnetic reso110
C&EN April 6, 1976
nance (NMR), and electron spin resonance (ESR). The year 1876 is a natural starting point for an account of organic chemistry in this country. The American Chemical Society was founded in 1876; Johns Hopkins University, with its graduate program in chemistry under Ira Remsen, opened in 1876 also; the Journal of the American Chemical Society and the American Chemical Journal were founded in 1879, and research in organic chemistry on a substantial and professional level started at several other universities in the 1875-80 period. Examination of both German and American scientific journals shows a notable up-
surge in organic training and research over these years. The general principles of structural organic chemistry had been stated by 1875. As G. N. Lewis pointed out in 1931, "Structural organic chemistry, although developed without mathematics, except of the most elementary sort, is one of the very greatest scientific achievements. An enormous mass of information was reduced to a wellordered system through the aid of a few simple principles." Remsen sets the stage
Ira Remsen (1846^1927) performed unique services to American
chemistry by starting the first, and, for about 30 years, the most impor tant program for training Ph.D. stu dents. He was an outstanding teacher of undergraduates as well as graduate students and the author of widely used textbooks in inorganic and organic chemistry. He edited the American Chemical Journal from 1879 until it merged with JACS in 1913. The influence of the Hopkins school on the development of organic chemistry in this country was very great. Of 130 Hopkins or ganic Ph.D.'s during the years 1879-1913, 107 were associated with Remsen personally; 75% of these 130 students went into college or university teaching initially and 66% spent their entire careers in teaching. Opportunities for Ph.D.'s in government research laboratories were just beginning in 1880 and in dustrial research positions became available only later. Remsen had one of the marks of a great teacher: He inspired many of his students with an abiding fasci nation with organic chemistry, and some of them became leaders of im portant university graduate pro grams. Among these were William A. Noyes (Illinois), Edward C. Franklin (Kansas, Stanford), James F. Norris (Massachusetts Institute of Technology), E. Emmet Reid (Johns Hopkins), W. R. Orndorff (Cornell), and Elmer P. Kohler (Bryn Mawr, Harvard). The first teaching experience of another Remsen Ph.D., Walter Jones, who later became a well-known bio chemist at Hopkins Medical School, gives an interesting glimpse into small college teaching in the 1890's. Jones, in his first year at Witten berg College in 1891, "offered courses in chemistry, mineralogy, zoology, and botany. It is possible that he may have offered a course in crystallography." Remsen's research was concerned mainly with aromatic sulfonic carboxylic acids, and grew out of his Ph.D. thesis with Rudolf Fittig in Germany. Although his research re sulted in the discovery of the sweet ening agent saccharin, which gave Johns Hopkins and synthetic or ganic chemistry wide publicity, if no money, Remsen's work in gener al was not as original or significant scientifically as that of some of his students and contemporaries.
existence of "free radicals," con taining carbon which had a valence of three instead of four, as demand ed in the classical structural theory. Gomberg was an example of the best kind of U.S. success story; he came to this country as a child from Russia with his penniless father, worked his way through Michigan and received a Ph.D. there. His dis covery of the trivalent carbon com pounds of the triphenylmethyl se ries aroused immediate interest and controversy here and abroad. Gomberg, although personally one of the most modest and unassuming of men, defended his elegant exper imental work with skill and persis tence and had the satisfaction of seeing his idea of trivalent carbon accepted in a few years (1). Gomberg's discovery accustomed chemists to the idea of trivalent carbon radicals, and thus contrib uted to the later applications by Morris S. Kharasch, Paul J. Flory, and others of the idea of chain reac tions in which the reaction interme diates were carbon free radicals. These radicals are more reactive than Gomberg's triarylmethyls, but they can be studied, as G. N. Lewis suggested, by taking advantage of the paramagnetic properties of the unpaired electron which they con tain. Electron spin resonance has in recent years allowed detailed work on low concentrations of free radi cals. Michael, the iconoclast
Arthur Michael (1853-1942) was for several decades the most pro ductive and original of U.S. organic chemists, and the most widely
ο ο JZ
a. c ο
Gomberg and free radicals
The single most important dis covery of U.S. organic chemistry be fore 1914 was the demonstration at the University of Michigan by Moses Gomberg (1866-1947) of the
Moses Gomberg
