When there is an excess of bromine, another molecule of it joins at the site of the remaining double bond to form 1,2,3,4-tetrabromobutane.

Diene conjugation

The conjugation of bonds in a non-reacting molecule is called the static conjugation effect.

If a compound with a system of conjugated bonds reacts, then due to the mutual overlap of p-electron clouds at the moment of reaction, a redistribution of electron density occurs throughout the entire system, which is called the dynamic conjugation effect. A characteristic feature of the system of conjugated bonds is that the redistribution of electron densities for the indicated reasons is transmitted throughout the entire system without noticeable weakening. Therefore, when an addition to the first atom of a conjugated system occurs, the electron density is redistributed throughout the entire system, and ultimately the last, fourth atom of the conjugated system turns out to be unsaturated (and therefore attaching). Thus, conjugated double bonds are a single system that behaves similarly to a single double bond.

The second very important feature of dienes with conjugated double bonds is the extreme ease of their polymerization.

Electrophilic substitution reactions(eng. substitution electrophilic reaction) - substitution reactions, in which the attack is carried out electrophile - a particle that is positively charged or has a deficiency of electrons. When a new bond is formed, the outgoing particle is electrofuge splits off without its electron pair. The most popular leaving group is the proton H+.

All electrophiles are Lewis acids.

General view of electrophilic substitution reactions:

(cationic electrophile)

(neutral electrophile)

There are aromatic (widespread) and aliphatic (less common) electrophilic substitution reactions. The nature of electrophilic substitution reactions specifically for aromatic systems is explained by the high electron density of the aromatic ring, which can attract positively charged particles.

Aromatic electrophilic substitution reactions play an extremely important role in organic synthesis and are widely used both in laboratory practice and in industry.

If, when a bond is broken, a common electron pair remains with one atom, then ions are formed - a cation and an anion. This mechanism is called ionic or heterolytic. It leads to the formation of organic cations or anions: 1) methyl chloride forms a methyl cation and a chloride anion; 2) methyllithium forms lithium cation and methyl anion.

Aromaticity criteria

There are several criteria by which a molecule can be classified as aromatic.

Hückel's rule

Molecules that obey Hückel's rule are aromatic: a planar monocyclic conjugated system containing (4n + 2)π-electrons (where n = 0,1,2...) is aromatic. This rule is derived directly from quantum chemical calculations of MOX.

Modern representations

An unsaturated cyclic or polycyclic diatropic molecule or ion can

be considered aromatic if all the atoms of the cycle are included in a completely conjugated system in such a way that in the ground state all π-electrons are located only in the bonding molecular orbitals of the annular (closed) shell.

Electron-donating substituents exhibit a +M- and +I- effect and increase the electron density in the conjugated system. These include the hydroxyl group-OH and amino group -NH 2. The lone pair of electrons in these groups enters into common conjugation with p-electronic benzene ring system and increases the length of the conjugated system. As a result, electronicdensity is concentrated in ortho and para positions:

Electron-withdrawing substituents exhibit an -M- effect and reduce the electron density in the conjugated system. These include nitrogroup-NO 2, sulfo group -SO 3 H, aldehyde -CHO and carboxyl-COUN groups. These substituents form a common conjugated system with the benzene ring, but the overall electron cloud shifts towards these groups. Thus, the total

the electron density in the ring decreases, and it decreases least of all in the meta positions.

AROMATICITY(from the Greek aroma, gender aromatos - incense), a concept characterizing a set of structural, energetic. properties and characteristics of the reaction. cyclical abilities structures with a system of conjugated connections. The term was introduced by F.A. Kekule (1865) to describe the properties of compounds structurally close to benzene, the founder of the class of aromatic compounds.

To the number of most important signs of aromaticity include the tendency to be aromatic. conn. to a substitution that preserves the system of conjugated bonds in the cycle, and not to an addition that destroys this system. In addition to benzene and its derivatives, such solutions are characteristic of polycyclic aromatic compounds. hydrocarbons (for example, naphthalene, anthracene, phenanthrene and their derivatives), as well as for isoelectronic heterocyclic conjugates. connections. It is known, however, that there are many connections. (azulene, fulvene, etc.), which also easily enter into substitution systems, but do not have all the other signs of aromaticity.

Reaction ability cannot serve as an accurate characteristic of aromaticity also because it reflects the properties of not only the basic. state of this compound, but also the transition state (activated complex) of the solution, in which this is the connection. enters. Therefore, more stringent criteria for aromaticity are associated with physical analysis. St. in the main electronic states cyclic. conjugated structures. The main difficulty is that aromaticity is not an experimentally determined characteristic. Therefore, there is no unambiguous criterion for establishing the degree of aromaticity, i.e. degree of similarity to St. benzene. Below are considered the most. important signs of aromaticity.

The structure of the electronic shell of aromatic systems.

The tendency of benzene and its derivatives to retain the structure of the conjugated ring in decomp. transformations means higher. thermodynamic and kinetic stability of this structural fragment. Stabilization (decrease in electronic energy) of a molecule or ion that has a cyclic structure, is achieved when all bonding molecular orbitals are completely filled with electrons and nonbonding and antibonding orbitals are vacant. These conditions are met when the total number of electrons in the cycle. polyene is equal to (4l + 2), where n = = 0,1,2... (Hückel's rule).

This rule explains the stability of benzene (form I) and cyclopentadienyl anion (II; n = 1). It made it possible to correctly predict the stability of cyclopropenyl (III; n = 0) and cycloheptatrienyl (IV; n = 1) cations. Due to the similarity of the electronic shells of the conn. II-IV and benzene, like higher cyclic ones. polyenes - , , annulenes (V-VII), are considered aromatic. systems.

Hückel's rule can be extrapolated to a series of conjugated heterocyclics. conn. - derivatives of pyridine (VIII) and pyrilium cation (IX), isoelectronic to benzene, five-membered heterocycles of type X (pyrrole, furan, thiophene), isoelectronic to the cyclopentadienyl anion. These compounds are also classified as aromatic. systems.

Derivatives of compounds II-X and other more complex structures obtained by isoelectronic substitution of methine groups in polyenes I-VII are also characterized by high thermodynamic properties. stability and general tendency to substitution reactions in the nucleus.

Cyclic. conjugated polyenes, which have 4n electrons in the ring (n=1,2...), are unstable and easily enter into addition reactions, because they have an open electron shell with partially filled nonbonding orbitals. Such connections, most a typical example of which is cyclobutadiene (XI), including canthiaromatic. systems.

