9—
The Great Break

Characterization and Causes

The chapter title refers to a sharp change in the fortunes of Kolbe's personal research and that of his school, as well as to a parallel change in the chemical community as a whole. Economists refer to an inflection point in a country's per capita economic output as the "take-off" that marks the beginning of an industrial revolution. Following this model, academic chemistry, led especially by the German organikers , achieved a kind of take-off during the 1850s and 1860s. Thereafter, the study of chemistry was transformed from a small affair conducted by elite scholars with an equally elite student clientele to the kind of routine mass education that is familiar in the modern world. A concomitant of this transformation was the relatively sudden recognition by political leaders of the potential applicability of chemical knowledge.

Kolbe's career followed this pattern, but with an uncharacteristically sharp inflection at the year 1858. First, let us look in table 2 at some rough-and-ready numerical measures of the size and research productivity of the Marburg research group, comparing Kolbe's first seven and a half years (from his arrival in May 1851 until late 1858) with the following year and a half (from the beginning of 1859 until mid-1860). To provide further reference points for comparison, data are also drawn from Bunsen's lab at Marburg during the five years before Kolbe's arrival (1846-1851) and average enrollment figures for the university as a whole.^[1]

During the fourteen years examined here, there was a gradual decline both in the prestige of the university and in its overall enrollment. Nonetheless, compared to the other changes being measured, the decline is small enough—about ten percent—that this factor can be neglected. Obviously, throughout the entire period, chemistry at Marburg became less popular, at least as indicated by the sizes of classes and numbers of majors. A factor independent of intrinsic merit operating at least in the 1850s must have been the circumstance that Kolbe was relatively young and still little known in comparison to his predecessor.

As far as research productivity is concerned, Bunsen's later years in Marburg must be regarded as quite successful, considering the time and place. Such was not the case with Kolbe's early Marburg period. In rough terms, he published personally a fourth as often as Bunsen had; his lab as a whole produced a third the annual number of papers; and even after taking into account his smaller number of Praktikanten, per capita productivity was half that of Bunsen's. His own research and that of his school was, to put it bluntly, moribund.

This situation was transformed starting at the end of 1858. In the ensuing eighteen months, his personal productivity was eight times what it had been, and that of his research group increased by a factor of seven. The transition between these periods was razor sharp. Kolbe's last paper before the transition point was his theoretical pro-

spectus, joint with Frankland, dated December 1856. In the fall of 1858 his lab was suddenly bursting with activity (if not with students), and in the last week of that year and the first week of 1859 he wrote or edited seven contributions by him and/or his students; they were published as a group in the March 1859 issue of the Annalen .^[3] In the course of 1859 he wrote five new solo papers and another one with a student, and he edited three more by students. Three additional papers came out of his lab by mid-1860. Although I have not tabulated it, in the next five years—his last in Marburg—he managed to maintain close to the same impressive level of productivity of this remarkable eighteen-month period. This activity made him internationally famous; by the mid-1860s he was generally regarded as (perhaps after Hofmann) the most eminent German chemist of his generation. It led to his call to Leipzig in 1865 and to Bonn in 1866 (the latter of which was refused).

Even superficial examination of the numbers in table 2 suffices to show that the explosion was not facilitated by any increase in numbers of students at his disposal; in fact, the numbers continued to decline. He reached simultaneously a low point in numbers and a high point in excitement in March 1860, when he wrote to Vieweg about how his theory had opened inviting prospects of discovery. "If only I had more hands," he cried, "that is, more capable students, who could help me to exploit this treasure trove before others use it." That semester he had but six auditors in his lecture, thirteen at various levels of competence in his practicum, and no chemistry majors at all. The university enrollment had fallen to a low of 216. Seven months later, he wrote Vieweg again, using identical phrases. He said he had been trying to exploit this theory for almost two years, with the help of some very good students, but distressingly small numbers of them.^[4]

Were these students, admittedly smaller in number, nonetheless of higher caliber than those he had in his early years in Marburg? That might go far in explaining the great break. Let us attempt at least an impressionistic qualitative comparison of the two periods.^[5] During the early Marburg period (1851-1858), he taught one man who would later be regarded as a master chemist, Peter Griess (1829-1888), and three others who could be fairly described as very good journeyman chemists, B. Wilhelm Gerland (ca. 1829-ca. 1905), the Englishman Frederick Guthrie (1833-1886), and the Irishman Maxwell Simpson (1815-1902). For two semesters in 1855-1856, the future industrialist Ludwig Mond (1839-1909) studied in Kolbe's classroom and laboratory, but he was only sixteen at the time and left no traces in publications or in Kolbe's correspondence. It is probable that his subsequent study with Bunsen at Heidelberg was of greater influence on him. Oddly, all three of these early German students of Kolbe would soon emigrate to England—Gerland probably in 1854, Griess in 1858, and

Mond in 1862—spending the rest of their lives working for various English chemical companies. After Marburg, Gerland and Guthrie studied with Frankland in Manchester, and Griess with Hofmann in London. Kolbe had inherited Gerland and Francis Wrightson (whom we met in chap. 6) from Bunsen's research group in 1851. Only a few of Kolbe's early Marburg students can be traced later than about 1858.

The foregoing applies to the period before 1858. During the period of his sudden efflorescence of activity, he had a very capable young man in his lab who later made a successful academic career at the Dresden Technische Hochschule, Rudolf Schmitt (1830-1898). Another worker, quite productive but probably in the "journeyman" category, was Eduard Lautemann, about whom little is known. He studied with Kolbe from 1857 to 1861, thereafter serving as assistant. He published his entire oeuvre of seventeen papers, some solo and many co-authored, during the period from 1859 to 1865, then traveled to India, began to study medicine, and vanished from sight. Adolf Claus (1840-1900), later a prominent structuralist, studied with Kolbe from 1858 and worked in the lab in 1859-1860 before transferring to Göttingen. He was a novice at the time, and there is no evidence that he did any significant research at Marburg.^[6]

Bearing in mind that the second period is much shorter than the first, an unequivocal choice between the cast of characters before and after 1858 on the basis of their quality is difficult. However, it is probably fair to suggest that, on the whole, Kolbe had no better student material to work with in 1859-1860 than he did before this time, and as we have seen, he had fewer of them. Thus, we cannot explain the change by looking at the students.

Another possible explanation for the transformation is the influence of external events. I have already related the debilitating fevers and acute rheumatic attacks that plagued Kolbe during virtually all of 1857 and the first half of 1858. During this period as an invalid, Kolbe's frustration was intensified by the fact that it was in December 1856 that he had written a short prospectus of his carbonic acid theory and was then physically unable to substantiate it by experimental efforts. A mineral water "cure" at Wiesbaden in late spring 1858 made him vigorous and healthy again. His arrival back in Marburg on 16 June marks the precise point when he began to generate a prolific research program. On his return he wrote

I have been back in Marburg for a week, and am fortunate to be able to tell you . . . that I am completely recovered, and feel healthier than I have in years. The Wiesbaden water really did me wonders, which I must all the more readily admit, since, to be honest, when I went to Wiesbaden I did not initially have much faith or belief in the therapeutic

power of such an innocent appearing rivulet. . . . Giving lectures is [now] easy for me, and it seems to me that I have never lectured better than I do now. In short, I feel newly reborn, and for this I cannot be sufficiently grateful to Providence.^[7]

Before 1857 he had been reasonably healthy, but he had had a number of other problems that tended to interfere with his scientific productivity: courtship, marriage, and founding a family; money troubles; rancorous collegial disputes; and efforts to make as rapid progress as possible on his voluminous textbook and on the Handwörterbuch for Vieweg.

But external events cannot provide anything approaching a full explanation. After 1858, as before, he was much occupied with his textbook, which still was far from complete, and with disputes with colleagues and acquaintances. He continued to be seriously underpaid, and ministerial support for his laboratory was so miserly that in the fall of 1860 he had to spend his own money to support it. His health, although improved, was still not good, and he continued to be afflicted by at least annual attacks of severe rheumatism, as well as regular influenzas and grippes. His mental health was also not good after 1858, and his wife suffered through two long and nearly fatal illnesses.^[8]

Finally, there is strong presumptive evidence (detailed in the previous chapter) that publications as late as the middle of 1858 by Ke-kulé, Wurtz, and others influenced the formulation of the definitive version of his theory in that year. It is not unreasonable to conjecture that the medically enforced idleness in Wiesbaden of May and June 1858, complained of bitterly in a letter to Vieweg,^[9] gave Kolbe the time to read and ponder the recent literature in a more relaxed fashion than would otherwise have been possible.

