Theory of the Mesostructure of Organic Compounds

> ……Die Konstitutionsformel soll ja doch schließlich Ausdruck des ganzen chemischen Verhaltens sein…… I. H. van’t Hoff.

Theory of the Mesostructure of Organic Compounds

> ……Die Konstitutionsformel soll ja doch schließlich Ausdruck des ganzen chemischen Verhaltens sein…… I. H. van’t Hoff.

Submitted 1928 | SovietRxiv: ru-192801.07711 | Translated from Russian

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I. I. Kotelkov, Prof. STI.

Theory of the Mesostructure of Organic Compounds

……Die Konstitutionsformel soll ja doch schließlich Ausdruck des ganzen chemischen Verhaltens sein…… I. H. van’t Hoff.

PREFACE

The present work was completed in 1920, and therefore I was able to use only the literature accessible at that time (up to 1914). I consider it necessary to print this work now without any changes, only with certain abridgments, in the form in which it was completed in December 1920. I am impelled to this decision by the following reasons: 1) the literature of wartime will remain inaccessible to us for a long time yet; 2) the reviews we have received (Pummerer, Henrich) show that the subject I am developing is being discussed very actively, and I do not consider it possible to delay publication further; 3) the basic laws and consequences of my work, as it seems to me, will not change as a result of using the newest literature. Only new examples could be cited, but since the old ones I cite have not yet been fully clarified, I think that replacing them would not play a major role; 4) as regards the principal problem of the rotation of the plane of polarization, I was able to use the Zentralblatt, so that the main question will be treated quite up to date.

Organic chemistry is a branch of the doctrine of matter concerned with carbon compounds, for which reason it is also called Kohlenstoffchemie. The basis for singling out this field was provided by the characteristic features of carbon compounds, which find expression in the sharply pronounced ability of carbon atoms to combine with one another. As is known, carbon atoms form what is called the skeleton of an organic compound; but just as a skeleton does not constitute the whole organism, so organic compounds do not consist of carbon alone. The overwhelming majority of organic compounds contain, along with carbon, other elements as well, of which hydrogen is the most frequently present. Without any exaggeration one may say that the number of organic compounds containing no hydrogen amounts to only a few. Carbon constitutes the firm basis of the structure of organic compounds and the real foundation of classification. Naturally, in investigations, and especially in theoretical interpretations and generalizations of various phenomena, the chief role is always and everywhere assigned to carbon. Until now very little attention has been paid to hydrogen—it has been the stepson of organic chemistry. Yet an exact delimitation of the phenomena in which the chief role is played by carbon from those in which the dominant significance belongs to hydrogen is sometimes very difficult. In investigating various phenomena, we everywhere and always have the joint presence of both carbon and hydrogen and their simultaneous influence; so that if until now we have explained most phenomena by the properties of the carbon atom, we have been making a certain logical error, for the phenomena may be based both on the properties of carbon and on the properties of hydrogen.

The present work is an attempt to clarify the significance of hydrogen in organic chemistry, for, as it seems to me, the latter plays not only an important but at times also a dominant role. This applies especially to the phenomenon of the emergence of secondary valences, which, as I shall try to prove below, almost never arise in carbon, but arise exclusively in hydrogen, which in such a case exhibits bivalence. I think that I shall be able to raise the significance of hydrogen to the same level as that of carbon. This also explains the somewhat paradoxical title of this paragraph.

INTRODUCTION.

Categories of Carbon Bonds and the Basic Idea.

Among the countless variety of carbon bonds, a variety both qualitative and quantitative, the following five categories may be outlined:

Fatty simple bond (in ethane).
Alicyclic simple bond (in hexamethylene).
Aromatic simple bond (in benzene).
Bond between carbon atoms in ethylene.
Carbon bond of acetylene.

The indicated categories of carbon bonds, as a simple arithmetic calculation shows, differ from one another in the “intensity of exchange affinity” between carbon atoms. They are arranged in order of increasing

of this intensity. The difference in the exchange of affinity between these categories is not a constant quantity. Without doubt, the difference between the second and the first categories is not so great as that between the second and the third. And the latter, in turn, is smaller than the difference between the fourth and the fifth. These categories are only certain intermediate states, between which there exists a large number of other bonds, and these gradations are measured by vanishingly small quantities. Moreover, I believe that each category (this is especially clear for the ethylenic bond) may approach any neighboring category; for we know both cases of complete inertness of the double bond and of very easy rupture of the ordinary bond with addition of other atoms. The benzene bond sometimes behaves like a naphthene bond, as, for example, in polysubstituted cycles; in other cases it represents a typical ethylenic complex, and so on.

If, in these limiting cases, we wished to note only the formal aspect, then it would be natural that the establishment of new categories would be entirely useless: it would merely be a new complication of the question. But besides arithmetical calculation there are also deeper reasons for establishing new categories. In accordance with what has been said above, I imagine very gradual, almost imperceptible transitions from one category to another, and, since until now we have neither a method nor a corresponding unit for measuring the force of affinity in all organic compounds, it is clear that we cannot regard this or that bond in one case as twice or three times stronger than in another. Therefore, for the sake of uniformity, I shall designate every carbon bond by a single stroke, and where the arithmetical calculation indicates a more intense exchange, I shall draw a heavier line. The relative width of these strokes will, of course, be entirely arbitrary. Thus we obtain the following designations (drawing 1).

I believe that the intensity of the exchange of affinity has a direct influence on the character of the hydrogen atom situated at the given carbon bond. Namely, the more intense the exchange, or the stronger the given carbon bond, the weaker the bond between carbon and hydrogen. In other words, the residual affinity of the hydrogen atom is directly proportional to the strength of the neighboring carbon bond—the more affinity is consumed in the mutual saturation of the carbon atoms, the more mobile is the hydrogen at this bond.

The basis for the assumption stated above I see in the following facts. As is known, the nitration of hydrocarbons proceeds under different conditions depending on whether we take an aliphatic compound, a naphthene, or an aromatic hydrocarbon. Thus concentrated nitric acid has almost no action on normal aliphatic hydrocarbons. Hydrogen is not replaced even on heating; only the oxidation reaction is accelerated. In a series of naphthenes the action of concentrated nitric acid proceeds somewhat more energetically. Thus, to obtain nitrocyclohexane from hexamethylene, heating only to $50^\circ$ is sufficient. Benzene, belonging to the next category, is nitrated so readily that it is sometimes necessary to resort to cooling. And such substances as phenol are readily nitrated even by dilute acid. As for the fourth category, here there is no corresponding experimental material, owing to the readily occurring oxidation reaction. The same may be said of acetylene.

Thus, in the first three categories the picture is sufficiently clear, since it is obvious that the stronger the carbon bond, the more readily nitration proceeds. Owing to purely technical difficulties we cannot obtain direct proof of the replacement of hydrogen at a double and a triple bond. However, we have a whole series of indirect indications.

If there is a double bond between two carbon atoms, then each of them saturates two units of affinity of its neighbor. Just as with that,

Thus also in the other the bond with hydrogen, as compared with a single bond, is very much weakened. Here we have two identical carbon atoms and, consequently, two groups of hydrogen atoms. In such a case we could test their activity at two points. However, it is enough for us to create suitable conditions at only one carbon atom, for even in such a case we could verify our assumptions. It is precisely under such conditions that secondary and tertiary carbon atoms are found. Indeed, although these atoms are not entirely under the same conditions of “intensity of affinity exchange” as in the case of a double or triple bond, they are nevertheless under more or less analogous ones.

\[ {}^{*}\mathrm{H}_2\mathrm{C}=\mathrm{CH}_2 \qquad\qquad {}^{*}\mathrm{H}_2\mathrm{C} \begin{matrix} \diagup & \mathrm{CH}_3\\ \diagdown & \mathrm{CH}_3 \end{matrix} \]

\[ {}^{*}\mathrm{HC}\equiv\mathrm{CH} \qquad\qquad {}^{*}\mathrm{HC} \begin{matrix} \diagup & \mathrm{CH}_3\\ - & \mathrm{CH}_3\\ \diagdown & \mathrm{CH}_3 \end{matrix} \]

The hydrogen atoms attached to such carbons are considerably more active than those in unbranched paraffins in the second case and at the end of the chain in the first; they are usually nitrated more readily than the others. But, of course, this indication is only indirect and is not especially convincing.

Almost the same may be said of the sulfonation reaction. Quite analogously to what was stated above, sulfuric acid does not react in the cold with fatty compounds, reacts better with naphthenes, well with aromatic hydrocarbons, and gives, with double and triple bonds, products of oxidation and addition.

Thus, in the first three categories we have a very clear gradation in the activity of the hydrogen atom and some indication of its easy replaceability at a double bond. As evidence of the very great mobility of the hydrogen of acetylene there serves its well-known capacity to be replaced by a metal—a capacity always characteristic only of very active hydrogen atoms. These latter are usually attached to carbon atoms burdened with complex radicals.

Thus, let us accept provisionally that the stronger the carbon bond, the more mobile is the hydrogen atom attached to it.

There exists a whole series of facts that compel us to accept the completely opposite for chlorine. The stronger the carbon bond, the more firmly is the halogen bound to the given carbon.

A halide in the fatty series, under the action of sodium hydroxide, is readily split off, a hydroxyl taking its place. Its mobility is characterized, among other things, by the ease with which, under the action of $\mathrm{SO}_3$, it is split off from carbon:

\[ \mathrm{C}_2\mathrm{H}_5\mathrm{Cl}+\mathrm{SO}_3 \longrightarrow \mathrm{C}_2\mathrm{H}_5\mathrm{OSO}_2+\mathrm{Cl} \]

The splitting off of a halide in naphthenes is considerably more difficult. Here the rate of reaction is already lower, and stronger heating is required than in the fatty series. The strength of a halide in the aromatic series is well known, and I shall not speak of it here. The removal of a halide standing at a double bond proves to be already a very difficult matter. Thus, for example, $\mathrm{KCN}$ does not react with $\mathrm{CH}_2:\mathrm{CHBr}$, and chlorine is less mobile in $\mathrm{CH}_2:\mathrm{CCl}.\mathrm{CH}_3$ than in $\mathrm{CH}_2:\mathrm{CH}.\mathrm{CH}_2\mathrm{Cl}$, etc.

The halogen derivatives of acetylene have so far been poorly investigated, since these are very inconvenient substances: they are poisonous, explosive, and ignite in air—

soul. In any case, with the well-known $HC:CCl$ and $HC:CBr$, $HC:CCN$ has still not been obtained, which obviously depends on the low mobility of the halogen. Thus, I believe that from the motley and not always correctly arranged series of facts we can draw the following conclusions:

The stronger the carbon bond in each individual case, the weaker the bond of hydrogen with the given carbon.
In many cases the halogen is bound the more firmly, the stronger the carbon bond.

I would refrain from putting forward these propositions if very important consequences did not follow directly from them. These consequences illuminate a vast number of facts that have hitherto seemed enigmatic and not connected by any general law. I regard all the subsequent exposition as a continuation of the proof of the undoubted reliability of the above-established fundamental propositions.

From the first proposition it follows directly that the weaker the bond of hydrogen with carbon, the greater the residual affinity of the former. This creates, to the highest degree, favorable conditions for the formation of a bond of hydrogen with other atoms than carbon, i.e. for the emergence, in its presence, of a secondary valence.

This secondary valence will obviously be the stronger, the stronger the neighboring carbon bond, i.e. it will be very weak in the saturated series, stronger in the naphthene series, strong in benzene, and it is possible that very strong with a double and triple carbon bond. This secondary valence, under certain conditions, will of course more readily be saturated by the secondary valences of such atoms as possess a great affinity for hydrogen, i.e. by halogens, oxygen, and nitrogen. The possibility is also not excluded that two residues of different hydrogen atoms will mutually saturate one another. Such conditions may arise not only within a single molecule, but also between different molecules, thus causing the formation of molecular compounds.

I believe that the strength of a halogen attached to carbon is in great dependence on the neighboring hydrogen. Namely, if a hydrogen atom possessing residual affinity is located in the neighborhood, then this residual affinity is saturated by the residual affinity of the halogen. This will determine the strength of the latter, for it will then be fully saturated and, consequently, more inert than before. Owing to the possible manifestation of trivalence in the halogen, cases are also not excluded in which one halogen will saturate two neighboring hydrogen residues. Since ordinarily the residues of hydrogen in the saturated series are very small, the halogen here is attached only to carbon; hence it is mobile. In the naphthene series hydrogen already possesses a larger residue, and therefore here the halogen is more firmly bound. The generally known strength of the halogen in the aromatic series is due to the large residues of the benzene hydrogens, which completely saturate the halogen. The same may be said of a double and a triple bond.

Thus, I imagine the structure of halogen derivatives of the above-mentioned categories in the following manner (drawing 2).

However, as I have already said in the second point on p. 5, the strength of the halogen does not always depend directly on the intensity of the exchange of affinity between carbon atoms. In reality the residue of the halogen is not saturated if there is no hydrogen with a sufficient residue adjacent to it; owing to this the former exhibits great activity. This is observed when the neighboring hydrogen is replaced by various radicals, for example by methyl. I shall speak of this in detail below.

All the subsequent exposition is devoted to proving that, if we accept that such dependencies take place, then it will become clear to us

a whole series of important problems of organic chemistry: thus, for example, the peculiar nature of benzene derivatives, the phenomena of addition, so-called “cryptochemical polymorphism,” many “stereochemical” phenomena, such as, for example, the phenomenon of steric hindrance and, what is especially important, the causes of “geometrical” isomerism. The last problem is fully explained by the theory proposed below. In addition, this theory makes it possible to introduce a considerable degree of clarity also into the question, now in such a hopeless state, of the dependence between structure and the magnitude of rotation of the plane of polarization. The problem of the structural causes of optical activity may also be posed somewhat more sharply than before.

The residual affinity of the hydrogen atom is nothing other than Werner’s “secondary valence,” i.e., it is a valence weaker than the principal one and of exactly the same quality. For convenience of nomenclature, however, I shall allow myself to call this secondary valence “mesovalence.” Accordingly, structural formulas with mesovalences we shall call “mesoformulas,” and such structures in general—“mesostructures.” The principal valence will then be called “protovalence,” and the corresponding structures “protostructures.” For formulas in which only the distribution of affinity is indicated, we shall introduce the term “distribution formulas.” The appended schemes illustrate what has been said above (drawing 3).

In accordance with the proposed terminology, the bond between oxygen and hydrogen in mesoformulas will be called a “mesobond,” and cycles containing such mesobonds—“mesocycles.”

PART I.

Theory of Aromatic Compounds.

Chapter I.