Rules that take into account the number of electrons in a cycle are useful for characterizing the properties of monocyclics. structures, but are not applicable to polycycles. When assessing the aromaticity of the latter, it is necessary to take into account how the electronic shells of each individual cycle of the molecule correspond to these rules. They should be used with caution in the case of multi-charged cyclic batteries. ions Thus, the electronic shells of the dication and dianion of cyclobutadiene meet the requirements of Hückel’s rule. However, these structures cannot be classified as aromatic, since the dication (n = 0) is not stable in a flat form, which provides cyclic structure. conjugation, and in a bent diagonally; The dianion (n=1) is generally unstable.

Energy criteria for aromaticity. Resonance energy. To determine quantities. measures of aromaticity characterizing increased thermodynamic stability aromatic conn., the concept of resonance energy (ER), or delocalization energy, was formulated.

The heat of hydrogenation of a benzene molecule, formally containing three double bonds, is 151 kJ/mol greater than the heat of hydrogenation of three ethylene molecules. This value, associated with ER, can be considered as energy additionally expended on the destruction of the cyclic. a system of conjugated double bonds of the benzene ring that stabilizes this structure. T. arr., ER characterizes the contribution of the cyclic. conjugation into the heat of formation (total energy, heat of atomization) of the compound.

A number of theoretical methods have been proposed. ER assessments. They differ ch. arr. choosing a comparison structure (i.e. a structure in which the cyclic conjugation is broken) with the cyclic. form. The usual approach to calculating ER is to compare the electronic energies of the cycle. structure and the sum of the energies of all isolated multiple bonds contained in it. However, the calculated t. arr. ER, regardless of the quantum chemical used. method, tend to increase with increasing system size. This often contradicts experiments. data about the saints aromatic. systems. Thus, the aromaticity in the series of polyacenesbenzene (I), naphthalene (XII), anthracene (XIII), tetracene (XIV) decreases (for example, the tendency to addition increases, the alternation of bond lengths increases), and the ER (given in units = 75 kJ/ mole) grow:

The ER values ​​calculated by comparing the electronic energies of cyclic cycles do not have this drawback. structure and similar acyclic. conjugate complete (M. Dewar, 1969). Calculated t. arr. quantities are usually called Dewar ER (ED). For example, the EDP of benzene (1.013) is calculated by comparing it with 1,3,5-hexatriene, and the EDP of cyclobutadiene by comparing it = = with 1,3-butadiene.

Connections with positive values ​​of ERD are classified as aromatic, those with negative values ​​are classified as anti-aromatic, and those with ERD values ​​close to zero are classified as non-aromatic. Although the EDP values ​​vary depending on the quantum chemical approximations. calculation method, relates. their order practically does not depend on the choice of method. Below are the ERD per electron (ER/e; in units), calculated using the modified version. Hückel molecular orbital method:

Naib. ERD/e, that is, max. benzene is aromatic. A decrease in ERD/e reflects a decrease in aromatic. St. The data presented are in good agreement with established ideas about the manifestations of aromaticity.

Magnetic criteria for aromaticity. Cyclic. The conjugation of electrons leads to the appearance of a ring current in the molecule, which causes exaltation of the diamagnosis. receptivity. Since the values ​​of the ring current and exaltation reflect the effectiveness of the cyclic. pairings, they may. used as quantities. a measure of aromaticity.

Aromatic compounds include compounds whose molecules support induced diamagnetic electronic ring currents (diatropic systems). In the case of annulens (n ​​= 0,1,2...) there is a direct proportionality between the strength of the ring current and the magnitude of the electric propulsion. However, for non-alternant hydrocarbons (for example, azulene) and heterocyclic. conn. this dependence becomes more complex. In some cases, the system may simultaneously both diatropic and anti-aromatic, for example. bicyclodecapentaene.

Presence of inducers. ring current in cyclic conjugated systems characteristically manifests itself in the proton magnetic spectra. resonance (PMR), because the current creates an anisotropic magnetic field. field that significantly affects the chemical shifts of protons associated with ring atoms. Signals of protons located in the internal parts aromatic rings shift towards a strong field, and the signals of protons located on the periphery of the ring shift towards a weak field. Yes, internal protons of annulene (form VI) and annulene (VII) appear at - 60°C in the PMR spectrum, respectively. at 0.0 and -2.99m. d., and external ones at 7.6 and 9.28 ppm.

For anti-aromatic Annulene systems, on the contrary, are characterized by paramagnetic properties. ring currents leading to a shift in the external protons into a strong field (paratropic systems). Yes, chem. shift ext. protons of annulene is only 4.8 ppm.

Structural criteria for aromaticity. The most important structural characteristics of the benzene molecule are its planarity and complete alignment of bonds. A molecule can be considered aromatic if the lengths of carbon-carbon bonds in it lie in the range of 0.136-0.143 nm, i.e. close to 0.1397 nm for the benzene(I) molecule. For non-cyclical of conjugated polyene structures, the lengths of the C-C bonds are 0.144-0.148 nm, and the lengths of the C=C bonds are 0.134-0.135 nm. An even greater alternation of bond lengths is typical for antiaromatics. structures. This is supported by rigorous non-empirical data. geometric calculations parameters of cyclobutadiene and exp. data for its derivatives.

Proposed various expressions for quantities. aromaticity characteristics based on the degree of alternation of bond lengths, for example. for hydrocarbons, the aromaticity index (HOMA d) is introduced:

where a = 98.89, X r is the length of the r-th bond (in A), n is the number of bonds. For benzene, HOMA d is maximum and equal to 1, for cyclobutadiene it is minimum (0.863).

Aromaticity- a concept that characterizes a set of special structural, energetic and magnetic properties, as well as features of the reactivity of cyclic structures with a system of conjugated bonds.

