The difficult marriage of theory and French organic chemistry in the 20th century

ELSEVIER

THEO CHEM

Journal of Molecular Structure (Theochem~ 424 (1998) X-206

The difficult marriage of theory and French organic chemistry in the 20th century’

Georges Bram”, NguyZn Trong Anhh**

“Insrifur de Chimie MolPculuire d’Orsay (ICMO) et Groupe d’Histoire et de Diducrique dec Sciences d’Or,wv (GHDSOI. hil~irnent 407

Universirk de Paris&d, 91405 Orxg Cedex. Frurlce

hl*thorcztoirr des Mhcanismes RPacrionnels (DCMR)‘. &ole Polwechniqur. 91128 Puinisecur Cedex Frtmw

Received 27 February 1997; accepted IO March 1997

Abstract

In the first half of this century, the postivism of many French organic chemists, who were reluctant to speculate about phenomena not directly observable, generated a certain scepticism for theories, with many unfortunate consequences. Thus. reaction mechanisms were not taught until the late 1950s and organic synthesis of complex molecules was consequently hampered. MO theory was practically ignored until 1965, when Woodward and Hoffmann published their epoch-making papers. The situation was restored in an astonishlingly short time, but the marriage between theory and French organic chemistry was, and still is, a difficult one. 0 1998 Elsevier Science B.V.

Krpwords: Atomic theory: Reaction mechanisms; MO theory; Opposition of the French establishment

At the end of the last century, in opposition with the views held by some more perceptive scientists (Wurtz. Grimaud) [1,2]?, several of the best French chemists (Berthelot, Dumas, Sainte-Claire Deville) still considered atomic theory to be rank speculation 131:

L’expkrience 2 la main, vous trouverez les

equivalents de Wenzel, les Cquivalents de Mitscherlich, mais vous chercherez vainement les atomes tels que votre imagination a pu les r&ver, en accordant 2 ce mot, consacrC

* Corresponding author. Fax: 00 33 01 69 33 30 10. ’ Dedicated to Professor L. Salem on the occasion of his 60th

birthday. ’ Associated with the CNRS. ’ Grimaud was put into forced retirement after he signed a petition

in favour of Captain Dreyfus.

malheureusement dans la langue des chimistes.

une confiance qu’il ne mCrite pas I.. .]. Si j’en Ctais le maitre, j’effacerais le mot ofome de lu

science..

[Jl. Since they were quite influential (Berthelot was at a

time Minister of Education), atomic theory was widely taught only after the deaths of their disciples” [5]. This was certainly one of the major causes of the decline of organic chemistry in France.

The same positivism generated a certain scepticism for theories and new ideas. This of course is not specific to France. In every country, there are always

?ththe 195Os, some highschool teachers continued to call it the atomic hypothesis. There were of course exceptions: in 1910. the Bohr atom was already discussed in Darzena’ course.

0166-1280/98/$19.00 0 1998 Elsevier Science B.V. All rights reserved

PI/ SO l66- 1280(97)0024 l-8

202 G. Bram, N. Trong AnWJoumal of Molecular Structure (Thenchem) 424 (1998) 201-206

very good scientists with conservative opinions. Thus Armstrong, at a meeting of the Council of the

Chemical Society (1925), proposed a motion stating

that

henceforth the absurd game of chemical noughts and crosses be taboo within the Society’s precincts and that, following the prac-

tice of the press in ending a correspondence, it be an instruction to the officers to give notice “That no further contributions to the mystics of

Polarity will be received, considered or published by the Society”