MESOSTRUCTURE OF BENZENE AND ITS DERIVATIVES.

From the third point, p. 2, it is clear that I conceive of the benzene bond as something integral. There are neither central bonds nor an alternation of single and double bonds. All the carbon bonds of benzene are completely identical, and the exchange of affinity, exceeding an ordinary bond, at the same time does not reach a double one. Each carbon atom possesses a certain small residue by which it holds a hydrogen atom. Owing to the equality of these residues, the C—H bonds are also identical, which accounts for the equivalence of the hydrogen atoms. Each hydrogen atom is not fully saturated, but, as follows from the basic propositions, in the present case, owing to the intensive exchange of affinity, only an insignificant part of the latter is directed toward the hydrogen atom. As a result, the hydrogen atoms possess a considerable residual affinity directed away from the molecule and, possibly, also mutually compensating. All that has been said can be illustrated by the scheme (drawing 4). As for the derivatives of benzene, they present an entirely different picture. As soon as any radical enters the nucleus under the influence of one cause or another, the latter reacts to the changed conditions by a complete “redistribution” of affinity. The exchange of affinity between some carbon atoms increases and decreases between others. This is also reflected in the hydrogen atoms, the bond of some of them with carbon becoming stronger and their residual affinity decreasing, while in others it becomes weaker, which greatly increases their mesovalences. I give schemes of such perturbations below; here I mention them only for the characterization of atomic bonds in benzene.

Thus, the proposed formula represents nothing fundamentally new—it is only an eclectic modification of the old ones. The main—

...uneven distribution of affinity we find in a whole series of authors (Flürscheim, Gebhard, and others); the principle of “redistribution of affinity” upon entry of a new substituent is at the present time accepted by almost all chemists. The especially weak bonding of hydrogen is expressed quite definitely by Obermüller in his theory of substitution. Everywhere, however, there is only silence about the significant residual affinities in hydrogen, and the phenomena arising from this are usually ascribed to the carbon atoms. Meanwhile, if it is accepted that the hydrogen atoms in benzene are indeed only weakly bound—which, as the experimental facts show, is beyond all doubt—then, proceeding from Werner’s theory, it is necessary to acknowledge that the hydrogen atoms of benzene must possess considerable mesovalence. It goes without saying that the principle of the dependence of this mesovalence on the intensity of the exchange of affinity of the carbon bond has until now been mentioned nowhere and is expressed here for the first time.

In addition to the generally known facts that speak in favor of the existence of considerable mesovalences in the hydrogen atoms of benzene, I shall take the liberty of recalling the remarkable ability of the methyl groups in hexamethylbenzene to be very readily replaced by halogen. This fact is, it seems to me, the only one known in the literature in which methyl can be replaced by halogen with such ease. It is clear that the carbon atoms of the nucleus can form only very small bonds with the methyl groups, that the greater part of their affinity is required for mutual compensation, and that they therefore cannot firmly bind the hydrogen atoms, i.e., that the hydrogen atom of the nucleus must possess strong mesovalence.

The second fact seems to me more convincing, and therefore I shall dwell on it in greater detail. This concerns the isomerism of benzene hexachlorides and hexabromides and the unexpected properties of these isomers. As regards benzene hexachlorides, their isomerism was first observed by Matthews.¹) Matthews obtained benzene hexachloride by passing chlorine through a solution of sodium hydroxide covered with a layer of benzene. The crystalline mass thus obtained was separated by steam distillation, whereby one of the isomers volatilized. Matthews called it the α-modification. It melted at 151°; the β-modification was isolated from the distillation residue, and its melting temperature was 310°. It differed from α by lesser solubility and greater stability: whereas the β-modification, on heating, readily decomposed into hydrochloric acid and trichlorobenzene and readily split off hydrochloric acid under the action of alcoholic caustic alkali, the α-modification decomposed with sodium hydroxide only on prolonged boiling and did not change under the action of barium cyanide; the β-modification was very readily decomposed by the latter. Attempts to convert one modification into the other failed; it likewise proved impossible to synthesize benzene hexachlorides from hydrochloric acid and trichlorobenzene.

The synthesis of benzene hexachloride had been undertaken even earlier than Matthews by Macken in 1887.²) Macken expected to obtain benzene hexachloride by replacing the hydroxyls of inosite with chlorine. Macken explains the negative result by the absence of a symmetrical structure in benzene hexachloride.

The first structural formulas of these compounds were given by Matthews. In his opinion, the α-modification is a derivative of cyclohexane, whereas the β-modification contains additional bonds between chlorine atoms, with one more ring being formed (diagram 5*).

The existence of this ring also accounted for the greater stability of this modification.

In the same year Friedel³) proposed regarding both isomers as stereoisomers, namely as Baeyer cis- and trans-isomers. In his opinion

¹) Soc. 59, 165 C. 1891. I. 661.
²) C. r. 104, 1719.
³) Bull. [3]5, 130. C. 1891. I. 661.

The α-modification has only four haloids on one side of the plane of the ring, whereas the β-modification has all six. Friedel, however, gives no proof of his assertion.

In 1898 a new communication appeared by Matthews¹, in which he attempts to explain the isomerism of benzene hexachlorides on the basis of Collie’s benzene formula (drawing 6).

According to Matthews, the lesser stability of the β-isomer is explained by the proximity of hydrogen and chlorine in the first scheme. He notes, however, that the formation of as-trichlorobenzene is not explained by Collie’s formula; in this connection he believes that Kekulé’s formula is of little help either.

Thereafter there is a rather long pause in the development of this topic, and only in 1912 does a communication by van der Linden appear on work in this field². Linden succeeded in isolating from the reaction mixture two more isomers, which he called γ- and δ-benzene hexachlorides. The γ compound was isolated and analyzed, and its properties were also investigated in detail; the δ-isomer, because of the small yields, was not investigated. The γ-isomer melts at 112°, the δ at 130°. Linden carried out a quantitative study of the decomposition reaction of benzene hexachlorides into hydrochloric acid and trichlorobenzene. Using thermal analysis, Linden found that in all cases the principal product formed is ac-trichlorobenzene. Other isomers are also obtained in small amounts. As regards the rate of decomposition, the α-isomer decomposed immediately upon addition of caustic potash; for β, four hours of boiling were required.

As regards the γ-isomer, in this communication there are no definite indications concerning it.

In the fact that two new isomers had been isolated, Linden saw the collapse of all the preceding formulas. Linden believes that cis-trans isomerism is most probable here, and since there are no grounds here for establishing one configuration or another, he gives no structures. (He assumes that hydrochloric acid is split off from two neighboring carbon atoms, which always and everywhere takes place.) In fact, the isolation of four isomers seems to argue in favor of Baeyer isomerism. Matthews’s initial formulas do not withstand criticism, if only because it is entirely incomprehensible why chlorine in one compound is monovalent, while in another, under the very same conditions, it is trivalent. Moreover, the application of Collie’s formula to the explanation of the isomerism is impossible already because Collie regards these states as certain definite ones, whereas in reality there is continuous motion of these atoms. If one were to suppose that, for some reason, the ratio between the phases of these vibrations could change, then the number of isomers would, without any exaggeration, be infinite.

A whole series of objections may also be brought against the naphthene formulas. As early as 1871, Zinin³ observed that zinc in alcoholic solution very readily removes haloid from benzene hexachloride, benzene again being obtained. Such a simple and easy transition from the naphthene series to the aromatic has never been observed anywhere. On the contrary, we know well that this transition is very difficult and that it is accompanied by large changes in the energy of the molecule. It also seems strange that all benzene hexachlorides are very stable with respect to strong acids, even on heating. As is known, nitric acid very readily oxidizes naphthenes even when there are no substituents in the ring. The presence of six haloids should naturally greatly weaken the nucleus and create especially favorable

conditions for oxidation. The instability of the hexasubstituted naphthenes is confirmed also by the fact that all attempts to synthesize benzene hexachloride from naphthenes have failed. The corresponding nitro addition compound, however, is very easy to obtain. Thus Macken obtained hexanitrohexamethylene from inosite¹. From all that has been said above I come to the conclusion that the haloid in benzene hexachloride is bound not to carbon, but to hydrogen. To the three isomers of Lindane I ascribe the following structure (drawing 7). Which of these formulas belongs to the α-, β-, or γ-isomer I find it difficult to say, although substance II should be the most stable, for here each chlorine is bound to two hydrogen atoms.

The above schemes illustrate better than others the properties of benzene hexachlorides. Thus, their so surprising lability, with easy reversion again to benzene, becomes understandable, for the benzene nucleus here remains completely untouched. Their stability with respect to acids is explained by the fact that the hydrogen atoms no longer have residues, and therefore the initial addition product, ordinarily necessary for substitution processes, cannot be formed.

By the same intactness of the benzene nucleus are explained the unsuccessful attempts at the transition from naphthenes to benzene hexachlorides. Linden’s failures in obtaining intermediate products of substitution with two or four haloids are likewise understandable, for upon the entry of two chlorine atoms there occur no changes in the distribution of affinity, owing to which the conditions remain the same and the reaction at once proceeds further. Moreover, when haloids add according to the above-indicated schemes, there occurs the formation of new rings from carbon, hydrogen, and chlorine, which in this case are five- and six-membered and, in consequence of this, according to modern views, very stable.

But the mechanism of formation of as-trichlorobenzene upon cleavage of hydrochloric acid is especially clear; this could not be explained by any of the preceding authors. I shall, however, speak of this somewhat below.

Thus, I maintain that the hydrogen atoms of benzene possess a very strong mesovalency, by which they bind the adding haloids. There is no doubt that in substitution reactions addition products are first formed, completely analogous to those mentioned above. The existence of such intermediate products is denied by no one, although up to now they have been very poorly characterized. I shall allow myself here to set forth my considerations on this question, while I believe that, for all their hypothetical nature, they nevertheless possess a certain degree of probability, since here, to a considerably greater extent than before, account is taken of the selective affinity of individual atoms.

If we imagine two neighboring hydrogen atoms of benzene according to scheme 1, drawing 8, then it is natural to suppose that the diatomic molecule of the haloid, possessing a greater affinity for hydrogen than for carbon, will add to 1 with the formation of scheme 2. However, as soon as the addition of bromine to hydrogen has occurred, the former will draw off from it more affinity than is present in its mesovalency. In consequence of this, the bond of carbon with hydrogen, already very weak without that, will weaken so much that a very slight influence will be sufficient to rupture it completely (scheme 3). The rupture of the bond between the haloids, whereby the other haloid replaces the liberated valency of carbon, can be explained by the same considerations. In this, generally speaking, no rupture between the haloid and the neighboring hydrogen occurs, for the affinity of bromine for hydrogen is considerably stronger than for carbon. This bond remains untouched. When bromine combines with carbon, it approaches the neigh—

to the neighboring hydrogen atom to such an extent that the mesovalency of the latter is saturated by the affinity of the halide, and thus a new meso-bond arises, i.e. the halide here is trivalent, according to scheme 4.

The situation will be somewhat different in the case of the action of nitric acid. It is obvious that the addition product here will be a complex, scheme 1, drawing 9, since oxygen has a much greater affinity for hydrogen than for nitrogen. Since in this reaction water is split off, the next stage will be scheme 2, where the group $\mathrm{NO}_2$ is joined by nitrogen to carbon. Finally, the mesovalency of the neighboring hydrogen is saturated by the second oxygen atom, which gives scheme 3. An entirely analogous reasoning may also be applied to the case of sulfonation, the action of cyanogen, etc.

As a result we obtain two categories of schemes: in the first case the mesovalencies of hydrogen are joined directly to the atom attached to the nucleus; in the second case they are directed toward the second atom from the nucleus. This circumstance, as will become clear later, appears to be very important.

The considerations given above may also be applied not only in the case of direct substitution of hydrogen of the nucleus. The substitution also of other atoms and radicals may be represented by the same schemes. Let us consider, for example, the substitution of sulfoxyl by hydroxyl. The structure of the sulfo group in the nucleus corresponds to scheme 1, drawing 10. Under the action of caustic potash there is formed a primary, very unstable addition product, 2. Then $\mathrm{KHSO}_3$ is split off and hydroxyl takes its place. At the next moment the mesovalency of the neighboring hydrogen is saturated by the oxygen residue (scheme 3). Oxidation and other processes may likewise be illustrated in a completely analogous way.

All that has been said above would, of course, be only metaphysics if we could not find factual substantiation for the proposed schemes. I shall allow myself here to recall certain properties of simple benzene derivatives. These properties have hitherto not been explained by any peculiarities of the structural formula.

The most important point here seems to be the strength of substituents in benzene, attaining a quite definite degree and limited by definite conditions. These conditions have hitherto stood in no connection whatever with structural peculiarities. As is known, a halide is very easily split off from a side chain, whereas its bond with the nucleus is very strong. In any case, this is true for monosubstituted derivatives.

I think that this is firmly based chiefly on the circumstance that the halide here is bound to three atoms, in contrast to the saturated aliphatic chain, where it is monovalent in the generally accepted sense of the word. This proposition is proved, among other things, also by the fact that substitution of hydrogen atoms neighboring the halide always weakens its position in the nucleus to an extraordinary degree. Thus, for example, in order to remove iodine from 3,5-iodoxylole one must heat the latter with HI and phosphorus to $182^\circ$, whereas from 2,6-iodoxylole the halide is removed already at $100^\circ$.

$Visible chemical structure diagram: two substituted benzene-ring schemes, each bearing $\mathrm{J}$ at the top and $\mathrm{CH}_3$ groups indicated at different positions.$

It is clear that in the first case it is also held by the neighboring hydrogen atoms, whereas in 2,6-iodoxylole it is attached only to one carbon.

Also generally known is the fact, enigmatic at first glance, of the unusual strength of chlorine in metachloronitrobenzene as compared with that in o-chloronitrobenzene. This fact is hard to explain even by the influence of groups through the medium of the nucleus, which, as we shall see below, could be applied to the case with iodoxylole.

It seems to me that this is very simply explained by the fact that in the first case the chlorine is connected with three atoms, while in the second only with two. The possibility of the union of the hydrogen atom situated between Cl and NO₂ with the oxygen of the nitro group is lost, owing to the greater affinity of hydrogen for chlorine than for oxygen. But in this case there may also be another factor at work, which I shall indicate below.

The same may be said also of the strength of the OH group. It is known that phenol is esterified with extreme difficulty, which is explained by the fact that its oxygen has no remaining affinity at all. When the neighboring hydrogens are replaced by various radicals, however, esterification proceeds considerably more easily.