I have gone through this examination of candidate causes for the great break in order to support the thesis that the most obvious explanation for the change—the acquisition by 1858 of an extremely powerful theory that was absent before this time—stands virtually alone in importance. The difficulties with which Kolbe had to contend were as great during the years soon after 1858 as compared to before this time. But he had the principal prerequisite for productive research, a good new theory, and that made all the difference.

Polyfunctionality

Chapter 8 detailed Kolbe's route to his carbonic acid theory. There were several essential novelties in this theory, as compared to his earlier beliefs; he now fully accepted carbon tetravalence for most, but

not all, organic compounds. He had also adopted a substitutionist viewpoint and given up all traces of the copula theory. The research of Wurtz and Debus in 1857 and 1858 had convinced him of the dibasicity of oxalic acid, hence the need to double his formula for it. Furthermore, by extension, he now accepted the generic category of polybasic acids.

Polybasic acids are examples of polyfunctional organic compounds. For years, Kolbe had resisted a direct theoretical confrontation with this kind of compound, and for good reason. His chemical instinct, developed to maturity in the electrochemical tradition, was to identify a single, central carbonaceous focus for a compound and to use that atom or radical as the theoretical centerpiece of the formula. Hetero-atoms, especially oxygen, were grouped together as much as possible. Polyfunctionality was possible to formulate in this style, and Kolbe often did this before 1858, but only when all but one functional group remained in the background and hence were formulable as substituents within the radicals attached to the carbon group at the focal point. To relinquish this viewpoint would be to accept the structuralists' (Gerhardtian) thesis of the chemical equality of all carbon atoms in the molecule, thus to relinquish the last vestige of dualism. To be sure, by the time of Gerhardt's death Kolbe saw much of value in the Frenchman's system. Where the type theorists had gone seriously wrong, he thought, was in their subsequent development of multiple and mixed types. As it happens, multiple and mixed types were a result of the typists' struggle with polyfunctionality.

Wurtz in particular was generating phenomenal numbers of novel polyfunctional organic amines, alcohols, acids, and aldehydes in the years from 1855 to 1861. Chief among these were the two- and three-carbon organic acids and alcohols. Wurtz succeeded in oxidizing glycol to glycolic acid and then to oxalic acid. Since glycol had been prepared from ethylene, Wurtz argued that oxalic acid must have as much carbon as ethylene; moreover, glycol was seen to be as much the alcohol of glycolic acid as of oxalic acid, and glycolic acid was formulated as "diatomic" and dibasic (which is to say that both hydroxyl and carboxyl hydrogen atoms were acid in character). In modern terms,^[10]

By analogous reactions, propylene was converted to propylene glycol and then to lactic acid, and analogous claims could be made for these as well:^[11]

Wurtz then found that phosphorus pentachloride could be used to replace both hydroxyl groups of lactic acid with chlorine atoms, to make "[chloro]lactyl chloride," and then by reaction with alcohol, "chloro-lactic [ethyl] ester."^[12] The existence of these compounds underlined for Wurtz the dibasic character of lactic acid and also its close relationship to propylene glycol, which underwent an analogous reaction with phosphorus pentachloride.

In the meantime, Heinrich Debus, a Bunsen protégé then at Queen-wood College, had developed a means of oxidizing alcohol to produce many of these same polyfunctional two-carbon compounds, but also including glyoxal (the dialdehyde) and glyoxylic acid (the aldehyde-acid). Kekulé and his student R. Hoffmann demonstrated how to make monochloroacetic acid, from which could be derived glycolic acid and glycocoll (glycine or aminoacetic acid). Strecker showed how to oxidize glycocoll to glycolic acid, and alanine (aminopropionic acid) to lactic acid. There seemed to be clear genetic relationships among all these compounds, and all could be formulated using multiple and mixed types.^[13]

Kolbe needed to respond to all of these novel reactions by providing interpretations consistent with his own ideas. Chapter 8 showed why Kolbe formulated glycol as a hydrated oxide,

rejecting Wurtz' claim that it is an alcohol. For Kolbe, the lone hydrogen in the brace meant that glycol cannot be oxidized to an acid since such oxidation requires a minimum of two hydrogen atoms attached to the carbonyl group. It could, however, be oxidized to a two-carbon homolog of glycerin, that is, replacing the lone hydrogen by a third oxygen function. In Kolbe's formulation, this would be 3HO.C₂ H₃ .C₂ O₃ , a triple oxide hydrate. That this reaction had not yet been accomplished was not a problem for Kolbe.^[14]

Wurtz had actually done what Kolbe considered impossible, in oxidizing ethylene glycol to glycolic acid, and propylene glycol to lactic acid. Kolbe responded that rearrangements must take place: in oxidizing glycol, one hydrogen of the methyl was replaced by a "hydrogen peroxide" radical (O₂ H, i.e., hydroxyl) so that the other carbon now had room for full oxidation to the acid. Consequently, there must be a

yet undiscovered alcohol whose oxidation yields glycolic acid without rearrangement, the "true" glycol or double alcohol, isomeric with Wurtz' compound and unrelated to ethylene. Milder oxidation of this hypothetical substance should also yield a new aldehyde isomeric with acetic acid. Finally, if Wurtz' compound, ethylene oxide hydrate, could be dehydrated, it should yield ordinary aldehyde. In short, Kolbe affirmed, ethylene glycol and propylene glycol are not alcohols at all and have no substantive genetic relationship to glycolic or lactic acids. The latter are derivatives of acetic and propionic acids, as Kekulé, Hoffmann, and Strecker had shown. To be sure, glycolic and lactic acids each possess a radical (O₂ H) substituted for hydrogen, but the acids are monobasic, not dibasic as Wurtz had asserted.

Kolbe made all these claims in fascicle 8/9 of his textbook, written in the summer or fall of 1858 and published early in 1859. The driving force of his resurgent research program begun late in 1858 was the examination and substantiation of these ideas, which he regarded as a direct outgrowth of his carbonic acid theory. That this theory was generating interpretations and predictions different from those of the type theorists validated Kolbe's sense that he had developed a powerful theory different from and superior to the school he so heartily despised—to what would soon be known as structure theory.

As we have seen, there were indeed some distinctive aspects of Kolbe's approach. Kolbe took formulation far more seriously and literally than did the type theorists, believing that discerning the constitutions of molecules was a straightforward process of applying rigorous deduction to skillfully gathered hard evidence, and he was convinced that one could arrive at ultimate formulas in this fashion. He accepted carbon tetravalence ("tetratomicity") for most organic compounds, but he could not countenance carbon chain formation. Kolbe's proximate radicals (such as methyl and carboxyl in acetic acid, or methyl, hydroxymethylene, carbon dioxide, oxygen, and water in lactic acid) were combined with one another as discrete molecular units and presumably coulombically. In formulating any compound, the goal was to identify a single governing radical, which he named the fundamental radical that held as many other proximate radicals together as equaled its combining capacity.

