2.1 Overview of Ingold's accomplishments

Sir Christopher K. Ingold was one of the senior founders of modern POC, though elements of POC go back to the 19th century, for example, to Nikolai Menshutkin's studies on the effect of structure (added substitutions) on ester hydrolysis and alkylation of amines.¹² Ingold's scientific prowess was very early recognized, of course by the number and quality of his publications (Figure 2). Ingold's productive career embraced both pre-World War II and post-World War II periods. While he is most remembered for contributions made in the first half of his career, it would be a mistake to underestimate the importance of his publications in the second half.

Not unexpectedly, there seems to be some shift in Ingold's research focus after 1942, as illustrated in the two-word clouds shown in Figure 3.

Ingold provided the experimental evidence and hence the mechanisms of nucleophilic substitution reactions (S_N1 and S_N2), which were also studied extensively and named by him.¹⁴ He had a hand in unraveling the mechanistic differences between unimolecular and bimolecular elimination reactions, E1 versus E2 reactions, again using Ingold's terminology.¹⁴ Independent from Linus Pauling, Ingold developed the concept of “mesomerism”¹⁵ to explain the special stability of aromatic compounds and “resonance-stabilized” transition states; Pauling called it “resonance.”¹⁶ Also independently, or perhaps not so independently (according to Sir Robert Robinson^17-21), Ingold devised the electronic theory of aromatic substitution.²² These discoveries are so fundamental to organic chemistry that they are among the first reactions studied by students in introductory chemistry courses.

Going beyond individual reaction mechanisms, as important as that science is, Ingold made contributions to all of chemistry.^{15, 17-19, 23-28} We cite two examples of Ingold's range of interests and seminal contributions to POC.

First, in 1946, Ingold and his colleagues published a series of 11 consecutive publications in the Journal of the Chemical Society comprising 112 pages establishing the hexagonal structure of benzene.^29-39 As mentioned above, Ingold was an author of only seven of these publications, but clearly his hand was active and central to all 11. In these studies, Ingold and his colleagues synthesized a series of deuterated benzenes and analyzed their infrared and Raman spectra, and “the structure of benzene, which had begun in 1865 by Kekulé, was finally solved in its entirety.”¹⁹

Second, much later in Ingold's career, a collaboration with R. S. Cahn and Vladimir Prelog led to the CIP R,S-rules for unambiguous nomenclature of chiral molecules.⁴⁰ Ingold also proposed the term “synartetic”^{18, 28} for rate accelerations that later would be termed—more successfully—“anchimeric” acceleration or assistance. His 1951 book Structure and Mechanism in Organic Chemistry¹⁴ “became the bible of a new generation of organic chemists” in the 1950s.⁶

We add that one philosopher of chemistry wrote about what he called “The Ingold Revolution in Organic Chemistry.”⁴¹

Figure 4 illustrates the citations to Ingold's publications from 1915 to 1969. Clearly, Ingold's publications had a significant impact on the research community. During these time periods, Ingold's publications were cited ~6500 times. In summary, it would be fair to say: Ingold was the premier leader in POC from the 1920s to the 1960s.

2.2 Ingold's school of Physical Organic Chemistry

Ingold's school was based mostly within the foundation Ingold laid for POC (its kinetics and mechanisms) as well as its nomenclature (that is taught to every first-year organic chemistry student). True, a number of his students became eminent scholars and researchers, for example, Peter de la Mare, Ronald S. Nyholm, Saul Patai, and C. W. Shoppee. Nonetheless, it was Ingold's own research achievements and his organization and nomenclature of the mechanisms of POC that are his legacy. And we ought not to forget the Cahn–Ingold–Prelog (CIP) system or sequence of priority rules to denote configuration.

2.3 On Ingold's nonexistent Nobel Prize

Why was it that Ingold never received a Nobel Prize? There are several possibilities that we will now consider. It could be any of these, or another, or most likely some combination.

First, perhaps he was not nominated, or not nominated frequently enough, or not nominated by sufficiently eminent scientists.

The Nobel Prize Nomination Archive incorporates a 50-year information blackout and was first made available in 1974,⁴² though little used until much more recently.^{5, 43-46} Speculations as to why Ingold was never selected for the NPch by Nobelist Derek H. R. Barton^{24, 47} (NP 1969) and others were often made in the absence of any idea as to the enormous volume of Ingold's nominations. We now know that during the period 1940–1970, Ingold received 112 nominations from 77 different individuals who lived in 22 different countries (Table 1). Of these 112 nominations, 13 different Nobel laureates nominated Winstein, several doing so on multiple occasions (Hans K. von Euler-Chelpin, NPch in 1929; Vladimir Prelog, NPch 1975; Tadeus Reichstein, NPphy/med 1950; Leopold Ruzicka, NPch 1939; and Sir Cyril Hinshelwood, NPch 1956). Table 1 also reveals a significant nationality-oriented bias. Table 2 reveals that among the non-recipients of the NPch, Ingold's 112 nominations from 77 different nominators far exceeded that of all other unsuccessful nominees. The closest to Ingold was Walter Rappe with 64 nominations from 34 different nominators.

