Nitro compounds: structure, nomenclature, basic methods of synthesis, physical and chemical properties. Chloronitroaromatic compounds and their toxic effects

NITRO COMPOUNDS, contain one or more in a molecule. nitro groups directly bonded to the carbon atom. N- and O-nitro compounds are also known. The nitro group has a structure intermediate between two limiting resonance structures:

The group is planar; the N and O atoms have sp 2 hybridization, the N-O bonds are equivalent and almost one-and-a-half; bond lengths, e.g. for CH 3 NO 2, 0.122 nm (N-O), 0.147 nm (C-N), ONO angle 127°. The C-NO 2 system is planar with a low barrier to rotation around the C-N bond.

Nitro compounds having at least one a-H atom can exist in two tautomeric forms with a common mesomeric anion. O-form called aci-nitro compound or nitronic compound:

Esters of nitronic compounds exist in the form of cis- and trans-isomers. There are cyclical ethers, e.g. Isoxazoline N-oxides.

Name nitro compounds are produced by adding the prefix “nitro” to the name. base connections, adding a digital indicator if necessary, e.g. 2-nitropropane. Name salts of nitro compounds are produced from the name. either the C-form, or the aci-form, or the nitronic acid.

NITRO COMPOUNDS OF ALIPHATIC SERIES

Nitroalkanes have the general formula C n H 2n+1 NO 2 or R-NO 2 . They are isomeric with alkyl nitrites (esters of nitric acid) with the general formula R-ONO. The isomerism of nitroalkanes is associated with the isomerism of the carbon skeleton. Distinguish primary RCH 2 NO 2 secondary R 2 CHNO 2 and tertiary R 3 CNO 2 nitroalkanes, for example:

Nomenclature

The names of nitroalkanes are based on the name of the hydrocarbon with the prefix nitro(nitromethane, nitroethane, etc.). According to systematic nomenclature, the position of the nitro group is indicated by a number:

^ Methods for obtaining nitroalkanes

1. Nitration of alkanes with nitric acid (Konovalov, Hess)

Concentrated nitric acid or a mixture of nitric and sulfuric acids oxidizes alkanes. Nitration occurs only under the influence of dilute nitric acid (specific weight 1.036) in the liquid phase at a temperature of 120-130°C in sealed tubes (M.I. Konovalov, 1893):

^ R-H + HO-NO 2 → R-NO 2 + H 2 O

For nitration Konovalov M.I. first time using nonaphthene

It was found that the ease of replacing a hydrogen atom with a nitro group increases in the series:

The main factors influencing the rate of the nitration reaction and the yield of nitro compounds are the acid concentration, temperature and process duration. For example, nitration of hexane is carried out with nitric acid (d 1.075) at a temperature of 140°C:

The reaction is accompanied by the formation of polynitro compounds and oxidation products.

The method of vapor-phase nitration of alkanes has gained practical importance (Hess, 1936). Nitration is carried out at a temperature of 420°C and a short stay of the hydrocarbon in the reaction zone (0.22-2.9 sec). Nitration of alkanes according to Hess leads to the formation of a mixture of nitroparaffins:

The formation of nitromethane and ethane occurs as a result of cracking of the hydrocarbon chain.

The nitration reaction of alkanes proceeds by a free radical mechanism, and nitric acid is not a nitrating agent, but serves as a source of nitrogen oxides NO2:

2. Meyer's reaction (1872)

The interaction of alkyl halides with silver nitrite leads to the production of nitroalkanes:

A method for producing nitroalkanes from alkyl halides and sodium nitrite in DMF (dimethylformamide) was proposed by Kornblum. The reaction proceeds according to the mechanism S N 2.

Along with nitro compounds, nitrites are formed in the reaction, this is due to the ambidentity of the nitrite anion:

^ Structure of nitroalkanes

Nitroalkanes can be represented by Lewis octet formula or resonance structures:

One of the bonds of a nitrogen atom with oxygen is called donor-acceptor or semipolar.
^

Chemical properties

Chemical transformations of nitroalkanes are associated with reactions at the a-hydrogen carbon atom and the nitro group.

Reactions involving the a-hydrogen atom include reactions with alkalis, nitrous acid, aldehydes and ketones.

