Bull. Hist. Chem. 19 (1996) 77
A PERSONAL HISTORY OF THE BENZIDINE REARRANGEMENT
nr . Sh n , x h Un v r t
What I have to say today amounts more to a personal pounds) and which I had been studying with E. E. Turner account rather than an honest-to-goodness history of the at Bedford College in London during the years benzidine rearrangements. Interest in the mechanism of 1945-1947. My arrangement with Henry Gilman broke these rearrangements spans this century from the early up in the fall, 1948, and I became an independent re- 1900s to the present day. Prominent in studies of the search associate supported by the Department of Chem- rearrangements and their mechanisms during these istry. In return for that support, I became an instructor ninety years is the name of the man whose memory we of a quiz section in sophomore organic chemistry when honor today, C. K. Ingold, associated also with his the section's graduate-student instructor left Ames on long-time colleague and collaborator E. D. Hughes and short notice. During one of the quiz-section periods a their younger coworker Derek Banthorpe. Also promi- student asked how the benzidine rearrangement, men- nent in these studies are the names of Paul Jacobson, tioned only briefly in his book, occurred (Eq. 1) this Michael Dewar, Robert Carlin, Miroslav Vecera, and equation shows two products, as is correct. George Hammond and me. I don't know how or why Carlin and Vecera took up the benzidine rearrangements. Carlin, of course, was much interested in the Fischer indole reaction, and that is connected with benzidine rearrangements, as you know. Possibly, that's how the rearrangements snared his interest. I would guess that Ingold's attraction and that of Dewar developed from their much broader interests in the electronic theories of organic reactions and the mechanisms of all molecular The student's book would have shown only the major rearrangements. As for me and George Hammond, our product, benzidine, 2). Of course, I had no idea, at all. interest in benzidine rearrangements was quite un- George Hammond had joined Iowa State College in the planned and entirely accidental. This is how it happened. fall, 1948, bringing to the Department a wonderful fresh- In early 1948 I went to Iowa State College as a ness and vigor in organic chemistry. I felt sure that postdoctoral fellow with Henry Gilman. I went there George would know the answer to the benzidine ques- with an arrangement, that I had proposed, to study un- tion and promised the student that I would find the an- der his guidance the mechanism of Grignard reactions, swer for him. It turned out that Hammond knew no more particularly those which I called anomalous (enoliza- than I about the rearrangement, and he suggested that I tion, condensation, and reduction of carbonyl corn- search it out in the 1iterature and report on it at one of
.1441, 78 Bull. Hist. Chem. (1996)
the Tuesday evening seminars he had started after arriv- First, it is time to turn to Ingold. The bulk of ing at Ames. I don't remember if I ever did answer the Ingold's experimental work on the benzidine rearrange- student's question, but it was responsible for 1eading me ment was published in the early 1960s. In that period. and Hammond into parts of our life-long research com- with his collaborators, Hughes and Banthorpe, he was mitments. Search of the literature turned up Dewar's it- intimately concerned with the kinetics and the effect of complex theory of the rearrangement and the earlier of acidity and hydrazoarene structure on them. We must his two experimental works in it(1). Hammond noticed go back to 1933, however, for Ingold's first publica- that in that work Dewar had assumed, but not verified, a tion of experimental work on the benzidine rearrange- first-order dependence on acid, and recommended that ment, and we shall see the very curious lapse in his I should check it out myself. At the time, I was devoted attention to the kinetics between that time and the 1960s. to studying anomalous Grignard reactions, measuring In 1933 Ingold and Kidd published their proof of the quantities of gaseous alkenes and alkanes they gave the intramolecularity of the benzidine rearrangement. rise to, and trying to tie them to a mechanism of reac- Their proof lay in rearranging a mixture of two similar tion(2). I knew nothing then about electron-transfer, radi- hydrazobenzenes, 2,2'-dimethoxy- (4 and cal ions, and esr, so the task I had set myself of solving 2,2'-diethoxyhydrazobenzene (4b and showing that the mechanism of Grignard reactions was, in fact, close only and b were formed; that is, a crossed benzi- to hopeless; but I didn't know it. Nevertheless, I accepted dine product was not obtained (Eq. 2)(3). Hammond's challenge to repeat Dewar's work on hydrazobenzene. Fortunately, Dewar had discovered the clever use of Bindschedler's Green and titanous chlo- ride in titrating hydrazo compounds, so it didn't take me long to learn how to measure the rate of disappear- ance of hydrazobenzene. The work was finished in two or three months, and I remember telephoning Hammond at home on a Sunday morning, after all of the acid-dependence had been plotted out, to tell him: Evidence for intramolecularity was already available "George, it's second order." Hammond's reply was: "I'll among the many examples of rearrangement of unsym- be over soon." Neither of us, I believe, had any idea that metrical hydrazobenzenes in Jacobson's tabulations(4). our work would keep us busy, separately, for years, or Ingold acknowledged this, but felt that the better test that it would trigger a new interest by Ingold. I am not would be with symmetrical hydrazobenzenes, such as certain of that triggering, in fact; but experimental work 4 and 4b, which, in the understanding of the time, could on the rearrangement seems to have begun again in not separate into halves of different polarity, and thus Ingold's laboratory in the mid 1950s after a lapse of 20 bias recombination, a possible flaw he saw in Jacobson's years. Certainly, Hammond and I were unaware that examples. An important criterion of the mixed rear- Carlin was already at work (at Carnegie Tech in Pitts- rangement test was that the chosen compounds should burgh), measuring rates of rearrangement with the more rearrange at similar rates. Under the conditions chosen laborious but informative spectroscopic analysis of re- by Ingold and Kidd for rearranging 4 and 4b, the rates actant and product concentrations. Carlin's very nice were too fast to be measured, so that the method was work not only confirmed my finding of second-order used of measuring the amount of product each gave acid-dependence for hydrazobenzene, but also disclosed within a specified time. In that way 4 was found to the mixed first- and second-order acid kinetics for rearrange about six times faster than 4b. Here we find o-hydrazotoluene, a key finding that was used later by the enigma, which unfortunately can never now be Ingold in establishing the foundations of further under- solved, of how Ingold overlooked in later years what standing. Hammond continued work on acid-catalyzed appears to have been known to him about benzidine benzidine rearrangements for some years at Iowa State kinetics in 1933.1n the paper of 1933, and in comment- and, later, at Caltech. I left the work on departing Ames ing on the need to know the relative rates of rearrange- and going, (coincidentally, and before Hammond), to ment of 4 and 4b, Ingold wrote(5): Caltech in 1949 for postdoctoral work with Carl Measurements indicating the speeds of benzidine Niemann on kinetics of chymotrypsin-catalyzed ester conversion have been recorded by Holleman and van hydrolysis. I had no thought at all of ever returning to Loon (Proc. K. Akad. Wetensch. Amsterdam 1903, the benzidine reaction. How that happened is told later 6 262)" and by Biilmann and Blom (J., 1924, 125, in this story. Bull. Hist. Chem. (1996) 79
1719), but under conditions corresponding to those sents the kinetic method in great detail (quantitative as- of our experiments on simultaneous isomerization, it say of 2, with time, as its dihydrogen sulfate) and under was not possible to obtain satisfactory direct mea- a variety of conditions, and ends again with the kinetic surements of velocity, owing to the rapidity of the equation, Éq. 3. It seems extraordinary that Ingold could reactions. have overlooked this. Further, van Loon was quite ex- Now, the attempts by Biilmann and Blom to correlate plicit about the mononuclear amine. It was obtained rates and acidity failed(7). But, Holleman and van Loon along with azobenene, but only when rearrangment of were explicit about the dependence on acidity in the hydrazobenzene was carried out at elevated tempera- formation of benzidine (2) from hydrazobenzene (1), tures and in relatively concentrated acid. van Loon rec- and said so with their Eq. 3 (modified slightly here): ognized that the formation of azobenene meant that aniline should be formed. He went on to isolate it, gave k[HCl]d[2]/dt(3)2 = (3) Furthermore, they included a drawing of the disproportionation reaction for its formation, and N,N'-diprotonated hydrazobenzene, leaving no question characterized it as its derivative benzanilide(9). as to how these earliest of kinetic ists saw the catalysis How could Ingold have glossed over van Loon's of rearrangement(6). It is possible that Ingold and Kidd work? We shall never be able to answer that question. overlooked the significance of these findings because Could he have relied on the reading by the less experi- they were very much more concerned with products. A enced Kidd? The question haunts us because of how second criterion for a successful mixture experiment was Ingold wrote eight years later about the role of acid in that the rearrangements be uncomplicated. Éach com- the benzidine rearrangement. I refer here to the paper ponent must give only a benzidine and none of the other by Hughes and Ingold on the "Theory of Aromatic Sub- possibilities in the family of products. Rearrangements stituents and Rearrangements with Special Reference of 4a and 4b satisfied that criterion, except that each to the Benzidine Change"(10). This paper is concerned also disproportionated. It was, in fact, the disproportion- particularly with the difference between Robinson's and ation and a way of avoiding its complications that led Ingold's views of the rearrangement and may well have Ingold and Kidd to choose the conditions of rearrange- been written in response to Robinson's sudden (appar- ment, the conditions that prevented them from measur- ently), awakened interest in the benzidine ing rates directly. That is, rearrangement of a mixture of rearrangemen(11). Robinson represented rearrange- 4a and 4b was carried out in dry ethanol containing hy- ment with a flow of electrons in protonated drogen chloride. Addition of dry ether to the solution hydrazobenzene(11). Ingold, however, went to great after rearrangement precipitated the hydrochlorides of pains to distance himself from the idea that protonation the two benzidines but left the disproportionation prod- preceded N-N bond scission. He and Hughes said (2): ucts in solution, thus effecting the clean separation de- We may collect these points as follows: (a) A nearby sired. The fact that disproportionation occurred im- proton (at least one) disturbs the electronic system pressed Ingold and Kidd. They noted that(5): of the benzidine (sic) molecule; (b) therefore, this proton (at least) is present in the transition state; that We know of no previous record of this reaction, al- is to say, its coordinates enter into the specification though van Loon ( . r . Ch ., 1904, 2 , 162) of the state; (c) but its covalent bonding with nitro- observed the formation of a mononuclear amine from gen does not precede the N-N heterolysis. a hydrazo-compound in the absence of an external reducing agent. In the same paper, Hughes and Ingold present drawings of electronic structures that could represent states be- Here, we find the second part of the enigma: The paper tween hydrazobenzene and benzidine, and they say of that Ingold and Kidd refer to is, in fact, one in Recueil these structures (Scheme 1)(13): by Lobry de Bruyn and Wolff(8) on Tyndall effects. van Loon's paper occurs earlier in the issue(9), and while he As we do not know yet whether one or two adding does indeed report the formation of mononuclear amine, protons are included in this state (the p-benzidine tran- the emphasis of this paper is on the relative yields of sition state) we shall omit them ... bcnzidine (2) and diphenyline (3) obtained from 1 and It is hard to understand how Ingold could say this eight on the rearrangement's kinetic order in acid. van Loon's years after having referred(3) to van Loon's papers. No paper is,in fact, the detailed report of the work described mention is made of these papers in the analysis by briefly earlier in the Proceedings(6), to which Ingold Hughes and Ingold(10). and Kidd also referred(3). van Loon's full paper(9) pre- 80 Bull. Hist. Chem. 19 (1996)
