Influence of Complex Formation on the Direction and Rate of Reactions in Organic Chemistry

B. V. Tronov

One of the fundamental propositions of the theory of chemical structure developed by the great Russian organic chemist A. M. Butlerov is the proposition concerning the mutual influence of atoms in molecules. The properties of each atom in a molecule depend on the nature of that atom, on the nature, number, and type of bonds of the atoms directly connected with it, and also on the composition and structure of the entire molecule as a whole. All atoms in a molecule influence one another.

A. M. Butlerov himself, his pupil V. V. Markovnikov, and many other chemists established a number of specific rules indicating precisely how certain atoms influence one another in various organic compounds. Butlerov and Markovnikov found, for example, that in the halogenation of saturated hydrocarbons the hydrogens in those units where there are the fewest hydrogen atoms are most readily substituted:

\[ (\mathrm{CH}_3)_3\mathrm{CH}+\mathrm{Cl}_2 \longrightarrow (\mathrm{C}_3\mathrm{H}_7)_3\mathrm{CCl}+\mathrm{HCl} \tag{1} \]

According to the well-known Markovnikov rule, when acids act on unsaturated hydrocarbons, the hydrogen of the acid adds to the more hydrogenated carbon atom, while the halogen or other acid residue adds to the less hydrogenated one:

\[ \mathrm{CH}_3-\mathrm{CH}=\mathrm{CH}_2+\mathrm{HBr}\longrightarrow \mathrm{CH}_3-\mathrm{CHBr}-\mathrm{CH}_3 \]

In the chemistry of aromatic compounds, substitution rules are of great importance; these describe the influence of substituents attached to the carbon atoms of the benzene ring on the direction of subsequent substitution reactions, and so forth. All these rules were formerly purely empirical; now they find explanation from the standpoint of electronic and wave-mechanical conceptions of the structure of atoms and molecules. The new theories also make it possible to broaden the previously known rules and to make new predictions about the course of reactions.

In general, great success has already been achieved in giving concrete form to the proposition concerning the mutual influence of atoms. However, in organic chemistry these successes relate almost exclusively to valent compounds. Complex organic compounds, in this respect, have as yet been very little investigated. In inorganic chemistry we know many examples showing how strongly the properties of some atom in a molecule sometimes change under the influence of complex attachment to other atoms of the same molecule. In weak acids, the anion of which is complexly attached to salts of heavy metals, there is a sharp increase in acidity. For example, the very weak acid HCN with iron cyanides gives the considerably stronger acids \(\mathrm{H}_4[\mathrm{Fe}(\mathrm{CN})_6]\) and \(\mathrm{H}_3[\mathrm{Fe}(\mathrm{CN})_6]\). The weak base \(\mathrm{Cu(OH)}_2\), with ammonia, is converted into the stronger base \([\mathrm{Cu}(\mathrm{NH}_3)_4](\mathrm{OH})_2\). Chloroplatinic—

tin and gold chlorides, by adding water, impart to it a rather strong acidity:

\[ \mathrm{PtCl_4 + 2HOH \longrightarrow H_2[PtCl_4(OH)_2],} \]

\[ \mathrm{AuCl_3 + HOH \longrightarrow H[AuCl_3(OH)].} \]

In complexes of platinum chloride with ammonia, where the \(\mathrm{NH_3}\) molecules are attracted to platinum through their nitrogen, the reactivity of the hydrogen atoms of ammonia increases. The ammoniates \([\mathrm{Pt(NH_3)_6}]\mathrm{Cl_4}\), \([\mathrm{Pt(NH_3)_5Cl}]\mathrm{Cl_3}\), and others are no longer bases but acids, close in strength to boric acid \([2, 322]\).

The mutual influence of addends transmitted through the central atom—the complex-forming agent—has been studied in detail. I. I. Chernyaev \([24]\) discovered the law of trans influence, which expresses the dependence of the mutual influence of addends on their spatial arrangement. It turned out that addends located in the trans position influence one another, increasing or decreasing reactivity; moreover, in terms of the strength of this influence, atoms (ions) and groups of atoms can be arranged approximately in the following series \([2, 295]\):

\[ \overline{\mathrm{NO_2}} > \mathrm{SC\overline{N}} > \overline{\mathrm{Br}} > \overline{\mathrm{Cl}} > \frac{1}{2}(\mathrm{H_2N{-}CH_2{-}CH_2{-}NH_2}) > \mathrm{NH_3} > \mathrm{H_2O}. \]

Theoretical explanations of the trans influence, based on electronic theory, have been proposed. The rule of trans influence has made it possible to explain and predict an enormous number of facts and is an extremely important regularity, which gives us the possibility of controlling, to a considerable extent, the course of reactions of complex compounds. Thanks to this regularity, many such compounds have been synthesized that previously could not be obtained in any way.

However, what has been said applies to inorganic chemistry. In organic chemistry we do not know such general regularities (the rule of trans influence is not applicable to purely organic complexes, i.e., those formed by the complex combination only of organogenic elements—carbon, hydrogen, oxygen, and nitrogen; these complexes have a tetrahedral structure, i.e., they have no cis and trans positions). Here we have, for the time being, only fragmentary information on the question of the mutual influence of atoms in complex compounds. It is known that esters of boric acid, on combining with alcohols, give complexes with very appreciable acidic properties:

\[ \mathrm{B(OCH_3)_3 + CH_3OH \longrightarrow [B(OCH_3)_4]H.} \]

Weaker acids are formed when alcohols combine with aluminum alcoholates:

\[ \mathrm{Al(OCH_3)_3 + CH_3OH \longrightarrow [Al(OCH_3)_4]H.} \]

The examples given indicate the influence of complex formation on the acidity of a certain group of organic compounds. As for other properties of organic substances, here too we know a number of cases of the influence of complexly attached molecules or ions on the reactivity of one compound or another. This influence undoubtedly explains the action of catalysts in many processes.

It is well known, for example, that many-element halides have a catalytic action in the halogenation of organic compounds, especially aromatic ones:

\[ \mathrm{C_6H_6 + Br_2\ (+FeBr_3) \longrightarrow C_6H_5Br + HBr.} \]

Most likely, what occurs here is complex addition of the catalyst to one of the carbons of the benzene ring. As a result, the bond of the carbon with hydrogen is loosened and the hydrogen is more readily replaced. It is also quite possible that the catalyst forms a complex with the halogen, which increases the activity of the latter:

\[ \mathrm{FeBr_3 + Br_2 \longrightarrow Br^{+}[FeBr_4]^{-}.} \]

In the bromination of benzene in the presence of pyridine, it is undoubtedly precisely the latter factor that operates—the formation of a complex of bromine with pyridine:

\[ \mathrm{C_5H_5N + Br_2 \longrightarrow [C_5H_5NBr]^{+}Br^{-}.} \]

Pyridine should not cause activation of benzene.

Analogously to halogenation in the presence of \(\mathrm{FeBr_3}\) and similar catalysts, some of the reactions grouped under the name of the Gustavson—Friedel—Crafts synthesis also proceed, namely the alkylation of aromatic compounds. Here, too, complex formation must most probably occur both with the benzene ring of the aromatic compound and with the other reagent. Then two complexes react with one another:

\[ \begin{array}{c} \mathrm{H_5C_6\cdots AlCl_3 + [CH_3]^{+}[AlCl_4]^{-} \longrightarrow H_5C_6 + H^{+}[AlCl_4]^{-} + AlCl_3.}\\ \quad | \qquad\qquad\qquad\qquad\quad |\\[-2mm] \mathrm{H}\qquad\qquad\qquad\qquad\quad \mathrm{CH_3} \end{array} \]

Serious new evidence for the long-expressed assumption of the intermediate formation of complexes of the type \(\mathrm{R^{+}[AlCl_4]^{-}}\) has been provided by experiments with labeled atoms [8, 3]. Aluminum chloride containing radioactive chlorine was mixed with ordinary \(\mathrm{AlCl_3}\) and brought into contact with benzene and tert-butyl chloride. Complete exchange of chlorine atoms occurred.

Acylation of benzene by acid chlorides, anhydrides, and certain esters has a different mechanism, but here as well complex formation plays the decisive role. For example, in the reaction of benzene with benzoyl chloride and \(\mathrm{AlCl_3}\), a complex of the acid chloride and aluminum chloride takes part. This complex adds, also at first in complex form, to the carbon of the benzene ring; then \(\mathrm{HCl}\) is eliminated and a complex of the ketone with \(\mathrm{AlCl_3}\) remains:

\[ \begin{array}{ccccccc} & \mathrm{C_6H_5} &&&& \mathrm{C_6H_5}\\ & | &&&& |\\ \mathrm{H_5C_6\cdots C} & {-} & \mathrm{O^{-}\cdots AlCl_3} & \longrightarrow & \mathrm{H_5C_6} & {-} & \mathrm{C^{+}{-}O^{-}\cdots AlCl_3 + HCl.}\\ | & | &&&&&\\ \mathrm{H} & \mathrm{Cl} &&&&& \end{array} \]

Strictly speaking, this reaction cannot be regarded as catalytic, since aluminum chloride must be taken in a stoichiometric ratio to the acid chloride. However, in its mechanism it is analogous to alkylation by unsaturated hydrocarbons:

\[ \begin{array}{ccc} \mathrm{H_2C} & \mathrm{H_2C^{+}} & \mathrm{H_2C^{+}}\\ \Vert & | & |\\ \mathrm{H_2C} & \mathrm{H_2C} & \mathrm{H_2C\cdots AlCl_3}\\ & \xrightarrow{\ } \quad +\ \mathrm{AlCl_3}\ \xrightarrow{\ } & \end{array} \]

Further, with benzene:

\[ \begin{array}{c} \mathrm{H_5C_6\cdots CH_2^{+}{-}CH_2^{-}} \\ | \qquad\qquad | \\[-1mm] \mathrm{H}\qquad\quad \mathrm{AlCl_3} \end{array} \ \longrightarrow\ \mathrm{H_5C_6{-}CH_2{-}CH_3 + AlCl_3} \]

The difference is that alkylbenzenes do not form stable complexes with \( \mathrm{AlCl_3} \) and reagents similar to it.

