Reactions of electrophilic substitution of arenes. Electrophilic substitution in aromatic systems
The most widely used benzene reaction is the replacement of one or more hydrogen atoms by an electrophilic group. Many important substances are synthesized in this way. The choice of functional groups that can thus be introduced into aromatic compounds is very wide, and in addition, some of these groups can be transformed into other groups after introduction into the benzene ring. The general reaction equation is:
Below are the five most common reactions of this type and examples of their use.
Nitration:
Sulfonation:
Dkylation according to Friedel-Crafts:
Friedel-Crafts acylation:
Halogenation (only chlorination and bromination):
The following reactions are often used to further transform compounds resulting from aromatic electrophilic substitution.
Side chain recovery:
Recovery of the nitro group:
Diazotization and further transformations
Aniline and its substituted compounds can be converted into highly reactive compounds called diazonium salts:
Diazonium salts serve as starting materials for the synthesis of a wide variety of aromatic compounds (Scheme 9-1). In many cases, the method of synthesis through diazonium salts is the only way to introduce any functional group into an aromatic compound.
The replacement of the diazonium group by chlorine and bromine atoms, as well as by the cyano group, is achieved by the interaction of diazonium salts with copper salts (1). Iodine and fluorine atoms cannot be introduced into the aromatic ring by direct halogenation. Aromatic iodides and fluorides are obtained by treating diazonium salts with potassium iodide and hydroboric acid, respectively.
Aromatic carboxylic acids can be obtained either by hydrolysis of the nitrile group, or by the action of carbon dioxide on a Grignard reagent (more on this reaction will be discussed in Chapter 12). Phenols in the laboratory are most often obtained by hydrolysis of diazonium salts.
Diagram 9-2. Reactions of diazonium salts
The diazonium group (and hence also the amino group and the nitro group) can be removed (i.e., replaced by a hydrogen atom) by acting on the diazonium salts of hypophosphorous acid
Finally, the interaction of diazonium salts with activated aromatic compounds leads to the formation of azo dyes. Dyes can be of very different colors depending on the nature of the substituents on both aromatic rings.
Nitrous acid, which is used to prepare diazonium salts, is a low-stable substance and is prepared in situ (i.e., directly in the reaction vessel) from sodium nitrite and hydrochloric acid. In the reaction scheme, treatment with nitrous acid can be shown in one of two ways, which are applied below:
Here are some examples of reactions of diazonium salts:
Obtaining practically important substances using electrophilic substitution reactions
Dyes. The synthesis of methyl orange is shown below. If you take the original compounds with other substituents in aromatic rings, then the color of the dye will be different.
Polymers. Polystyrene is obtained by polymerization of styrene (see Chap. 6), which, in turn, can be synthesized as follows. Benzene is acylated according to Friedel-Crafts, using acetic anhydride instead of acetyl chloride, the resulting ketone is reduced to an alcohol, which is then dehydrated using potassium hydrogen sulfate as an acid catalyst:
Medications. in the synthesis of sulfanilamide (streptocide), the first two steps are reactions that we have already encountered. The third stage is the protection of the amino group. This is necessary to prevent the interaction of chlorosulfonic acid with the amino group. After the group has reacted with ammonia, the protecting group can be removed.
Streptocid was one of the first antimicrobials of the sulfonamide group. It is applied even now.
Electrophilic substitution reactions allow many different groups to be introduced into the aromatic ring. Many of these groups can then be transformed during synthesis.
Mechanism of aromatic electrophilic substitution
It has been established that electrophilic substitution in aromatic compounds proceeds in two stages. First, an electrophile (which can be generated by various methods) is attached to the benzene ring. In this case, a resonantly stabilized carb cation is formed (below in parentheses). This cation then loses a proton and turns into an aromatic compound.
Here, for clarity, the formulas of aromatic compounds are shown with double bonds. But you, of course, remember that in fact there is a cloud of delocalized electrons.
Below are the mechanisms of the two reactions, including the electrophile generation step. Haogenation
Electrophile generation:
Substitution:
Friedel-Crafts acylation Electrophile generation:
Substitution:
Influence of deputies
When a substituted benzene reacts with an electrophile, the structure of the substituent already present on the benzene ring has a significant effect on the orientation of the substitution and on its rate.
According to their effect on the rate and orientation of electrophilic substitution, all possible substituents can be divided into three groups.