Ingold's nomination chronology continued into the year after he died; in fact, it accelerated in his later years (Figure 5). That Ingold received 16 nominations in 1969, the year before he died, was certainly a message delivered to the Academy—a message that was ignored. Ingold's overall nomination chronology was marked with an interesting and certainly not random up-down-up sequence in the mid and late 1960s. This feature is observed in the nomination chronologies of other NPch nominees and suggests some type of organized behavior.⁴⁸ Clearly, possibility #1 is discredited.

Second, perhaps Ingold's achievements were judged insufficient for a Nobel Prize by the Nobel Committee for Chemistry and/or the Royal Swedish Academy of Sciences (the “Academy”). The recipient of many awards, Ingold was elected a Fellow of the Royal Society (FRS) in 1924, at the extraordinarily early age of 30. Judging scientific accomplishments—especially prior to bibliographic analyses, and even with bibliographic analysis—is a momentous task.

Admittedly, comparing the achievements of individuals at the highest level is even more difficult. But that is what the Nobel Committee for Chemistry and the Academy have been doing since 1901. The Nobel Committee for Chemistry had (and has) the luxury of enlisting the assistance from the entire membership of the Royal Swedish Academy of Sciences and, even more impressively, from the entire body of scientists worldwide—to serve as consultants to the Committee. Ingold's enormous nomination record clearly demonstrates that the well-placed chemists, all selected by the Nobel Committee to serve as nominators and for their advice and recommendations, had judged Ingold's achievements and impact to be at the highest level within their community. Clearly, possibility #2 is discredited.

Third, perhaps Ingold was always the “bridesmaid” and never the “bride” when compared to pressing nominations of other well-deserving candidates. That is, perhaps Ingold was consistently judged as being less deserving than those chosen for the NPch. But if the Nobel Committee sincerely wanted to award Ingold the Prize, they could have awarded the 1956 Nobel Prize jointly with Sir Cyril Hinshelwood and Nikolay Semenov who were laureated “for their researches into the mechanism of chemical reactions.” That is exactly what Ingold also achieved, though from a physical organic chemical perspective rather than a physical chemistry perspective. Or they could have broadened the 1961 Nobel Prize received solely by Melvin Calvin “for his research on the carbon dioxide assimilation in plants.” Calvin actually determined the mechanism of biochemical reactions; the citation could have been for “the mechanism of chemical and biochemical reactions.” In other words, the argument that there was too much competition, that there were “no available slots” for Ingold falls flat. Possibility #3 is discredited.

Fourth, perhaps not awarding the NPch to Ingold was an “error and oversight of the Nobel Prize Committee.” Much has been written on errors and oversights of the Royal Swedish Academy of Sciences and the Nobel Prize.^{6, 15, 17-20, 23-25, 28, 41, 47, 49-52} Errors and oversights, unfortunate as they are, do happen. But in the face of 112 nominations over a 31-year period for Ingold, simple errors and oversights do not happen to organizations as astute as the Royal Swedish Academy of Sciences and their Nobel Committee for Chemistry. Intentionality happens. Possibility #4 is discredited.

We simply do not believe any of the previous four reasons are viable. Ingold's chemistry was deserving of an NPch. Ingold received more than enough nominations from more than enough eminent chemists to justify an NPch. There were several opportunities, over the years, for the Royal Swedish Academy of Sciences to have Ingold jointly share a Nobel Prize “slot” such that no other deserving candidate would have been excluded. The Nobel Committee for Chemistry is such a deliberate body, they do not make careless errors or oversights. They are strategic and deep thinkers.

There are three other explanations that may have relevance.

First, as Friedman has discussed,³ the NPch in the 1930s and 1940s and into the 1950s were heavily influenced by German chemists, though the latter years brought more Americans into the NPch fold. Ingold had four nominations from Germans; Robinson, not a single German nominated him (see Table 1). Woodward had nominations from nine Germans.

Second, perhaps the Nobel Committee for Chemistry was not particularly disposed to favor an award in POC. An examination of the list of NPch laureates reveals no fully physical organic laureate until perhaps Vladimir Prelog in 1975. True, other laureates contributed to POC, for example, Robinson with his electronic theory of organic chemistry; Barton with conformational analysis; even Calvin, with the mechanism of photosynthesis. But few would classify these chemists as physical organic chemists.