V. V. Korshak and N. I. Lebedev [3], in explaining the catalytic action of aluminum chloride, attach great importance to the fact that the molecules of this catalyst are dimeric. These authors believe that \( \mathrm{Al_2Cl_6} \) acts as a dipole, loosening, in the case of the alkylation of benzene by alkyl halides, on the one hand the halogen–carbon bond in the molecule \( \mathrm{RX} \), and on the other hand the hydrogen–carbon bond in benzene:

\[ \begin{array}{ccccc} \mathrm{Cl_2Al}^{+} & \overset{\ominus}{\mathrm{Cl}}{-}\mathrm{R}^{\oplus} & \mathrm{Cl_2Al}^{+} & \overset{\ominus}{\mathrm{Cl}}\cdots \mathrm{R}^{+} & \\[-2pt] \mathrm{Cl_4Al}^{-} & \mathrm{H}^{\oplus}{-}\mathrm{Ar}^{\ominus} & \longrightarrow & \mathrm{Cl_4Al}^{-} & \mathrm{H}^{\oplus}\cdots \mathrm{Ar}^{\ominus} \end{array} \longrightarrow \mathrm{Al_2Cl_6} + \mathrm{ArH} + \mathrm{HCl} \]

In alkylation by olefins, the double bond in the molecules of the latter is polarized in the same way.

It should be noted, however, that by no means all catalysts used in the reactions under consideration are dimeric. For example, antimony pentachloride, with monomeric molecules, also exerts a strong catalytic action. An interesting fact was observed in a kinetic study of the reaction of toluene with acetyl chloride in the presence of halides of many elements [26]. With antimony pentachloride the reaction began at once, whereas in the presence of aluminum chloride the process at first proceeded very slowly, and then the reaction rate increased sharply. At the same time, in the presence of already prepared \( \mathrm{HCl} \), the reaction proceeds at a high rate.

Is this not explained by the fact that the \( \mathrm{Al_2Cl_6} \) molecule itself is only slightly active, while with the hydrogen chloride that is evolved decomposition occurs with the formation of \( \mathrm{AlCl_3} \) and \( \mathrm{H[AlCl_4]} \), or \( 2\mathrm{H[AlCl_4]} \), which in fact are strong catalysts?

The esterification of alcohols by weak acids in the presence of strong acids, and the reverse reaction, the hydrolysis of esters, are based on the intermediate formation of complex compounds with the catalyst, namely with the H-ion:

\[ \begin{aligned} &\begin{array}{c} \mathrm{CH_3}\\[-2pt] |\\[-2pt] {}^{+}\mathrm{C}{-}\mathrm{O}{-}\mathrm{H}\cdots\mathrm{O}{-}\mathrm{CH_3}\\[-2pt] | \qquad\quad |\\[-2pt] \mathrm{OH}\qquad \mathrm{H}^{+} \end{array} \;\rightleftarrows\; \begin{array}{c} \mathrm{CH_3}\\[-2pt] |\\[-2pt] \mathrm{HO}{-}\mathrm{C}{-}\mathrm{O}{-}\mathrm{CH_3}\\[-2pt] | \qquad |\\[-2pt] \mathrm{OH}\ \mathrm{H}^{+} \end{array} \;\rightleftarrows\; \begin{array}{c} \mathrm{CH_3}\\[-2pt] |\\[-2pt] {}^{+}\mathrm{C}{-}\mathrm{O}{-}\mathrm{CH_3} + \mathrm{H_2O}\\[-2pt] | \qquad |\\[-2pt] \mathrm{O}^{-}\ \mathrm{H}^{+} \end{array} \;\rightleftarrows\; \begin{array}{c} \mathrm{CH_3}\\[-2pt] |\\[-2pt] {}^{+}\mathrm{C}{-}\mathrm{O}{-}\mathrm{CH_3}\\[-2pt] |\\[-2pt] \mathrm{O}^{-} \end{array} + \mathrm{H_2O}\cdots\mathrm{H}^{+}. \end{aligned} \]

Under the influence of acids as catalysts, the reactions of hydrolysis of simple ethers, formation and hydrolysis of acetals and ketals, etc., proceed.

Numerous polymerization and condensation reactions are catalytic; moreover, very often one must regard the formation of intermediate complex compounds as unquestionable. For example, in the processes of polymerization and condensation of aldehydes and ketones, catalysts are ions prone to complex formation, \( \overset{+}{\mathrm{H}} \), \( \mathrm{OH}^{-} \), molecules of \( \mathrm{ZnCl_2} \) and similar reagents, the ion \( \mathrm{CN}^{-} \) in benzoin condensation, etc. In this connection, complex-forming catalysts of different types—for example, the ions \( \overset{+}{\mathrm{H}} \) and \( \mathrm{OH}^{-} \)—must add to different atoms of the reacting molecules, and this very often leads to the formation of different products. Thus, acetaldehyde polymerizes with acids or peroxides to paraldehyde, gives aldol with alkalis, and with aluminum alcoholates there occurs mutual

oxidation–reduction of two aldehyde groups with formation of a complex ester:

\[ \mathrm{CH_3{-}C(=O){-}H + O{=}C(H){-}CH_3 \rightarrow CH_3{-}C(=O){-}O{-}CH_2{-}CH_3.} \]

A characteristic example of the influence of complex formation on the direction of a reaction is provided by the condensation processes of aldehydes and ketones with hydroxylamine, phenylhydrazine, etc. If acetaldehyde and \(\mathrm{NH_2OH}\) are taken, then, as it would seem one should expect, when the double bond in the carbonyl group of the aldehyde is cleaved, the most mobile hydrogen of the hydroxylamine molecule should add to the oxygen; and this should be the hydroxyl hydrogen:

\[ \mathrm{CH_3{-}C(=O){-}H + HONH_2 \rightarrow CH_3{-}C(H)(OH)(ONH_2).} \]

In reality, hydrogen atoms depart—first one, then another—from nitrogen. An oxime is obtained:

\[ \mathrm{CH_3{-}C(=O){-}H + H_2NOH \rightarrow CH_3{-}C(H){=}NOH + H_2O.} \]

This can be explained only by complex formation. The double bond of the carbonyl group has a polar character. The positively charged carbon atom attracts the unshared electron pair of the nitrogen of the \(\mathrm{NH_2OH}\) molecule. The complex bond that arises then passes into a valence bond, and one of the hydrogen atoms bonded to nitrogen jumps to the carbonyl oxygen. Water is then eliminated at the expense of the hydroxyl formed at carbon and the second hydrogen bonded to nitrogen:

\[ \mathrm{ CH_3{-}\overset{+}{C}(H){-}\overset{-}{O} + NH_2OH \rightarrow CH_3{-}C(H)(O)(NH_2OH) \rightarrow CH_3{-}C(H)(OH)(NHOH) \rightarrow CH_3{-}C(H){=}NOH + H_2O. } \]

In the molecule \(\mathrm{C_6H_5NHNH_2}\) the hydrogen of the NH group should be the most reactive. However, on interaction with an aldehyde or ketone, it is not this hydrogen but the hydrogen atoms of the \(\mathrm{NH_2}\) group that depart; this process also begins with complex addition, and it is precisely the nitrogen of the amino group, having stronger basic properties, i.e. the more active electron pair, that adds complexly to the carbonyl carbon:

\[ \mathrm{ CH_3{-}\overset{+}{C}(H){-}\overset{-}{O} \rightarrow CH_3{-}C(H)(OH)(NH_2{-}NHC_6H_5) \rightarrow CH_3{-}C(H)(OH)(NH{-}NHC_6H_5) \rightarrow CH_3{-}C(H){=}N{-}NH{-}C_6H_5 + H_2O. } \]

There are very many reactions in organic chemistry that begin with the formation of unstable complex compounds. In order to understand these reactions better, in particular, in order to master more effectively

catalytic processes based on the formation of intermediate complexes, we must:

1. Determine the electronic type of reactivity of the atoms and atomic groups that make up the molecules of the organic compounds under study, and also the type of reactivity of the reagents with which we wish to act on the compounds being studied, and of the catalysts that accelerate or slow the reaction.

2. Determine how the type of reactivity of the directly reacting atoms and atomic groups is influenced by other parts of the molecules of the compounds taken.

For a preliminary judgment of the electronic type of reactivity of particular atoms or atomic groups, theoretical considerations of electronic and quantum physics are of great importance. As will be shown below, these considerations sometimes make it possible to explain features in the course of reactions that at first sight seem strange [20]. A more complete solution of the questions posed requires extensive experimental work on the physical and chemical investigation of the compounds of interest to us. A substantial part of this work should consist of studying complex-formation processes, and specifically simple complex formation, not complicated by deeper changes in the molecules. Thus, to determine the reactivity of the carbonyl group in aldehydes and ketones, one carries out, for example, a kinetic study of their reactions with hydroxylamine or phenylhydrazine. But these reactions proceed in a complex manner, with intermediate stages. In principle it would be better first to study the interaction of carbonyl compounds with tertiary amines (of course, not aromatic ones), where nothing can occur except the simple formation of complexes.

In determining the ability of a given substance to form complexes, one may take as the second component of the systems under study a great variety of compounds; however, the most reliable results should be obtained with compounds that possess reactivity of only one type [23]. Such compounds include amines with sufficiently clearly expressed basic properties; in them electron-donor activity is manifested, or in any case strongly predominates. Simple ethers also belong to the electron donors. Strong acids, on the contrary, are typical electron acceptors. Such also are many boron compounds, salts of heavy metals, and others.

Tomsk organic chemists have undertaken a systematic investigation of several classes of organic compounds with respect to their ability to form complexes with typical inorganic and organic reagents. Along with these investigations, separate processes of organic synthesis are being studied in which complex formation has been proved or should be regarded as probable. In studying these processes, allowance is made for the possibility of complex formation not only in the organic compounds themselves, but also between inorganic substances, which can have a very strong effect on the activity of a reagent toward organic compounds.

The results of some works in this series are presented below.