reactions. in view of this it is unnecessary to repeat the historical account.... In Jacobson's historical account van Loon's kinetic work is recorded but second-order acid dependence is not dis- closed. Jacobson's failure to state the kinetics of rear- rangement explicitly is another benzidine enigma. Pos- sibly, he neglected the specifics of the kinetics because It I seem to dwell at unseeming length on van Loon's of his lack of kinetics training to which he refers. Cer- papers, it is not for the purpose of uncovering a flaw in tainly, had Jacobson dwelt on the kinetics and their mean- Ingold's benzidine work, but to set the following his- ing, the history of the rearrangements must have been torical point. None of the writers, not just Ingold, of the different. This is what Jacobson said(17): early years appears to have paid any attention to van Loon's second-order acid dependence. Had they done Ein weiterer Einblick—besonders auch in Bezug auf die Art, in welcher die als Hervorrufer der so, in fact, the history of the benzidine rearrangements Umlagerung wirkenden Säuren an dem Vorgang would certainly have taken a different turn, and it is cer- teilnehmen—dürfte in erster Linie durch tain, too, that neither Hammond nor I would have had reaktionskinetische Erforschung der Umlagerung zu any part in it. erwarten sein, auf die ich wegen Mangel an Zeit and It is remarkable that as early as 1918 the Robinsons Schulung verzichten musste. In dieser Richtung were writing about the mechanism of the benzidine re- liegen einstweilen (ref. 2) nur einige in Holleman's arrangement in connection with their interest in the Laboratorium durchgeführte Versuche von van Loon Fischer indole reaction and its role in their preparation (ref. 3) vor; aus ihnen wird der Schluss gezogen dass of tetraphenylpyrrole(14). They ruled out the possibil- die Geschwindigkeit, mit der verschiedenen Säuren die Umlagerung von Hydrazobenzol bewirken, durch ity, voiced occasionally at that time, that ihre Ionization bestimmt wird. p-aminodiphenylamine (i.e., p-semidine) was an inter- mediate in the formation of benzidine, by showing that If only Robinson had followed up Jacobson's lead, and p-semidine was unaffected by being heated with con- had found van Loon's paper, how different the history centrated hydrochloric acid. They fitted the mechanism would have been. of the benzidine rearrangement into a generalized It was left to Hughes and Ingold to call all of us to scheme covering other "enimic to enamic" rearrange- order by pointing out in 1952 that Hammond and I in ments without being specific about protonation. 1950 had only re-discovered what van Loon had reported I am not aware that Robinson engaged directly in in 1904(18). I remember feeling chagrined at reading any experimental work on the benzidine rearrangement. that 1952 review, because it made me feel that I had Yet, remarkably, his address as President of the Chemi- missed the boat in 1949, and that the more perceptive cal Society in 1941 was devoted largely to the mecha- English group had caught it in 1952. In fact, the failure nism(11). In that address he formulated the, now, curi- of Hammond and me to find van Loon's work indicates ous alternating flow of electrons, to which I referred how peripheral was our interest in the rearrangement in above, beginning with monoprotonated hydrazobenzene, 1949. I made no further literature search after finding from which Hughes and Ingold distanced themselves as Dewar's paper(1), relying on his account of the rear- noted above. Insofar as this history is concerned, rangement; and even after I took up benzidine chemis- Robinson's monoprotonation(15), which was continued try again in the late 1950s, I still failed to read the litera- by all writers up to 1950, is all the more remarkable, ture carefully, so that I was unaware until going over because he, like others, referred to Jacobson's exhaus- Ingold and Kidd much, much later that, in some way, tive summary without, apparently, reading or heeding Ingold himself had then missed the same boat. Strangely, its last paragraph. Robinson called attention to Carlin, a very careful experimenter, referred to van Jacobson's summary in the following way(16): Loon's work, not for its kinetic import but for informa- tion on products(l9). In turn, Dewar(20), in support of Paul Jacobson, who devoted a large part of his ex- his pi-complex theory of the rearrangement, referred to perimental work to the study of the benzidine and semidine transformations of substituted this information on van Loon's products in Carlin's pa- hydrazobenzenes has published a summary of every- per, but apparently did not check into van Loon's paper thing known on the subject in 1922 (Annalen, 428, itself. The consequences for the pi-complex theory, based 76) together with a discussion of the course of the therefore on monoprotonated hydrazoarenes, were se- Bull. Hist. Chem. ( 6 81
vere. That story has been recounted elsewhere and need which more is said later), the types of products formed. not be retold here(21). This, then, was the end of Ingold's search for an answer Between 1933 and 1957(22) Ingold published no to the mechanism of the benzidine rearrangements; that experimental work on the benzidine rearrangement. is, the establishment of the PTS theory. Further experi- During those years appeared an outpouring of papers mental work continued at UCL but mainly in the hands on mechanistic organic chemistry, particularly on nu- of Derek Banthorpe. In all, the series reached to Part cleophilic substitution, elimination, and aromatic sub- XXVII in 1973(24). Ingold's participation in the last stitution, especially nitration. Interest in the benzidine papers was small, there being three papers bearing his rearrangement appears to have been peripheral until its name, in 1967(25) and 1968(26). It is sobering to rec- grand resurgence in the early 1960s. The paper in 1957, ognize that the benzidine papers were published when bearing also the name (C.A.Bunton) of one of the con- Ingold was in his 70s and after he had offically retired tributors to this Symposium, established the relation- in 1961. Ingold and I were corresponding about the re- ship between rate of rearrangement and acidity func- arrangements in 1967. On June 20 of that year he tion. It established also that acid catalysis was specific wrote(27): rather than general. This paper, then, was the forerun- When I wrote the other day, ner of the series of 15 experimental papers in the Jour- I had not seen Banthorpe (who is largely concerned with biosynthetic work nal of the Chemical Society spanning the years now-a-days)(28) and did not know (or had forgot- 1962-1964, that were to follow from the group of ten) that, during the year in which I have been with- Hughes, Ingold, Banthorpe, and coworkers. These pa- drawn from the benzidine problem, he has been go- pers reported the detailed kinetics and product studies ing on with it we have more rate-product studies of rearrangements of a variety of hydrazoarenes, cho- than I told you of .... I don't think the new data alter sen so as to illustrate the scope in kinetics in benzidine my general appraisal of the position, as I wrote it in rearrangements, then being uncovered at UCL. The UCL my letter (June 7). But as the area of consistency is group was primed by Carlin's discovery of mixed order larger than I thought it was, I feel rather more assur- (1.6) acid catalysis to show that some hydrazoarenes ance than I did. rearranged under second-order acid catalysis (e.g., Thus, the benzidine story for Ingold came to an end es- hydrazobenzene) and some by first-order catalysis (e.g., sentially in 1964 with the PTS theory, in his 71st 1,1'-hydrazonaphthalene), while others could exhibit year(29). both orders, depending on the acidity of the solution. In July, 1963, the IUPAC meeting on Pure and Ap- The UCL group found the solvent, ring-deuterium iso- plied Chemistry was held in London. I had been look- tope, and salt effects that characterized the course of ing forward to seeing the UCL group and talking about protonation at nitrogen and the polar nature of the tran- the rearrangements; but Hughes died in June, 1963, sition state in rearrangement. Discovering the duality of Banthorpe was on holiday while the IUPAC meeting was acid catalysis must have been particularly pleasing to on, and Ingold's time was sought by many international Ingold in that it resembled an earlier duality in mecha- visitors. At a pub lunch, our only meeting, he asked, nistic pathways he had discovered, namely the S 1/S 2 "What is the remaining question to be answered in ben- and E1/E2 reactions. The series of investigations in- zidine rearrangements?" Éven after 20 years I was still cluded thermal rearrangements, whose kinetics I had somewhat intimidated by the residue of awe inculcated studied myself a little earlier and to which I refer later. in me in my two undergraduate years at Aberystwyth(30) The series represented the completion of the develop- and sensed that Ingold was asking a question to which ment of the polar-transition-state (PTS) theory of rear- he already had an answer. My answer was pragmatic: to rangement, the beginnings of which can be seen in the find how disproportionation fitted with rearrangement. paper by Hughes and Ingold in 1941(10). Part XV of His answer, which indeed he had had all along was: to the series, called "A Collective Discussion," is 37 pages know what the transition state was like. This was the long(23). It summarizes the results and meaning of the question he had posed at the "Symposium on The Tran- preceding parts in the series and is also an analysis of sition State" in Sheffield in April, 1962, at which he other theories and their shortcomings. The massive un- displayed his now famed drawing of a transition state dertaking was designed to support the PTS theory, show- hidden in the clouds (Fig. 1)(31). In the printed version ing how it accounted not only for ways in which sub- he wrote(32): stituents affected the kinetics of rearrangements, but also, with the exception of the p-semidine rearrangement (of
QC= 82 ll. t. Ch . ( 6
the UCL group had discovered. An important criterion was that both protons were in place in the transition state. Again, heterolysis was such that one half of the TS bore two positive charges and the other half had the charac- ter of a primary amine. In the PTS theory, product type (benzidine, diphenyline, semidine) was determined by the dispositions of polarity in the rings, the dispositions being affected by the placement and nature of substitu- ents. Examples of Ingold's TS drawings(23) are shown in Scheme 2(34).
