The structure of the nitro group. Preparation methods and chemical properties of nitro compounds
Nitration of aromatic compounds is the main way to obtain nitro compounds. The process of nitration as a special case of electrophilic substitution in the aromatic series has already been considered earlier. Therefore, it seems appropriate to focus on the synthetic possibilities of this reaction.
Benzene itself is nitrated quite easily and with good results.
Under more severe conditions, nitrobenzene is also able to nitrate with the formation m- dinitrobenzene
Due to the deactivating effect of two nitro groups, introduce a third nitro group into m-dinitrobenzene is possible only with great difficulty. 1,3,5-Trinitrobenzene was obtained in 45% yield by nitration m-dinitrobenzene at 100-110 about C and the duration of the reaction is 5 days.
The difficulties in obtaining trinitrobenzene by direct nitration of benzene led to the development of indirect methods. According to one of them, trinitrotoluene, which is more accessible than trinitrobenzene, is oxidized to 2,4,6-trinitrobenzoic acid, which is easily decarboxylated when heated in water.
Similarly, indirect methods have to be resorted to if it is necessary to obtain 1,2-dinitrobenzene. In this case, the ability of the amino group to be oxidized to the nitro group in O-nitroaniline
Even in those cases where the preparation of nitro compounds by nitration should not have encountered any special difficulties, one has to turn to indirect methods. So, it is not possible to obtain picric acid by nitration of phenol, because Phenol is not nitrated with nitric acid, but oxidized. Therefore, the following scheme is usually used
The subtleties of this scheme are that, due to the deactivation of the ring by chlorine and two already existing nitro groups, it is not possible to introduce a third nitro group into it. Therefore, chlorine in dinitrochlorobenzene is preliminarily replaced by hydroxyl, which the nitro groups just contribute to (bimolecular substitution). The resulting dinitrophenol easily accepts another nitro group without being oxidized to a noticeable degree. The existing nitro groups protect the benzene ring from oxidation.
Another non-obvious way to obtain picric acid is the sulfonation of phenol to 2,4-phenol disulfonic acid, followed by nitration of the resulting compound. In this case, simultaneously with nitration, the replacement of sulfo groups by nitro groups occurs
One of the most important aromatic nitro derivatives, trinitrotoluene, is obtained in technology by the nitration of toluene, which proceeds according to the following scheme
Chemical properties
Aromatic nitro compounds are capable of reacting both with the participation of the benzene ring and the nitro group. These structural elements affect each other's reactivity. So, under the influence of the nitro group, nitrobenzene is reluctant to enter into the electrophilic substitution reaction and the new substituent accepts m-position. The nitro group affects not only the reactivity of the benzene ring, but also the behavior of neighboring functional groups in chemical reactions.
Consider the reactions of aromatic nitro compounds at the expense of the nitro group.
16.2.1. Recovery. One of the most important reactions of nitro compounds is their reduction to aromatic amines, which are widely used in the production of dyes, drugs, and photochemicals.
The possibility of converting a nitro group into an amino group by the reduction of nitro compounds was first shown by Zinin in 1842 using the example of the reaction of nitrobenzene with ammonium sulfide
Subsequently, the reduction of aromatic nitro compounds was the subject of deep study. It was found that, in the general case, the reduction is complex, proceeding through a number of stages with the formation of intermediate products. Amines are only the end product of the reaction. The result of the reduction is determined by the strength of the reducing agent and the pH of the medium. In electrochemical reduction, the composition of the products depends on the magnitude of the potential at the electrodes. By varying these factors, it is possible to delay the recovery process at intermediate stages. In neutral and acidic media, the reduction of nitrobenzene proceeds sequentially through the formation of nitrosobenzene and phenylhydroxylamine
When the reduction is carried out in an alkaline medium, the resulting nitrosobenzene and phenylhydroxylamine are able to condense with each other to form azoxybenzene, in which the nitrogen and oxygen atoms are linked by a semipolar bond
The proposed mechanism of condensation resembles the mechanism of aldol condensation
The reduction of azoxybenzene to aniline goes through azo- and hydrazobenzenes
All of the intermediates mentioned above for the reduction of nitrobenzene to aniline can be obtained either directly from nitrobenzene or starting from each other. Here are some examples
16.2.2. Influence of the nitro group on the reactivity of other functional groups. In the study of aromatic halogen derivatives, we have already met with the case when a suitably located nitro group (nitro groups) significantly influenced the nucleophilic substitution of the halogen (bimolecular substitution of the aromatic halogen). For example O- and P-dinitrobenzenes, it was found that the nitro group can contribute to the nucleophilic substitution of not only the halogen, but even another nitro group
The mechanism of bimolecular substitution of a nitro group by a hydroxyl group can be represented as the following two-stage process
The carbanion formed at the first stage of the reaction under consideration is resonantly stabilized due to the contribution of the limiting structure 1, in which the nitro group withdraws electrons from the very carbon of the benzene ring, which has an excess of them.
A feature of the nucleophilic substitution of one nitro group under the influence of another nitro group is that the reaction is very sensitive to the location of the nitro groups relative to each other. It is known that m-dinitrobenzene does not react with an alcohol solution of ammonia even at 250 o C.
Other examples of promoting nitro group substitution, in this case hydroxyl, are the transformations of picric acid
16.2.3. Complex formation with aromatic hydrocarbons. A characteristic property of aromatic nitro compounds is their tendency to form complexes with aromatic hydrocarbons. Bonds in such complexes are electrostatic in nature and arise between electron-donor and electron-acceptor particles. The complexes under consideration are called π -complexes or complexes with charge transfer.
π –Complexes in most cases are crystalline substances with characteristic melting points. If necessary π -complex can be destroyed with the release of hydrocarbons. Due to the combination of these properties π -complexes are used for isolation, purification and identification of aromatic hydrocarbons. Especially often picric acid is used for complexation, the complexes of which are incorrectly called picrates.
Chapter 17
Amines
According to the degree of substitution of hydrogen atoms in ammonia for alkyl and aryl substituents, primary, secondary and tertiary amines are distinguished. Depending on the nature of the substituents, amines can be fatty-aromatic or purely aromatic.
