Chemistry for Everyone
The Story of the Wagner–Meerwein Rearrangement† Ludmila Birladeanu Department of Chemistry and Chemical Biology, Harvard University, Cambridge MA 02138;
[email protected] “When we see that we may produce hundreds of compounds from simple hydrocarbons and chlorine and that from each one of them we may obtain a great number of others … we ask with some anxiety whether, in a few years time, it will be possible to find our way in the labyrinth of organic chemistry.” This was written by Auguste Laurent in 1854, toward the end of his life (1). To facilitate navigation through this labyrinth, Laurent formulated the principle of “least structural change”, which states that molecules tend to undergo the fewest possible changes in structure during a chemical reaction. As examples, in a substitution reaction, the new substituent occupies the position liberated by the departing one; in eliminations, the hydrocarbon skeleton remains unchanged. Laurent’s principle became the general guiding concept on which the determination of the structure of organic compounds was based. Yet only a few years after the principle was enunciated a reaction was discovered that eventually shattered its infallibility. In 1860, Fittig published a paper on the elimination of water from a C6 alcohol (known today as pinacol) that he had obtained on heating acetone with sodium (2). He recognized the product as a C6 ketone and named it “pinacoline” (pinacolone today), but did not propose structures for either the starting alcohol or the product. The structure of pinacol was inferred a few years later by Linnemann from its oxidation to acetone (3), while that of pinacoline was finally established as methyl tert-butyl ketone in 1874 by Butlerov, of structural theory fame, who accomplished its synthesis from trimethylacetyl chloride and dimethyl zinc (4). Additional confirmation came from oxidation to trimethylpyruvic and trimethylacetic acid. The formation of pinacoline from pinacol had clearly involved a shift of a methyl group (eq 1). Thus it was established inescapably that a basic change in the carbon skeleton had occurred during the loss of water. This “pinacol rearrangement” became the first definitive example of a reaction in violation of Laurent’s principle. H3C
CH3
H3C [H ]
H3C
OH
OH
H3C
CH3
(1)
H3C H3C
†
CH3 H
H 3C
CH3
H 3C
CH3
HCl
This paper is dedicated to the memory of Costin D. Nenitzescu and Saul Winstein.
858
C
X
X
COOH H2C
C
(3)
COOH H2SO4
C
COOH
H2C
C
H2C
H
O
H
OH OH
(4)
O
H
Considering hydrogen migration of this type to be a general phenomenon, Erlenmeyer proposed in a footnote its application to the pinacol rearrangement. He wrote, “My assumption is that on acid-catalyzed elimination of water from pinacol a methyl group participates as shown below [eq 5], giving a tertiary alcohol, which I consider unable to exist and which rearranges in statu nascendi into the ketone by migration of the hydroxyl hydrogen.” CH3
H3C OH
(2)
C
Does it break away from its original point of attachment and return subsequently to the adjacent carbon atom, or does it migrate without separating? Finding the answers to this and other mechanistic questions became an irresistibly fascinating area of organic research and remained a center of attention for more than a century. The resulting insights revolutionized the theory of organic chemistry. The first attempt to understand the mechanism of the pinacol rearrangement was made by Erlenmeyer in 1881, in a paper dealing with the acid-catalyzed dehydration of glyceric and tartaric acids to pyruvic acid. He had formulated these reactions as loss of water to give an intermediary enol acid, followed by migration of hydrogen from oxygen to carbon to yield the keto acid (7) (eq 4).
CH3
H3C
CH2 OH
H3C
CH3
H 3C
C
H
OH
R
C
C
A closely related rearrangement (eq 2) was discovered by Couturier (5) in the acid-catalyzed dehydration of pinacolyl alcohol, which had been obtained by Friedel on reduction of pinacoline with sodium amalgam (6 ). In addition to the expected tert-butylethylene, tetramethylethylene was produced. Here was a second example in which a methyl group had shifted. H3C
R
H3C
O
H3C
CH3
These discoveries gave rise to an insistent question of mechanism: How does the methyl group, or more generally an R group, migrate from one carbon atom to its neighbor (eq 3)?