His approach made it difficult for him to deal with polyfunctionality in organic compounds, especially when the functional groups in a single molecule were not all the same. Once he was compelled to confront polyfunctionality by the work of Wurtz, Debus, Kekulé, and others, his theory became much more powerful. But even thereafter, his discomfort with the phenomenon is revealed in many subtle ways. This discomfort was the ultimate source of his strong disagreement with

Wurtz over the nature of glycolic and lactic acids; rather than alcohol-acids, Kolbe was convinced that they were ordinary monofunctional acetic and propionic acids, merely with a substituent O₂ H group. Kolbe even admitted publicly that it had been difficult for him to reach the conclusion that O₂ H could replace H in organic compounds.^[15]

Despite these differences, Wurtz' and Kolbe's chemical ideas were substantially similar. All of Kolbe's reasoning and all of his formulas could easily be translated into type notation, and vice versa. Their disagreements were usually unrelated to the distinctions that did exist between their theories. Wurtz could point to the genetic relationship between glycol and glycolic and oxalic acids to argue that glycol was a dialcohol corresponding to a reduced form of the two acids, but he then ran into trouble explaining—or rather, did not even try to re-solve—the precise genetic relationship between ethylene and glycol, a point seized upon by Kolbe. Kolbe could easily account for the latter genetic relationship, but had to suppose a rearrangement and to posit undiscovered isomeric alcohols to explain the former. This set of problems was eventually solved, at least in principle, by Alexander Crum Brown's argument in 1864 that ethylene was not in fact CH₃ CH, as virtually everyone had assumed by analogy to carbonic oxide, but rather CH₂ CH₂ .^[16]

Predictions Unfulfilled:
Hydroxyacids

In the fall of 1858, Kolbe put his student Carl Ulrich on the problem of hydrolyzing and reducing Wurtz' chlorolactyl chloride. Ulrich found a way to remove the two chlorine atoms in two clean stages, first by generating chloropropionic acid and then by reducing this to propionic acid by means of nascent hydrogen. The fact that the process occurred in two stages neatly underlined Kolbe's point that the two hydroxyl functions of lactic acid were not equivalent, hence lactic acid was not dibasic as Wurtz claimed. Moreover, Ulrich had transformed a lactic acid derivative into propionic acid, proving the close relationship Kolbe had been asserting.^[17]

Simultaneously with Ulrich's paper, Kolbe published a summary of his views on the constitution of lactic acid. He rehearsed all of the arguments just published in his textbook; regarding the nonalcoholic character of glycols, he stressed that aldehyde had never been produced from glycol. Debus' glyoxal, interpreted by its creator as a double aldehyde, had been prepared from alcohol, not glycol, and in any case, there was no proof that it was an aldehyde.^[18]

In a long article published simultaneously with Kolbe's and Ulrich's,

Wurtz developed his thoughts on reactions of polyatomic alcohols (derivatives of glycerin and glycol) on which he had done so much valuable work.^[19] It was the first time Wurtz used Williamson's atomic weights (barred O's and C's indicating doubled conventional equivalents), and he thoroughly discussed the incipient theory of "molecular structure," as he termed it here. Wurtz attempted to build a case for the crucial role his research on polyatomic alcohols had played for the rise of this theory.

I will force myself to be brief; for although I attribute a high value to theory, which must be the foundation and the end of all science, I believe that, above all, facts should be allowed to speak for themselves, and that in chemistry, theory consists only in the direct and judicious interpretation of that which experiment teaches us.

Among other things, "the theory" had suggested to Wurtz that there ought to be an intermediate member between glycerin and normal alcohol; this thought had led to his discovery of glycol. He reported that he was continuing to produce large numbers of glycol derivatives in his lab, as predicted by the theory.^[20] The mere existence of glycols was unimportant; what mattered was that it fulfilled predictions, and transformed the "hitherto vague and unsupported hypothesis" of polyatomic radicals into substantiated fact.^[21]

Wurtz noted that polyfunctionality means that type or radical formulas in general capture only partial views of molecules, but they are nonetheless of enormous value. "I realize that many people abuse them. But abuse does not condemn use."^[22] He felt that one must not reject rational formulas, but that one must also not abuse them by putting too much trust in them. "It is wrong to present these things as the law and the prophets." Formulas cannot provide ultimate depictions of "the intimate constitutions of compounds," but rather should serve as guides to the prediction and interpretation of reactions.^[23] Wurtz cited A. S. Couper and Kolbe as two men who had erred by believing their formulas too literally. Kolbe had often averred that multiple types are imaginary, hence useless, because (for instance) the double water type H₄ O₂ as the basis for formulating sulfuric acid does not exist in nature. Wurtz responded that this objection "is not serious," for the advocates of such types, including himself, had always been careful to specify that the cause of cohesion of multiple types is a polyatomic radical. Williamson had formulated the hydroxyls of sulfuric acid as held together by a diatomic SO₂ radical, and Wurtz had formulated the three fatty acids of triglycerides as held together by the triatomic glyceryl radical.^[24]

When Kolbe's and Ulrich's papers appeared in the spring of 1859,

Wurtz responded almost immediately with new compounds supporting new arguments. Chlorolactyl chloride was the starting material for both esterification of the acid group and acylation of the alcohol group, producing "lactobutyric ester" (butyryl ethyl lactate). Wurtz also prepared an ethyl ether/ethyl ester from the same starting material, using two moles of Williamson's sodium ethoxide. These reactions once more emphasized the difunctionality of lactic acid. However, Wurtz conceded the point deduced from Ulrich's reactions, namely, the non-equivalence of those two functions. Lactic acid is not dibasic in the same sense that oxalic acid is, Wurtz admitted. However, it is nonetheless diatomic (that is, it has two replaceable hydrogen atoms).^[25] Here he was following Kekulé's ideas and language from a paper on glycolic acid published the preceding year.^[26]

Wurtz took this occasion to stress once more the alcoholic character of the glycols and their close relationship to the hydroxyacids. Kolbe's name for ethyl alcohol was "ethyl oxide hydrate" and that for glycol "ethylene oxide hydrate." These two names show even more analogy than Wurtz' "alcohol" and "glycol." Kolbe had said he feared that the definition of "alcohol" would be stretched beyond all recognition or meaning by the inclusion of the glycols in this class. "Let him be reassured on this point," Wurtz wrote; polybasic acids such as oxalic acid have not destroyed the concept of acid! As for the fact that glycol had not yet been converted into an aldehyde, this was but a temporary situation. Debus' glyoxal was indeed the aldehyde analog of glycol, even though it had been prepared from alcohol and not glycol. In any case, no one was denying that methyl alcohol is an alcohol, even though no one had isolated a methyl aldehyde. Finally, several glycols had been converted to acids, analogous to ethyl alcohol being converted to acetic acid, which was Kolbe's own criterion for alcoholic character. As for Kolbe's argument that lactic acid is monobasic, "or rather monatomic," Wurtz thought that his reactions had shown this thesis to be untenable. Besides, where were all of Kolbe's hypothesized isomeric alcohols and aldehydes, the so-called true reduced analogs to the hydroxyacids? Wurtz believed that it was Kolbe, not he, who dwelt in the land of hypothesis.^[27]

Kekulé was in complete accord with Wurtz on the matter of formulas and their interpretation, and also on the power of structure theory. As he wrote Lothar Meyer in 1860, "We and science quietly wend our way between the mischief of those who make a game of constitutional formulas, and the indolence of those who deny [rational] formulas, toward the star of a fundamental synthesis beckoning from afar."^[28] As it happened, the first fascicle of Kekulé's textbook was being printed while Wurtz' papers just described were being published.

In this fascicle, Kekulé emphasized that rational formulas are de-

rived solely from reactions, and that one must be allowed to write different formulas for the same compound, depending on what functionality was in question for a given reaction. He wrote, "It is clear that even for acetic acid—and all the more so for more complicated compounds—a completely comprehensive rational formula is not appropriate for ordinary use, even if one can be specified in the present state of the science." Rather, one uses whatever formula most clearly makes the point in question. Type notation is handy for many, even most situations, he felt. It clarifies, for example, the different chemical behavior of the "typical" hydrogen in alcohol, or the "typical" hydrogen in acetic acid, from the other hydrogens in the compound. However, type formulas, too, have their limitations.