Aromatic amines are named by adding the ending "amine" to the names of the groups associated with nitrogen. In complex cases, the amino group with a smaller substituent is designated by the prefix "amino" (N-methylamino-, N,N-dimethylamino), which is added to the name of the more complex substituent. Below are the most common amines and their names
Acquisition Methods
We have already encountered many of the methods for preparing amines in the study of aliphatic amines. When applying these methods to the synthesis of aromatic amines, some features are encountered, therefore, without fear of repetition, we will consider them.
17.1.1. Recovery of nitro compounds. The reduction of nitro compounds is the main method for both laboratory and industrial production of amines, which can be carried out in several ways. These include catalytic hydrogenation, atomic hydrogen reduction, and chemical reduction.
Catalytic reduction is carried out with molecular hydrogen in the presence of finely ground nickel or platinum, copper complex compounds on carriers. When choosing a catalyst and reduction conditions, it must be borne in mind that other functional groups can be reduced in this case. In addition, the catalytic reduction of nitro compounds must be carried out with some care due to the extreme exothermicity of the reaction.
When using ammonium sulfide as a chemical reducing agent, it becomes possible to reduce only one of several nitro groups
17.1.2. Amination of halogen derivatives. Difficulties that arise during the amination of aromatic halogen derivatives by the "elimination - addition" mechanism are known. However, as has already been mentioned more than once, electron-withdrawing substituents in the benzene ring, properly located, greatly facilitate the substitution of the halogen in aryl halides, directing the process along a bimolecular mechanism. For comparison, below are the conditions for the amination of chlorobenzene and dinitrochlorobenzene
17.1.3. Splitting according to Hoffmann. Cleavage of acid amides according to Hoffmann makes it possible to obtain primary amines, which contain one carbon less than the original amides.
The reaction proceeds with the migration of phenyl from the carbonyl carbon to the nitrogen atom (1,2-phenyl shift) according to the following proposed mechanism
17.1.4. Alkylation and arylation of amines. Alkylation of primary and secondary aromatic amines with halogenated alkyls or alcohols makes it possible to obtain secondary and tertiary fatty aromatic amines.
Unfortunately, with the participation of primary amines in the reaction, a mixture is obtained. This can be avoided if the starting amine is first acylated and then alkylated
This method of protecting the amino group makes it possible to obtain pure secondary aromatic amines, as well as tertiary amines with different substituent radicals.
Arylation of amines makes it possible to obtain pure secondary and tertiary aromatic amines
Chemical properties
Aromatic amines react both with the participation of the amino group and the benzene ring. In this case, each functional group is influenced by another group.
Reactions on the amino group
Due to the presence of an amino group, aromatic amines enter into numerous reactions. Some of them have already been considered: alkylation, acylation, reaction with aldehydes to form azomethines. Other reactions to which attention will be paid are easily predictable, but they have certain peculiarities.
Basicity
The presence of a lone pair of electrons at the nitrogen atom, which can be presented to form a bond with a proton, provides aromatic amines with the main properties
Of interest is the comparison of the basicity of aliphatic and aromatic amines. As has already been shown in the study of aliphatic amines, it is convenient to judge the basicity of amines by the basicity constant K in
Let's compare the basicity of aniline, methylamine and ammonia
Ammonia 1.7. 10-5
Methylamine 4.4. 10-4
Aniline 7.1. 10 -10
It can be seen from these data that the appearance of an electron-donating methyl group increases the electron density at the nitrogen atom and leads to an increase in the basicity of methylamine compared to ammonia. At the same time, the phenyl group weakens the basicity of aniline by more than 105 times compared to ammonia.
The decrease in the basicity of aniline compared to aliphatic amines and ammonia can be explained by the conjugation of the lone pair of nitrogen electrons with the electron sextet of the benzene ring
This reduces the ability of the lone pair of electrons to accept a proton. This trend is even more pronounced for aromatic amines, which contain electron-withdrawing substituents in the benzene ring.
So, m-nitroaniline as a base is 90 times weaker than aniline.
As might be expected, electron-donating substituents on the benzene ring enhance the basicity of aromatic amines.
Fatty-aromatic amines under the influence of an alkyl group exhibit greater basicity than aniline and amines with electron-withdrawing groups in the ring.
Limit open-chain nitro compounds (non-cyclic) have the general formula C n H 2n+1 NO 2 . They are isomeric to alkyl nitrites (esters of nitrous acid) with the general formula R-ONO. The differences are:
Alkyl nitrites have lower boiling points
Nitro compounds are highly polar and have a large dipole moment
Alkyl nitrites are easily saponified by alkalis and mineral acids to form the corresponding alcohols and nitrous acid or its salt.
Reduction of nitro compounds leads to amines, alkyl nitrites to alcohols and hydroxylamine.
Receipt
According to the Konovalov reaction - by nitration of paraffins with dilute nitric acid when heated. All hydrocarbons enter into the liquid-phase nitration reaction, but the reaction rate is low and the yields are low. The reaction is accompanied by oxidation and the formation of polynyrocompounds. The best results are obtained with hydrocarbons containing a tertiary carbon atom. Vapor-phase nitration proceeds at 250-500 o C with nitric acid vapor. The reaction is accompanied by cracking of hydrocarbons, resulting in all kinds of nitro derivatives, and oxidation, which results in the formation of alcohols, aldehydes, ketones, acids. Unsaturated hydrocarbons are also formed. Nitric acid can be replaced by nitrogen oxides. Nitration proceeds by the S R mechanism.
Interaction of halogen derivatives of saturated hydrocarbons with silver nitrite when heated. The attacking particle is the NO 2 - ion, which exhibits dual reactivity (ambivalence), i.e. add a radical on nitrogen (S N 2) to form a nitro compound R-NO 2 or oxygen to form a nitrous acid ester R-O-N=O.(S N 1). The mechanism of the reaction and its direction strongly depend on the nature of the solvent. Solvating solvents (water, alcohols) favor the formation of ether.
Chemical properties
When reducing nitro compounds, primary amines are formed:
Primary and secondary nitro compounds are soluble in alkalis with the formation of salts. Hydrogen atoms at the carbon bound to the nitro group are activated, as a result, in an alkaline environment, the niro compounds are rearranged into the aci-nitro form:
When an alkaline solution of a nitro compound is treated with a mineral acid, a strongly acidic aci form is formed, which quickly isomerizes into the usual neutral form:
Nitro compounds are referred to as pseudoacids. Pseudoacids are neutral and non-conductive, but nevertheless form neutral alkali metal salts. Neutralization of nitro compounds with alkalis occurs slowly, and true acids - instantly.