Perhaps Robinson was able to indirectly (or not so indirectly) influence the Nobel Committee for Chemistry to believe that Ingold's greatest achievement—the electronic theory of organic chemistry—was actually Robinson's achievement.

We wonder, was Robinson so powerful? Is there any collaborative evidence to support the hypothesis of Robinson's influence on the selection of Nobel Prizes in Chemistry? Table 3 provides a partial and indirect answer. Robinson nominated nine individuals for the NPch (not counting Winstein, who died prematurely); seven of them became Nobel laureates. If Robinson was so influential in securing an NPch for his nominees, could he be so influential in the opposite?

2.4 Summary

We believe that the major cause for Ingold's lack of a Nobel Prize was the spite of Robinson. And we have one other supporting explanation, and that involves Saul Winstein. We shall discuss that other explanation below.

We understand that our conclusion is speculative, just as many are explanations (or mechanisms) in “hard chemistry” speculative, when complete data are unavailable. We justify our analysis because we examined many possible explanations (in chemistry, many possible hypotheses) and were led by the available evidence.

3.1 Overview of Winstein's accomplishments

Ingold shared the distinction of being one of the “early-era” pioneers of modern POC. Saul Winstein was a “later-era pioneer” of modern POC (Figure 1). Winstein, a generation younger than Ingold, was his successor and the enhancer in transforming POC into the modern era. Ingold was most active in the 1920–1950 time period and Winstein from 1945 to 1970 time period though they did somewhat overlap in the 1950s (Figure 4).

We can add to the concepts named by Streitwieser the following: homoconjugation, solvent separated ion pairs, normal and special salt effects, common rate depression, external return, and homoallylic, homobenzylic, and homoconjugative participation.^{8, 62-66} And there is more: the Grunwald–Winstein equation,^{67, 68} which provides the linear free energy relationship between relative rate constants and the ionizing power of various solvent systems^{67, 69}; the Winstein–Kosower⁷⁰/Goering–Schewene⁷¹ diagrams, which illustrate the relationship between activation energies (kinetics) and equilibrium distributions (thermodynamics); and the Winstein–Holness equation, which provides the total reaction rate constant for a compound existing in multiple conformations, each of which reacted to give a different product.^{72, 73}

While the term “nonclassical ions” was actually first proposed by John D. Roberts,⁷⁴ it was Winstein who is most associated with establishing the validity and usefulness of this term. And this is just a partial listing of Winstein's accomplishments, achieved before his premature death at 57 years 2 months.^{62, 64, 65, 75-78} The word cloud extracted from the titles of Winstein's publications (Figure 6) reveals few direct overlaps in interests with Ingold (Figure 3). For Winstein, major topics include solvolysis, neighboring group(s) effects and participation, replacement reactions, acetolysis and solvolysis ions, [ion] pairs, and so forth. Indeed, there is a developing pattern that progresses from Ingold's pre- and post-1942 word clouds to Winstein's word cloud, a marker in the development of the discipline.

Returning to Figure 4, we note that citations to Winstein's publications exceeded Ingold's in number but also in its rate of acceleration. No doubt that number would have continued to increase substantially had Winstein not died in 1969. Indeed, his list of publications increased by 21 in 1971 (Figure 1), 2 years after his death. These were undoubtedly due to his students, who were publishing their results. Surely Winstein's impact on chemistry would have continued. At his death, he was at the height of his scientific productivity and influence.

Barton was no minor figure in organic chemistry. And he was certainly being poetically modest. Nonetheless, Barton placed Winstein in the same scientific hierarchy as Robinson and Woodward. We have one more datapoint provided by Barton. On November 12, 1969, Winstein received an undated handwritten letter from Barton. Barton was undoubtedly responding to a letter of congratulations Winstein had sent Barton on the occasion of the announcement that Barton would receive the NPch in December 1969 (Figure 7).

Ironically, Winstein was dead within a week of receiving Barton's letter, having suffered a massive heart attack while swimming in the pool at his home.

By the time of his death, Winstein had already garnered numerous awards, including the ACS Award in Pure Chemistry (1948), election to the National Academy of Sciences (1955), Richards Medal of the ACS (1962), election to the American Academy of Arts and Sciences (1966), ACS James Flack Norris Award in Physical Organic Chemistry (1967), and the Franklin Memorial Award for Outstanding Contributions to Chemistry (1968). He was awarded the US National Medal of Science posthumously in 1971 by President Richard M. Nixon.