1. Activating orthopara-orientants. In the presence of a substituent of this group in an aromatic compound, it reacts faster than unsubstituted benzene, and the electrophile goes to the ortho and para positions to the substituent and a mixture of ortho and para disubstituted benzenes is formed. This group includes the following substituents:
2. Deactivating meta-orienting agents. These substituents slow down the reaction compared to benzene and direct the electrophile to the meta position. This group includes:
3. Deactivating ortho-, paraorientants. This group includes atoms of alogens.
Orientation examples for electrophilic substitution:
Explanation of the influence of substituents
Why do different substituents have such a different effect on the nature of the electrophilic substitution? The answer to this question can be obtained by analyzing the stability of the intermediates formed in each case. Some of these intermediate carbocations will be more stable, others less stable. Recall that if a compound can react in more than one way, the reaction will take the route that produces the most stable intermediate.
Shown below are the resonance structures of intermediate particles formed during the electrophilic attack of a cation in the ortho-meta- and para-positions of phenol, which has a powerful activating substituent - ortho, para-orienting, toluene, which has a substituent with the same, but much less pronounced properties, and nitrobenzene, available in which the nitro group is a megd orientant and deactivates the ring:
When an electrophile is attacked in both the ortho and para positions of the phenol, more resonance structures can be written for the emerging intermediate than for the intermediate upon meta substitution. Moreover, this "extra" structure (circled in a box) makes a particularly large contribution
into the stabilization of the cation, since in it all atoms have an octet of electrons. Thus, a more stable cation arises in the ortho- or para-orientation of the attack of the electrophile than in the attack to the meta-position; therefore, the substitution occurs predominantly in the ortho- and para-positions. Since the cation arising from such a substitution is more stable than the cation formed from unsubstituted benzene, phenol enters into electrophilic substitution reactions much more easily than benzene. Note that all substituents that strongly or moderately activate an aromatic ring in electrophilic substitution reactions have a single lone atom attached to the ring. These electrons can be fed into the ring. In this case, a resonant structure arises with a positive charge on an electronegative atom (oxygen or nitrogen). All this stabilizes the intermediate and increases the reaction rate (resonant activation).
In the case of toluene, substitution in both the ortho- and d-positions results in a more stable cation than when an electrophile attacks in the meta-position.
In the boxed resonant structures, the positive charge is on the tertiary carbon atoms (tertiary by carbocation, see Chapter 5). When attacked in the meta position, the tertiary carbocation does not occur. Here again, the ortho- and para-substitution goes through slightly more stable intermediate species than the meta-substitution and than the substitution in benzene itself. Therefore, the substitution in toluene is directed to the ortho and para positions and proceeds somewhat faster than the substitution in Lysol (activation due to the inductive effect).
All deactivating groups, including the nitro group, have the property of withdrawing electrons from the aroma ring. The result of this is the destabilization of the intermediate cation. Especially
(click to view scan)
the intermediates that arise upon attack in the ortho and para positions are strongly destabilized, since the partial positive charge is located directly next to the nitro group (the corresponding resonance structures are circled). Therefore, meta-substitution is preferred over ortho- and para-substitution. Nitrobenzene undergoes electrophilic substitution much more difficult than benzene, since the electron density in the ring is lowered and the mutual attraction of the aromatic ring and the electrophile is weakened.
Electrophilic addition reactions proceed in two stages through the formation of an intermediate cation. Different substituents on the benzene ring have different effects on the rates and orientations of substitution. This influence can be explained taking into account the stability of the intermediates formed in each case.
Electrophilic substitution reactions(English) substitution electrophilic reaction ) - substitution reactions, in which the attack is carried out electrophile- a particle that is positively charged or has a deficit of electrons. When a new bond is formed, the outgoing particle - electrofuge split off without its electron pair. The most popular leaving group is the proton H+.
General view of electrophilic substitution reactions:
(cationic electrophile)
(neutral electrophile)
There are reactions of aromatic (widespread) and aliphatic (not common) electrophilic substitution. The specificity of electrophilic substitution reactions specifically for aromatic systems is explained by the high electron density of the aromatic ring, which is capable of attracting positively charged particles.
Aromatic electrophilic substitution reactions play an extremely important role in organic synthesis and are widely used both in laboratory practice and in industry.
Aromatic electrophilic substitution reactions
For aromatic systems, there is actually one mechanism of electrophilic substitution - S E Ar. Mechanism S E 1(by analogy with the mechanism S N 1) is extremely rare, and S E 2(corresponding by analogy S N 2) does not occur at all.