r . Reproduction (with permission of the Royal Society of Chemistry) of Fig. 8, Ref. 31, showing Ingold's cloud over the transition state of the rearrangement of The PTS theory was the most comprehensive of all of hydrazobenzene. the theories that had appeared on the mechanism of the benzidine rearrangements. The earliest of theories pro- Fortified by these reminders of partly solved prob- posed, for example, by Tichwinsky(35) and by lems, let us now face an unsolved one, that of the Stieglitz(36) called for scission of the N-N bond into mechanism of the benzidine rearrangement, the tran- two fragments, either with or without prior protonation, sition states of which must be like nothing else in and the recombination of the fragments. This this world. intermolecularity was essentially disposed of by He summarized what was then known and outlined how Jacobson, who quoted thereto his 65 examples of rear- it could be explained with polar transition states. He rangement of unsymmetrical hydrazo compounds, not concluded(33): one of which had given evidence of crossed products(4). Jacobson came down on the side of intramolecular rear- I do not change my view that the problem of the tran- rangement without understanding fully how it occurred. sition state of the benzidine rearrangement is un- solved. I have offered certain tentative interpretations The formation of benzidine from hydrazobenzene was only in order to show how it may be possible to fit described by him as nothing more than an exchange re- known facts into a picture. To establish the unique action in which two para hydrogens changed place in- correctness of the picture is another matter. tramolecularly with a single bond. It is interesting to see Jacobson's diagram for this exchange and compare The unique correctness, from his point of view, became it with our modern representation of a sigmatropic shift. the PTS theory. According to the theory, the transition Jacobson represented the para hydrogens as migrating state of each rearrangement became polar by the het- to the nitrogen atoms at the time of forming the new erolysis of the N-N bond of the hydrazoarene. Heteroly- single bond. Analogously, the semidine rearrangement sis for first-order-acid cases was initiated by was represented as the intramolecular replacement of a monoprotonation at one of the nitrogen atoms and led para hydrogen by a phenylimino group, the hydrogen to two dissimilar halves of the PTS, one bearing posi- migrating at the same time to the second nitrogen atom. tive charge and the other being neutral. Which half bore The role of the acid was not explained, however, nor the charge depended on the relative basicities of the two was protonation shown. Jacobson was candid about his nitrogen atoms and the relative capabilities the rings had interpretation, moreover, acknowledging that the objec- to delocalize the charge. These relative conditions were tion could be raised that it was not a clarification but controlled by substituents in the rings. In only a rephrasing of the facts. It was this open appraisal second-order-acid cases the dominant role in causing of his position that he followed with his observation, heterolysis was attributed to the first of the two protons. that is quoted earlier, on the need for kinetics. Nevertheless, pre-equilibrium diprotonation was called Some years before Ingold's interest in the benzi- for by the solvent deuterium kinetic isotope effect and dine rearrangements was reawakened, a simple and very the acidity function dependence at high acidities, which clever explanation for them was given by Dewar. This Bull. Hist. Chem, 19 (1996) 83
came to be known as Dewar's pi-complex theory of the was irrelevant to consider the way in which the N-N rearrangement. It was first proposed in 1945(39) and bond cleaved (that is, homo- or heterolytically) because incorporated a year later in a general theory of a num- complexation via overlapping pi-orbitals accompanied ber of related rearrangements(20). The pi-complex cleavage. The essence of the Czech view, then, was in theory was initially very attractive. The basic idea of it opposition to the PTS theory, first in its view of was that the N-N bond of a protonated hydrazoarene two-proton catalysis and next in favor of one calling for broke heterolytically and led intramolecularly into a some intermediate complex. It was not that the group complex of the two halves, These could then rotate, de- had compelling new evidence to support an pending on their structure, to the conformation favoring intermediate-complex theory, but that it was, for them, product formation. Dewar's earliest presentation(39) of the better way of understanding the rearrangements. this idea is shown in Scheme 3. Here, then, a sort of plateau was reached in the years 1964-1966, in which the choice of PTS versus intermediate-complex theories became a matter of opin- ion. Dewar and Marchand put it aptly in 1965(42) in saying that kinetic evidence could throw no light on the nature of intermediates in the reactions. Now, the PTS and pi-complex theories had one thing in common, namely that each had one view and one only The theory assumed at the start that monoprotonated of all of the rearrangements. In the PTS case, all rear- hydrazobenzene rearranged(20,39), and this assumption rangements were one-step in type; that is, concerted in was maintained in Dewar's experimental work by his today's terminology. In contrast, the pi-complex theory failing to measure acid dependence in the rearrangements showed all rearrangements as being two-step in type; of hydrazobenzene itself and three other that is, a pi-complex was formed in a rate-determining hydrazobenzenes(1). The finding of second-order acid step and, after the appropriate rotational adjustment, dependence by Hammond and me in 1950(40), and a collapsed in a fast step to product. little later by Carlin(41) was bad news for the Distinction between these two possible pathways pi-complex theory. This was unfortunate, in a sense, because could not be made with any of the great body of experi- an intrinsically clever idea received the criticism due mental evidence that had so far been assembled. It was only to one of its faulty props. The story of the succes- made only later with work on heavy-atom kinetic iso- sion of flaws in parts of the theory has been described tope effects (KIE) at Texas Tech. I can finish this ac- already(21). The theory received a pummelling because count, then, by returning to where benzidine rearrange- of them but continued to be promulgated by Dewar af- ments and I parted company in 1949. ter being shorn of faults. As far as I can tell, the last of During 1949-1951 I had a postdoctoral fellowship Dewar's writings on the pi-complex theory of the benzi- with Carl Niemann at Caltech. Failing to get a teaching dine rearrangement was in 1965(42). position, I joined the research laboratories of the U. S. A major supporter of an intermediate-complex (pi- Rubber Co., in Passaic, NJ, in late 1951, and spent three or molecular) theory was Vecera, who published a sub- happy years there, until the fall, 1954. The urge to "do stantial amount of experimental work, initially on the my own thing" took me to the small and unknown Texas chromatographic analysis of products(43) and later on Technological College (now Texas Tech University) in the mechanism of rearrangement; but the sparse atten- September, 1954. The head of the (then) Chemistry and tion paid to his work by others does not reflect its wide Chemical Engineering Department, Joe Dennis, had scope. Possibly, the reason is that the publications were decided views on building a research and graduate de- mainly in Czech and in German. The last of the series partment. It was not a publish-or-perish department and of papers, published, this time in English(44), was aimed there was no such thing as tenure (that came later, and I specifically at expressing the difference of opinions and received tenure by "grandfathering"); but there was a conclusions the Czech group had from those of Ingold moral obligation to begin a research program. One of and his coworkers, which had been laid out in great de- my first efforts in this direction was to study the oxygen tail in the summary paper(23) mentioned earlier. The oxidation of alkenes in acetic anhydride that I had dis- Czech view was that the major driving force for rear- covered at U. S. Rubber(45). The reaction encompassed rangement was the cleavage of the N-N bond and the a Criegee rearrangement and that led me, at Texas Tech, resonance (delocalization) energy of the fragments. It to study the decomposition of acetyl peroxide in 84 Bull. Hist. Chem. 19 (1996)