Nitration of Aromatic Compounds

To explain the nitration reaction of aromatic compounds, many diverse theories have been proposed. Understanding this reaction as a simple replacement of hydrogen by a nitro group:

\[ \mathrm{C_6H_5H + HONO_2 \to C_6H_5NO_2 + H_2O} \]

has long since ceased to satisfy chemists. For a long time the theory of Wieland was generally accepted, according to which nitration, like other processes

substitution, begins with the rupture of one of the double bonds in the benzene nucleus:

\[ \ce{C6H6 + HO-NO2 -> C6H6(OH)(NO2) -> C6H5NO2 + H2O.} \]

Against such an explanation speaks the fact that, in the nitration of benzene, mononitrobenzene is obtained in very good yield. Meanwhile, after the rupture of one double bond a system with two double bonds is formed, which should be very unstable toward the further action of nitric acid and other reagents. Experience shows that in those cases where rupture of the double bonds of the benzene ring actually occurs—for example, in hydrogenation, ozonization, and the action of halogens under conditions favoring addition—after the first double bond the remaining two are also very readily broken:

\[ \ce{C6H6 + 3H2 (+ Ni) -> C6H12.} \]

The theory proposed by me [9], according to which benzene adds to the double bond of nitric acid, is free of the indicated drawback:

\[ \ce{C6H5H + O=N(=O)-OH -> C6H5-N(=O)(OH)-OH -> C6H5-N(=O)=O + H2O.} \]

However, this theory also could not explain certain facts [10]. According both to Wieland’s theory and to my first theory, benzene should be nitrated not only by free nitric acid, but also by its esters:

\[ \ce{C6H5H + O=N(=O)-OCH3 -> C6H5-N(=O)(OH)-OCH3 -> C6H5-N(=O)=O + HOCH3.} \]

In fact, methyl nitrate and ethyl nitrate act not only on benzene, but also on the considerably more active xylene and even on anisole only if a catalyst is also added. In the presence of aluminum chloride nitration proceeds very readily [11, 22]. In this way the nitration reaction with complex esters becomes adjacent to the catalytic syntheses of Gustafson—Friedel—Crafts. The mechanism of the reaction must be thought to be the same as the mechanism of the synthesis of ketones from benzene with acid chlorides:

\[ \ce{ C6H6 + CH3COCl...AlCl3 -> C6H6...COCH3Cl...AlCl3 -> C6H5COCH3...AlCl3 + HCl } \]

\[ \begin{gathered} \mathrm{C_6H_6} + \mathrm{CH_3ONO}\cdots \mathrm{AlCl_3} \longrightarrow \mathrm{C_6H_6}\cdots \mathrm{CH_3ONO}\cdots \mathrm{AlCl_3} \\ \longrightarrow \mathrm{C_6H_5NO_2}\cdots \mathrm{AlCl_3} + \mathrm{HOCH_3} \end{gathered} \]

The most noticeable difference in the results of the process is that nitration with mixed esters, for example ethyl nitrate, does not require the addition of aluminum chloride in a stoichiometric ratio [22]. But this difference is not of a fundamental character; it must obviously be explained by the low stability of the nitrobenzene complex with aluminum chloride.

To test the reaction mechanism presented here, we attempted to isolate the intermediate complex compounds [20], first of all the complex of the nitrate with \(\mathrm{AlCl_3}\), and then the ternary compound with benzene. For this purpose, aluminum chloride was first dissolved in ethyl nitrate at a temperature of about \(-20^\circ\) (a mixture of snow with \(\mathrm{NaCl}\)). From the resulting colorless solution the excess nitrate was distilled off in vacuo. The remaining almost white solid substance was analyzed for aluminum and chlorine. The analysis indicated considerable decomposition with liberation of \(\mathrm{HCl}\). The liberation of nitrogen oxides was also observed. Nevertheless, some portion of the active complex remained even after several hours. Addition of benzene gave a raspberry-colored solution, which then became decolorized and, after the usual treatment, gave nitrobenzene.

An analogous experiment was carried out with stannic chloride—a catalyst of the same type as \(\mathrm{AlCl_3}\), but weaker. A solution of \(\mathrm{SnCl_4}\) in ethyl nitrate also decomposes on evaporation in vacuo, but with liberation of stannic chloride. On mixing this solution, a raspberry coloration also appeared, and then nitrobenzene was isolated from the mixture. When the third catalyst tested by us, antimony pentachloride, was added to ethyl nitrate, an explosion occurred at once. If, however, \(\mathrm{SbCl_5}\) is added to a mixture of benzene with ethyl nitrate, then, as in the preceding cases, a raspberry coloration appears, and nitrobenzene can subsequently be isolated from the mixture. When we had first diluted antimony pentachloride and ethyl nitrate with carbon tetrachloride, then on mixing these solutions, also at a temperature of about \(-20^\circ\), a dark-blue heavy oil separated, which could be freed from excess nitrate by new portions of \(\mathrm{CCl_4}\). With benzene this oil gave a red solution, and on further treatment—nitrobenzene. The yield of the latter increases if more ethyl nitrate is added. The dark oil is evidently the complex \(\mathrm{C_2H_5ONO_2}\) with \(\mathrm{SbCl_5}\). We were unable to carry out an analysis of this compound. The ternary compound with benzene could not even be isolated.

The results of all the experiments described permit one to state with confidence that, in the nitration of benzene by esters of nitric acid in the presence of the chlorides of aluminum, tin, and antimony, unstable compounds of these chlorides with the mixed esters are first formed. The complex nature of these intermediate products has not been proved directly, but is very probable. This is indicated in particular by the easy decomposition of the tin complex into its components.

The binary compounds can probably also react with benzene with formation of complexes. The process is completed by formation of the complex

nitrobenzene with a metal halide. These complexes decompose rather readily:

\[ \mathrm{C_6H_5{-}N(=O){-}O\cdots AlCl_3 \rightleftharpoons C_6H_5{-}N(=O){-}O + AlCl_3,} \]

as a result of which the yield of nitrobenzene, calculated on the amount of chloride taken, considerably exceeds 100%. With \(\mathrm{AlCl_3}\) the maximum yield obtained by us reached 129%; with \(\mathrm{SbCl_5}\) the yield was up to 205%; with \(\mathrm{FeCl_3}\), 197%.

The nitration of benzene with nitric acid itself proceeds without the addition of any catalysts, i.e., not under the same conditions as do other substitution reactions. This suggests the thought that here the catalyst may be \(\mathrm{HNO_3}\) itself. Such an assumption is confirmed by the following facts:

a) a kinetic study of the nitration reaction of benzene showed [28] that this reaction is bimolecular with respect to nitric acid;

b) according to the results of experiments carried out in our laboratory by A. M. Petrova and then by A. N. Krivosheya, when \(\mathrm{HNO_3}\) is diluted with benzene the rate of consumption of the acid decreases. Carrying out experiments under identical conditions of temperature and time (addition of \(\mathrm{HNO_3}\) to benzene over two hours with cooling by snow, then heating for half an hour to \(70^\circ\)), A. M. Petrova obtained a yield of nitrobenzene, at the molecular ratio \(\mathrm{C_6H_6:HNO_3}=0.5\), of 81.6%, the maximum possible; at the ratio \(1:1\), 46.8%; \(2:1\), 36.4%; \(4:1\), 25.3%; \(8:1\), 9.0%.

This fact, strange at first glance, can be explained by assuming that the actual nitrating reagent is not a molecule, but some product of interaction of two (or a larger number of) molecules, for example, the dimer \((\mathrm{HNO_3})_2\), the reaction of formation of the dimer being reversible:

\[ 2\mathrm{HNO_3}\rightleftharpoons(\mathrm{HNO_3})_2. \]

Naturally, dilution of the acid with some solvent, including benzene, must shift the equilibrium toward decomposition into individual molecules.

It was found, moreover, that with a large excess of benzene the direction of the reaction also changes. A considerable amount of oxalic acid is formed, i.e., the monomer \(\mathrm{HNO_3}\) acts as an oxidizing agent and not as a nitrating agent. Even with toluene, when a large excess of the latter was taken, the appearance of oxalic acid was observed, together with nitrotoluene, benzoic acid, and para-nitrobenzoic acid.

Having accepted that nitric acid, specifically its second molecule, is itself the catalyst of nitration, I arrived at the following explanation of the course of this reaction [16]:

\[ \begin{aligned} &\mathrm{C_6H_5{-}C(H)} +\mathrm{O{=}N(OH){-}O\cdots HONO_2} \longrightarrow \mathrm{C_6H_5{-}C(HO){-}N(OH){=}O\cdots HONO_2} \rightleftharpoons \\ &\mathrm{C_6H_5{-}C{-}N(OH)_2{-}O\cdots HONO_2} \longrightarrow \mathrm{C_6H_5{-}C{-}N(=O){-}O\cdots HONO_2 + H_2O} \rightleftharpoons \\ &\rightleftharpoons \mathrm{C_6H_5{-}C{-}N(=O)(=O) + HNO_3\cdot H_2O.} \end{aligned} \]

Two molecules of \(\mathrm{HNO_3}\) form a complex dimer with a hydrogen bond, which also adds, as a complex, to one of the carbon atoms of the benzene ring. The complex bond of carbon with nitrogen then changes into a valence bond, and the hydrogen is displaced to one of the oxygen atoms of nitric acid. Subsequently a molecule of water is eliminated from the two hydroxyls. The final product is a complex of nitrobenzene with \(\mathrm{HNO_3}\), reversibly decomposed by water. Kinetic analysis of the nitrobenzene–nitric acid system [12] has proved the existence even of two complex compounds:

\[ \mathrm{C_6H_5NO_2 \cdot HNO_3} \quad \text{and} \quad \mathrm{C_6H_5NO_2 \cdot 2HNO_3}. \]

Esters of nitric acid, which have no active hydrogen, cannot form nitrating dimers and therefore do not act on benzene. With a catalyst of the aluminum chloride type, complexes are formed

\[ \begin{gathered} \mathrm{RO - N = O \ldots AlCl_3,}\\ \|\\ \mathrm{O} \end{gathered} \]

which react with benzene analogously to the dimer

\[ \begin{gathered} \mathrm{HO - N = O \ldots HONO_2.}\\ \|\\ \mathrm{O} \end{gathered} \]

In subsequent works by other authors, the electrolytic dissociation of the nitric acid dimer is taken into account, with formation of the nitracidium cation

\[ \mathrm{H_2NO_3^+} \]

and, finally, the appearance of the nitronium cation \(\mathrm{NO_2^+}\), which is quite capable of being formed as a result of dehydration of nitracidium:

\[ \begin{gathered} \mathrm{O = N = O \ldots HONO_2} \rightleftarrows \left[ \begin{array}{c} \mathrm{O - N - OH}\\ \vert\\ \mathrm{OH} \end{array} \right]^+ + \mathrm{NO_3^-} \rightleftarrows \left[ \mathrm{O = N = O} \right]^+ + \mathrm{H_2O} + \mathrm{NO_3^-}. \\[-0.5em] \vert\\ \mathrm{OH} \end{gathered} \]

