Write the reaction equations for the nitration of toluene and the combustion of benzene. Nitration of aromatic hydrocarbons

Preparation via diazo compound

Methods in this group are much less numerous, but are distinguished by high yields, low levels of by-product impurities, simplicity and variety of execution.

The simplest and most reliable method of this group is to carry out the Sandmeyer reaction. We can give 2 examples of different ways of carrying out just this stage:

2.3 Other methods

PhBr + TfOMe, anthranilic acid in the Borodin-Hunsdiecker reaction, reaction of o-dibromobenzene and MeMgBr, etc. - have advantages over other methods and have a lower preparative value, although they are of interest.

Selected synthesis path - analysis, description of methods for performing experimental stages

The main criterion for choosing one or another method, described in detail above, is reliability and availability. This corresponds to the path toluene - nitrotoluene - o-toluidine - o-bromotoluene.

Toluene nitration

0.15 mol of an aromatic nitro compound is placed in a 250 ml three-neck flask equipped with a stirrer, dropping funnel, and internal thermometer (the device should not be sealed). Then slowly add the nitrating mixture, pre-cooled to at least 10 °C, with good stirring and a cooling ice bath, the temperature of the reaction mixture should be in the range of 5-10 °C.

Then stir at room temperature for another 2-3 hours. After this, the reaction mixture is carefully poured into 300 ml of ice water and mixed well. The organic layer is separated, and the aqueous layer is extracted with ether. The combined organic extracts are washed with water, 2 N. sodium bicarbonate solution until neutral, then again with water. heater. The extracts are dried over CaCl 2 and distilled. The P-isomer is frozen with a mixture of ice and salt and washed with a small amount of cold petroleum ether. (Careful separation is sufficient, this method leaves about 4% of the p-isomer: freezing for 8 hours with a mixture of ice and salt (2:1). A good method of separation is the reduction of the p-isomer with an alkaline reducing agent. P-toluidine can be separated due to its basic properties Separation is best achieved by fractional distillation followed by crystallization 11). From the filtrate by vacuum distillation on a 30 cm column In Game with electrical heating, the o-isomer is isolated. The yield of o-isomer is 40%. The boiling points of o- and p-nitrotoluene are 96°C/9 mm, respectively. and 105°C/10 mm, melting point of p-toluidine 52-54°C.

Nitration of benzene can be carried out with small amounts of starting materials without isolating a pure product. To obtain nitrobenzene using the equation:

C 6 H 6 + HNO 3 à C 6 H 5 NO 2+ H 2 O

concentrated nitric acid (specific gravity 1.4) is required. The reaction mixture should not be heated above 50-60°C. When dilute acid is used, the nitration reaction does not occur; with increasing temperature, a noticeable formation of dinitrobenzene begins.

It follows from the equation that the reaction requires equimolecular amounts of the starting materials. However, in this case, the reaction will not reach completion, since the released water will dilute the nitric acid, and it will lose its nitrating property. Consequently, in order to complete the reaction, it is necessary to take more nitric acid than should be according to theory. But to prevent the reaction from becoming too violent, nitric acid must be dissolved in concentrated sulfuric acid, which does not deprive nitric acid of its nitrating effect and binds the water released during the reaction.

To prevent the possibility of an increase in temperature during the reaction, do not mix all the substances at once, but gradually add benzene to the mixture of acids. 8 ml of concentrated sulfuric acid and 5 ml of concentrated nitric acid are poured into a small flask. Cool the mixture under running water. Then 4 ml of benzene is added to the cooled mixture in small portions, constantly shaking the flask to achieve greater mixing of liquids that do not dissolve in each other (the mixture of acids makes up the bottom layer, benzene makes up the top layer). After adding all the benzene to achieve completeness of the reaction, the flask is closed with a stopper with a vertical tube (benzene vapor is volatile) and heated in a water bath preheated to 60°C

Shake the flask from time to time to better mix the liquids.