cycloalkenes. Out of that came the discovery that, as had been carried out by starting with an azoarene and unstable as it may be, the acetoxy radical could be reducing it with metal and acid to the hydrazoarene, trapped by an alkene(46). At the same time I returned which then rearranged. Hammick and Munro tried to to the benzidine rearrangement and Jacobson's wonder- find whether p-semidine rearrangements could occur ful summary(4). In that summary Jacobson listed other without following that procedure, but unfortunately agents, beside mineral acid, that cause benzidine rear- chose a rather complicated case as the test, the rearrange- rangements; and I was struck by his reference of the, ment of p-ethoxyhydrazobenzene. The p-semidine prod- until then, sole observation of a rearrangement caused uct of that rearrangement is so sensitive to oxidation by heating with base. This was the work of that Hammick and Munro failed to isolate it and con- Meisemheimer and Witte, who had rearranged cluded, therefore, that it had not been formed, thus sup- 2,2'-hydrazonaphthalene by heating it in alcoholic so- porting the idea that a metal ion should have been used. dium hydroxide(47). A search of the literature showed, But, Charles Baldwin and Harvey Harris showed at however, that Krolik and Lukashevich had pinpointed Texas Tech, that, if handled properly, the rearrange- the rearrangement as being thermal and not in need of ments of p-ethoxy- and p-methoxyhydrazobenzene took the base(48). I decided then to begin studying the mecha- place in the absence of heavy-metal ions(55). Ingold nism of that rearrangement. My notebooks show that I and I corresponded about the p-semidine rearrangement. began the work on February 4, 1955, first with On May 22, 1967, I wrote about our work on the hydrazobenzene, whose study was fruitless, and next on p-ethoxy- and p-methoxy cases at Texas Tech(56): March 3 with 2,2'-hydrazonaphthalene in ethanol. The If the p-semidine rearrangement turns out to be a valid first-order kinetics were soon uncovered and led to fur- intramolecular acid-catalyzed one, for which assis- ther study with a series of solvents(49). Thereafter the tance by a metal ion is not needed, I would say that work was taken over by my first graduate students, John this rearrangement would best be interpreted as go- Trisler and Robert Snell(50). It was never my intention ing through an intermediate other than the common to return to acid-catalyzed rearrangements, because I was place ones. I do not see how the breaking of the N-N now becoming enmeshed in a new field for me, radical bond and formation of the p-C-N bond could be con- ions and esr spectroscopy. Yet, when papers began com- certed and so be represented with one transition state. ing out from Ingold's group and the battle lines between Perhaps I am not being sufficiently imaginative over this. The p-semidine rearrangement (if intramolecu- them and Dewar were being drawn, I was attracted to lar, etc.) would be similar to the quinamine rearrange- join the fray. I did not begin a systematic study in the ment, and I have the same feeling about requiring an sense of the UCL one. At that time, I felt more in tune intermediate in that one(57). with the pi-complex than the PTS theory, but began checking out the cases that were crucial to arguments Ingold replied on June 6(60): for the both of them, but which had never been investi- You were right to feel that we cannot get rid of the gated properly. In time, for example, it was found by para-semidine problem as easily as Hammick and Tommy Chamness with 4,4 d t rt Munro wanted to. However, I find no great difficulty b t lh dr z b nz n ( and by Jim Stanley with in picturing a transition state with an N-to-para polar 4,4'-hydrazobiphenyl(52) that these bulky hydrazo com- bond of about 3A long. There would be plenty of pounds rearranged and by second-order acid catalysis, strength in such a bond and direction is no problem. contrary to what Dewar was saying about them and their Ingold's letter included tables of rate data, including consequent role in the it-complex theory. those for p-methoxy-and some other p-substituted Insofar as the PTS theory was concerned, we took hydrazobenzenes. Nevertheless, I was disappointed in up at Texas Tech the only class of rearrangements, the the UCL group for writing an updated history, with the p-semidine, that had been deliberately excluded from p-semidine rearrangement as a chief new point(25), consideration by Banthorpe, Hughes, and Ingold(53). without acknowledging Baldwin's and Harris's work, We thought it odd that the p-semidines had not been and for Banthorpe and Cooper's publishing the examined at UCL. The reason for the exclusion was their p-methoxy work as the first recorded one-proton con- acceptance(53) of an earlier, faulty proposal by version of a p-semidine(61). Hammick and Munro(54), that heavy-metal ions were Very little more of consequence was done at Texas necessary to effect p-semidine rearrangements. The rea- Tech with acid-catalyzed rearrangements in those years. son for this proposal was that it was thought, also erro- Work was carried out on photo-benzidine rearrange- neously, that all the rearrangements listed by Jacobson ments, however, since that fitted in more with my inter- Bull. Hist. Chem. 19 (1996) 85
ests in radical ions and esr(62). Thus, acid-catalyzed tillation techniques to solving questions about other re- rearrangements were abandoned at Texas Tech in the arrangements, such as the Claisen and quinamine, and late 1960s. I felt then that nothing new could be done in to continue now with Diels-Alder reactions. Thus, the solving the benzidine mechanism until someone came question that an undergraduate asked over 40 years ago, along with an entirely new approach. It was certainly and which affected my research life so dramatically, can not in my thoughts that it would come along at Texas now be answered more-or-less reasonably. Tech. But, that is what happened and also in a It is amusing now to look back and wonder how all more-or-less accidental way. I met Prof. C. A. of us, who were the major workers in the benzidine re- Bunton(63) by chance at a meeting of the American arrangements, could have missed the connection be- Chemical Society and we fell into a discussion of ben- tween them and the blossoming of ideas in pericyclic zidine rearrangements. Bunton had continued his inter- reactions. Perhaps we were too far in the woods to see est in them since leaving England but not in a major the trees. way(64). Our discussion turned to one's not being cer- The first papers by Woodward and Hoffmann on tain that N-N bond breaking was rate-limiting, and that orbital-symmetry control of pericyclic reactions ap- measuring the nitrogen KIE would give the answer. At peared in 1965(72). At about that time Ingold's interest that time I did not know how to go about measuring a in benzidine rearrangements was diminishing, and it may nitrogen KIE, so Bunton suggested that I solicit the help be understandable that he did not see or comment on of Prof. A. N. Bourns at McMaster University, a recog- their relationship to sigmatropic shifts. It would be in- nized expert in measuring KIE with isotope-ratio mass teresting to know why others in the field failed to see or spectrometric data. That suggestion bore fruit, and even- comment, too. For my own part, I can believe only that tually with the help of one of Prof. Bourns' former co- I was not sufficiently alert. The first workers to suggest workers, Dr. Peter Schmid, the nitrogen KIE was at last that benzidine formation may be a [ , ] g tr p shift obtained(65). When the nitrogen KIE result was pub- were, in fact, not benzidine practitioners at all, but those lished I heard from an old friend, Prof. Harold Kwart, very active indeed in Claisen rearrangements. From H. who pointed out that he could measure heavy atom KIE Schmid's laboratory in Switzerland came a succession without needing to use isotope-ratio mass spectrometry, of truly beautiful papers on these rearrangements, but, instead, by using whole molecule-ion quadrupole crammed full of splendidly worked out examples. mass spectrometry(66). We undertook to do that with Schmid's group applied frontier molecular orbital treat- the rearrangement of hydrazobenzene, but this time to ment to those rearrangements and noted that benzidine do it properly; that is, on the separated products, benzi- formation might be included among [5,5]-sigmatropic dine and diphenyline. At