H3C
O C H2
H
O
H2C
(5)
H
This “nonexistent alcohol” had been formulated as a substituted cyclopropane, but at the time, cyclopropane was not known. Its first synthesis was reported one year later by Freund (8), and its chemistry was first described in the 1890s, primarily by Gustavson (9). No significant developments in the field of molecular rearrangements occurred for almost two decades. Then Zelinsky reopened the possibility of a role for three-membered rings in these rearrangements (10). As shown by Gustavson, not only were substituted cyclopropanes (such as 1,1-dimethylcyclopropane) more difficult to obtain than the parent, but once formed, they were much more susceptible to ring-opening reactions. Zelinsky was specifically interested (for theoretical
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Chemistry for Everyone
reasons unfortunately not stated) in 1,1,2-trimethylcyclopropane as a potential intermediate in the dehydration of pinacolyl alcohol to tetramethylethylene. This trisubstituted cyclopropane turned out to be stable in the presence of mild acids such as oxalic acid. Zelinsky recognized the possibility of isolating this cyclopropane, if the dehydration of pinacolyl alcohol could be effected with as weak an acid as oxalic instead of the much stronger acids commonly used. Under these mild conditions, the dehydration did in fact occur, but the only isolable product was tetramethylethylene. Nevertheless, Zelinski persisted: “These results show that pinacolyl alcohol must isomerize into dimethylisopropylcarbinol, because only this alcohol can yield tetramethylethylene. The isomerization could take place in two ways: by interchange of a methyl and hydroxyl group, or by dehydration to 1,1,2-trimethylcyclopropane, followed by the re-addition of water under the influence of acid, to give the rearranged alcohol. I consider the formation of the cyclic compound as intermediate highly probable. Its intermediacy would also explain the puzzling transformation of pinacol into pinacoline, a reaction involving the reshuffling of all the atoms” (Scheme I).
H
Camphene crystalline
CH3
CH3
CH3
-H2O
+H2O
CH2
H 3C
HO
OH
H3C
CH3
CH3
C
-H2O H3C
CH3
Scheme I
OH CH
CH2
CH
(CH3)2C
H H Isoamyl Alcohol
CH
H Alkylidene
CH2 (H3C)2C CH2
(CH3)2C
CH
CH2
~H
(CH3)2C
CH
CH3 (CH3)2C
H "New" Alkylidene
CH
Trimethylethylene
Scheme II
Isoborneol
Borneol Oil from Dryobalanopa Aromatica
Oxidation
Camphor
MPVO
Scheme III
Mechanisms involving cyclopropane as an intermediate were also invoked by Nef for rearrangements occurring in the formation of olefins obtained from certain alkyl halides, alcohols, and esters of inorganic acids by elimination. In detail he had envisioned these reactions, as exemplified by the transformation of isoamyl alcohol into trimethylethylene (11), as “dissociations” into alkylidenes, cyclization to the corresponding cyclopropane, and “dissociation” of the ring to a new alkylidene, followed by hydrogen migration and formation of the rearranged olefin (Scheme II). The pinacol rearrangement was represented by an analogous but even more complicated scheme.
(CH3)2HC
C10H17Cl "Artificial Camphor"
O CH3
CH3
CH3
HCl
n
OH
HO
Pinene Oil of Turpentine
CH3
tio
H 3C
CH3
CH3
HCl
ida
HO
KOH
Ox
CH3
CH3
H 3C
CH3
n
H3C
CH3
-H2O
tio
H
OH
ida
CH2
OH
H 3C
H3C
VO
+H2O
Ox
CH3 -H O 2
H
CH3
CH3
MP
H3C
H 3C
HC l
CH3
The hypothesis of cyclopropane as an obligatory intermediate dominated thinking in the field of molecular rearrangements for two decades. The final chapters in the quest for understanding might have revolved around the simple compounds we have seen in the discovery of the rearrangements. In fact, the final resolution involved far more complex examples that had come to light during the fascinating, but quite separate elucidation of the structure and chemistry of certain bicyclic monoterpenes. The events in this complex story began in the early 1800s, with the list of those involved reading like a Who’s Who of early organic chemistry. The main compounds involved in this saga were the monoterpenes pinene and camphene; their oxygenated derivatives camphor, borneol, and isoborneol; and the bornyl and isobornyl halides. None of these structures had been established prior to the 1890s, although camphor and borneol had been known since antiquity and the valuable properties of oil of turpentine, which consists mainly (>95% ) of pinene, were recognized as early as the 13th century. All that was known were empirical formulas and a few reactions relating one compound to another (Scheme III). The field was bedeviled by controversy, frustration, and recrimination of a highly personal sort!