There are several cases where different hydrogen atoms should be equivalent according to the type theory, and are not. For instance, glycolic acid, as well as lactic acid, behave like monobasic acids, although they contain two typical hydrogen atoms. . . . One behaves just like the typical hydrogen of alcohol, the other just like the typical hydrogen of acetic acid. The different behavior of these two hydrogen atoms is apparently caused by the different positions they occupy with respect to the other atoms, particularly oxygen. One hydrogen atom lies in the neighborhood of two oxygen atoms, like that of acetic acid; the other lies in the neighborhood of one oxygen atom, like that of alcohol.^[29]

Given the context of the rest of this fascicle, in which Kekulé laid out his founding version of structure theory, there can be little doubt what he had in mind here: lactic acid is hydroxyacetic acid, an alcohol-acid. He indicated here the via media between Wurtz and Kolbe, while also implying the first adequate fully resolved formula for the compound. The implication was made explicit in papers published by Kekulé, W. H. Perkin, and Alexander Crum Brown, all in 1861; Crum Brown made clear that he was only reading between the lines of Kekulé's 1859 quotation, just cited.^[30]

But Kolbe never blinked. On the attack once more, he and his student Lautemann published another trio of articles on lactic acid in the February 1860 issue of the Annalen . Given the task by his mentor of converting lactic directly into propionic acid—in other words, foregoing the chloro intermediate—Lautemann found success with his fifth attempted reducing agent, hydrogen iodide. (This marked a significant methodological innovation in organic chemistry, for hydrogen iodide proved to be a very versatile reducing agent.) Concurrently, Kolbe discovered how to convert lactic acid to alanine (Strecker had accomplished the reverse). Both reactions tightened the analogies to the monobasic series, in this case propionic acid.^[31]

In short, Kolbe thought that his proof of lactic acid as monobasic

was irrefutable and that Wurtz' own work had only further confirmed this.^[32] But just for good measure, he added more arguments to finish Wurtz off. Lactic acid forms no salts with two different metals and has no acid salts, nor does it have a diester. What Wurtz called a diester—his diethyl product using sodium ethoxide—is actually oxyäthylpropionsaures Aethyloxyd , a substituted monoester. As for Wurtz' butyryl ethyl lactate, Kolbe surmised that the compound was actually Oxybutyroxylpropionsäureäther , a hydroxy ketone monoester. Finally, Kolbe excoriated Wurtz for suggesting that both of their different formulas might apply equally to ethyl chloropropionate.

I confess I do not have so broad a chemical conscience, and could never countenance such a doctrine, even if it had to do with more than simply a weak hypothesis. I believe that with these words Wurtz has passed judgment on his own hypothesis. . . . The symbolic expressions for our views on the proximate components of a compound and on their relative positions may of course change. But to assign a compound two different rational formulas at the same time , i.e., to maintain that it possesses sometimes one set of atomic groupings as proximate components, and at other times another set. . . is to maintain an impossible proposition.^[33]

This gave Wurtz another opening. As far as their chemical consciences were concerned,

Mine is less delicate concerning formulas. I envision them as expressing the mode of derivation, parental ties, and reactions of compounds, and in no way share the opinion of M. Kolbe, who endeavors to express the exact grouping of the atoms with the aid of his rational formulas. He pretends to know the nature and role of the groups in organic compounds. . . . I express merely parental ties. I express certain reactions, and everyone will agree that it is impossible to express all reactions by means of formulas of this kind.

Wurtz then carefully reiterated his position: lactic acid is indeed monobasic, which explains the absence of dimetal and acid salts. It is, however, diatomic, that is, it has alcohol character, a fact that Kolbe was trying to ignore. Wurtz had no intention of contesting Kolbe's key assertion that lactic acid is related to propionic acid; but it is just as clearly related to propylene glycol, for the latter oxidizes smoothly to lactic acid. Wurtz pointed out that the products of hydrolyzing butyryl ethyl lactate were consistent only with his, and not with Kolbe's, formulation of the compound. Finally, Wurtz presented a table directly comparing his and Kolbe's formulas for the same set of lactic acid derivatives and suggested that chemists choose between them. One might differ over issues of esthetics and informational content, but there is no question that Wurtz' were more compact and simpler.^[34]

The following year Wurtz let fly another volley, in conjunction with his student Charles Friedel. They directly compared the two ethyl compounds of lactic acid, namely, the ethyl ester and the ethyl ether; the former was neutral, while the latter was fully as acidic as the parent acid. It would be hard to imagine a clearer demonstration of the replaceability of both "typical" hydrogen atoms and also their chemical nonequivalence.^[35]

Kolbe let loose his own shot. "The efforts of some chemists," he wrote in a paper co-authored with Lautemann, "to demonstrate alcohols and aldehydes also for dibasic acids, e.g., to claim ethylene oxide hydrate as the alcohol and glyoxal as the aldehyde of the dibasic oxalic acid, are unscientific frivolities that deserve no notice here."^[36] This was a strange outburst, both in the unjust violence of expression, as well as in its logic. Kolbe himself had repeatedly suggested that dibasic acids must have reduced forms—he had simply denied that glycol and glyoxal are the reduced forms of oxalic acid.^[37]

Debus was moved to respond. It is possible, he wrote, to recast the Kolbe-Lautemann assertion into "a decent form." However,

Before the judgment of Messrs. Kolbe and Lautemann can make the slightest claim for consideration, the concepts indicated by the words "aldehyde" and "alcohol" must be clarified. Then there must be derived from these concepts, or from a general principle, or from an a priori intuition, and not for example from any set of empirical observations, the impossibility that dibasic acids may correspond to aldehydes or alcohols. Messrs. Kolbe and Lautemann have not to my knowledge offered any demonstration of this sort, and therefore their verdict loses all foundation.

Debus also pointed out that Kolbe had predicted precisely what he was now claiming to be impossible. And since he had predicted such alcohols and aldehydes, what proof had he that glycol and glyoxal were not those compounds?^[38]

Kolbe's search for these missing substances led him to speculate on a possible isomerism phenomenon in glycolic and lactic acids. Might it not be reasonable to think that they could exist in two modifications each? In particular, perhaps the conventional glycolic acid is hydroxymethyl formic acid and is produced from the oxidation of chloroacetic acid. In contrast, Debus' oxidized alcohol may not be identical to this compound but rather it may be the isomer methoxy formic acid, a monoester of carbonic acid. Similarly, perhaps conventional lactic acid is hydroxyethyl formic acid, while the known isomeric compound, lactic acid from meat, is ethoxy formic acid; or the other way around.^[39] He privately speculated on the further possibility that oxalic acid may be analogous to glycolic acid, in the sense of being monobasic but di-

atomic. In this case, there should be two chemically distinct ethyl oxalates; a yet unknown isomer of oxalic acid should also exist that is truly dibasic and homologous with malonic and succinic acids.^[40] Nothing concrete came of these ideas. Wurtz, too, had suggested the possibility of isomeric glycolic acids, but as early as 1858 Kekulé had asserted the identity of all candidate isomers.

Few of Kolbe's colleagues shared his sense of triumph over Wurtz in the matter of glycolic and lactic acids. Disagreeing with Wurtz over what must have seemed to most observers to be relatively subtle structural or even semantic distinctions, Kolbe generated many predictions, few of which were realized. None of his putative alcohols and aldehydes isomeric with Wurtz' and Debus' compounds, which he considered the true reduced analogs of the acids derived from glycols, were ever found, nor were the predicted isomers of glycolic, lactic, and oxalic acids or ethyl oxalates ever prepared. He himself, in conjunction with Guthrie, refuted his own prediction that one could dehydrate glycols to yield ordinary aldehydes.^[41] He also conceded Wurtz' refutation of his interpretation of the constitution of butyryl ethyl lactate.^[42] He ultimately adopted Wurtz' and Kekulé's view and language regarding the nature of lactic acid—that it was monobasic and diatomic—but he regarded this as his victory, not Wurtz'.^[43]

In the end, his strong uncollegial language in a matter that was even under the most favorable interpretation contestable, and that many considered a losing cause, could only do Kolbe damage. This was one more repetition of the sort of unpleasant polemics that he had waged over the previous ten years against Gerhardt and Williamson. By March 1860, despite his newly productive research program, Kolbe felt isolated and under attack from most sides. The newer type theory continued to attract adherents, including such respected establishment figures as Will, Kopp, and Strecker, a fact that thoroughly mystified Kolbe. Liebig had been acting unfriendly toward Kolbe for years, Berzelius was long dead, and his own mentors Wöhler and Bunsen, although supportive, were neither interested nor active in theoretical matters. In later years, he often reminded the chemical community of this period in which, as he put it, he was considered a "crank."^[44]

This unhappy situation was transformed in 1860 due to Kolbe's work with diacids and his predictions of secondary and tertiary alcohols.

