Many substitution reactions open the way to obtaining a variety of compounds that have economic applications. A huge role in chemical science and industry is given to electrophilic and nucleophilic substitution. In organic synthesis, these processes have a number of features that should be taken into account.
variety of chemical phenomena. Substitution reactions
Chemical changes associated with the transformations of substances are distinguished by a number of features. The final results, thermal effects may be different; some processes go to the end, in others a change in substances is often accompanied by an increase or decrease in the degree of oxidation. When classifying chemical phenomena according to their end result, attention is paid to the qualitative and quantitative differences between the reactants and the products. According to these features, 7 types of chemical transformations can be distinguished, including substitution, following the scheme: A-B + C A-C + B. A simplified record of a whole class of chemical phenomena gives an idea that among the starting substances there is a so-called "a particle that replaces an atom, ion, or functional group in a reagent. The substitution reaction is typical for limiting and
Substitution reactions can occur in the form of a double exchange: A-B + C-E A-C + B-E. One of the subspecies is the displacement, for example, of copper with iron from a solution of copper sulfate: CuSO 4 + Fe = FeSO 4 + Cu. Atoms, ions or functional groups can act as an “attacking” particle
Substitution homolytic (radical, SR)
With a radical mechanism for breaking covalent bonds, an electron pair common to different elements is proportionally distributed among the "fragments" of the molecule. Free radicals are formed. These are unstable particles, the stabilization of which occurs as a result of subsequent transformations. For example, when ethane is obtained from methane, free radicals appear that participate in the substitution reaction: CH 4 CH 3. + .H; CH 3 . + .CH 3 → C2H5; H. + .H → H2. Homolytic bond breaking according to the given substitution mechanism is of a chain nature. In methane, H atoms can be successively replaced by chlorine. The reaction with bromine proceeds similarly, but iodine is unable to directly replace hydrogen in alkanes, fluorine reacts too vigorously with them.
Heterolytic cleavage method
With the ionic mechanism of substitution reactions, electrons are unevenly distributed among the newly formed particles. The binding pair of electrons goes completely to one of the "fragments", most often, to that bond partner, towards which the negative density in the polar molecule was shifted. Substitution reactions include the formation of methyl alcohol CH 3 OH. In bromomethane CH3Br, the cleavage of the molecule is heterolytic, and the charged particles are stable. Methyl acquires a positive charge, and bromine acquires a negative one: CH 3 Br → CH 3 + + Br - ; NaOH → Na + + OH - ; CH 3 + + OH - → CH 3 OH; Na + + Br - ↔ NaBr.
Electrophiles and nucleophiles
Particles that lack electrons and can accept them are called "electrophiles". These include carbon atoms bonded to halogens in haloalkanes. Nucleophiles have an increased electron density, they "donate" a pair of electrons when creating a covalent bond. In substitution reactions, nucleophiles rich in negative charges are attacked by electron-starved electrophiles. This phenomenon is associated with the displacement of an atom or other particle - the leaving group. Another type of substitution reaction is the attack of an electrophile by a nucleophile. It is sometimes difficult to distinguish between two processes, to attribute substitution to one type or another, since it is difficult to specify exactly which of the molecules is the substrate and which is the reagent. Usually in such cases the following factors are taken into account:
- the nature of the leaving group;
- nucleophile reactivity;
- the nature of the solvent;
- structure of the alkyl part.
Substitution nucleophilic (SN)
In the process of interaction in an organic molecule, an increase in polarization is observed. In equations, a partial positive or negative charge is marked with a letter of the Greek alphabet. The polarization of the bond makes it possible to judge the nature of its rupture and the further behavior of the "fragments" of the molecule. For example, the carbon atom in iodomethane has a partial positive charge and is an electrophilic center. It attracts that part of the water dipole where oxygen, which has an excess of electrons, is located. When an electrophile interacts with a nucleophilic reagent, methanol is formed: CH 3 I + H 2 O → CH 3 OH + HI. Nucleophilic substitution reactions take place with the participation of a negatively charged ion or a molecule that has a free electron pair that is not involved in the creation of a chemical bond. The active participation of iodomethane in SN 2 reactions is explained by its openness to nucleophilic attack and the mobility of iodine.