1. Formation of salts

Nitro compounds belong to pseudoacids - they are neutral and do not conduct electric current, but they interact with aqueous solutions of alkalis to form salts, upon acidification of which the aci form of the nitro compound is formed, which then spontaneously isomerizes into a true nitro compound:

The ability of a compound to exist in two forms is called tautomerism. Nitroalkane anions are ambident anions with dual reactivity. Their structure can be represented in the following forms:

2. Reactions with nitrous acid

Primary nitro compounds react with nitrous acid (HONO) to form nitrolic acids:

Nitrolic acids, when treated with alkalis, form a blood-red salt:

Secondary nitroalkanes form pseudonitroles (heme-nitronitroso-alkanes) of blue or greenish color:

Tertiary nitro compounds do not react with nitrous acid. These reactions are used for the qualitative determination of primary, secondary and tertiary nitro compounds.

3. Synthesis of nitro alcohols

Primary and secondary nitro compounds react with aldehydes and ketones in the presence of alkalis to form nitro alcohols:

Nitromethane with formaldehyde gives trioxymethylnitromethane NO 2 C (CH 2 OH) 3. When the latter is reduced, amino alcohol NH 2 C (CH 2 OH) 3 is formed - the starting material for the production of detergents and emulsifiers. Tri(hydroxymethyl)nitromethane trinitrate, NO 2 C(CH 2 ONO 2) 3, is a valuable explosive.

Nitroform (trinitromethane) reacts with formaldehyde to form trinitroethyl alcohol:

4. Reduction of nitro compounds

Complete reduction of nitro compounds into the corresponding amines can be achieved by many methods, for example, the action of hydrogen sulfide, iron in hydrochloric acid, zinc and alkali, lithium aluminum hydride:

Methods of incomplete reduction are also known, as a result of which oximes of the corresponding aldehydes or ketones are formed:

5. Interaction of nitro compounds with acids

The reactions of nitro compounds with acids are of practical value. Primary nitro compounds, when heated with 85% sulfuric acid, are converted into carboxylic acids. It is assumed that stage 1 of the process is the interaction of nitro compounds with mineral acids to form the aci form:

Aci salts of primary and secondary nitro compounds form aldehydes or ketones in the cold in aqueous solutions of mineral acids (Nef reaction):

. Aromatic nitro compounds. Chemical properties

Chemical properties. Reduction of nitro compounds in acidic, neutral and alkaline media. The practical significance of these reactions. The activating effect of the nitro group on nucleophilic substitution reactions. Polynitro compounds of the aromatic series.

1. Nitro compounds

1.2. Reactions of nitro compounds

1. NITRO COMPOUNDS

Nitro compounds are hydrocarbon derivatives 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 causes it to have a strong -I effect. Along with the strong -I effect, the nitro group has a strong -M effect.

Ex. 1. Consider the structure of the nitro group and its effect on the direction and rate of the electrophilic substitution reaction in the aromatic ring.

1.1. Methods for obtaining nitro compounds

Almost all methods for obtaining nitro compounds have already been discussed in previous chapters. Aromatic nitro compounds are usually obtained by direct nitration of arenes and aromatic heterocyclic compounds. Nitrocyclohexane is produced industrially by nitration of cyclohexane:

(1)

Nitromethane is also obtained in the same way, but in laboratory conditions it is obtained from chloroacetic acid as a result of reactions (2-5). The key stage of these is reaction (3), which occurs via the SN2 mechanism.

Chloroacetic acid Sodium chloroacetate

Nitroacetic acid

Nitromethane

1.2. Reactions of nitro compounds

1.2.1. Tautomerism of aliphatic nitro compounds

Due to the strong electron-withdrawing properties of the nitro group, the a-hydrogen atoms have increased mobility and therefore primary and secondary nitro compounds are CH-acids. Thus, nitromethane is a fairly strong acid (pKa 10.2) and in an alkaline environment 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.

1.2.2. Condensation of aliphatic nitro compounds with aldehydes and ketones

A nitro group can be introduced into aliphatic compounds by an aldol reaction between a nitroalkane anion and an aldehyde or ketone. In nitroalkanes, the a-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 a-hydrogen atoms. With aliphatic aldehydes, addition reactions usually occur, and with aromatic aldehydes, only condensation reactions occur.