Especially convincing in this respect are the properties of carboxylic acids and aromatic ketones. Under certain conditions carboxylic acids can lose their carboxyl, eliminating it in the form of CO₂, with hydrogen taking the place of the carbon. The simplest case is such a loss upon raising the temperature. Here too relations are revealed that are quite inexplicable from the point of view of classical structural theory. Thus, for example, benzoic acid loses carboxyl only at 400°; its substituted derivatives at considerably lower temperatures. Particularly readily decomposed are O-substituted acids, as is shown by the following table:

Acid	Temperature
benzoic	400°
o-oxybenzoic	220°
3,4,5-trioxybenzoic	200°
2,4,6-trinitrobenzoic	100°
2,4,6-trioxybenzoic	100°

It is clear that in all these cases the carboxyl is greatly weakened by the fact that it loses the neighboring H atoms with which it had been connected. This is also confirmed by the circumstance that removal of the carboxyl from the nucleus likewise lowers the decomposition temperature. Thus phenylacetic acid decomposes already at 300°, in contrast to 400° for benzoic acid. At the same time the other isomeric substituted benzoic acids possess very considerable stability: m-oxybenzoic acid, for example, distils without decomposition.

The same considerations may be applied to the heterocyclic series, for the least stable acids of the pyridine series will be those whose carboxyl stands next to nitrogen. And with the latter, as is known, there is no hydrogen atom.

Another area of phenomena stands extremely close to that just described. Klages¹) observed as early as 1899 that aromatic ketones in which both ortho-hydrogen atoms are substituted decompose very readily under the action of phosphoric acid into fatty acids and the corresponding hydrocarbons, whereas unsubstituted ones are very stable. The same relations were also found by Hoogewerff²) under the action of sulfuric acid on the corresponding ketones. It must be supposed that in the present case the considerations adduced above also play a role. Stable compounds have the carbonyl oxygen attached

¹) B. 32, 1549.
²) C. 1901. II. 1117.

to two H atoms; when these atoms are replaced by mesobond radicals, however, they are annihilated, and the group possesses a considerable residual affinity, which determines its activity.

I shall mention one more circumstance which, it seems to me, speaks in favor of the proposed structures. As is known, phenol is a considerably stronger acid than the alcohols of the fatty series. It must be supposed that such a weak bond of hydrogen with oxygen is due here to the fact that oxygen, if one may put it so, is exhausted by the mesovalences of the neighboring H atoms. So much affinity goes to this that hydrogen cannot hold firmly to it. The situation is different in the fatty series: there are no mesobonds there, and therefore oxygen is attached only to carbon and hydrogen, the latter of course having a small residue, owing to the considerable strength of the bond with oxygen.

Such suppositions are also confirmed by the circumstance that, when neighboring H atoms are replaced by $CH_3$, the acidity of phenol drops sharply: the electrical conductivity of $O$-cresol is considerably lower than that of phenol, and, unlike the latter, it is insoluble in ammonia.

All the phenomena set forth above nevertheless represent only a small part of those perturbations which occur in the nucleus when a substituent enters it. One of the most important causes of a complete change in the properties of benzene is the redistribution of affinity between the carbon atoms on the one hand, and between carbon and hydrogen on the other. The point is that there exist two categories of groups, differing more or less sharply in their relation to the carbon atom of the nucleus: some groups generally form strong bonds with the latter, while others form weak ones. To the first group belong $COOH$, $SO_3H$, $NO_2$, $CN$; to the second category belong $OH$, $NH_2$, $CH_3$, and the haloids.

As can be seen, this division corresponds perfectly to the influence of these groups on the activity of the double bond. It is known that $COOH$, $SO_3H$, $NO_2$, $CN$ greatly weaken the activity of the double bond if they are joined to the carbon at it. Hydroxyl, the amido group, and methyl, however, usually activate it, i.e. the rate of the addition reaction to it of various addenda increases considerably when the hydrogen at the double bond is replaced by these radicals. This is usually explained by the fact that groups of the first category take much affinity from the C atom, owing to which the partial valence inherent in these atoms is so diminished that, in other cases, the presence of a double bond in the compound is not detected at all. The activating action of hydroxyl, etc., must be explained by the opposite assumption, namely, that these radicals form weaker bonds with carbon than it had with hydrogen, and consequently the resulting excess goes to increase the partial valence. The circumstance that the haloids, despite the fact that they weaken the double bond, nevertheless form a weak bond with the carbon of the nucleus and that, despite this, they nevertheless sit firmly in the nucleus, will be clarified somewhat below.

Since we accept, in principle, an unequal distribution of affinity, we must admit that, upon the entry into the nucleus of substituents so different in their consumption of affinity, two types of phenomena must naturally arise: upon the entry of a heavy group, affinity will be distributed according to one scheme; upon the entry of a light group, the scheme of distribution will be different. Let us consider the first case, the scheme of which will have the following form (drawing 11, scheme I).

If a radical requiring from carbon 1 of the nucleus a greater amount of affinity than the former H is attached to it, then obviously this carbon will be able to saturate only a small part of the affinity of its neighbors. The latter in turn, having received a certain excess of affinity because of the weakening

the 1—2 and 1—6 bonds, will be able to hold more firmly, both the carbons 3 and 5 and their own hydrogen atoms. Precisely the same reasoning is applicable also with respect to carbons 3 and 5: as a result of the strengthening of the 3—2 and 5—6 valences, their bond both with carbon 4 and with their own H atoms will be weakened. Carbon atom 4, having two weakened carbon bonds, will be able to hold its hydrogen atom very firmly. In the “distribution formula” depicted here, strong carbon bonds are denoted by heavy lines, weakened ones by thin lines, and weakened C—H bonds by dotted lines.

Repeating entirely analogous reasoning for the case of the entry of a light substituent, we obtain the following scheme (drawing 11, scheme II).

In both schemes, for greater clarity, the different strength of the C—H bonds is illustrated by their different distance from the nucleus.

I have given these formulas without taking into account mesobonds, which, of course, may also occur in the present case.

If it is assumed that the entering substituent, in the case where it contains atoms possessing selective affinity for hydrogen, enters, as was set forth above, into combination with neighboring H atoms, then this will make it possible to bring into the system an abundant quantity of factual material that has hitherto not been connected by any regularities. As we have seen, substituents that form a weak bond with carbon are OH, NH₂, etc. According to the schemes given in drawing 9, they will be joined to hydrogen through O and N, i.e. the mesovalences will be at atoms joined directly to carbon. Those forming strong bonds, i.e. COOH, SO₃H, NO₂, will also be joined to oxygen, but not to one joined in this case to the carbon of the nucleus, rather to one separated from it by some other atom. In both the one case and the other, the consequences of this will be completely identical. If the mesovalence of hydrogen takes some part of the affinity from the hydroxyl oxygen of phenol, then naturally its bond with carbon will be weakened still more, and this in turn will lead to an increase in the difference between the strengths of the individual bonds in the nucleus, i.e. the unevenness of the distribution of affinity will increase.

If, however, the mesovalence of hydrogen in benzoic acid is directed toward the carbonyl oxygen of the carboxyl, then this will cause a weakening of the oxygen bond with carbon, i.e. the latter will be able to strengthen its bond with the nucleus. Consequently, here too the phenomenon of uneven distribution of affinity will be sharpened, for the bond of the carboxyl with the nucleus is stronger than the C—H bond.

Such an influence of mesovalences on the bond with the nucleus and the consequent changes in the distribution of affinity are evidently decisive in a whole series of cases, for it turns out that all groups having an atom akin to hydrogen directly joined to the carbon of the nucleus form weak bonds with the latter. At the same time, groups joined by the mesovalence of hydrogen to the atom second from the nucleus always form strong bonds. Thus, weak bonds are given by OH, NH₂, halides; strong ones by COOH, SO₃H, CN.

Thus, according to what has been stated above, the final distribution formulas for two categories of monosubstituted benzenes will have the following form (drawing 12).

As is seen from these schemes, four different types of C-H bonds are outlined here.

Bonds where carbon has one strong valence and one weak one, while a weak one goes to hydrogen, i.e. atoms 2,6 in bromobenzene and 3,5 in benzoic acid.
Bonds where, under the same conditions, H has a strong bond, i.e. 3,5 in bromobenzene and 2,6 in benzoic acid.

The bond of atom 4 in bromobenzene: very weak, since the carbon has two strong bonds.
The bond of atom 4 in benzoic acid—very strong, since the carbon has two weak valences.

The following chapter is devoted to clarifying the meaning of these gradations.

Chapter II.

THE THEORY OF DIRECTING.

Even a sufficiently cursory glance at the distribution formulas of bromobenzene and benzoic acid is enough to understand that the entry of a second substituent in both cases will occur at entirely different positions of the nucleus. The newly entering substituent will, of course, replace the more weakly bound hydrogen, since it is precisely here that, according to the mechanism set forth on p. 9, the elimination of hydrogen halide, water, etc., will occur with the greatest ease, and the given isomer will prevail in the reaction mixture. Such “points of least resistance” in the first scheme will be atoms 2, 4, and 6, i.e. here much of the p- and little of the o-isomer will be obtained; in the second scheme, substitution will proceed at atoms 3 and 5 and, to a considerably lesser extent, at atom 2. In other words, the first category of substituents will be o-p-directing groups, while the second will be m-directing.

Thus an entirely new criterion is established for o-p-directing groups on the one hand and for m- on the other. O-p-directing groups will be groups that saturate the mesovalences of the hydrogen affinities of the atom directly joined to the carbon of the nucleus; m-directing groups, by contrast, will be those that saturate them in the second atom from the nucleus.

The proposed theory very much resembles Flürscheim’s theory,¹) but the resemblance is only external. The difference between these two theories reduces, in its main features, to the following:

The distribution of affinity in Flürscheim’s theory is directly opposite to that proposed, since Flürscheim takes into account not the “absolute” character of the individual group and its relation to the double bond, but its actual strength in the nucleus. As I have already indicated, the true strength in the nucleus depends on several factors and cannot be regarded as characteristic of a given group.
Flürscheim leaves H-atoms entirely out of account, ascribing the principal role in the substitution reaction to carbon atoms possessing, in his opinion, residual affinity. Because of such an assumption, Flürscheim does not mark any distinction between o- and m-hydrogens (see Holleman’s criticism).²)
As the characteristic sign of a group’s directing action, Flürscheim points to the presence, in m-directors, of unsaturated O and N atoms, without explaining at all why their presence conditions m-direction.

The arguments adduced, it seems to me, are sufficient to clarify the essential difference between Flürscheim’s theory and the one proposed. This difference becomes still clearer, and the grounding of the new theory more solid, from the discussion of the factual material presented below.

As is known, Holleman, comparing the strength of the directing action of various groups, arranged them in a certain series in order of decreasing influence.

On the other hand, the investigations of the same author and of other chemists made it possible to judge the relative amounts in which various isomers are formed upon the entry of a second substituent. A comparison of these results is given in the appended table.

¹) B. 39, 2015.
²) J. f. prakt. Ch. 74, 157 (1906).

	Cl	Br	J	SO₃H	NO₂
OH	4 (2)	4 (2)	4 (2)	4 (2)	4 (2)
NH₂	4 (2)	4	4	4 (2)	4 (2)
Cl	4 (2) (3)	4 (2) (3)	4	4	4 (2)
Br	4 (2) (3)	4 (2) (3)	—	4	4 (2)
J	4	4	4	4	4 (2)
CH₃	4 (2)	4 (2)	4 (2)	4 (2) (3)	4 (2) (3)
COOH	3	3	3	3 (4)	3 (2) (4)
SO₃H	—	3	—	3 (4)	3 (2) (4)
NO₂	3	3	—	3 (2) (4)	3 (2) (4)
CN	—	—	—	—	3

Here the radicals located in the nucleus and placed in the vertical row are arranged in decreasing order of their directing strength, i.e., according to the proposed theory, in the order of strengthening of the bonds with carbon at the substituted hydrogens. In the horizontal row are placed the second entering groups; the numbers in the cells denote the isomers obtained, with the one whose yields are greatest placed first. Analysis of the data in this table, in many respects, testifies to the reality of the existence of meso-bonds at hydrogen. Thus we see that in all cases the yields of the o-isomer are very small. If we recall the schemes shown in Fig. 12, we shall see that the o-hydrogens do indeed possess a very small residue, for they are almost always joined to unsaturated atoms of the substituent. The M-directing groups either do not give o-isomers at all, or give them only in negligible amounts; this is explained by the fact that the o-hydrogens here are especially strongly saturated, for each of them has one oxygen. Moreover, their bond with the nucleus possesses increased strength by virtue of the phenomenon of nonuniform distribution of affinity.

I said that the o-hydrogens are almost always joined to the substituent. Indeed, there may sometimes be cases when this connection is absent, if the substituent has no unsaturated atom. Such groups include, for example, CH₃.

Here the mesovalence of the o-hydrogens remains unsaturated, and one should expect large yields of the corresponding isomer.

Experiment fully confirms this assumption, for, for example, in the substitution of toluene, the o-isomer is usually obtained even in greater amount than the para. In the general case, the yields of o- and p- are almost identical. The absence of a bond with neighboring hydrogens also explains the weakest directing power of methyl.

The meso-bonds here do not intensify the nonuniform distribution of affinity, as occurs in other cases, and at the same time they do not weaken the para- and ortho-bonds.

Thus, we can now state in final form the foundations of the theory of direction. All groups are divided into two categories: some groups have an unsaturated atom directly attached to the nucleus, or do not have it at all. These will be o-p-directing. The strength of their direction will be

decrease as the force of affinity of these unsaturated atoms for hydrogen decreases, for this determines the uneven distribution of affinity. This force will be weakest in groups that have no unsaturated atoms. The second category of groups has the unsaturated atom second from the nucleus, and here no exceptions to this rule are observed. These will be m-directing groups. Here the directing force will increase in the reverse order as compared with the first category, i.e., as the affinity for hydrogen decreases, which can be explained in exactly the same way as in the first category. Here the strongest will be COOH, and the weakest NO₂: precisely in the former there is only one oxygen for two hydrogens, whereas in the latter there is one oxygen for each hydrogen. Of course, the bond with the nucleus will be increased more strongly in the carboxyl than in the nitro group.

In the proposed scheme there is also a quite definite place for phenyl, whose o,p-directing action fitted poorly into the framework of previous theories. Indeed, this group, as is known, greatly weakens the double bond and, consequently, according to Holleman it ought to be m-directing. Since it weakens the double bond, this means that it takes much affinity from carbon, i.e., forms a strong bond with it. And this, according to Flürscheim, is also a sign of m-direction. The vague term “steric influence” of Obermüller’s theory also does little to clarify the essence of the matter, for this influence in phenyl must be very great, which, likewise according to Obermüller, is characteristic of m-directors. From the point of view of the proposed theory the question is quite clear: the carbon of the nucleus, possessing only a very small affinity for hydrogen, of course can in no way saturate the mesovalence of the o-hydrogens, and this is the sign of o,p-direction.