[61. He also dismissed Robinson’s curved arrow, saying

that “a bent arrow never hit the mark” [7]. The difference was that in Great Britain, Armstrong

faced some formidable opponents (Robinson, Ingold, Lowry...), whereas in France, speculations on reaction mechanisms were almost unanimously frowned upon in the first half of this century. Berthelot wanted to reduce chemistry to “positive laws and facts” [8]. Freundler expressed the wish that “people soon renounces these more or less fantastic intermediates they try desperately to invent in the vain hope of finding an explanation, which in fact explains nothing

at all. In any cases, these interpretations should be banished from the teaching of organic chemistry” [9]. Two examples will illustrate this positivism in

research and teaching. Tiffeneau spent more than 40 years studying

rearrangements [lo], which he rationalized using “affinity capacity” and “migratory aptitude”. He

showed keen mechanistic perceptions and, as early as 1907, made a clear distinction between transition

state and intermediate. Thus, he introduced in his

schemes “intermediate structures’ ’ with “dangling valencies”, specifying that they are transient and therefore different from “intermediate products”,

which could be isolated [I 11. He later remarked that if a positive charge was put on the carbon, and a negative charge on the oxygen, the intermediate structure he proposed for pinacolic rearrangement would be very similar to Ingold’s [ 121. Yet, Tiffeneau never openly accepted Robinson-Ingold’s ideas. In the late 1930s he asked one of his most brilliant co-workers, B. Tchoubar, to study these theories “ci la mode en Angleterre ’ ’ . Tchoubar rapidly recognized their importance. She pointed out that affinity capacities

and migratory aptitudes could be advantageously replaced by the electronic approach and, to examplify it, wrote a short note on the mechanism of the now

called Tiffeneau-Demjanov rearrangement. Tiffeneau was highly interested but refused finally to submit it to the Academic des Sciences: “after

all, they are only interpretations” [13]. In his organic chemistry textbook, Prevost stated

that

the Markovnikov rule, the Holleman rule, the affinity capacity and migratory aptitude hypotheses, the theories of variable affinity, of negative groups, do not explain experimental

facts but only present them in a pretentious, falsely scientific language. The theory of steric hindrance is hardly less arbitrary. The charac-

teristics these theories attribute to various groups are not well defined, seldom measurable and often contradictory” [ 141.

Prevost considered that “modern theories of

reactivity” require too much mathematics and

physics, are only applicable in some narrow fields and are thus out of place in an undergraduate course. He was reluctant to speculate about reaction

mechanisms, which cannot be directly observed and therefore, preferred for his own teaching an adapted

version of Lapworth-Lowry ideas. In ionic reactions, heterolyses are assumed for saturated reagents and rr systems are represented with alternating charges. Recombinations then take place between (the formal) ions of opposite charges. According to Prevost, this “ionic hypothesis, even if it does not explain all the facts, has the great advantage of using a very s+nple

language, of being an indisputable mnemonics and of englobing several earlier empirical theories. It does

not essentially differ from the modern theory, in the domains where both are applicable. . . ” .6

It that Prevost was a more likeable person than these harsh comments may have led us to believe. In the early 1960s. during an oral examination, he admonished a student for not citing Raney nickel among hydrogenation catalysts: “Nickel is cheap, palladium and platinum are expensive. Never forget, Mister, the price of the chemicals.” The second question was about oxidation. Prevost waited and waited and the reagent was not mentioned. At the end, he exploded: “Have you ever heard of the iodo-silver benzoate complex? Ah Monsieur, I’argent, c’est bien trop cher!” Prevost laughed and gave the student a good mark.

’ Ref. [ 141, p. 6.

G. Brum. N. Trong AnWJourmrl of Molrrulnr Structum (TheochernJ 424 (199X) 201-206 303

There is nothing fundamentally wrong with

PrCvost’s teaching philosophy. The problem, however, is that although no theory is perfect, all theories are not equivalent. And it is sometimes simpler to use a sophisticated theory than trying to preserve a more elementary one with ad hoc additions. Careful perusal

of PrCvost’s textbook shows the “ionic hypothesis” treatment to be rather unsatisfactory. Quite often, difficulties’ are dodged with the statement: “This can be theoretically justified, but the explanations are outside the scope of this book.” Many unnecessary notions (desmotropism, allelotropic mixtures, pseudoform, metamers, ditropic and monotropic transpositions.. .) are introduced. For allylic rearrangements, we end up with Kirmann-PrCvost’s syionie and mttaionie

which are more complicated and less enlightening than the resonance theory he wanted so much to avoid.”

In the 19.50~ the reputation of French organic chemistry was at its lowest ebb.”