The nitronium cation in the modern literature [5] is considered the principal nitrating reagent when benzene is acted upon by concentrated \(\mathrm{HNO_3}\) or by a sulfuric–nitric nitrating mixture, where the same processes of complex formation, electrolytic dissociation, and dehydration must occur:

\[ \begin{gathered} \mathrm{O = N = O} + \mathrm{HOSO_2OH} \rightleftarrows \mathrm{O = N = O \ldots HOSO_2OH} \rightleftarrows \\ \vert \qquad\qquad\qquad\qquad \vert\\ \mathrm{OH}\qquad\qquad\qquad\quad \mathrm{OH} \end{gathered} \]

\[ \rightleftarrows \left[ \begin{array}{c} \mathrm{O = N - OH}\\ \vert\\ \mathrm{OH} \end{array} \right]^+ + \left[ \mathrm{OSO_2OH} \right]^- \rightleftarrows \left[ \mathrm{O = N = O} \right]^+ + \mathrm{H_2O} + \left[ \mathrm{OSO_2OH} \right]^- . \]

or, perhaps, from two molecules of \(\mathrm{HNO_3}\) and one molecule of \(\mathrm{H_2SO_4}\), ions are formed

\[ \mathrm{NO_2^+} \quad \text{and} \quad \mathrm{SO_4^{=}}. \]

The cation \(\mathrm{NO_2^+}\) again adds complexly to benzene. Then the complex bond changes into a valence bond (the unshared pair of electrons of the carbon atom of the polar form of benzene begins to move—

are concentrated around both atomic nuclei—carbon and nitrogen), while hydrogen passes to the oxygen atom:

\[ \left[ \mathrm{C_6H_6\cdots NO_2} \right]^+ \;\longrightarrow\; \left[ \mathrm{C_6H_5{-}N(=O){-}O\cdots H} \right]^+ \;\rightleftarrows\; \mathrm{C_6H_5{-}N(=O){-}OH}^+ \]

The complex of nitrobenzene with a proton is the cation of the ionized complex \(\mathrm{C_6H_5NO_2\cdot HNO_3}\).

Without objecting to the nitronium scheme of the reaction, I nevertheless consider it not settled whether benzene cannot also be nitrated by nitracids, and perhaps directly by the complex \((\mathrm{HNO_3})_2\). This dimer, in its structure, is analogous to the complexes of nitric-acid esters with aluminum chloride; and such complexes, apparently, act on benzene directly, without the formation of nitronium. This is indicated by the color of the intermediate compound that arises when benzene is added—crimson, and not reddish-brown, as occurs when benzene is mixed with concentrated nitric acid.

Syntheses of Gustavson—Friedel—Crafts

The synthetic methods united under the name of the Friedel—Crafts reaction, or more correctly the Gustavson—Friedel—Crafts reaction, are based on the action of a definite group of catalysts, of which the most common is aluminum chloride. The principal directions of these syntheses are alkylation and acylation. Alkylation of aromatic compounds is carried out with the aid of organohalogen compounds, unsaturated hydrocarbons, simple ethers, and certain esters:

\[ \mathrm{C_6H_6 + ClCH_3\,(+AlCl_3)\rightarrow C_6H_5CH_3 + HCl,} \]

\[ \mathrm{C_6H_6 + C_2H_4\,(+AlCl_3)\rightarrow C_6H_5CH_2CH_3,} \]

\[ \mathrm{C_6H_6 + C_2H_5OC_2H_5\,(+AlCl_3)\rightarrow C_6H_5{-}CH_2{-}CH_3 + HOC_2H_5,} \]

\[ \mathrm{2\,C_6H_6 + (CH_3O)_2SO_2\,(+AlCl_3)\rightarrow 2\,C_6H_5CH_3 + H_2SO_4.} \]

Acylation proceeds with acid halides, anhydrides, free acids (with difficulty), and certain esters:

\[ \mathrm{C_6H_6 + C_6H_5COCl\,(+AlCl_3)\rightarrow C_6H_5COC_6H_5 + HCl} \]

\[ \mathrm{2\,C_6H_6 + SOCl_2\,(+AlCl_3)\rightarrow C_6H_5SO.C_6H_5 + 2\,HCl,} \]

\[ \mathrm{C_6H_6 + O\!\left<\begin{matrix}CO\\[-2pt]CO\end{matrix}\right>\!C_6H_4\,(+AlCl_3) \rightarrow C_6H_4\!\left<\begin{matrix}CO\\[-2pt]CO\end{matrix}\right>\!C_6H_4 + H_2O} \]

\[ \mathrm{C_6H_6 + CH_3COOH\,(+AlCl_3)\rightarrow C_6H_5COCH_3 + H_2O.} \]

To this same category should be assigned the nitration of benzene by esters of nitric acid in the presence of the same catalysts.

To explain the reactions occurring in these syntheses, many theories have been proposed, not one of which has received general recognition. The reason for this should be regarded chiefly as the diversity of the processes united under the common name. Common to all these processes is the use of such catalysts, which are known as very active complex-

complex-formers of the electron-acceptor type. These include \(AlCl_3\), \(FeCl_3\), \(SnCl_4\), \(SbCl_5\), \(BF_3\), \(HF\), \(H_2SO_4\) [13], etc.

All the reactions under consideration undoubtedly begin with the complex addition of the catalyst either to benzene (in general, to the aromatic compound; some compounds of other classes are also capable of analogous reactions, but syntheses with them proceed worse) or to the reagent acting on benzene. The complex of this reagent with the catalyst is sometimes added to benzene, and sometimes enters into another interaction with benzene; moreover, the molecule \(C_6H_6\), in its turn, must apparently be activated by a second molecule of catalyst.

The assumption of double activation in many alkylation processes is confirmed by the following facts:

1. In the alkylation of benzene by certain reagents it is necessary to take an amount of aluminum chloride greater than one molecule per molecule of alkylating reagent. Otherwise the reaction proceeds not with a lower yield, as might have been expected, but does not proceed at all. There are indications of this in the literature [7, 680]. The experiments we carried out, for example with ethyl ether and with ethyl acetate [27], led to the same result. When we took, per 1 mole of a simple or complex ether, \(1/2\) mole of aluminum chloride, ethylbenzene could not be obtained at all.

2. When alkyl halides act on benzene in the presence of \(SnCl_4\), \(AlCl_3\), and many other metal halides, the latter may be added in very small amounts, apparently because the organic halides here give very weak complex compounds. Weak complexes are also formed with benzene and its homologues, as well as with the hydrogen halides liberated in the reaction. Therefore activation of benzene and of the halogen derivative proceeds without hindrance.

Interesting results, of great importance for elucidating the mechanism of the reactions occurring in these syntheses, were obtained by the use of antimony pentachloride. \(SbCl_5\) differs from all catalysts used in the Friedel—Crafts reaction in that it readily gives up two chlorine atoms. Antimony pentachloride by itself acts vigorously on benzene, giving chlorobenzene and antimony trichloride:

\[ C_6H_6 + SbCl_5 \rightarrow C_6H_5Cl + HCl + SbCl_3. \]

When we added \(SbCl_5\) to a mixture of benzene with ethyl nitrate or with benzoyl chloride, containing 2 moles of benzene per 1 mole of the other reagent, chlorination of benzene was not observed, i.e., antimony pentachloride immediately entered into interaction with the nitrate or acid chloride. The complexes formed reacted further with benzene, which therefore required no additional activation.

When \(SbCl_5\) was added to a mixture of benzene with butyl chloride, bromide, or iodide, there was likewise no chlorination of benzene at all, but there was also no alkylation. Thus, the \(SbCl_5\) molecule at once gives a complex with \(C_4H_9Cl\), etc.; but this complex, on the one hand, cannot itself react with unactivated benzene, and on the other hand is more stable than the complex of butyl chloride with aluminum chloride and does not liberate a noticeable amount of \(SbCl_5\). However, if the complex were of low stability, one would have expected not alkylation but chlorination, since antimony pentachloride reacts vigorously with benzene.

Experiments carried out with molecular ratios of \(SbCl_5\) and \(C_4H_9Cl\) equal to 0.95 : 1 and 1.3 : 1 showed that in the first case there was almost no chlorination, while in the second it occurred to a fairly considerable extent (31% based on the excess amount of \(SbCl_5\), in comparison with the complex \(C_4H_9Cl \cdot SbCl_5\)). Alkylation was not observed.

In experiments with benzyl chloride, even at a molecular ratio
\(C_6H_6 : C_6H_5CH_2Cl : SbCl_5 = 1 : 0.125 : 0.025\), i.e., with a large excess of the organic halide, diphenylmethane was obtained in a yield of up to 47.5% [14]; considerable amounts of higher condensation products, mainly dibenzylbenzenes, were also formed. This fact cannot be explained by the low stability of the \(C_7H_7Cl\) complex with \(SbCl_5\), since in that case chlorination of benzene would have occurred. It remains to assume that the benzyl radical-cation arising upon electrolytic dissociation of the \(C_7H_7Cl \cdot SbCl_5\) complex is itself sufficiently active to be attracted to a benzene molecule and expel a proton:

\[ \mathrm{C_6H_6} + \mathrm{CH_2C_6H_5^{+}} \longrightarrow \left[\mathrm{C_6H_6{-}CH_2C_6H_5}\right]^{+} \longrightarrow \mathrm{C_6H_5CH_2C_6H_5} + \mathrm{H^{+}} . \]

Comparison of the action of \(AlCl_3\), \(SbCl_5\), and \(FeCl_3\) on the reaction of benzene with such a typical acylating reagent as \(C_6H_5COCl\) led to new results. Experiments carried out by A. M. Petrova with various amounts of catalysts showed that, with aluminum chloride, the yield of benzophenone indeed does not exceed one gram-molecule per gram-molecule of \(AlCl_3\) consumed; but in the presence of antimony pentachloride and ferric chloride the yield, calculated per catalyst, may be much greater, reaching approximately 300%.

Table 1

With antimony pentachloride and ferric chloride the reaction is therefore truly catalytic. There is no reason to assume any difference in the mechanism of the synthesis, especially if one compares aluminum and iron chlorides, both of which are bimolecular. The difference in the results may be explained by the different stability of the ketone complexes with the catalysts.