known abroad. Michael came from a prosperous family of Buffalo, N.Y., and was educated informally in Germany and France; he had no college or university degrees except for honorary doctorates. His chemical work in Germany resulted in 16 publications, some with Siegmund Gabriel of the Uni versity of Berlin and some with other students. His chemical publi cations-cover nearly seven decades and number more than 225. Mi chael became professor at Tufts College in 1880 and married Helen C. DeS. Abbott, who was a gifted scientist and writer herself; she had published many papers before she worked with Michael. The Michaels took an 18-month trip around the world as a honeymoon; one of his polemical papers was written in Egypt, where they were boating on the Nile. Michael then set up a pri vate laboratory on the Isle of Wight, off the south coast of England, and published a stream of papers with his wife and research assistants as collaborators. He returned to Tufts in 1894, taught there until he re tired in 1907, and then set up a pri vate laboratory on his estate in Newton Center, Mass. He was given an appointment at Harvard and continued research, mainly with postdoctorates, until his death. Mi chael was widely acquainted with fields outside organic chemistry, and had a notable collection of Ori ental art (2). Michael's career has been de scribed briefly to show how differ ent it was from the usual pattern for a scientist. It is not surprising, therefore, that he was original and sometimes iconoclastic in his chem ical views. Michael generalized the reaction that bears his name, the addition of a carbanion or some other nucleophile to a conjugated system; the reaction was actually first described by Ludwig Claisen. Michael also carried out much use ful synthetic work, including the first synthesis of a naturally occur ring glycoside. It is frequently stat ed that he first proved trans addi tion to a C = C . An examination of Michael's vo luminous publications shows that although some of his results could be most reasonably explained by trans addition, Michael himself hes itated at the time to draw this con clusion. He distrusted the cis-trans system of J. H. Van't Hoff, J. A. LeBel, and Johannes Wislicenus all his life and particularly objected to their conclusion, based on the hydroxylation of maleic and fumaric acids by potassium permanganate, that all addition was cis. A concluApril 6, 1976 C&EN
111
sive proof of trans addition was not given until 1911, when several other groups did it simultaneously. Michael was sure that cis addition was not general, but he felt that the whole scheme of stereochemistry was dubious. Michael showed that elimination reactions took place by the same stereochemical path as addition reactions, and hence if addition to C = C was trans, elimination must be trans, because the original compound was regenerated. The two laws of thermodynamics, the conservation of energy and the increase of entropy, became known to chemists during Michael's formative years. Michael stated as a general law that chemical reactions occurred to give the maximum neutralization of free energy, or of chemical potential, or the maximum increase of entropy, his actual expression varying in different papers (3). This proposition is open to some criticism, in spite of its general truth. It is well known now, and indeed was recognized by Michael, that some reactions are under kinetic control and yield initially the thermodynamically less stable products that may change to the more stable products with time. This dichotomy between kinetics and thermodynamics is a fundamental fact in modern thinking about reaction mechanisms. A second limitation on Michael's entropy law was that he never defined the meanings of his thermodynamic terms clearly. And even if they had been clearly defined, there were no exact measurements available to determine the preferred thermodynamic course of a given reaction. Michael was thus far ahead of his time, and his application of his thermodynamic principles to organic reactions depended on his very wide knowledge of organic and inorganic chemistry. Michael made much use of an idea of Friedrich August Kekulé, which can be traced farther back than Kekulé, that reactions occurred by two molecules combining to give a "polymolecule," which then broke up to yield products. This idea has obvious similarities to modern ideas of the transition state between reactants and products. Michael developed a numerical scheme for indicating and predicting the influence of atoms on each other, but the insight and knowledge on which the scheme is based are more impressive than the scheme itself. He was able to give an explanation of Markovnikov's rule of addition to unsymmetrically substituted C = C , such as in (CH3)2C=CH2, which is similar to 112
C&EN April 6, 1976