about the same time, I solic- shifts in charged systems(73). Schmid went no further ited the help of another old friend from Gordon Confer- than that. A more extensive recognition that benzidine ence days, Dr. Clair Collins, an expert in measuring 14C formation was an allowed [5,5]-sigmatropic shift, KIE, at Oak Ridge National Laboratories(69). Our col- whereas other products come from rearrangements that laborative results were, to me, astonishing. They showed are formally forbidden, is to be found in the 1971 book that benzidine formation was a concerted process by Alder, Baker, and Brown(74). I was not aware of whereas diphenyline formation was not(70,71). It may this perceptive writing until almost 20 years later and seem odd for me to be saying that I was astonished, be- can only admit to another lapse in alertness. It is appar- cause as soon as the results were obtained we could see ent that Alder and his colleagues must have written about that is exactly what they should have been. Benzidine the rearrangements some time before 1971(75). In a formation is a [5,5}-sigmatropic shift, with which the brief review of the rearrangements(77) I described KIE were consistent. That being so, the diphenyline Schmid's view(73) but even then did not appreciate fully formation could not be concerted because it is a that the answer to the benzidine rearrangements lay in [3 ,5]-sigmatropic shift, forbidden by orbital-symmetry it. constraints from being concerted, unless antarafacially. A summary of the KIE results for the rearrange- The hydrazobenzene results led us at Texas Tech to ments of hydrazobenzene, 4-methoxyhydrazobenzene go further with a- and p-semidine and o-benzidine rear- (an allowed p-semidine rearrangement), 2,2'- rangements (in the naphthalene series), with thermal re- dimethoxyhydrazobenzene (a benzidine rearrangement), arrangements, and with the disproportionation reaction. 2 , 2 '-hydrazonaphthalene,N- 2 - Successful characterization of pertinent examples en- naphthyl-N'-phenylhydrazine (each o-benzidine rear- couraged us to extend the mass spectrometric and scin- rangements), 4,4'-dichlorohydrazobenzene (an o- and a 86 Bull. Hist. Chem. 19 (1996) p-semidine rearrangement with loss of CI), and the dis- '3C probably, was, we think, not good enough. Yet, the proportionation of 4,4'-diiodohydrazobenzene has been motion we sought was found. The results for labelling given earlier and need not be repeated here(21). After at the para carbon atoms confirmed our earlier finding, that summary, however, the nitrogen and carbon KIE that formation of 2 is concerted while formation of 3 is for the rearrangement of hydrazobenzene were re-mea- not. The new measurements for the para carbons do fit sured and are given here in Table I. The motive for eq. 4, whereas our earlier ones with 2 itself did not(71). remeasuring these KIE lay in our intention of measur- It is notable that the nitrogen KIE (Table I) are not much ing KIE for rearrangements of [1- 4 C]- and different from each other. They tell us that there is not [1,] '- C2]hydrazobenzene and our wanting to have for much difference in the breaking of the N-N bond in the comparison contemporary measurements for [4- 4C]- transition states for the two products, but for a reason and [4,4'-1 C2] 1abelling. We recognized that the earlier still unknown, 16% (the yield of 3) of the molecules do KIE, determined on benzidine and diphenyline them- not follow a pericyclic path. Nevertheless, they do not selves(70,71), might be quantitatively wrong. enter an intermolecular path either, and perhaps, after The 1,1'-positions of hydrazobenzene are not di- all, a pi-complex prevails for this pathway. Thus, here rectly involved in bond breaking and forming, so that we may have the pathways of both earlier theorists, the ordinarily one would not make these positions candi- concerted (Ingold) for 2 and pi-complex (Dewar) for 3. dates for KIE measurements. We had found, however, We now know, then, that the benzidine rearrange- that labelling the C-1 and C-B positions of allyl phenyl ments follow the dictates of sigmatropic reactions. This ether, also not formally involved in bonding, gave rise still does not lift Ingold's cloud completely from ob- to significant KIE in its rearrangement to scuring the transition state(s). We do not know the ge- 2-allylphenol(78). The KIE arise from the motion of ometry of the TS in concerted rearrangement, and we these atoms in the six-atom array of a [3,3]-sigmatropic do not know what maintains intramolecularity in shift. We felt, therefore, that analogous, coupled motion non-concerted ones. Perhaps this is as far as we shall of the 1,1'-positions of rearranging hydrazobenzene get—until someone comes along with a newer approach. might be discernable with KIE measurements. Our data One of the puzzles of benzidine formation is that for both benzidine and diphenyline formation are given. benzidine and not 2,2'-diaminobiphenyl (6, an o-benzi- dine) is formed. Formation of 6 is an allowed reaction, Table I. KIE for Rearrangement of Hydrazobenzene (1) to Ben- a [3,3]-sigmatropic shift. That type shift occurs in the zidine (2) and Diphenyline (3)(79) rearrangement of hydrazonaphthalenes, both under acid catalysis and by heating(67,80). At one time it was sug- gested, briefly, that benzidine was formed by a succes- sion of migrations, first to the ortho and next to the para positions(81). That suggestion was made when the so-called "cartwheel" mechanism of the nitramine rear- rangement was popular. Had the double migration, now recognized as double 13,3]-shifts, prevailed, it would a) All measurements were made on the bis(trifluoroacetyl) de- have been remarkable that it could compete almost ex- rivatives. b) For two atoms. clusively with aromatization by loss of protons leading to 6. Later, my colleagues and I were able to exclude The results in Table I from labelling at the 1,1'-posi- tions show KIE for forming 2 but none for forming 3. That is, the coupled motion of the 1,1'carbon atoms, anticipated for the ten-atom array in a [5,5]-pericyclic reaction, is detectable. In contrast coupled motion for diphenyline formation cannot be detected. The KIE at the I- and 1,1'-positions for 2 are very small and not precise, By this I mean that the logarithmic ratio (eq. 4) the double migration by finding no ME for forming 2 from [2,2'6,6 -' C4]1(84). We do not really know why 6 is not formed, although I have suggested earlier that ei- ther the bent cyclohexadienyl shape of the rings in the expected for 4C and "C KIE (single atoms) is not met diprotonated TS does not allow for the close-enough by our results. The precision of our measurements, for ll. t. Ch . ( 6 8
ppr h f th ortho rb n , r th t h r nd l Betrachtungen über Möglichkeiten ihrer Deutung," tr n d tr b t n , b n l th p n d tr b t n n Justus Liebigs Ann. Chem., 1922, 428,76-121. th n l n t n r d l, ll f r pr f rr d b nd n t 5. Ref. 3, p. 985. th para p t n ( . If th l tt r rr t, t ll 6. A. . Holleman and J. Potter van Loon, "The Transfor- mation of Benzidine," Proc. Konl. Akad. Wetensch. rr p nd th In ld S. Amsterdam, 0 , 6, 262-267. There is an earlier report I ll nd th p r n l nt b r t rn n t v n in these Proceedings ,5 (II), 377-379 (1903) by van Loon n nd n t r nt nd p rh p l t xp r about his work on the rearrangement of hydrazobenzene, nt l r n th b nz d n r rr n nt. In th communicated by Prof. C. A. Lobry De Bruyn on No- n p r t n f 2 nd th t p n d r vember 29, 1902, as mentioned by Holleman in the sec- n th KIE, r. S b t p rf r h d th r t f ond communication. The earlier communication reports 2 . h r n f r ll 84: 6( , r th r th n th the yield of benzidine obtained (as the sulfate) under 0: 0 ft n t d(8 . In h f r t r p rt, th br various conditions. In 0.l N HCl it was 84%, a result of r n ( f. 6 , nd n h f ll p p r( , v n n interest to us in our work in 1992 (Ref. 79). Further, van r rd d th t n 0.l CI nd 0 th n l 84 f Loon freed his hydrazobenzene from remaining azobenzene by reduction with zinc dust and ammonia, a b nz d n f r d. d d n t r p rt th nt f procedure used still. In Lobry De Bruyn's communica- d ph n l n , th t b n t d ff lt t bt n. I t tion it is reported, too, that the rate of rearrangement h t ff t v n n h 0 r h d f n was dependent on acid concentration but increased more n t nd 0 r n ld . h h t I d ff t C. rapidly than the concentration. That was a forewarning K. In ld nd M. . S. r, h r n l t n d of an order in acid greater than first. t th p rt fr ll th r pr t t n r nd d d 7. É. Biilmann and J. H. Blom, "Electrometric Studies on nt t n. Azo- and Hydrazo-compounds," J. Chem. Soc., 24, 125,1719-1731. ACK OW E GME S 8. C. A. Lobry de Bruyn and L. K. Wolff, "L'application de la Methode optique de Tyndall permet-elle la Dem- I r t f l t th t d nt nd p td t r l r r onstration de la Presence des Molécules dans les Disso- h t l nt d xp r nt l r t th r t f th lutions?" Rec. Tray. Chim . Pays Bas, 04, 23.155-168. b nz d n t d t x h. h t d r p 9. J. P. van Loon, "Quelques observations sur la transfor- p rt d f r n r b r nt fr th b rt A. mation benzidinique," Rec. Tray. Chim. Pays Bas, 04, 23,62-97. W l h nd t n nd f r t b r nt fr th 10. É. D. Hughes and C. K. Ingold, "Note on the Theory of t n l S n nd t n, f r h h I h ll l Aromatic Substituents and Rearrangements with Spe- b nd bt d. I h t th n l r f. n C rf nt n, cial Reference to the Benzidine Change," J. Chem. Soc., Un v r t t v n A t rd , f r h h lp n bt n n 4 , 608-613. f r (v r f. n En b rt , Un v r t t t 11. R. Robinson, "Mechanism of the Benzidine Transfor- Gr n n n , p f v n n th nd f r pr v d mation and Some Allied Topics," J. Chem. Soc., 4 , n h t r l n t b t ll n. h d bt I h v f r 220-240. th h lp nd t h n f d d fr nd r ld 12. Ref. 10, p. 610. K rt r bl . 