CH3
We begin with Kindt’s observation in 1802 (12) that treatment of oil of turpentine with dry hydrogen chloride produced a substance that smelled like camphor. Kindt named this substance “artificial camphor”. Its composition was correctly established as C10H17Cl by Dumas in 1832 (13). Oppermann investigated the action of lime and other bases on artificial camphor, presumably with the goal of removing hydrogen chloride and recovering pinene, which is a liquid. Instead he obtained a partially crystalline substance of composition C10H16 (14). Dumas repeated Oppermann’s experiments and named the crystalline hydrocarbon camphene (15). Surprisingly, neither he nor Oppermann reacted to the observation that pinene had not been regenerated. Three decades would elapse before Berthelot confronted and resolved this problem. Borneol, another important participant in the story, was found to yield camphor on oxidation (16 ). Gerhardt observed that the two were related as “alcohol and aldehyde” (17). That borneol was indeed an alcohol was ultimately shown by Berthelot, who obtained esters on treatment with various organic acids. He also found that borneol could be prepared from camphor on treatment with alcoholic potassium hydroxide, the first example of a Meerwein–Ponndorf–Verley– Oppenauer (MPVO) equilibration. A second alcohol of the same composition but different rotatory power was also
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Chemistry for Everyone
formed in this reaction and was subsequently named isoborneol. Berthelot further discovered the oxidation of camphene to camphor (18), a mysterious transformation of an olefin into a ketone that remains perplexing to this day. Camphor turned out to be the central compound in all these transformations. Not surprisingly, solving its structure challenged many of the influential organic chemists of the day. More than 12 incorrect structures were proposed. Not until Bredt identified and established the structure of the three major oxidation products of camphor—camphoric, camphanic, and camphoronic acid—could its correct structure finally be formulated (19). This formula accounted for all the products obtained on oxidation and immediately gained universal acceptance. We return to “artificial camphor”, which for many years had been regarded as a derivative of pinene. This belief had to be abandoned when Berthelot, repeating Dumas’s experiment, at long last recognized the implication of the fact that treatment of “artificial camphor” with bases had failed to regenerate liquid pinene but had produced crystalline camphene instead. Therefore “artificial camphor” could not be a derivative of pinene, but was a derivative of camphene (18). This conclusion signaled the possibility of a structural rearrangement in the conversion of pinene to “artificial camphor”. Subsequently, Wagner recognized “artificial camphor” to be identical to bornyl chloride obtained by treating borneol with hydrogen chloride. Now the time had come for elucidating the structure of camphene (incidentally, the only crystalline, easily purifiable hydrocarbon in the bicyclic monoterpene series). The task was formidable. Berthelot’s finding that camphene afforded camphor on oxidation led to numerous constitutional formulas simplistically related to those put forward for camphor. Thus, when Bredt finally came up with the correct structure for camphor, he could propose two structures for camphene, giving preference to structure 2. CH3 H2C