Although aromaticity is one of the most important and most fruitful concepts in chemistry (not just organic), there is no generally accepted short definition of this concept. Aromaticity is understood through a set of special characteristics (criteria) inherent in a number of cyclic conjugated molecules to one degree or another. Some of these criteria are of an experimental, observable nature, but the other part is based on the quantum theory of the structure of molecules. Aromaticity has a quantum nature. It is impossible to explain aromaticity from the standpoint of classical structural theory and resonance theory.
Aromaticity should not be confused with delocalization and conjugation. In the molecules of polyenes (1,3-butadiene, 1,3,5-hexatriene, etc.) there is a clear tendency towards delocalization of electrons and the formation of a single conjugated electronic structure, which is manifested in the spectra (primarily electronic absorption spectra) , some change in bond lengths and orders, energy stabilization, special chemical properties (electrophilic 1,4-addition in the case of dienes, etc.). Delocalization and conjugation are necessary but not sufficient conditions for aromaticity. Aromaticity can be defined as the property in which a conjugated ring of unsaturated bonds exhibits greater stability than would be expected from conjugation alone. However, this definition cannot be used without experimental or calculated data on the stability of the cyclic conjugated molecule.
In order for a molecule to be aromatic, it must contain at least one ring, each of the atoms of which has a p-orbital suitable for the formation of an aromatic system. This particular cycle (ring, system of rings) is considered aromatic in the full sense of the word (if the criteria listed below are met).
This cycle should be 4n+2(i.e. 2, 6, 10, 14, 18, 22, etc.) p-electrons.
This rule is called a rule or Hückel's aromaticity criterion. The source of this rule is highly simplified quantum chemical calculations of idealized cyclic polyenes made in the early days of quantum chemistry. Further research has shown that this simple rule fundamentally gives correct aromaticity predictions even for very complex real systems.
The rule, however, must be used correctly, otherwise the forecast may be incorrect.

Which orbitals are considered suitable for the formation of an aromatic system? - Any orbitals perpendicular to the plane of the cycle, and
a) belonging to multiple (endocyclic double or triple) bonds included in the cycle;
b) corresponding to lone pairs of electrons in heteroatoms (nitrogen, oxygen, etc.) or carbanions;
c) corresponding to six-electron (sextet) centers, in particular carbocations.

Aromaticity criteria.

Energy(increasing thermodynamic stability due to delocalization of electrons, the so-called delocalization energy - DE).

You can imagine benzene as a derivative of three ethylene molecules and compare the energies of the initial fragments and the final molecule. Each ethylene molecule has 2 p-electrons (6 in total) in molecular orbitals (MO) of the same energy (α + β), and benzene has 6 electrons located in three bonding molecular orbitals, giving a total more negative value of the energy of the system (α and β is less than 0).

The apparent energy advantage is 2β = 36 kcal/mol or 1.56 eV - this is the EER (empirical resonance energy).
The energy criterion is the most inconvenient and unclear of all. The energy values ​​for this criterion are always calculated, because, as a rule, it is impossible to select the corresponding non-aromatic molecule for comparison. Therefore, one should be calm about the fact that there are many different estimates of the delocalization energy even for classical aromatic molecules, but for more complex systems these values ​​are completely absent. You can never compare different aromatic systems in terms of the magnitude of delocalization energies - you cannot conclude that molecule A is more aromatic than molecule B, because the delocalization energy is greater.
Structural- a very important, if not the most important, criterion, since it is not theoretical, but experimental in nature. The specific geometry of molecules of aromatic compounds lies in the tendency towards a coplanar arrangement of atoms and equalization of bond lengths. In benzene, the alignment of bond lengths is perfect - all six C-C bonds are the same in length. For more complex molecules, the alignment is not perfect, but it is significant. The criterion is taken as a measure of the relative deviation of the lengths of conjugated bonds from the average value. The closer to zero, the better. This quantity can always be analyzed if structural information is available (experimental or from high-quality quantum chemical calculations). The tendency towards coplanarity is determined by the advantage of the parallel arrangement of the axes of atomic p-orbitals for their effective overlap.
Magnetic(the presence of a ring current is a diatropic system, the effect on the chemical shifts of protons outside and inside the ring, examples are benzene and -annulene). The most convenient and accessible criterion, since the 1H NMR spectrum is sufficient to evaluate it. For an accurate determination, theoretical calculations of chemical shifts are used.
Chemical- tendency towards substitution reactions rather than addition reactions. The most obvious criterion that clearly distinguishes the chemistry of aromatic compounds from the chemistry of polyenes. But it doesn't always work. In ionic systems (for example, in the cyclopentadienyl anion or tropylium cation), substitution cannot be observed. Substitution reactions sometimes occur in non-aromatic systems, but aromatic systems are always capable of addition reactions to some extent. Therefore, it is more correct to call the chemical criterion a sign of aromaticity.

Representation of the energy of an aromatic system.

General formula:

E j (orbital energy of level j) = α + m j β
α is the Coulomb integral, the energy of the C2p orbital,
β - resonance integral, interaction energy of 2 atomic orbitals on neighboring atoms
m j = 2сos(2jπ/N), where N is the number of carbon atoms in the cycle.

The simplest and most visual graphic representation of energy is frost circle. To construct it, it is necessary to inscribe an aromatic molecule into a circle, pointing its vertex down, then the points of contact of the polygon and the circle will correspond to the energy levels of the MO. An energy scale is applied vertically, all levels below the horizontal diameter are binding, and above are loosening. Electrons are filled from the lowest orbital according to Pauli's rule.

The most favorable state will be when all bonding orbitals are completely filled.
Later, many more assumptions about the structure of benzene appeared:

However, even to this day, the C 6 H 6 molecule continues to present surprises. Bodrikov I.V.: “I have to admit that now there is no person in the world who knows what benzene is” (2009)

(one of the hydrogens moves to a position perpendicular to the ring)

values ​​of the lengths of single and double bonds. In the benzene molecule, all bond lengths are equal (1.395 angstroms), whereas in conjugated acyclic polyenes they alternate. In butadiene, for example, the C 1 -C 2 bond length is 1.34 Å, and the C 2 -C 3 bond length is 1.48 Å. In general, bond lengths tend to alternate in non-aromatic compounds rather than in aromatic structures. Typical values ​​of the lengths of the most important bonds of acyclic compounds are given in table. These values ​​can be compared with the bond lengths in some heteroaromatic systems, as shown in Fig. 1.

Table. Typical lengths of single and double bonds (Å) between sp 2 -hybridized atoms

C-C	1.48	C=C	1.34
C-N	1.45	C=N	1.27
C-O	1.36	C=O	1.22
C-S	1.75	C=S	1.64
N-N	1.41	N=N	1.23

The bond lengths in the four six-membered heterocycles shown in Fig. 1, will be intermediate between the values ​​for single and double bonds. The C–C bond lengths in the three six-membered monocycles differ slightly and are close to the values ​​for benzene. On this basis, we can conclude that there is significant cyclic delocalization of π electrons in these compounds. For five-membered heterocycles we see a significant alternation of bonds. Since molecules contain different heteroatoms, it would be inappropriate to compare bond lengths, but we can say that in oxygen-containing heterocycles the localization of bonds is more pronounced. However, even in these compounds, the bond lengths differ from the bond lengths of “pure” single and double bonds. In all of these five-membered heterocyclic systems, cyclic delocalization exists, but it is less than for six-membered heterocycles. In the two presented five-membered bicyclic systems (indole and indolizine), the degree of localization of bonds is much higher than, for example, in pyrrole, and this pattern is also observed in the case of other condensed systems in comparison with their monocyclic analogues.