We paid special attention to the reaction of benzene with esters. These compounds can either alkylate or acylate aromatic compounds, and the direction of the reaction is determined chiefly by the composition and structure of the ester. To elucidate the causes promoting the occurrence of one or the other reaction, experiments were carried out with a large number of esters of mineral and organic acids [7]. In contrast to the experiments of many other investigators, in our work the catalysts were taken in amounts not exceeding one molecule per ester group. The temperature conditions were also fairly mild—6 hours of heating on a water bath. We did not seek to obtain the greatest possible yield of product, but set ourselves the goal of clarifying more precisely the mechanism of the processes, in particular of testing the supposition of double activation in alkylating reagents.

The results of experiments with ethyl nitrate and diethyl sulfate confirmed what had been found in earlier work from our laboratory [11, 12]. With ethyl nitrate only nitration occurred, i.e., acylation. The formation of ethylbenzene could not be detected at all. Of the metal chlorides taken, the best catalysts here proved to be AlCl₃ and SbCl₅, and they can be used in considerably smaller amounts than molecule for molecule. The yield of nitrobenzene reached 81% with AlCl₃ and 83.6% with SbCl₅, calculated on nitrate. SnCl₄ is a less active catalyst, and ZnCl₂ did not act at all. With diethyl sulfate, only alkylation took place, and only under the influence of aluminum chloride. FeCl₃, ZnCl₂, SnCl₄, SbCl₅, and BiCl₃ proved to be completely inactive.

How is one to explain the difference in the direction of the reactions with nitrates and sulfates? HNO₃ and H₂SO₄ are acids of almost identical strength, and one might have expected their esters to react in the same direction. However, according to the laws of quantum physics, the electronic structure of the molecules \((\mathrm{C_2H_5O})\mathrm{C_2H_5ONO_2}\) and \({}_2\mathrm{SO_2}\) must be different. Nitrogen cannot be pentavalent. In complex esters of nitric acid, as in nitro compounds, it must be tetracoordinate positive, i.e., one of the double bonds of nitrogen with oxygen must be semipolar:

\[ \mathrm{C_2H_5O{-}\overset{+}{N}(=O){-}\overset{-}{O}} \qquad \mathrm{C_6H_5{-}\overset{+}{N}(=O){-}\overset{-}{O}} \]

Sulfur is in the next row of the periodic system. It can quite well be hexavalent, as is indicated by facts such as the existence of sulfur hexafluoride, SF₆, which has the properties of a typical covalent compound. Consequently, in molecules of sulfuric acid esters, as well as in sulfones, the double bonds of sulfur with oxygen may quite well be covalent:

\[ \mathrm{C_2H_5O{-}S(=O)_2{-}OC_2H_5} \qquad \mathrm{C_6H_5{-}S(=O)_2{-}C_6H_5} \]

The covalent structure of sulfones is indicated by their physical properties [6] and by their low ability to form complexes, whereas nitro compounds are among the best complex formers in organic chemistry [23].

The difference in the electronic structure of alkyl nitrates and dialkyl sulfates suggests that with catalysts, for example with AlCl₃, they must react differently. In ethyl nitrate the strongest electron donor must be the oxygen atom semipolarly bonded to nitrogen. In diethyl sulfate there is no such oxygen, and formation of a complex with ether oxygen is entirely possible. The first complex is added to the carbon of benzene by the nitrogen atom, whose positive charge is intensified by addition of the catalyst. The nitration reaction will then proceed:

\[ \mathrm{ C_6H_6 + C_2H_5O{-}\overset{+}{N}(=O){-}\overset{-}{O}\cdots AlCl_3 \longrightarrow C_6H_5{-}\overset{+}{N}(=O){-}\overset{-}{O}\cdots AlCl_3 + C_2H_5OH } \]

In the sulfate complex, the bond of carbon with oxygen is simply cleaved, which will then lead to alkylation of benzene, whose molecule must also be activated by the catalyst:

\[ \ce{ [C6H6\cdots C(H)\cdots AlCl3] + C2H5O-S(=O)2-OC2H5\cdots AlCl3 -> [C6H6\cdots C(C2H5)\cdots AlCl3] + C2H5O-S(=O)2-OH\cdots AlCl3 } \]

and so on.

The complex of diethyl sulfate with aluminum chloride is apparently only slightly stable. This is evident from the fact that even with 0.5 mole of \(\ce{AlCl3}\) per mole of ester, alkylation of benzene took place, although with a small yield: \(17\%\) of ethylbenzene and \(10.9\%\) of diethylbenzenes.

The considerations advanced are confirmed by the results of experiments with esters of other mineral acids. \(\ce{Si(OC2H5)4}\), in which the silicon atom should not exhibit great activity in complex-formation reactions, gave with benzene and \(\ce{AlCl3}\) only ethylbenzene. \(\ce{PO(OC2H5)3}\), which probably also has a covalent double bond of P with O, likewise proved to be a reagent alkylating benzene. However, experiments with \(\ce{B(OC4H9)3}\) led to acylation. Diphenylboric acid was obtained. This must be explained by the fact that the boron atom creates, in a free corner of the tetrahedron, a strong positive field \([2, 424]\). Therefore the complex of tributyl borate with \(\ce{AlCl3}\) is attracted to the carbon of the benzene ring:

\[ \ce{ [C6H6\cdots C(H)\cdots B(OC4H9)2-O-C4H9\cdots AlCl3] -> [C6H6-C(B(OC4H9))-O-C4H9\cdots AlCl3] + HOC4H9 } \]

In the same way, a second benzene ring may add, first complexly and then valently. The ester of diphenylboric acid \(\ce{(C6H5)2B(OC4H9)}\) is obtained; saponification of the latter gives the free acid.

It is interesting that diethyl sulfate, in contrast to ethyl nitrate, acted on benzene only in the presence of aluminum chloride. The absence of reaction with \(\ce{SnCl4}\) or \(\ce{SbCl5}\) could be explained by the fact that in the case of benzene and diethyl sulfate the catalyst is the doubled molecule of aluminum chloride, \(\ce{Al2Cl6}\). However, an experiment with ferric chloride, which also exists in the dimeric form \(\ce{Fe2Cl6}\), gave a negative result. It is possible that aluminum chloride is simply the stronger complex-forming agent, or, perhaps, that only it, having added to the ether oxygen of the sulfate, cleaves the bond of this oxygen with the alkyl sufficiently.

With the methyl ester of benzenesulfonic acid, as was to be expected, only alkylation of benzene occurred. In esters of carboxylic acids, theoretically one may expect both alkylation and acylation, since the carbonyl group can assume a form with a semipolar bond:

\[ \ce{ R-C(=O)(OR') -> R-\overset{+}{C}(-\overset{-}{O})(OR') } \]

The form with the covalent bond must add the catalyst to the ether oxygen, which will lead to alkylation of benzene:

\[ \begin{aligned} &\mathrm{Ph{-}C(H)\cdots AlCl_3} \;+\; \mathrm{R'O(R){-}C{=}O \cdots AlCl_3} \;\longrightarrow\; \mathrm{Ph{-}C(R')\cdots AlCl_3} \;+\; \mathrm{HO(R){-}C{=}O \cdots AlCl_3} \\[6pt] &\mathrm{Ph{-}C(R')\cdots AlCl_3} \;\longrightarrow\; \mathrm{Ph{-}C{-}R'} \;+\; \mathrm{AlCl_3}. \end{aligned} \]

Complex formation of the catalyst with the oxygen atom of the semipolar form of the carbonyl should lead to the formation of a ketone:

\[ \mathrm{Ph{-}C(H)\cdots C(OR')(R){-}O\cdots AlCl_3} \;\longrightarrow\; \mathrm{Ph{-}C{-}C^{+}(R){-}O^{-}\cdots AlCl_3} \;+\; \mathrm{HOR'}. \]

It is not excluded that one and the same ester may be capable of forming complexes of both types. In such a case the direction of the reaction will depend to a large extent on the strength of the bond between the ether oxygen and the hydrocarbon radical. According to the literature data, esters of carboxylic acids predominantly alkylate benzene, but when the ether oxygen is bonded to an aromatic radical, acylation occurs [7, 673]. Under our experimental conditions acylation took place only with glyceryl triacetate, and the two catalysts used, \(\mathrm{AlCl_3}\) and \(\mathrm{SbCl_5}\), gave almost the same yield of acetophenone: 28 and 29%. Both chlorides were taken in the amount of one molecule for each ester group. \(\mathrm{CH_3COOC_6H_5}\) did not react under the same conditions. Nor did \(\mathrm{CH_3COOC_2H_5}\), \(\mathrm{CH_3COOC_4H_9}\), \(\mathrm{CH_3COOC_5H_{11}}\), \(\mathrm{CO(OC_2H_5)_2}\), or, taken for comparison, the simple ethers \((\mathrm{C_2H_5})_2\mathrm{O}\) and \((\mathrm{C_5H_{11}})_2\mathrm{O}\) (diisoamyl ether) react. In the experiments with diethyl ether, however, 4 moles of ether were taken per 1 mole of \(\mathrm{AlCl_3}\) or \(\mathrm{SbCl_5}\). Formation of complexes with metal chlorides, one must suppose, also occurred in the experiments with a negative result. This is evident from the fact that antimony pentachloride nowhere caused chlorination of benzene, i.e., it was deactivated by the ether. However, the complexes formed did not act on benzene.

Alkylation was observed by us with the ethyl esters of oxalic, malonic, chloroacetic, \(\alpha\)-bromobutyric, and cyanoacetic acids. In these cases the halogens and the CN groups entering into the acid residue did not themselves react, but only influenced the reactivity of the ester group. With a large excess of chloroacetic ester (4 moles per 1 mole of aluminum chloride), a negative result was obtained.

Simple and compound ethers with a benzyl radical are distinguished by great reactivity. The simple ether \((\mathrm{C_6H_5CH_2})_2\mathrm{O}\), with \(\mathrm{AlCl_3}\) as catalyst, gave diphenylmethane in a yield of 91.5%, although the ether and aluminum chloride were taken in an equimolecular ratio. With stannic chloride a yield of 79.9% was obtained, and with antimony pentachloride, for some reason, only 40.5%. Benzyl acetate reacted with benzene under the same conditions in the presence of \(\mathrm{AlCl_3}\) in 79%, with \(\mathrm{SnCl_4}\) in 66%, with \(\mathrm{SbCl_5}\) in 33%, and with \(\mathrm{BiCl_3}\) in 14%,

with AlI₃—11.2%; no reaction occurred with CuCl₂, ZnCl₂, ZnBr₂. The difference between benzyl esters and esters containing terminal radicals may sometimes be due to the lower stability of complexes containing the radicals C₆H₅CH₂ (although, as has already been said, this reason cannot explain the results of experiments with antimony pentachloride).