Primary and secondary nitro compounds react with nitrous acid, tertiary ones do not react:
Alkaline salts of nitrolic acids in solution are red, pseudonitrols are blue or greenish-blue.
Primary and secondary niro compounds condense in the presence of alkalis with aldehydes, forming nitro alcohols (nucleophilic addition):
Aci-forms of primary and secondary nitro compounds in aqueous solutions under the action of mineral acids form aldehydes or ketones:
Primary nitro compounds, when heated with 85% sulfuric acid, transform into carboxylic acids with the elimination of hydroxylamine. This occurs as a result of hydrolysis of the resulting aci-form.
N- and O-nitro compounds are also known (see also Organic nitrates).
The nitro group has a structure intermediate between the two limiting resonance structures:
PHYSICAL PROPERTIES OF SOME ALIPHATIC NITRO COMPOUNDS
* At 25°C. ** At 24°C. *** At 14°C.
In the IR spectra of nitro compounds, there are two characteristic. bands corresponding to antisymmetric and symmetric stretching vibrations of the N-O bond: for primary nitro compounds, respectively. 1560-1548 and 1388-1376 cm -1 , for secondary 1553-1547 and 1364-1356 cm -1 , for tertiary 1544-1534 and 1354-1344 cm -1 ; for nitroolefins RCH=CHNO 2 1529-1511 and 1351-1337 cm -1 ; for dinitroalkanes RCH(NO 2) 2 1585-1575 and 1400-1300 cm -1 ; for trinitroalkanes RC(NO 2) 3 1610-1590 and 1305-1295 cm -1; for aromatic H. 1550-1520 and 1350-1330 cm -1 (electron-withdrawing substituents shift the high-frequency band to the region 1570 -1540, and electron-donor - to the region 1510-1490 cm -1); for H. 1610-1440 and 1285-1135 cm -1; nitrone ethers have an intense band at 1630-1570 cm, the C-N bond has a weak band at 1100-800 cm -1 .
In the UV spectra of aliphatic nitro compounds l max 200-210 nm (intense band) and 270-280 nm (weak band); for and nitronic acid esters respectively. 220-230 and 310-320 nm; for gem-dinitrocomponent. 320-380 nm; for aromatic H. 250-300 nm (the intensity of the band sharply decreases when the coplanarity is violated).
In the PMR spectrum, chem. shifts of a-H-atom depending on the structure 4-6 ppm In the NMR spectrum 14 N and 15 N chem. shift 5 from - 50 to + 20 ppm
In the mass spectra of aliphatic nitro compounds (with the exception of CH 3 NO 2), the peak mol. absent or very small; main the fragmentation process is the elimination of NO 2 or two to form a fragment equivalent to . Aromatic nitro compounds are characterized by the presence of a peak mol. ; main the peak in the spectrum corresponds to that obtained by elimination of NO 2 .
Chemical properties. The nitro group is one of the most strong electron-withdrawing groups and is able to effectively delocalize negative. charge. In the aromatic conn. as a result of induction and especially it affects the distribution: the kernel acquires a partial posit. a charge that is localized mainly in the ortho and para positions; Hammett constants for the NO 2 group s m 0.71, s n 0.778, s + n 0.740, s - n 1.25. So arr., the introduction of the NO 2 group dramatically increases the reaction. ability org. conn. in relation to the nucleoph. reagents and makes it difficult to react with electrophore. reagents. This determines the widespread use of nitro compounds in org. synthesis: the NO 2 group is introduced into the desired position org. Comm., carry out decomp. reactions associated, as a rule, with a change in the carbon skeleton, and then transformed into another function or removed. In the aromatic In a row, a shorter scheme is often used: nitration-transformation of the NO 2 group.
Mn. transformations of aliphatic nitro compounds take place with a preliminary. into nitronic acids or the formation of the corresponding . In solutions, the equilibrium is usually almost completely shifted towards the C-form; at 20 °C, the proportion of aci-form for 1 10 -7, for nitropropane 3. 10 -3 . Nitronic acids in free. the form is usually unstable; they are obtained by careful acidification with H. Unlike H., they conduct current in solutions and give a red color with FeCl 3 . Aci-N.-stronger CH-acids (pK a ~ 3-5) than the corresponding nitro compounds (pK a ~ 8-10); the acidity of nitro compounds increases with the introduction of electron-withdrawing substituents in the a-position to the NO 2 group.
The formation of nitronic acids in the aromatic N. series is associated with the benzene ring in the quinoid form; for example, forms with conc. H 2 SO 4 colored salt product f-ly I, o-nitrotoluene shows as a result vnutrimol. transfer to form a bright blue O-derivative:
Under the action of bases on primary and secondary N., nitro compounds are formed; ambident in reactions with electrophiles are able to give both O- and C-derivatives. So, when H. is alkylated with alkyl halides, trialkylchlorosilanes, or R 3 O + BF - 4, O-alkylation products are formed. Recent m.b. also obtained by the action of diazomethane or N,O-bis-(trimethylsilyl)acetamide on nitroalkanes with pK a
Acyclic alkyl esters of nitronic acids are thermally unstable and decompose according to intramol. mechanism:
p-tion can be used to obtain. Silyl ethers are more stable. See below for the formation of C-alkylation products.
Nitro compounds are characterized by reactions with cleavage of the C-N bond, by N=O, O=N O, C=N -> O bonds, and reactions with the preservation of the NO 2 group.
R-ts and and with r and ry v o m s vyaz z and C-N. Primary and secondary N. at loading. with a miner. acids in the presence of an alcoholic or aqueous solution form carbonyl compounds. (see Neph reaction). R-tion passes through the interval. formation of nitronic acids:
As a source Comm. silyl nitrone ethers can be used. The action of strong acids on aliphatic nitro compounds can lead to hydroxamic acids, for example:
The method is used in industry for the synthesis of CH 3 COOH and from nitroethane. Aromatic nitro compounds are inert to the action of strong acids.