The bond order can sometimes be estimated using vicinal spin-spin coupling constants (SSICs) in NMR spectra. For example, the coupling constants Jab and Jbc on neighboring carbon atoms a, b and c, distant from the heteroatom, should be equal if the Caa-Cb and Cb-Cc bonds are equal in length. The value of the Jab:Jbc ratio should be in the range from 0.5 to 1.0, depending on the degree of alternation of connections. By comparing these values ​​in a series of similar compounds, it is possible to determine the degree of localization of bonds. For example, changes in the Jab:Jbc ratio for four compounds are presented in Fig. 2, make it possible to estimate the degree of bond fixation in isoindole, for which it is impossible to obtain data using X-ray diffraction analysis.

Effects of ring currents and chemical shifts in PMR spectra

The chemical shifts of proton signals in benzenes are greater than in similar acyclic polyenes. In particular, this is attributed to the influence of a "diamagnetic ring current". When a solution of a benzenoid compound is placed in a magnetic field, the molecules align at regular angles to the field and a diamagnetic ring current occurs due to the presence of delocalized π electrons. This creates a secondary magnetic field that is opposite to the applied field inside the loop, but enhances it outside the loop (Figure 3). Thus, hydrogen nuclei lying in the region above or below the center of the ring are shielded, and those lying on the periphery are deshielded. The changes are more difficult to observe in 13 C NMR spectra, since the 13 C chemical shifts are much larger and the additional shielding and deshielding caused by the ring current is relatively less noticeable.

The existence of a diamagnetic ring current, manifested in a shielding and deshielding effect on the chemical shifts of protons, has been proposed to be considered a diagnostic test for the aromatic character of a compound. This is justified by the fact that a theoretical connection has been established between diamagnetic susceptibility and resonance energy. But this criterion should be used with caution, since ring current effects increase with cycle size and are therefore quite significant in large annulenes and heteroannulenes. From a practical point of view, in order to detect shielding and deshielding, it is necessary to have suitable non-aromatic reference compounds for comparison, and such compounds are not easy to find for some heterocyclic systems. Chemical shifts are influenced by several factors other than the diamagnetic ring current, such as the disruption of the distribution of π electrons by the heteroatom and the influence of the nature of the solvents. The magnitude of chemical shifts for many heterocycles strongly depends on the nature of the solvent. However, we can see the qualitative influence of ring currents by comparing the NMR spectra of pyridine, furan and thiophene and their dihydrogen analogues (Fig. 4).

Comparisons with non-aromatic systems of this type are criticized because it is indeed difficult to find suitable model compounds for some simple heterocycles, such as pyrrole. Indirect methods are used to assess the influence of the diamagnetic ring current: for example, the values ​​of the chemical shifts of the methyl groups of heterocycles shown in Fig. 5 were compared with the values ​​calculated for linear models. The observed downfield shifts were taken as a criterion for assessing the relative aromaticity of heterocycles. However, in general, the “ring current effect” should be considered a qualitative indicator of aromaticity rather than a quantitative one.

Other physical methods for studying electronic structure

There are several experimental methods for studying electronic energy levels or electron density distributions. They cannot be considered criteria for aromaticity, but provide independent experimental assessments of the consistency of calculations of the energies of molecular orbitals of heterocycles.

Ultraviolet absorption spectra has been used for many years as a qualitative method to determine the similarity of bonding patterns in different compounds. The regions that are defined by π→π* transitions are similar to those of the carbocyclic analogues, although the spectra of many heterocycles contain additional energy transitions that can be attributed to n→π* absorption.

The energy levels of filled molecular orbitals can be calculated using photoelectron spectroscopy. Electrons are ejected from occupied molecular orbitals when molecules are irradiated with high-energy ultraviolet light in the gas phase. The energies of these electrons are directly related to the ionization potentials caused by the removal of electrons from various molecular orbitals. Spectral analysis involves determining the spectral regions of the electronic states of molecular ions and, therefore, identifying the orbitals from which electrons were emitted. The method thus serves as an experimental test for predicted changes in the bond levels of a series of heterocyclic compounds. For example, analogues of pyridine were obtained in which the nitrogen atom was replaced by other elements of group V (P, As, Sb, Bi). The study of photoelectron spectra showed that π-bonding in these compounds is similar to π-bonding in benzene and pyridine molecules. The π bonding orbitals resemble those shown in Fig. 6. Ionization energies associated with the π 2 level (Fig. 6) decrease with increasing heteroatom size, as it becomes more electropositive. The photoelectron spectrum of silabenzene also corresponds to that expected for its benzene analogue.

An additional technique that can measure electron affinity and estimate the energy levels of unoccupied orbitals is known as electron transmission spectroscopy. An electron from the electron beam is temporarily captured by an unoccupied orbital of the molecule, and an anion with a very short lifetime (10 -12 -10 -15 s) is formed. Values ​​characterizing electron affinity are obtained by analyzing changes in the electron scattering spectrum. This method was used to determine the electron affinities of some aromatic heterocycles. Using these methods, the data calculated from the energies of the π-orbitals of aromatic heterocycles (shown in Figs. 6 and 7) were confirmed.

Thermochemical Assessment of Aromaticity: Empirical Resonance Energies

Two thermochemical methods are commonly used to assess the stabilization of aromatic compounds: standard enthalpy of combustion and standard enthalpy of hydrogenation. The heat of combustion of pyridine, for example, is the enthalpy change according to the equation

C 5 H 5 N (g.) + 25/4 O 2 → 5CO 2 (g.) + 5/2 H 2 O (l.) + 1/2 N 2 (g.)

and the value can be determined experimentally using calorimetry. The method can also be applied to determine the experimental value of the heat of formation of a compound. The atomic heat of formation of pyridine is the enthalpy change according to the equation

C 5 H 5 N (g) → 5C (g) + 5H (g) + N (g)

The value can be obtained from the heat of combustion if we use the known values ​​of the heats of combustion and atomization of carbon, hydrogen and nitrogen.

The heat of formation can be calculated by adding the individual binding energies for the molecule: for pyridine these should be the values ​​corresponding to the localized structure (the Kekule structure). The difference between the experimental (numerically smaller) and calculated values ​​will be a measure of stabilization of the delocalized system; it is called the empirical resonance energy. The obtained values ​​depend on the bond energies used in the calculation, as well as on the choice of the “localized bond” model system.