Electrophilic substitution (SE)
An organic molecule may contain a nucleophilic center, which is characterized by an excess of electron density. It reacts with an electrophilic reagent that lacks negative charges. Such particles include atoms with free orbitals, molecules with areas of low electron density. In carbon, which has a “-” charge, interacts with the positive part of the water dipole - with hydrogen: CH 3 Na + H 2 O → CH 4 + NaOH. The product of this electrophilic substitution reaction is methane. In heterolytic reactions, oppositely charged centers of organic molecules interact, which makes them similar to ions in the chemistry of inorganic substances. It should not be overlooked that the transformation of organic compounds is rarely accompanied by the formation of true cations and anions.
Monomolecular and bimolecular reactions
Nucleophilic substitution is monomolecular (SN1). The hydrolysis of an important product of organic synthesis, tertiary butyl chloride, proceeds according to this mechanism. The first stage is slow, it is associated with gradual dissociation into carbonium cation and chloride anion. The second stage is faster, the carbonium ion reacts with water. substitution of a halogen in an alkane for an hydroxy group and obtaining a primary alcohol: (CH 3) 3 C-Cl → (CH 3) 3 C + + Cl - ; (CH 3) 3 C + + H 2 O → (CH 3) 3 C-OH + H +. The single-stage hydrolysis of primary and secondary alkyl halides is characterized by the simultaneous destruction of the carbon bond with the halogen and the formation of a C–OH pair. This is the mechanism of nucleophilic bimolecular substitution (SN2).
Heterolytic substitution mechanism
The substitution mechanism is associated with electron transfer, the creation of intermediate complexes. The reaction proceeds the faster, the easier it is to form the intermediate products characteristic of it. Often the process goes in several directions at the same time. The advantage is usually obtained by the way in which the particles that require the least energy costs for their formation are used. For example, the presence of a double bond increases the probability of the appearance of the allyl cation CH2=CH—CH 2 + , compared to the ion CH 3 + . The reason lies in the electron density of the multiple bond, which affects the delocalization of the positive charge dispersed throughout the molecule.
Benzene substitution reactions
The group for which electrophilic substitution is characteristic is arenas. The benzene ring is a convenient target for electrophilic attack. The process begins with the polarization of the bond in the second reactant, resulting in the formation of an electrophile adjacent to the electron cloud of the benzene ring. The result is a transitional complex. There is still no full-fledged connection of an electrophilic particle with one of the carbon atoms, it is attracted to the entire negative charge of the “aromatic six” of electrons. At the third stage of the process, the electrophile and one carbon atom of the ring are connected by a common pair of electrons (covalent bond). But in this case, the “aromatic six” is destroyed, which is unfavorable from the point of view of achieving a stable sustainable energy state. There is a phenomenon that can be called "proton ejection". There is a splitting of H + , a stable bond system, characteristic of arenes, is restored. The by-product contains a hydrogen cation from the benzene ring and an anion from the composition of the second reagent.
Examples of substitution reactions from organic chemistry
For alkanes, the substitution reaction is especially characteristic. Examples of electrophilic and nucleophilic transformations can be given for cycloalkanes and arenes. Similar reactions in the molecules of organic substances occur under normal conditions, but more often when heated and in the presence of catalysts. Electrophilic substitution in the aromatic nucleus is one of the widespread and well-studied processes. The most important reactions of this type are:
- Nitration of benzene in the presence of H 2 SO 4 - goes according to the scheme: C 6 H 6 → C 6 H 5 -NO 2.
- Catalytic halogenation of benzene, in particular chlorination, according to the equation: C 6 H 6 + Cl 2 → C 6 H 5 Cl + HCl.
- Aromatic proceeds with "fuming" sulfuric acid, benzenesulfonic acids are formed.
- Alkylation is the replacement of a hydrogen atom from the benzene ring with an alkyl.