present ideas. Much of Michael's work dealt with tautomeric compounds, and he maintained all his life that the sodium derivative of an enol, such as Ο / (CH 3 C—CHCOOR) e Na® had the sodium bound by a nonionic bond to the enolic oxygen. This structure, he said, was better neu tralized, with the positive sodium on the negative oxygen. This re quired an ad hoc explanation of the action of CH3I on the above sodium derivative, which forms CH 3 C CH(CH 3 )COOR with the CH3 on C rather than on 0. Michael was an indefatigable po lemicist, and seldom gave up a posi tion once taken. He was a keen and Roger Adams sometimes caustic critic of other people's work, and he spoke with more authority than any other U.S. Adams and structural organic chemistry organic chemist of his time. For several decades after 1914, Before 1914, important work was done at Yale on pyrimidine and pu the leading figure in U.S. organic was Roger Adams rine bases by Treat B. Johnson, chemistry William H. Wheeler, and their stu (1889-1971). Educated at Harvard, dents, by John V. Nef and Julius Adams was a contemporary of Stieglitz at Chicago on reaction James B. Conant, Frank C. Whitmechanisms, particularly rear more, and Henry Gilman as a stu rangements, by Charles L. Jackson dent. (This group recalls the later at Harvard on aromatic compounds, quartet, also of outstanding ability, by Claude S. Hudson at various of Arthur C. Cope, Ralph Connor, government laboratories on sugar Karl Folkers, and C. F. Koelsch at chemistry, by Elmer P. Kohler at Wisconsin in the early thirties.) Bryn Mawr on 1,4-addition, by P. After a brief but highly successful A. Levene at Rockefeller Institute teaching career at Harvard, Adams on nucleic acids, sugars, and other moved to the University of Illinois natural products, by S. F. Acree at in 1916, where William A. Noyes Johns Hopkins and J. F. Norris at had laid the foundation of a great MIT on reaction mechanisms, and department. Adams remained at Il by W. A. Noyes at Rose and Illinois linois, aside from his public service activities, for the rest of his life, in on camphor derivatives (4). By 1914, American organic chem spite of many offers of other aca istry was well established in private demic positions and of university and state universities, industrial re headships. Adams served as chair search laboratories were developing, man at Illinois, after Noyes' retire and many state and national gov ment, from 1926 to 1954. ernment laboratories had active re Any adequate account of Adams' search programs. Johns Hopkins personality and accomplishments was no longer the dominant center would require a very long essay in for research training, and many lib deed (5). His career coincided with eral arts colleges were giving sound a dramatic expansion in industrial undergraduate work in organic research in this country, an expan chemistry. The country was still de sion on which he exerted a strong pendent on Germany for dyes, influence, both personally and drugs, and organic chemicals for re through his students. This expan search; the interruption of trade sion caused a similar increase in the with Germany by World War I number of undergraduate and grad caused widespread disruption in in uate students in organic chemistry, dustry and teaching. The situation and the Illinois department was a was alleviated by mobilization of leader in the growth of other out academic and industrial chemists to standing departments, particularly make the U.S. independent of Ger in middle western universities. man supplies of chemicals and to Adams had extraordinary ability, work on problems of chemical war both administrative and scientific, fare. combined with a personality of
$Â Union Carbide w a s a m o n g earliest producers of olefins, o r g a n i c s A $3000-a-year fellowship launched late in 1914 at Pittsburgh's then fledgling Mellon Institute for Industrial Research planted the seed from which has flowered today's far-flung synthetic oliphatic chemicals industry. Prest-O-Lite Co. had been producing acetylene since 1904 from calcium carbide for use in bicycle and automobile headlights and for oxyacetylene welding and cutting. Uncomfortable in being dependent on the sole U.S. carbide producer, Union Carbide Co., it was anxious to find another source for acetylene. The task fell to George 0. Curme Jr., who had earned his Ph.D. in chemistry at the University of Chicago just the year before. Curme found that he could make acetylene on a lab scale by cracking kerosine with an electric arc. But the process also produced appreciable amounts of other hydrocarbons, particularly ethylene and propylene, and he quickly saw that if it was to be commercially viable he would have to find uses for these by-products as well. So he undertook a systematic study of olefin chemistry. Curme's research was a technical success. But it might well have ended up on the commercial shelf when, in 1917, Prest-O-Lite merged with Union Carbide, as well as with Linde Air Products Co. and National Carbon Co., to form Union Carbide & Carbon Corp. Clearly, Prest-O-Lite no longer needed to fear for adequate carbide supplies. Perhaps it was because defense needs by then had sparked an interest in developing a domestic chemical capability. Perhaps it was the foresight of the new company's management. Perhaps it was the persuasiveness of Curme himself, who had turned up some promising synthetic leads. In any event, the research at Mellon continued, with Curme's project being merged with fellowships there that had been set up by Union Carbide in 1915 to uncover new uses for carbide and acetylene and