The heats of hydrogenation of aromatic compounds can be used to calculate empirical resonance energies by comparison with experimental values ​​for suitable model compounds. For example, compare the heat of hydrogenation of benzene [ΔH = -49.7 kcal/mol (-208 kJ/mol)] with that for 3 moles of cyclohexene [ΔH = -28.4 kcal/mol (-119 kJ/mol), [ΔH = -85.3 kcal/mol (-357 kJ/mol)]. The difference of 35.6 kcal/mol (149 kJ/mol) corresponds to the empirical resonance energy of benzene. A slightly different value is obtained if the model system is chosen in a different way. Thus, the heats of hydrogenation of the first and second double bonds of 1,3-cyclohexadiene are extrapolated to obtain the heat of hydrogenation by adding a third mole of hydrogen to a hypothetical “cyclohexatriene.” The sum of the three values ​​is then taken as the value for the localized model, as shown below (calculated by extrapolation):

C 6 H 10 + H 2 → C 6 H 12 ΔH = -28.4 kcal/mol (-119 kJ/mol)
1,3-C 6 H 8 + H 2 → C 6 H 10 ΔH = -26.5 kcal/mol (-111 kJ/mol)
C 6 H 6 + H 2 → C 6 H 8 ΔH = -24.6 kcal/mol (-103 kJ/mol)

The total heat of hydrogenation of this localized model is - 79.5 kcal/mol (- 333 kJ/mol), and thus the empirical resonance energy of benzene is 29.8 kcal/mol (125 kJ/mol).

However, it is absolutely clear that one should not attach too much importance to the absolute values ​​of resonance energies. Values ​​obtained by similar methods for a series of compounds can only provide an acceptable relative estimate of the degree of stabilization. Most values ​​for heterocyclic compounds are based on heats of combustion values, since many of the model systems needed to measure the heats of hydrogenation are not readily available. Literature data vary over a very wide range, mainly due to the chosen binding energies. Some comparable values ​​(obtained by similar methods) are presented in table.

Table. Empirical resonance energies

Molecular orbitals and delocalization energy

Let us consider heterocycles, completely unsaturated and flat or almost flat, with a closed ring of atoms with interacting p-orbitals. In the Hückel approximation, electrons in π-molecular orbitals are considered separately from electrons located in α-orbitals. The energies of π molecular orbitals can be expressed using two constants. The first, the Coulomb integral, denoted by the symbol α, reflects the approximate value of the attractive force of the electron of an individual atom. In the carbon π electron system, α represents the energy of an electron in an isolated p orbital before overlap. The second constant, the resonance integral, means the measure of stabilization achieved through the interaction of neighboring p-orbitals. This quantity is denoted by the symbol β.

The energies of the six π-orbitals of benzene, calculated using the Hückel method, are shown in Fig. 8, a. Two π-orbitals of ethylene are presented for comparison in Fig. 8, b. The six π electrons occupying the three bonding orbitals of benzene will have a total energy of (6α + 8β), whereas the six π electrons occupying the three isolated bonding orbitals of ethylene will have a total energy of (6α + 6β). Thus, the π-electron system of benzene is more stable by an amount of 2β, which is called the delocalization energy of benzene. Obviously, the delocalization energy will be the same for pyridine and other six-membered heterocycles, if we ignore the effect that occurs when replacing a carbon atom with a nitrogen atom. In practice, such effects can be compensated for by using parameters that correct for the uneven distribution of the π electron density.

This delocalization energy does not correspond to the empirical resonance energy, since the latter is calculated for a model with alternating bond lengths, and the former is based on a hypothetical localization model with a geometry identical to that of the delocalized system. In order to establish the relationship between them, we must add to the empirical resonance energy the energy necessary to compress a structure with alternating simple and multiple bonds to a structure with non-alternating bonds. This deformation energy, calculated for benzene, is 27 kcal/mol (113 kJ/mol), i.e., a very significant value compared to the empirical resonance energy. Therefore, it is more useful to recognize that delocalization energies are relative quantities than to determine their numerical values.

Calculated resonance energies

The problem with measuring aromatic stabilization based on a simple nonconjugated π-electron system model is that “delocalization energy” is not a unique property of cyclic systems. For example, based on the simple Hückel MO method, it can be shown that the delocalization energy of butadiene is 0.472β; other acyclic conjugate systems also have some delocalization energy. When trying to find a measure of aromaticity, it is necessary to evaluate the additional contribution to the total delocalization energy due to the fact that the compound has a cyclic structure. In this regard, it has been suggested that when calculating resonance energies one should use the bond energies of non-aromatic systems rather than non-conjugated systems as reference structures. The π bond energy of linear polyenes has been shown to be directly proportional to chain length. Each additional "single" or "double" C-C bond in a polyene contributes to the total π-energy in the same way as in the case of butadiene or hexatriene. This, of course, does not mean that conjugation is absent, but it does show that conjugation also affects the binding energy in non-cyclic systems. Consequently, it is possible to calculate the “reference” π-bond energies for any cyclic or acyclic π-system by adding the values ​​corresponding to certain types of bonds. This additive principle applies to π bonds with heteroatoms as much as it applies to carbon-carbon bonds.

Cyclic systems in which additional π-bond energy is observed compared to the calculated reference values ​​are called “aromatic”. The additional stabilization energy was called the “Dewar resonance energy,” but the principle of calculating resonance energies was adopted later. Cyclic systems whose resonance energies are close to zero [no more than 2.5 kcal/mol (10 kJ/mol)] are classified as “non-aromatic”. Several cyclic systems for which the calculated resonance energy is negative (they have a lower binding energy than the reference structure) are called "anti-aromatic".

Resonance energies based on the Dewar model can be calculated by the Hückel MO method, even though the method ignores σ and π interactions. This is due to the fact that the σ- and π-contributions to the binding energy are directly proportional to the order of a given bond. Therefore, π-resonance energies are directly proportional to the total resonance energies. As for the bonds with the heteroatom, the values ​​of the Coulomb and resonance integrals need to be modified. In this case, values ​​must be obtained that best coincide with the experimental values ​​of the heats of atomization of known compounds, which are then used to calculate the energies of various types of π bonds in units of the resonance integral β. The total π-bond energy of the reference structure (i.e., the structure with the dominant valence) is calculated by adding the contributions of the individual bonds, which are then compared with the total t-bond energy calculated by the Hückel MO method.