13. Ref. 10,p. 6I1. 14. G. M. Robinson and R. Robinson, "A New Synthesis of E E E CES A O ES Tetraphenylpyrrole," J. Chem. Soc.,1918,113,639-645. 15. I am not sure whether it is correct to saddle Robinson I. M. J. S. Dewar, "The Kinetics of Some Benzidine Rear- with monoprotonation only. Drawings in his paper be- rangements, and a Note on the Mechanism of Aromatic gin with monoprotonation but include others showing Substitution," J. Chem. Soc., 46, 777-781. diprotonation. It is not clear whether Robinson knew that 2. (a) H. J. Shine and É. E. Turner, "Grignard Agents as two protons were required initially in hydrazobenzene's Condensing Agents," Nature, 46, 158,170. (b) H. J. rearrangement. Shine and É. É. Turner, "The Anomalous Reactions of 16. Ref. 1I,p. 220. Grignard Reagents (I)," J. Inst. Petrol., 0, 6, 73-80. 17. Ref. 4, p. 121: "Further insight — particularly regarding (c) H. J. Shine, "The Anomalous Reactions of Grignard the way acids cause the rearrangement — should be an- Reagents. Part II," J. Chem, Soc., , 8-I2. ticipated primarily from kinetic studies of the rearrange- 3. C. K. Ingold and H. V. Kidd, "The Mechanism of Aro- ment, which I must forgo because of lack of time and matic Rearrangements. Part II. The Benzidine Change," training. For the time being (Ref. 2), the only completed J. Chem. Soc., , 984-988. effort in this direction is by van Loon (Ref. 3), from 4. P. Jacobson, "Zusammenfassung der Erfahrungen über Holleman's laboratory; from it the conclusion is drawn die Umlagerung von Hydrazoverbindungen, nebst
W . 4 , 88 ll. t. Ch . ( 6
that their ionization determines the velocity with which 27. Letter from Sir Christopher Ingold to H. J. Shine, June various acids cause the rearrangement of 20, 1967. hydrazobenzene." Jacobson's Ref. 2 is to an announce- 28. Banthorpe's switch to biosynthetic work became com- ment, by Stieglitz and Curme, Jr. n Berichte 1913, 46, plete some years later. In response to my enquiring for 9I2, of other rate measurements Reference 3 is to van some additional information about the preparation of Loon in Rec. Tray. Chim. 1904, 23, 62 and to Lapworth D PO2 in the UCL work, he replied in a letter of Febru- in . Chem. Soc. 1908, 93, 2188. Lapworth's work is a ary 20, 1979, that he had disposed of his laboratory note- brief qualitative description that the speed at which ben- books and gave me helpful information from memory. zidine sulfate precipitates from a solution of A clean sweep had been made, evidently. hydrazobenzene in ethanol, acidified with a little sulfu- 29. An indication of his diminishing interest in benzidines ric acid, is inversely proportional to the amount of added may be inferred, also, from his visit to Texas Tech on water. Ref. 2 is a report of first-order kinetics in the ther- May 25, I964, from Vanderbilt, where he was a visitor mal decomposition of hydrazobenzene in ethanol into for several months under the NSF Senior Foreign Sci- azobenzene and aniline. Stieglitz and Curme refer briefly entist Fellowship Program. He wrote, on March 19, I964, to van Loon's work and to their intention to submit later that "in order not to bring coals to Newcastle I think I their recent measurements of rates in the acid-catalyzed had better lecture on something else than benzidine re- benzidine rearrangement. arrangements (which we can still talk about privately). I 18. E. D. Hughes and C. K. Ingold, "Aromatic Rearrange- am warmed up just now on organo-metallic substitu- ments," Quart. Rev., 1952, 6, 34-62. tions and could keep going for an hour on that." He 19. R. B. Carlin, "The Rearrangement of lectured on "Substitutions on Organo-metallic Com-
3,3 ' ,5 ,5' -Tetramethylhydrazobenzene,"J. Am. Chem. Soc., pounds." In 1964 the air journey required changing 1945, 67, 928-933. planes at Love Field. Ingold had a four-hour lay-over 20. M. J. S. Dewar, "The Mechanism of Benzidine-type Re- and spent the time in the comfortable mezzanine lounge arrangements, and the Role of it-Electrons in Organic available then, writing on the next edition of his book. Chemistry," J. Chem. Soc., 1946, 406-408. 30. Ingold was a remote figure to me, and maybe to other 21. H. J. Shine, "Reflections on the pi-Complex Theory of undergraduates, at that time (1942-1944).1 met him and Benzidine Rearrangements," J. Phys. Org . Chem., 1989, Hughes at the beginning of my two years at the inter- 2, 491-506. view all new undergraduates had to have with them be- 22. C. A. Bunton, C. K. Ingold, and M. M. Mhala, "Kinetic fore embarking on course work. I blotted my copy book Form of the Benzidine and Semidine Rearrangements," by showing up late, after all interviews were finished, J. Chem. Soc., 1957, 1906-1913. having gone walking on the sea front to kill time. Ingold 23. D. V. Banthorpe, (the late) E. D. Hughes, and Sir Chris- was testy with me about that. I cannot remember talking topher Ingold. (With an Addendum, by D. V. Banthorpe, to him again except in some group meetings that were R. Bramley and J. A. Thomas), "Mechanism of Benzi- held when the students and faculty tried, but failed, to dine and Semidine Rearrangements. Part XV. A Collec- make an arrangement to hold classes during the long tive Discussion," J. Chem. Soc., 1964, 2864-2901. summer vacation. Ingold would walk along the long 24. D. V. Banthorpe and M. O'Sullivan, "Mechanism of Ben- promenade at Aberystwyth but be oblivious to passing zidine and Semidine Rearrangements. Part XXVII. Ki- students. Hughes had more personal contact with un- netics, Products and Solvent Isotope Effects for dergraduates, it seems, especially during laboratory pe- Acid-catalysed Rearrangements of Some N-Substituted riods. Ingold taught, of course, and very well. In con- Hydrazoarenes," J. Chem. Soc., 1973, 551-556. trast, Hughes was a terrible lecturer, reading from his 25. D. V. Banthorpe, A. Cooper, and C. K. Ingold, "Acid meticulous notes and continuing his reading each pe- Conversion of Hydrazoarenes," Nature, 1967, 216, riod from where he ended the time before. 232-235. 31. C. K. Ingold, "Structures of Some Transition States," 26. (a) D. V. Banthorpe, A. Cooper, and C. K. Ingold, The Chemical Society Special Publication No. I6. The "Mechanism of Benzidine and Semidine Rearrange- Transition State. A Symposium held at Sheffield on the ments. Part XVIII. Kinetics and Products of the Acid 3rd and 4th of April, I962, 118-139. Conversion of 4-Acetamidohydrazobenzene, Products 32. Ref. 31, p. 122. from 4-Aminohydrazobenzene, Normality of p-Semidine 33. Ref. 31, p. 137. Formation, and Crossed Analogues of Disproportion- 34. Ref. 23, p. 2893. ation," J. Chem. Soc., 1968, 609-614. (b) D. V. 35. M. M. Tichwinsky, "The Benzidine Rearrangement," J. Banthorpe, C. K. Ingold and M. O'Sullivan, "Mecha- Russ. Phys. Chem., 1903, 35, 667-675. nism of Benzidine and Semidine Rearrangements. Part 36. J. Stieglitz, "On the 'Beckmann Rearrangement' II," Am. XXI. Kinetics and Products of the Acid Conversion of Chem. J., 1903, 29, 49-67. In a footnote (p. 62) Stieglitz
2,2' -Dibromo- and of 4,4 ' -Dibromohydrazobenzene," J. draws on the ideas in that rearrangement to derive "at Chem. Soc., 1968, 624-627. last, a complete explanation of the benzidine rearrange- ll. t. Ch . ( 6 8