To be sure, good papers were published in “classi- cal” synthetic chemistry (DuPont, Kirmann, Prkvost,

Vavon.. .) or polymer chemistry (Champetier), but studies in many important fields were scarce. Chemistry of natural products was almost non-

existent. Reaction mechanisms, in the Robinson- lngold sense, were conspicuously absent in teaching as well as in research. Instead, what was found in many textbooks was chemical equations in which

some atoms were boxed together:

[---F; 0 1 R-CjOH + &-&H - , __---_A R-&OR’ + H,O

I L______.__________

This kind of schemes was later termed “la chimie au lasso”” by the young Turks. These schemes were useful as mnemonics but did not much help the student in understanding why the Hz0 oxygen came

?%&&example, why, in propene and in styrene, must we put a formal rzr~ufive charge on the terminal carbon atom?

‘Ref. [14],pp. Ill, 118, 119. 121. ’ Woodward hesitated for a long time before accepting in his lab a

German chemist (H. G. V.) who, convinced of the necessity of French-German reconciliation. has spent one year in France after hia Ph.D. I” To he fair. “lasso chemistry” was not specific to French text-

hooks. See. for example, [IS).

from RC02H and not R’OH, or whether esteritication

should be conducted in neutral, acidic or basic medium. Naturally, planning long syntheses without a thorough understanding of mechanisms was not easy and it came as no surprise that the Velluz team at Roussel-Uclaf, who pioneered the use of reaction

mechanisms in France, was one of the few groups capable of synthesizing complex molecules. The

weakness of the dyestuff industry”. entailed a lack of interest for MO theory and consequently. photochemical studies were often carried out in an almost

purely empirical manner. Use of spectroscopies was not widespread and Jacques related that the day he defended his thesis. Mrs Ramart-Lucas gave

him, “solennellement, comme s’ils ktaient, eux aussi, des diplhmes”, three UV spectra of his compounds [ 17 1.

The situation was restored in a astonishingly short

time, thanks to several favourable factors. In the tirst place, up to the late sixties, research funds were abun-

dant and numerous positions were created every year. Many of the new Professors, Maitres or Directeurs de recherches were well aware of the failures of the Uni-

versity, and quite decided to fight its sclerosis. They updated the courses, introduced new research themes and began to send their students abroad for postdoc-

toral stays. The GECO (Groupe d’&udes de Chimie Organique), created in 1959 by G. Ourisson and a bunch of iconoclasts, played an important role in this respect.

In the 1960s. most of the gap had been bridged. The creation of the lnstitut des substances naturelles in Gif

filled a crying need. “Lassoing mechanisms” were fast losing ground after the publication of the books by Mathieu and Allais [IS]. by Julia [ 191 and by Tchoubar (201. Conformation4 analysis and

I After a promising start, the French dyestuff industry soon lagged behind its rivals. One reason for this setback was the vigourous opposition to atomic theory by Berthelot and his acolyteb. Also the French pateni laws, which protected the product rather than the process, did not encourage the search for new \ynthese\ ([16]). As a result. industrial organic chemistry foundered some- what and before long. many people began to think that the future ol the Industry rather lies in inorganic chemlstrq. In an unpublished study on the chemistry cursus at the Ecole Polytechnique. P. Four- nier notes that a~ the beginning of this century. there was \ome lobbying for reducing the part of organic chemistry, “which ha\ no use whatsoever”.

204 G. Bram, N. Trong Ant/Journal of Molecular Structure (Theochem) 424 (1998) 201-206

spectroscopic methods became parts of the undergraduate cursus in most Universities. Noteworthy

contributions in these domains appeared [2 1,221, and French chemists actively participated in develop-

ping NMR and mass spectrometry for structural determinations.