Owing to this, only part of the catalyst is bound by the ester; the other part can activate benzene. The same circumstance may be important in the above-mentioned ethyl esters of halogen-substituted and cyano-substituted acids, as well as of dicarboxylic acids. The halogens and the CN and COOR groups have an electron-withdrawing character and must weaken the electron-donating activity of the ester oxygen, i.e., its ability to form complexes with AlCl₃, etc.

Halogenation of Aromatic Compounds

Halogens act on aromatic compounds in different directions. With chlorine or bromine, benzene enters into addition or substitution reactions:

\[ \ce{C6H6 + 3Cl2 -> C6H6Cl6} \]

\[ \ce{C6H6 + Cl2 -> C6H5Cl + HCl} \]

Light and soda, as well as the absence of catalysts that accelerate the substitution process, favor the first direction of halogenation. As our investigations have shown, the action of soda consists in its neutralizing the hydrogen halide liberated during substitution. Apparently, benzene itself reacts with chlorine or bromine in two directions, addition of the halogen predominating, while substitution initially proceeds only to a negligible extent. However, the accumulating hydrogen halide belongs to the catalysts that accelerate further substitution. This has been directly demonstrated by the experiments of N. I. Oranskii [18] and L. A. Pershina [19]. It has also been shown that water, likewise absorbing hydrogen halides, directs the reaction of benzene with bromine exclusively toward the formation of hexabromocyclohexane, while the overall consumption of bromine is slowed.

As was indicated above, replacement of hydrogen atoms in the bromination and chlorination of benzene proceeds in the presence of the same catalysts as in the Friedel–Crafts syntheses. The catalyst, for example FeBr₃ in bromination in the presence of iron, adds as a complex to the carbon of the benzene ring and loosens the bond of this car—

with hydrogen bromide. It is possible that this occurs at the expense of a second molecule of catalyst and activation of the halogen, owing to formation of the complex \(\overset{+}{\mathrm{Br}}[\mathrm{FeBr}_{4}]^{-}\). Activation of the benzene ring in chlorination and bromination is not necessary, since bromination of benzene can also be carried out in the presence of pyridine. In this case one may assume only complex formation of the halogen with pyridine. In the resulting complex \([\mathrm{C}_{5}\mathrm{H}_{5}\mathrm{NBr}]^{+}\mathrm{Br}^{-}\), one atom of halogen enters into the composition of the cation, which increases its reactivity.

With ferric bromide, pyridine, and many other catalysts, the reaction is homogeneous in character; but bromination of benzene is also accelerated by certain substances that are completely insoluble in it. In our laboratory the rate of bromination of benzene was determined in the presence of numerous catalysts; in decreasing order of reaction rate, the latter were arranged as follows: Fe, Zn, Bi, Hg, Te, Cu, Cd, Pb, Mg, I, \(\mathrm{C}_{6}\mathrm{H}_{5}\mathrm{I}\), Co, Mn, Al, Sb, Sn, Ni, As, P, S, Se, \(\mathrm{CaCl}_{2}\), without catalysts, Ag, \(\mathrm{SiCl}_{4}\), \(\mathrm{CH}_{3}\mathrm{COOH}\), \(\mathrm{C}_{6}\mathrm{H}_{5}\mathrm{NO}_{2}\), \(\mathrm{H}_{2}\mathrm{O}\), \(\mathrm{C}_{6}\mathrm{H}_{4}(\mathrm{NO}_{2})_{2}\), \(\mathrm{C}_{6}\mathrm{H}_{2}(\mathrm{NO}_{2})_{3}\mathrm{OH}\).

The simple substances taken with bromine should have been converted into bromides, which probably were in fact the catalysts; silver slowed bromination, evidently owing to removal of hydrogen bromide.

Especially interesting here is the strongly accelerating action of zinc, which can very well be recommended for carrying out the bromination of benzene in organic-synthesis laboratories. In activity, zinc in our work far surpassed even aluminum. However, in experiments with ready-made bromides of certain elements we obtained a different series of activities:

\[ \mathrm{FeBr}_{3} > \mathrm{AlBr}_{3} > \mathrm{ZnBr}_{2} > \mathrm{IBr}_{2} > \mathrm{SbBr}_{3} > \mathrm{AsBr}_{3} > \mathrm{CuBr}_{2} > \mathrm{S}_{2}\mathrm{Br}_{2} > \mathrm{PBr}_{3}. \]

Zinc bromide now was markedly inferior to ferric bromide and aluminum bromide. It turned out, moreover, that \(\mathrm{FeBr}_{3}\) and \(\mathrm{AlBr}_{3}\), in the amounts we used (molecular ratio \(\mathrm{C}_{6}\mathrm{H}_{6}:\mathrm{Br}_{2}:\) catalyst equal to \(2:1:0.01\)), dissolved completely in the reaction mixture, whereas zinc bromide proved to be entirely insoluble. With \(\mathrm{FeBr}_{3}\) and \(\mathrm{AlBr}_{3}\) we therefore have homogeneous catalysis; with \(\mathrm{ZnBr}_{2}\), heterogeneous catalysis, the catalysts being similar to one another in composition and structure. It may be thought that with \(\mathrm{ZnBr}_{2}\) similar complex bonds of benzene and bromine with metal ions arise, although this ion remains in the crystal lattice.

The fact that ready-made \(\mathrm{ZnBr}_{2}\) occupied a lower position in the series of catalysts than metallic zinc is probably due to the different magnitude of the grains. Zinc was taken in the form of dust, i.e., in a very finely divided state; the pieces of bromide, possibly, were larger.

The most difficult of the halogens to introduce into the benzene molecule is iodine, the least active one. Direct iodination of benzene itself, its homologs, and many derivatives requires especially strong activation, and at the same time activation both of the halogen and of the benzene ring. Such double activation is best achieved with fuming nitric acid, as indicated in the literature [4], or with a nitrating mixture by the method developed in our laboratory [17]. Iodine is apparently activated by transition into the cationic state:

\[ \mathrm{I}_{2}+\mathrm{HNO}_{3}\rightarrow \overset{+}{\mathrm{I}}(\mathrm{NO}_{3})^{-}+\mathrm{HI}. \]

At the same time nitric acid also activates benzene. If the nitronium scheme of nitration is accepted, then the complex should first be formed:

\[ \left[ \begin{array}{c} \mathrm{C}_{6}\mathrm{H}_{6}\cdots \mathrm{O}\!\cdot\!\mathrm{NO}_{2} \\ \quad\quad\;\;\; | \\ \quad\quad\;\;\; \mathrm{H} \end{array} \right]^{+} \]

Such a complex passes, with greater or lesser speed, into the nitro compound, i.e., the unshared pair of electrons of the benzene carbon begins to move around both atomic nuclei, carbon and nitrogen; the complex bond becomes covalent. Following this, the proton shifts to one of the oxygen atoms of the nitro group:

\[ \left[ \begin{array}{c} \text{Ph}\!-\!C\cdots NO_2 \\ \quad H \end{array} \right]^+ \longrightarrow \text{Ph}\!-\!C-\overset{+}{N}(=O)-\overset{-}{O}\cdots H \rightleftarrows \text{Ph}\!-\!C-\overset{+}{N}(=O)-\overset{-}{O} + H^+ \]

The transition of the complex bond between the carbon and nitrogen atoms into a covalent bond occurs at a definite rate, different for different compounds. If this rate is not very high and if some reagent is present in the solution that is capable of replacing hydrogen with a loosened bond—for example, activated halogen—then substitution of hydrogen by halogen may quite well occur before the complex has had time to rearrange into the nitro compound, after which the complex-bound nitronium is split off in unchanged form:

\[ \left[ \text{Ph}\!-\!C\cdots NO_2 \begin{array}{c} \quad H \end{array} \right]^+ + I^+ \longrightarrow \text{Ph}\!-\!C-I + H^+ + (NO_2)^+ \]

The rate of conversion of the nitronium complex into the nitro compound depends on the activity of the electrons of the carbon atom. The strongest negative charge, i.e., the most active electron pair, is possessed by the para positions (to a lesser extent the ortho positions) of aromatic amines and phenols. In accordance with this, phenol, under the action of nitric acid in the presence of iodine, is chiefly nitrated rather than iodinated. In naphthalene, with its somewhat smaller negative charges, nitration also predominates. Benzene itself is mainly iodinated, but is also partly nitrated. Benzene derivatives with strongly deactivating, i.e., meta-directing, substituents should practically undergo iodination exclusively. Consequently, for such compounds the method of iodination in the presence of nitric acid or of a nitrating mixture should give better yields and purer iodo derivatives.

For our investigation we chose first of all benzoic acid, since the product of its iodination—meta-iodobenzoic acid—has practical application. Having carried out a large number of experiments on the iodination of benzoic acid in the presence of a sulfuric–nitric nitrating mixture, we developed a procedure that makes it possible to obtain meta-iodobenzoic acid in yields of up to 75% of theory. This method must be regarded as the best of all existing ones. It is interesting that in none of 44 experiments were appreciable amounts of nitro derivatives obtained.

Iodination of benzaldehyde under the same conditions likewise led to meta-iodobenzoic acid. However, iodination with the additional addition of carbamide (to destroy the nitrogen oxides, which would oxidize the aldehyde group) made it possible to prepare meta-iodobenzaldehyde as well, although in a yield of only 20–25%.

Nitrobenzene was directly iodinated to meta-iodonitrobenzene.

Iodination of benzene under conditions altered in comparison with the preceding experiments made it possible to obtain iodobenzene free from nitrobenzene. The yield reached 80% of theory. Here it is very important to take as much as possible

less nitric acid. Toluene was also iodinated, with a total yield of ortho- and para-iodotoluenes of up to 95% (para-iodotoluene was isolated in an amount of 70%). Iodobenzene gave 55% para-diiodobenzene and about 20% of an oil consisting mainly of ortho-diiodobenzene. From para-nitrotoluene, 70% iodinitrotoluene was obtained.