Thus, nitromethane adds to cyclohexanone,

(7)

1-Nitromethylcyclohexanol

but condenses with benzaldehyde,

The addition reaction with formaldehyde involves all three hydrogen atoms of nitromethane to form 2-hydroxymethyl-2-nitro-1,3-dinitropropane or trimethylolnitromethane.

By condensation of nitromethane with hexamethylenetetramine we obtained 7-nitro-1,3,5-triazaadamantane:

(10)

Ex. 3. Write the reactions of formaldehyde (a) with nitromethane and (b) with nitrocyclohexane in an alkaline medium.

1.2.3. Reduction of nitro compounds

The nitro group is reduced to an amino group by various reducing agents (11.3.3). Aniline is produced by hydrogenation of nitrobenzene under pressure in the presence of Raney nickel under industrial conditions.

(11) (11 32)

In laboratory conditions, instead of hydrogen, hydrazine can be used, which decomposes in the presence of Raney nickel to release hydrogen.

(12)

7-nitro-1,3,5-triazaadamantane 7-amino-1,3,5-triazaadamantane

Nitro compounds are reduced with metals in an acidic environment followed by alkalization

(13) (11 33)

Depending on the pH of the medium and the reducing agent used, different products can be obtained. In a neutral and alkaline environment, the activity of conventional reducing agents towards nitro compounds is less than in an acidic environment. A typical example is the reduction of nitrobenzene with zinc. In excess hydrochloric acid, zinc reduces nitrobenzene to aniline, while in a buffer solution of ammonium chloride it reduces to phenylhydroxylamine:

(14)

In an acidic environment, arylhydroxylamines undergo rearrangement:

(15)

p-Aminophenol is used as a developer in photography. Phenylhydroxylamine can be further oxidized to nitrosobenzene:

(16)

Nitrosobenzene

By reducing nitrobenzene with tin(II) chloride, azobenzene is obtained, and with zinc in an alkaline medium, hydrazobenzene is obtained.

(17)

(18)

By treating nitrobenzene with a solution of alkali in methanol, azoxybenzene is obtained, while the methanol is oxidized to formic acid.

(19)

Methods for incomplete reduction of nitroalkanes are known. One of the industrial methods for producing nylon 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 - nylon:

Reduction of the nitro group of aldol addition products (7) is a convenient way to obtain b-amino alcohols.

(20)

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:

(11 34)

m-Dinitrobenzene m-Nitroaniline

(21)

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 buffer solution of ammonium chloride.

Exercise 5. Complete the reactions:

(A) (b)

In systematic nomenclature, amines are named by adding the prefix amine to the name of the hydrocarbon. By rational nomenclature they are considered alkyl or arylamines.

Methaneamine Ethanamine N-Methylethanamine N-Ethylethanamine

(methylamine) (ethylamine) (methylethylamine) (diethylamine)

N,N-Diethylethanamine 2-Aminoethanol 3-Aminopropane

triethylamine) (ethanolamine) acid

Cyclohexanamine Benzolamine N-Methylbenzenamine 2-Methylbenzenamine

(cyclohexylamine) (aniline) (N-methylaniline) (o-toluidine)

Heterocyclic amines are named after the corresponding hydrocarbon by inserting the prefix aza-, diaza- or triaza- to denote the number of nitrogen atoms.

1-Azacyclopeta- 1,2-Diazacyclopeta- 1,3-Diazacyclopeta-

2,4-diene 2,4-diene 2,4-diene

3. Nitro compounds. Methods of preparation and 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 (saturated and unsaturated), acyclic, aromatic and heterocyclic nitro compounds are distinguished. Based on the nature of the carbon atom to which the nitro group is bonded, nitro compounds are divided into primary, secondary And tertiary.

Methods for obtaining aliphatic nitro compounds

Direct nitration of alkanes in the liquid or gas phase under the influence of 50-70% aqueous nitric acid at 500-700 o C or nitrogen tetroxide at 300-500 o C is of industrial importance only for the production of the simplest nitroalkanes, since nitration under these conditions is always is 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 the preparation of nitroalkanes is still the alkylation reaction of the nitrite ion, discovered by W. Meyer back in 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 a 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), which are not linked into a single mesomeric system.

