Nitriles are named in various ways:
CH 3 CN CH 2 =CHCN PhCN NC(CH 2) 4 CN
ethanenitrile propenenitrile benzenecarbonitrile adiponitrile
(acetonitrile) (acrylonitrile) (benzonitrile)
Methods for producing nitriles
3.1.1. Preparation of nitriles by dehydration of amides
The dehydration of amides, which we discussed in the previous section, can serve as the last stage in the chain of transformations of a carboxylic acid into the nitrile of this acid:
All these reactions are often combined in one process, passing a mixture of carboxylic acid and ammonia through aluminum oxide at 500 o C:
Exercise 46. Write the reaction of the industrial method for producing adiponitrile from adipic acid.
3.1.2. Preparation of nitriles by oxidative ammonolysis of hydrocarbons
When studying the oxidation of hydrocarbons, we saw that hydrocyanic acid (formic acid nitrile) and nitriles of other acids are obtained by oxidative ammonolysis of the corresponding hydrocarbons according to the scheme:
Exercise 47. Write the reactions for the preparation of (a) acrylonitrile, (b) benzonitrile, (c) acetonitrile and (d) terephthalic acid nitrile by oxidative amonolysis of the corresponding hydrocarbons.
3.1.3. Preparation of nitriles by the Kolbe reaction
When halohydrocarbons react with potassium cyanide in aqueous ethanol using the S N 2 mechanism, nitriles are formed:
Since the cyanide anion is an ambident ion, isonitriles are formed as a by-product, which are removed by shaking the reaction mixture with dilute hydrochloric acid.
Exercise 48. Write the reactions for the preparation through the corresponding halohydrocarbons of (a) propionitrile from ethylene, (b) butyronitrile from propylene, (c) succinic acid dinitrile from ethylene, (d) vinyl acetic acid nitrile from propylene, (e) phenylacetic acid nitrile from toluene, ( f) adipic acid dinitrile from acetylene.
Exercise 49. Complete the reactions:
Reactions of nitriles
3.2.1. Hydrogenation of nitriles
Nitriles are easily hydrogenated into amines. Hydrogenation is carried out either with hydrogen at the time of separation (C 2 H 5 OH + Na) or catalytically:
Exercise 50. Write the hydrogenation reactions of (a) propionitrile, (b) butyronitrile, (c) succinic acid dinitrile, (d) vinylacetic acid nitrile, (e) phenylacetic acid nitrile, (f) adipic acid dinitrile.
3.2.2. Hydrolysis of nitriles
Nitriles, obtained from metal alkyl halides and cyanides by nucleophilic substitution, are good starting products for the preparation of carboxylic acids. To do this, they are subjected to hydrolysis in the presence of acids or bases:
Exercise 51. What acids are formed during the hydrolysis of the following nitriles:
(a) propionitrile, (b) butyronitrile, (c) succinic acid dinitrile, (d) vinylacetic acid nitrile, (e) phenylacetic acid nitrile, (f) adipic acid dinitrile.
According to this scheme, phenylacetic acid is obtained from available benzyl chloride:
Exercise 52. Propose a scheme for the preparation of phenylacetic acid starting from toluene. Describe the mechanisms of the corresponding reactions.
Malonic acid is mainly obtained from chloroacetic acid according to the following scheme:
Exercise 53. Based on ethylene and other necessary reagents, propose a scheme for the production of butanedioic (succinic) acid.
Exercise 54. Using the corresponding halohydrocarbons and nitriles, propose schemes for the preparation of the following acids: (a) propionic acid from ethylene, (b) butyric acid from propylene, (c) succinic acid from ethylene, (d) vinyl acetic acid from propylene, (e) phenylacetic acid from toluene, ( e) adipic acid from acetylene.
From the available cyanohydrins, α-hydroxy acids are obtained:
Exercise 55. Based on the corresponding aldehydes and ketones and other necessary reagents, propose schemes for the preparation of (a) 2-hydroxypropionic acid and
(b) 2-methyl-2-hydroxypropionic acid.
Alcoholysis of nitriles
Nitriles react with hydrogen chloride to form iminochlorides:
iminochloride
The action of hydrogen chloride in alcohol on nitriles leads to the formation of imino ester hydrochlorides, further hydrolysis of which gives esters:
Methyl methacrylate is industrially obtained from acetone via cyanohydrin:
acetone acetone cyanohydrin methyl methacrylate
Methyl methacrylate polymer - polymethyl methacrylate is used in the manufacture of safety glass (plexiglass).