Aliphatic nitro compounds containing mobile H in the b-position to the NO 2 group, under the action of bases, easily eliminate it in the form of HNO 2 with the formation of . Thermal flows in the same way. decomposition of nitroalkanes at temperatures above 450°. Vicinal dinitrocomponents. when treating Ca in hexamstanol, both NO 2 groups are cleaved off, Ag-salts of unsaturated nitro compounds can dimerize upon loss of NO 2 groups:
Nucleof. substitution of the NO 2 group is not typical for nitroalkanes, however, when thiolate ions act on tertiary nitroalkanes in aprotic solvents, the NO 2 group is replaced by . P-tion proceeds by an anion-radical mechanism. In the aliphatic and heterocyclic. conn. the NO 2 group at is relatively easily replaced by a nucleophile, for example:
In the aromatic conn. nucleoph. the substitution of the NO 2 group depends on its position with respect to other substituents: the NO 2 group, which is in the meta position with respect to the electron-withdrawing substituents and in the ortho and para positions to the electron donor, has a low reaction. ability; reaction the ability of the NO 2 group, located in the ortho- and para-positions to electron-withdrawing substituents, increases markedly. In some cases, the substituent enters the ortho position to the leaving NO 2 group (for example, when aromatic N. is loaded with an alcoholic solution of KCN, the Richter reaction):
R-ts and and about with I z and N \u003d O. One of the most important reactions is reduction, leading in the general case to a set of products:
Azoxy-(II), azo-(III) and hydrazo compounds. (IV) are formed in an alkaline environment as a result of intermediate nitroso compounds. with and . Carrying out the process in an acidic environment excludes the formation of these substances. Nitroso-compound. recover faster than the corresponding nitro compounds, and select them from the reaction. mixtures usually fail. Aliphatic N. are reduced in azoxy or by the action of Na, aromatic - by the action of NaBH 4, the treatment of the latter with LiAlH 4 leads to. Electrochem. aromatic N. under certain conditions allows you to get any of the presented derivatives (with the exception of nitrosocompound.); by the same method it is convenient to obtain from mononitroalkanes and amidoximes from gem-dinitroalkanes:
R-tion on bonds O \u003d N O and C \u003d N O. Nitro compounds enter into 1,3-dipolar reactions, for example:
Naib. this reaction easily proceeds between nitrone ethers and or. In products (mono- and bicyclic dialkoxyamines) under the action of nucleoph. and elektrof. N - O bond reagents are easily cleaved, which leads to decomp. aliphatic and hetero-cyclic. conn.:
For preparative purposes, stable silyl nitrone esters are used in the reaction.
R-ts and with the preservation of the NO 2 group. Aliphatic N., containing an a-H-atom, are easily alkylated and acylated with the formation, as a rule, of O-derivatives. However, mutually mod. dilithium primary H. with alkyl halides, anhydrides or halides of carboxylic acids leads to products of C-alkylation or C-acylation, for example:
Known examples vnutrimol. C-alkylation, for example:
Primary and secondary nitro compounds react with aliphatic. and CH 2 O with the formation of p-amino derivatives (p-tion Mannich); preformed methylol derivatives of nitro compounds or amino compounds can be used in the reaction:
Easily enter into addition reactions of nitroolefins: with in a slightly acidic or slightly alkaline medium with the latter. Henri retroreaction they form carbonyl Comm. and nitroalkanes; with nitro compounds containing a-H-atom, poly-nitro compounds; add other CH-acids, such as, and malonic acids, Grignard reagents, as well as nucleophiles such as OR -, NR - 2, etc., for example:
Nitroolefins can act as dienophiles or dipolarophiles in reactions and cycloadditions, and 1,4-dinitrodienes can act as diene components, for example:
Receipt. In industry, lower nitroalkanes are obtained by liquid-phase (Konovalov's district) or vapor-phase (Hess method) mixtures, and isolated from natural or obtained by processing (see Nitration). Higher N., for example, nitrocyclohexane, an intermediate product in the production of caprolactam, are also obtained by this method.
In the laboratory, nitric acid is used to obtain nitroalkanes. with activated a methylene group; a convenient method for the synthesis of primary nitroalkanes is the nitration of 1,3-indanedione with the last. alkaline a-nitroketone:
Aliphatic nitro compounds also receive interaction. AgNO 2 with alkyl halides or NaNO 2 with esters of a-halocarboxylic acids (see Meyer reaction). Aliphatic N. are formed at and; - a method for obtaining gem-di- and gem-trinitro compounds, for example:
Nitroalkanes can be obtained by heating acyl nitrates to 200 °C.
Mn. methods for the synthesis of nitro compounds are based on olefins, HNO 3 , nitronium, NO 2 Cl, org. nitrates, etc. As a rule, a mixture of vic-dinitro compounds, nitronitrates, nitronitrites, unsaturated nitro compounds, as well as conjugated addition products of the NO 2 group and a solvent or their products is obtained, for example:
3. Nitro compounds. Methods of obtaining and the most important properties.
Nitro compounds- organic substances containing the nitro group -N0 2 .
The general formula is R-NO 2 .
Depending on the radical R, aliphatic (limiting and unsaturated), acyclic, aromatic and heterocyclic nitro compounds are distinguished. According to the nature of the carbon atom to which the nitro group is attached, nitro compounds are divided into primary, secondary and tertiary.
Methods for the preparation of aliphatic nitro compounds
Direct nitration of alkanes in the liquid or gas phase under the action of 50-70% aqueous nitric acid at 500-700 ° C or nitrogen tetroxide at 300-500 ° C is of industrial importance only for obtaining the simplest nitroalkanes, since nitration under these conditions is always accompanied by cracking of hydrocarbons and leads to a complex mixture of a wide variety of nitro compounds. This reaction was not widely used for this reason.
The most common laboratory method for obtaining nitroalkanes is still the alkylation reaction of the nitrite ion, discovered by V. Meyer as early as 1872. In the classical method of W. Meyer, silver nitrite reacts with primary or secondary alkyl bromides and alkyl iodides in ether, petroleum ether or without solvent at 0-20 o C to form a mixture of nitroalkane and alkyl nitrite.