The reactivity of the ambident nitrite ion with two independent nucleophilic centers (nitrogen and oxygen) differs sharply from the reactivity of enolate ions with two nucleophilic centers linked into a single mesomeric system.

The ratio of N- and O-alkylation products (nitroalkane/alkylnitrite) in the Meyer reaction of alkyl bromides and iodides with silver nitrite depends critically on the nature of the alkyl group in the alkyl halide. The yields of primary nitroalkanes reach 75-85%, but they sharply decrease to 15-18% for secondary and to 5% for tertiary nitroalkanes.

Thus, neither tertiary nor secondary alkyl halides are suitable for the synthesis of nitroalkanes when reacting with silver nitrite. The Meyer reaction appears to be the best method for preparing primary nitroalkanes, arylnitromethanes and -nitroesters of carboxylic acids.

To prepare nitroalkanes, only alkyl bromides and alkyl iodides should be used, since alkyl chlorides, alkyl sulfonates and dialkyl sulfates do not react 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 the subsequent nitrosation of the nitroalkane by the parallelly formed alkyl nitrite, 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%, i.e. lower than with alkylation of silver nitrite (75-80%). However, secondary nitroalkanes can be prepared in good yield by alkylation of sodium nitrite in DMF.

Tertiary alkyl halides undergo elimination under the action of 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 reacting 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 formed is decarboxylated to nitromethane. For the preparation of nitromethane homologues, the Kolbe method is not important due to the low yield of nitroalkanes. The idea of ​​this method was ingeniously used in the development of the 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 -nitro-substituted carboxylic acid.

Nitration of carbanions with alkyl nitrates is also widely used to obtain dinitroalkanes. For this purpose, the enolate ions of cyclic ketones are treated with two equivalents of alkyl nitrate. Ring opening followed by decarboxylation leads to the -nitroalkane.

Methods for obtaining aromatic nitro compounds

Aromatic nitro compounds are most often obtained by nitration of arenes, which was discussed 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 the interaction of trifluoroacetic acid anhydride and 90% hydrogen peroxide. Oxidation of an amino group to a nitro group using 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 preparation 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 predominates in equilibrium. For nitromethane at 20 o the concentration of the aci form does not exceed 110 -7 of the nitroalkane fraction, for 2-nitropropane it increases to 310 -3. The amount of the aci form increases for phenylnitromethane. Isomerization of an aci-nitro compound into a nitro compound occurs slowly. 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 to isolate both tautomeric forms of phenylnitromethane in individual form back in 1896. Phenylnitromethane is completely soluble in cold aqueous sodium hydroxide solution. When it is treated with aqueous acetic acid at 0 o, a colorless solid is formed, which is the aci form of phenylnitromethane. It turns red instantly when treated with iron(III) chloride and is quantitatively titrated with bromine.

On standing, the solid aci form slowly isomerizes into the more stable liquid form of phenylnitromethane. For simple nitroalkanes, for example, nitromethane, nitroethane and 2-nitropropane, the aci form cannot be isolated in individual form, since it quite easily isomerizes into the nitro form 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 compared to the nitro form. For nitromethane in water, pKa ~ 10.2, while for its aci form CH 2 =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 CH acid. Let us recall that a similar pattern is observed for keto- and enol forms of carbonyl and 1,3-dicarbonyl compounds, where enol turns out to be 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, similar to the enolization of aldehydes and ketones.

Reactions of ambident anions of nitroalkanes.

When a base acts on both the nitro and aci forms of a nitro compound, a mesomeric ambident anion is formed, common to both of them, in which the charge is delocalized between the oxygen and carbon atoms.

Ambient anions of nitroalkanes are in all respects close analogues of enolate ions of carbonyl compounds and are characterized by the same substitution reactions as 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, carbon, or both centers of the ambident anion of the nitroalkane.

Halogenation of alkali salts of nitro compounds occurs only at the carbon atom; the reaction can be stopped at the stage of introducing one halogen atom.

Nitrosation of primary nitroalkanes also occurs only at the carbon atom and leads to the formation of so-called nitrolic acids.