Ex. 56. What product is formed as a result of the sequential action of potassium cyanide on benzyl chloride, ethanol in the presence of hydrogen chloride, and finally water? Write the appropriate reactions.
Ex. 57. What product is formed as a result of the sequential action of hydrocyanic acid on acetaldehyde, and then methanol in the presence of sulfuric acid? Write the appropriate reactions.
Nucleophilicis a reaction in which a reagent attacks the substrate with its nucleophile; it is denoted by an index N (nucleophlle).
In electrophilic reactions, the reagent is usually called an electrophile. In organic chemistry, the electrophilicity of a reagent characterizes its ability to interact with a carbon atom of the substrate that carries a full or partial negative charge.
In fact, the mechanism and result of any electrophilic-nucleophilic reaction is determined not only by the properties of the reagent, but also by the properties of the substrate, the resulting reaction products, the solvent and the conditions for its implementation. Therefore, the division of electrophilic-nucleophilic reactions into nucleophilic and electrophilic only based on the properties of the reagent is conditional. In addition, as can be seen from the above diagrams, in these reactions the electrophiles and nucleophiles contained in the substrate and reagent always interact with each other. In many reactions, only conditionally one component can be considered a substrate and the other a reagent.
Free radical reactions. Homolytic decay is characteristic of non-polar or low-polar bonds. It is accompanied by the formation of free radicals - particles with an unpaired electron.
Homolysis of a covalent bond can be considered as the cleavage of this bond by an exchange mechanism. To carry out homolysis of a bond, energy (heat, light) is required sufficient to break this bond. The presence of an unpaired electron is the reason for the low stability of free radicals (the lifetime in most cases is a fraction of a second) and high reactivity in free radical reactions. The presence of a free radical (R۰) in the system can lead to the formation of new radicals due to its interaction with existing molecules: R۰ + A – B → R – A + ۰B
Free radical reactionsare accompanied by the interaction of free radicals with molecules or with each other with the formation of new free radicals (nucleation or development of a chain) or only molecules (chain termination).
Free radical reactions are characterized by a chain mechanism, which includes three stages: initiation, development and chain termination. These reactions stop when free radicals disappear from the system. Free radical reactions are designated by the index R (radical).
Radical particles, depending on their electron affinity, can both accept electrons (i.e., be oxidizing agents) and donate electrons (i.e., be reducing agents). In this case, the affinity of a radical for an electron is determined not only by its properties, but also by the properties of its reaction partner. The features of free radical oxidation-reduction processes occurring in the body are considered separately when describing the properties of certain classes of organic compounds.
In complexation reactions, radicals can be both complexing agents and ligands. In the case of charge transfer complexes, radical formation can occur within the complex due to intramolecular oxidation-reduction between the complexing agent and the ligand.
The formation of radicals most easily occurs during the homolysis of nonpolar simple bonds between atoms of the same element:
C1 2 → C1۰ + ۰С1 HO-OH → СО۰ + ۰ОН
R-O-O-R" → RO۰ + ۰OR" R-S-S-R" →RS۰ + ۰SR"
Homolysis of a low-polarity CH bond produces alkyl radicals in which the unpaired electron is located at the carbon atom. The relative stability of these radicals depends on the type of substitution of the carbon atom bearing the unpaired electron, and increases in the series: CH 3< CH 2 R < CHR 2 < CR 3 . Это объясняется положительным индуктивным эффектом алкильных групп, который, повышая электронную плотность на атоме углерода, способствует стабилизации радикала.
The stability of free radicals increases significantly when it is possible to delocalize the unpaired electron due to the π-electrons of neighboring multiple bonds. This is especially clearly observed in the allylic and benzyl radicals:
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allylic radical benzyl radical
When familiarizing yourself with possible reaction mechanisms in substrate and reagent molecules, reaction centers should be distinguished by their nature: nucleophilic, electrophilic And radical.
According to the final result of the chemical transformation, the simplest organic reactions are classified into reactions: substitution, addition, elimination (elimination) And regrouping.
Substitution reactions. Substitution refers to the replacement of an atom or group with another atom or group. In a substitution reaction, two different products are always formed. This type of reaction is designated by the symbol S (substitution).
Substitution reactions include: halogenation and nitration of alkanes, esterification and alkylation of carboxylic acids, as well as numerous reactions of simple polar molecules (H 2 O, NH 3, NGal) with ethers, alcohols and halogen derivatives.