great charm and force; he never lost any of the Yankee twang in his speech, although his headquarters were in Illinois for many decades. He followed the progress of his research people with intense interest, both during their work with him and in.their later careers. It is almost invidious to single out individuals from the more than 200 Ph.D. students and postdoctorates who worked with him. However, the contributions to industrial research of Ernest H. Volwiler (Abbott Laboratories), Wallace H. Carothers and Theodore L. Cairns (Du Pont), and William E. Hanford (Olin) are well known. Wendell M. Stanley, a Nobel Laureate for his work on viruses (Rockefeller, Berkeley), Samuel M. McElvain (Wisconsin), John R. Johnson (Cornell), Ralph L. Shriner (Iowa), Carl R. Noller (Stanford), and Nathan Kornblum (Purdue) are representative of his Ph.D.'s who had successful research
Laboratory, called "The Shack," at Mellon Institute. From left, Glenn D. Bagley, George O. Curme Jr., his brother Henry R. Curme, J. Compton, others unidentified
by Linde shortly later to work on inorganic synthesis. Wartime power shortages led Curme, who continued to head the work, to shift his attention from arc cracking of petroleum fractions to thermal cracking of natural gas liquids as a source of ethylene and other olefins. Linde's plant at Buffalo aided the work by preparing pure fractions of the olefins for Curme to work with. By 1920, Curme and his group had synthesized a raft of ethylene derivatives: ethylene oxide, ethylene glycol, ethylene dichloride, diethyl sulfate, ethanol, and isopropanol. Results looked so promising that Union Carbide then formed a new subsidiary, Carbide & Carbon Chemicals Corp., to develop commercial processes and markets for these products. A small gas processing plant hidden away deep in an inaccessible mountain valley at Clendenin, W.Va., was acquired and converted to use as a pilot plant. Union Carbide was firmly in the organic chemicals business to stay.
and teaching careers. Adams' accomplishment in building up and maintaining an outstanding department, with colleagues highly distinguished in their own right, deserves emphasis. Adams' research was mainly synthetic and structural. Among its highlights were the development of the "Adams platinum" catalyst for hydrogénation, the structural determination and synthesis of chaulmoogric and hydnocarpic acid (used at the time in treating leprosy), the stereochemistry of biphenyls and of deuterium compounds, the determination of the structure of gossypol (the yellow pigment in cottonseed meal), the structure of the Senecio alkaloids, and the structure of constituents of marijuana. Adams and his colleague, Carl S. Marvel, were responsible for starting 'Organic Syntheses," a result of the Illinois work on methods of preparing compounds previously ob-
tained from Germany. This annual publication of tested methods of synthesis and of applications of new reactions is still, in its sixth decade, a vital publication. Adams also started "Organic Reactions," which has been equally useful and of which more than 20 volumes have appeared. The public service activities of Adams, in addition to his research, administrative and consulting work, showed his boundless energy and the high respect which he enjoyed. President and chairman of the board of ACS, president of the American Association for the Advancement of Science, member of the National Defense Research Committee, adviser to the American military governments in Germany and Japan, member of the board of the National Science Foundation: These were only some of the capacities in which he served science and the national interest. April 6, 1976 C&EN
113
éfe M o n s a n t o , n o w w i d e l y diversified, w a s founded to produce s a c c h a r i n
At the turn of the century, John Francis Queeny, chief purchasing agent for a St. Louis drug supply house, had an idea: Money could be made by manufacturing saccharin, which at that time was imported from Germany. He tried to persuade his employers to undertake the venture, but they wanted no part of manufacturing. However, they had no objection to his trying it on his own. So in 1901, at age 42, Queeny, with $1500 of his own money, went into the saccharin business. To avoid conflict with his employers (he stayed with them several more years), he gave his new two-employee company not his own name but his wife's maiden name. Thus began Monsanto Chemical Works. The young firm prospered, modestly. By 1914 it had diversified into caffeine, vanillin, phenacetin, chloral hydrate, phenolphthalein, glycerophosphates, and coumarin. Then World War I brought frantic expansion. Monsanto outgrew its original site in St. Louis, and acquired a plant in East St. Louis, 111., to assure adequate supplies of sulfuric, nitric, and hydrochloric acids.