S E Ar reactions
reaction mechanism S E Ar or aromatic electrophilic substitution reactions(English) Electrophilic aromatic substitution ) is the most common and most important of the aromatic substitution reactions and consists of two steps. At the first stage, the electrophile is attached, at the second stage, the electrofuge is split off:
During the reaction, an intermediate positively charged intermediate is formed (in the figure - 2b). It bears the name Weland intermediate, aronium ion or σ-complex. This complex, as a rule, is very reactive and is easily stabilized by rapidly eliminating the cation.
The rate-limiting step in the vast majority of reactions S E Ar is the first stage.
Speed reaction S E Ar is usually presented in the following form:
| Reaction rate = k** |
Relatively weak electrophiles usually act as an attacking particle, so in most cases the reaction S E Ar proceeds under the action of a Lewis acid catalyst. More often than others, AlCl 3, FeCl 3, FeBr 3, ZnCl 2 are used.
In this case, the reaction mechanism is as follows (using the example of benzene chlorination, FeCl 3 catalyst):
1. At the first stage, the catalyst interacts with the attacking particle to form an active electrophilic agent:
2. At the second stage, in fact, the mechanism is implemented S E Ar:
Typical aromatic electrophilic substitution reactions
| Reaction rate = k** |
In substituted benzenes, the so-called ipso-attack, that is, the replacement of an existing substitute with another:
Aliphatic electrophilic substitution reactions
Reactions S E 1
reaction mechanism S E 1 or monomolecular electrophilic substitution reactions(English) substitution electrophilic unimolecular ) is similar to the mechanism S N 1 includes the following stages:
1. Ionization of the substrate with the formation of a carbanion (slow stage):
2. Electrophilic attack of the carbanion (fast stage):
Most often an outgoing particle in extremely rare reactions S E 1 is a proton.
Reactions S E 2
reaction mechanism S E 2 or bimolecular electrophilic substitution reactions(English) electrophilic bimolecular substitution ) is similar to the mechanism S N 2, occurs in one stage, without intermediate formation of an intermediate:
The main difference from the nucleophilic mechanism is that the attack of the electrophile can be carried out both from the front and from the rear, which as a result can lead to a different stereochemical result: both racemization and inversion.
An example is the ketone-enol tautomerization reaction:
Ketone-enol tautomerization
Notes
| Chemical reactions in organic chemistry | |
|---|---|
| Substitution reactions | Nucleophilic substitution reactions Electrophilic substitution reactions Reactions of radical substitution |
| Addition reactions | Nucleophilic addition reactions Electrophilic addition reactions Radical addition reactions Simultaneous addition reactions |
| Elimination reactions | Heterolytic elimination reactions Pericyclic elimination reactions Radical elimination reactions |
| rearrangement reactions | Nucleophilic rearrangements Electrophilic rearrangements Radical rearrangements |
| Oxidation and reduction reactions | Oxidation reactions Reduction reactions |
| Other | Nominal reactions in organic chemistry |
Wikimedia Foundation. 2010 .
- - (English addition electrophilic reaction) addition reactions, in which the attack at the initial stage is carried out by an electrophile particle, positively charged or having a deficit of electrons. At the final stage, the resulting ... ... Wikipedia
Electrophilic substitution reactions are more difficult than those of benzene, which is due to the strong electron-withdrawing effect of the nitro group. The substitution occurs in the meta position, since the nitro group is an orientant of the second kind (S E 2 arom).
Therefore, electrophilic substitution reactions are carried out only with strong reagents (nitration, sulfonation, halogenation) under more stringent conditions:
Nucleophilic substitution reactions
In nucleophilic substitution reactions (S N 2 arom), the nitro group directs the nucleophile to the ortho and para positions.
For example, the fusion of nitrobenzene with KOH at 100 0 C leads to the production of ortho- and para-nitrophenols:
An attack to the ortho position is more preferable, since the negative inductive effect of the nitro group, acting at a small distance, creates a greater shortage of electrons in the ortho than in the para position.
The presence of two and especially three nitro groups in the meta position relative to each other further promotes reactions with nucleophilic reagents.