Predictions Fulfilled:
Diacids and Novel Alcohols

In his major theoretical article, "On the Natural Connection of Organic and Inorganic Compounds," Kolbe made predictions that

were more successful. Having accepted the dibasic character of oxalic acid, he now proposed two "carbonic acid radicals" for other known diacids, such as succinic, malic, and tartaric acids. All three of these substances were known to have the same number of carbon atoms (four) and two carboxyl groups. Succinic acid has no other functional groups, whereas malic and tartaric acids have one and two additional atoms of oxygen (two and four equivalents), respectively. Kolbe suggested in his paper that malic and tartaric acids may have a similar relation to succinic acid as lactic and glyceric acids have to propionic acid, namely, that they may contain one and two (O₂ H) groups, respectively, substituted for H. He named them Oxy- and Dioxybernsteinsäure .^[45] When, late in 1859, Lautemann discovered that hydrogen iodide was capable of directly reducing the (O₂ H) group of lactic acid to H, Kolbe reasoned that he could test his prediction by attempting to reduce malic and tartaric acids to succinic acid by using the same reagent. He assigned the task to his promising young assistant, Rudolf Schmitt.

The reduction occurred uneventfully, and Kolbe sent the paper to Liebig. Liebig rushed it into print, fitting it into the very next issue after the one that carried Kolbe's prediction.^[46] Ironically, Liebig had recently published a different hypothesis regarding the constitutions of malic and tartaric acids.^[47] He wrote Kolbe a very friendly letter:

. . . the real purpose of this letter is to express to you the great satisfaction which your paper on the natural connection of organic and inorganic compounds gave me; the preparation of succinic from malic and tartaric acids is the triumph of your theory; I am only sorry that I recently gave a different interpretation of the constitution of these two acids, but I willingly recognize that yours is better.^[48]

To say that Kolbe was pleased by this letter is more than a small understatement. For the past six years, Liebig had been cool and sometimes even hostile toward him, at first apparently because of the one-sided and polemical character of parts of his book and then because in an article in the Handwörterbuch Kolbe had ignored Liebig's analytical method for mercury. Kolbe had been mystified by Liebig's unfriendliness. At first he supposed Liebig's residence in the Bavarian capital and association with King Maximilian II had made him an arrogant courtier; he then suspected that enemies were whispering in Liebig's ear.^[49] He replied to Liebig, delighted to see, as he put it, that his enemies had failed to sway Liebig's good opinion of him. A more public expression of approval, he hinted, would hasten the end to the influence of those who view the goal of chemistry as the "decoration of Gerhardt's schemata." To Vieweg he declared his intention of using Liebig's letter to pry more money out of the Kurhessian ministry.^[50]

Kolbe was still earning the same miserable salary he had accepted in 1851.

Feeling like the proverbial cat that swallowed the canary, he immediately wrote his closest friend, Vieweg, enclosing Liebig's letter. He added that he had long been convinced that his ideas would eventually triumph, and he now predicted that in a few years no one would even mention "the completely unscientific manner of treating chemistry of Gerhardt and his consorts, which unbelievably even Strecker has adopted . . ." Liebig's letter could make this happen all the faster; he asked Vieweg to return it as soon as possible so that he could make appropriate use of it with his Ministerium.^[51]

From this time onward, Liebig strongly supported Kolbe's research. Kolbe's discoveries, Liebig wrote him in December 1860, had the effect on him like that "of a trumpet on an old war horse," and he invited Kolbe to continue sending him his "gems" for publication. The following year Liebig averred to Kolbe that "the important thing is always that one starts down the right path, and all your work demonstrates that you are on the right path." There is much good work being done now in organic chemistry, Liebig continued, but also much playing around with formulas, and in most work one cannot discern the "scientific idea" that one must have as a goal, to clarify the physiological origins of various compounds.^[52] Liebig meant this praise sincerely; to Vieweg, to Fehling, and to Volhard he wrote in much the same terms about Kolbe.^[53] In February 1862 Liebig satisfied Kolbe's request for a public statement of approval, and in December of that year he proposed Kolbe as foreign member of the Bavarian Academy of Sciences.^[54]

Liebig's approval appears to have been founded on two general areas of agreement. First, like Kolbe, Liebig took conventional equivalents to be the chemical atoms themselves, and so for both of them such Gerhardtian types as HOOH (two molecules of water in equivalents but one molecule of water in atomic weights) were imaginary and therefore absurd.^[55] Second, Liebig felt that organic chemistry only made sense when it is pursued in conjunction with physiology. Since carbonic acid plays such a central role in physiology—especially for biosynthesis in plant physiology, from which most organic compounds dealt with in mid-nineteenth century organic laboratories were derived—Kolbe's carbonic acid theory made sense to Liebig in a way that the more abstract and schematic Gerhardtian theory did not.^[56]

Other predictions by Kolbe concerned novel alcohols. Kolbe, like the structuralists, formulated ethyl alcohol as a carbon atom (which for Kolbe was the double atom C₂ , his "Grundradikal") combined with two hydrogens, a methyl group, and what became known as a hydroxyl

radical. In his major theoretical paper, Kolbe pointed out that if one or both of these two hydrogen atoms were replaced by one or two additional methyl radicals, two novel substances would be formed. They would retain the hydroxyl group, but they would not be oxidizable to an aldehyde or an acid since each of these oxidation reactions requires abstraction of two hydrogens from the same carbon. They would therefore fail the defining criterion for alcohols, but could be termed "pseudoalcohols."^[57] These compounds are what modern chemists call isopropyl alcohol and tertiary butyl alcohol.

Of course, alcohols were familiar substances, long known to chemists chiefly as products of fermentation. The best known was ordinary (ethyl) alcohol, but it was also known that the so-called fusel oil, a higher boiling residue that remained after the redistillation of grain or potato alcohol, contained alcohol-like materials. The major constituent of fusel oil was found to be amyl alcohol (C₅ H₁₁ OH), but there was also a sizable amount of butyl alcohol (C₄ H₉ OH) and a much smaller amount of propyl alcohol (C₃ H₇ OH), along with a number of trace constituents. These three compounds were initially thought to be simple homologs of ethyl alcohol. The amyl and butyl alcohols were later found to possess branched-chain structures (for example, the latter is [CH₃ ]₂ CHCH₂ OH), and so they were eventually given the names iso butyl and iso amyl alcohols, the prefix designed to distinguish them from the straight-chain (or "normal") primary alcohols such as ethyl alcohol, or propyl alcohol from fusel oil. In the same way that ethyl alcohol could be dehydrated to ethylene, so could propyl, butyl, and amyl alcohols be dehydrated to the homologous olefins propylene, butylene, and amylene. During the 1850s, Berthelot demonstrated how to convert these olefins back to the alcohols by aqueous distillation from dilute sulfuric acid solution.

In the summer of 1862, Wurtz' student Charles Friedel published a note in which he described the reduction of acetone to a three-carbon alcohol, using nascent hydrogen generated from sodium amalgam. He refused to identify his product with propyl alcohol from fusel oil, saying the matter needed study.^[58] Four months later (12 November 1862) Kolbe learned of this paper by reading a German abstract. The next day he sent Emil Erlenmeyer, editor of the biweekly Zeitschrift für Chemie , a short article on Friedel's compound, asking that it appear in the next issue. "The subject interests me all the more," Kolbe wrote in his cover letter, "since I expect to find through Friedel's work a confirmation of my view (based on purely theoretical speculations) concerning the existence of such new alcohol-like compounds."^[59] In this paper, Kolbe suggested that Friedel's new alcohol was the isomeric propyl alcohol he had predicted years earlier. The

test would be to oxidize the compound; a secondary alcohol must yield acetone, whereas the known (primary) propyl alcohol would give propionic acid. He also suggested, presumably by comparing boiling points, that Friedel's product was the same as that propyl alcohol produced by Berthelot years earlier by hydrating propylene. But he said he did not want to forestall Friedel and so was leaving it for him to complete the investigation.^[60]

A few months later Friedel reported the oxidation experiment and confirmed Kolbe's prediction. But he added a mild protest. What other product than acetone could have been expected when the reduction product of acetone was oxidized?! Obviously, no one could imagine this was common propyl alcohol. He had been perfectly well aware of what he had when he published his first paper; he only wanted to be able to present clean results devoid of conjecture and had been having troubles over impurities, so he had temporized. In rebuttal, Kolbe conceded he could not prove that his idea had formed the basis for Friedel's reaction, but thought it curious that Friedel had not made the discovery until Kolbe's interpretation had appeared in print. His conclusion was that the episode clearly demonstrated the fruitfulness of his own theory and the barrenness of type theory.^[61]