The duration of heating may be determined not so much by the need to achieve completeness of the reaction, but by the availability of time in the lesson. When working in a mug, heating should continue for 30-40 minutes. In the lesson, it is possible to demonstrate the formation of nitrobenzene after heating for 10 minutes and even without additional heating at all, if the reaction went well when benzene was added to a mixture of acids.

Nitrobenzene is placed in a layer on top of the acid mixture. Pour the contents of the flask into a glass with plenty of water. In this case, the acids dissolve in water, while nitrobenzene collects at the bottom of the glass in the form of a heavy yellowish liquid. If time permits, drain some of the liquid from the nitrobenzene and separate it using a separating funnel.

When significant quantities of nitrobenzene are obtained and it is necessary to purify it, nitrobenzene is washed with water, a diluted (5 percent) alkali solution, then again with water, each time separating the liquids using a separating funnel. The nitrobenzene is then dehydrated by heating it with granular calcium chloride until the liquid becomes clear. Heating is necessary in order to reduce the viscosity of nitrobenzene and thus achieve more complete contact with calcium chloride. Finally, nitrobenzene can be distilled from a small flask with an air cooler at a temperature of 204-207°C. To avoid decomposition of dinitrobenzene residues, dry distillation is not recommended.

Nitration of aromatic hydrocarbons

a) Nitration of benzene (traction!). In a small flask, mix 4 ml of concentrated sulfuric acid ( = 1.84) with 3 ml of concentrated nitric acid ( = 1.4). 3 ml of benzene is added dropwise to the resulting mixture, shaking the contents of the flask vigorously (the temperature should not rise above 40 C), cooling with water if necessary. Having closed the flask with a stopper with an air cooler, heat it for 15 minutes in a water bath to 60 0 C, shaking frequently. The reaction mixture is then cooled and poured into a glass with 20 ml of ice water, thereby forming two layers. The aqueous layer is drained, and the oil (nitrobenzene) that has precipitated at the bottom is washed twice more with water. After separation from water, crude nitrobenzene is poured into a dry test tube, 2-3 pieces of calcined CaCl2 are added and heated in a water bath until the nitrobenzene becomes transparent. Nitrobenzene is distilled from a small Wurtz flask or test tube with a downward tube at 207-210 0 C. (Nitrobenzene cannot be distilled to dryness! An explosion is possible!).

Write the equation for the nitration of benzene. What is the role of sulfuric acid in the nitration of aromatic compounds? Explain the mechanism of nitration of aromatic compounds.

c) Nitration of toluene. When toluene is nitrated, a mixture may form ortho- And pair- nitrotoluenes. Monitoring the process and identifying reaction products can be carried out using thin layer chromatography. Chromatography is carried out on a silufol plate using carbon tetrachloride as an eluent. Prepare a nitrating mixture of 3 ml of concentrated nitric acid ( = 1.1) and 1 ml of concentrated sulfuric acid. The nitrating mixture is added dropwise into a test tube with 2 ml of toluene while cooling and shaking the reaction mixture. Then the test tube is closed with a stopper with a vertical tube and heated in a water bath, shaking frequently. After 10 minutes, a sample of the reaction mass is taken with a capillary and a sample of the solution and “witnesses” are applied to the starting line of the silufol plate. ortho - And pair- nitrotoluenes (in toluene). The plate is lowered into a chamber containing carbon tetrachloride and the appearance of nitrotoluenes is noted.

The next sample of the solution is taken after 40 minutes, and the third - after 1 hour. The change in the composition of the reaction medium is noted.

How does the ratio of nitrotoluene isomers change during the reaction? Write the equation for the reaction of toluene nitration. Consider the reaction mechanism. Explain the effect of the structure of an aromatic compound on the ease of nitration.

Nitration

The nitration reaction is one of the most studied aromatic substitution reactions. For preparative purposes, nitration is usually carried out with a mixture of concentrated nitric and sulfuric acids, the so-called nitrating mixture . At the first stage of the reaction, the formation of nitronium ion + NO 2 occurs, which is an electrophilic agent:

HO-NO 2 + H 2 SO 4 H 2 O + -NO 2 + HSO 4 -

H 2 O + -NO 2 + H 2 SO 4 H 3 O + + HSO 4 - + + NO 2

The presence of nitronium ion in this solution was confirmed spectroscopically. Nitric acid in concentrated sulfuric acid is almost completely converted into a nitronium cation. The insignificant effectiveness of nitric acid itself in the nitration reaction of benzene is explained by the low content of the + NO 2 ion.