ment." However, Curme(37) reported that the theory of the Rearrangement of Hydrazobenzene and Discus- had now been abandoned because of work by Wieland sion of its Reaction Mechanism," Coll. Czech. Chem. and also because of the measurements by Stieglitz and Commun., 66, 31, 3486-3499. This is part VI of a se- Curme(38), (referred to earlier n this history), of the ries, although the title says part V. Part V is M. Vecera velocity of the benzidine rearrangement. and J. Petránek, Coll. Czech, Chem. Commun., 60, 37. G. O. Curme,Jr.,"The Thermal Decomposition of Sym- 25 , 2005-2012. metrical Diarylhydrazines A Reaction of the First Or- 45. (a) H. J. Shine and R. H. Snyder, "The Oxidation of Hy- der," J. Am. Chem. Soc., , 35, 1143-1I73. drocarbons. I. The Oxidation of Cyclohexene in Acetic 38. J. Stieglitz and G. O. Curme, Jr., "Die Umwandlung von and Propionic Anhydride Solutions," J. Am. Chem. Soc., Hydrazobenzol in Azobenzol und Aniline-eine Reaktion 8, 80, 3064-3066. (b) R. H. Snyder, H. J. Shine, K. erster Ordnung," Ber. Dtsch. Chem. Ges., , 46, A. Leibbrand, and P. O. Tawney, "The Oxidation of 9Il-920. I have been unable to find any report of these Hydrocarbons. Part II. The Oxidation of Cyclopentene, rate measurements in the literature. They are not included 3-Methylcyclohexene, and Tetralin in Acetic Anhydride in Curme's h. . dissertation, "The Thermal Decom- Solution," J. Am. Chem. Soc., , 81, 4299-4300. position of Symmetrical Diarylhydrazines A Reaction 46. (a) H. J. Shine and J. R. Slagle, "The Oxidation of Hy- on the First Order" (University of Chicago, 1913; I thank drocarbons. III. The Decomposition of Acetyl Peroxide Dissertation Abstracts, Ann Arbor, MI, for providing a in Cyclohexene Solutions," J. Am. Chem. Soc., , copy.), although he again refers therein to them and the 81,6309-6313. (b) H. J. Shine and D. M. Hoffman, "The hope to report them within a short time. Curme says that Decomposition of Acetyl Peroxide. The Effect of Io- a method of measuring rates different from van Loon's dine," J. Am. Chem. Soc., 6 , 83,2782. (c) H. J. Shine, was used, b t does not describe it. However, in the ther- J. A. Waters, and D. M. Hoffman, "The Decomposition mal decomposition of hydrazobenzene the rate of dis- of Acetyl Peroxide in Solution. III. Kinetics and Use of appearance was measured from its reduction of iodine, Radical Traps ,"J. Am. Chem. Soc., 1963, 85, 3613-3621. the excess of iodine being back titrated. In the disserta- 47. J. Meisenheimer and K. Witte, "Reduction von tion, Curme again notes that Stieglitz'es earlier theory 2-Nitronaphthalin," Ber. Dtsch. Chem. Ges., 0 , 46, of the benzidine rearrangement(36) has been abandoned. 4153-4I64. 39. M. J. S. Dewar, "The Mechanism of the Benzidine and 48. L. G. Krolik and V. O. Lukashevich. "Characteristics of Related Rearrangements," Nature, 4 , 156, 784. the Rearrangement of Hydrazocompounds in the Naph- 40. G. S. Hammond and H. J. Shine, "The Mechanism of thalene Series," (translation), Dokl. Akad. Nauk CCCR, the Benzidine Rearrangement. I. The Effect of Acid Con- 4 , 65(l), 37-40. centration on Rate," J. Am. Chem. Soc., 0, 72, 49. H. J. Shine, "The 'Thermal' Rearrangement of Hydrazo 220-221. Compounds. I. 2,2'-Hydrazonaphthalene," J, Am. Chem. 41. R. B. Carlin, R. G. Nelb, and R. C. Odioso, "The Benzi- Soc., 6, 78,4807-4809. dine Rearrangement. III. Kinetics of the Rearrangements 50. (a) H. J. Shine and . L. Snell, "The 'Thermal' Rear- of Hydrazobenzene," J. Am. Chem. Soc., , 73, rangement of Aromatic Hydrazo-Compounds," Chem. 1002-I007. Ind. (London), , 706-707. (b) H. J. Shine and J. C. 42. M. J. S. Dewar and A. P. Marchand, "Physical Organic Trisler, "The Thermal Rearrangements of Hydrazo Com- Chemistry: it-Complexes as Intermediates in Organic pounds. III. The Kinetics and Mechanism of the Rear- Reactions," Ann. Rev. Phys. Chem., 6 , 16, 321-346. rangement of 2,2'-Hydrazonaphthalene in Polar Sol- This is a review of pi-complexes as intermediates in or- vents," J. Am. Chem. Soc., 60, 82, 4054-4058. (c) H. ganic reactions, among which the role of it-complexes J. Shine, F. T. Huang, and R. L. Snell, "The Thermal in the benzidine rearrangements is advocated strongly. Rearrangement of Hydrazo Compounds. IV. The The quinamine rerrangement is treated analogously. Intramolecularity of the Rearrangement," J. Org . Chem.., 43. (a) M. Vecera, J. Petránek, and J. Gasparic, "Umlagerung 6 , 26, 380-383. Substitutierter Aromatischer Hydrazoverbindungen," 51. H. J. Shine and J. T. Chamness, "The Benzidine Coll. Czech. Chem. Commun., ,22, 1603-1612. (b) Rearrangment. VI. 4 ,4'-Di-t-butylhydrazobenzene ," J. Gasparic, J. Petránek, and M. Vecera, Tetrahedron tt., 6 , No. 10, 641-644. (b) H. J. Shine "Papierchromatographische Trennung und and J. T. Chamness, "The Benzidine Rearrangement. Identifizierung von Benzidin und seiner Isomeren," VIII. The Rearrangement and Disproportionation of Mikrochim. Acta, , 6, 1026-1030. (c) M. Vecera, 4 ,4'-Di-t-butylhydrazobenzene and 4-t-Butyl- J. Gasparic, and . Petránek, "Thermal Rearrangement 4'-chlorohydrazobenzene," J. Org . Chem.., 6 , 32, of Aromatic Hydrazo Compounds," Chem. Ind. (Lon- 901-905. don), , 299. 52. (a) H. J. Shine and J. P. Stanley, "The Benzidine Rear- 44. V. Sterba and M. Vecera, "On the Rearrangement of rangement of p-Hydrazob iphenyl ," J. Chem. Soc. Chem. Aromatic Hydrazo Compounds. V. Effect of Tempera- Commun.. 6 , 294. (b) H. J. Shine and J. P. Stanley, ture, Medium and Salt Concentrations on the Kinetics "The Benzidine Rearrangement. 1X. p-Hydrazobiphenyl.
1Z117.74 ,41•717.. 90 Bull. Hist. Chem. 19 (1996)
The Mechanism of Rearrangement and Disproportion- On October 4, 1974, Bunton wrote: "1 will be very in- ation ," J. Org . Chem.., 1967, 32, 905-910. terested to know how your ''N isotope work comes out. 53. Ref. 23,p. 2883. Our mechanistic ideas would be very well clarified if 54. D. L. Hammick and D. C. Munro, "The Stereochemis- we knew with a degree of certainty that N-N bond break- try of Semidine Transformations," J. Chem. Soc., 1950, ing was rate 1imiting." A letter of mine to Bunton on 2049-2052. November 12, 1975, says, "We have our samples sealed, 55. H. J. Shine, C. M. Baldwin, and J. H. Harris, "The waiting for mass spectrometry." The samples at that time p-Semidine Rearrangement. 4-Ethoxy- and were, in fact, the mixed hydrochlorides of benzidine 4-Methoxyhydrazobenzene," Tetrahedron Lett., 1968, and diphenyline. We did not think far enough ahead to No. 8, 977-980. separate the products, wanting to know only if we could 56. Letter from H. J. Shine to Sir Christopher Ingold, May find a nitrogen KIÉ for their formation. Thus, the an- 22, 1967. swer we obtained was really for the disappearance of 57. My imaginativeness was indeed puny. Éventually, with hydrazobenzene. At that time, Peter Schmid was, in fact, heavy atom KIE, Henryk Zmuda showed the a postdoctoral worker with Dr. Keith Ingold in the Na- p-semidine(58), and Bogdan Boduszek the tional Research Council laboratories in Ottawa. Ingold quinamine(59) rearrangement to be concerted. graciously agreed that Schmid could return to McMaster 58. H. J. Shine, H. Zmuda, H. Kwart, A. G. Horgan, and M. for a month to make our measurements. Brechbiel, "Benzidine Rearrangements. 17. The Con- 66. I had known Harold Kwart since 1951 when I worked certed Nature of the One-Proton p-Semidine Rearrange- for, and he was a consultant for, U. S. Rubber. Our fami- ment of 4-Methoxyhydrazobenzene," J. Am. Chem. Soc., lies became friends and we would meet periodically, par- 1982, 04, 5181-5184. ticularly at Gordon Conferences. Nevertheless, I had not 59. B. Boduszek and H. J. Shine, "The Mechanism of the kept up with Kwart's work well enough to know what Quinamine Rearrangements," J. Am. Chem. Soc., 1988, he had been doing with mass spectrometry and KIE. He 110, 3247-3252. See also Ref. 73. had, in fact, pioneered the technique of measuring iso- 60. Letter from Sir Christopher Ingold to H. J. Shine, June topic ratios with the selected ion monitoring (SIM) mode 6, 1967. of a quadrupole mass spectrometer. He worked with a 61. D. V. Banthorpe and A. Cooper, "Mechanism of Benzi- very old Hewlett Packard instrument that belonged to dine and Semidine Rearrangements. Part XVII. Kinet- the Chemical Éngineering Department at the University ics and Products of the Acid Rearrangements of of Delaware. My impression, on seeing it, was that 2,2'-Dimethoxy- and 4-Methoxy-hydrazobenzene," J. Kwart's group was keeping it going with "baling wire" Chem. Soc., 1968, 605-609. Banthorpe and Cooper ac- repairs. The first nitrogen KIE on separated benzidine knowledged having heard about the work at Texas Tech. and diphenyline were measured with that instrument. At In the sense that theirs was the first recorded one-proton the time we, in Lubbock, did not know enough about case they were correct. Kinetics were omitted at Texas the technique and its demands on sample character to Tech. More on the p-semidine rearrangement is discussed send Kwart anything but benzidine (a solid) and in Ref. 26a. diphenyline (an oil), themselves. Therefore, it was very 62. (a) J.