Six months after Kolbe's rebuttal, in the summer of 1864, A. M. Butlerov identified a "tertiary pseudobutyl alcohol," trimethyl methyl (modern tertiary butyl) alcohol. He had obtained this new compound the previous year from the reaction of phosgene with methyl zinc, but had not immediately been able to specify its constitution. Butlerov noted that once more a prediction by Kolbe had been fulfilled. By this time, predictions of new isomers based on structure-theoretical precepts were rapidly proliferating. Butlerov argued, for example, that in addition to the known normal butyl alcohol and his new tertiary compound, exactly two more butyl alcohols should exist: a branched-chain primary (isobutyl) alcohol and a secondary butyl alcohol. (Here Butlerov was repeating a statement published a few months earlier by Kolbe.) As for the next higher homolog, no fewer than eight amyl alcohols should exist: four primary, three secondary, and one tertiary —or, by another manner of accounting, three associated with a straight-chain carbon skeleton, four with a branched-chain, and one containing a quaternary carbon atom. As far as lower homologs were concerned, structure theory appeared to predict a single methyl and a single ethyl alcohol. A similar analysis applied to the higher alcohols as well, and Butlerov was not slow to use the reaction that had given him t -butyl alcohol for the synthesis of new hexyl and octyl alcohols.^[62]

The secondary butyl alcohol predicted by Kolbe and Butlerov was first prepared by V. H. de Luynes about the time of Butlerov's paper. This appears to have been a fortuitous event, and de Luynes did not

attempt to determine the compound's constitution. Definitive identifications and structural assignments of all four isomers of butyl alcohol were first made in 1869 by Adolph Lieben, a student of Bunsen and Wurtz then working at the University of Turin.^[63]

The formula for the butyl alcohol found in fusel oil by Wurtz was at first structurally indeterminate, but presumably the substance was assumed to be normal butyl alcohol.^[64] Oxidation, however, did not yield normal butyric acid. In the meantime, Kolbe not only predicted the existence of an isobutyric acid (dimethyl acetic acid), but suggested no less than two different synthetic routes to it: isopropyl alcohol to isopropyl iodide to isopropyl cyanide, whose hydrolysis should yield isobutyric acid, or reduction of the hydroxyl group of acetonic acid (dimethylhydroxyacetic acid) using Lautemann's reducing reagent, hydrogen iodide.^[65] Even while making corrections and exchanging proofs of the article containing these ideas with his editor Erlenmeyer, Erlenmeyer informed Kolbe of his current attempts to produce isobutyric acid by oxidizing the butyl alcohol from fusel oil. Erlenmeyer published this work shortly before V. V. Markovnikov independently published essentially the same reaction. Erlenmeyer and Markovnikov both concluded that their starting material contained a branched carbon chain, i.e., that it was isobutyl alcohol, because they found that Kolbe's suggested syntheses from isopropyl compounds yielded the same product.^[66] In 1867 Frankland and Duppa removed any possible doubt about these structural assignments by ethylating and dimethylating ethyl acetate, yielding butyric and isobutyric acids, respectively.^[67]

Of all these new alcohols, isoamyl proved perhaps the most interesting—and intractable. It had long been known (simply as amyl alcohol) as the major component of fusel oil, as had the associated olefin amylene. Wurtz published a series of articles in 1862-1864 on these compounds, and especially on rehydrated amylene, which he called amylene hydrate, an alcohol-like material differing in properties from the original natural alcohol.^[68] Wurtz had the ill luck to have tackled a problem whose solution was beyond the capabilities of the science of his day. In fact, dehydration and rehydration of the natural alcohol had the effect of transferring the hydroxyl group two carbons down the chain, transforming a primary into a tertiary alcohol. The work was also hindered because fusel oils are complex mixtures from which it is difficult to isolate pure materials and because fusel oils from different sources often have quite different compositions (as Kolbe himself had discovered in his very first independent chemical research).

Erlenmeyer oxidized amyl alcohol from fusel oil; he obtained a valeric acid distinct from the normal variety. That this was isovaleric acid, i.e., a branched-chain structure, Erlenmeyer showed by produc-

ing the same compound by chain lengthening of isobutyl alcohol (converting to iodide, then to cyanide, and then hydrolyzing). Since isobutyl was by then known to be branched, the same had to be true for isovaleric acid.^[69]

As for Wurtz' amylene hydrate, Erlenmeyer and Kolbe independently suggested that it was a secondary alcohol.^[70] As early as December 1863, Kolbe was privately predicting that oxidation of amylene hydrate would yield diethyl ketone or, less likely, methyl propyl ketone. "Wurtz' most recent papers," he wrote Frankland, "are examples of how not to work, [they are] loose and sloppy." In February 1864 he claimed to have isolated what was "without question" the latter oxidation product and suggested that amylene hydrate was therefore methyl propyl carbinol (2-amyl alcohol); this was published in the Annalen later that year. However, the oxidation was not clean; from elemental analysis Kolbe concluded that he got only around fifty percent yield, the remainder being unreacted starting material. His formula assignment was based on an involved argument regarding boiling point regularities.^[71] Wurtz' investigation of the same reaction, published in the meantime, was just as problematical, but not consistent with Kolbe's results; he found that the carbon chain was broken, with the chief products being acetic acid and acetone. Ever cautious, Wurtz refused to draw any conclusions regarding the constitution of amylene hydrate.^[72] In fact, it was eventually established that amylene hydrate as prepared and identified by Wurtz does produce acetic acid and acetone upon oxidation. Straight-chain amyl alcohols are essentially absent in all fusel oils, and so Kolbe's published results are not easily explicable. He is vulnerable here to the suspicion of having found what he needed to find in order to verify his prediction.

At the same time that all of this was developing, Frankland and Baldwin F. Duppa published on the alkylation of oxalic ester, using zinc alkyls. A particularly interesting product was the diethyl compound, found to be isomeric with leucic acid (the latter was leucine, a six-carbon amino acid, converted by Strecker to a hydroxyacid by replacing its amino group by a hydroxyl group). Privately to Frankland and publicly in his paper on isomerism, Kolbe formulated it as diethyl glycolic acid. Although Kolbe did not realize it, this was consistent with Frankland's own formulation.^[73]

The New Complexion of Organic Chemistry

A final brief case study from this period further illustrates the new atmosphere in the discipline and is one more curious instance of hot pursuit by simultaneous workers on a set of fruitful new structural in-

vestigations. A variety of actors were involved: Hugo Müller, a student of Wöhler and Liebig, assistant to Warren De la Rue and a close friend of Kekulé from his London years; Hans Hübner, a student of Wöhler and of Kekulé before becoming Privatdozent at Göttingen; Wurtz' protégés Lieben, Friedrich Beilstein, and Maxwell Simpson (the latter also a former Kolbe student); and Simpson's British countrymen Crum Brown, W. H. Perkin, and Duppa. The relevant reactions all involved the Kolbe-Frankland technique of replacing halogen with cyanide, then hydrolyzing the cyanide to carboxyl. The net effect of this sequence is to replace a halide with a carboxyl group, thus adding a carbon atom. By such means, the chlorine in Kekulé's monochloroacetic acid could be used to form a second carboxyl group and so transform acetic to malonic acid; an analogous route, apparently, could transform propionic to succinic acid—in short, monoacids into diacids. A closely related route is to start with ethylene bromide, which would give rise to succinic acid by double hydrolysis. Working with Kekulé in Ghent in 1862, Hübner published on cyanoacetyl compounds, but did not report hydrolysis to malonic acid. About the same time, Simpson published on the ethylene bromide to succinic acid route.^[74]

From the summer of 1863 to January 1864, Kolbe described in letters to Frankland his work on this kind of malonic acid synthesis; he mentioned that on 17 January 1864 he had learned that his former student Crum Brown was working on the same problem. (Crum Brown's project in Kolbe's lab in 1862 had concerned diacids). On 12 February Kolbe sent Frankland and Erlenmeyer identical copies of a preliminary notice, with the request that the former translate and communicate it to the very next meeting of the Chemical Society, and the latter print it "as soon as possible ."^[75] Erlenmeyer dutifully inserted the note into the next issue of his Zeitschrift für Chemie , and Frankland had the paper read in English at the Chemical Society on 18 February.^[76]