The proposed theory, it seems to me, also satisfactorily explains two further questions usually associated with every new attempt in this field. Measurement of reaction rates upon the entry of a second substituent has shown that the rate of p-substitution is usually very much greater than that of m-substitution. Holleman, proceeding from Kekulé’s benzene formula, explains this phenomenon by the circumstance that p-substitution occurs when there is present in the nucleus a substituent that activates the double bond. In such a case the rate of this substitution, which takes place at the ends of the conjugated system, considerably exceeds the rate of addition at the site of the third double bond. If, however, there is in the nucleus a group that increases the activity of the double bond, then addition at the ends of the conjugated system does not occur, and only addition at the third double bond takes place. Since the latter is not activated by anything, it also proceeds slowly. However, Holleman’s explanation encounters an insurmountable difficulty in the case of diphenyl. Here in the nucleus there is a phenyl group, which very strongly lowers the activity of the double bond, yet substitution nevertheless occurs at the o,p positions. Halogens, which give o,p-substitution, likewise cannot by any means be classed among groups that activate the double bond.

The difference in the rates of substitution reactions is apparently based on the fact that in the one case and in the other we have hydrogen atoms possessing mesovalences of different strength. As I indicated at the end of the preceding chapter, in monosubstituted benzenes we shall in general have four types of hydrogen atoms, differing in the strength of their attachment to the nucleus. In accordance with the distribution of affinity in a p-directed nucleus, the p-atom will be the most weakly bound and the o-atoms somewhat more strongly bound; in an m-directed nucleus the most weakly bound atoms will be atoms 3 and 5. But in both these cases the strength of attachment of the one and the other atoms will be unequal. Thus, the p-atom in bromobenzene will be attached to a carbon bearing two strong carbon bonds, whereas the m-atoms of benzoic acid will be attached to a carbon atom possessing one strong and one weak valence, i.e., they will be attached more strongly than the p-atom in bromobenzene. This is illustrated in the distribution formulas of fig. 12 by the longer line.

the line of bonds at the p-atom of bromobenzene in comparison with the m-atoms of benzoic acid. If we now recall the substitution mechanism set forth on p. 9, it will become clear to us that the rate of detachment of the elements of water, hydrogen halides, etc., in the first case will be considerably greater than in the second. But this is not all. According to the proposed mechanism, one more H-atom is needed for the transfer of the substituent to the valence being liberated. In bromobenzene such atoms will be atoms 3 and 5, whereas in benzoic acid only atom 4, since atoms 2 and 6 are bonded with the carboxyl. But atoms 3 and 5 of bromobenzene are more weakly bound to the nucleus than atom 4 of benzoic acid, since the former are situated at a C-atom with one strong and one weak valence, whereas the latter is at such an atom with two weak valences; that is, atoms 3 and 5 of bromobenzene will possess a stronger mesovalence than atom 4 of benzoic acid. Thus the rate of the addition reaction of the substituting reagent in bromobenzene will be greater than in benzoic acid. Therefore, both in the first phase of the substitution process, i.e. in the phase of formation of the primary addition product, and in the second phase, i.e. in the elimination of $\mathrm{H_2O}$, $\mathrm{HCl}$, etc., the rate of reaction in the p-directed nucleus will be greater than in the m-directed one. Hence it is clear, of course, that the rate of the entire substitution process in the first case will be greater than in the second.

A second fact unexplained up to now is the difference in the strength of the halogen in the m- and o-p-positions in chloronitrobenzene. The point is that the halogen in o-chloronitrobenzene is very weakly bound and is readily split off under the action of various agents, whereas in m-chloronitrobenzene it is attached very firmly. It is also weakly bound in p-chloronitrobenzene.

If we assume that the entry of one substituent into the nucleus causes there an uneven distribution of affinities and thereby produces mesobonds, then it is natural to suppose that the same will occur also upon the entry of subsequent substituents; moreover, of course, each newly entering one will exert its influence according to its nature. These influences will undoubtedly be combined with the influence of the substituent already present, as a result of which, for each particular case, we shall obtain a certain special distribution formula. Of course, the relative directing strength will also make itself felt here, and the picture in general will prove very complex. Having designated here a unit for comparison and at least an approximate difference in the degree of direction, one could draw up distribution formulas for all possible cases of substitution; however, without taking into account the directing strength of individual groups, let us see what the distribution formulas will be for the various chloronitrobenzenes.

By adding together two distribution formulas, composed according to the above-stated principles for nitrobenzene and for chlorobenzene, we shall obtain the following three schemes (drawing 13).

Here the designations of the strength of individual bonds do not in principle differ from the former ones: thickening of a line is an increase in strength, its transition into a dotted line is weakening. As is evident from the schemes obtained, the position of chlorine in all three cases is quite different. Thus in o-chloronitrobenzene it stands at a carbon atom having one strong and one weak valence. In this respect its position in the m-isomer is identical. However, whereas in o-chloronitrobenzene it is joined with an H-atom possessing a considerable mesovalence, in the m-isomer beside it is an H-atom firmly attached to the nucleus and therefore little active. This circumstance, as we know, plays a very substantial role in substitution reactions, since the first phase will consist in the formation of an addition product. It is clear that the rate will be greater for the o-isomer than for the meta-, i.e. the chlorine in the latter case will seem to be attached more firmly.

Comparing now the m-isomer with the p-isomer, we can draw the very same conclusions. In the p-isomer, the H-atoms neighboring chlorine undoubtedly possess a greater residue than the H-atoms of the m-isomer. Consequently, here too the substitution reaction will proceed faster than in m-chloronitrobenzene. It is clear that here it will also proceed faster than in chlorobenzene itself, since here the bond of chlorine with hydrogen is not as strong as in the latter.

If we now, in accordance with the principles set forth above, construct distribution formulas for all possible pairs of substituents, then from this we can derive a series of regularities for the entry of a third one. However, for reasons of economy of space, I shall not speak of this here. I shall mention only one interesting limiting case.

In constructing all possible distribution formulas for four radicals (two ortho and two meta), it turned out that in isomers I and II (drawing 14) the distribution of affinity is completely uniform. This gave reason to suppose that the given compounds must be especially stable. And indeed, for example, 4,6-dioxybenzene-1,3-dicarboxylic acid is a very stable and well-studied substance. Isomers III, IV, and V, however, have such weakened bonds in their distribution formulas that the corresponding compounds apparently should not exist. Quite unexpectedly, this fully coincided with the literature data. Thus, 2,5-dioxybenzene-1,4-dicarboxylic acid is still unknown. The acids 3,6-dioxybenzene-1,2-dicarboxylic and 2,5-dioxybenzene-1,4-dicarboxylic proved to be very unstable, for immediately upon formation they rearranged into the corresponding quinoid form. Such a difference in the degree of stability of such closely related isomers cannot but seem very strange, and the coincidence of their properties with the distribution schemes indicates that the latter evidently have some grounds beneath them. However, until a detailed and thorough study of this question has been made, I shall not present these schemes here.

Let us now recall the fact that we had previously left completely unexplained, namely the formation of ac-trichlorobenzene upon the decomposition of benzenehexachlorides. Now, I think, it can be given proper illumination. Suppose that in one of the schemes given in drawing 7, let us say the first, under the influence of one or another cause—for example, with an increase in temperature, as in fact occurs during decomposition—HCl splits off at some point in the molecule (drawing 15). Then immediately the neighboring chlorine will take the vacated place, and with its entry into the nucleus the phenomena just analyzed will take place: that is, the affinity in the nucleus will be distributed unevenly, as a result of which the bonds of carbon with the various H-atoms will change substantially. These perturbations will be of quite a definite type, for chlorine belongs to the number of o-p-directing groups. Consequently, with its entry into the nucleus the bond of the p-hydrogen, and somewhat less that of the o-hydrogen, will be greatly weakened. This will cause the further splitting off of HCl first at the p-carbon, to which chlorine atom 3 will then move, and then at the o-atom, to which chlorine atom 5 will move; that is, precisely ac-trichlorobenzene will be obtained. This is the normal course of the reaction, and therefore the yields of this isomer will be predominant. The possibility is also not excluded of the simultaneous splitting off of the first two particles of HCl, or else splitting off at the m-atom, but this is probably negligible; hence the yields of the other isomers are small. With slight changes, this reasoning can be repeated for other forms as well. Thus, the formation of ac-trichlorobenzene rests here exclusively on the phenomena of p-direction by a chlorine atom.

The structure of naphthalene from the point of view set forth above will appear as follows. Since we assign groups requiring much affinity to the meta-directors, it is obvious that the “benzene chain” may also be assigned to the latter, by which one should understand a torn benz—

benzene nucleus. Thus, if we introduce two “benzene chains” into the benzene nucleus in the ortho position, we obtain the protoformula of naphthalene; and if we designate the redistribution of affinity that has occurred, we obtain a distribution formula which in the present case will fully coincide with the mesoformula, i.e., if we introduce one meta-directing agent into the nucleus, we obtain Scheme I, drawing 16. To construct the mesoformula for two meta-directing agents we proceed in the same way as on p. 17, i.e., we combine the schemes for both the first and the second case (drawing 16). With analogous reasoning concerning the second nucleus of naphthalene we obtain the same scheme, which gives us the following mesoformula (drawing 17).

Even a superficial glance at the structure is sufficient to convince us that the $\alpha$-H atoms are weakly, and the $\beta$—strongly, attached to the rings. This fully corresponds to the basic property of naphthalene—the easy substitutability of the $\alpha$-H atoms.

With this I shall conclude the consideration of the phenomena of directing action and shall now turn to the next category of phenomena, which stand in direct connection with everything set forth above.

Chapter III.

STERIC HINDRANCE.

The bond of the mesovalences of hydrogen with groups situated adjacent to them has a direct influence on the bond of these groups with the nucleus; moreover, in $p$-directing agents this bond is weakened, while in $m$-directing agents it is strengthened. Since we assume that this influence is transmitted in the group in the direction toward the nucleus, it is natural that those bonds which go from the atom first from the nucleus to other atoms will likewise experience the influence of mesobonds. Thus we have explained the more acidic character of phenol in comparison with fatty alcohols. If, from this point of view, we analyze the distribution of affinity in the carboxyl, we shall come directly to what bears the name of Meyer’s “law of esterification.”

In the scheme for benzoic acid shown in drawing 12 the distribution of affinity in the carboxyl is not indicated. We shall now fill this gap and see how affinity is distributed in the carboxyl of benzoic acid itself and in the carboxyl of its o-substituted derivatives. Since, according to the proposed hypothesis, the o-hydrogen atoms of benzoic acid are connected with the oxygen of the carboxyl, the latter consumes little affinity from the carbon. This causes a strengthening of the bond with the nucleus and, at the same time, a strengthening of the bond with the oxygen of the hydroxyl. The increased strength of the bond of the hydroxyl oxygen with the carbon will entail a weakening of the bond of the former with its hydrogen. This may be illustrated by Scheme I, drawing 19. An entirely different picture is obtained when the neighboring H atoms are replaced by some radicals.

In such a case mesobonds are absent and, consequently, the oxygen will be more firmly bound to the carbon. This will cause a weakening of the C–C and C–O bonds in comparison with the preceding case and, consequently, the carboxyl hydrogen will be attached more firmly to the oxygen than in benzoic acid (Scheme II).

Thus, in both cases under consideration there will be an essential difference in the distribution of affinity in the carboxyl, and consequently also in the activity of its individual atoms: in benzoic acid the hydrogen will be bound more weakly, in dimethylbenzoic acid more firmly. Since the process of esterification in both the one and the other case ultimately consists in the removal of water, it is natural that this removal will proceed more easily in benzoic acid than in its o-substituted derivatives. We find completely opposite relations in derivatives of benzaldehyde.

As is known, E. Fischer found that benzaldehyde is acetylated considerably more difficultly than its o-substituted derivatives. This fact was considered quite ...

contradicting the “law of esterification” and in any case excluding any “steric” influences. If we look at the question from the point of view of mesotheory, the relations will be quite clear.

In the case of acetalization, one particle of water is split off from two particles of alcohol and one of aldehyde. Thus, the greater the residue at oxygen, i.e., the more weakly it is attached to carbon, the more readily the reaction will proceed. But oxygen, obviously, possesses a large residue in substituted benzaldehydes, for in benzaldehyde itself it is bound to o-hydrogen atoms and, consequently, is fully saturated. The replacement of o-hydrogens by radicals, however, breaks the mesobonds, and the residual affinity of oxygen is released (diagram 18).

I shall now give several examples with p-dirigents. Hantzsch¹) found that the condensation of benzaldehyde with aniline:

\[ \mathrm{C_6H_5 \cdot NH_2 + OHC \cdot C_6H_5 \rightleftarrows C_6H_5 \cdot N : HC \cdot C_6H_5 + H_2O} \]

proceeds freely with aniline itself, whereas symmetrical tribromo- and trinitroanilines do not react with benzaldehyde. Here the same explanations are appropriate as in the preceding cases. Aniline itself has the following structure (I), diagram 20, while its substituted derivatives have no mesobonds (II). Naturally, the elimination of hydrogen from the amido group will occur more readily in the first case than in the second, for here the bond of nitrogen with the amido hydrogens is represented as weakened.

The absence of the reaction forming a quaternary base in o-substituted amines is also explained by the same relations. In the first case we have weakly bound H atoms; consequently they have large residues and can retain the haloid. In the case where hydrogen is replaced by a radical, the bond between H and N in the amido group becomes stronger, the residues at H are smaller, and, by virtue of this, the formation of a quaternary base is hindered.

The relations in quinones appear somewhat more complex. Here the replacement of an H atom adjacent to the CO group usually entails an unusually low rate of the oxime-formation reaction. Compared with the preceding case, this one is more complex because it is rather difficult here to decide to which category of “hindrances” the given phenomena should be assigned. The question is complicated also by the circumstance that the distribution of affinity in the quinone ring will evidently be quite different than in benzene; that is, quinone in this respect will approach aliphatic compounds, since its double bond, in its activity, differs essentially from benzene bonds, and, moreover, owing to the bond of the ring carbon with the whole oxygen atom, there can be no question of an even distribution of affinity. Therefore this case ought to be considered elsewhere; I dwell on it here because it bears directly on the phenomena of “hindrance” in aromatic ketones, and this latter circumstance is of outstanding importance for us.