Secondary nitroalkanes under the same conditions give pseudonitroles.

Nitrolic acids are colorless and, when shaken with a solution of sodium hydroxide, form salts that are colored red.

In contrast, pseudonitroles have a blue color in a neutral environment. These compounds can be used to identify primary and secondary nitroalkanes. Tertiary nitroalkanes do not react at 0°C or below with nitrous acid.

Alkylation of ambident anions of nitroalkanes occurs, in contrast to halogenation and nitrosation, predominantly at the oxygen atom with the formation of aci-form esters as intermediate compounds, which are called nitrone esters. Esters of the aci-form of nitroalkanes can be isolated in individual form by alkylation of nitroalkane salts with trialkyloxonium tetrafluoroborates in methylene chloride at -20 o.

Nitron ethers are thermally unstable and above 0-20° they undergo redox decomposition into an oxime and a 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 alkaline 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 nitroalkane anions 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.

If a benzyl halide contains one or more strong electron-withdrawing groups, 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 according to 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 α-nitro-substituted esters, nitriles, etc., facilitating 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 reaction direction 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 when reacting 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 a type of aldol-crotonic condensation of carbonyl compounds.

The anion of a nitroalkane, rather than a 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 should be carefully controlled to exclude 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 the reaction is very difficult to stop at the stage of formation of -hydroxynitroalkane.

Michael addition of nitroalkane anions to an activated double bond andMannich reaction involving nitroalkanes.

Anions of primary and secondary nitroalkanes add via multiple bonds

,-unsaturated carbonyl compounds, esters and cyanides in a similar way to what happens when enolate ions are added to the activated double bond.

For primary nitroalkanes, the reaction can go further with the participation of a second mole of CH 2 =CHX. Nitroalkane anions are prepared in a Michael addition reaction in the usual manner using sodium ethoxide or diethylamine as the base.

-Nitroalkenes can also be used as Michael acceptors in the addition reaction of conjugation-stabilized carbanions. Addition of nitroalkane anions to  - nitroalkenes 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 undergo Mannich reactions with primary and secondary nitroalkanes and formaldehyde.

In terms of its mechanism and scope of application, this reaction is no different from the classic version of the Mannich reaction with the participation of 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 organomagnesium compounds, as well as lithium aluminum hydride, do not act on the nitro group. The nitro group is one of 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 preprimary 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 an amino group under industrial conditions. The catalyst uses copper on silica gel as a carrier. The catalyst is prepared by depositing copper carbonate from a suspension in a sodium silicate solution and subsequent reduction with hydrogen upon 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 o and is easily regenerated during oxidation with air. 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, platinum is avoided as catalysts for the production of aromatic amines. palladium or Raney nickel.

Another method for the reduction of nitro compounds is reduction with a metal in an acidic or alkaline medium.

The reduction of the nitro group to the amino group occurs in several stages, the sequence of which varies greatly in acidic and alkaline environments. Let us consider sequentially the processes that occur during the reduction of nitro compounds in acidic and alkaline environments.

When reducing in an acidic environment, 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., sensitive to the action of other reducing agents.

The reduction of nitro compounds to primary amines in an acidic medium occurs stepwise and includes three stages with the transfer of two electrons at each stage.

In an acidic environment, each of the intermediate products is quickly reduced to the final product aniline and they cannot be isolated individually. However, in aprotic solvents in a neutral environment, intermediate reduction products can be detected.

When nitrobenzene is reduced with sodium or potassium in THF, the radical anion nitrobenzene is first formed due to the transfer of one electron from the alkali metal.

The alkali metal cation is bonded in 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.

Nitrosobenzene, like other aromatic nitroso compounds, has a high oxidizing potential and is very quickly reduced to N-phenylhydroxylamine. Therefore, nitrosobenzene cannot be isolated as a reduction intermediate, although electrochemical reduction data clearly 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 upon protonation is converted to N-arylhydroxylamine.

The last stage of the reduction of arylhydroxylamine to the 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 reduction product of nitrobenzene. Phenylhydroxylamine is obtained by reducing nitrobenzene with zinc in an aqueous solution of ammonium chloride.