C
CO
H2C
H2C
CH Camphor
C
CH2
H 2C
H2C
C 1
5 CH2
3 H2C
6 CHOH
2 H2C
8 H3C·C·CH3
2 H 2C
1
C
CH
H 2C
CH
H C4
3 H 2C
5 CH2 6 CH
C
H C4
8 C
5 CH2
8 H3C·C·CH3
H 2C 2
1C
7 CH
C6 H
C 1
CH3 CH3 CH2 7
7 CH2
3
Borneol
Camphene
OH
H3C H3C
H 3C
CH3
H 3C
CH3
CH3
H3C
H
Tetramethylethylene
Pinacolyl Alcohol
Scheme IV
Disregarding any mechanistic considerations, the acidcatalyzed transformation of pinacolyl alcohol into tetramethylethylene formally involves the elimination of a molecule of water and the shift of a methyl group from one carbon atom to the neighboring carbon, replacing the OH group in the process. The equivalent formulation of the dehydration of borneol or isoborneol involves the shifting of the methylene group at C-2 from C-1 to C-6, to afford the olefin camphene. To facilitate the perception that the two transformations are identical the formulas are redrawn in Scheme V. CH3
H 3C
HO
H
CH2
CH2
H 2C
H 3C
OH
H2C
CH2 CH3
H 3C
CH3
H Isoborneol
H
CH CH2
H3C·C·CH3
H3C·C·CH3 CH2
H C4
3 H 2C
CH3
CH3
H3C·C·CH3
obtained oxidation products” (Scheme IV).
H 3C
CH
CH3
CH2 CH2
CH2
CH3
2
H3C
Camphene
Wagner challenged this interpretation in 1899, in a remarkable paper entitled “The Structure of Camphene” (20). He recognized that the results of the oxidation of camphene and some of its derivatives were incompatible with those expected on the basis of Bredt’s formula 2. Wagner made the revolutionary suggestion that the acid-catalyzed dehydration of borneol into camphene involved a molecular rearrangement and, by implication, that camphor and camphene did not have the same skeleton. He wrote: “This suggestion is prompted by the following reasoning: based on Bredt’s accepted camphor formula, the structure of borneol is reminiscent of that of pinacolyl alcohol. Both are secondary alcohols with a tertiary radical as one of the substituents. Couturier had shown that treatment of pinacolyl alcohol with hydrogen chloride, followed by elimination of the added hydrogen chloride with base, gives tetramethylethylene [5]. A similar formulation, applied to the rearrangement of borneol into camphene, leads to a formula for the latter that predicts correctly all the previously
860
HO
CH3 H
CH3
H3C CH3
Pinacolyl Alcohol
H3C
CH3
H3C
CH3
Tetramethyletylene
Scheme V
Wagner’s “astonishing insight” (as aptly noted by Meerwein [21]) was the major breakthrough that brought the two lines of investigation together. It shed light on the whole field— “Lux facta est”—and made possible the construction of correct hypotheses for the previously confusing transformations then known. The modern representation of the structure of bicyclic monoterpenes is shown below. Unfortunately, Wagner died
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four years later, in 1903, before he could see the full impact of his contribution.1 H 3C
CH3
CH3
H3C
CH3
H3C
CH3
CH3
H
Cl
CH3
Cl
CH3
At this time, Meerwein was considering an alternative mechanism that had been stimulated by Tiffeneau (26 ). It involved elimination of water from the carbon atom bearing the hydroxyl group, leaving two free valences that would be transformed into a double bond by migration of an alkyl group. Meerwein extrapolated this mechanism to rearrangements like that of camphane dichloride to camphene (Scheme VI).