So, for example, when meta-dinitrobenzene reacts with alkali or with sodium amide, one of the hydrogen atoms in the ortho or para positions is replaced by the group Oh, or at NH 2 :
2,4-dinitrophenol
2,6-dinitroaniline
Symmetrical trinitrobenzene reacts with alkali to form picric acid:
2,4,6-trinitrophenol
picric acid
Influence of the nitro group on reactivity
other groups in the benzene ring
Nucleophilic substitution of the nitro group
If the nitro groups are in ortho- and para-positions with respect to each other, then they activate each other and nucleophilic substitution of the nitro group is possible with the departure of the nitrite ion:
Nucleophilic substitution of halogens and other groups
The nitro group activates the nucleophilic substitution not only of the hydrogen atom, but also of other groups located in the benzene ring in the ortho and para positions relative to the nitro group.
The halogen atoms, -OH, -OR, -NR 2 and other groups are easily replaced by nucleophiles.
The role of the nitro group is not only to create a positive charge on the carbon atom associated with the substituting group, but also to stabilize the negative ϭ-complex, because the nitro group contributes to the delocalization of the negative charge.
For example, the halogen in ortho- and para-nitrochlorobenzenes under the influence of the nitro group is easily replaced by nucleophilic particles:
:Nu: -- = HE -- , NH 2 -- , I -- , -- OCH 3
The presence of two and especially three nitro groups accelerates nucleophilic substitution, and this is most pronounced in cases where the nitro groups are in the ortho or para position relative to the group being replaced:
2,4-dinitrochlorobenzene
The halogen atom is most easily replaced in 2,4,6-trinitrochlorobenzene (picryl chloride):
2,4,6-trinitrochlorobenzene
(picryl chloride)
Reactions related to the mobility of hydrogen atoms
alkyl radicals
Due to the strongly pronounced electron-withdrawing character, the nitro group has a significant effect on the mobility of hydrogen atoms of alkyl radicals located in the ortho and para positions with respect to it.
a) condensation reactions with aldehydes
In para-nitrotoluene, the hydrogen atoms of the methyl group under the influence of the nitro group acquire high mobility and, as a result, para-nitrotoluene enters into condensation reactions with aldehydes as a methylene component:
b) the formation of nitronic acids
Hydrogen atoms at the α-carbon atom due to ϭ, π-conjugation have high mobility and can migrate to the oxygen of the nitro group with the formation of tautomeric nitronic acid.
The formation of nitronic acids in aromatic nitro compounds with a nitro group in the ring is associated with the transformation of the benzene ring into a quinoid structure:
For example, ortho-nitrotoluene exhibits photochromism: bright blue nitronic acid is formed (quinoid structures are often intensely colored:
ortho-nitrotoluene nitronic acid
Under the action of concentrated nitric acid or a mixture of concentrated nitric and sulfuric acids (nitrating mixture), the hydrogen atoms of the benzene ring are replaced by a nitro group:
nitrobenzene
Nitration is preceded by the formation of an electrophilic reagent NO 2 - nitronium cation.
In the reaction of benzene nitration with a nitrating mixture nitronium cation (NO 2 ) formed by protonation of nitric acid with concentrated sulfuric acid present:
Further nitration is difficult, since the nitro group is a substituent of the second kind and makes it difficult for reactions with electrophilic reagents:
nitrobenzene 1,3-dinitrobenzene 1,3,5-trinitrobenzene
Benzene homologues (toluene, xylenes) nitrate more easily than benzene, since alkyl groups are substituents of the first kind and facilitate reactions with electrophilic reagents:
1,3,5-trinitrobenzene
toluene ortho-nitrotoluene para-nitrotoluene
1,3,5-trinitrobenzene
1.2. Sulfonation reactions.
When benzene and its homologues are treated with concentrated sulfuric acid or sulfur trioxide, hydrogen atoms in the benzene nucleus are replaced by a sulfo group:
benzenesulfonic acid
reaction mechanism
Sulfonation is preceded by the formation of an electrophilic reagent HSO + 3 - hydrosulfonium ion:
3H 2 SO 4 → H 3 O + + HSO + 3 + 2HSO - 4
π-complex σ-complex
H + + HSO - 4 → H 2 SO 4
An even more active electrophilic reagent is sulfur trioxide, in which there is a deficit of electron density on the sulfur atom:
σ-complex
bipolar ion
Benzene homologues are sulfonated more easily than benzene, since alkyl groups are substituents of the first kind and facilitate reactions with electrophilic reagents:
1.3. halogenation reactions.