Two days later a few unnamed Marburgers visited Göttingen and informed Hübner of Kolbe's work. Hübner, who thought he had reserved the topic to himself by his earlier publication, was indignant and crestfallen over all the effort he had now spent in vain in trying to isolate pure malonic acid product. Beilstein, then a fellow Göttingen Privatdozent, was nearly as angry. He described the affair in a letter to Kekulé, with whom he had studied in Heidelberg before going to Wurtz, saying that Kolbe had "stolen" malonic acid from Hübner in the "unkindest possible manner." The situation was even worse than it may seem, Beilstein continued. In the fall of 1863 he had visited Marburg; Kolbe had asked him about Hübner's work and how far along it was, and Beilstein had reported to Kolbe fully and freely. A few short months later, Kolbe was now claiming the reaction as entirely new.^[77]

Kekulé immediately reported the scandal to friend Müller in Lon-

don, for he knew Müller was interested in the diacids. Müller responded by confessing to Kekulé that he had "committed the same sin as Kolbe, by preparing not only malonic acid, but also succinic acid." He had been working for some time on this reaction, he said. He remembered Hübner's work on similar approaches, but it had not given clean results and had not been continued; in any case, he knew of no publication by Hübner on cyanoacetic acid, which was the important point. He also happened to know that Perkin and Duppa were working on the same reaction, but so far without success. He happened to have been present at the meeting of the Chemical Society on 18 February when Kolbe's note was read on this very subject. He was disconcerted, but had the presence of mind to report extemporaneously on his own results; the Society then resolved to published Kolbe's and Müller's notes together.

Ultimately this is a dirty trick, but I squandered the synthesis of succinic acid from ethylene [as Simpson's paper had already appeared]; the synthesis [of succinic] from propionic acid I intend to hang on to as tightly as possible. Kolbe may well be angry that I am contending with him about the further development of his own reaction, namely the introduction of CO₂ by the intermediate unit CN. In any case, I believe I can only do what my duty and obligation is. I am now working on preparing mono- and dibromosuccinic acid, possibly in order to produce the acids C₅ H₆ O₆ and C₆ H₆ O₈ . I hope that ultimately I don't end up by encroaching on you in this direction.^[78]

Frankland reported the events of 18 February to Kolbe. Kolbe responded by sending Frankland a letter to deliver to Müller proposing a collaborative approach. But in his cover letter to Frankland, Kolbe expressed concern that he might be too trusting. Was Müller a "Gentleman"? Perhaps Frankland should just keep the letter. "From what I hear, Müller is a good friend of Kekulé's, whom I do not consider a gentleman. I confess, this friendship between Müller and Kekulé makes me a bit doubtful. I place the matter entirely in your hands."^[79] Frankland did deliver Kolbe's letter, and Müller agreed to Kolbe's proposal. Müller's article appeared together with Kolbe's in the April issue of the Journal of the Chemical Society , and they resolved to stay in touch about their research plans. They subsequently agreed that Kolbe would henceforth work on cyanoacetic and cyanomalonic acids, and Müller on dicyanoacetic and cyanosuccinic acids.^[80]

Three months later Beilstein reported these events to Adolf Baeyer, whom he had befriended while both were working in Kekulé's Heidelberg lab in 1857. Not only had Kolbe acted unethically toward Hübner, Beilstein thought, but Simpson had also stolen a closely related

reaction from Adolf Lieben. (Beilstein claimed to know this because he had been Simpson's neighbor in Wurtz' lab in 1858-1859, where Lieben also then worked.) Finally, Beilstein claimed that Müller had behaved even worse, for Beilstein knew (presumably through Hübner) that Hübner had told Müller directly about his work on this reaction as early as the fall of 1861.^[81] Müller also failed to keep his word to Kolbe, publishing an article in the summer of 1864 on the reaction of trichloroacetic acid with potassium cyanide without letting Kolbe know. Kolbe was understandably wroth, and contact between the two ceased.^[82]

It is diffcult to assess blame in such matters at this distance of time, nor for our purposes is it useful or necessary to do so. What seems clear, at least, is that the practice of organic chemistry had suddenly become far more ruthless than it had ever been, and traditional customs of courtesy and ethics were often slighted or even ignored. Müller provided an appropriate postscript to all of this in a letter to Kekulé: "Doing chemistry these days is an accursed business; you never know when you are going to be overtaken by someone else."^[83] Kolbe and Erlenmeyer were not necessarily being paranoid when they speculated that some scientists used collegial visits to rival laboratories for espionage purposes.^[84]

Beilstein's complaint was slightly different, but rooted in the same phenomenon:

Everywhere we see indicated isomerisms and possibly existent compounds, which are becoming so numerous that even all the masses of material now known appears by comparison as but a drop. I was involuntarily reminded of the old saying, "Organic chemistry is the science of nonexistent bodies." Do these billions of compounds really exist? . . . I could never imagine that the dear Lord would want to make life so hard for chemists.^[85]

Beilstein was fundamentally nontheoretical and was genuinely distressed at the sudden diversity. He criticized Butlerov's textbook privately for making too many predictions of novel structural isomers. "Our students are already frightened by the mass of material; imagine their faces when they have predicted for them the existence of God knows how many additional compounds. . . . I am firmly convinced that experiment will considerably diminish the numerous isomerisms."^[86] Liebig's reaction was not very different; he wrote to Hofmann, "Through isomerisms, organic chemistry is gradually becoming enough to make one mad."^[87] The explorers of Wöhler's primeval jungle were emerging with daunting numbers of new chemical species.

Whether the issue was subtle distinctions between predicted be-

havior of polyfunctional compounds (as in the matter of lactic acid derivatives), or a sudden proliferation of similar isomers, all of which had to be interpreted according to structure-theoretical precepts, and many of which were being worked on simultaneously (such as the new alcohols), or cases of multiple discoveries of new reactions with consequent hurt feelings and priority disputes (as in the diacids), the new pattern was clear. Chemistry, particularly organic chemistry, had seen a sudden acceleration, essentially an explosion, datable to around the year 1860. This acceleration produced noticeable changes in the way work was done and reported, and was felt by all who were active in the field.

Later Years in Marburg

All the research activity described in the foregoing sections had a significant and very positive effect on Kolbe's career. From an average of twelve students per semester in Kolbe's practica of 1859-1860, the number increased to an average of twenty-two during the years 1860-1865. Average attendance at his lectures increased in the same period from thirteen to nineteen, and chemistry majors increased from essentially none to about nine per semester. At the same time, the average enrollment at Marburg increased only about two percent.^[88]

These changes came none too soon for Kolbe. On the last day of 1860, he wrote Vieweg

I may boldly assert that over the last two years no German university laboratory, even including Göttingen, has produced so many truly good chemical papers as has mine; at the same time Göttingen, Heidelberg, and even Giessen (where for a decade almost nothing has been accomplished) are overflowing with students.