-D. Cheng and H. J. Shine, "Photobenzidine Rear- difficult to handle diphenyline, something we were bliss- rangements. V. Mechanistic Aspects. Rearrangement of fully unconcerned about in Lubbock. As we learned, Mixtures of Different N,N'-Dimethylhydrazo Aromat- when we repeated the work ourselves years later in Lub- ics, and the Nature of the Excited State," J. Org . Chem., bock with our own quadrupole mass spectrometer, the 1974, 39, 2835-2838. (b) J.-D. Cheng and H. J. Shine, early results were correct in finding KIE but quantita- "Benzidine Rearrangements. XIII. The Role of tively wrong. My collaboration with Harold Kwart con- Reductive Scission. Reactions of N,N'- tinued until his mass spectrometer became inoperable. Dimethylhydrazobenzenes in Acid Solutions," J. Org . At the same time, Kwart became increasingly ill with Chem., 1975, 40, 703-710. stomach cancer. We continued our contacts, neverthe- 63. Clifford A. Bunton was a lecturer at UCL when I was an less, even during his final days in the Sloan-Kettering undergraduate, in Aberystwyth, so that my acquaintance Hospital in New York. We spoke almost daily by tele- with him went back many years. phone, always about chemistry, and, on learning that I 64. C. A. Bunton and R. J. Rubin, "Benzidine Rearrange- was planning on trying to measure KIE in photochemi- ment in the Presence and Absence of Micelles, Évidence cal reactions, his last conversation with me was to ad- for Rate-Limiting Proton Transfer," J. Am. Chem. Soc., vise me to read up on the Russian work on magnetic 1976, 98, 4236-4246. isotope effects. Kwart died on March 31, 1983. When 65. H. J. Shine, G. N. Henderson, A. Cu, and P. Schmid, Kwart's mass spectrometer became unusable, he recom- "Benzidine Rearrangements. 14. The Nitrogen Kinetic mended that I seek the help of Prof. Joe San Filippo, Jr., Isotope Effect in the Acid-Catalyzed Rearrangement of then at Rutgers University. San Filippo had one of the Hydrazobenzene," J. Am. Chem. Soc. 1977, 99, best HP instruments and had it programmed to handle 3719-3723. The final answer took a long time to come. SIM data beautifully. We collaborated for a few years ll. t. Ch . (1996) 91
nt h b d ff b th t p f pl r 6. h U f v At K n t I t p Eff t n nd n , b (tr fl r t l d r v t v f n , r S lv n th M h n f th A d C t l z d r d dl t h l tr n lt pl r . O r b n t ff fr r n nt f dr z h nz n . h C n rt d th p tr t r f n ll n bl d t t r n, t nz d n nd th n n rt d th t th x h Un v r t f nd , n t th h h l ph n l n ." J. Am. Chem. Soc., 82, 104, 2 0 2 0 . d l th t S n l pp h d, b t l r n th t ld 2. . . W d rd nd . ff nn, "S l t n l f r d th j b, h v r. S n l pp ndl v h S tr p t n ," J. Am. Chem. Soc., 6 , 87, p t r pr r f r h ndl n th th nd f SIM n . 2 2 . Wh n pd t d th p t r f l t f r th . G . rät r nd . S h d, " h r h U ndl n p tr t r nd f nd th t t r d n l r th r v n nt 2,4 d n l ph n läth rn n 4 ( nt th n , f nd t h t h t nd r r d t 2 ,4 d n l ph n l [ , ] tr p h n th C p t r S n p rt nt t th tr n U l r n n," Helv. Chim. Acta, , 53, 26 2 0. l t n f r . h , ft r r f nd r n n th h p b l t th t th n n r rr n nt p tr tr d rt r ttl d n r n tr p n l p nt d t n th p p r. S pr d l nd. S f rth r f r nt r n KIE f. . 4. . W. Ald r, . r, nd . M. r n, th t p r t p tr tr r l d . Mechanism in Organic Chemistry, W l Int r n , In t ll , n 8 86, (th t , r ft r r r nd n, , pp. 2 2 4. th t r S h d n C n d , h d t r . r. Ald r t ld ( 6 , n f t, th t h n l d d th v l l b r t r , Kr r G hr n, f r th r f b nz d n r rr n nt n h Un v r t l t r nt . h r f l f r n tr n KIE, b t n t f r r b f r th b r tt n. C KIE, n th r rr n nt f 2 n phth l ph 6. M t n f r. . W. Ald r nd . . Sh n , Un v r t n lh dr z n (6 . h t f r l n l f r t l, l , I 8 . h h, nd, lth h Kr r G hr n n r l . . . Sh n , "Ar t rr n nt ," n MTP Intl. dr pp d t pr f r t $4 pl , h d t b n Rev. Sci., Org. Chem., S r. I, . ll n r, Éd., , 3, d n th . I l rn d l t b t th t hn fr Mr. 6 0 p. 84. r ld Kr r b l tt r nd ph n d n . rt 8. . K p z S b t , W. S b t , W. . n t l , x h p rt nt f G n r d S nd r , r., nd . . Sh n , "Cl n rr n nt
t t f th rt G SI A 2 t p r t p f All h n l Éth r. l 4C nd b 4C K n t I t p tr t r, h h r. Y l z l rn d t , nd n th t Éff t . A Cl r r f th r n t n Str t r ," J. bt n d n tr n KIÉ n S l r rr n nt Am. Chem. Soc., 2, 114, 44 44 . th n t r ll b nd nt t rt n t r l (68 . W. S b t , . K p z S b t , nd . . 6 . ( . . Sh n , . K p z S b t , nd W. Sh n , " h nz d n nd ph n l n rr n nt
S b t , " v At K n t I t p Eff t n v t d. 4C nd l,l C 2 K n t I t p Eff t , th A d C t l z d rr n nt f 2 r n t n St t ff r n , nd C pl d M t n n phth l ph n lh dr z n . rr n nt Sh n 0 At S tr p rr n nt," J. Am. Chem. t b C n rt d r ," J. Am. Chem. Soc., 8 , Soc., , 115, 0 0 6. 107, 6674-6678. (b Ibid., 8 , 109, 1286; a rr 80. . . Sh n , E. Gr z , W. S b t , M. t n. r n ll, nd . S n l pp , r., " v At K 68. I. Y l z nd . . Sh n , " v At K n t I n t I t p Éff t n th A d C t l z d nd h r t p Éff t n th C t l z d S l rr n l rr n nt f 2 ,2 dr z n phth l n nt f M th l 2 (4 n tr ph n x th n n ," r n t n St t ff r n n th r C n rt d r G zz. Chim. Ital., 8 , 119, 60 60 . r n nt ," . Am. Chem. Soc.,1985 , 107, 2 8 22 . 6 . A n, b f r n xp r n nt C ll n 8 . S. r n t n, C. A. nt n, nd E. . h , " h pl f b nz d n nd d ph n l n , nd n th n Intr l l r rr n nt f h n ln tr n nd r r l t t v l r ht b t nt t t v l r n . th nz d n nd S d n Ch n ," Chem. Ind. (Lon- C ll n thr ll d th h ph n ll b t th f r t b n don), 6, 8 . h nt rv nt n f t p r z d n r nt : " nr , h v rb n KIÉ." t n p rt f th rl t p l t n n h n ll n th ll b r t n th C ll n t rn d t f b nz d n r rr n nt , b t n t, f r , n th n nt ll t n nt n . x h d d, n f t, h v n f th d bl r t n d r b d h r . h t , nt r. Cl r C ll n d d l 2 , 88. nt n d rl r n th d n f b n n r , 0. . . Sh n , . d , K. . r , . K rt, A. G. th p d n th ht b Ch tt (82 t pr r n, C. C ll n , nd . M x ll, "M h n f d b nz d n f r t n. An l l , Ch tt pr th nz d n rr n nt. K n t I t p Éff t p d th t th d n ht l b n nt r d t nd r n t n St t . Ev d n f r C n rt d r t p n th t b nz d n , lth h, h n t d, th t r n nt," . Am. Chem. Soc., 8 , 103, 6. pr d t h d h th rt p d d t t n. r (8 l . . . Sh n , . d , K. r , E K rt, A. G. d n rl p l t n th t th r th o- r p d n r n, nd M. r hb l," nz d n rr n nt . 92 Bull. Hist. Chem. 19 (1996)
rearrangement preceded benzidine formation. It is in- 85. The ratio of yields 79:15 is also reported by Vecera for teresting that each f these speculations was made as a rearrangement in 50% ethanol 0.l M in HCI at 20. C by-analogy addendum, to a discussion of another piece (Ref. 86,p. I996). of chemistry, the diazoaminobenzene rearrangement in 86. M. Vecera, L. Synek, and V. Sterba, "Ober die Chattaway's case and the Crum-Brown and Gibson Rule Umlagerung Aromatischer Hydrazoverbindungen IV. in Fry's. Untersuchung der Sauren Katalyse und des Eintlusses 82. F. D. Chattaway, "The Transformation of Diazoamido- des Mediums und der Temperatur bei der Umlagerung into Aminoazocompounds and of Hydrazobenzene into von Hydrazobenzol," Coll. Czech. Chem. Commun., Benzidine," Proc. Chem. Soc. (London), 02, 18, 60, 25, 1992-2004. 175-177. 83. H. S. Fry, "Die Konstitution des Benzols vom ABOUT THE AUTHOR Standpunkte des Korpuskular-atomistischen Begriffs der positiven und negativen Wertigkeit. I. Eine Interpreta- Henry J. Shine is a Paul Whitfield Horn Professor of tion der Regel von Crum Brown und Gibson," Z. Chemistry at Texas Tech University, Lubbock, TX Physikal. Chem., , 76, 385-397. 79400. He retired from full-time activities in January, 84. L. Kupczyk-Subotkowska, . . Shine, W. Subotkowski, 1996, but continues teaching and research with a modi- and .1. Zygumnt, "Bond-Forming Carbon Kinetic Iso- fied-service appointment. His research interests are in tope Effects in Benzidine Rearrangements," Gazz. Chico. free radical and ion radical reactions, and in using heavy Ital., 8 , 117,513-516. This paper is dedicated to the atom kinetic isotope effects in solving mechanisms of memory of Prof. Gabriello Illuminati (1922-1986), whom I met first in 1948 when we were both postdoctoral organic reactions. He is the author of "Aromatic Rear- fellows with Prof. H. Gilman at Iowa State College. rangements."
EUGENE GARFIELD POSTDOCTORAL FELLOWSHIP IN THE HISTORY OF SCIENTIFIC INFORMATION
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