A serious problem remained however. The majority of the experimentalists still showed little interest in

MO theory. It is true that before 1965, quantum chemistry was important mostly in four domains rather neglected by French chemists: (1) spectroscopy

(almost entirely left to physicists); (2) coordination chemistry, which will be strongly developped only in the 1970s thanks to the volontarist policy of the

CNRS (Cantacuzene, Maurel); (3) chemistry of conjugated systems and photochemistry; and (4) valence and chemical bonding. The first three topics were

practically not taught12, and the last one, which could not be avoided, rather badly handled. Generally only Lewis theory was covered. The contributions of

quantum theory were skipped or, when they were mentioned, often misrepresented. For example, con-

fusion between orbitals and states was commonplace. Thus, in several textbooks, p and d states were represented by drawings like the following:

2% Prevost, who understood mesomerism better than

many of his contemporaries, made however this surprising comment:

L’hypothese (de la mesomerie) revient non plus

a admettre que le benzene oscille entre les cinq schemas proposes13, mais qu’il a une constitu- tion unique qui participe de celle de chacun de ces cinq schemas. II est evident qu’un esprit positif peut difficilement concevoir la significa-

tion physique de ce compromis.‘4

A textbook on chemical bonding stated that for

“It appears the first modem French textbook on coordination chemistry is that by Mathey and Sevin [23]. Almost all the previous textbooks did not go beyond Werner complexes. See, for example,

r241.

Most of the French organic chemists were therefore at a loss when appeared the Woodward-Hoffmann papers. We knew they were important but could not

undertand them. Most of the times, the books we con- sulted or the lectures we attended did not help much: there were too much mathematics and physics and not enough organic chemistry. Clearly, in courses centered on the subtleties of hermitian operators, on the probabilist interpretation of wave functions or on

the technical difficulties of the self-consistent field’“, we could hardly find the key information we were looking for (i.e. the mysterious “orbital symmetry” was linked to the Coulson formulae for conjugated polyenes). l6 Students and chemists of the Gif-Orsay area were privileged: in 1967, L. Salem gave a

graduate course on pericyclic reactions. Lionel was one of the few theoreticians who could give simple but not oversimplified explanations. In fact, although his course was intended for experimentalists, theoretical difficulties were extensively discussed. For

example, it was pointed out that the derivation of the selection rules for photochemical sigmatropic

rearrangements was far from obvious; that the path- way followed by the photochemical Diels-Alder reaction depended on which partner was excited. Whenever possible, a physical interpretation was

given. Thus, it was stressed that in SN2 reactions, the HOMO(nucleophile) - LUMO(substrate) inter-

action not only creates a bonding between the nucleophile and the substrate but also induces the C-X (X being the leaving group) bond breaking, by populating the a:x antibonding orbital [26]. It was

an exciting course in which what was taught was living science, with new discoveries and problems still to be solved. It was also comforting to find that our failure to understand some papers was due not only to our ignorance, but also to real underlying difficulties.

” The two Kekul6 and the three Dewar formulae. I4 Ref. [14], p. 113.

‘5ocourses often culminated at the Hz ion molecule. “For an exception, see [25].

butadiene “there is in fact union of the four p orbitals to give a single MO containing the four ?r electrons”.

When in the 1950s a young Clermont-Ferrand Professor, A. Kergomard, gave an introductory course

based on Coulson’s “Valence”, he was severely criticized by an older colleague: “You are using a hydraulic press just to crack some hazelnuts!”

G. Brutn. N. Trong AnWJourml qf Molecular Structure (Theochrm) 424 11998) 201-206 205

The year 1965 marked a turning point. The

Woodward-Hoffmann rules removed a crucial

psychological blockage: quantum chemistry was recognized as something useful for the understanding of everyday chemistry, not an esoteric knowledge reserved for some happy few with a strong back- ground in mathematics. Later, an explosion of papers by Hoffmann, Fukui. Dewar. Zimmerman, Salem,

Klopman, Hudson, Houk and many others confirmed the point: MO theory, and especially the frontier orbital approximation, could be employed by experimentalists the way they used spectroscopy, emphasiz- ing the applications and skipping purely theoretical

considerations.” Dewar argued convincingly that perturbation theory is the method of choice for chemical problems [27]. Hoffmann’s papers [28] detailed in a

very didactic manner every step: how to model a problem, how to make calculations and how to interpret them. They also proved that “the theoretical chemist is not a mathematician, thinking mathemati- cally, but a chemist, thinking chemically” [29]. Jorgensen and Salem’s book [30] explained how to construct MOs of a large molecule from the orbitals of smaller fragments and thus supplemented nicely the Hoffmann papers. At that time, few of us had

access to computers and the orbital drawings in this book were therefore quite helpful.