In the presence of Lewis acid catalysts (AlCl 3 ; AlBr 3 ; FeCl 3 ; FeBr 3 ; ZnCl 2 ) at room temperature, the hydrogen atoms of the benzene ring are replaced by halogen atoms:
Moreover, chlorine replaces hydrogen in the aromatic nucleus more actively than bromine, and it is practically impossible to carry out iodination and fluorination of arenes due to insufficient activity of iodine and excessive activity of fluorine.
The role of the catalyst is to form either a positive halogen ion or a complex of a halogen with a Lewis acid with halogen-halogen bond polarization:
1) the formation of a positive halogen ion:
2) formation of a complex of a halogen with a Lewis acid with polarization of the halogen-halogen bond:
Further halogenation is difficult, since halogens hinder reactions with electrophilic reagents, but are ortho- and para-orientants:
bromobenzene 1,2-dibromobenzene 1,4-dibromobenzene
Benzene homologues are halogenated more easily than benzene, since alkyl groups are substituents of the first kind and facilitate reactions with electrophilic reagents:
toluene ortho-chlorotoluene para-chlorotoluene
Electrophilic substitution is undoubtedly the most important group of reactions for aromatic compounds. There is hardly any other class of reactions that has been studied in such detail, in depth and comprehensively, both from the point of view of the mechanism and from the point of view of application in organic synthesis. It was in the field of electrophilic aromatic substitution that the problem of the relationship between structure and reactivity was first posed, which is the main subject of study in physical organic chemistry. In general, this type of reactions of aromatic compounds can be represented as follows:
ArE+H+
1. Literature review
1.1 Electrophilic substitution in the aromatic series
These reactions are characteristic not only for benzene itself, but also for the benzene ring in general, wherever it is located, as well as for other aromatic cycles - benzenoid and non-benzenoid. Electrophilic substitution reactions cover a wide range of reactions: nitration, halogenation, sulfonation and Friedel-Crafts reactions are characteristic of almost all aromatic compounds; reactions such as nitrosation and azo coupling are inherent only in systems with increased activity; reactions such as desulfurization, isotopic exchange, and numerous cyclization reactions, which at first glance seem quite different, but which also prove to be appropriate to refer to reactions of the same type.
Electrophilic agents E + , although the presence of a charge is not necessary, because an electrophile can also be an uncharged electron-deficient particle (for example, SO 3 , Hg(OCOCH 3) 2, etc.). Conventionally, they can be divided into three groups: strong, medium strength and weak.
NO 2 + (nitronium ion, nitroyl cation); complexes of Cl 2 or Br 2 with various Lewis acids (FeCl 3 , AlBr 3 , AlCl 3 , SbCl 5 etc.); H 2 OCl + , H 2 OBr + , RSO 2 + , HSO 3 + , H 2 S 2 O 7 . Strong electric saws interact with compounds of the benzene series containing both electron-donating and practically any electron-withdrawing substituents.
Medium strength electrophiles
Complexes of alkyl halides or acyl halides with Lewis acids (RCl . AlCl 3 , RBr . GaBr 3 , RCOCl . AlCl 3 etc.); complexes of alcohols with strong Lewis and Bronsted acids (ROH . BF 3 , ROH . H 3 PO 4 , ROH . HF). They react with benzene and its derivatives containing electron-donating (activating) substituents or halogen atoms (weak deactivating substituents), but usually do not react with benzene derivatives containing strong deactivating electron-withdrawing substituents (NO 2, SO 3 H, COR, CN, etc.) .
Weak electrophiles
Diazonium cations ArN +є N, iminium CH 2 \u003d N + H 2, nitrosonium NO + (nitrosoyl cation); carbon monoxide (IY) CO 2 (one of the weakest electrophiles). weak electrophiles interact only with benzene derivatives containing very strong electron-donating substituents (+M)-type (OH, OR, NH 2, NR 2 , O-, etc.).
1.1.2 Mechanism of electrophilic aromatic substitution
At present, aromatic electrophilic substitution is considered as a two-stage addition-elimination reaction with the intermediate formation of an arenonium ion, called the σ-complex
I-Arenium ion (
-complex), usually short-lived. Such a mechanism is called S E Ar, i.e. S E (arenonium). In this case, at the first stage, as a result of the attack of the electrophile, the cyclic aromatic 6-electron π-system of benzene disappears and is replaced in intermediate I by the non-cyclic 4-electron conjugated system of the cyclohexadienyl cation. At the second stage, the aromatic -system is restored again due to the elimination of a proton. The structure of the arenonium ion I is depicted in various ways:
The first formula is the most commonly used. The σ-complex will be much better stabilized by donor substituents in the ortho and para positions than by donor substituents in the meta position.