Other systems are also used as nitrating agents, in which either a cation + NO 2 or a compound of the general formula NO2-Y is generated where Y is a good leaving group. Some of these systems that have found the greatest application are presented in Table 1 in order of increasing activity.

Table 1. Nitrating reagents.

Using the example of the nitration reaction of alkylbenzenes, the influence of spatial factors on the direction of electrophilic substitution is clearly visible. Thus, during the nitration of toluene (methylbenzene) ortho-isomer is formed as the main product, and upon transition to ethyl-, iso-drank- and especially to rubs-butyl-benzene, its yield decreases significantly (see Table 2).

Table 2. Influence of spatial factors on the ratio of ortho-, para-isomers in the nitration reaction (NO 2 +)

When studying the nitration of alkylbenzenes, the so-called ipso-substitution , when an electrophilic attack occurs at the carbon atom of the benzene ring that already contains a substituent, for example:

Unlike nitration, during halogenation the attack of the aromatic substrate can be carried out by various electrophiles. Free halogens, for example, Cl 2 and Br 2 (note 35) can easily attack the activated aromatic ring (for example, phenol), but are not able to react with benzenes and alkylbenzenes (photochemical activation can, however, in the latter case lead to the occurrence of radical side chain substitutions; see section IV.3). To polarize the attacking halogen molecule, it is necessary Lewis acid catalysis such as AlCl 3, FeBr 3, etc.; in this case, the so-called “electrophilic end” appears in the halogen molecule (the energy required for the formation of the Hal + cation is significantly higher). This makes electrophilic substitution much easier:

Halogenation proceeds very vigorously if reagents are used in which the halogen, as a result of polarization, has a strong positive charge or even exists as a cation. Yes, very inert meta-dinitrobenzene can be brominated with bromine in concentrated sulfuric acid in the presence of silver sulfate. It is assumed that in this case a bromine cation is formed intermediately:

2Br 2 + Ag 2 SO 4 2Br + + 2AgBr + SO 4 2-

The reactivity of elemental iodine in electrophilic substitution reactions in the aromatic ring is negligible, so direct iodination is possible only in the case of phenol and aromatic amines. Iodination of other aromatic compounds is carried out in the presence of an oxidizing agent (usually nitric acid). It is believed that under these conditions the role of the electrophilic agent is played by the I- + OH 2 ion.

For the halogenation of arenes, it can also be used mixed halogens, for example, bromine monochloride (BrCl) or iodine (ICl):

Halogenation in vivo. As an example of electrophilic aromatic halogenation occurring in living organisms, we can cite the reaction of iodination of the amino acid tyrosine during the biosynthesis of iodine-containing thyroid hormones to 3-iodotyrosine and then to 3,5-diiodotyrosine:

The details of the mechanism of sulfonation have been studied in less detail compared to nitration and halogenation. Benzene itself is sulfonated rather slowly with hot concentrated sulfuric acid, but quickly with oleum, SO 3 in inert solvents, or a complex of SO 3 with pyridine. The nature of the electrophilic species depends on the reaction conditions, but it is probably always SO 3, either in a free state or bound to a “carrier”, for example, in the form of H 2 SO 4. SO 3 (H 2 S 2 O 7) in sulfuric acid. Small amounts of SO 3 are formed in H 2 SO 4:

2H 2 SO 4 SO 3 + H 3 O + + HSO 4 -

The attack of the aromatic substrate is carried out by the sulfur atom since it is strongly positively polarized, that is, electron-deficient:

Sulfonation is reversible process. This is of practical importance: when sulfonic acids are treated with steam, the SO 3 H group is replaced by hydrogen. Thus, it is possible to introduce the SO 3 H group as a substituent that orients subsequent reactions in the required manner (see section IV.1.B), and then remove it. The sulfonation of naphthalene has some interesting features (see section IV.1.D).