In order to compare the aromaticity of other heterocycles, it is convenient to calculate the resonance energy per π-electron (PEE) by dividing the resonance energy by the number of π-electrons in the molecule. For known systems, these values ​​correlate well with other aromaticity criteria; Some data for the most important heterocycles are given in Table. The method can also be used to predict the degree of aromaticity of heterocyclic compounds that have not yet been synthesized. In table Some calculated values ​​of aromatization energies are also given, which represent the difference in energies of analogues with localized and delocalized structures.

Table. Resonance energies per π-electron (REE) and aromatization energies of “certain heterocyclic compounds”

Aromaticity is a special property of some chemical compounds, due to which the conjugated ring of unsaturated bonds exhibits abnormally high stability; greater than what would be expected with only one conjugation. Aromaticity is not directly related to the smell of organic compounds, and is a concept that characterizes the totality of structural and energetic properties of certain cyclic molecules containing a system of conjugated double bonds. The term "aromaticity" was proposed because the first representatives of this class of substances had a pleasant odor. The most common aromatic compounds contain six carbon atoms in the ring; the ancestor of this series is benzene C 6 H 6 . X-ray diffraction analysis shows that the benzene molecule is flat, and the length of the C-C bonds is 0.139 nm. It follows that all six carbon atoms in benzene are in sp 2-hybrid state, each carbon atom forms σ bonds with two other carbon atoms and one hydrogen atom lying in the same plane, bond angles are 120º. Thus, the σ-skeleton of the benzene molecule is a regular hexagon. Moreover, each carbon atom has a non-hybrid p-orbital located perpendicular to the flat skeleton of the molecule; all six are non-hybrid p-electrons interact with each other, forming π-bonds, not localized in pairs, but combined into a single π-electron cloud. Thus, circular conjugation occurs in the benzene molecule. Graphically, the structure of benzene can be expressed by the following formula:

Circular conjugation gives an energy gain of 154 kJ/mol - this value is conjugation energy - the amount of energy that must be expended to destroy the aromatic system of benzene.

To form a stable aromatic system it is necessary that p-electrons were formally grouped into 3, 5, 7, etc. double bonds; mathematically this is expressed Hückel's rule : cyclic compounds that have a flat structure and contain (4n + 2) electrons in a closed conjugation system, where n is a natural series of numbers, have increased thermodynamic stability.

31 . Electrophilic substitution reactions in benzene (halogenation, nitration, sulfonation, alkylation, acylation). An idea of ​​the mechanism of electrophilic substitution reactions in the aromatic series, σ- and π-complexes.

Halogenation

To introduce a halogen into the aromatic ring, complexes of halogens with Lewis acids are used as reagents. The role of the latter is to polarize the halogen-halogen bond, as a result of which one of the atoms acquires a positive charge, while the other forms a bond with the Lewis acid due to its vacant d-orbitals.

Nitration

Benzene and its homologues are converted into nitro compounds by the action of a nitrating mixture, which consists of concentrated sulfuric and nitric acids (2:1). The nitrating particle (electrophile) is the nitronium cation NO 2 +, the existence of which in the nitrating mixture is proven by the cryoscopic method: measurements of the freezing temperatures of nitric and sulfuric acids and their mixture indicate the presence of four particles in the solution.

Sulfonation

The sulfonation reaction of arenes is believed to occur in oleum under the action of sulfur trioxide, and in sulfuric acid with the participation of the HSO 3 + cation. Sulfur trioxide exhibits electrophilic character due to the polarity of the S–O bonds.

Friedel-Crafts alkylation

One of the ways to obtain benzene homologues is the alkylation reaction. The transformation is named after S. Friedel and J. M. Crafts, who discovered it. As a rule, haloalkanes and aluminum halides are introduced into the reaction as catalysts. It is believed that the catalyst, a Lewis acid, polarizes the C-halogen bond, creating a deficiency of electron density on the carbon atom, i.e. the mechanism is similar to the halogenation reaction

Friedel-Crafts acylation

Similar to the alkylation reaction is the acylation reaction of aromatic compounds. Anhydrides or halides of carboxylic acids are used as reagents; aromatic ketones are the products. The mechanism of this reaction involves the formation of a complex between the acylating reagent and the Lewis acid. As a result, the positive charge on the carbon atom increases incomparably, making it capable of attacking the aromatic compound.

It should be noted that, unlike the alkylation reaction, in this case it is necessary to take an excess of the catalyst relative to the amount of reagents, because the reaction product (ketone) is itself capable of complexation and binds a Lewis acid.

Electrophilic substitution reactions of σ- and π-complexes 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 evenly on both sides of the ring. Such shielding of the ring carbon atoms 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 disrupted and its stability would decrease. Preservation of aromaticity is possible if an electrophilic particle replaces a 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:

The formation of a pi complex is due to the pi bond in the compound, and the sigma complex is formed due to the sigma bond.

Formation of a π-complex. The resulting electrophile X+ (for example, a Br+ ion) attacks the electron-rich benzene ring, forming a π-complex.

Transformation of a π-complex into a σ-complex. The electrophile takes 2 electrons from the π-system, forming a σ-bond with one of the carbon atoms of the benzene ring. Difference between pi and sigma bonds: A sigma bond is stronger, a sigma bond is formed by hybrid orbitals. A pi bond is formed by unhybridized pi orbitals. A pi bond is more distant from the centers of the atoms being connected, so it is less strong and easier to break.

32. Aromatic hydrocarbons. The influence of substituents in the benzene ring on the isomeric composition of the products and the reaction rate. Activating and deactivating substituents. Ortho-, para- and meta-orientators. Radical substitution and oxidation reactions in the side chain.

An essential feature of the reactions for the production and transformation of aromatic hydrocarbon derivatives is that new substituents enter the benzene ring in certain positions relative to existing substituents. The patterns that determine the direction of substitution reactions in the benzene ring are called orientation rules.

The reactivity of a particular carbon atom in the benzene ring is determined by the following factors: 1) the position and nature of the existing substituents, 2) the nature of the active agent, 3) the reaction conditions. The first two factors have a decisive influence.

Substituents on the benzene ring can be divided into two groups.

Electron donors (of the first kind) are groups of atoms capable of donating electrons. These include OH, OR, RCOO, SH, SR, NH 2, NHR, NR 2, NHCOR, -N=N-, CH 3, CH 2 R, CR 3, F, CI, Br, I.

Electron-withdrawing substituents (of the second kind) are atomic groups capable of withdrawing and accepting electrons from the benzene nucleus. These include S0 3 H, N0 2, CHO, COR, COOH, COOR, CN, CC1 3, etc.