The nitrite ion is one of the degenerate ambident anions with two independent nucleophilic centers (nitrogen and oxygen) that are not linked into a single mesomeric system.
The reactivity of an ambident nitrite ion with two independent nucleophilic centers (nitrogen and oxygen) differs sharply from the reactivity of enolate ions with two nucleophilic centers bound into a single mesomeric system.
The ratio of N- and O-alkylation products (nitroalkane/alkyl nitrite) in the Meyer reaction of alkyl bromides and iodides with silver nitrite depends crucially on the nature of the alkyl group in the alkyl halide. Yields of primary nitroalkanes reach 75–85%, but they sharply decrease to 15–18% for secondary nitroalkanes and to 5% for tertiary nitroalkanes.
Thus, neither tertiary nor secondary alkyl halides are suitable for the synthesis of nitroalkanes by reaction with silver nitrite. The Meyer reaction seems to be the best way to prepare primary nitroalkanes, arylnitromethanes, and -nitroesters of carboxylic acids.
To obtain nitroalkanes, only alkyl bromides and alkyl iodides should be used, since alkyl chlorides, alkyl sulfonates and dialkyl sulfates do not interact with silver nitrite. From -dibromoalkanes, -dinitroalkanes are easily obtained.
N. Kornblum (1955) proposed a modified general method for the preparation of primary and secondary nitroalkanes, as well as dinitroalkanes and nitro-substituted ketones.
This method is based on the alkylation of alkali metal nitrites with primary or secondary alkyl halides in the dipolar aprotic solvent DMF. In order to prevent subsequent nitrosation of the nitroalkane by the alkyl nitrite formed in parallel, it is necessary to introduce urea or polyhydric phenols - resorcinol or phloroglucinol - into the reaction mixture. The yield of primary nitroalkanes by this method does not exceed 60%; lower than with the alkylation of silver nitrite (75-80%). However, secondary nitroalkanes can be obtained in good yield by alkylation of sodium nitrite in DMF.
Tertiary alkyl halides undergo elimination under the action of the nitrite ion and do not form nitro compounds. Esters of -chloro- or -bromo-substituted acids are smoothly converted into esters of -nitro-substituted acids with a yield of 60-80% when interacting with sodium nitrite in DMSO or DMF.
Another common method for the synthesis of nitroalkanes is the oxidation of ketone oximes with trifluoroperacetic acid in acetonitrile.
In addition to oximes, primary amines can also be oxidized with peracetic acid or m-chloroperbenzoic acid:
More than a hundred years ago, G. Kolbe described a method for producing nitromethane by reacting sodium chloroacetate and sodium nitrite in an aqueous solution at 80-85 o C:
The intermediate nitroacetic acid anion is decarboxylated to nitromethane. For the preparation of nitromethane homologues, the Kolbe method is of no value due to the low yield of nitroalkanes. The idea of this method was ingeniously used in the development of a modern general method for the preparation of nitroalkanes. Dianions of carboxylic acids are nitrated by the action of alkyl nitrate with simultaneous decarboxylation of the α-nitro-substituted carboxylic acid.
Nitration of carbanions with alkyl nitrates is also widely used to obtain - dinitroalkanes. For this purpose, enolate ions of cyclic ketones are treated with two equivalents of alkyl nitrate. Opening of the ring followed by decarboxylation leads to the -nitroalkane.
Methods for the preparation of aromatic nitro compounds
Aromatic nitro compounds are most often obtained by nitration of arenes, which was considered in detail in the study of electrophilic aromatic substitution. Another common method for preparing nitroarenes is the oxidation of primary aromatic amines with trifluoroperacetic acid in methylene chloride. Trifluoroperacetic acid is obtained directly in the reaction mixture by reacting trifluoroacetic acid anhydride and 90% hydrogen peroxide. The oxidation of the amino group to the nitro group with trifluoroperacetic acid is important for the synthesis of nitro compounds containing other electron-withdrawing groups in the ortho and para positions, for example, for the production of ortho and para dinitrobenzene, 1,2,4 trinitrobenzene, 2,6 dichloronitrobenzene and etc..
Reactions of aliphatic nitro compounds:
Primary and secondary nitroalkanes are in tautomeric equilibrium with the aci form of the nitro compound, otherwise called nitronic acid.
Of the two tautomeric forms, the nitro form is much more stable and dominates in equilibrium. For nitromethane at 20 o the concentration of the aci-form does not exceed 110 -7 of the fraction of nitroalkane, for 2-nitropropane it increases to 310 -3. The amount of aci-form increases for phenylnitromethane. The isomerization of the aci-nitro compound to the nitro compound is slow. This makes it possible to determine the concentration of the aci-form by titration with bromine with a very high degree of accuracy.
The low rate of interconversion of two tautomeric forms allowed A. Ganch back in 1896 to isolate both tautomeric forms of phenylnitromethane individually. Phenylnitromethane is completely soluble in cold aqueous sodium hydroxide solution. When treated with aqueous acetic acid at 0°, a colorless solid is formed, which is the aci form of phenylnitromethane. It instantly turns red when treated with iron(III) chloride and titrated quantitatively with bromine.
On standing, the solid aci form slowly isomerizes to the more stable liquid form of phenylnitromethane. For simple nitroalkanes, for example, nitromethane, nitroethane, and 2-nitropropane, the aci form cannot be isolated in an individual form, since it isomerizes into the nitro form quite easily at 0 o and the content of the aci form can only be judged from titrimetric bromination data.
The concentration of the two tautomeric forms for any compound is always inversely proportional to the acidity of the tautomeric forms, the aci form of nitroalkanes is in all cases a stronger acid than the nitro form. For nitromethane in water, pKa ~ 10.2, while for its aci-form CH 2 \u003d N (OH) -O, pKa ~ 3.2. For 2-nitropropane, this difference is much smaller, pKa (CH 3) 2 CHNO 2 is 7.68, and for (CH 3) 2 C=N(OH)-O pKa is 5.11.
The difference in pKa values for the two forms is not unexpected since the aci form is an O-H acid, while the nitro form is a C-H acid. Recall that a similar pattern is observed for the keto- and enol forms of carbonyl and 1,3-dicarbonyl compounds, where enol is a stronger O-H acid compared to the C-H acidity of the keto form.