In 1920 Queeny took his first step into foreign manufacturing by acquiring a 50% interest in what became the Graesser-Monsanto Chemical Works at Ruabon, Wales. That move was in response to a British tariff that threatened to cut Monsanto out of markets it had developed during the war. But 1921 brought near collapse as European chemical companies did indeed recapture many of their former markets. With a $132,000 operating loss, $3.2 million in debts, and credit tight, Queeny had to issue new stock to obtain capital. In the process he lost majority control of the company. Business picked up in 1922, but it was four more years before Monsanto was in good financial shape again. In 1928 Queeny, incurably ill of cancer, turned the presidency over to his only son, Edgar Monsanto Queeny, then 30. John Queeny died five years later. Under Edgar's leadership, the company entered the rapidly growing rubber additives business and expanded production of basic chemicals. Shortly after the turnover in management, story has it, the elder Queeny complained, "I don't know what I'm going to do with that boy Edgar. He wants to change everything. He's going to ruin Monsanto." At that time the company had assets of about $8 million. Monsanto did suffer a serious setback in the depression year 1931, but thereafter sales rose steadily for the rest of the decade. Edgar was fortunate, or wise, or both, in his choice of fields for expansion. For example, the company went into the phosphate business in 1933. The advent of synthetic detergents, automatic washing machines, and dishwashers boosted the market for phosphates beyond all expectations. Moves into plastics, synthetic fibers, and herbicides were similarly blessed. Today Monsanto is one of the top four U.S. chemical companies, with assets of $2.9 billion and with 61,000 employees worldwide. So old John Queeny was only half right: Edgar changed Monsanto, but he didn't ruin it.
ψβ His scientific and administrative work was honored by dozens of medals, honorary degrees, and awards. Adams' career epitomizes the de velopment of structural organic chemistry and of industrial research in this country in the years between the world wars. Another side of or ganic chemistry was the study of re action mechanisms and physical or ganic chemistry in general, which became characteristic of this coun try. This interest had been present since 1875, although Remsen was not much concerned with theory, but the work of Michael, Nef, Stieglitz, Acree, and Gomberg was the forerunner of a major effort in U.S. chemistry. Physical organic chemistry opens up
James B. Conant at Harvard, a friend of Roger Adams, had pub lished a series of original papers on oxidation-reduction potentials of quinones, on irreversible oxidations, 114
C&EN April 6, 1976
including work on hemoglobin, free radical formation by one electron transfer, reactivity of organic halides with sodium iodide in acetone, the structure of chlorophyll, and numerous other problems that stand out as pioneering work in the literature of the 1920's. Conant gave up chemistry for the Harvard presi dency in 1933, but his student Paul D. Bartlett started 40 years of re search and teaching at Harvard in 1934 in physical organic chemistry. Bartlett's work was outstanding, and his influence as a teacher was great; his career might well be used as a background for the rise of physical organic chemistry. I have, however, chosen a different ap proach to the subject. Both Conant and Howard J. Lucas of California Institute of Technology developed active schools of research in physical or ganic chemistry, and Louis P. Hammett of Columbia published some key papers on strong acid solutions. Hammett discovered, in 1934, a
broadly successful linear free ener gy relationship (a correlation be tween rates and equilibria of reac tions), which connected rates of re action of substituted aromatic compounds with the dissociation constants of the correspondingly substituted benzoic acids. Hammett's book, "Physical Organic Chemistry," published in 1940, ex ercised a great influence on later work and came to be recognized as one of the American chemical clas sics, worthy to stand with those of Willard Gibbs, G. N. Lewis, Linus Pauling, and Paul Flory (6). The shared electron theory of valence of Lewis (1916, 1923) and the develop ment of the quantum mechanical theory of bonding by Pauling and others gave a satisfactory theoreti cal basis for the simple structural postulates of organic chemistry, in cluding the stereochemical aspects, and the behavior of aromatic sys tems. Most of Hammett's book, and much of the work of the Conant-
Bartlett-Lucas-Winstein groups, as well as Christopher K. Ingold's work in England, dealt with reac tions in which ions reacted or could be reasonably postulated as inter mediates. A different system of re actions, in which a free radical, a structure with an unpaired electron, was the intermediate, grew up in the 1930's, and became of very great importance, both theoretically and practically. Free radical chemistry was due primarily to the work of Morris S. Kharasch (1895-1957) of the University of Chicago. I have chosen him for discussion because his work has not had the recogni tion it deserves from organic chem ists in general.