- Acylation is the formation of ketones.
- Formylation is the replacement of hydrogen with a CHO group and the formation of aldehydes.
Substitution reactions include reactions in alkanes and cycloalkanes, in which halogens attack the available C-H bond. The preparation of derivatives may be associated with the substitution of one, two or all hydrogen atoms in saturated hydrocarbons and cycloparaffins. Many of the low molecular weight haloalkanes find use in the production of more complex substances belonging to different classes. The progress made in studying the mechanisms of substitution reactions gave a powerful impetus to the development of syntheses based on alkanes, cycloparaffins, arenes, and halogen derivatives of hydrocarbons.
It is formed when atomic orbitals overlap and the formation of common electron pairs. As a result of this, an orbital common to two atoms is formed, on which a common pair of electrons is located. When the bond is broken, the fate of these common electrons can be different.
Exchange mechanism for the formation of a covalent bond. Homolytic bond breaking
An orbital with an unpaired electron belonging to one atom can overlap with an orbital of another atom that also contains an unpaired electron. In this case, the formation of a covalent bond occurs according to the exchange mechanism:
H + H -> H: H, or H-H
The exchange mechanism for the formation of a covalent bond is realized if a common electron pair is formed from unpaired electrons belonging to different atoms.
The process opposite to the formation of a covalent bond by the exchange mechanism is bond breaking, in which one electron goes to each atom. As a result, two uncharged particles with unpaired electrons are formed:
Such particles are called free radicals.
free radicals- atoms or groups of atoms having unpaired electrons.
The mechanism of breaking a covalent bond, in which free radicals are formed, is called hemolytic or homolysis (homo is the same, that is, this type of bond breaking leads to the formation of identical particles).
Reactions that take place under the action and with the participation of free radicals are called free radical reactions.
The hydroxyl anion is attracted to the carbon atom (attacks the carbon atom), on which the partial positive charge is concentrated, and replaces the bromine, more precisely, the bromide anion.
In the 1-chloropropane molecule, the electron pair in the C-Cl bond is shifted towards the chlorine atom due to its greater electronegativity. In this case, the carbon atom, which has received a partial positive charge (§ +), draws electrons from the carbon atom associated with it, which, in turn, from the following:
Thus, the inductive effect is transmitted along the chain, but quickly decays: it is practically not observed already after three st-couplings.
Consider another reaction - the addition of hydrogen bromide to ethene:
CH2=CH2 + HBr -> CH3-CH2Br
At the initial stage of this reaction, a hydrogen cation is added to a molecule containing a multiple bond:
CH2=CH2 + H+ -> CH2-CH3
The electrons of the n-bond have shifted to one carbon atom, the neighboring one has a positive charge, an unfilled orbital.
The stability of such particles is determined by how well the positive charge on the carbon atom is compensated. This compensation occurs due to the shift in the electron density of the a-bond towards the positively charged carbon atom, i.e., the positive inductive effect (+1). 
The group of atoms, in this case the methyl group, from which the electron density is drawn, has a donor effect, which is denoted by +1.
mesomeric effect. There is another way of influence of some atoms or groups on others - the mesomeric effect, or the conjugation effect.
Consider a 1,3-butadiene molecule:
CH2=CH CH=CH2
It turns out that the double bonds in this molecule are not just two double bonds! Since they are close, there is an overlap P-bonds that make up neighboring doubles, and a common for all four carbon atoms is formed P- electron cloud. In this case, the system (molecule) becomes more stable. This phenomenon is called conjugation (in this case P - P- conjugation). 
Additional overlap, conjugation of n-bonds separated by one o-bond, leads to their "averaging". The central simple bond acquires a partial "double" character, becomes stronger and shorter, and the double bonds somewhat weaken and lengthen.
Another example of conjugation is the effect of a double bond on an atom that has an unshared electron pair.
So, for example, during the dissociation of a carboxylic acid, the unshared electron pair remains on the oxygen atom:
This leads to an increase in the stability of the anion formed during dissociation and an increase in the strength of the acid.