Addition reactions. By addition we mean the introduction of atoms or groups into the molecule of an unsaturated compound, accompanied by the breaking of π bonds. In this case, double bonds turn into single bonds, and triple bonds into double or single bonds. This type of reaction is indicated by the symbol A (addition).
Elimination reactions. Elimination refers to the removal of atoms or groups from an organic molecule to form a multiple bond. Therefore, elimination reactions are the opposite of addition reactions. This type of reaction is designated by the symbol E (elimination).
Each of the organic reactions of substitution (S), addition (A) or elimination (E) can be electrophilic (E), nucleophilic (N) or radical (R). Thus, in organic chemistry there are nine typical reactions, denoted by the symbols S, A or E with the subscripts R, N or E:
The given types of organic reactions should be considered model ones, since they are not always realized in their pure form. For example, substitution and elimination can occur simultaneously:
With further acquaintance with specific classes of organic compounds, we will consider their following chemical properties: acid-base, complexing, redox, electrophilic-nucleophilic, as well as the ability for free radical interaction. Particular attention will be paid to the peculiarities of the occurrence of the reactions under consideration in biological systems.
The types of reactions characteristic of various classes of hydrocarbons, the mechanism of their occurrence and the biological significance of the processes are presented in Table 10.
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Organic reactions can be divided into two general types.
Hemolytic reactions. These reactions proceed by a radical mechanism. We'll look at them in more detail in the next chapter. The kinetics and mechanism of reactions of this type were discussed in Chap. 9.
Heterolytic reactions. These reactions are essentially ionic reactions. They can, in turn, be divided into substitution, addition and elimination reactions.
Substitution reactions
In these reactions, an atom or group of atoms is replaced by another atom or group. As an example of reactions of this type, we give the hydrolysis of chloromethane with the formation of methanol:
The hydroxyl ion is a nucleophile. Therefore, the substitution in question is called nucleophilic substitution. It is designated by the symbol SN. The replaced particle (in this case, a chlorine ion) is called a leaving group.
If we denote the nucleophile by the symbol and the leaving group by the symbol, then we can write the generalized equation for the reaction of nucleophilic substitution at a saturated carbon atom in the alkyl group R as follows:
A study of the rate of reactions of this type shows that reactions can be divided into
Reactions of the type For some reactions of the SN type, the kinetic equation for the reaction rate (see Section 9.1) has the form
Thus, these reactions are first order in the substrate but zero order in the reactant. The kinetics characteristic of a first order reaction is a reliable indication that the rate-limiting step of the reaction is a unimolecular process. Therefore, reactions of this type are indicated by the symbol.
The reaction has zero order with respect to the reagent since its rate does not depend on the concentration of the reagent. Therefore, we can write:
Since the nucleophile does not participate in the rate-limiting step of the reaction, the mechanism of such a reaction must include at least two steps. The following mechanism has been proposed for such reactions:
The first stage is ionization with the formation of a carbocation. This stage is limiting (slow).
An example of this type of reaction is the alkaline hydrolysis of tertiary alkyl halides. For example
In the case under consideration, the reaction rate is determined by the equation
Reactions of the type For some reactions of nucleophilic substitution SN the rate equation has the form
In this case, the reaction is first order in the nucleophile and first order in . In general, it is a second order reaction. This is sufficient reason to believe that the rate-limiting stage of this reaction is a bimolecular process. Therefore, the reaction of the type under consideration is denoted by the symbol Since both the nucleophile and the substrate simultaneously participate in the rate-limiting stage of the reaction, we can think that this reaction proceeds in one stage through a transition state (see Section 9.2):
Hydrolysis of primary alkyl halides in an alkaline medium proceeds according to the mechanism
This reaction has the following kinetic equation:
So far we have considered nucleophilic substitution only at the saturated carbon atom. Nucleophilic substitution is also possible at an unsaturated carbon atom:
Reactions of this type are called nucleophilic acyl substitution.
Electrophilic substitution. Electrophilic substitution reactions can also occur on benzene rings. In this type of substitution, the benzene ring supplies the electrophile with two of its delocalized -electrons. In this case, an intermediate compound is formed - an unstable complex of an electrophile and a leaving group. For a schematic representation of such complexes, an open circle is used, indicating the loss of two -electrons:
An example of electrophilic substitution reactions is the nitration of benzene:
Nitration of benzene is carried out in an installation with a reflux condenser at a temperature of 55 to 60 ° C using a nitrating mixture. This mixture contains equal amounts of concentrated nitric and sulfuric acids. The reaction between these acids leads to the formation of a nitroyl cation
Addition reactions
In reactions of this type, an electrophile or nucleophile is added to an unsaturated carbon atom. We will consider here one example each of electrophilic addition and nucleophilic addition.