Thus, affinity in quinone is distributed unevenly, since here there is an ordinary aliphatic double bond and, by virtue of this, the hydrogen at it possesses a somewhat larger residue than benzene hydrogen. This follows directly from the fundamental propositions set forth in the introduction. By these residues hydrogen is attached to the quinone oxygen (diagram 21). If one assumes that, in oxime-formation reactions, the formation of a primary addition product takes place, then the reaction with hydroxylamine will proceed through the following phases (diagram 22).

If, however, we replace the hydrogen by CH, for example, the mesobonds will disappear. Nor will the formation of the primary addition product take place, i.e., the entire reaction will not proceed.

¹) B 23, 2776.

This is also confirmed by the fact that chloranil, which undoubtedly possesses a considerable residue precisely at oxygen, nevertheless gives no oximes. Nor do the o-substituted aromatic ketones give oximes; according to what has been set forth above, they are considerably less stable than their unsubstituted analogues. The latter circumstance is a direct consequence of the presence of a residue at oxygen.

The oximation reaction also proceeds slowly in unsubstituted aromatic ketones. This circumstance also led to the establishment of the term “chemical hindrance”; namely, Rupe¹, by the action of carbamic-acid chloroanhydride on β-benzoylphenylhydrazine, did not obtain the expected triazole:

\[ \begin{array}{ccc} \begin{array}{c} \mathrm{NH.CO.C_6H_5}\\ |\\ \mathrm{C_6H_5.NH} \end{array} \;+\; \mathrm{Cl.CO.NH_2} & \longrightarrow & \begin{array}{c} \mathrm{NH.CO.C_6H_5}\\ |\\ \mathrm{C_6H_5.N.CO.NH_2} \end{array} \end{array} \quad\longrightarrow\quad \begin{array}{c} \mathrm{N{=}C.C_6H_5}\\ \;\;\backslash \mathrm{N}\\ \mathrm{C_6H_5N}\;\;\; \mathrm{C.OH} \end{array} \]

Meanwhile, this reaction did proceed in the acetyl derivative (I). The triazole was also obtained when substance (II) was taken,

\[ \begin{array}{c} \mathrm{NH.CO.CH_3}\\ |\\ \mathrm{C_6H_5.NH} \end{array} \qquad \mathrm{(I)} \]

\[ \begin{array}{c} \mathrm{NH.CO.CH_2.C_6H_5}\\ |\\ \mathrm{C_6H_5.NH} \end{array} \qquad \mathrm{(II)} \]

on the one hand, i.e., when the phenyl was separated from the CO group by $\mathrm{CH_2}$, and when one acted on these or other hydrazines not with $\mathrm{Cl.CO.NH_2}$, but with phosgene. Without going here into details, I shall simply give the course of the process as it appears to me. The primary product here, apparently, will not be the one indicated by Rupe, but the following:

\[ \begin{array}{ccccc} \begin{array}{c} \mathrm{NH.CO.CH_3}\\ |\\ \mathrm{C_6H_5.NH} \end{array} \;+\; \mathrm{Cl.CO.NH_2} & \longrightarrow & \begin{array}{c} \mathrm{N{-}C.CH_3}\\ | \quad \mathrm{NH}\\ \mathrm{C_6H_5.NH}\quad \mathrm{COCl} \end{array} & \longrightarrow & \begin{array}{c} \mathrm{N{=}C.CH_3}\\ \;\;\backslash \mathrm{N}\\ \mathrm{C_6H_5.N{-}C.OH} \end{array} \end{array} \]

i.e., first here the carbonyl passes into the enol; then water is split off, and, with subsequent splitting off of HCl and tautomerization, the corresponding triazole is obtained. I see grounds for this in the circumstance that it would be exceedingly strange if replacement of $\mathrm{CH_3}$ by phenyl in a distant corner of the molecule could influence the stability of an atom remote from the phenyl, at N and C. The hindrance to the primary enolization, however, is perfectly clear, for in the case of phenyl the carbonyl oxygen will be sufficiently saturated by the o-hydrogens of the former to enter into enolization with the nitrogen hydrogen. In a subsequent communication Rupe² took cyclohexyl instead of phenyl, and the reaction proceeded well. It proceeded, as I have mentioned, also in the case where a $\mathrm{CH_2}$-group stood between the phenyl and the carbonyl. It is clear that in the latter case the carbonyl oxygen was completely free and could enolize; in the case of cyclohexyl, even if mesovalences existed, they were of such a weak order that they could not offer any particular hindrance.

Meso-bonds at the carbonyl standing next to a benzoyl residue are the cause of the emergence of extremely important phenomena, the description and investigation of which will be the subject of one of the chapters of the following part. I shall now proceed to set forth the most important consequences of the proposed hypothesis, consequences,

as it seems to me, the most convincing. If the preceding exposition may in many respects arouse doubts, if in many places there were understatements, ambiguities, and exaggerations, if much of what was said here had to be taken on trust and many proofs suffered from the substantial logical defect idem per idem, then the picture of the phenomena set forth in the following part will, I hope, smooth out this impression.

PART II.

Theory of Isomerism.

Chapter I.

CRYPTOCHEMICAL POLYMORPHISM.

It is usually assumed that the molecules of polymorphic substances, for unknown reasons, possess the ability to arrange themselves in a crystal in different ways, which is what has, in fact, “explained” polymorphism up to now. However, there exists a fairly significant number of cases in which substances of completely identical structure, crystallizing in different systems, have revealed physical differences not only in the solid state, but also in the liquid state, whether molten or dissolved. This material was collected quite recently (1914) and gave rise to doubt concerning the former explanation of the phenomena of polymorphism.

Indeed, on closer examination this explanation cannot but appear one-sided. Since there are no direct experimental data whatever speaking in favor of the identity of the structure of polymorphic substances in the solid state, another proposition may also be advanced to explain the phenomena of polymorphism—namely, that polymorphic substances are in fact structural isomers, but that these structural differences have not yet been detected. It would be very difficult to raise any fundamental objections to this proposition, which was expressed already by Pasteur, and outstanding authorities in chemical science are beginning to incline toward this view. In place of polymorphism, other doctrines are beginning to be advanced, such as Werner’s “valence isomerism,” Hantzsch’s “chromoisomerism,” and others. In the present chapter I make an attempt to apply the theory of mesostructure to the explanation of the phenomena of polymorphism. From this point of view we shall consider the structure of a whole series of substances that display the phenomenon of polymorphism.

As is known, there are two modifications of benzophenone with melting points of 48° and 26°. The second modification is formed simultaneously with the first; ordinarily, however, it is obtained by heating and distilling the higher-melting form. When the molten 26° form is inoculated with a crystal of the 48° form, benzophenone crystallizes as the latter, which in fact furnished grounds for recognizing here the phenomena of polymorphism. Only quite recently (1914) did Schaum discover a certain difference in the refraction and viscosity of the two forms in the liquid state. The same difference was also observed for p-tolyl phenyl ketone. This gave grounds for assuming “chemical” isomerism here, and Schaum proposed calling this phenomenon “cryptochemical polymorphism.”

Stobbe generally believes that, with the development of experimental technique, it will probably be possible to detect differences in the physical properties of all such polymorphic substances in the liquid state and, in this way, to reduce polymorphism to a certain structural isomerism.

Applying here the principles set forth in the first part, we could give the following structures for the two benzophenones (Drawing 23), and in the second case the C–O bond is conceived as perpendicular to the plane of the paper.

According to these formulas, the principal role in the occurrence of isomerism still belongs to the mesovalences of hydrogen, which saturate the oxygen residue. This is confirmed by the fact that both benzophenones give only one oxime, for, as we shall see later, the OH group can have meso-bonds only with one ortho-H atom, and the latter are equivalent in benzophenone. That it is precisely the ortho-hydrogens that take part here is confirmed partly by the fact that polymorphism is also observed in p-dimethylbenzophenone, partly by the fact that, owing to the p-directing influence of the nucleus, the m-atoms will possess a very small residue.

A completely analogous relation is observed in a whole series of other ketones. Thus, for example, β-dinaphthyl ketone has three modifications with melting points 125°, 140°, and 164°. The proposed theory predicts in this case precisely three isomers (Drawing 24); in the last case the carbonyl oxygen is again conceived as above the plane of the drawing. Of course, at the present state of affairs it is very difficult to decide which particular isomer corresponds to one or another formula. Only special investigations could shed light on this question, for, for example, methyl-substituted dinaphthyl ketones have not yet been prepared.

The two modifications of fluorenketone obtained by Stobbe¹ can also be included within the circle of phenomena under consideration. Here, however, it is rather difficult to decide not only what formula to assign to one or the other modification, but also which H atoms in particular take part in the isomerization.

Benzil is far more favorable in this respect. Its two modifications with melting points 95° and ca. 314° apparently have the following structures (Drawing 25), i.e., in one case the carbonyl oxygen is saturated by the mesovalences of the hydrogen of the nearest phenyl and by the hydrogen of the other phenyl; in the other case it is bound only with the hydrogens of the nearest phenyl. In both the one and the other scheme, five- and six-membered rings are formed, which further increases the probability of the meso-bonds that are formed, for, as is known, five- and six-membered rings are the most stable, and, moreover, sterically the atoms occupying the 1,5- or 1,6-positions in a chain are the closest to one another. The formation of heterocycles in the present case does not in the least diminish the plausibility of what has been said, for three or even four carbon atoms in a chain are quite sufficient for determining its configuration. Later we shall see that the formation of rings is the decisive factor that makes it possible to prove definitively the correctness of the proposed structures.

In order finally to make clear the principle of constructing mesoformulas, I shall also give the structures of methylphenylpicramides.

The two modifications of methylphenylpicramide, 108° and 128°, may be constructed in the following manner (Drawing 26). In the first case an eight-membered ring is formed here, but its stability may be considerable, for the central N directs the two bonds going to the nuclei at a certain angle to the plane of the drawing, and, moreover, the nuclei themselves, in a certain position, may also account for the absence of harmful strains in this ring. Besides, the latter may in general be absent here, since the ring includes four atoms with a valence of less than four.

Probably the isomerism of 3-methyluric acid and of a whole series of other “crypto-isomers” may also be interpreted in this plane.

I think that what has been set forth above is sufficient to clarify the essence of the matter definitively. Much of what has been said will appear somewhat arbi—

free and, probably, with the accumulation of factual material, as the result of investigations directed precisely along these lines, much will have to be changed. However, there is some hope that the principle will remain unshakable, and this hope is supported by the quite perfect coincidence of the number of isomers with that predicted by the mesotheory.

Chapter II.

GEOMETRICAL ISOMERISM.

A. Isomerism of ethylene derivatives.

According to the principle set forth in the introduction, that the residual affinity of hydrogen is directly dependent on the degree of intensity of exchange affinity among neighboring carbon atoms, we may expect considerable residues in the hydrogen standing at a double bond. In connection with this, one must expect the manifestation, in unsaturated compounds, of very strong meso-bonds. Among the fundamental properties of unsaturated compounds belongs, as is known, the manifestation in them, under certain conditions not yet fully precisely defined, of a peculiar isomerism. This latter could not hitherto be assigned to any one kind of structural isomerism, for the ethylene isomers, according to the most careful investigations, had an identical structure, at any rate wherever the question was considered from the standpoint of Frankland’s valency. Since until now the manifestation of this kind of isomerism had always been connected with the presence of a double bond, the cause of the given phenomenon was naturally referred to it. Where isomerism was observed even in the absence of a double bond, the Van ’t Hoff theory of “optical” isomers, which until then had conveniently explained all perplexities, reigned; in those cases in which a double bond was present but no isomerism, it was thought that its ascertainment was merely a question of time and experimental technique.

In 1881 Van ’t Hoff expressed the idea that isomerism in the present case is based on spatial relations.

In 1887 Wislicenus proclaimed the theory according to which isomerism in unsaturated compounds is conditioned by the “rigidity” of the double bond. I shall not enter here into the details of Wislicenus’s well-known doctrine, which occupies a prominent place in every textbook of organic chemistry: a definite direction of the units of affinity in space, their likening to certain material rods, the absence, by virtue of this, of free rotation about the double bond—rotation which for an ordinary bond must unquestionably be admitted—these are the basic propositions on which the whole structure rests.

After the principle of the immutability of the units of affinity began to seem to chemists more and more ephemeral; after it became quite evident that the infinite diversity of the activity of organic compounds is based not solely on a different joining of atoms, but also on the strength and firmness of their bonds, it was natural that the doctrine of the rigidity of the double bond began to lose ground. Subsequent explanations of geometrical isomerism yielded nothing new in this direction, while the recognition of the double bond as an ordinary one and of the carbon attached to it as trivalent definitively turned the phenomenon of geometrical isomerism into a huge question mark. Moreover, all the physical properties of the isomers differ greatly from one another, to just as strong a degree as in true structural isomers. Thus the classical fumaric and maleic acids have, as is known,

m.p. 280° and 130°, respectively. They also differ greatly in dissociation constant, in solubility, in heat of solution, in specific gravity, and in a whole series of other properties. In short, by all indications these are genuine structural isomers. Their similarity to the latter is further confirmed by the circumstance that geometrical isomers in many cases also exhibit differences in chemical properties. Thus, some isomeric halogen derivatives behave differently with respect to alcoholic KOH; isomeric acids give salts crystallizing with different water content; in many isomers the reaction of bromine addition at the site of the double bond proceeds at different rates, and so on. In a word, everything here argues that a mere difference in the distances between atoms and groups is insufficient, and that before us are true structural isomers, the difference in whose structure has until now remained unexplained.

Finally, even from a purely logical point of view, the doctrine of the rigidity of the double bond does not withstand criticism, for the number of predicted cis-trans isomers does not correspond to that found experimentally. If, in the case of a smaller number of isomers, one may still assume that such isomers will be found in time, then in the case where the number of isomers actually existing exceeds the number theoretically predicted, one has to leave this question unanswered.

According to Wislicenus, the manifestation of geometrical isomerism rests on the rigidity of the double bond and on the different spatial arrangement of atoms and groups caused thereby. It would be very difficult to object, in substance, to the first supposition, since in this field we still have nothing but illustrative hypotheses. We know nothing about the nature of atomic bonds, and only quite recently has electronic theory seemed to be opening a path into this field. It is possible that there is no rotation around a double bond, but at present we have no grounds for making such an assumption, for, on closer examination, the phenomenon of geometrical isomerism rests not merely on the presence of a double bond and of different radicals at it. I wish here to prove that these radicals must also be of a quite definite nature.