The shift in electron density in conjugated systems involving n-bonds or unshared electron pairs is called the mesomeric effect (M).
Main reaction mechanisms
We have identified three main types of reacting particles - free radicals, electrophiles, nucleophiles and three corresponding types of reaction mechanisms:
Free radical;
electrophilic;
nucleophilic.
In addition to classifying reactions according to the type of reacting particles, organic chemistry distinguishes four types of reactions according to the principle of changing the composition of molecules: addition, substitution, elimination, or elimination (from English to eliminate - remove, split off), and rearrangement. Since addition and substitution can occur under the action of all three types of reactive particles, several main reaction mechanisms can be distinguished.
In addition, we will consider the cleavage or elimination reactions that take place under the influence of nucleophilic particles - bases.
1. What are homolytic and heterolytic breaks of a covalent bond? What mechanisms of covalent bond formation are they characteristic of?
2. What are called electrophiles and nucleophiles? Give examples of them.
3. What are the differences between mesomeric and inductive effects? How do these phenomena illustrate the position of A. M. Butlerov’s theory of the structure of organic compounds on the mutual influence of atoms in the molecules of organic substances?
4. In the light of the concepts of inductive and mesomeric effects, consider the mutual influence of atoms in molecules:
Support your conclusions with examples of chemical reaction equations.
Lesson content lesson summary support frame lesson presentation accelerative methods interactive technologies Practice tasks and exercises self-examination workshops, trainings, cases, quests homework discussion questions rhetorical questions from students Illustrations audio, video clips and multimedia photographs, pictures graphics, tables, schemes humor, anecdotes, jokes, comics parables, sayings, crossword puzzles, quotes Add-ons abstracts articles chips for inquisitive cheat sheets textbooks basic and additional glossary of terms other Improving textbooks and lessonscorrecting errors in the textbook updating a fragment in the textbook elements of innovation in the lesson replacing obsolete knowledge with new ones Only for teachers perfect lessons calendar plan for the year methodological recommendations of the discussion program Integrated LessonsAll chemical reactions are accompanied by the breaking of some bonds and the formation of others. In principle, organic reactions obey the same laws as inorganic ones, but they have a qualitative originality.
So, if ions usually take part in inorganic reactions, molecules take part in organic reactions.
Reactions proceed much more slowly, in many cases requiring a catalyst, or selection of external conditions (temperature, pressure).
Unlike inorganic reactions that occur quite unambiguously, most organic reactions are accompanied by one or another number of side reactions. In this case, the yield of the main product often does not exceed 50%, but it happens that the yield is even less. But in some cases, the reaction can proceed quantitatively, i.e. with 100% yield. Due to the fact that the composition of the products is ambiguous in organic chemistry, the equations of chemical reactions are rarely used. Most often, the reaction scheme is written, which reflects the starting materials and the main reaction product, and instead of the “=” sign between the right and left parts of the scheme, “” or the reversibility sign is used.
There are two approaches to the classification of organic reactions: according to the nature of chemical transformations and according to the mechanisms of their occurrence.
According to the nature of chemical transformations, there are:
|
Substitution reactions (S - from English. Substitution - substitution) |
One atom or group of atoms is replaced by another atom or group of atoms: |
|
Addition reactions (Ad - from English. Addition - accession) |
Two or more molecules form one new substance. Attachment goes, as a rule, through multiple bonds (double, triple): |
|
Elimination reactions (E - from the English. Elimination - elimination, removal) |
Reactions of derivatives of hydrocarbons in which the functional group is split off together with hydrogen atoms to form a -bond (double, triple): |
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Regroupings (Rg - from English. Re-grouping - regrouping) |
Intramolecular reactions of redistribution of electron density and atoms: (Favorsky rearrangement). |
Classification of organic reactions according to the mechanism of occurrence.
The mechanism of a chemical reaction is the path that leads to the breaking of an old bond and the formation of a new one.