Aci-nitro compounds are fairly strong acids that form salts even when reacting with sodium carbonate, in contrast to the nitro form of nitroalkanes, which does not react with the carbonate ion. Tautomeric transformations of both forms of nitroalkanes are catalyzed by both acids and bases, similarly to the enolization of aldehydes and ketones.
Reactions of ambident anions of nitroalkanes.
Under the action of a base on both the nitro form and the aci form of the nitro compound, a mesomeric ambident anion common to both of them is formed, in which the charge is delocalized between the oxygen and carbon atoms.
The ambident anions of nitroalkanes are in all respects close analogues of the enolate ions of carbonyl compounds and are characterized by the same substitution reactions as for the enolate ions.
The most typical and important reactions involving nitroalkane anions are: halogenation, alkylation, acylation, condensations with carbonyl compounds, Mannich and Michael reactions - all those that are typical for enolate ions. Depending on the nature of the electrophilic agent and, to some extent, on the structure of the nitroalkane, substitution can occur with the participation of either oxygen or carbon, or both centers of the ambident nitroalkane anion.
Halogenation of alkaline salts of nitro compounds is carried out only at the carbon atom, the reaction can be stopped at the stage of introduction of one halogen atom.
Nitrosation of primary nitroalkanes is also carried out only at the carbon atom and leads to the formation of so-called nitrolic acids.
Secondary nitroalkanes give pseudonitrols under the same conditions.
Nitrolic acids are colorless and, when shaken with sodium hydroxide solution, form red salts.
In contrast, pseudonitrols have a blue color in a neutral medium. These compounds can be used to identify primary and secondary nitroalkanes. Tertiary nitroalkanes do not react at 0° or below with nitrous acid.
Alkylation of ambident anions of nitroalkanes proceeds, in contrast to halogenation and nitrosation, predominantly at the oxygen atom with the formation of aci-form esters as intermediates, which are called nitrone esters. Esters of the aci-form of nitroalkanes can be isolated individually by alkylating salts of nitroalkanes with trialkyloxonium tetrafluoroborates in methylene chloride at -20 o.
Nitron ethers are thermally unstable and above 0-20° undergo redox decomposition into oxime and carbonyl compound.
The oxime is always formed as the end product of the reduction of the nitroalkane, while the aldehyde is the end product of the oxidation of the alkylating agent. This reaction has found wide application in the synthesis of aromatic aldehydes.
When alkali salts of 2-nitropropane react with substituted benzyl halides, the end products are acetone oxime and an aromatic aldehyde.
An even more important role is played by the alkylation of ambident anions of nitroalkanes under the action of allyl halides to obtain ,-unsaturated aldehydes.
As follows from the above examples, in contrast to enolate ions, nitroalkane anions undergo regioselective O-alkylation. Such a sharp difference in the behavior of two related classes of ambident anions is due to the high degree of charge localization on the oxygen atom of the nitroalkane anion.
In the presence of one or several strong electron-withdrawing groups in the benzyl halide, such as NO 2 , NR 3 , SO 2 CF 3 , etc., the reaction mechanism and its regioselectivity change. In this case, C-alkylation of the nitroalkane anion is observed by a mechanism involving radical anions, which is essentially similar to the S RN 1 mechanism of aromatic nucleophilic substitution.
The discovery of the anion-radical mechanism of C-alkylation of nitroalkanes and other ambident anions allowed N. Kornblum in 1970-1975 to develop an extremely effective method for the alkylation of ambident anions using -nitro-substituted esters, nitriles, etc., which contribute to the implementation of the anion-radical chain process.
It should be noted that in these reactions substitution occurs even at the tertiary carbon atom.
C-alkylation can be made practically the only direction of the reaction in the case of alkylation of nitroalkane dianions. Nitroalkane dianions are formed by treating primary nitroalkanes with two equivalents of n-butyllithium in THF at -100 o.
These dianions also undergo regioselective C-acylation upon interaction with acyl halides or anhydrides of carboxylic acids.
Condensation of nitroalkane anions with carbonyl compounds(Henri's reaction).
Condensation of anions of primary and secondary nitroalkanes with aldehydes and ketones leads to the formation of -hydroxynitroalkanes or their dehydration products - ,-unsaturated nitro compounds.
This reaction was discovered by L. Henri in 1895 and can be considered as a kind of aldol-crotonic condensation of carbonyl compounds.
The anion of the nitroalkane, and not the carbonyl compound, takes part in the condensation, since the acidity of nitroalkanes (pKa ~ 10) is ten orders of magnitude higher than the acidity of carbonyl compounds (pKa ~ 20).
Effective catalysts for the Henri reaction are hydroxides, alkoxides and carbonates of alkali and alkaline earth metals.
The alkalinity of the medium must be carefully controlled to avoid aldol condensation of carbonyl compounds or the Canizzaro reaction for aromatic aldehydes. Primary nitroalkanes can also react with two moles of a carbonyl compound, so the ratio of reactants must be observed very carefully. During the condensation of aromatic aldehydes, only -nitroalkenes are usually formed, and it is very difficult to stop the reaction at the stage of formation of -hydroxynitroalkane.
The addition of nitroalkane anions to an activated double bond according to Michael andMannich reaction involving nitroalkanes.
Anions of primary and secondary nitroalkanes add via a multiple bond
,-unsaturated carbonyl compounds, esters and cyanides in the same way as it happens when enolate ions are attached to an activated double bond.
For primary nitroalkanes, the reaction can go further with the participation of the second mole of CH 2 =CHX. The nitroalkane anions in the Michael addition reaction are prepared in the usual manner using sodium ethoxide or diethylamine as the base.
α-Nitroalkenes can also be used as Michael acceptors in addition reactions of conjugated carbanions. Addition of nitroalkane anions to - nitroalkenam is one of the simplest and most convenient methods for the synthesis of aliphatic dinitro compounds.
This type of addition can also occur under Henri reaction conditions as a result of dehydration of the condensation product of an aldehyde or ketone with a nitroalkane and subsequent addition of the nitroalkane.
Primary and secondary aliphatic amines enter into the Mannich reaction with primary and secondary nitroalkanes and formaldehyde.
In terms of its mechanism and scope, this reaction is no different from the classical version of the Mannich reaction involving carbonyl compounds instead of nitroalkanes.