CH3
H
H
H3C
Pinene
CH3
H3C
Borny l Chloride Artificial Camphor
CH3
Isobornyl Chloride
CH3
H 3C
CH3
H
CH3
CH3
OH
H 2C
H 2C 2Na
C
C
CCl2
H3C
CHBr
a
(6)
H 3C
H 3C 2,6-Dibromobornane
C CH3
C
C
H2C
CH
C
CH2
CH3
Ruzicka hoped to distinguish between the two mechanistic hypotheses—tricyclene as an intermediate versus a divalent carbon atom—by examining tertiary alcohols, which are unable to lose the elements of water from the same carbon atom (27). He synthesized two tertiary alcohols, methyl borneol and methyl fenchol, which on treatment with potassium hydrogen sulfate both underwent dehydration with rearrangement (Scheme VII). Divalent carbon as a credible intermediate was thus excluded. However, Ruzicka’s hope to distinguish between the two mechanistic hypotheses was logically unacceptable. From the fact that divalent carbon was not an intermediate it could not be concluded that tricyclene was the intermediate. CH3
CH3
C
C
CH3
H2C
Tricyclene
Tricyclene became widely accepted as intermediate, particularly because small amounts of this hydrocarbon had been isolated from the dehydration of borneol to camphene (22). This acceptance was entirely justifiable, but for one insurmountable flaw. When the transformations discussed above were performed with optically active starting materials, the products were invariably optically active, as had been shown by Laffont (23). Tricyclene has a plane of symmetry (is achiral)—as was clearly pointed out by Semmler, who correctly argued that if tricyclene were an intermediate in the rearrangement of (for example) optically active borneol, the resulting camphene would have to be optically inactive (24). That it was in fact optically active was in complete contradiction. Nonetheless, in two subsequent papers, Semmler ignored his own conclusion and accepted tricyclene as an intermediate, only to reject it again in his final paper on the subject. To further complicate matters, at about the same time, Lipp reported that optically active isoborneol always yields racemic camphene (25); only later was this “observation” shown to be in error.
CH3
H 2C
C
C CH2
OH H3C·C·CH3 H2C CH2 CH Methylborneol
H 2C
C CH
OH CH3 CH3
Metylfenchol CH3 C
C
c
CH
Scheme VI
CH3
b
H2C
CH2
CH3
BrHC
CH3 CH3
CH2
CH
H 2C
Camphor
Zn
CH3
CH3
H3C·C·CH3
CH3
H3C
C
O
Now that the structural interrelationships involved in these strange reshufflings of atoms were clear—the transformation of borneol and isoborneol into camphene, camphene into isobornyl chloride, and pinene into bornyl chloride, to name just a few—the overriding question became “How do these transformations occur?” The similarity to the retropinacol rearrangement, in which cyclopropane derivatives were widely favored intermediates, led to a consistent assumption that a cyclopropane must also be an intermediate in these transformations. An attractive candidate already existed in tricyclene, whose structure was correctly inferred by Semmler from its preparation by the action of zinc dust on 2,6-dibromocamphane. Its close relation to both camphene and the camphane system in the bornyl and isobornyl derivatives is apparent from the two possible modes of ring opening (a–c and a–b, eq 6). CH3
H 3C
H 3C
CH2
CH H3C·C·CH3
H Isoborneol
H 3C
H3C
CH3
C
H3C
H 2C
OH Borneol
OH
C
H3C
H 3C
CH3
H3C
Camphene
CH2
H 2C CH2
CH3
H 2C CH
CH3
H 2C
CH2
H3C·C·CH3 H 2C CH2 CH Methylfenchene
Methylcamphene CH3
C HC C H3C·C·CH3 H 2C
CH3
CH2 CH
Methyltricyclene
Scheme VII
Remarkably, both methylborneol and methylfenchol gave identical mixtures of methylcamphene and methyl-αfenchene, consistent with their rearrangement via a common intermediate. The only compound Ruzicka could identify as a possible intermediate was a methyltricyclene. Concerning Semmler’s 1902 contention that an achiral compound like tricyclene was unacceptable as intermediate in reactions where both starting material and product are optically active, Ruzicka had this to say: “One must note that the carbonyl group of camphor finding itself between two optically active carbon atoms will be, to a great extent, asymmetrically reduced,