There are two mechanisms for breaking a covalent bond:
1. Heterolytic (ionic). In this case, the bonding electron pair completely passes to one of the bonded atoms:
2. Homolytic (radical). The common electron pair breaks in half with the formation of two particles with free valences - radicals:
The nature of the decay mechanism is determined by the type of the attacking particle (reagent). There are three types of reagents in organic chemistry.
1. Nucleophilic reagents (N - from Latin Nucleophilic - having an affinity for the nucleus).
Particles (atoms, groups, neutral molecules) containing excess electron density. They are divided into strong, medium strength and weak. The strength of a nucleophile is a relative concept, depending on the reaction conditions (solvent polarity). In polar solvents strong nucleophiles: , as well as neutral molecules with unshared electron pairs (in nonbonding orbitals) . Medium strength nucleophiles: . Weak nucleophiles: anions of strong acids - as well as phenols and aromatic amines.
2. Electrophilic reagents (E - from lat. Electrophilic - having an affinity for an electron).
Particles (atoms, groups, neutral molecules) that carry a positive charge or a vacant orbital, as a result of which they have an affinity for negatively charged particles or an electron pair. To the number strong electrophiles include a proton, metal cations (especially multiply charged ones), molecules that have a vacant orbital on one of the atoms (Lewis acids) -, oxygen-containing acid molecules that have high charges on an oxidized atom ().
It often happens that a molecule contains several reaction centers, and of different nature - both nucleophilic and electrophilic.
3. Radicals (R).
Depending on the type of reagent and the route of heterolytic bond cleavage, various products are formed in the substrate molecule. This can be represented in general terms:
Reactions proceeding according to such schemes are called electrophilic substitution reactions (SE), since the reaction is essentially a substitution, and the attacking agent is an electrophilic particle.
Reactions proceeding according to such schemes are called nucleophilic substitution reactions (SN), since the reaction is essentially a substitution, and the attacking agent is a nucleophilic species.
If the attacking agent is a radical, then the reaction proceeds by a radical mechanism.
>> Chemistry: Types of chemical reactions in organic chemistry
The reactions of organic substances can be formally divided into four main types: substitution, addition, elimination (elimination) and rearrangement (isomerization). It is obvious that the whole variety of reactions of organic compounds cannot be reduced to the framework of the proposed classification (for example, combustion reactions). However, such a classification will help to establish analogies with the classifications of reactions that take place between inorganic substances already familiar to you from the course of inorganic chemistry.
As a rule, the main organic compound participating in the reaction is called the substrate, and the other component of the reaction is conditionally considered as a reagent.
Substitution reactions
Reactions that result in the replacement of one atom or group of atoms in the original molecule (substrate) with other atoms or groups of atoms are called substitution reactions.
Substitution reactions involve saturated and aromatic compounds, such as, for example, alkanes, cycloalkanes or arenes.
Let us give examples of such reactions.
Reaction classification
There are four main types of reactions in which organic compounds participate: substitution (displacement), addition, elimination (cleavage), rearrangement.
3.1 Substitution reactions
In reactions of the first type, substitution usually occurs at the carbon atom, but the substituted atom may be a hydrogen atom or some other atom or group of atoms. In electrophilic substitution, a hydrogen atom is most often replaced; an example is classical aromatic substitution:
In nucleophilic substitution, it is more often not the hydrogen atom that is replaced, but other atoms, for example:
NC - + R−Br → NC−R +BR -
3.2 Addition reactions
Addition reactions can also be electrophilic, nucleophilic, or radical, depending on the type of species initiating the process. Attachment to conventional carbon-carbon double bonds is usually induced by an electrophile or a radical. For example, adding HBr
may begin with an attack on the double bond by the H + proton or the Br· radical.
3.3 Elimination reactions
Elimination reactions are essentially the reverse of addition reactions; the most common type of such reaction is the elimination of a hydrogen atom and another atom or group from neighboring carbon atoms to form alkenes:
3.4 Rearrangement reactions
Rearrangements can also occur through intermediates that are cations, anions, or radicals; most often these reactions go with the formation of carbocations or other electron-deficient particles. The rearrangements may involve a significant rearrangement of the carbon skeleton. The actual rearrangement step in such reactions is often followed by substitution, addition, or elimination steps leading to the formation of a stable end product.