Arylhydroxylamines are easily reduced to amines when treated 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 that cannot otherwise be isolated as intermediates in the reduction of nitro compounds.

Aromatic nitroso compounds readily dimerize in the solid state, and their dimers are colorless. In liquid and gaseous states they are monomeric and green in color.

The reduction of nitro compounds by metals in an alkaline medium differs from reduction in an acidic medium. In an alkaline environment, nitrosobenzene reacts rapidly with a 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 the old method when using As 2 O 3 or glucose as a reducing agent.

Azoxybenzene, when exposed to zinc in an alcoholic alkali solution, is reduced first to azobenzene, and when exposed to excess zinc, further to hydrazobenzene.

In synthetic practice, azoxybenzene derivatives can be reduced to azobenzene by the action of 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. Reduction of azoxybenzene produces a more stable trans isomer, which upon irradiation with UV light is converted to a cis isomer.

Unsymmetrical azobenzene derivatives are obtained by 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 in a yield close to quantitative.

Azobenzene is reduced by zinc dust and alcohol alkali to hydrazobenzene. Hydrazobenzene is thus the end product of the reduction of nitrobenzene by a metal in an alkaline medium. In air, colorless hydrazobenzene easily oxidizes to orange-red colored azobenzene. At the same time, hydrazobenzene, as well as azobenzene and azoxybenzene, is reduced to aniline under the action of sodium dithionite in water or tin (II) chloride in hydrochloric acid.

The overall process of reduction of aromatic nitro compounds by metals in acidic and alkaline environments can be represented as the following sequence of transformations.

In an acidic environment:

In an alkaline environment:

In industry, aniline is produced by the catalytic reduction of nitrobenzene on a copper or nickel catalyst, which has replaced the old method of reducing nitrobenzene with cast iron turnings in an aqueous solution of ferric chloride and hydrochloric acid.

The reduction of a nitro group to an amino group by 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.

During the stepwise reduction of polynitro compounds with sodium sulfide, this inorganic reagent is converted into sodium tetrasulfide, which is accompanied by the formation of an alkali.

High alkalinity of the environment leads to the formation of azoxy and azo compounds as by-products. In order to avoid this, sodium gyrosulfide should be used as a reducing agent, where alkali is not formed.

1. Nitro compounds

1.2. Reactions of nitro compounds

1. NITRO COMPOUNDS

Nitro compounds are hydrocarbon derivatives 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 causes it to have a strong -I effect. Along with the strong -I effect, the nitro group has a strong -M effect.

Ex. 1. Consider the structure of the nitro group and its effect on the direction and rate of the electrophilic substitution reaction in the aromatic ring.

1.1. Methods for obtaining nitro compounds

Almost all methods for obtaining nitro compounds have already been discussed in previous chapters. Aromatic nitro compounds are usually obtained by direct nitration of arenes and aromatic heterocyclic compounds. Nitrocyclohexane is produced industrially by nitration of cyclohexane:

Nitromethane is also obtained in the same way, but in laboratory conditions it is obtained from chloroacetic acid as a result of reactions (2-5). The key stage of these is reaction (3), which occurs via the SN2 mechanism.

Chloroacetic acid Sodium chloroacetate

Nitroacetic acid

Nitromethane

1.2. Reactions of nitro compounds

1.2.1. Tautomerism of aliphatic nitro compounds

Due to the strong electron-withdrawing properties of the nitro group, the a-hydrogen atoms have increased mobility and therefore primary and secondary nitro compounds are CH-acids. Thus, nitromethane is a fairly strong acid (pKa 10.2) and in an alkaline environment 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.

1.2.2. Condensation of aliphatic nitro compounds with aldehydes and ketones

A nitro group can be introduced into aliphatic compounds by an aldol reaction between a nitroalkane anion and an aldehyde or ketone. In nitroalkanes, the a-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 a-hydrogen atoms. With aliphatic aldehydes, addition reactions usually occur, and with aromatic aldehydes, only condensation reactions occur.

Thus, nitromethane adds to cyclohexanone,

1-Nitromethylcyclohexanol

but condenses with benzaldehyde,

The addition reaction with formaldehyde involves all three hydrogen atoms of nitromethane to form 2-hydroxymethyl-2-nitro-1,3-dinitropropane or trimethylolnitromethane.