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and the resulting borneol will have one additional asymmetric carbon. Consequently, its tricyclene may be considered an optically active species.” Meerwein, who strongly supported Semmler’s chirality argument, responded curtly: “Ruzicka’s explanation is so unclear that further elaboration is unwarranted” (28). Today it is hard to understand how a major organic chemist like Leopold Ruzicka, who was awarded the Nobel prize for his work on terpenes, could defend a hypothesis in conflict with one of the most compelling generalities in the science: that achiral molecules cannot give rise to chiral ones in the absence of an asymmetric environment. When molecular rearrangements were discovered in the 1860s, however, they appeared so incomprehensible that the only way older theories could accommodate them was by assuming that they proceeded by a sequence of “normal” reactions, even though these puzzling reactions might have involved a new phenomenon not yet understood. For example, the formation of tert-butyl bromide (along with the expected isobutyl bromide) in the reaction of isobutyl alcohol with HBr was interpreted as elimination of water to give an olefin, followed by the Markovnikov readdition of HBr. (CH3)2CHCH2OH
[H ]
(CH3)2C
CH2
+HBr
(CH3)3CBr
(7)
Clearly, the familiar elimination–addition mechanism was unable to account for the migration of alkyl groups; thus the intermediacy of cyclopropane was introduced. By the late 1890s, ring closures and ring openings of the three-membered ring were well established, so that explanations based on familiar sequences of known reactions could remain in place. To dismiss the optical activity argument seems to have been the less objectionable alternative. In 1920 Meerwein and van Emster published a seminal paper entitled “On the Reaction Mechanism of the Isoborneol– Camphene Rearrangement”. This paper began with another look at Tiffeneau’s proposal of a divalent carbon species as intermediate (29). The authors’ goal was to examine a reaction that would lead, without doubt or question, to such an intermediate. The chosen precursor was the known complex of camphor hydrazone and mercuric oxide, which, they felt confident, would be accepted as proceeding by way of “the divalent carbon species”. If Tiffeneau’s mechanism were correct, camphene should have been the product. In reality, tricyclene was formed almost exclusively (Scheme VIII). CH H 2C
CH HgO
CH2
H3C·C·CH3 H 2C C
-[N2+H2O+Hg] N.NH2
H 2C
CH2
H3C·C·CH3 H 2C C
CH H2C CH2 H3C·C·CH3 HC
CH
C
CH3
CH3
Camphor hydrazone
CH3 Tricyclene
Camphene
Scheme VIII
This experiment marked the end of the divalent carbon hypothesis, but happened to provide by far the best available synthesis of tricyclene! Meerwein and van Emster seized the opportunity to reinvestigate the role of tricyclene in
862
the isoborneol–camphene rearrangement. They found that tricyclene remained unchanged under conditions where isoborneol was completely transformed into camphene (heating with 33% sulfuric acid). The same result had been obtained earlier by Lipp with zinc chloride (30). Meerwein and van Emster also found that the rate of addition of monochloroacetic acid to camphene to yield isobornyl chloroacetate was much faster than the rate of its addition to tricyclene. These experiments supplemented and confirmed the optical activity argument against tricyclene and definitively excluded its role in the rearrangement of isoborneol to camphene. In his summary Meerwein stated, “at the present time, the mechanism of these strange transformations cannot be affirmatively answered.” What a sobering thought! After decades of research all the old hypotheses failed and one was back to ground zero! But not for long. After only two years, an astounding new approach was presented in another pioneering work of Meerwein and van Emster entitled “Equilibrium Isomerism among Bornyl Chloride, Isobornyl Chloride and Camphene Hydrochloride” (1922) (31). This extraordinary work opens with a discussion of the unexpected behavior of camphene hydrochloride. Unlike its isomers, isobornyl chloride and bornyl chloride, camphene hydrochloride possesses an extremely labile chlorine atom, which may be quantitatively removed in a few minutes by treatment with water or alcohol. Even at low temperature, it reverts to camphene. It also rearranges to isobornyl chloride— slowly on standing, faster on heating or in contact with acids. Eventually equilibrium is reached among all three isomers; at room temperature this equilibrium is almost completely shifted towards the thermodynamically more stable bornyl chloride. To ascertain that equilibrium was indeed established, Meerwein and van Emster studied the kinetics of the rearrangement and uncovered a strong dependence on solvent. Fastest in solvents of high ionizing