The application of the theory of mesostructures in this field smooths over, to a sufficient degree, all the roughnesses mentioned above and introduces into the question under study a considerable measure of clarity and, most importantly, logical consistency. If we compare all known cases of geometrical isomerism and carry out a detailed analysis of their structures without any preconceived idea, we shall see that, for isomerism to arise, three conditions are necessary, without which this kind of isomerism is never observed. Namely, the molecule must contain:

1) Hydrogen atoms with mesovalences.

2) Certain unsaturated atoms possessing affinity for hydrogen, such as, for example, oxygen, nitrogen, chlorine, etc.

3) There must exist not merely one single possibility for the formation of a mesobond.

If we recall that hydrogen at a double bond, according to the fundamental propositions of mesotheory, possesses a considerable residue, it will become clear that the double bond is needed only in order that mesovalence should appear in hydrogen. In other words, geometrical isomerism rests not on the presence of the double bond, but on the manifestation of mesovalence in the hydrogen atom. It is perfectly obvious that, once there is hydrogen with a residue and an unsaturated atom with affinity for it, all the conditions are present for the formation of a mesobond upon closure, of course, of the corresponding rings. And if there is not just one such possibility, then, under certain conditions, mesobonds may arise either between some atoms or between others; i.e., we obtain, both in the present case and in the case described in the preceding chapter, exactly the same phenomenon—

… phenomenon, which is conditioned by entirely identical circumstances, and for which we shall introduce the new term “mesoisomerism.”

Thus it is now clear how one may represent the structures of fumaric and maleic acids from the point of view of mesotheory, i.e. in the present case the hydrogen at the double bond in maleic acid will be bound to the carbonyl oxygen of its own carboxyl, while in fumaric acid to that of another, foreign one; moreover, in maleic acid there occurs entirely free rotation around the double bond (drawing 27). As is evident from these formulas, they fully correspond to the chemical properties of these acids. It is quite obvious, for example, that the formation of the anhydride from fumaric acid is impossible, whereas maleic acid can readily give it. Owing to the difference in structure, they will naturally also possess different physical properties.

The structures of other ethylene isomers will be built in an entirely analogous way: the hydrogen at the double bond in one will be bound to its own unsaturated atom, i.e. to the atom standing at the same carbon of the double bond; in the other, to a foreign one, i.e. one standing at the other carbon of the double bond.

Thus, the fundamental condition for the emergence of isomerism is the possibility of different combination of hydrogen with a residue in one part of the molecule and with an atom having affinity for it in another. This proposition is confirmed by the following facts.

Geometrical isomerism in the ethylene series is never observed among hydrocarbons: it has been established exclusively in halogen derivatives, acids, and ketones, i.e. in compounds having a halogen and unsaturated oxygen. In this field, despite the very large number of unsaturated hydrocarbons, geometrical isomerism is known only in three of their representatives, namely in 2-butene, stilbene, and allylpropylene.

As regards 2-butene, its isomerism was discovered by Wislicenus, and it was found that one isomer has a boiling point of $1.2^\circ$—$2.7^\circ$, while the other $1^\circ$—$1.5^\circ$ at 754 mm.

But Wislicenus inferred the existence of isomerism in this case not from this sign alone, for, taking only this into account, it would be extremely difficult to believe that before us are two different substances, since in order to lower the boiling point by $1^\circ$ only an utterly negligible amount of impurity is needed. Nor does that long roundabout path of proving the different structure of the two butenes, which Wislicenus undertook, give more convincing results. Let us first consider the method of obtaining the two isomers. The starting substances are tiglic and angelic acids, and it is assumed that the difference in their structure is of a purely steric character, since here there is a double bond, drawing 28, schemes I and II.

These acids are acted upon by hydriodic acid, yielding two different halogen derivatives.

The subsequent phase is the decomposition of these two acids under the action of an aqueous solution of soda into $\mathrm{CO_2}$, $\mathrm{NaJ}$, and butene, and here, too, the formation from hydroiodostereoisomers of isomeric butenes is assumed. However, as is known, the question of the structure of angelic acid can in no way be considered definitively settled, since alongside formula 2 structure 3 is also possible. If this were so, the hydroiodo acids would be merely simple structural isomers 4 and 5, and on splitting off hydrogen iodide from them we would obtain one and the same butene. It is possible that with acid 4 a small amount of $\alpha$-butene is formed. It boils at $5^\circ$, and this impurity would be very difficult to separate from 2-butene. This circumstance probably also accounts for the difference in the boiling temperatures of both “isomers.”

Now let us trace the further changes of butene. Bromine acts upon it and two dibromides are obtained, two only according to Wislicenus’s supposition, for up to the present only one 2,3-dibromobutene is known, namely the one boiling at 158°. Wislicenus, however, regards this product as a mixture, because under the action of alcoholic KOH it yields one third of one bromobutene and two thirds of another. But these isomers, too, could not be isolated in the pure state. The conclusion concerning the different activity of Br in the supposed isomers is based on Holtz’s observation. Holtz¹) found that the two monobromopseudobutylenes prepared by him in the above-described manner passed into crotonylene with different velocities under the action of alcoholic caustic alkali. However, these two bromides had boiling temperatures—one, obtained from the above-mentioned dibromide by the action of alcoholic KOH, of 87–88°, the other from crotonylene and HBr, of 83–84°. As may be seen, the difference in boiling temperatures here is only 3–4°, which makes one doubt very much the distinction between these bromides. As regards the difference in the rate of their reaction with alcoholic caustic alkali, here, in the only place that seems more or less convincing, we have nothing except an observation—no measurement of the reaction rate was made, and the conclusion was drawn “by eye.” True, subsequently so small a difference in boiling temperatures induced Wislicenus to repeat Holtz’s work, and he succeeded, for the product from the dibromide and alcoholic KOH, in raising the boiling temperature to 94°. However, Wislicenus did not investigate more closely the second case, i.e. the bromide from crotonylene, for it is possible that there too, with more careful work, the boiling temperature would have risen, and thus sufficient grounds for comparing the results would not have been obtained.

On the basis of all that has been said above I venture to assert that there exists only one 2-butene and one 2-bromo-2-butene, and, consequently, this case does not belong to “stereoisomerism.”

The second case, with allylpropene, has been so little investigated, and the boiling temperatures of its isomers are so close (identical), that there can be no doubt about the absence of isomerism here as well.

But if very great doubts may arise for us about the existence of isomerism in 2-butene and allylpropene, then with regard to stilbene there can be no two opinions: here isomerism is not subject to the slightest doubt. Both isomers differ very greatly in boiling temperature, both have been isolated in the pure state, and the conditions of their mutual conversion have been studied. For this, actually the only case of isomerism in a hydrocarbon, one must make a certain assumption, namely, that mesobonds here can arise also between two unsaturated hydrogens, an assumption not in the least contradicting the fundamental principles. Thus, for stilbene we obtain the structures (drawing 29-i).

Thus, with the sole exception of isomerism in ethylene derivatives, it is observed only in halogen derivatives, acids, and ketones, i.e. compounds having atoms that possess a strong affinity for hydrogen.

The probability of this proposition is further confirmed by the remarkable circumstance that, with the replacement of hydrogen by CH₃, isomerism necessarily disappears. Thus, two isomers are known for fumaric acid; two isomers are also known for methylfumaric acid—citraconic, 91°, and mesaconic, 202°. Dimethylfumaric acid, however, is known only in one form, and its stereoisomer has not been obtained to this day. The theory of mesostructures does not predict it either, for here there is no hydrogen with a residue.

The replacement of hydrogen by chlorine, however, does not lead to the disappearance of isomerism, especially in those cases where hydrogen with a residue still remains in the molecule. Especially

¹) C. 1889. I. 416.

interesting in this respect is methylchlorostilbene, known in two modifications: a liquid with boiling point $316^\circ$ and a solid melting at $117^\circ$. For them one may imagine the following structure (drawing 30).

It is noteworthy that, under the action of alcoholic caustic alkali, chlorine is split off here only with great difficulty, which is in complete agreement with the principle set forth in the introduction.

In those cases where the presence of a number of isomers nevertheless does not correspond to the proposed theory, one must in general very much doubt the existence of isomerism: the constants of the isomers are usually as close to one another as in 2-butene, despite the invariably very considerable difference in the case of genuine isomers. The following compounds should be assigned to the number of such doubtful isomers:

\[ \begin{array}{c@{\qquad\qquad}c} \begin{array}{c} \mathrm{CH_3{-}C.H.}\\ \|\\[-2pt] \mathrm{Cl{-}C.H.} \end{array} & 35^\circ\ \text{and}\ 38^\circ \\[2.2em] \begin{array}{c} \mathrm{CH_3{-}C.H.}\\ \|\\[-2pt] \mathrm{Br.{-}C.H.} \end{array} & 63^\circ\ \text{and}\ 59^\circ \\[2.2em] \begin{array}{c} \mathrm{Cl.{-}C.H.}\\ \|\\[-2pt] \mathrm{Cl.{-}C.CH_3} \end{array} & 78^\circ\qquad 75^\circ \\[2.2em] \begin{array}{c} \mathrm{Cl{-}C.H.}\\ \|\\[-2pt] \mathrm{J.CH_2.C.H.} \end{array} & 162^\circ\qquad 150^\circ \end{array} \]

and others.

Let us now examine two interesting cases of isomerism, representing a mixture of physical isomerism with geometrical isomerism and explicable, from the proposed point of view, by the methods set forth both in the preceding chapter and in the present one—methods which, in principle, of course, do not differ in any way.

Stobbe¹, by acting with alcoholic caustic alkali on the product of condensation of nitrobenzaldehyde with deoxybenzoin under the influence of HCl, obtained two $o$-nitrobenzaldezoxybenzoins and three each of $m$- and $p$-nitrobenzaldezoxybenzoins.

\[ \mathrm{NO_2.C_6H_4.COH + C_6H_5.CH_2.CO.C_6H_5} \longrightarrow \mathrm{NO_2.C_6H_4.CH:C.CO.C_6H_5 + H_2O} \]
\[ \hspace{9.5em}\mathrm{\vert} \]
\[ \hspace{9.1em}\mathrm{C_6H_5} \]

The latter isomers in no way fit within the framework of stereoisomerism, and Stobbe assigned them to a certain new kind of isomerism, without, however, giving any explanation of this phenomenon. The question of polymorphism was already excluded by the fact that the isomers, in the molten state, possessed entirely different properties. Their solutions were also different in optical respect.

In order to construct mesoformulas for all these substances, let us make some preliminary calculations. First let us construct mesoformulas for disubstituted benzenes. Since one radical is metadirectional, while the other is para, then, according to the above-mentioned principle of superposition, we shall obtain for the three derivatives the following schemes (drawing 29-a).

As is evident, the o-m-isomers have only one o-H atom with free mesovalence. The pair of isomers, however, has two unsaturated o-H atoms. The distributive formula of the condensation product will be as follows (drawing 31).

Here the bond between carbon atoms 1 and 2 will be very weakened, since both carbons carry very heavy radicals. Atom 1 is especially overloaded. Since atom 2 has a very weak bond, it will greatly consume affinity from phenyl II, and this, as we know, will also bring about m-diradicalization of the latter and the loss of mesovalences at the o-H atoms. Thus phenyl II will take no part in the isomerization, and for the carbonyl oxygen there remain the H atoms of phenyl I, phenyl III, and C atom 3, i.e., three possibilities. If the $\mathrm{NO_2}$ group of phenyl III is in the o-position, then there is no doubt that its O will saturate the mesovalence of the H atom at C atom 3, and then only two possibilities will remain for the carbonyl oxygen, namely at phenyl I and at the o-H atom of phenyl II. Thus, for the o-isomers we obtain drawing 32, and for the m-isomers and p-isomers drawing 33.

Thus here the inequality in the number of isomers among o-, m-, p-substituted compounds depends on the binding by the o-nitro group of the H atom at C atom 3 and, in this way, on the exclusion of its influence.

Another case is the much-studied cinnamic acids. It turned out (1914) that the 68°, 58°, and 42° acids have different solutions, for they can be crystallized back unchanged. Moreover, the 68° and 58° acids, when their melts were heated, gradually changed into the 42° acid. The character of the mutual transitions of these acids in the crystalline state also indicates that what is present here is isomerism, and not polymorphism.

But a single glance at the structure of the cinnamic acids is enough to be convinced that here there is a mass of possibilities for the manifestation of mesoisomerism: here there is a p-diradicalized nucleus having two o-hydrogen atoms with a residue; there are two hydrogens at a double bond, and there is also the unsaturated oxygen of the carboxyl. Thus, bearing in mind the above-mentioned formulas of stilbene, we could give the following schemes for the cinnamic acids (drawing 34). The question of which particular substance is to be assigned this or that formula appears, in the present case, very difficult. From this point of view the formation of the 133° acid and of the 68° acid from benzalmalonic acid upon removal of $\mathrm{CO_2}$ is extremely important. It is clear that, depending on the destruction of one or the other carboxyl, the following two isomers are obtained:

\[ \begin{array}{ccc} \begin{array}{c} \mathrm{C_6H_5\cdots\cdots H}\\ \vdots\\ \vdots\quad C\\ \vdots\quad \Vert\\ \vdots\quad C\\ \mathrm{HOOC}\quad\quad H \end{array} & \rightleftarrows & \begin{array}{c} \mathrm{C_6H_5}\quad\quad H\\ \vdots\quad\quad\vdots\\ \vdots\quad C\\ \vdots\quad \Vert\\ \vdots\quad C\\ \mathrm{HOOC}\quad\quad \mathrm{COOH} \end{array} \quad \longrightarrow \quad \begin{array}{c} \mathrm{C_6H_5}\quad\quad H\\ \vdots\quad\quad\vdots\\ \vdots\quad C\\ \vdots\quad \Vert\\ \vdots\quad C\\ H\quad\quad \mathrm{COOH} \end{array} \end{array} \]

moreover, since in the 133° acid the phenyl and carboxyl are not in immediate proximity, the first formula may be adopted for it, and in the preceding structures the third. Then for the 63° acid the formula will be the second. This is also supported by the easy transition of allo-acid under the action of $\mathrm{H_2SO_4}$ into truxone:

\[ \begin{array}{ccccc} \begin{array}{c} \mathrm{C_6H_5\cdots\cdots H}\\ \vdots\\ \vdots\quad C\\ \vdots\quad \Vert\\ \vdots\quad C\\ \mathrm{HOOC}\quad\quad H \end{array} & + & \begin{array}{c} \mathrm{H\cdots\cdots C_6H_5}\\ C\\ \Vert\\ C\\ H\quad\quad \mathrm{COOH} \end{array} & \longrightarrow & \begin{array}{cccc} \mathrm{C_6H_5}\!\cdot\!\mathrm{CH} & \cdot & \mathrm{CH}\!\cdot\!\mathrm{C_6H_5}\\ | && |\\ \mathrm{CO} & \cdots & \mathrm{CH}\!\cdot\!\mathrm{CH}\!\cdot\!\mathrm{CO} \end{array} \end{array} \]

As is known, Rupe¹ prepared a series of methyl-substituted cinnamic acids, and it turned out that substitution of the p-atom of the nucleus completely destroys isomerism. This circumstance is well explained by the mesotheory. The distribution formula of cinnamic acid has the following form (Fig. 35, scheme I). If we now introduce into the nucleus one more ortho-directing radical in the para-position, then H-atoms 2 and 6 lose their mesovalences (see scheme II, Fig. 12), so that they are entirely excluded. Moreover, the bond of the nucleus with the carbon is extremely weakened as a consequence of the very strong directing ability of methyl. And this will cause strengthening of the bonds of C-atom 7 with hydrogen and the loss by it also of mesovalence. Thus for the carboxyl there will probably be the sole possibility of forming a mesobond with the H-atom at C-atom 8, i.e. there will be no isomerism. In this way we obtain mesoformula II.