The described method of halogenation also makes it possible to obtain good yields of bromo derivatives, but attempts to chlorinate benzoic acid in the presence of a nitrating mixture did not give a positive result. Depending on the experimental conditions, either nitration occurred, or the benzoic acid remained unchanged. This fact can be explained only by the fact that chlorine, being more electronegative than bromine and iodine, is not converted by nitric acid into the cationic state and therefore is not activated. Molecular chlorine should act on aromatic compounds more strongly than molecular bromine and, all the more, iodine, but positively charged bromine and iodine prove to be more active than neutral chlorine.

The iodination of compounds with a strongly loosened benzene ring, namely phenols and aromatic amines, was also studied. Here the reaction was carried out under milder conditions. Phenol or amine was taken in benzene or in ethyl alcohol. The concentration of the compound to be iodinated was 0.9 mole per liter, and that of iodine 0.1 mole per 1 mole of substance. To determine the influence of complex formation, substances with different types of reactivity were added, for example pyridine, nitrobenzene (both in equimolecular ratio to the compound being iodinated), concentrated hydrochloric acid (0.1 ml per 0.025 mole of phenol or amine), and sodium iodide (0.4642 g). Mixtures of phenols with amines were also taken. The iodination was carried out at 20°. The experiments were performed in separate flasks, the contents of which were titrated with sodium thiosulfate at definite time intervals.

Considerations based on electronic theory led one to expect the following effect from the additives taken.

Amines, including pyridine and, to a lesser extent, aromatic amines, are complex-forming agents of the electron-donor type. Their complex addition, for example to phenol, should increase the negative charge throughout the molecule of the latter; i.e., in their presence the halogenation reaction should proceed more readily. Acids are electron-acceptor reagents. The proton of hydrochloric acid, having added to the nitrogen of aniline or to the oxygen of phenol, should strengthen the positive charges and weaken the negative charges throughout the molecule of the substance being iodinated, i.e., hinder the halogenation reaction. Nitrobenzene should act in the same way; in complex formation with amines and phenols it functions as an electron acceptor [23].

The change in reactivity of the halogen itself is also important. Amines with halogens give complexes, one atom of halogen entering into the composition of the complex cation. This should make it more active. This explains the accelerating action of pyridine in the bromination of benzene, and the same should be expected in the iodination of aromatic compounds:

\[ \mathrm{C_5H_5N + I_2 \to [C_5H_5NI]^+ I^-}. \]

Aniline should accelerate the iodination of phenol, and from two sides: because of activation of iodine and because of the formation of a complex bond of nitrogen with hydroxyl hydrogen,

\[ \mathrm{C_6H_5OH \ldots NH_2C_6H_5}. \]

Iodide salts should exert a strong retarding action. The iodide ion forms complex anions with molecular iodine: \(\mathrm{I_3'}\), \(\mathrm{I_5'}\), \(\mathrm{I_7'}\), \(\mathrm{I_9'}\).

Here all the iodine is incorporated into the complex with a negative charge, which should greatly hinder the formation of iodine cations. Finally, solvents should also have an effect on the reaction rate. In a polar alcohol, reactions associated with polarization will proceed faster.

These considerations are confirmed by experimental results. I cite some data concerning the iodination of phenol and aniline [15].

Table 2

Rate of iodination in benzene solution

Table 3

Rate of iodination in alcoholic solution

Separate experiments showed that, under our reaction conditions, iodine had absolutely no effect on pyridine, alcohol, or a mixture of alcohol with pyridine. Naturally, nitrobenzene also did not react. It was also found that, in the iodination of a mixture of phenol with aniline, about 90% of the iodine went to the aniline and 10% to the phenol. But phenol, too, it turns out, accelerates the iodination of aniline, which so far has not found a theoretical explanation. Activation of iodine by phenol is possible.

Dehalogenation of Organic Compounds by Iodide Salts

As the results of the experiments described in the preceding chapter showed, the reactivity of halogens can be increased by converting them into the state of positive ions, simple or complex:

$$ \mathrm{I_2 + HNO_3 \rightarrow I^+(NO_3)^- + HI} $$

$$ \mathrm{I_2 + C_5H_5N \rightarrow [C_5H_5NI]^+ + I^-} $$

When molecular iodine enters into the composition of complex anions, for example \(I_3^-\), its activity, on the contrary, decreases sharply. This is demonstrated by the retardation of the iodination of phenols and aromatic amines in the presence of iodide salts. The long-known dehalogenating action of iodide salts on many organic chlorides and bromides must be explained in the same way. With the aid of NaI or KI it is possible to remove two atoms of chlorine or bromine from adjacent units of molecules of an organic compound, for example:

\[ \mathrm{CH_2Br \cdot CH_2Br + 2NaI \longrightarrow CH_2{=}CH_2 + 2NaBr + I_2} \]

Iodide salts are even recommended as reagents for determining the structure of organic dihalides [25]. In organic synthesis, a method for lengthening the carbon skeleton of molecules based on such a dehalogenating action of inorganic iodides may be of great importance. Let us take two examples from the work of Finkelstein [27], who studied this phenomenon in considerable detail:

\[ \begin{array}{c} \mathrm{COOC_2H_5} \\ | \\ 2\,\mathrm{CHBr} \\ | \\ \mathrm{COOC_2H_5} \end{array} \;+\;2\mathrm{NaI} \longrightarrow \begin{array}{cc} \mathrm{COOC_2H_5} & \mathrm{COOC_2H_5} \\ | & | \\ \mathrm{CH} & -\ \mathrm{CH} \\ | & | \\ \mathrm{COOC_2H_5} & \mathrm{COOC_2H_5} \end{array} \;+\;2\mathrm{NaBr}+I_2 \]

\[ 2\,(\mathrm{C_6H_5})_2\mathrm{CClI} +2\mathrm{NaI} \longrightarrow (\mathrm{C_6H_5})_2\mathrm{CCl{-}CCl}(\mathrm{C_6H_5})_2 +2\mathrm{NaCl}+I_2 \]

\[ (\mathrm{C_6H_5})_2\mathrm{CCl{-}CCl}(\mathrm{C_6H_5})_2 +2\mathrm{NaI} \longrightarrow (\mathrm{C_6H_5})_2\mathrm{C{=}C}(\mathrm{C_6H_5})_2 +2\mathrm{NaCl}+I_2 \]

Such a direction of the reactions is in some cases explained by the extraordinary instability of the corresponding iodo derivatives. For example, \((\mathrm{C_6H_5})_2\mathrm{CI{-}CI}(\mathrm{C_6H_5})_2\) cannot exist at all. Even bromine does not add to tetraphenylethylene. Iodomalonic ester also cannot be obtained in any way. But ethylene iodide is quite accessible and sufficiently stable in the free state. Why, then, is it not formed in the present case?

It was found [29] that the decomposition of \(\mathrm{C_2H_4I_2}\) is accelerated in the presence of iodide ions, but much in the course of this reaction, as also in the mechanism of dehalogenation of the corresponding compounds with other halogens, remained unclear.

Since molecular iodine with anions \(I^-\) gives complex anions, the most probable cause of the dehalogenating action of iodide salts on organohalogen compounds may be considered to be precisely the energy of formation of these complexes. In order to test this assumption and, incidentally, to decide which of the possible complex anions \(I_3'\), \(I_5'\), \(I_7'\), or \(I_9'\) plays the decisive role here, L. A. Pershina determined the rate of decomposition of diiodopropyl alcohol, both by itself and in the presence of various amounts of sodium iodide. The experiments were carried out at \(25^\circ\) in the solvents ethyl alcohol and acetone. The rate of iodine liberation in the presence of preformed \(\mathrm{NaI_3}\) was also determined.

We give the results of the experiments with alcoholic solutions at the same concentration of diiodopropanol, but in the presence of different amounts of sodium iodide.

Here, first of all, it is interesting that only at an equivalent ratio of sodium iodide to diiodopropanol does the dehalogenation reaction proceed fairly rapidly to completion. At a ratio of 1:2 the process rather quickly reaches consumption of 50% of the diiodopropyl alcohol, and then slows sharply. At a ratio of 1:3, retardation already sets in at about 30%; finally, for the composition 1:4 we have retardation at approximately 20–25%. All this corresponds precisely to the composition of the anion \(I_3'\), whose energy of formation must therefore be regarded as the principal factor causing the diiodination—

Table 4

tion. The formation of the ions \(I_5'\), \(I_7'\), \(I_9'\) is of secondary importance. The addition of the ready-made complex \(NaI_3\), as was to be expected, accelerates the cleavage of iodine from diiodopropyl alcohol, but many times more weakly than the addition of sodium iodide.

With monohalogen derivatives, under the action of iodide salts, simple replacement of chlorine or bromine by iodine sometimes occurs. We observed such replacement (experiments of A. S. Samarin, V. M. Aksenenko, and others) with esters of halogen-substituted monocarboxylic acids of the limiting series, with benzyl chloride, with chloroacetophenone, for example,

\[ (CH_3)_2CBr\cdot COOC_2H_5 + NaI \longrightarrow (CH_3)_2CI\cdot COOC_2H_5 + NaBr \]

\[ C_6H_5CH_2Cl + NaI \longrightarrow C_6H_5CH_2I + NaBr. \]