power, the rate decreased in the order SO 2 > CH3NO2 > CH3CN > C 6H 5NO2 > C6H5OCH3 > C6H6 > petroleum ether > ether. This sequence correlated with that observed in the ionization of triphenylchloromethane, determined quantitatively by conductivity measurements by Hantzsch (32). In this important paper, Hantzsch proposed that the species undergoing dissociation were “carbonium salts”, [(C6H5)3C]+[X᎑]. Such conductivity measurements were not available to Meerwein in the camphene hydrochloride system because the rates of the rearrangement were much too fast to be measured in the required ionizing solvents. The rearrangement of camphene hydrochloride was also accelerated by salts that form complexes with triphenylchloromethane. These include stannic tetrachloride, zinc chloride, antimony pentachloride, antimony trichloride, and mercuric chloride, but not phosphorus trichloride or silicon tetrachloride. The results prompted Meerwein to write: “The so-established extensive parallelism between camphene hydrochloride and triarylhalomethanes entitles us to assume that it, too, undergoes ionization, although for reasons mentioned above, direct proof by conductivity measurements is here not possible.” Meerwein had thus recognized that the key to understanding these rearrangements was ionization to a positively charged ion, within which the structural change subsequently occurred. The first and rate-determining step was formulated
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as the ionization of camphene hydrochloride to the hydrocamphene cation, followed by a rapid 1,2-bond shift to the isobornyl cation. H2C
CH
H2C
CH
C(CH3)2
H 2C H2C
CH2
CH CH2
C
CH3
H2C
CH
C(CH3)2
C·CH3
Cl
CH2
Cl
C·CH3
H 2C
(8)
HC
Cl
Camphene hydrochloride
CH
C(CH3)2
1
Note 1. This great chemist was born in Kazan, Russia, in 1849. His name bears the initials E. E. (for Egor Egorovich) in papers published in the Journal of the Russian Physico-chemical Society, whereas when publishing in German journals, it appears with the first name Georg. Nothing was ever simple when dealing with terpenes!
2
Meerwein’s hypothesis of carbocations as intermediates was one of the conceptually great breakthroughs in physical organic chemistry. It opened the door to a vast suite of organic chemical reactions and the refinement of their mechanisms. Some of the greatest chemists (Ingold, Winstein, Roberts, Bartlett, Brown, Whitmore, and others) became involved in this research. The record is filled with intense, often bitterly personal controversies. But there can be no question about the immensely constructive influence of Meerwein’s insight on the development of organic chemistry. Ionic mechanisms became an intrinsic part of its arsenal. A change from “Wagner” rearrangements to “Wagner–Meerwein” rearrangements was more than justified. Dethroning cyclopropane from its revered position as the intermediate in molecular rearrangements had been a long, hard struggle. One would have thought that the ionic mechanism would have quickly put to rest any further consideration of cyclopropane derivatives as intermediates. But the fires continued to be fueled by the much more complicated behavior of the fenchols and were fanned by many, including Semmler, Ashan, Wallach, Quist, Toivonen, Meerwein, and in great measure by Komppa, who dedicated 30 years of his scientific life (1911–1940) to the elucidation of the role of cyclopropanes in the rearrangement of fenchols and other bicyclic monoterpenes. The embers were at last extinguished by Doering and Wolf. This chapter, however, is more germane to the subject of hydride transfer as a means of generating carbocations, and so is not pursued here. The advent of nuclear magnetic resonance (in particular, 13C NMR), and the discovery in the 1960s of experimental techniques that made it possible to obtain stable solutions of simple alkyl carbocations enabled their direct observation. From accepted intermediates carbocations became observable entities. These modern techniques have revealed still other deep-seated rearrangements, which our existing knowledge cannot adequately explain. And so, the story continues… Acknowledgment I am deeply grateful to Frank H. Westheimer for his thorough reading of the manuscript and his very helpful advice.
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JChemEd.chem.wisc.edu • Vol. 77 No. 7 July 2000 • Journal of Chemical Education
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