However, although this circumstance is quite understandable, it is very difficult without special assumptions to explain the fact of the formation of two isomers among the dimethylcinnamic acids. It is possible that here either the methyl group or even, perhaps, the p-H-atom takes part. As we shall see below, sometimes the methyl group is not an inert radical, and it is possible that here also, under certain conditions, mesovalences arise.

We encounter another interesting case in the so-called oxylepidines. For these compounds five isomers are known, whereas the classical theory predicts only two. These five isomers have the following melting points: 161°, 162°, 152°, 220°, 232°. According to the mesotheory there should have been six isomers here. Oxylepidine has the following protoformula (Fig. 36).

Mesobonds may arise here between the O-atoms and the o-H-atoms of the nucleus. If we denote all possible combinations, we obtain the following picture:

\[ \begin{aligned} \text{I.}\quad & A \circ\cdot\circ\cdot\circ\cdot\circ\; O \;\circ\cdot\circ\cdot\circ\cdot\circ\; A; \qquad & A_1 \circ\cdot\circ\cdot\circ\cdot\circ\; O_1 \;\circ\cdot\circ\cdot\circ\cdot\circ\; A_1 \\ \text{II.}\quad & B \circ\cdot\circ\cdot\circ\cdot\circ\; O \;\circ\cdot\circ\cdot\circ\cdot\circ\; B; \qquad & B_1 \circ\cdot\circ\cdot\circ\cdot\circ\; O_1 \;\circ\cdot\circ\cdot\circ\cdot\circ\; B_1 \\ \text{III.}\quad & A \circ\cdot\circ\cdot\circ\cdot\circ\; O \;\circ\cdot\circ\cdot\circ\cdot\circ\; B; \qquad & A_1 \circ\cdot\circ\cdot\circ\cdot\circ\; O_1 \;\circ\cdot\circ\cdot\circ\cdot\circ\; B_1 \\ \text{IV.}\quad & A \circ\cdot\circ\cdot\circ\cdot\circ\; O \;\circ\cdot\circ\cdot\circ\cdot\circ\; B; \qquad & A_1 \circ\cdot\circ\cdot\circ\cdot\circ\; O_1 \;\circ\cdot\circ\cdot\circ\cdot\circ\; A_1 \\ \text{V.}\quad & B \circ\cdot\circ\cdot\circ\cdot\circ\; O \;\circ\cdot\circ\cdot\circ\cdot\circ\; B; \qquad & A_1 \circ\cdot\circ\cdot\circ\cdot\circ\; O_1 \;\circ\cdot\circ\cdot\circ\cdot\circ\; A_1 \\ \text{VI.}\quad & B \circ\cdot\circ\cdot\circ\cdot\circ\; O \;\circ\cdot\circ\cdot\circ\cdot\circ\; B; \qquad & A_1 \circ\cdot\circ\cdot\circ\cdot\circ\; O_1 \;\circ\cdot\circ\cdot\circ\cdot\circ\; B_1 \end{aligned} \]

Here, in order to save space, I denote only the mesobonds of the molecule—the whole mesoformula can readily be represented from them.

With this I shall finish the consideration of ethylenic isomers and shall now turn to isomerism in nitrogenous compounds. One further weighty argument in favor of free rotation about the double bond and of the mesotheoretical explanation of geometrical isomerism will be considered in the chapter on optical isomerism.

B. Nitrogenous compounds.

As is known, isomerism in these compounds, manifested chiefly in oximes and diazo compounds, is at present explained by the theory of Hantzsch and Werner, which in principle differs in no way from the above-mentioned theory of Wislicenus. It is assumed that in the present case, as with ethylenic compounds, the double bond between nitrogen and the carbon of type II is rigid; consequently, rotation about it cannot occur. This conditions a different spatial relationship between the hydroxyl of the isonitroso group and the radicals at the carbon, by virtue of which different substances are obtained.

Various recent interpretations, although they are not always based on the rigidity of the double bond, nevertheless give explanations suitable only for all substances containing a given complex. Why in one case, with a C=N bond, there is isomerism, while in others there is not—this no theory explains.

Already in the preceding chapter we analyzed in detail the fundamental aspect of the question, so that concerning the rigidity of the C=N bond one could say literally the same thing. In the present chapter I shall indicate only those cases, special for the given class of compounds, in which the phenomena of isomerism do not fit within the framework of the Hantzsch–Werner theory.

According to the latter authors, the isomerism of oximes is conditioned by the presence of a double bond. Exactly as in the case of ethylenic compounds, in some cases this definition is too broad, for there exists a very large number of oximes in which isomerism could not be detected, despite very careful special searches; in other cases it is too narrow, for oximes are known in which the number of isomers exceeds the theoretically predicted number. Thus the Hantzsch–Werner theory provides for two isomers, syn- and anti-, in all monoximes. However, up to the present time there has not yet been a single case in which isomerism was discovered if both radicals at the “oxime” carbon atom were aliphatic and saturated. Nor is it observed when one radical is aliphatic and the other aromatic. On the other hand, such a compound as, for example, methylbenzylglyoximic acid

\[ \begin{array}{cc} \mathrm{C_6H_5} & \mathrm{OCH_3}\\ & \mathrm{C}\\ & |\\ & \mathrm{NOH} \end{array} \]

is known in three well-characterized isomers with m.p. 44°, 64°, and 101°. For dioximes the Hantzsch–Werner theory predicts three isomers: syn-, anti-, and amphi-. However, for example, all attempts to obtain any isomers of dimethylglyoxime have led to nothing, and it is still known only in one form. One form is found in methylphenylglyoxime

\[ \tag{2} \mathrm{CH_3 \cdot C - C \cdot CH_3} \qquad \mathrm{C_5H_6 \cdot C - C - CH_3} \]
\[ \begin{array}{ccccc} & \| & \| & & \| \quad \|\\ & \mathrm{NOH} & \mathrm{NOH} & & \mathrm{NOH}\quad \mathrm{NOH} \end{array} \]

Already from this brief survey it is evident that the isomerism of oximes is conditioned by certain more complex circumstances than merely the mere presence of a double bond. Since this kind of isomerism is related to the isomerism of ethylenic compounds, the same explanations inevitably suggest themselves here. Just as in ethylenic compounds, here too a hydrogen with residual affinity is necessary, some atom with affinity for something, and, in addition, the possibility of formation of meso-bonds must not be unique—and only when these three conditions are observed is the manifestation of isomerism possible. If even one of these conditions is absent, there will be no isomerism.

Applying now to this class of substances the fundamental principle of mesotheory, we can outline the following mesoformulas for oximes: for aldoximes (drawing 37), for ketoximes (drawing 38), and for dioximes (drawing 40).

As is seen from these schemes, they differ very little from the classical ones—the vectoriality of the hydroxyl is also evident here; the whole difference lies only in the fact that this vectoriality is motivated by meso-bonds, and not by the rigidity of the double bond. Of course, for aliphatic radicals that have no hydrogen with residual affinity,

such schemes cannot be given, which is quite consistent with the absence of isomerism there. The configuration of the isomers can be transferred here in its entirety, and we shall here call syn- and anti-compounds the same things that are meant by these terms in the classical theory.

I shall now present the factual material proving that the mesostructures depicted above have been constructed correctly. The circumstance that here again and again hydrogen with a residue plays a role is evident from the fact that replacing it by $\mathrm{CH}_3$ completely destroys isomerism.

Thus, for example, methylphenylglyoxime is known only in one form (drawing 39).

Here, with the disappearance of one phenyl group, the hydrogen with the residue has also disappeared, and consequently only one form has become possible, in which both oxygens are saturated by the o-hydrogens of phenyl. Thus, in the radicals the active agent is hydrogen.

For the isonitroso group three cases are possible: either $\mathrm{N}$, or $\mathrm{O}$, or $\mathrm{H}$ may combine with hydrogen. That this is not $\mathrm{H}$ is evident from the circumstance that replacing it, for example, by an acetyl group is in no way reflected in the isomerism: the number of isomeric acetyl derivatives corresponds exactly to the number of oximes. Thus diphenylglyoxime has three acetyl derivatives, $113^\circ$, $124^\circ$, and $147^\circ$. Consequently, two possibilities remain, $\mathrm{O}$ and $\mathrm{N}$. Here we might obtain an indication by replacing the entire hydroxyl by some radical, for example by $\mathrm{CH}_3$; if the isomerism were preserved, it would be clear that nitrogen combines with hydrogen. However, if such cases have been observed, subsequent investigation has revealed their untenability. Thus Scheiber¹), repeating Luxmoore’s work²), found that those N-substituted oximes which had previously been considered isomeric proved to be only different hydrates of one and the same substance. Thus, replacement of the whole hydroxyl destroys isomerism, which indicates that nitrogen plays no role here; there remains only one possibility for oxygen, which is also accepted in the formulas depicted above. The possibility of oxygen combining with both o-hydrogens with manifestation of full tetravalency is improbable, for mono-ortho-substituted oximes, e.g. o-chlorobenzaldoxime and o-nitrobenzaldoxime, are known in two forms.

Let us dwell further on certain interesting details that fit poorly into the classical theory, and at times even contradict it. I have already mentioned cases of the appearance of a greater number of isomers than is predicted by the Hantzsch–Werner theory, for example in methylbenzhydroxamic acid. For the latter one could give the following three structures (drawing 41).

Entirely analogous relations are observed for the liquid dioximes, which are known only in two forms. The proposed theory predicts precisely two isomers, as opposed to the three classical ones (drawing 42).

As one of the examples proving the existence of a residue in naphthene, I shall cite the isomerism of hexahydrobenzophenone oxime (drawing 43).

It is also easy to understand the difficulties in determining the configuration by means of the Beckmann rearrangement in the oxime of acetacrylic acid. It is known in two modifications, $206^\circ$ and $189^\circ$. Their mesostructure will be as follows (drawing 44).

It is clear that the Beckmann rearrangement will give no results, for both oximes, in Hantzsch’s terminology, are anti-compounds.

The difference in the degree of stability of the isomeric oximes also argues in favor of the existence of meso-bonds, for the modification in which the oxygen is combined with the hydrogen having the larger residue proves also to be more stable—

¹) A. 365, 125.
²) Soc. 69, 177.

... Thus, with respect to ketoximes it is known that the radicals at carbon, in their “attracting” force with respect to the hydroxyl, are arranged in the following series:

\[ \mathrm{COOH \cdot CH_2;\ COOH \cdot CH_2 \cdot CH_2;\ C_6H_5;\ COOH;\ C_6H_4 \cdot X;\ C_6H_5 \cdot CO;} \]

\[ \mathrm{C_4H_3S;\ C_4H_3O;\ C_nH_{2n+1};\ CH_3.} \]

It is not difficult to see that hydrogen in this series, as one proceeds from left to right, becomes precisely less and less mobile. The greatest mobility of the hydrogen of the first radical is explained by the very intense exchange of affinity between $\mathrm{CH_2}$ and $\mathrm{COOH}$, the former, as is known, always taking much affinity from carbon (diagram 45).

Quite analogously to ethylenic compounds, isomeric oximes differ also in their chemical properties. Thus anti- and amphibenzil dioximes crystallize with one particle of alcohol, whereas the syn-isomer does not give molecular compounds. Antibenzylmonoxime crystallizes with $1/2\ \mathrm{C_6H_6}$; its isomer does not combine with benzene. Other chemical differences, such as: splitting off of nitrile, alkylation, and the Beckmann rearrangement, in no way contradict either theory, and therefore I shall not speak of them.

As for other nitrogen-containing compounds, here the general picture changes little. Thus, hydrazones, semicarbazides, and other compounds, like oximes, can very often be obtained in the form of two isomers, which classical theory counts among the stereoisomers. Of course, all these cases also fit perfectly within the framework of the proposed theory.

Somewhat better studied, and very important from a theoretical point of view, is the isomerism in diazo compounds, which sometimes exist in two forms. There are no facts in this field that plainly contradict Hantzsch’s theory; the only somewhat strange feature is the special stability of the diazocyanides, which possess a sharply expressed difference in physical properties and are therefore the best studied. Isomerism in other diazo compounds has been observed only in the salts of sulfo acids and in the salts of aryl diazotates. The difference here is expressed in unequal color. Applying the theory of mesostructures here, we could give the following formulas for these compounds, diagram 46.

The at first glance somewhat unexpected meso-bond of nitrogen with metals is motivated by the circumstance that the diazohydrates themselves very readily transform into nitrosamines:

\[ \mathrm{ C_6H_5 \cdot N^{O} \cdot O \cdot O \cdot H \atop \begin{array}{c} \|\\[-0.4em] N \cdots O \end{array} \quad \longrightarrow \quad C_6H_5 \cdot NH \atop \begin{array}{c} |\\[-0.4em] NO \end{array} } \]

i.e., here oxygen is not attached to the nitrogen located at the nucleus. In all other respects these formulas differ little from those proposed earlier here, and therefore I shall not give a detailed justification of them.

(Conclusion follows.)

SUMMARY

The stronger the carbon bond, the more weakly the hydrogen is bound to it and, consequently, the greater its residual affinity. This residual affinity I call “mesovalency”—it is completely identical with Werner’s secondary valency.

For halides the relations are completely the reverse, which is explained both by the formation of a bond between the halides and hydrogen and by the specificity of the bond of the halide with carbon.

The bond obtained as a result of the mutual saturation of mesovalences is called a “mesobond.”