In those cases where the halogen is attached to a carbon atom bonded to two electronegative groups, the action of \(NaI\) leads to complication of the molecular skeleton, similarly to what was found by Finkelstein in the example of bromomalonic ester and diphenyldichloromethane. V. M. Aksenenko carried out the reactions:

\[ 2\,C_6H_5CHCl\cdot COOC_2H_5 + 3\,NaI \longrightarrow \begin{array}{c} C_6H_5{-}CH{-}COOC_2H_5\\ \big|\\ C_6H_5{-}CH{-}COOC_2H_5 \end{array} + 2NaCl + NaI_3, \]

\[ 2\,C_6H_5CHBr\cdot COOC_2H_5 + 3\,NaI \longrightarrow \begin{array}{c} C_6H_5{-}CH{-}COOC_2H_5\\ \big|\\ C_6H_5{-}CH{-}COOC_2H_5 \end{array} + 2NaBr + NaI_3, \]

\[ 2\,C_6H_5\cdot CHClCN + 3NaI \longrightarrow \begin{array}{c} C_6H_5{-}CH{-}CN\\ \big|\\ C_6H_5{-}CH{-}CN \end{array} + 2NaCl + NaI_3, \]

\[ 2\,C_6H_5\cdot CHBrCN + 3NaI \longrightarrow \begin{array}{c} C_6H_5{-}CH{-}CN\\ \big|\\ C_6H_5{-}CH{-}CN \end{array} + 2NaBr + NaI_3, \]

\[ 2\,CH_3CO\cdot CHClCOOC_2H_5 + 3NaI \longrightarrow \begin{array}{c} CH_3CO\cdot CH{-}COOC_2H_5\\ \big|\\ CH_3CO\cdot CH{-}COOC_2H_5 \end{array} + 2NaCl + NaI_3, \]

\[ 2\,CH_3CO\cdot CHBr\cdot COOC_2H_5 + 3NaI \longrightarrow \begin{array}{c} CH_3CO\cdot CH\cdot COOC_2H_5\\ \big|\\ CH_3CO\cdot CH\cdot COOC_2H_5 \end{array} + 2NaBr + NaI_3, \]

\[ 2\,CH_3CO\cdot CHI\cdot COOC_2H_5 + NaI \longrightarrow \begin{array}{c} CH_3CO\cdot CH\cdot COOC_2H_5\\ \big|\\ CH_3CO\cdot CH{-}COOC_2H_5 \end{array} + NaI_3. \]

These reactions sometimes proceeded very smoothly. For example, in the chlorobenzylidene case the yield reached 100%. In some cases the process is complicated. Thus, A. S. Samarin and student Koganitskaya found that under the action of iodide salts on chloromalonic ester still another peculiar reaction takes place [21]. With bromomalonic ester, ethane-tetracarboxylic ester is obtained smoothly. Under the same conditions, the ester of chloromalonic acid, first, reacts considerably more slowly and, second, together with ethane-tetracarboxylic ester gives also the ester of an unsaturated ethylenetetracarboxylic acid:

\[ (\mathrm{COOC_2H_5})_2\mathrm{C}=\mathrm{C}(\mathrm{COOC_2H_5})_2 . \]

The formation of this compound was proved by its melting point, and also by reduction to the readily identifiable

\[ (\mathrm{COOC_2H_5})_2\mathrm{CH}-\mathrm{CH}(\mathrm{COOC_2H_5})_2 . \]

The mechanism of the reaction has not been fully elucidated. The assumption of intermediate iodination of ethane-tetracarboxylic ester to
\((\mathrm{COOC_2H_5})_2\mathrm{CI}-\mathrm{CI}(\mathrm{COOC_2H_5})_2\) was not confirmed, since ethane-tetracarboxylic ester could not, under any conditions, be not only periodinated, but even perbrominated. Presumably, one may admit the formation of free radicals, which can react with new molecules of chloromalonic ester, etc.

\[ \begin{aligned} &2\,\mathrm{COOC_2H_5.CHCl.COOC_2H_5}+3\,\mathrm{NaI} \longrightarrow 2\,\mathrm{COOC_2H_5.CH.COOC_2H_5}+2\,\mathrm{NaCl}+\mathrm{NaI_3} \\[-2mm] &\hspace{9.7cm}\big| \\[1mm] &\mathrm{COOC_2H_5.CH.COOC_2H_5} +\mathrm{COOC_2H_5.CHCl.COOC_2H_5} \longrightarrow \\[-2mm] &\hspace{1.7cm}\big| \\[-1mm] &\longrightarrow \mathrm{COOC_2H_5.CH_2.COOC_2H_5} +\mathrm{COOC_2H_5.CCl.COOC_2H_5} \\[-2mm] &\hspace{10.1cm}\big| \\[2mm] &2\,\mathrm{COOC_2H_5.CCl.COOC_2H_5} \longrightarrow \begin{matrix} \mathrm{COOC_2H_5.CCl.COOC_2H_5}\\ \mathrm{COOC_2H_5.CCl.COOC_2H_5} \end{matrix} \\[-1mm] &\hspace{2.7cm}\big| \\[-1mm] &\mathrm{COOC_2H_5.CCl.COOC_2H_5} \hspace{4.2cm} \mathrm{COOC_2H_5.C.COOC_2H_5} \\[-1mm] &\hspace{2.7cm}\big| \hspace{4.9cm}\big\| \\[-1mm] &\mathrm{COOC_2H_5CCl.COOC_2H_5} +3\,\mathrm{NaI} \longrightarrow \mathrm{COOC_2H_5.C.COOC_2H_5} +2\,\mathrm{NaCl}+\mathrm{NaI_3}. \end{aligned} \]

As we see, the reaction of organohalogen compounds with iodide salts can proceed in diverse directions. This reaction deserves great attention as one of the methods for complicating the carbon skeleton of molecules. The advantage of such a method is that it is not hindered by solvents which interfere with work using metals or organometallic compounds.

Amination of aromatic hydroxy derivatives in the presence of complex-forming catalysts

B. V. Koyan, under the direction of L. P. Kulev, studied the reaction of hydroxy derivatives of anthraquinone with aromatic amines, which is important in dye synthesis. In this reaction, hydroxyl is replaced by the residue of an aromatic amine:

\[ \begin{array}{c} \text{quinizarin} \end{array} \qquad \begin{array}{c} \mathrm{CO\ OH}\\[-1mm] \text{anthraquinone nucleus}\\[-1mm] \mathrm{CO\ OH} \end{array} +\mathrm{H_2N.C_6H_5} \longrightarrow \begin{array}{c} \mathrm{CO\ NHC_6H_5}\\[-1mm] \text{anthraquinone nucleus}\\[-1mm] \mathrm{CO\ OH} \end{array} +\mathrm{H_2O}. \]

The reaction proceeds upon heating with catalysts, among which, in the work cited, the following were tested (in order of decreasing activity): boric acid, zinc chloride, hydrochloric acid, pyrocatechin, orthophosphoric acid aniline, hydroquinone, orthophosphoric acid, acetic acid, metaphosphoric acid, and resorcinol. The best catalyst proves to be boric acid, whose action some authors have attempted to explain by the intermediate formation of complex esters.

Such an interpretation is conceivable for the reaction with boric acid and with certain other catalysts, but it is in no way suitable for the action of hydrogen halides. Moreover, the authors of this explanation entirely fail to take into account the possibility of interaction of amines with the same catalysts. L. P. Kulev and V. V. Kolin drew attention, first, to the fact that amines are good complex-forming agents; second, to the capacity for complex formation of all the catalysts used in these syntheses; and to the fact that, in particular, boric acid must be very active with respect to complex formation, since the boron atom in it has a strong positive electric field.

A large number of experiments were carried out with various oxy derivatives and amines, as well as with separately prepared amine–catalyst complexes. One of the boric esters, regarded as an intermediate product, was also studied, and it proved to be only slightly active. The results of the experiments demonstrate quite convincingly that the intermediate stage of the aramination process is complex formation between the amine and the catalyst; moreover, the preformed complexes reacted with the oxy derivatives more rapidly. A dependence of the rate of aramination on the stability of the complexes was also established. Less stable complexes are more active. This latter fact points to the great complexity of the course of the reaction. Evidently, the complex addition of the catalyst to the hydroxyl group, loosening the bond between oxygen and carbon, is also of importance here. Thus, the process of aramination probably requires double activation, similarly to the alkylation of benzene by the Gustavson–Friedel–Crafts method.

Conclusion

The examples examined clearly show how great the importance of complex formation is in organic chemistry. The appearance of a complex bond at some point in a molecule affects the properties of all atoms in that molecule, increasing or decreasing their reactivity. At the same time, the change in reactivity is selective in character. By making use of this, we can deliberately direct a reaction in the direction desired by us through a corresponding change in conditions, in particular by applying suitable catalysts and choosing these catalysts on the basis of definite theoretical considerations.

From this standpoint, the detailed study of complex organic compounds, with clarification of the general regularities of complex formation and of the mutual influence of atoms in complex compounds, is extremely important for the development of methods of organic synthesis. The further development of the chemistry of complex organic compounds, making use of the achievements of the far-advanced chemistry of inorganic complexes, should become one of the principal tasks of Soviet organic chemists.

Conclusions

1. One of the fundamental propositions of the theory of chemical structure developed by A. M. Butlerov states that the properties of each atom in a molecule depend not only on the nature of that atom and on the atoms directly bonded to it, but also on the composition and structure of the entire molecule as a whole, i.e., all atoms in a molecule mutually influence one another.

2. The proposition concerning the mutual influence of atoms is valid not only for valence compounds, but also for complex compounds.

3. Many reactions of organic chemistry begin with the formation of complex compounds; moreover, in the complexes that arise, the properties of the molecules and their parts that have combined may differ sharply from the properties of the same molecules and their parts outside the complex.

4. The work presents a number of examples from the literature showing how complex formation affects the direction and rate of reactions in organic chemistry. In particular, the action of many catalysts is explained by complex formation.

5. The work of many investigators has shown that the process of nitration of benzene with nitric acid or with a nitrating mixture begins with the formation of a complex of benzene with a dimer of nitric acid or with a complex of nitric and sulfuric acids (the author’s original opinion); it may be, as is now thought, with the intermediate formation of cations arising as a result of electrolytic dissociation and dehydration.

6. The explanation of reactions grouped under the name of the Gustavson—Friedel—Crafts synthesis has been refined. In particular, in the alkylation of benzene with alkyl halides and with simple and complex esters, the necessity of double activation (of both benzene and the second reagent) has been demonstrated; the difference in the direction of the reactions of benzene with esters of nitric and sulfuric acids, etc., has been explained.

7. The action of catalysts in many halogenation reactions of organic compounds has been explained by complex formation. The iodination of aromatic compounds in the presence of an azotosulfuric nitrating mixture has been studied in detail; the necessity of double activation in the iodination of weakly active aromatic substances has been demonstrated. It has been observed that under these conditions iodination and bromination proceed readily, but not chlorination. The latter fact is explained by the absence of activation of chlorine.

8. The indication that the iodination of many organic compounds proceeds more readily in the presence of pyridine has been confirmed by new examples. This is explained by the fact that the iodine molecule forms a complex with pyridine, one iodine atom entering into the composition of the complex cation and, owing to the positive charge, becoming more active.

9. It has been shown that the cause of the dehalogenating action of iodide salts on certain organohalogen compounds is the formation of the complex anion \(I'_3\).

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