A detailed description of a chemical reaction in stages is called a mechanism. From an electronic point of view, the mechanism of a chemical reaction is understood as a method of breaking covalent bonds in molecules and a sequence of states through which the reacting substances pass before being converted into reaction products.
4.1 Free radical reactions
Free radical reactions are chemical processes in which molecules with unpaired electrons take part. Certain aspects of free radical reactions are unique compared to other types of reactions. The main difference is that many free radical reactions are chain reactions. This means that there is a mechanism by which many molecules are converted into a product through a repetitive process initiated by the creation of a single reactive species. A typical example is illustrated with the following hypothetical mechanism:
The stage at which the reaction intermediate is generated, in this case A·, is called initiation. This stage takes place at high temperature, under the action of UV or peroxides, in non-polar solvents. The next four equations in this example repeat the sequence of two reactions; they represent the development phase of the chain. Chain reactions are characterized by the chain length, which corresponds to the number of developmental stages per initiation stage. The second stage proceeds with the simultaneous synthesis of the compound and the formation of a new radical, which continues the chain of transformations. The last step is chain termination, which includes any reaction that destroys one of the reaction intermediates necessary for chain propagation. The more stages of chain termination, the shorter the chain length becomes.
Free radical reactions proceed: 1) in the light, at high temperature or in the presence of radicals, which are formed during the decomposition of other substances; 2) inhibited by substances that easily react with free radicals; 3) proceed in non-polar solvents or in the vapor phase; 4) often have an autocatalytic and induction period before the start of the reaction; 5) kinetically they are chain.
Radical substitution reactions are characteristic of alkanes, and radical addition reactions are characteristic of alkenes and alkynes.
CH 4 + Cl 2 → CH 3 Cl + HCl
CH 3 -CH \u003d CH 2 + HBr → CH 3 -CH 2 -CH 2 Br
CH 3 -C≡CH + HCl → CH 3 -CH=CHCl
The connection of free radicals with each other and chain termination occurs mainly on the walls of the reactor.
4.2 Ionic reactions
The reactions in which heterolytic rupture of bonds and the formation of intermediate particles of the ionic type are called ionic reactions.
Ionic reactions proceed: 1) in the presence of catalysts (acids or bases and are not affected by light or free radicals, in particular, arising from the decomposition of peroxides); 2) are not affected by free radical scavengers; 3) the nature of the solvent affects the course of the reaction; 4) rarely occur in the vapor phase; 5) kinetically, they are mainly reactions of the first or second order.
According to the nature of the reagent acting on the molecule, ionic reactions are divided into electrophilic And nucleophilic. Nucleophilic substitution reactions are characteristic of alkyl and aryl halides,
CH 3 Cl + H 2 O → CH 3 OH + HCl
C 6 H 5 -Cl + H 2 O → C 6 H 5 -OH + HCl
C 2 H 5 OH + HCl → C 2 H 5 Cl + H 2 O
C 2 H 5 NH 2 + CH 3 Cl → CH 3 -NH-C 2 H 5 + HCl
electrophilic substitution - for alkanes in the presence of catalysts
CH 3 -CH 2 -CH 2 -CH 2 -CH 3 → CH 3 -CH (CH 3) -CH 2 -CH 3
and arenas.
C 6 H 6 + HNO 3 + H 2 SO 4 → C 6 H 5 -NO 2 + H 2 O
Electrophilic addition reactions are characteristic of alkenes
CH 3 -CH \u003d CH 2 + Br 2 → CH 3 -CHBr-CH 2 Br
and alkynes
CH≡CH + Cl 2 → CHCl=CHCl
nucleophilic addition - for alkynes.
CH 3 -C≡CH + C 2 H 5 OH + NaOH → CH 3 -C (OC 2 H 5) = CH 2