Benzene has no central bonds; its carbon bonds constitute something integral, as a result of which its hydrogen atoms possess considerable mesovalence.
Chlorine in benzene hexachlorides is bonded not to carbon, but to hydrogen.
The substitution reaction proceeds in such a way that the mesobonds formed in the primary addition product remain untouched also in the reaction product.
Each substituent entering the nucleus combines not only with the carbon of the nucleus, but also with neighboring o-H atoms, with the formation of mesobonds, if, of course, the entering radical has unsaturated atoms.
Upon entry of a substituent, a redistribution of affinity takes place, which in one case causes weakening of the ortho-para hydrogens, and in another case of the meta hydrogen. The arising of mesobonds intensifies this phenomenon.
Radicals having unsaturated atoms attached directly to the nucleus are ortho-para directors, while meta directors are those which have an unsaturated atom not joined to the nucleus. The cause of directing lies in the nonuniform distribution of affinity.
An explanation has been proposed for a whole series of problems directly connected with the theory of orientation, such as, for example, the rate of substitution reactions, the different strength of radicals in the nucleus, etc. A scheme is given for constructing mesoformulas for the cases in question.
On the basis of the principles set forth above, the mesoformula of naphthalene has been constructed.
The phenomenon of steric hindrance is based not on the volume of the radical, but on the arising of mesobonds between this radical and the neighboring ortho hydrogens, and also on the nonuniform distribution of affinity.
Physical isomerism is structural isomerism; it is encountered only in those compounds where there is not merely a single possibility for the arising of mesobonds. The number of known isomers in the overwhelming majority of cases corresponds to the number of these possibilities.
From this point of view, the isomerism of benzophenone, β-dinaphthylketone, benzil, and methyl-phenyl-pyramidones has been considered, and mesoformulas have been constructed for these cases.
The isomerism of ethylene derivatives rests not on the presence of the double bond as such and on its rigidity, but on the presence of hydrogen atoms with mesovalence and of certain atoms possessing affinity for them. Isomerism arises only when there are several possibilities for the formation of mesobonds.
Ethylene isomerism is never observed if the radicals at the double bond are fatty and saturated, which is explained by the absence in such radicals of hydrogen atoms with mesovalences.
Replacement of hydrogen atoms with mesovalence by other radicals destroys the phenomenon of isomerism, despite the presence of a double bond and of various radicals at the latter.
The number of known isomers in the overwhelming majority of cases corresponds to that predicted by the proposed theory.
From this point of view, the isomerism of fumaric and maleic acids, stilbene, nitrobenzal-deoxybenzoin, cinnamic acids, and oximes has been considered. For these cases, mesoformulas have been constructed.

The isomerism of 2-butene and allylpropylene appears to be highly dubious.
The isomerism of oximes is not caused by the presence of a double bond and its rigidity, but by the emergence of a meso-bond between oxygen of the isonitroso group and hydrogen of the radical located at the carbon atom.
If this radical has an unsaturated atom, then the hydrogen and the isonitroso group take part in the isomerization.
Isomerism is completely eliminated by replacing the hydrogen atom with mesovalency, or else the hydroxyl of the isonitroso group, by some inert radical.
Here, too, the number of known isomers corresponds to that predicted by the meso-theory.
From this point of view, the isomerism of such oximes has been considered for which the number of isomers does not correspond to that predicted by the classical theory.
The series of radicals in which the latter are arranged by Werner according to the strength of their influence on the isonitroso group is fully explained by the meso-theory.
Both isomers of acetacrylic acid are anti-compounds.
In the proposed system, the isomerism of diazo compounds also finds a rational place and is explained in an entirely analogous manner.
Thus, all the above-considered categories of isomerism are explained by one common cause and are united under a general concept. For the latter the term “mesoisomerism” is proposed, and three conditions for its occurrence are established. At present there is no longer any need whatsoever, in explaining these phenomena, to resort to spatial formulas and representations.

Fig. 1

Schematic forms numbered 1–5, showing mesomeric arrangements with $ \mathrm{H} $, $ \mathrm{Cl} $, $ \mathrm{C} $, and dotted/solid valence connections.

Fig. 2

Intramolecular formation.

Labile form.

Mesomerism.

Spatial form.

Fig. 3

Structural schemes designated I, II, III, IV, V, with arrows indicating transformations and the liberation/addition of $ \mathrm{HBr} $.

Fig. 4

Cyclohexane-type spatial scheme with hydrogen atoms shown by solid and dotted bonds.

Fig. 5

Polycyclic scheme with substituents $a$, $b$, $c$ and hydrogens $H$.

Fig. 6

Scheme with forms I, II, III and transitions between mesomeric structures.

Fig. 7

Three fused-ring spatial schemes designated I, II, III, with substituents $a$, $b$, $c$, $H$, and dotted interactions.

Fig. 8

Reaction scheme involving forms I, II, III, with arrows and addition/elimination of $ \mathrm{HBr} $.

Fig. 9

Two mesomeric structural schemes with hydroxyl groups, carbonyl oxygen, and arrows indicating transformation between forms.

Fig. 10

Three-dimensional cyclohexane-type mesomeric scheme designated I.

Fig. 11

Two cyclohexane-type spatial forms designated I and II, with substituent $ \mathrm{NO_2} $.

Fig. 12

Three schemes involving cyclohexane-type forms and $ \mathrm{NO_2} $, with arrows indicating transitions.

Fig. 13

Reaction scheme of cyclohexane-type forms involving $ \mathrm{CO_2H} $ and mesomeric transformation.

Fig. 14

Scheme with three numbered forms:

$ \mathrm{CHC{-}CHC} $
$ \mathrm{HC{-}CH} $
$ \mathrm{HC{-}CH_2} $
$ \mathrm{HC{-}CH} $
$ \mathrm{HC{-}CH} $

with corresponding mesomeric structural representations.

Fig. 15

Cyclohexane-type scheme with substituent $ \mathrm{CO_2H} $, hydrogen atoms, and dotted intramolecular interactions.

Fig. 16

Cyclohexane-type scheme with substituent $ \mathrm{NO_2} $, hydrogen atoms, and dotted intramolecular interactions.

Fig. 17

Two cyclohexane-type spatial forms involving $ \mathrm{NO_2} $, with arrows indicating transformation and addition of a second cyclic form.

Fig. 14

Structural diagrams I–V, with positions marked $m$ and $p$.

Fig. 15

Sequence of structural diagrams involving $Cl$ and $H$ substituents on a cyclohexane ring, connected by arrows.

Fig. 16

Combination of two cyclohexane structural diagrams, followed by an arrow to a substituted cyclohexane diagram with positions marked $m$ and hydrogens $H$.

Fig. 17

Fused-ring structural diagram with hydrogens $H$ indicated at the outer positions.

Fig. 18

Two structural diagrams with $H$, $O$, and $CH_3$ substituents.

Fig. 21

Ring structural diagram with alternating $C$ and $O$ atoms and hydrogens $H$ indicated by dotted connections.

Fig. 19

Two structural diagrams labeled I and II, with $H$, $O$, and $CH_3$ substituents.

I

II

Fig. 22

Reaction scheme:

\[ \begin{aligned} &\text{cyclic structure with } C,\ O,\ H \;+\; OHNH_2 \;\longrightarrow\; \text{intermediate with } H\!-\!OH,\ O\!\cdots NH_2 \;\longrightarrow\; \text{cyclic product with } C{=}N,\ OH,\ H. \end{aligned} \]

Fig. 20

Two structural diagrams labeled I and II, with $N$, $H$, and $R$ substituents.

I

II

[Structural chemical diagrams.]

Fig. 23

[Structural chemical diagrams.]

Fig. 24

There is yet another isomer possible. J. K.

[Structural chemical diagrams, including the repeated formula $C_6H_5 \cdot CO \cdot CO \cdot C_6H_5$.]

Fig. 25

[Structural chemical diagrams.]

Fig. 26

Fig. 25

Fig. 26

Fig. 27

any cis–cis, cis–trans

trans. $\mathrm{CH:CH\cdot CH_2\cdot COOH}$

trans. $\mathrm{CH:CH\cdot CH\cdot COOH}$
$\mathrm{CH_3}$

Structures labeled: I, II, III.

Fig. 28

Structures labeled: IV, V.

Fig. 29

Fig. 30

Fig. 31

Structures labeled: I, II, III.

Fig. 32

(The visible page consists entirely of chemical structural diagrams and figure/equation labels; no continuous body text is visible.)

Equation 52.
Chemical structural scheme with cyclohexane rings, carbonyl and nitro groups, and labels including $ \mathrm{NO_2} $, $ \mathrm{C_6H_5} $, $ \mathrm{CH_3} $, $ \mathrm{C} $, $ \mathrm{O} $, and $ \mathrm{H} $. The scheme includes structures marked I, II, and III.

Fig. 33.
Chemical structural diagrams showing mesomeric/associated forms of substituted cyclohexane derivatives, including labels I and II, and substituents $ \mathrm{NO_2} $, $ \mathrm{C_6H_5} $, $ \mathrm{CH_3} $, $ \mathrm{C} $, $ \mathrm{O} $, and $ \mathrm{H} $.

Equation 54.
Chemical structural schemes labeled I, II, III, and IV, containing groups $ \mathrm{HO} $, $ \mathrm{O} $, $ \mathrm{C} $, and $ \mathrm{H} $, with dotted intramolecular interactions indicated.

Fig. 34.
Four related cyclic structural formulas labeled I, II, III, and IV, showing hydrogen-bond or mesomeric interactions by dotted lines and containing $ \mathrm{HO} $, $ \mathrm{O} $, $ \mathrm{C} $, and $ \mathrm{H} $ groups.

Equation 53.
Chemical structural schemes labeled I and II, with numbered ring positions and dotted interactions involving $ \mathrm{H} $, $ \mathrm{C} $, $ \mathrm{O} $, $ \mathrm{OH} $, and $ \mathrm{CH_3} $.

Fig. 35.
Chemical structural diagrams showing cyclic systems with numbered positions and intermolecular/mesomeric interactions, including labels I and II and groups $ \mathrm{HO} $, $ \mathrm{O} $, $ \mathrm{C} $, $ \mathrm{H} $, and $ \mathrm{CH_3} $.

Fig. 36.
Linear conjugated structural scheme:

\[ A_1 - C(=O) - C = C - C(=O) - A \]

with cyclic substituents labeled $ A_1 $, $ B_1 $, $ B $, and $ A $.

[Chemical structural diagrams]

Fig. 37

[Chemical structural diagrams]

Fig. 38

[Chemical structural diagram]

Fig. 39

[Chemical structural diagrams]

Fig. 40

[Chemical structural diagrams]

Fig. 41

\[ -\mathrm{CH_3} \]

\[ \mathrm{H{-}C{-}C{-}Cl} \]

\[ \begin{gathered} \mathrm{H{-}C{-}C{-}Cl}\\ \mathrm{HON \qquad NOH} \end{gathered} \]

\[ -\mathrm{CH_3} \]

\[ \begin{gathered} \mathrm{H{-}C{-}C{-}Cl}\\ \mathrm{HO{-}N \qquad N{-}O} \end{gathered} \]

\[ \begin{gathered} \mathrm{N{=}C{-}Cl}\\ \mathrm{HO \qquad C{=}N{-}O} \end{gathered} \]

Fig. 42

Fig. 39

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes with dotted intramolecular linkages}\\ \mathrm{C{=}N,\quad O{-}H,\quad N{-}OH} \end{gathered} \]

Fig. 43

\[ \mathrm{CH_3C{-}CH{=}CH{-}COOH} \]

\[ \begin{gathered} \mathrm{CH_3C{-}CH{=}CH{-}COOH}\\ \mathrm{\|}\\ \mathrm{NOH} \end{gathered} \]

\[ \begin{gathered} \mathrm{CH_3C{-}C{=}CH{-}COOH}\\ \mathrm{\| \qquad H}\\ \mathrm{N{-}O{-}H} \end{gathered} \]

\[ \begin{gathered} \mathrm{CH_3C{-}C{=}C{-}COOH}\\ \mathrm{\| \qquad H}\\ \mathrm{N{-}O{-}H} \end{gathered} \]

Fig. 44

\[ \begin{gathered} \mathrm{HOOC{-}C{-}C{-}COOH}\\ \mathrm{\quad \|}\\ \mathrm{\quad N{-}O{-}H} \end{gathered} \]

\[ \begin{gathered} \mathrm{HOOC{-}C{-}C{-}C}\\ \mathrm{\qquad \| \qquad \|}\\ \mathrm{\qquad HN \qquad O}\\ \mathrm{\qquad N{-}O{-}H} \end{gathered} \]

\[ \mathrm{HOOC{-}CH_2{-}C{-}COOH} \]

\[ \begin{gathered} \mathrm{HOOC{-}CH_2{-}C{-}COOH}\\ \mathrm{\qquad \|}\\ \mathrm{\qquad NOH} \end{gathered} \]

Fig. 45

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes}\\ \mathrm{{-}N\cdots N,\quad N{=}N{-}C} \end{gathered} \]

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes}\\ \mathrm{{-}N{=}N{-}C,\quad H\cdots N{=}C} \end{gathered} \]

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes}\\ \mathrm{{-}N\cdots R,\quad N{-}O} \end{gathered} \]

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes}\\ \mathrm{{-}N{=}N,\quad H\cdots O{-}R} \end{gathered} \]

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes}\\ \mathrm{{-}N\cdots K,\quad N{-}SO_2} \end{gathered} \]

\[ \begin{gathered} \text{cyclohexane-substituted structural schemes}\\ \mathrm{{-}N{=}N,\quad H\cdots O{-}S(=O){-}OK} \end{gathered} \]

Fig. 46

B. 47, 63. ↩↩↩↩↩↩
B 1903, 1094. ↩↩
C. 1871, 284. ↩

Submission history

[v1] 1928

Theory of the Mesostructure of Organic Compounds

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Theory of the Mesostructure of Organic Compounds

PREFACE

CONTENTS

INTRODUCTION.

Categories of Carbon Bonds and the Basic Idea.

PART I.

Theory of Aromatic Compounds.

Chapter I.

MESOSTRUCTURE OF BENZENE AND ITS DERIVATIVES.

Chapter II.

THE THEORY OF DIRECTING.

Chapter III.

STERIC HINDRANCE.

PART II.

Theory of Isomerism.

Chapter I.

CRYPTOCHEMICAL POLYMORPHISM.

Chapter II.

GEOMETRICAL ISOMERISM.

A. Isomerism of ethylene derivatives.

B. Nitrogenous compounds.

SUMMARY

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Theory of the Mesostructure of Organic Compounds