Like halogens, alkyl halides can be so highly polarized Lewis acids(aluminum and zinc chlorides, boron trifluoride, etc.) that they become capable of electrophilic substitution in the aromatic ring:

R-Cl + AlCl 3 R +... Cl ...- AlCl 3 R + AlCl 4 -

In addition to alkyl halides, alkenes or alcohols can be sources of carbocations for the halogenation of aromatic compounds. In this case, the presence of a protic acid is necessary to protonate the alkene or alcohol. In the case of alcohols, an additive is required no less than equimolar amount of acid (since the water released during the reaction deactivates an equimolar amount of the catalyst), whereas in reactions involving alkyl halides and alkenes it is sufficient to add a small amount of catalyst.

In the laboratory, Friedel-Crafts alkylation has limited use, since this reaction usually produces mixtures of products, due to a number of reasons:

1) The resulting alkylation product undergoes electrophilic aromatic substitution reactions more easily than the starting compound (Alk is an electron-donating group), therefore the product is then preferentially alkylated. If one wants to obtain monoalkylation products, then it is necessary to take a large excess of the aromatic compound.

2) Like sulfonation, the Friedel-Crafts alkylation reaction reversible(see also section IV.1.D).

3) Even under mild conditions, primary and secondary alkyl halides give preferentially secondary or tertiary alkylarenes, respectively, since alkylation occurs under conditions approaching S N 1 reactions. (note 37) Regrouping can be avoided if you work at low temperatures.

The Friedel-Crafts acylation of aromatic compounds is the most important method for the synthesis of fatty aromatic ketones. Carboxylic acid derivatives, such as acyl halides and anhydrides, have a polar carbonyl group and are in principle capable of electrophilic substitution in aromatic systems:

The electrophilic activity of these compounds, however, is low and must be enhanced by the action of Lewis acids. In this case, the acid catalyst, as a rule, attacks the oxygen atom carbonyl compound and, by shifting the electron density, increases the positive charge of the neighboring carbon atom. As a result, a polarized complex is formed (and, in the limit, an acyl cation), acting as an electrophile:

An important difference between the acylation reaction with acyl halides and the alkylation reaction with alkyl halides is that in the first of these reactions more than 1 mole Lewis acid required, while in the second only catalytic amounts are needed. This is due to the fact that the Lewis acid forms a complex with both the acylating derivative of the carboxylic acid and the ketone, the reaction product. When reacting with anhydrides, the resulting acid binds another mole of catalyst, so that in total at least two moles are needed. In each case, upon completion of the reaction, the resulting ketone complex with aluminum chloride (or other Lewis acid) must be hydrolytically destroyed (hydrochloric acid with ice).

No polyacylation is observed because the resulting ketone is significantly less reactive than the parent compound (see section IV.1.B). Therefore, it is often preferred to obtain alkylbenzenes not by direct alkylation, but by Friedel-Crafts acylation followed by reduction. Aromatic compounds with strongly deactivating substituents, such as nitro or cyano groups, are also not Friedel-Crafts acylated.

Control tasks

2. Draw a potential energy diagram for an electrophilic aromatic substitution reaction in which the slow step is the formation
-complex (for example, nitration of benzene with nitronium borofluoride;
see section IV.1.A).

3. Which product is predominantly formed during bromination: a) pair-nitrotoluene; b) meta-nitrobenzenesulfonic acids; V) ortho-nitrophenol.

4. Adrenaline (1-(3,4"-dihydroxyphenyl)-2-methylaminoethanol) is the first hormone isolated from the adrenal medulla; it is currently synthesized in three stages from pyrocatechol. Write the equation for the first stage of this synthesis - the reaction of acylation of catechol (1,2-dihydroxybenzene) with chloroacetic acid chloride and explain the mechanism).

5. One of the qualitative reactions to proteins is the xanthoprotein reaction, indicating the presence of aromatic amino acids. It involves treating the protein with nitric acid when heated. Write the equation for the xanthoprotein reaction with tyrosine (see Section I), formed as a result of protein hydrolysis.