Polar reagents acting on aromatic compounds can be divided into two groups: electrophilic and nucleophilic. The most common processes for aromatic compounds are alkylation, halogenation, sulfonation and nitration. These processes occur during the interaction of aromatic compounds with electrophilic reagents. Reactions with nucleophilic reagents (NaOH, NH 2 Na, etc.), for example, hydroxylation and amination reactions, are also known.

Substituents of the first kind facilitate reactions with electrophilic reagents, and they orient the new substituent in ortho- And pair- provisions.

Substituents of the second kind complicate reactions with electrophilic reagents: they orient the new substituent to the meta position. At the same time, these substituents facilitate reactions with nucleophilic reagents.

Let us consider examples of reactions with different orienting effects of substituents.

1. Deputy of the first kind; electrophilic reagent. The reaction-facilitating effect of the substituent, o-, p-orientation:

2. Deputy of the second kind; electrophilic reagent. The action of a substituent that hinders the reaction; m-orientation:

3. Deputy of the first kind; nucleophilic reagent; m-orientation. Obstructive action of the deputy. Examples of such reactions with an indisputable mechanism are unknown.

4. Deputy of the second kind; nucleophilic reagent, o-, p-orientation:

Orientation rules for electrophilic substitution in the benzene ring are based on the mutual influence of the atoms in the molecule. If in unsubstituted benzene C 6 H 6 the electron density in the ring is distributed evenly, then in substituted benzene C 6 H 5 X, under the influence of substituent X, a redistribution of electrons occurs and areas of increased and decreased electron density appear. This affects the ease and direction of electrophilic substitution reactions. The entry point of a new substituent is determined by the nature of the existing substituent.

Orientation rules

The substituents present on the benzene ring direct the newly introduced group to certain positions, i.e. have an orienting effect.

According to their directing action, all substituents are divided into two groups: orientants of the first kind And orientants of the second kind.

Orientants of the 1st kind ( ortho-para ortho- And pair- provisions. These include electron-donating groups (electronic effects of the groups are indicated in parentheses):

R ( +I); -OH( +M,-I); -OR ( +M,-I); -NH 2 ( +M,-I); -NR 2 (+M,-I)+M-effect in these groups is stronger than -I-effect.

Orientants of the 1st kind increase the electron density in the benzene ring, especially on the carbon atoms in ortho- And pair-positions, which favors the interaction of these particular atoms with electrophilic reagents. Example:

Orientants of the 1st kind, increasing the electron density in the benzene ring, increase its activity in electrophilic substitution reactions compared to unsubstituted benzene.

A special place among the 1st kind orientants is occupied by halogens, which exhibit electron-withdrawing properties: - F (+M<–I ), -Cl (+M<–I ), -Br (+M<–I ).Being ortho-para-orientants, they slow down electrophilic substitution. Reason - strong –I-the effect of electronegative halogen atoms, which reduces the electron density in the ring.

Orientants of the 2nd kind ( meta-orientators) direct subsequent substitution predominantly to meta-position. These include electron-withdrawing groups:

NO 2 ( –M, –I); -COOH( –M, –I); -CH=O ( –M, –I); -SO3H ( –I); -NH 3 + ( –I); -CCl 3 ( –I).

Orientants of the 2nd kind reduce the electron density in the benzene ring, especially in ortho- And pair- provisions. Therefore, the electrophile attacks carbon atoms not in these positions, but in meta-position where the electron density is slightly higher. Example:

All orientants of the 2nd kind, generally reducing the electron density in the benzene ring, reduce its activity in electrophilic substitution reactions.

Thus, the ease of electrophilic substitution for the compounds (given as examples) decreases in the order:

toluene C 6 H 5 CH 3 > benzene C 6 H 6 > nitrobenzene C 6 H 5 NO 2.

Side chain radical substitution and oxidation reactions

The second most important group of reactions of alkyl aromatic hydrocarbons is free radical substitution side chain hydrogen atom in a-position relative to the aromatic ring.

Preferential substitution in a-position is explained by the high stability of the corresponding alkyl aromatic radicals, and therefore the relatively low strength a-C-H-bonds. For example, the energy of breaking the C-H bond in the side chain of the toluene molecule is 327 kJ/mol - 100 kJ/mol less than the energy of the C-H bond in the methane molecule (427 kJ/mol). This means that the stabilization energy of the benzyl free radical C 6 H 5 -CH 2 · is equal to 100 kJ/mol.

The reason for the high stability of benzyl and other alkyl aromatic radicals with an unpaired electron is a-carbon atom is the possibility of distributing the spin density of the unpaired electron in a non-bonding molecular orbital covering carbon atoms 1", 2, 4 and 6.

As a result of distribution (delocalization), only 4/7 of the spin density of the unpaired electron remains with the non-ring carbon atom, the remaining 3/7 of the spin density is distributed between one pair- and two ortho- carbon atoms of the aromatic nucleus.

Oxidation reactions

Oxidation reactions, depending on the conditions and nature of the oxidizing agent, can proceed in different directions.

molecular oxygen at a temperature of about 100 o C, it oxidizes isopropylbenzene via a radical chain mechanism to a relatively stable hydroperoxide.

33. Condensed aromatic hydrocarbons: naphthalene, anthracene, phenanthrene, benzopyrene. Their structural fragments in natural and biologically active substances (steroids, alkaloids, antibiotics).

Naphthalene - C 10 H 8 solid crystalline substance with a characteristic odor. Insoluble in water, but soluble in benzene, ether, alcohol, chloroform. Naphthalene is similar in chemical properties to benzene: it is easily nitrated, sulfonated, and interacts with halogens. It differs from benzene in that it reacts even more easily. Naphthalene is obtained from coal tar.

Anthracene is colorless crystals, melting point 218° C. Insoluble in water, soluble in acetonitrile and acetone, soluble in benzene when heated. Anthracene is obtained from coal tar. Its chemical properties are similar to naphthalene (it is easily nitrated, sulfonated, etc.), but differs from it in that it more easily enters into addition and oxidation reactions.

Anthracene can photodimerize under the influence of UV radiation. This leads to a significant change in the properties of the substance.

The dimer contains two covalent bonds formed as a result of cycloaddition. The dimer decomposes back into two anthracene molecules when heated or under UV irradiation with a wavelength below 300 nm. Phenanthrene is a tricyclic aromatic hydrocarbon. Phenanthrene appears as shiny, colorless crystals. Insoluble in water, soluble in organic solvents (diethyl ether, benzene, chloroform, methanol, acetic acid). Solutions of phenanthrene glow blue.