Reactions of aromatic nitro compounds:
The nitro group is highly stable with respect to electrophilic reagents and various oxidizing agents. Most nucleophilic agents, with the exception of organolithium and magnesium compounds, as well as lithium aluminum hydride, do not act on the nitro group. The nitro group is among the excellent nucleophilic groups in activated aromatic nucleophilic substitution (S N A r) processes. For example, the nitro group in 1,2,4-trinitrobenzene is easily replaced by hydroxide, alkoxide ions or amines.
The most important reaction of aromatic nitro compounds is the reduction of their pre-primary amines.
This reaction was discovered in 1842 by N.N. Zinin, who was the first to reduce nitrobenzene to aniline by the action of ammonium sulfide. Currently, catalytic hydrogenation is used to reduce the nitro group in arenes to the amino group under industrial conditions. Copper is used as a catalyst on silica gel as a carrier. The catalyst is prepared by applying copper carbonate from a suspension in sodium silicate solution and then reducing with hydrogen while heating. The yield of aniline over this catalyst is 98%.
Sometimes in the industrial hydrogenation of nitrobenzene to aniline, nickel is used as a catalyst in combination with vanadium and aluminum oxides. Such a catalyst is effective in the range of 250-300 about and is easily regenerated by air oxidation. The yield of aniline and other amines is 97-98%. The reduction of nitro compounds to amines can be accompanied by hydrogenation of the benzene ring. For this reason, the use of platinum as a catalyst is avoided in the preparation of aromatic amines. palladium or Raney nickel.
Another method for the reduction of nitro compounds is metal reduction in an acidic or alkaline medium.
The reduction of the nitro group to the amino group occurs in several stages, the sequence of which differs greatly in acidic and alkaline media. Let us consider successively the processes that occur during the reduction of nitro compounds in acidic and alkaline media.
When reducing in an acidic medium, iron, tin, zinc and hydrochloric acid are used as a reducing agent. An effective reducing agent for the nitro group is tin(II) chloride in hydrochloric acid. This reagent is especially effective in cases where the aromatic nitro compound contains other functional groups: CHO, COR, COOR, etc., which are sensitive to the action of other reducing agents.
The reduction of nitro compounds to primary amines in an acidic medium proceeds stepwise and includes three stages with the transfer of two electrons at each stage.
In an acidic environment, each of the intermediate products is rapidly reduced to the final product of aniline, and they cannot be isolated individually. However, in aprotic solvents in a neutral medium, intermediate reduction products can be detected.
In the reduction of nitrobenzene with sodium or potassium in THF, the radical anion of nitrobenzene is first formed due to the transfer of one electron from the alkali metal.
The alkali metal cation is bound into a contact ion pair with the oxygen atom of the nitro group of the radical anion. Upon further reduction, the radical anion is converted into a dianion, which, after protonation, gives nitrosobenzene.
Nitrozobenzene, like other aromatic nitroso compounds, has a high oxidizing potential and is very rapidly reduced to N-phenylhydroxylamine. Therefore, nitrosobenzene cannot be isolated as a reduction intermediate, although electrochemical reduction data unambiguously indicate its formation.
Further reduction of nitroso compounds to N-arylhydroxylamine includes two similar stages of one-electron reduction to the radical anion and then to the dianion of the nitroso compound, which is converted to N-arylhydroxylamine upon protonation.
The last step in the reduction of arylhydroxylamine to a primary amine is accompanied by heterolytic cleavage of the nitrogen-oxygen bond after protonation of the substrate.
In a neutral aqueous solution, phenylhydroxylamine can be obtained as a product of the reduction of nitrobenzene. Phenylhydroxylamine is obtained by reducing nitrobenzene with zinc in an aqueous solution of ammonium chloride.
Arylhydroxylamines are easily reduced to amines by treatment with iron or zinc and hydrochloric acid.
Since phenylhydroxylamine is a reduction intermediate, it can not only be reduced to aniline but also oxidized to nitrosobenzene.
This is probably one of the best methods for obtaining aromatic nitroso compounds, which cannot otherwise be isolated as an intermediate in the reduction of nitro compounds.
Aromatic nitroso compounds readily dimerize in the solid state, and their dimers are colorless. In the liquid and gaseous state, they are monomeric and colored green.
The reduction of nitro compounds with metals in an alkaline medium differs from the reduction in an acidic medium. In an alkaline environment, nitrosobenzene reacts rapidly with the second reduction intermediate, phenylhydroxylamine, to form azoxybenzene. This reaction is essentially similar to the addition of nitrogenous bases to the carbonyl group of aldehydes and ketones.
Under laboratory conditions, azoxybenzene is obtained in good yield by reducing nitro compounds with sodium borohydride in DMSO, sodium methoxide in methyl alcohol, or in the old way using As 2 O 3 or glucose as a reducing agent.
Under the action of zinc in an alcoholic solution of alkali, azoxybenzene is first reduced to azobenzene, and under the action of excess zinc, further to hydrazobenzene.
In synthetic practice, azoxybenzene derivatives can be reduced to azobenzene by the action of a trialkyl phosphite as a reducing agent. On the other hand, azobenzene is easily oxidized to azoxybenzene by peracids.
Azobenzene exists as cis and trans isomers. The reduction of azoxybenzene results in a more stable trans isomer, which is converted to the cis isomer upon irradiation with UV light.
Asymmetric azobenzene derivatives are obtained by the condensation of nitroso compounds and primary aromatic amines.
When aromatic nitro compounds are reduced with lithium aluminum hydride in ether, azo compounds are also formed with a yield close to quantitative.
Azobenzene is reduced by zinc dust and alcohol alkali to hydrazobenzene. Hydrazobenzene is thus the end product of metal reduction of nitrobenzene in an alkaline medium. In air, colorless hydrazobenzene readily oxidizes to orange-red azobenzene. At the same time, hydrazobenzene, as well as azobenzene and azoxybenzene, is reduced to aniline by the action of sodium dithionite in water or tin (II) chloride in hydrochloric acid.
The overall process of reduction of aromatic nitro compounds with metals in acidic and alkaline media can be represented as the following sequence of transformations.