Similar explanations were offered by Donald H. Hey and William A. Waters in England (9). Kharasch went on to develop and elucidate whole families of free rad ical reactions, initiated in various ways, to form halides, carboxylic acids, sulfonic acids, and other classes from saturated hydrocar bons. He also developed free radical additions of carbon tetrahalides to olefins, radical decompositions of hydroperoxides, radical additions of mercaptans to olefins, and modifi cation of Grignard reactions by a radical process initiated by cobaltous ions. One of his last reactions was the cuprous salt decomposition of peresters to form allylic esters:
Kharasch extends free radical chemistry
Γ J + C (i H,C—0—0—C 4 H 9 (t)
Kharasch was born in the Ukraine but came to this country as a youth, and took his undergrad uate degree and Ph.D. at Chicago, the latter in 1919. There is a story, possibly apocryphal, that on his final Ph.D. oral exam Kharasch was asked a type of question then in vogue. The examiner had a com pound in mind, and Kharasch could ask the examiner as many questions as he needed, until he was able to name the compound. Kharasch im mediately realized that the com pound was glucose, but he proceed ed to ask the examiner a series of elaborate and detailed questions about the most esoteric physical and chemical properties of glucose and its derivatives. Not until the examiner had to admit that he had reached the limit of his knowledge
James B. Conant
Morris
Kharasch
did Kharasch relent and name the compound. This story illustrates Kharasch's brilliance, his originality, and the ir reverence toward conventional au thority that were to mark his career. After a short stay at the Universi ty of Maryland, and some research on organic mercury compounds, which he tried to use to determine relative electronegativities of organ ic groups, Kharasch returned to Chicago, where he remained the rest of his life (7). The free radicals discovered by Gomberg all had a high concentra tion of aromatic groups. The idea had gradually developed, with ex periments to support it, that addi tion polymerization of styrene and vinyl acetate, for example, was a chain reaction; the evidence is dis cussed by Wallace H. Carothers in his remarkable review of condensa tion and addition polymerization in 1931 (8). It was not realized in 1931 that free radicals were the initiators and chain carriers. Kharasch and his student, Frank R. Mayo, showed in 1933 that the direction of addition of hydrogen bromide to allyl bromide depended on the presence or absence of per oxides. In absence of oxygen, the product was the "normal" Markovnikov one, BrCH 2 CHBrCH 3 , but in presence of oxygen or added perox ides, the product was the "abnor mal" one, BrCH 2 CH 2 CH 2 Br. Khar asch provided many other examples of the "peroxide effect" and, in 1937, explained the effects of perox ides as due to the initiation of a free radical chain reaction involving bromine atoms and organic radicals.
| | )
- ^
+ HOC4H9(t)
Kharasch was fond of pointing out that the textbook picture of sat urated ("paraffin") hydrocarbons as unreactive only applied to the ionic series of reactions; as his work showed, the paraffins are highly re active materials toward a variety of free radical forming reagents. Khar asch's career is a good illustration of the value of a few talented skeptics, who question critically some of the accepted scientific dogmas. The detailed conceptual scheme for addition polymerization as a free radical chain process was de veloped by Flory in 1937 (10) simul taneously with Kharasch's peroxide effect mechanism. Two of the out standing workers on addition poly merization were Mayo and Cheves Walling, both students of Kharasch. The polymerization problem was one of such practical importance and theoretical interest that many able academic and industrial re searchers worked on it, including Bartlett, Marvel, Charles C. Price, William 0 . Baker, Frederick T. Wall, Flory, Charles G. Overberger, and many others. An excellent re view is given by Walling in "Free Radical Reactions in Solution" (1957). Current work (Glenn Rus sell, Kornblum, Joseph Bunnett) on radical anion chain reactions owes something to Kharasch, as well as to Leonor Michaelis of Rockefeller University, who showed, in the early 1930's, the existence of radical anions ("semiquinones") formed from hydroquinones by one electron oxidation. Herbert C. Brown (Purdue), a postdoctoral fellow with Kharasch April 6, 1976 C&EN
115
Herbert C. Brown