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.

1.2.3. Reduction of nitro compounds

The nitro group is reduced to an amino group by various reducing agents (11.3.3). Aniline is produced 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 to release hydrogen.

7-nitro-1,3,5-triazaadamantane 7-amino-1,3,5-triazaadamantane

Nitro compounds are reduced with metals in an acidic environment followed by alkalization

Depending on the pH of the medium and the reducing agent used, different products can be obtained. In a neutral and alkaline environment, the activity of conventional reducing agents towards nitro compounds is less than in an acidic environment. A typical example is the reduction of nitrobenzene with zinc. In excess 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 rearrangement:

p-Aminophenol is used as a developer in photography. Phenylhydroxylamine can be further oxidized to nitrosobenzene:

Nitrosobenzene

By reducing nitrobenzene with tin(II) chloride, azobenzene is obtained, and with zinc in an alkaline medium, hydrazobenzene is obtained.

By treating nitrobenzene with a solution of alkali in methanol, azoxybenzene is obtained, while the methanol is oxidized to formic acid.

Methods for incomplete reduction of nitroalkanes are known. One of the industrial methods for producing nylon 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 - nylon:

Reduction of the nitro group of aldol addition products (7) is a convenient way to obtain b-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 buffer solution of ammonium chloride.

Exercise 5. Complete the reactions:

Reaction with nitrous acid. A characteristic qualitative reaction to primary and secondary nitro compounds is the reaction with nitrous acid.

For tertiary aliphatic nitro compounds There are no specific detection reactions.

Detection of aromatic nitro compounds. Aromatic nitro compounds are usually pale yellow in color. In the presence of other substituents, the intensity and depth of color often increases. To detect aromatic nitro compounds, they are reduced to primary amines, the latter are diazotized and combined with β-naphthol:

This reaction, however, is not specific, since amines are formed during the reduction of not only nitro compounds, but also nitroso, azooxy, and hydrazo compounds. In order to make a final conclusion about the presence of a nitro group in a compound, it is necessary to carry out a quantitative determination.

Qualitative reactions of N-nitroso compounds

Reaction with HI. C-Nitroso compounds can be distinguished from N-nitroso compounds by their relation to an acidified solution of potassium iodide: C-Nitroso compounds oxidize hydroiodic acid, N-nitroso compounds do not react with hydroiodic acid.

Reaction with primary aromatic amines. C-Nitroso compounds condense with primary aromatic amines, forming colored azo compounds:

Hydrolysis of N-nitroso compounds. Pure aromatic and fatty aromatic N-nitroso compounds (nitrosamines) are easily hydrolyzed by alcohol solutions of HCl, forming a secondary amine and nitrous acid. If hydrolysis is carried out in the presence of a-naphthylamine, then the latter is diazotized by the resulting nitrous acid, and the diazo compound enters into an azo coupling reaction with excess a-naphthylamine. An azo dye is formed:

The reaction mixture turns pink; Gradually the color becomes purple.

Qualitative reactions of nitriles

In the analysis of nitriles RC≡N, ArC≡N, their ability to hydrolyze and be reduced is used. To detect the C≡N group, hydrolysis is carried out:

Nitriles are most conveniently characterized by the acids that are obtained by their hydrolysis. The acid is isolated from the hydrolyzate by steam distillation or extraction and converted into one of the derivatives - an ester or an amide

Qualitative reactions of thiols (thioalcohols, thioesters)

The most important properties of thiols used in the analysis are the ability to substitute a hydrogen atom in the -SH group and the ability to oxidize. Substances containing the -SH group have a strong unpleasant odor, which weakens with increasing number of carbon atoms in the molecule.

Reaction with HNO 2. Substances containing the SH group give a color reaction when exposed to nitrous acid:

In addition to thiols, thioacids RCOSH also give this reaction. If R is a primary or secondary alkyl, a red color appears; if R is a tertiary alkyl or aryl, the color is first green and then red.

Mercaptide formation. A characteristic qualitative reaction of thiols is also the formation of precipitation of heavy metal mercaptides (Pb, Cu, Hg). For example,

Lead and copper mercaptides are colored.