Given the political situation and the reputation of the despised Kurhessian prime minister Daniel Hassenpflug, no one wanted to come to Marburg, Kolbe thought. Foreign students, the real mark of success, were especially notable in their absence; only in rare semesters were there any at all.^[89]

If Kolbe's great break as far as research is concerned occurred in 1858-1860, a similar break as far as student numbers are concerned came in summer semester 1862. Classroom enrollment and total numbers of Praktikanten were still about the same, but now he had five real chemistry majors as well as a number of advanced workers in the lab, including no fewer than six who already had Ph. Ds. Two of these six were his long-term prize students, his assistant Lautemann and his former assistant Schmitt. A third was a certain H. Scheuch, who pub-

lished one article from the Marburg lab but is otherwise obscure. A fourth was Bunsen's former student Carl Graebe (1841-1927), who stayed just that one semester and never offcially matriculated; he returned to Heidelberg that fall as assistant to Bunsen. He subsequently spent four extraordinarily productive years as assistant to Baeyer; his teaching career included periods at Königsberg and Geneva, and he was also involved with the early history of the Hoechst dye firm.^[90]

The fifth of Kolbe's Ph.D. workers that summer was Jacob Volhard (1834-1910), a former student of Will and Kopp at Giessen, who had served as assistant successively to Bunsen, Liebig, and Hofmann before his arrival in Marburg. Volhard's stints in Munich and London were relatively long ones (four and two years, respectively). He has been called Hofmann's oldest German student, but it appears that it was more Liebig's recommendation than Hofmann's that led him to Marburg. After working with Kolbe for three semesters, he returned to Munich, where he occupied the lower academic ranks for the next sixteen years. He accepted calls to Erlangen in 1879 and Halle in 1882. In his single publication from Kolbe's lab, Volhard insisted on using the reformed weights for carbon and oxygen—the first such publication from one of Kolbe's students. No doubt this was due to Hofmann's influence, from whom he had just come.^[91]

The last of the six was the Scots chemist Alexander Crum Brown (1838-1922), who had studied with the English Liebigians William Gregory and Lyon Playfair at Edinburgh and London, but who had also been strongly (if indirectly) influenced by Frankland, Kekulé, and Wurtz. After leaving Kolbe, he spent a year with Bunsen before returning to Edinburgh, where he succeeded in making a fine academic career.^[92] In addition to these advanced workers, we also know that Edmund Drechsel (1843-1897) was in Kolbe's lab in 1862 as well. Drechsel later worked with Volhard in Munich and with Kolbe and Carl Ludwig in Leipzig. He became a well-regarded physiological chemist and physiologist, teaching for many years at Leipzig and at Berne.^[93]

It was just at this time that Kolbe began to attract a steady stream of Russian chemists. The first to come, in that busy summer of 1862, was Konstantin Zaitsev (or in German transliteration, Saytzeff); the following semester he was joined by his brother Aleksandr Mikhailovich Zaitsev (1841-1910), who subsequently became far more famous. After two semesters, Konstantin left the lab, but Aleksandr remained there until Kolbe left for Leipzig. In the spring of 1863 three new Russians arrived, and in the following year came three more; in Kolbe's last semester in Marburg, Nikolai Aleksandrovich Menshutkin (1842-1907) studied with him. Butlerov, then at Kazan where many of these

men studied, must have advised several of them to travel to Marburg for foreign education.^[94]

We can follow the rise in Kolbe's fortunes by following his increasingly proud reports to Vieweg and to Frankland. In winter semester 1862/63, there were eighteen Praktikanten, and in the following semester twenty. In summer semester 1864 no fewer than thirteen of the eighteen Praktikanten came from outside Kurhessen. In the fall of 1864 the overall number jumped to twenty-nine, which, counting a few unmatriculated advanced workers, exceeded the capacity of the lab. Moreover, ever larger numbers of foreign Germans—Prussians, Saxons, Bavarians, and so on—were enrolling. Even non-German foreigners such as the nine Russians named, three Englishmen, two Scotsman, two Swiss, and two Americans enrolled during Kolbe's last two Marburg years. One of the Americans was Charles W. Eliot (1834-1926), who attended Kolbe's practicum in winter semester 1864/ 65; four years after that he became the president of Harvard University.^[95] One of the Englishmen was E. T. Chapman, who later published some excellent research in organic chemistry before his untimely death in 1872. Most of the foreigners at the entire university, Kolbe bragged in one letter, were his students, and the University's matriculation registry bears out the boast.^[96]

By the early 1860s Kolbe had earned a remarkable international reputation. A knowledgeable anonymous reviewer writing in the Westminster Review in 1866 thought that "the Marburg laboratory has played a very considerable part in the chemical history of the last seven years," and he referred to Kolbe as "one of the few chemists who have succeeded in forming a school." Kolbe's pupils—he named Lautemann, Griess, Guthrie, and Ulrich—he thought were "distinguished for a certain kind of originality, and for great practical skill." Moreover, the writer regarded Kolbe as next to Liebig "the most successful chemical teacher in Germany."^[97]

No detailed descriptions or university records of Kolbe's laboratory practicum have survived, but the general course was given in chapter 5. All surviving testimony indicates that Kolbe's teaching was conscientious, effective, and deeply appreciated by his students. We have cited comments regarding the Marburg years from Guthrie, Graebe, and Volhard, also in chapter 5. Kolbe hated the lab, referring to it as a "junk box" (Rumpelkasten ). He suffered regularly from breathing the fumes—hydrogen cyanide was a common reagent—and considered the lack of ventilation to be positively dangerous, with good reason.^[98]

In 1862 Kolbe was still working in essentially the same laboratory that he had inherited from Bunsen, which the latter had had constructed over twenty years earlier.^[99] The lecture room was renovated

in the summer of 1856, but the modest extent of the alterations is indicated by the fact that the work cost only 145 thalers. Moreover, the laboratory budget was wholly inadequate, a fact that Kolbe brought to the attention of the administration by ignoring it as regularly as possible. This did little to win him friends among his superiors and among colleagues in oversight committees. In the fall of 1860 the budget was increased from 700 to 800 thalers, but Kolbe was made personally responsible for any overages—a ruling that enraged him for weeks, so intensely that he could not work. Moreover, the budget was only designed to pay for equipment, instruments, and lecture experiments, not the consumption of chemicals by Praktikanten, who had to foot that bill themselves. He complained that his salary was barely half as much as would suffice to keep a family in proper style, particularly since his income from student fees was exceptionally low until around 1862.

But Kolbe's sudden success in research dramatically increased his local power and leverage; Liebig's public approval after 1860 undoubtedly also helped. In July 1861 Kolbe received his first raise in Marburg, from 600 to 700 thalers; eighteen months later it was raised again to 800. In early 1865 his salary increased once more, to 1000 thalers (but to add a note of perspective, Bunsen was earning 1200 thalers when he left in 1851). Finally, in May 1863 his often-reiterated proposal to renovate and expand his lab was finally accepted, and the work began immediately. Considering that no new spaces had to be constructed, the total cost of this renovation was relatively large, about 2000 thalers. The extent to which Kolbe's stock had risen can be seen by the fact that during that same summer, his laboratory budget was raised to 1000 thalers and a salary line for a second assistant was authorized. By the end of his Marburg years, Kolbe was making more than four times what he had been earning earlier from student fees, and his prestige was such that he could simply ignore all budgetary restrictions.

The laboratory space was completed astonishingly quickly, by the beginning of the next term (11 November 1863). The new lab was expanded to fill the entire west wing of the Deutsches Haus, including the space previously devoted to the lecture room, and could now be divided into sections for beginners, advanced workers, and large-scale general operations. The servant's residence in a small adjoining space was converted to a private lab for the institute director and was separated from the main lab by a glass partition. Smaller spaces were created to serve as a stockroom, a eudiometry room, a wardrobe, and a roofed open-air area for working with hazardous fumes. The east wing of the old building was converted to a large, light and airy lecture room, displacing the collections of the zoological institute. On the

second floor of the east wing, spaces were prepared for a balance and equipment room, a general storeroom, and a darkroom for photographic and spectrographic work.

A significant expense must have been incurred by Kolbe's insistence that every two work spaces be provided with water taps (connected to a reservoir filled from the nearby Lahn River) and every station equipped with gas for Bunsen burners. This was a comparative novelty at that time and was made possible by the simultaneous laying of gaslight installation for the city of Marburg. The lab was also equipped with a hundred gas illumination burners, so for the first time, work could continue after sunset. The net effect of this renovation was to more than double the total actual laboratory space—all three sections together measured about eighty by twenty-five feet—and to increase capacity by half, from about twenty to around thirty Praktikanten. The only thing that Kolbe still desired was an on-site residence for himself.^[100]

Kolbe was immoderately proud of his new lab. It was not just a good, it was an "elegantly outfitted laboratory," somewhat smaller but even better equipped than Bunsen's in Heidelberg and very similar to that in Göttingen. He reported to Vieweg that the gas burners, both at the bench and overhead, allowed him and his students to work about twice as fast as was previously possible. To his administration, he predicted a "new era" in the history of the chemical institute.^[101]

This new era, at least under Kolbe's aegis, was of short duration. Less than two years later he exchanged Marburg for Leipzig.