and an outstanding research worker in his own right, has written his per sonal and scientific autobiography in detail ("Boranes in Organic Chemistry," Cornell, 1972). I will mention three fundamental contributions to organic chemistry by Brown. The first was a detailed study of steric hindrance, using quantitative measurements on the stability of the "salts" of Lewis acids and bases, such as RaNiBR^. He found, for example, that 2,6-ditert- butyl pyridine did not react with the Lewis acid boron trifluoride at all and showed decreased ba sicity to protons, compared to less highly substituted pyridines. Brown developed the complex metal hydrides, L1AIH4 (lithium aluminum hydride), NaBH 4 (sodi um borohydride), and their many variants into highly specific reduc ing agents for most unsaturated groups. Metal hydride reduction is more specific than catalytic reduc tion in many cases and also offers an ideal way to introduce deuterium or tritium by using complex deuterides or tritiated materials. These compounds and the organoboranes mentioned below probably repre sent the most important synthetic developments in organic chemistry since the discovery of the Grignard reagent and the Diels-Alder reac tion. The trialkylboranes have been made readily accessible by Brown's work, by addition of the readily pre pared boron hydride to olefins, and have been shown to be readily con vertible, in ordinary laboratory equipment, to a wide variety of compounds, such as alcohols, ke tones, amines, and other products. They undergo 1,4-addition to con jugated systems, act as free radical 116
C&EN April 6, 1976
sources, and can take part in free radical chain reactions. Brown's work shows indomitable industry, originality, and an in stinct for detecting promising leads. A flowering off physical organic chemistry
The modern blooming of physical organic chemistry may be profitably discussed in connection with the ca reer of John D. Roberts. Roberts took his B.S. and Ph.D. at the Uni versity of California, Los Angeles, the latter with W. G. Young, who was a Ph.D. student of Lucas at Caltech. Roberts thus represents the West Coast schools of physical organic chemistry, which developed very strong groups at UCLA, Cal tech, Berkeley, and elsewhere. Rob erts, after a year at Harvard with Bartlett as research fellow, spent a very productive period (1946-53) at MIT before returning to Caltech. Roberts combines synthetic skill
John D. Roberts
with a thorough command of chem ical kinetics. He is a bold and origi nal experimenter, with a flair for detecting and developing new tech niques and instrumentation (11). He was one of the first organic chemists to apply 14C to mechanis tic studies; at MIT he studied isomerizations of 14C alkyl halides by aluminum chloride. He investigated the preparation and reactions, in cluding solvolysis, of 3- and 4-membered ring compounds, coining in the process the term "nonclassical carbonium ion" (12). Some of Roberts' best work at MIT showed that the transmission of electronic effects through "space," or through saturated car bon chains, as in substituted 2,2,2bicyclooctanecarboxylic acids, was as effective as through an aromatic ring. Another major discovery was the demonstration that a strong base with aryl halides eliminated HX to form a symmetrical interme diate or "benzyne," an aromatic ring with a "triple bond" in it. This was proved conclusively by 14C tracer studies. Roberts was probably the first or ganic chemist to work actively with nuclear magnetic resonance and to comprehend its almost limitless potentialities for structure determi nation and for measuring reaction rates, such as proton shifts and rates of rotation around single bonds. He pioneered XH NMR, and later at Caltech developed 13C and 15 N NMR into an important tech nique for organic chemists. The whole field of NMR, including 19 F and 3 1 P, has expanded into a disci pline of its own, with its own jour nals and reviews. The use of NMR in studying the "pseudorotation" of phosphorus compounds by Frank H. Westheimer, in determining the purity of optically active com pounds by William H. Pirkle, and in establishing aromatic character in ring systems by Virgil Boekelheide, merely illustrates the versa tility of the technique. Although Roberts was not directly responsi ble for all of this, he played a major role as a catalyst in NMR studies. I cannot discuss in similar detail the contributions to physical organ ic chemistry of Bartlett, Ronald Breslow, Cope, Donald J. Cram, Er nest L. Eliel, Kurt Wislow, Andrew Streitwieser, Westheimer, Winstein, and others. I also shall forgo an account of organic photochemis try, which has, like NMR, become a field by itself (13), and will only mention the names of Ο. Ε. Chap man, William G. Dauben, George S. Hammond, Peter A. Leermakers, Nicholas J. Turro, Peter J. Wagner,
Ν. Yang, and Howard Ε. Zimmer man as among the leaders.
*