The variety of subjects-many of them of direct

interest to experimentalists-studied by Salem and his grouplx certainly helped to convince many French organic chemists that interesting experiments may be suggested by calculations. Let us illustrate this new attitude by two examples. In 1974, Pierre and Handel showed that if Lit and Na’ are trapped with [2.1. I ] and [2.2.1 I cryptands, ketone reductions by LiAIHj and NaBHA no longer occur, at least in non-protic solvents ]31]. Loupy, Seyden and Tchoubar pointed out that the main effect of cationic complexation is a lowering of the substrate’s LUMO. Therefore, if a

carbonyl compound has a low enough LUMO, it can be reduced even without electrophilic assistance.

I ’ To detect carbonyl groups by IR spectra, it is not necessary to knou how to derive the selection rules. Ix Inter alia: photochemistry (Salem. Devaquet, Bigot), asymmetric

mduction (Salem, Anh. Eisenstein), organometallic chemistry (Eisenntein, Sevin, Jean. Volatron), heterogeneous catalysis (Salem. Minot). electrochemistry (Salem), valence bond theory (Hihertyl. dynamics (Chapuiaat. Jean, Leforestier), etc.

Indeed, benzaldehyde does react with LiA1H3 in the

presence of [2.1. I]. The rate is diminished but remains acceptable, the yield in benzyl alcohol being 45% after 1 mn [32].

Using STO-3G calculations. Loupy and Seyden found that in the LUMO of free acrolein. the largest coefficient is on CA, whilst in the LUMO of the clrr complex, the largest coefficient is on Cz. They consequently predicted that conjugated addition with

LiAlHj is possible on the free compound. Indeed, when cyclohexenone is reduced by LiAIHJ (ether, room temperature, 15 mn). I,2 addition is dominant (98% cyclohexenol, 2% cyclohexanone. for a total yield of 98%). In the presence of [2. I. 11, the regio- selectivity is inverted: 77% cyclohexanone, 23% cyclohexenol (total yield 80%) 1331. Some 15 years

later. a graduate student (c. Bezard) pointed out to one of us that if the Loupy-Seyden argument is correct, then a Diels-Alder reaction between an electron-rich diene and a conjugated aldehyde, if catalyzed by a Lewis acid, should give a dihydropyran as the major product. A rapid literature search contirms his

reasoning 1341. Since - 1985, a chasm seems again to develop in

France between theory and organic chemistry. So many new results are published every year that most chemists tend to stay in their specialized tield. Fewer

and fewer experimentalists are doing their own calculations, even routine ones. At the same time,

occasional collaborations are made more difficult, because a paper may be rejected for technical reasons, if the referees feel that the calculations are not of a high enough level. This may mean several months of supplementary calculations, even when the problem

has been clzemicall~ solved. The fact that most of the French applied theoreticians have left organic chemistry for organometallic or solid state chemistry does not help either. These trends are reflected in the teaching. In several universities. the Woodward- Hoffmann rules are taught. but not perturbation

theory. Under the influence of the pharmaceutical industry, more place is given in the normal cursus to molecular mechanics than to MO theory. However, more changes can be anticipated. Starting in 1995. a minimal knowledge of frontier orbital theory is required of the candidates to the competitive exami- nations for engineering schools (“Grandes &oles”). Considering the traditional rivalry between the

206 G. &am, N. Trong AnhLJourd of Molecular Structure (Theochem) 424 (1998) 201-206

universities and the Grandes lkoles, it is probable that

in the near future, a larger place will be made for theoretical chemistry in the universities.

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[33] A. Loupy, J. Seyden-Penne, Tetrahedron Lett. (1978) 257 1. [34] S. Danishefsky, J.F. Kerwin Jr, J. Org. Chem. 47 (I 982) 3 183.

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The difficult marriage of theory and French organic chemistry in the 20th century