3.2 The Winstein school of Physical Organic Chemistry

Saul Winstein was a well-liked and much-admired chemist's chemist.^{9, 54, 63, 64} It did him no harm to be on the opposite side of the nonclassical carbocation debate with H. C. Brown who was not much loved by his peer group.^{54, 80} It can well be said that Winstein's way of doing science spread out after him like the waves of a speeding boat, and not just by his many former students and postdoctoral associates of whom there were many. According to Donald J. Cram and William G. Young, Winstein had 72 Ph.D. students and 86 postdoctoral fellows, about 100 obtaining academic positions (Table 4).^{64, 75} Many of these continued Winstein's tradition as physical organic chemists or applied POC in their research in other subdisciplines of chemistry. For example, Dale Poulter at Utah investigated the isoprene biosynthetic pathway with emphasis on the mechanisms of the enzyme-catalyzed transformations. Winstein's approach to POC clearly seeped into Poulter's biosynthetic research program.^81-85

3.3 On Winstein's nonexistent Nobel Prize

According to the Nobel Prize Nomination Archive, Winstein received 24 nominations over 6 years, 22 of which came in the last 3 years of his life (Table 5). While Winstein's 24 nominations certainly did not compete with Ingold's numbers (over many more years), 24 is on par with or far greater than the number of nominations received by other laureates, for example, Sanger (NPch in 1958, 17), Libby (1960, 28), Calvin (1961, 22), Kendrew (1962, 10), Perutz (NP 1963, 13), Hodgkin (1964, 24), Mulliken (1966, 23), Eigen (1967, 31), Norrish (1967, 8), Porter (1967, 13), and Hassel (1968, 18). And with time, Winstein's number of nominations certainly would have increased substantially—just as his number of publications and citations to his publications were rising (Figures 2 and 4, respectively).

Any effort to compare Winstein's number of nominations with that of other nominees is hampered by the fact that Winstein's premature death limited the number of years he could have been nominated. To circumvent this limitation, we compared Winstein's number of nominations in three consecutive years with several Nobel laureates. (Why might this triplet be a marker for Nobel success? Because of Winstein's premature death at 57 years old, the total number of nominations is an unfair predictor. We thus considered taking the maximum value, for each nominee, of the sum of a few consecutive years as a predictor.) As can be seen in Table 6, Winstein's 22 nominations within three consecutive years almost reaches the top 10 for Nobel laureates and is second (with Reppe) only to Ingold among all non-recipients.

We also note that the number of Winstein's nominations went from a high of 10 in 1967 to seven in 1968 and five in 1969. Analysis of the Nobel Prize Archive for chemistry has revealed many instances of a chronological trend “high, then low, then high again.”⁴⁸ For example, in the same time period, from 1958 to 1965, Woodward's nomination record was 5, 7, 12, 14, 6, 19, 7, and 18 (NPch in 1965). Heyrovsky's record from 1954 to 1959 was 1, 1, 12, 4, 1, and 11 (NPch in 1959). There is every reason to believe that Winstein's future number of nominations would have increased substantially from the five he received in 1969, that is, 12, 7, 5, ???, interrupted by Winstein's death in 1969.

The main purpose of preparing Table 6 was to examine Winstein's nomination record against other nominees while controlling for his premature death and thus lessoned opportunities for receiving the NPch. Nonetheless, Table 6 provides some interesting observations. Most of the Nobel laureates received their highest number of nominations (in this sequence) in the year of their award. Nernst received 22 nominations the year following his Nobel Prize; that is odd. Georg Wittig's sequence of high nominations was a decade before his NPch. And Pauling appears twice on this list.

It is worth pointing out that the chemical community understood the pairing of Ingold and Winstein as the premier physical organic chemists of the 20th century. In 1967, Rolf Huisgen, Costin Neniţescu, and Yeshayau Pocker each nominated both Ingold and Winstein; Pocker also nominated Louis Plack Hammett. In 1969, both Stanley J. Christol and Paul von R. Schleyer nominated Ingold and Winstein. Within this small sample, it is clear that several nominators envisioned a joint Ingold–Winstein Nobel Prize.

Of note is the fact that Robinson was one of Winstein's nominators.

Returning to Barton's letter (Figure 7), it is also interesting to note that, up to and including 1969, Barton made only five nominations for the NPch, three for R. B. Woodward, and two for Carl Djerassi (Table 7). It is noteworthy that despite his complimentary and even promising letter to Winstein (Figure 7), Barton himself had not nominated Winstein. Rather, in 1969, Barton nominated another academic also from a California university, Carl Djerassi (Stanford).

Barton's behavior seems to be artfully political. But perhaps Barton had been informed via the grapevine⁸⁷ that Winstein's year was coming shortly and felt it was unnecessary to nominate him again. It should be noted that Barton was a major “player” within the chemistry community, in addition to his being a Nobel laureate. For example, Barton was the Chair of Pergamon Press, the publisher of Tetrahedron and Tetrahedron Letters, then the premier international organic chemistry journals.