An example of electrophilic addition is the reaction between hydrogen bromide and an alkene. To obtain hydrogen bromide in the laboratory, a reaction between concentrated sulfuric acid and sodium bromide can be used (see Section 16.2). Hydrogen bromide molecules are polar because the bromine atom has a negative inductive effect on hydrogen. Therefore, the hydrogen bromide molecule has the properties of a strong acid. According to modern views, the reaction of hydrogen bromide with alkenes occurs in two stages. In the first stage, a positively charged hydrogen atom attacks the double bond, which acts as a source of electrons. As a result, an activated complex and a bromide ion are formed:
The bromide ion then attacks this complex, resulting in the formation of an alkyl bromide:
An example of nucleophilic addition is the addition of hydrogen cyanide to any aldehyde or ketone. First, the aldehyde or ketone is treated with an aqueous solution of sodium cyanide. Then an excess amount of any mineral acid is added, which leads to the formation of hydrogen cyanide HCN. The cyanide ion is a nucleophile. It attacks the positively charged carbon atom on the carbonyl group of the aldehyde or ketone. The positive charge and polarity of the carbonyl group is due to the mesomeric effect, which was described above. The reaction can be represented by the following diagram:
Elimination reactions
These reactions are the reverse of addition reactions. They lead to the removal of any atoms or groups of atoms from two carbon atoms connected to each other by a simple covalent bond, resulting in the formation of a multiple bond between them.
An example of such a reaction is the elimination of hydrogen and halogen from alkyl halides:
To carry out this reaction, the alkyl halide is treated with potassium hydroxide in alcohol at a temperature of 60 °C.
It should be noted that treatment of an alkyl halide with hydroxide also leads to nucleophilic substitution (see above). As a result, two competing substitution and elimination reactions occur simultaneously, which leads to the formation of a mixture of substitution and elimination products. Which of these reactions will be predominant depends on a number of factors, including the environment in which the reaction is carried out. Nucleophilic substitution of alkyl halides is carried out in the presence of water. In contrast, elimination reactions are carried out in the absence of water and at higher temperatures.
So let's say it again!
1. During hemolytic cleavage of a bond, two shared electrons are distributed evenly between atoms.
2. During heterolytic bond cleavage, two shared electrons are distributed unevenly between atoms.
3. A carbanion is an ion containing a carbon atom with a negative charge.
4. A carbocation is an ion containing a carbon atom with a positive charge.
5. Solvent effects can have a significant impact on chemical processes and their equilibrium constants.
6. The effect of the chemical environment of a functional group within a molecule on the reactivity of that functional group is called the structural effect.
7. Electronic effects and steric effects are collectively called structural effects.
8. The two most important electronic effects are the inductive effect and the mesomeric (resonant) effect.
9. The inductive effect is the shift of electron density from one atom to another, which leads to polarization of the bond between the two atoms. This effect can be positive or negative.
10. Molecular particles with multiple bonds can exist in the form of resonant hybrids between two or more resonant structures.
11. The mesomeric (resonance) effect consists in the stabilization of resonant hybrids due to the delocalization of -electrons.
12. Steric hindrance can occur when bulky groups in a molecule mechanically impede the reaction.
13. Nucleophile is a particle that attacks a carbon atom, supplying it with its electron pair. The nucleophile is a Lewis base.
14. An electrophile is a particle that attacks a carbon atom, accepting its electron pair. The nucleophile is a Lewis acid.
15. Hemolytic reactions are radical reactions.
16. Heterolytic reactions are mainly ionic reactions.
17. The replacement of any group in a molecule with a nucleophilic reagent is called nucleophilic substitution. The group being replaced in this case is called the leaving group.
18. Electrophilic substitution on a benzene ring involves the donation of two delocalized electrons to some electrophile.
19. In electrophilic addition reactions, an electrophile is added to an unsaturated carbon atom.
20. The addition of hydrogen cyanide to aldehydes or ketones is an example of nucleophilic addition.
21. In elimination (elimination) reactions, some atoms or groups of atoms are separated from two carbon atoms connected to each other by a simple covalent bond. As a result, a multiple bond is formed between these carbon atoms.