In an acidic environment:
In an alkaline environment:
In industry, aniline is obtained by catalytic reduction of nitrobenzene on a copper or nickel catalyst, which replaced the old method of reducing nitrobenzene with cast iron shavings in an aqueous solution of ferric chloride and hydrochloric acid.
The reduction of the nitro group to the amino group with sodium sulfide and sodium hydrosulfide is currently only relevant for the partial reduction of one of the two nitro groups, for example, in m-dinitrobenzene or 2,4-dinitroaniline.
With the stepwise reduction of polynitro compounds using sodium sulfide, this inorganic reagent is converted into sodium tetrasulfide, which is accompanied by the formation of alkali.
The high alkalinity of the medium leads to the formation of azoxy and azo compounds as by-products. In order to avoid this, sodium hydrosulfide should be used as a reducing agent, where no alkali is formed.
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Nitrocompounds are derivatives of hydrocarbons in which one or more hydrogen atoms are replaced by a nitro group -NO 2 . Depending on the hydrocarbon radical to which the nitro group is attached, nitro compounds are divided into aromatic and aliphatic. Aliphatic compounds are distinguished as primary 1o, secondary 2o and tertiary 3o, depending on whether a nitro group is attached to the 1o, 2o or 3o carbon atom.
The nitro group -NO2 should not be confused with the nitrite group -ONO. The nitro group has the following structure:
The presence of a total positive charge on the nitrogen atom determines the presence of a strong -I-effect. Along with a strong -I-effect, the nitro group has a strong -M-effect.
Ex. 1. Consider the structure of the nitro group and its influence on the direction and rate of the electrophilic substitution reaction in the aromatic nucleus.
Methods for obtaining nitro compounds
Almost all methods for obtaining nitro compounds have already been considered in previous chapters. Aromatic nitro compounds are obtained, as a rule, by direct nitration of arenes and aromatic heterocyclic compounds. Nitrocyclohexane under industrial conditions is obtained by nitration of cyclohexane:
Nitromethane is also obtained in the same way, however, under laboratory conditions, it is obtained from chloroacetic acid as a result of reactions (2-5). The key step among them is reaction (3) proceeding via the SN2 mechanism.
Chloroacetic acid Sodium chloroacetate
Nitroacetic acid
Nitromethane
Reactions of nitro compounds
Tautomerism of aliphatic nitro compounds
Due to the strong electron-withdrawing properties of the nitro group, -hydrogen atoms have increased mobility and therefore primary and secondary nitro compounds are CH-acids. So, nitromethane is a rather strong acid (pKa 10.2) and in an alkaline medium it easily turns into a resonance-stabilized anion:
Nitromethane pKa 10.2 Resonance stabilized anion
Exercise 2. Write the reactions of (a) nitromethane and (b) nitrocyclohexane with an aqueous solution of NaOH.
Condensation of aliphatic nitro compounds with aldehydes and ketones
The nitro group can be introduced into aliphatic compounds by an aldol reaction between the nitroalkane anion and an aldehyde or ketone. In nitroalkanes, -hydrogen atoms are even more mobile than in aldehydes and ketones, and therefore they can enter into addition and condensation reactions with aldehydes and ketones, providing their -hydrogen atoms. With aliphatic aldehydes, addition reactions usually take place, and with aromatic ones, only condensations.
So, nitromethane is added to cyclohexanone,
1-nitromethylcyclohexanol
but condenses with benzaldehyde,
All three hydrogen atoms of nitromethane participate in the addition reaction with formaldehyde and 2-hydroxymethyl-2-nitro-1,3-dinitropropane or trimethylolnitromethane is formed.
By condensation of nitromethane with hexamethylenetetramine, we obtained 7-nitro-1,3,5-triazaadamantane:
Ex. 3. Write the reactions of formaldehyde (a) with nitromethane and (b) with nitrocyclohexane in an alkaline medium.
Recovery of nitro compounds
The nitro group is reduced to the amino group by various reducing agents (11.3.3). Aniline is obtained by hydrogenation of nitrobenzene under pressure in the presence of Raney nickel under industrial conditions.
In laboratory conditions, instead of hydrogen, hydrazine can be used, which decomposes in the presence of Raney nickel with the release of hydrogen.
7-nitro-1,3,5-triazaadamantane 7-amino-1,3,5-triazaadamantane
Nitro compounds are reduced with metals in an acid medium, followed by alkalization
Depending on the pH of the medium and the reducing agent used, various products can be obtained. In a neutral and alkaline environment, the activity of conventional reducing agents with respect to nitro compounds is less than in an acidic environment. A typical example is the reduction of nitrobenzene with zinc. In an excess of hydrochloric acid, zinc reduces nitrobenzene to aniline, while in a buffer solution of ammonium chloride it reduces to phenylhydroxylamine:
In an acidic environment, arylhydroxylamines undergo a rearrangement:
p-Aminophenol is used as a developer in photography. Phenylhydroxylamine can be further oxidized to nitrosobenzene:
Nitrosobenzene
Reduction of nitrobenzene with tin (II) chloride produces azobenzene, and with zinc in an alkaline medium, hydrazobenzene.
Treatment of nitrobenzene with a solution of alkali in methanol gives azoxybenzene, while the methanol is oxidized to formic acid.
Known methods of incomplete recovery and nitroalkanes. One of the industrial methods for producing capron is based on this. By nitration of cyclohexane, nitrocyclohexane is obtained, which is converted by reduction into cyclohexanone oxime and then, using the Beckmann rearrangement, into caprolactam and polyamide - the starting material for the preparation of fiber - capron:
Reduction of the nitro group of aldol addition products (7) is a convenient way to obtain α-amino alcohols.
1-Nitromethylcyclohexanol 1-Aminomethylcyclohexanol
The use of hydrogen sulfide as a reducing agent makes it possible to reduce one of the nitro groups in dinitroarenes:
m-Dinitrobenzene m-Nitroaniline
2,4-Dinitroaniline 4-Nitro-1,2-diaminobenzene
Exercise 4. Write the reduction reactions of (a) m-dinitrobenzene with tin in hydrochloric acid, (b) m-dinitrobenzene with hydrogen sulfide, (c) p-nitrotoluene with zinc in a buffered ammonium chloride solution.
Exercise 5. Complete reactions:
