Electrophilic substitution reactions are more difficult than those of benzene, which is due to the strong electron-withdrawing effect of the nitro group. The substitution occurs in the meta position, since the nitro group is an orientant of the second kind (S E 2 arom).

Therefore, electrophilic substitution reactions are carried out only with strong reagents (nitration, sulfonation, halogenation) under more stringent conditions:

1. Nucleophilic substitution reactions

In nucleophilic substitution reactions (S N 2 arom), the nitro group directs the nucleophile to the ortho and para positions.

For example, the fusion of nitrobenzene with KOH at 100 0 C leads to the production of ortho- and para-nitrophenols:

An attack to the ortho position is more preferable, since the negative inductive effect of the nitro group, acting at a small distance, creates a greater shortage of electrons in the ortho than in the para position.

The presence of two and especially three nitro groups in the meta position relative to each other further promotes reactions with nucleophilic reagents.

So, for example, when meta-dinitrobenzene reacts with alkali or with sodium amide, one of the hydrogen atoms in the ortho or para positions is replaced by the group Oh, or at NH 2 :

2,4-dinitrophenol

2,6-dinitroaniline

Symmetrical trinitrobenzene reacts with alkali to form picric acid:

2,4,6-trinitrophenol

picric acid

1. Influence of the nitro group on reactivity

other groups in the benzene ring

Nucleophilic substitution of the nitro group

If the nitro groups are in ortho- and para-positions with respect to each other, then they activate each other and nucleophilic substitution of the nitro group is possible with the departure of the nitrite ion:

Nucleophilic substitution of halogens and other groups

The nitro group activates the nucleophilic substitution not only of the hydrogen atom, but also of other groups located in the benzene ring in the ortho and para positions relative to the nitro group.

The halogen atoms, -OH, -OR, -NR 2 and other groups are easily replaced by nucleophiles.

The role of the nitro group is not only to create a positive charge on the carbon atom associated with the substituting group, but also to stabilize the negative ϭ-complex, because the nitro group contributes to the delocalization of the negative charge.

For example, the halogen in ortho- and para-nitrochlorobenzenes under the influence of the nitro group is easily replaced by nucleophilic particles:

:Nu: -- = HE -- , NH 2 -- , I -- , -- OCH 3

The presence of two and especially three nitro groups accelerates nucleophilic substitution, and this is most pronounced in cases where the nitro groups are in the ortho or para position relative to the group being replaced:

2,4-dinitrochlorobenzene

The halogen atom is most easily replaced in 2,4,6-trinitrochlorobenzene (picryl chloride):

2,4,6-trinitrochlorobenzene

(picryl chloride)

Reactions related to the mobility of hydrogen atoms

alkyl radicals

Due to the strongly pronounced electron-withdrawing character, the nitro group has a significant effect on the mobility of hydrogen atoms of alkyl radicals located in the ortho and para positions with respect to it.

a) condensation reactions with aldehydes

In para-nitrotoluene, the hydrogen atoms of the methyl group under the influence of the nitro group acquire high mobility and, as a result, para-nitrotoluene enters into condensation reactions with aldehydes as a methylene component:

b) the formation of nitronic acids

Hydrogen atoms at the α-carbon atom due to ϭ, π-conjugation have high mobility and can migrate to the oxygen of the nitro group with the formation of tautomeric nitronic acid.

The formation of nitronic acids in aromatic nitro compounds with a nitro group in the ring is associated with the transformation of the benzene ring into a quinoid structure:

For example, ortho-nitrotoluene exhibits photochromism: bright blue nitronic acid is formed (quinoid structures are often intensely colored:

ortho-nitrotoluene nitronic acid

Electrophilic substitution reactions are characteristic of aromatic, carbocyclic, and heterocyclic systems. As a result of the delocalization of p-electrons in the benzene molecule (and other aromatic systems), the p-electron density is distributed uniformly on both sides of the cycle. Such screening of the carbon atoms of the cycle by p-electrons protects them from attack by nucleophilic reagents and, conversely, facilitates the possibility of attack by electrophilic reagents.

But unlike the reactions of alkenes with electrophilic reagents, the interaction of aromatic compounds with them does not lead to the formation of addition products, since in this case the aromaticity of the compound would be violated and its stability would decrease. The preservation of aromaticity is possible if the electrophilic particle replaces the hydrogen cation.

The mechanism of electrophilic substitution reactions is similar to the mechanism of electrophilic addition reactions, since there are general patterns of reactions.

General scheme of the mechanism of electrophilic substitution reactions S E:

In the first step of the reaction, p-complex with an electrophilic particle (fast stage), which then turns into s-complex(slow stage) due to the formation s- bonds of one of the carbon atoms with an electrophilic particle. For education s- In connection with the electrophilic particle, a pair of electrons “breaks out” from the conjugation, and the resulting product acquires a positive charge. IN s-complex aromaticity is broken, since one of the carbon atoms is in sp 3 hybridization, and four electrons and a positive charge are delocalized on five other carbon atoms.

To regenerate a thermodynamically favorable aromatic system, heterolytic cleavage of the C sp 3 -H bond occurs. As a result, the H + ion is split off, and a pair of bond electrons goes to restore the conjugation system, while the carbon atom that split off the proton changes hybridization atomic orbitals from sp 3 to sp 2 . The mechanism of reactions of nitration, sulfonation, halogenation, alkylation, acylation of aromatic compounds includes an additional step not specified in general scheme- the stage of generating an electrophilic particle.

Reaction equationnitrationbenzene looks like:

In nitration reactions, the generation of an electrophilic particle occurs as a result of the interaction of nitric and sulfuric acids, which leads to the formation of the nitronium cation NO 2 +, which then reacts with an aromatic compound:

In the benzene molecule, all carbon atoms are equivalent, substitution occurs at one of them. If substituents are present in the molecule, then the reactivity and direction of the electrophilic attack is determined by the nature of this substituent. According to the influence on the reactivity and direction of attack, all substituents are divided into two groups.

Orientants of the first kind. These substituents facilitate electrophilic substitution compared to benzene and direct the incoming group to the ortho and para positions. These include electron-donating substituents that increase the electron density in the benzene nucleus. As a result of its redistribution to positions 2,4,6 (ortho- and para-positions), partial negative charges arise, which facilitates the attachment of an electrophilic particle to these positions with the formation s-complex.

Orientants of the second kind. These substituents make electrophilic substitution reactions more difficult than benzene and direct the incoming group to one of the meta positions. These include electron-withdrawing substituents that reduce the electron density in the benzene ring. As a result of its redistribution in positions 3,5 (meta-positions), partial negative charges arise and the addition of an electrophilic particle with the formation s-complex going under tough conditions.

Halogen atoms direct the electrophilic particle to the ortho- or para-positions (due to the positive mesomeric effect), but at the same time hinder the reaction, since they are electron-withdrawing substituents (-I>+M). Reactions of halogen derivatives of benzene with electrophilic reagents proceed under severe conditions.

In reactions sulfonation the role of the electrophilic particle is played by the SO 3 molecule, which is formed as a result of the reaction: 2H 2 SO 4 «SO 3 + H 3 O + + HSO 4 -. The sulfur atoms in this molecule are characterized by a strong deficit of electron density and the presence of a partial positive charge, and, therefore, it is the S atom that, as an electrophile, must bind to the carbon atom of the benzene ring of toluene.

The methyl group in toluene is an orientant of the first kind, and as an electron-donating substituent, it facilitates the substitution reaction and directs the incoming group to the ortho and para positions. In practice, substitution products are also formed in the meta position, but their amount is significantly less than the amount of substitution products in the ortho-para position.

Halogenation benzene and many aromatic compounds, the action of the halogen itself proceeds only in the presence of catalysts such as ZnCl 2 , AlCl 3 , FeBr 3 , etc. The catalysts are usually Lewis acids. A bond is formed between the metal atom and the halogen atom by the donor-acceptor mechanism, which causes the polarization of the halogen molecule, enhancing its electrophilic character. The resulting adduct can undergo dissociation with the formation of a complex anion and a halogen cation, which further acts as an electrophilic particle:

They can also be used as halogenating agents. aqueous solutions BUT-Hal in the presence strong acids. The formation of an electrophilic particle in this case can be explained by the following reactions:

The mechanism of further interaction of Br + or Cl + cations is no different from the mechanism of nitration with NO 2 + cations. Let us consider the reaction mechanism using the example of aniline bromination (we restrict ourselves to the formation of monosubstituted products). As is known, aniline devalues ​​bromine water, eventually forming 2,4,6-tribromaniline, which is released as a white precipitate:

The resulting electrophilic species attacks the p-electrons of the benzene ring, forming a p-complex. From the resulting p-complex, two main s-complexes in which the carbon-bromine bond occurs in the ortho- and para-positions of the cycle. At the next stage, the elimination of a proton occurs, which leads to the formation of monosubstituted aniline derivatives. In excess of the reagent, these processes are repeated, leading to the formation of aniline dibromo and tribromo derivatives.

Alkylation(replacement of a hydrogen atom by an alkyl radical) of aromatic compounds is carried out by their interaction with haloalkanes (Friedel-Crafts reaction). The interaction of primary alkyl halides, for example, CH 3 Cl, with aromatic compounds in the presence of Lewis acids differs little in its mechanism from halogenation reactions. Consider the mechanism using the example of methylation of nitrobenzene. The nitro group, as an orienting agent of the second kind, deactivates the benzene ring in electrophilic substitution reactions and directs the incoming group to one of the meta positions.

IN general view the reaction equation is:

The generation of an electrophilic particle occurs as a result of the interaction of a haloalkane with a Lewis acid:

The resulting methyl cation attacks the p-electrons of the benzene ring, resulting in the formation of a p-complex. The resulting p-complex then slowly turns into s-complex (carbocation), in which the bond between the methyl cation and the carbon atom of the cycle occurs mainly in positions 3 or 5 (i.e., in meta positions, in which partial negative charges arise due to the electronic effects of the nitro group). The final step is the elimination of a proton from s-complex and restoration of the conjugated system.

Alkenes or alcohols can also be used as alkylating agents in the alkylation of benzene instead of alkyl halides. For the formation of an electrophilic particle - a carbocation - the presence of an acid is necessary. The reaction mechanism in this case will differ only at the stage of generating an electrophilic particle. Consider this using the example of benzene alkylation with propylene and propanol-2:

Electrophilic particle generation:

In the case of using propylene as a reagent, the formation of a carbocation occurs as a result of the addition of a proton (according to the Markovnikov rule). When propanol-2 is used as a reagent, the formation of a carbocation occurs as a result of the elimination of a water molecule from protonated alcohol.

The resulting isopropyl cation attacks the p-electrons of the benzene ring, which leads to the formation of a p-complex, which then turns into s- complex with disturbed aromaticity. The subsequent elimination of a proton leads to the regeneration of the aromatic system:

Reactions acylation(replacement of the H + cation with an acyl group R-C+ =O) occur in a similar way. Consider the example of the acylation reaction of methoxybenzene, the equation of which can be represented as follows:

As in the previous cases, an electrophilic particle is generated as a result of the interaction of acetic acid chloride with a Lewis acid:

The resulting acylium cation first forms a p-complex, from which mainly two s-complexes in which the formation s- the bonds between the cycle and the electrophilic particle occur predominantly in the ortho and para positions, since partial negative charges arise in these positions due to the electronic influence of the methoxy group.

Aromatic heterocycles also enter into electrophilic substitution reactions. At the same time, five-membered heterocycles - pyrrole, furan and thiophene - more easily enter into S E reactions, since they are p-excess systems. However, when carrying out reactions with these compounds, it is necessary to take into account their acidophobicity. The instability of these compounds in an acidic environment is explained by the violation of aromaticity as a result of the addition of a proton.

When carrying out reactions, an electrophilic particle replaces a proton in the a-position; if both a-positions are occupied, then the substitution proceeds at the b-position. Otherwise, the mechanism of electrophilic substitution reactions is similar to the cases considered above. As an example, we give the bromination of pyrrole:

The reaction mechanism involving aromatic heterocycles includes all the stages discussed above - the generation of an electrophilic particle, the formation of a p-complex, its transformation into s- complex (carbocation), the removal of a proton, leading to the formation of an aromatic product.

When carrying out electrophilic substitution reactions involving p-deficient aromatic systems, such as pyridine and pyrimidine, one must take into account their initially lower reactivity (the deficit of p-electron density hinders the formation of the p-complex and its transformation into s- complex), which decreases even more when reactions are carried out in an acidic medium. Although the aromaticity of these compounds is not disturbed in an acidic medium, the protonation of the nitrogen atom leads to an increase in the deficit of p-electron density in the cycle.

Pyridine can be alkylated, sulfonated, nitrated, acylated, and halogenated. However, in most cases, the more nucleophilic nitrogen atom, rather than the pyridine carbon atoms, forms a bond with the electrophilic particle.

In the case of a reaction in the pyridine ring, the substitution occurs at one of the b-positions, in which partial negative charges arise.

Arenes are characterized by three types of reactions:

1) electrophilic substitution S E Ar (destruction S-N connections);

2) addition reactions (destruction of the p-bond);

3) reactions with the destruction of the benzene ring.

Electrophilic substitution in arenes (S E Ar)

Electrophilic substitution reactions proceed according to the general scheme through the formation of π- and σ-complexes

As follows from the presented scheme, the aromatic substitution S E Ar proceeds by the addition-elimination mechanism. Behind the addition of an electrophilic agent X + an aromatic substrate with the formation of a σ-complex is followed by the elimination of a proton with the formation of a reaction product.

Electrophilic substitution reactions in arenes generally follow a second-order kinetic equation ( v = k2[X+]).

Let's consider the stepwise flow of the process.

Stage 1 Formation of π-complexes

.

π–Complexes – coordination compounds in which the electron donor is an aromatic compound having easily polarizable π-electrons. π-complexes – not classic chemical compounds, in which the electrophilic particle binds to covalent bond with any covalent atom of the reactant. Most π-complexes easily decompose when heated or when exposed to water.

The ability to form π-complexes in arenes increases in the series:

C 6 H 6< C 6 Н 5 СН 3 < п - СН 3 –С 6 Н 4 –СН 3 ~ п - СН 3 –О–С 6 Н 4 СН 3 <

<м - СН 3 –С 6 Н 4 -СН 3 < 1,3,5 (СН 3) 3 С 6 Н 3

The greater the π-electron density of a compound, the more easily it forms π-complexes.

Stage 2 Formation of σ-complexes

σ-Complexes are cations, in the formation of which the reagent X + forms a covalent bond with one of the carbon atoms due to 2 π-electrons of the benzene nucleus, while this C-atom passes from sp 2-states in sp 3-hybridization, in which all four of its valences are at an angle of ~109 0 . The symmetry of the benzene nucleus is broken. Group X and the hydrogen atom are in a plane perpendicular to the plane of the benzene nucleus.

The stability of σ-complexes increases with an increase in the basicity of the benzene ring

This step is the slowest step in the entire reaction and is called limiting.

Stage 3 Detachment of a proton from a σ-complex

In the last stage, the proton is split off from the σ-complex and the 6π-electron cloud (aromatic structure) is restored. This process proceeds with an energy gain of ~42 kJ/mol. In many reactions, the removal of a proton at the final stage is facilitated by the corresponding base present in the solution.

According to the considered mechanism, the following reactions proceed in arenes.

However, the proposed scheme should not be considered as absolutely proven and universal. In various processes, the course of the reaction is influenced by:

Ø substrate structure;

Ø chemical activity of the reagent;

Ø conditions for the process;

Ø the nature, activity of the catalyst and other factors, which may lead to deviation in particular cases from the proposed process scheme.

Consider some examples of electrophilic substitution in benzene.

Example 1 Bromination of benzene

Molecular bromine is too weak an electrophilic agent and, in the absence of a catalyst, does not react with benzene.

Most often, the benzene bromination reaction is carried out in the presence of iron (III) bromide, which plays the role of a Lewis acid, the latter is obtained in the reaction mass by direct interaction of bromine with iron

Stage 1 Formation of electrophilic reagent E + .

The bromine molecule is activated according to the scheme of an acid-base reaction with a Lewis acid.

Stage 2 Formation of π-complex 1.

Free bromonium ion or ion in the composition of an ion pair is an active electrophilic agent capable of reacting with benzene; in this case, the π-complex 1

The role of the electrophilic agent at this stage can also be performed by the donor-acceptor complex .

Stage 3 Rearrangement of π-complex 1 and formation of σ-complex, or arenonium ion.

This is the slowest step in the entire reaction.

Stage 4 Rearrangement of the σ-complex into the π-complex 2 of the substitution product. The proton is split off from the carbon atom, which is being replaced; in the cycle, an aromatic sextet of electrons is formed again - rearomatization is observed

Stage 5 Dissociation of the π-complex 2 with the formation of a substitution product

The mechanism of electrophilic bromination of benzene is illustrated by the energy diagram of the reaction shown in Fig.11.

Rice. 11. Energy diagram of the reaction

electrophilic bromination of benzene;

PS - transition state.

Stages 2 and 5, which include π-complexes of the starting arene and the substitution product, are often omitted in schemes of the mechanism of electrophilic aromatic substitution. With this approach, the proper electrophilic aromatic substitution includes only three stages.

Stage 1" - the formation of an electrophilic agent.

Stage 2" – formation of the σ-complex, bypassing the π-complex 1.

Stage 3" is the decay of the σ-complex with the formation of a substitution product, bypassing the π-Complex 2.

Example 2 Nitration of Arenes

Nitration consists in replacing the hydrogen atom of the benzene ring with the nitro group NO 2. Benzene reacts with concentrated nitric acid slowly even when heated. Therefore, nitration is most often carried out by the action of a more active nitrating agent - nitrating mixture- mixtures of concentrated nitric and sulfuric acids. Nitration of arenes with a nitrating mixture is the main method for obtaining aromatic nitro compounds.

Nitration of benzene with a nitrating mixture is carried out at 45–50 0 C. Since the nitration reaction is irreversible, nitric acid is used in a minimal excess (5–10%), achieving almost complete conversion of benzene.

Sulfuric acid in the composition of the nitrating mixture is necessary to increase the concentration of the electrophilic agent - nitronium ion NO 2 +.

Stage 1 Formation of an electrophilic agent.

The active electrophilic agent in nitration is the nitronium ion, which is potentially found in a whole genus of compounds.

For example: HO _ NO 2 , O 2 N _ O _ NO 2 , etc.

Their propensity to form a nitronium ion increases with an increase in the electronegativity of the substituent associated with the nitro group.

The hydroxyl group as such cannot be split off, therefore, the nitronium ion from nitric acid is formed only in an acidic environment.

In the simplest case, nitric acid can protonate itself ("self-protonization")

However, the equilibrium is shifted to the left, so nitric acid nitrates weakly.

When concentrated sulfuric acid is added, the concentration of - cation increases greatly

The nitrating effect of a mixture of nitric and sulfuric acid (nitrating mixture) is much stronger than that of nitric acid alone. A further increase in reactivity can be achieved by using fuming nitric acid and oleum.

Stage 2 Formation of the σ-complex

Stage 3 Ejection of a proton with the formation of a substitution product

In practice, it is necessary to coordinate the activity of the nitrating agent with the reactivity of the aromatic nucleus.

Thus, for example, phenols and ethers of phenols are nitrated with already dilute nitric acid, while the nitration of benzaldehyde, benzoic acid, nitrobenzene, etc. requires a mixture of fuming nitric acid with sulfuric acid.

m-Dinitrobenzene is hardly nitrated even with a mixture of fuming nitric and sulfuric acids (5 days, 110 0 C; 45% yield).

In nitration, the most common side reaction is oxidation. It is favored by an increase in the reaction temperature. The oxidation process is determined by the release of nitrogen oxides. Aldehydes, alkylaryl-ketones and, to a lesser extent, alkylbenzenes are also subject to oxidation during nitration.

Example 3 Alkylation of Arenes

R-HIg, ROH, R-CH=CH 2 can be used as alkylating agents in the presence of appropriate catalysts (eg AICI 3 , AIBr 3 , H 2 SO 4 ).

Catalysts generate (form) an electrophilic particle - carbocation

Alkylation reactions have three major limitations:

1) the reaction is difficult to stop at the stage of monoalkylation, i.e. it proceeds further, with the formation of polyalkylbenzenes; an excess of arene is usually used to suppress polyalkylation;

2) if there are only electroacceptor substituents in the arena (for example, -NO 2), then the alkylation reaction cannot be carried out;

3) the alkylation reaction is accompanied by a rearrangement of the alkyl radical.

The rearrangement of an alkyl radical into the most stable one is a characteristic property of carbocations

Orientation rules

Hydrogen substitution reactions in benzene proceed in the same way at any carbon atom, since the benzene molecule is symmetrical. However, if benzene already has a substituent, then the positions remaining free for electrophilic substitution reactions become unequal.

The patterns that determine the directions of substitution reactions in the benzene nucleus are called orientation rules.

–activating group- a substituent that makes the benzene ring more reactive in electrophilic substitution reactions compared to unsubstituted benzene.

–Deactivating group- a substituent that makes the benzene ring less reactive in electrophilic substitution reactions compared to unsubstituted benzene.

- o-, p-orientant- a substituent that directs the attack of the electrophile mainly to the o- or p-position of the benzene ring.

– m-orientator is a substituent that directs the attack of the electrophile mainly to the m-position of the benzene ring.

In general, electrophilic substitution in monosubstituted benzene can proceed in three directions

The reactivity of carbon atoms in this case is determined by three factors:

1) the nature of the existing substituent;

2) the nature of the acting agent;

3) reaction conditions.

According to their influence on the orientation in these reactions, all substituents are divided into two groups: substituents of the first kind (ortho-, para-orienting agents) and substituents of the second kind (meta-orienting agents).

Introduction

Electrophilic substitution reactions - substitution reactions in which the attack is carried out by an electrophile (a particle having a deficit of electrons), and when a new bond is formed, the particle is split off without its electron pair (SE-type reactions).

General view of the reaction

Electrophilic agents

Electrophilic agents can be conditionally divided into 3 groups:

.Strong electrophiles:

.NO2+(nitronium ion); complexes of Cl2 or Br2 with various Lewis acids (FeCl3, AlBr3, AlCl3, SbCl5, etc.); H2OCl + , H2OBr + , RSO2+ , HSO3+ , H2S2O7 .

.Medium strength electrophiles:

Complexes of alkyl halides or acyl halides with Lewis acids (RCl. AlCl3,. AlCl3, etc.); complexes of alcohols with strong Lewis and Bronsted acids (ROH. BF3, ROH. H3PO4, ROH. HF).

.Weak electrophiles:

Cations of diazonium, iminium CH2=N+ H2, nitrosonium NO+ (nitrosoyl cation); carbon monoxide (IV) CO2.

Strong electrophiles interact with compounds of the benzene series containing both electron-donating and practically any electron-withdrawing substituents. Electrophiles of the second group react with benzene and its derivatives containing electron-donating (activating) substituents or halogen atoms, but usually do not react with benzene derivatives containing strong deactivating electron-withdrawing substituents (NO2, SO3H, COR, CN, etc.). Finally, weak electrophiles interact only with benzene derivatives containing very strong electron-donating (+M)-type substituents (OH, OR, NH2, NR2, O-, etc.).

Mechanism types

There are two possible mechanisms for replacing a proton in an aromatic molecule by an electrophilic reagent.

.The elimination of a proton can occur simultaneously with the formation of a new bond with the electrophilic reagent E, and the reaction in this case will go in one stage:

For a synchronous process, the charge change on the substrate during the reaction should be relatively small. In addition, since the CH bond is broken at the rate-determining stage of the reaction, it can be expected that, under a synchronous mechanism, the reaction should be accompanied by a significant kinetic hydrogen isotope effect.

Initially, the electrophilic agent is attached to π- system of the aromatic nucleus, a low-stable intermediate is formed. Next, a proton is split off from the resulting cation under the action of a base, which can be a solvent molecule:

Reactions proceeding according to this mechanism should be characterized by a high rate sensitivity to the electronic effects of substituents, since the intermediate is a cation. In addition, if the rate-determining step is the first step, in which C-H bond breaking does not occur, the reaction should not be accompanied by a significant kinetic isotope effect.

The interaction of aromatic compounds with electrophilic reagents can lead to the formation of two types of complexes, which can be intermediates in electrophilic substitution reactions. If the electrophilic agent does not significantly destroy the electronic π- aromatic nucleus system, are formed π- complexes.

Existence π- complexes is confirmed by UV spectroscopy data, changes in solubility, vapor pressure, freezing temperatures. Education π- complexes has been proven, for example, for the interaction of aromatic hydrocarbons with hydrogen chloride or the Ag+ ion:

Since the electronic structure of the aromatic ring changes insignificantly (one can draw an analogy between these complexes and complexes with charge transfer), upon formation π -complexes, there are no significant changes in the spectra, no increase in electrical conductivity is observed. Influence of electronic effects of substituents in the aromatic ring on stability π- complexes is relatively small, since the charge transfer in π -complexes small.

When aromatic hydrocarbons are dissolved in liquid hydrogen fluoride, the aromatic hydrocarbon molecule is protonated with the formation of an arenonium ion, and complexes of a different type are obtained - δ- complexes.

Sustainability δ -complexes (arenonium ions), in contrast to the stability -complexes depends very strongly on the number and nature of substituents in the benzene ring. .

education δ -complexes contributes to the stabilization of the counterion due to interaction with boron(III) fluoride or other Lewis acids:

In the presence of Lewis acids δ -complexes are also formed with hydrogen chloride.

Intermediate δ- the complex has several resonant structures and is very reminiscent of the "superallyl cation" in that the positive charge in it is distributed over three of the five available p-orbitals. This system includes two identical ortho-carbon atoms with respect to the sp3-hybridized carbon atom and one para-carbon atom with respect to the same atom. The two equivalent meta positions of the ring carry no formal charge, but they certainly have a slightly electropositive character due to the adjacent positively charged carbons:

At education δ -complexes there is a sharp increase in the electrical conductivity of the solution.

The main route for the conversion of arenonium ions in solution is proton abstraction with the regeneration of the aromatic system.

Since an integer positive charge is localized in the aromatic ring during the formation of the arenon ion, the influence of the electronic effects of substituents on the relative stability δ -complexes should be much more than in the case π- complexes.

Thus, it can be expected that the electrophilic substitution reaction will proceed through the formation step first π- complex and then δ- complex.

Isomeric δ- complexes

In a transitional state prior to formation δ -complex, between the C6H5X monosubstituted benzene molecule and the positively charged electrophile E+, the charge is shared between the attacking electrophile and the benzene ring. If the transition state is “early” (similar to reagents), then the charge in the benzene ring is small and is mainly localized on the electrophile, and if the transition state is “late” (similar to the arenonium ion), then the charge is mainly localized on the carbon atoms of the benzene ring. For reactions of monosubstituted benzenes, four complexes can exist: ortho-, meta-, para-, and ipso-:

ortho- meta- pair- ipso-

In accordance with this, there can be four different transition states, the energy of which depends on the degree of interaction of the substituent X with the positive charge of the ring. In the "late" transition state, the polar effect of the X substituent should be more pronounced than in the "early" transition state, but the effect of the same substituent should be qualitatively the same.

Hydrogen substitution products are formed from ortho-, meta-, and para-complexes (by elimination of a proton), but a substitution product of the X group can be formed from the ipso complex by elimination of the X+ cation. ipso-substitution is characteristic of organometallic compounds; as a rule, in them the metal is replaced more easily than the proton:

Substituent classification

Currently, substituents are divided into three groups, taking into account their activating or deactivating effect, as well as the orientation of the substitution in the benzene ring.

1.Activating ortho-para-orienting groups. These include: NH2, NHR, NR2, NHAc, OH, OR, OAc, Alk, etc.

2.Deactivating ortho-para-orienting groups. These are the halogens F, Cl, Br and I.

These two groups (1 and 2) of substituents are called orientants of the first kind.

3.Deactivating meta-orienting groups. This group consists of NO2, NO, SO3H, SO2R, SOR, C(O)R, COOH, COOR, CN, NR3+, CCl3, etc. These are orientants of the second kind.

Naturally, there are also groupings of atoms of an intermediate nature, which determine the mixed orientation. For example, these include: CH2NO, CH2COCH3, CH2F, CHCl2, CH2NO2, CH2CH2NO2, CH2CH2NR3+, CH2PR3+, CH2SR2+, etc.

Examples of the influence of orientants:

Basic reactions of electrophilic aromatic substitution

Nitration.

One of the most widely studied substitution reactions in aromatic systems is nitration.

Different arenas are nitrated in a wide variety of conditions. Most often, nitric acid mixed with sulfuric acid or nitric acid in organic solvents: acetic acid, nitromethane, etc. is used as a nitrating agent.

Unsubstituted benzene is usually nitrated with a mixture of concentrated nitric and sulfuric acids at 45-50°C. This reagent is called a nitrating mixture.

It has been established that in electrophilic nitration, regardless of the nature of the nitrating agent, the active electrophile is the nitronium ion NO2+. In an excess of concentrated sulfuric acid, nitric acid is quantitatively converted to nitronium hydrogen sulfate:

When sulfuric acid is diluted with water, the concentration of the NO2+ ion decreases and, at the same time, the nitration rate drops sharply. However, very reactive arenes are nitrated even under conditions where it is impossible to detect the NO2+ ion in solution by any physical methods. There is evidence that even in the absence of sulfuric acid, nitration is carried out by the nitronium ion.

Under such conditions, the reactions of very active arenes have zero kinetic order with respect to the aromatic substrate (the slow stage is the formation of NO2+ without the participation of ArH). Under the same conditions, for less reactive arenes, the kinetic order with respect to ArH is first; the rate-limiting stage is already the process of substitution itself. A similar effect was observed, for example, in the nitration of toluene with an aqueous solution of nitric and sulfuric acids. At a low concentration of H2SO4, the order with respect to toluene was zero, and at a higher concentration, it was first.

When a nitrating mixture (HNO3 + H2SO4) is used as a reagent, the concentration of nitronium ions in the solution is always quite high and is constant with an excess of the reagent, so nitration can be considered as a two-stage process.

The slow stage of this two-stage process is the formation -complex. This is proved by the absence of the kinetic isotope effect of hydrogen during the nitration of arenes and deuteroarenes. However, the introduction of very bulky groups on both sides of the substituting hydrogen can greatly reduce the rate of the k2 step and lead to the appearance of an isotope effect.

Halogenation (for example, bromination) of benzene by the action of the halogen itself proceeds only in the presence of catalysts such as ZnCl2, FeBr3, A1Br3, etc. The catalysts are usually Lewis acids. They cause some polarization of the halogen molecule, thereby enhancing its electrophilic character, after which such a polarized molecule attacks π -electrons of an aromatic ring by a site carrying a positive charge:

After the bromine bond is cleaved, bromine is formed δ- complex with benzene, from which the resulting negatively charged complex -Br FeBr3 abstracts a proton, giving bromine-benzene.

Aqueous solutions of HO-Hal can also be used as halogenating agents, of course in the presence of strong acids. There is reliable evidence that, for example, during chlorination, the chlorinating agent is the Cl + ion formed as a result of the reaction:

The mechanism of further interaction of Cl+ ions with benzene does not differ from the mechanism of nitration with NO2+ ions. The similarity of these two processes is confirmed by the fact that the acid HOCl itself, like HNO3, interacts very weakly with benzene; in both cases, strong acids are required to release Cl+ and NO2+ ions by protonation of "carrier molecules":

Further evidence that the substitution agents are halogen cations or complexes containing a polarized halogen was obtained by studying reactions between interhalides and aromatics. So, for example, the action of BrCl leads only to bromination, and ICl only to iodination, i.e., a less electronegative halogen is always introduced into the molecule of an aromatic compound, which in the initial molecule of the interhalide compound carries a partial positive charge, for example:

δ+ δ- →Cl

Sulfonation.

There is still no consensus as to the true nature of the electrophilic sulfonating agent. The data of kinetic measurements do not provide an unambiguous answer to this question, since aqueous and anhydrous sulfuric acid contains a large number of potential electrophilic agents, the relative concentration of which depends on the H2O/SO3 ratio.

At a concentration of sulfuric acid below 80%, the following equilibria are mainly established:

At a higher concentration of sulfuric acid in the range of 85-98%, the state of sulfuric acid is mainly described by the equations:

In 100% sulfuric acid and in oleum, in addition to H2S2O7, there are other polysulfuric acids - H2S3O10; H2S4O13 etc. All this makes it extremely difficult to interpret data on the sulfonation kinetics.

In aqueous sulfuric acid at a concentration below 80%, the sulfonation rate correlates linearly with the activity of the H3SO4+ ion. At a sulfuric acid concentration above 85%, a linear correlation with the activity of H2S2O7 is observed. These two species appear to be the two main real electrophilic agents for the sulfonation of aromatic compounds in aqueous sulfuric acid. They can be considered as a SO3 molecule coordinated respectively with an H3O+ ion or sulfuric acid. When passing from 85% to 100% sulfuric acid, the concentration of the H3O+ ion sharply decreases, while the concentration of H2SO4 increases. In 91% acid = , but since H2S2O7 (SO3 . H2SO4) is a stronger electrophilic agent than H3SO4+ (H3O+ . SO3), it dominates as an electrophile not only in 91%, but even in 85% sulfuric acid.

Thus, the mechanism of sulfonation can be represented, apparently, as follows:

The kinetic isotope effect kH/kD at sulfuric acid concentrations below 95% is negligible. However, upon sulfonation with 98–100% H2SO4 or oleum, the kinetic isotope effect kH/kD is observed in the range of 1.15–1.7; stage (2) becomes the rate-determining stage. At a sulfuric acid concentration below 95%, a proton from -complex is cleaved off by the hydrosulfate ion HSO4-, and at a higher concentration of sulfuric acid, H2SO4 itself plays the role of a very weak base. Therefore, the rate of stage (2) decreases sharply, and a kinetic isotope effect is observed.

In oleum, the rate of sulfonation increases sharply. The electrophilic agent in this case, apparently, is the non-complexed SO3. Stage (2) is slow.

Alkylation according to Friedel-Crafts.

The S. Friedel-J. Crafts reaction (1877) is a convenient method for the direct introduction of an alkyl group into an aromatic ring. Alkylation of aromatic compounds is carried out under the action of alkyl halides, only in the presence of a suitable Lewis acid as a catalyst: AlBr3, AlCl3, GaBr3, GaCl3, BF3, SbF5, SbCl5, FeCl3, SnCl4, ZnCl2, etc.

The most active catalysts are anhydrous sublimated aluminum and gallium bromides, antimony pentafluoride, aluminum and gallium chlorides, iron (III) halides, SbCl5 are less active, SnCl4 and ZnCl2 belong to inactive catalysts. In general, the activity of Lewis acids as benzene alkylation catalysts decreases in the series AlBr3> GaBr3> AlCl3> GaCl3> FeCl3> SbCl5> TiCl4> BF3> BCl3> SnCl4> SbCl3. The most common catalyst for this reaction is pre-sublimated aluminum chloride.

For example, the mechanism of the benzylation reaction with benzyl chloride in nitrobenzene in the presence of anhydrous AlCl3 as a catalyst is as follows:

where B: \u003d AlCl4-; H2O or other base. The reaction rate is limited by the second stage.

The exact structure of the intermediate (RCl .AlCl3) is unknown. In principle, it is possible to represent a whole range of structures from the molecular complex to dissociated carbocations.

The participation of free carbocations as alkylating agents is unlikely.

If the alkylating agents were free carbocations, then the slow stage would be the stage of their formation (k1), and the reaction with arenes would be fast and the third order should not be observed. It is highly unlikely that the alkylating agent is a molecular complex. At low temperatures, it is sometimes possible to isolate complexes of alkyl halides with Lewis acids. They are characterized by a slow exchange of halogens according to the scheme:

The exchange rate increases in the series prim.R< втор.R<трет.R, что можно объяснить и ион-парным строением, и структурой координационного аддукта.

Many researchers working in this field believe that the structure of the RX. MXn gradually changes from the structure of the coordination adduct in the case of R=CH3 to the structure of an ion pair in the case of R=t-Bu, but this has not yet been confirmed experimentally.

The ability of the halogen atom in RX to complex with AlCl3 or another hard Lewis acid sharply decreases from fluorine to iodine, as a result of which the activity of alkyl halides as alkylating agents in the Friedel-Crafts reaction also decreases in the series RF> RCl> RBr> RI. For this reason, alkyl iodides are not used as an alkylating agent. The difference in the activity of alkyl fluorides and alkyl bromides is so great that it allows selective substitution of fluorine in the presence of bromine in the same molecule.

Friedel-Crafts acylation

The introduction of an acyl group into an aromatic ring using an acylating agent and a Lewis acid is called a Friedel-Crafts acylation. Acylating agents are usually acid halides and anhydrides in the presence of aluminum halides, boron trifluoride or antimony pentafluoride as Lewis acids. Acyl halides and acid anhydrides form 1:1 and 1:2 donor-acceptor complexes with Lewis acid. It was found by spectral methods that aluminum chloride, boron trifluoride and antimony pentafluoride are coordinated to the carbonyl oxygen atom, since it is more basic than the neighboring chlorine atom. The electrophilic agent in the acylation reaction of aromatic compounds is either this donor-acceptor complex or the acylium cation formed during its dissociation.

It can be assumed that the slow stage of the reaction is the attack of one of the three electrophiles (RCO+ , RCOCl . AlCl3, RCOCl . Al2Cl6) on the arene, leading to -complex. The effectiveness of these acylating species depends on the nature of the substrate, acyl halide and solvent, as well as on the amount of catalyst taken.

In the acylation of arenes with acyl halides catalyzed by aluminum chloride or bromide in polar aprotic solvents (nitrobenzene, nitromethane, etc.), the acylium cation is the acylating agent, while in a low-polarity medium (methylene chloride, dichloroethane, or tetrachloroethane), a donor-acceptor complex takes part in the reaction . The nature of the acyl halide also influences the formation and stability of the acyl salts. Mechanism of Friedel-Crafts Acylation of Arenes Under the Action of a Donor-Acceptor Complex

described by the following diagram:

An aromatic ketone is a stronger Lewis base than an acyl halide and forms a stable complex with AlCl3 or another Lewis acid. Therefore, for the acylation of aromatic compounds with acyl halides, a slightly more equimolar amount of catalyst is required, and for acylation with acid anhydrides, two moles of catalyst (because they contain two carbonyl oxygen atoms). The ketone is isolated by decomposing its complex with AlCl3 with water or hydrochloric acid.

Acylation according to Friedel-Crafts is completely devoid of the disadvantages that are inherent in the alkylation reaction. During acylation, only one acyl group is introduced, since aromatic ketones do not enter into further reaction (as well as other arenes containing strong electron-withdrawing groups: NO2, CN, COOR). Another advantage of this reaction over alkylation is the absence of rearrangements in the acylating agent. In addition, disproportionation reactions of the reaction products are not typical for acylation.

Bibliography

substitution aromatic molecule reaction

1.Kurts A L., Livantsov M.V., Livantsova L.I. Electrophilic substitution in the aromatic series: Methodological development for students of the third year. - Moscow, 1997.

2.Dneprovsky A.S. and other Theoretical foundations of organic chemistry / A.S. Dneprovskiy, T.I. Temnikova: Textbook for universities. - 2nd ed., Revised. - L.: Chemistry, 1961. - 560s.

3.Terney A. Modern organic chemistry. Volume 1: Textbook. - Mir, 1981.-680s.

.Reutov O.A., Kurts A.L., Butin K.P. Organic Chemistry: Textbook - M.: MGU, 1999. - 560s.

.Sykes P. Reaction mechanisms in organic chemistry. Per. from English. ed. Prof. Warsaw Ya. M. Ed. 3rd, M., "Chemistry", 1977. - 320s.

The most widely used benzene reaction is the replacement of one or more hydrogen atoms by an electrophilic group. Many important substances are synthesized in this way. The choice of functional groups that can thus be introduced into aromatic compounds is very wide, and in addition, some of these groups can be transformed into other groups after introduction into the benzene ring. The general reaction equation is:

Below are the five most common reactions of this type and examples of their use.

Nitration:

Sulfonation:

Dkylation according to Friedel-Crafts:

Friedel-Crafts acylation:

Halogenation (only chlorination and bromination):

The following reactions are often used to further transform compounds resulting from aromatic electrophilic substitution.

Side chain recovery:

Recovery of the nitro group:

Diazotization and further transformations

Aniline and its substituted compounds can be converted into highly reactive compounds called diazonium salts:

Diazonium salts serve as starting materials for the synthesis of a wide variety of aromatic compounds (Scheme 9-1). In many cases, the method of synthesis through diazonium salts is the only way to introduce any functional group into an aromatic compound.

The replacement of the diazonium group by chlorine and bromine atoms, as well as by the cyano group, is achieved by the interaction of diazonium salts with copper salts (1). Iodine and fluorine atoms cannot be introduced into the aromatic ring by direct halogenation. Aromatic iodides and fluorides are obtained by treating diazonium salts with potassium iodide and hydroboric acid, respectively.

Aromatic carboxylic acids can be obtained either by hydrolysis of the nitrile group, or by the action of carbon dioxide on a Grignard reagent (more on this reaction will be discussed in Chapter 12). Phenols in the laboratory are most often obtained by hydrolysis of diazonium salts.

Diagram 9-2. Reactions of diazonium salts

The diazonium group (and hence also the amino group and the nitro group) can be removed (i.e., replaced by a hydrogen atom) by acting on the diazonium salts of hypophosphorous acid

Finally, the interaction of diazonium salts with activated aromatic compounds leads to the formation of azo dyes. Dyes can be of very different colors depending on the nature of the substituents on both aromatic rings.

Nitrous acid, which is used to prepare diazonium salts, is a low-stable substance and is prepared in situ (i.e., directly in the reaction vessel) from sodium nitrite and hydrochloric acid. In the reaction scheme, treatment with nitrous acid can be shown in one of two ways, which are applied below:

Here are some examples of reactions of diazonium salts:

Obtaining practically important substances using electrophilic substitution reactions

Dyes. The synthesis of methyl orange is shown below. If you take the original compounds with other substituents in aromatic rings, then the color of the dye will be different.

Polymers. Polystyrene is obtained by polymerization of styrene (see Chap. 6), which, in turn, can be synthesized as follows. Benzene is acylated according to Friedel-Crafts, using acetic anhydride instead of acetyl chloride, the resulting ketone is reduced to an alcohol, which is then dehydrated using potassium hydrogen sulfate as an acid catalyst:

Medications. in the synthesis of sulfanilamide (streptocide), the first two steps are reactions that we have already encountered. The third stage is the protection of the amino group. This is necessary to prevent the interaction of chlorosulfonic acid with the amino group. After the group has reacted with ammonia, the protecting group can be removed.

Streptocid was one of the first antimicrobials of the sulfonamide group. It is applied even now.

Electrophilic substitution reactions allow many different groups to be introduced into the aromatic ring. Many of these groups can then be transformed during synthesis.

Mechanism of aromatic electrophilic substitution

It has been established that electrophilic substitution in aromatic compounds proceeds in two stages. First, an electrophile (which can be generated by various methods) is attached to the benzene ring. In this case, a resonantly stabilized carb cation is formed (below in parentheses). This cation then loses a proton and turns into an aromatic compound.

Here, for clarity, the formulas of aromatic compounds are shown with double bonds. But you, of course, remember that in fact there is a cloud of delocalized electrons.

Below are the mechanisms of the two reactions, including the electrophile generation step. Haogenation

Electrophile generation:

Substitution:

Friedel-Crafts acylation Electrophile generation:

Substitution:

Influence of deputies

When a substituted benzene reacts with an electrophile, the structure of the substituent already present on the benzene ring has a significant effect on the orientation of the substitution and on its rate.

According to their effect on the rate and orientation of electrophilic substitution, all possible substituents can be divided into three groups.

1. Activating orthopara-orientants. In the presence of a substituent of this group in an aromatic compound, it reacts faster than unsubstituted benzene, and the electrophile goes to the ortho and para positions to the substituent and a mixture of ortho and para disubstituted benzenes is formed. This group includes the following substituents:

2. Deactivating meta-orienting agents. These substituents slow down the reaction compared to benzene and direct the electrophile to the meta position. This group includes:

3. Deactivating ortho-, paraorientants. This group includes atoms of alogens.

Orientation examples for electrophilic substitution:

Explanation of the influence of substituents

Why do different substituents have such a different effect on the nature of the electrophilic substitution? The answer to this question can be obtained by analyzing the stability of the intermediates formed in each case. Some of these intermediate carbocations will be more stable, others less stable. Recall that if a compound can react in more than one way, the reaction will take the route that produces the most stable intermediate.

Shown below are the resonance structures of intermediate particles formed during the electrophilic attack of a cation in the ortho-meta- and para-positions of phenol, which has a powerful activating substituent - ortho, para-orienting, toluene, which has a substituent with the same, but much less pronounced properties, and nitrobenzene, available in which the nitro group is a megd orientant and deactivates the ring:

When an electrophile is attacked in both the ortho and para positions of the phenol, more resonance structures can be written for the emerging intermediate than for the intermediate upon meta substitution. Moreover, this "extra" structure (circled in a box) makes a particularly large contribution

into the stabilization of the cation, since in it all atoms have an octet of electrons. Thus, a more stable cation arises in the ortho- or para-orientation of the attack of the electrophile than in the attack to the meta-position; therefore, the substitution occurs predominantly in the ortho- and para-positions. Since the cation arising from such a substitution is more stable than the cation formed from unsubstituted benzene, phenol enters into electrophilic substitution reactions much more easily than benzene. Note that all substituents that strongly or moderately activate an aromatic ring in electrophilic substitution reactions have a single lone atom attached to the ring. These electrons can be fed into the ring. In this case, a resonant structure arises with a positive charge on an electronegative atom (oxygen or nitrogen). All this stabilizes the intermediate and increases the reaction rate (resonant activation).

In the case of toluene, substitution in both the ortho- and d-positions results in a more stable cation than when an electrophile attacks in the meta-position.

In the boxed resonant structures, the positive charge is on the tertiary carbon atoms (tertiary by carbocation, see Chapter 5). When attacked in the meta position, the tertiary carbocation does not occur. Here again, the ortho- and para-substitution goes through slightly more stable intermediate species than the meta-substitution and than the substitution in benzene itself. Therefore, the substitution in toluene is directed to the ortho and para positions and proceeds somewhat faster than the substitution in Lysol (activation due to the inductive effect).

All deactivating groups, including the nitro group, have the property of withdrawing electrons from the aroma ring. The result of this is the destabilization of the intermediate cation. Especially

(click to view scan)

the intermediates that arise upon attack in the ortho and para positions are strongly destabilized, since the partial positive charge is located directly next to the nitro group (the corresponding resonance structures are circled). Therefore, meta-substitution is preferred over ortho- and para-substitution. Nitrobenzene undergoes electrophilic substitution much more difficult than benzene, since the electron density in the ring is lowered and the mutual attraction of the aromatic ring and the electrophile is weakened.

Electrophilic addition reactions proceed in two stages through the formation of an intermediate cation. Different substituents on the benzene ring have different effects on the rates and orientations of substitution. This influence can be explained taking into account the stability of the intermediates formed in each case.