Its chemical properties are similar to naphthalene. Benzpyrene, or benzopyrene, is an aromatic compound, a representative of the family of polycyclic hydrocarbons, a substance of the first hazard class.

Formed during the combustion of hydrocarbon liquid, solid and gaseous fuels (to a lesser extent during the combustion of gaseous fuels).

In the environment it accumulates mainly in soil, less in water. It enters plant tissues from the soil and continues its movement further in the food chain, while at each stage the BP content in natural objects increases (see Biomagnification).

It has strong luminescence in the visible part of the spectrum (in concentrated sulfuric acid - A 521 nm (470 nm); F 548 nm (493 nm)), which allows it to be detected in concentrations up to 0.01 ppb by luminescent methods.

34. Halogen derivatives of hydrocarbons. Classification, nomenclature, isomerism.

Halogen derivatives can be classified in several ways:

1. in accordance with the general classification of hydrocarbons (i.e. aliphatic, alicyclic, aromatic, saturated or unsaturated halogen derivatives)

2. by the quantity and quality of halogen atoms

3. according to the type of carbon atom to which the halogen atom is attached: primary, secondary, tertiary halogen derivatives.

According to IUPAC nomenclature, the position and name of the halogen is indicated in the prefix. Numbering begins from the end of the molecule to which the halogen atom is closest. If a double or triple bond is present, then it is this that determines the beginning of the numbering, and not the halogen atom: The so-called “rational nomenclature” for compiling the names of halogen derivatives. In this case, the name is constructed as follows: hydrocarbon radical + halide.

Some halogen derivatives have trivial names, for example, the inhalation anesthetic 1,1,1-trifluoro-2-bromo-2-chloroethane (CF 3 -CBrClH) has the trivial name fluorotane. 3. Isomerism

3.1. Structural isomerism 3.1.1. Isomerism of substituent positions

1-bromobutane 2-bromobutane

3.1.2. Isomerism of the carbon skeleton

1-chlorobutane 2-methyl-1-chloropropane

3.2. Spatial isomerism

Stereoisomerism can occur when there are four different substituents on one carbon atom (enantiomerism) or when there are different substituents on a double bond, for example:

trans-1,2-dichloroethene cis-1,2-dichloroethene

35. Reactions of nucleophilic substitution of the halogen atom, their use in the synthesis of organic compounds of various classes (alcohols, ethers and esters, amines, thiols and sulfides, nitroalkanes, nitriles).

- makes it possible to obtain representatives of almost all classes of organic compounds (alcohols, ethers, amines, nitriles, etc.), therefore these reactions are widely used in the synthesis of medicinal substances. Basic reaction mechanisms

Substitution of a halogen at an sp 3 -hybrid carbon atom can be carried out by both S N 1 and S N 2 mechanisms. The substitution of the halogen at the sp 2 -hybrid carbon atom (in aryl and vinyl halides) occurs either by the type of addition-elimination or by the type of elimination-addition and is much more difficult than for the sp 3 -hybrid. - S N 1 mechanism includes two stages: a) dissociation of alkyl halide into ions; b) interaction of a cation with a nucleophile Nucleophilic attack of a contact ion pair, in which the asymmetry is largely preserved, leads to a reversal of the configuration. In a solvate-separated ion pair, one side of the cation is shielded by the solvated halide ion and nucleophile attack is more likely on the other side, resulting in preferential configuration reversal, but selectivity is reduced and racemization is increased. Complete racemization is possible only with the formation of a free cation (c). However, complete racemization is not usually observed for optically active halides via the S N 1 mechanism. Racemization ranges from 5 to 20%, therefore, practically no solvated cation is formed.

The formation of a carbocation can cause a number of side processes: isomerization of the carbon chain, elimination (EI), etc.

Nucleophile Nu - attacks the substrate from the side opposite to the leaving group. In this case, the reaction proceeds in one stage with the formation of a transition state in which sp 3 -hybridization of the central carbon atom changes to sp 2 - with a p-orbital perpendicular to the plane of location of the hybrid orbitals. One lobe of the etor orbital overlaps with the nucleophile, and the second with the leaving group. The C-Nu bond is formed simultaneously with the cleavage of the C-Y bond.

The rate of conversion of starting substances into reaction products depends on: 1) the magnitude of the positive charge on the carbon atom of the substrate, 2) spatial factors, 3) the strength of the nucleophile and 4) in the kinetic region, the concentration of both the nucleophile and the alkyl halide. With a large excess of nucleophile, the reaction can proceed in the first or fractional order. (The terms S N 1 and S N 2 indicate only molecularity, not the order of the reaction.)

The reaction is always accompanied by a reversal of the configuration. A side reaction may be the elimination of E2.

The S N Ar (addition-elimination) mechanism is usually realized in the presence of electron-withdrawing substituents that create d+ (direct the nucleophile) and stabilize the s-complex. In heterocycles, their role is played by the heteroatom. In contrast to the S N 2 mechanism for alkyl halides, the nucleophile forms a new bond before the old one breaks.

Pyridine and quinoline can be considered as analogues of nitrobenzene. As in nitrobenzene, the position of the halogen in the ring is of great importance. 3-Halopyridines are similar to halobenzenes, 2-,4-substituted ones are similar to nitrohalobenzenes, while 4-halopyridine is more active than 2-substituted. The reactivity of alkyl halides in nucleophilic substitution reactions in protic solvents decreases (the ability of groups to leave decreases) in the following order: RI > RBr > RCl > RF.

In the case of activated haloarenes, the appearance of a positive charge at the reaction center depends not only on the number, location and nature of other substituents in the nucleus, but also on the nature of the replaced halogen. Therefore, halogen atoms can be replaced with increasing ease in row I< Br < Cl < F .Катализ замещения галоген в аренах медью – один из важных технологических приемов, позволяющий ускорить реакцию замещения неактивированного галогена в аренах, снизить температуру реакции (~ на 100 о С), увеличить селективность процесса и выход продукта. Предполагают, что реакция идет через стадию образования медь-органических комплексов

Aromatic substrates (aryl halides) must be activated, otherwise the yield of the target product (ester) may be low due to side processes. The replacement of halogen in primary and secondary alkyl halides with an amino group is carried out by heating them with an alcoholic, aqueous or aqueous-alcoholic solution of ammonia, a primary or secondary amine under pressure (in an autoclave). This produces a mixture of salts of primary, secondary, tertiary amines and quaternary ammonium salts