π -Complexes
As is known, arenes are π-bases and can form donor-acceptor complexes with many electrophilic reagents. formation of molecular complexes of composition 1:1 (G.Brown, 1952).
These complexes are not colored; their solutions in aromatic hydrocarbons are nonconductive. Dissolution of gaseous DCl in benzene, toluene, xylenes, mesitylene, and pentamethylbenzene does not result in the exchange of H for D. Since the solutions of the complexes do not conduct electric current, they are not ionic particles; These are not arenonium ions.
Such donor-acceptor complexes are called π-complexes. For example, crystals of benzene complexes with bromine or chlorine with a composition of 1:1, according to X-ray diffraction data, consist of chains of alternating molecules of a π-donor of composition (C 6 H 6) and an acceptor (Cl 2 ,Br 2), in which the halogen molecule is located perpendicular to the plane of the ring along axis passing through its center of symmetry.
σ-complexes (arenonium ions)
When HCl and DCl are introduced into a solution in alkylbenzenes AlCl 3 or AlBr 3, the solution begins to conduct an electric current. Such solutions are colored and their color changes from yellow to orange-red when passing from para-xylene to pentamethylbenzene. In the ArH-DCl-AlCl 3 or ArH-DF-BF 3 systems, the hydrogen atoms of the aromatic ring are already exchanged for deuterium. The electrical conductivity of the solutions definitely indicates the formation of ions in the ternary system arene-hydrogen halide-aluminum halide. The structure of such ions was determined using 1 H and 13 C NMR spectroscopy in the ArH-HF (liquid)-BF 3 or ArH-HF-SbF 5 system in SO 2 ClF at low temperature.
1.1.3 Substituent classification
Monosubstituted C 6 H 5 X benzenes may be more or less reactive than benzene itself. If an equivalent mixture of C 6 H 5 X and C 6 H 6 is introduced into the reaction, then the substitution will occur selectively: in the first case, C 6 H 5 X will predominantly react, and in the second case, mainly benzene.
Currently, substituents are divided into three groups, taking into account their activating or deactivating effect, as well as the orientation of the substitution in the benzene ring.
1. Activating ortho-para-orienting groups. These include: NH 2 , NHR, NR 2 , NHAc, OH, OR, OAc, Alk, etc.
2. Deactivating ortho-para-orienting groups. These are the halogens F, Cl, Br and I.
3. Deactivating meta-orienting groups. This group consists of NO 2 , NO, SO 3 H, SO 2 R, SOR, C(O)R, COOH, COOR, CN, NR 3+ , CCl 3 and others. These are orientants of the second kind.
Naturally, there are also groupings of atoms of an intermediate nature, which determine the mixed orientation. These, for example, include: CH 2 NO, CH 2 COCH 3, CH 2 F, CHCl 2, CH 2 NO 2, CH 2 CH 2 NO 2, CH 2 CH 2 NR 3 +, CH 2 PR 3 +, CH 2 SR 2 + id.
1.2 Electrophilic substitution in π-excess heterocycles
Furan, pyrrole and thiophene are highly reactive with common electrophilic reagents. In this sense, they resemble the most reactive benzene derivatives, such as phenols and anilines. The increased sensitivity to electrophilic substitution is due to the asymmetric charge distribution in these heterocycles, resulting in a greater negative charge on the carbon atoms of the ring than in benzene. Furan is somewhat more reactive than pyrrole, while thiophene is the least reactive.
1.2.1 Electrophilic substitution of pyrrole
While pyrrole and its derivatives are not prone to nucleophilic addition and substitution reactions, they are very sensitive to electrophilic reagents, and the reactions of pyrroles with such reagents proceed almost exclusively as substitution reactions. Unsubstituted pyrrole, N- and C-monoalkylpyrroles, and, to a lesser extent, C,C-dialkyl derivatives polymerize in strongly acidic media, so most of the electrophilic reagents used in the case of benzene derivatives are not applicable to pyrrole and its alkyl derivatives.
However, in the presence of electron-withdrawing groups in the pyrrole ring that prevent polymerization, for example, such as ester groups, it becomes possible to use strongly acidic media, nitrating and sulfonating agents.
protonation
In solution, reversible addition of a proton is observed at all positions of the pyrrole ring. The nitrogen atom is protonated most rapidly, the addition of a proton at position 2 is twice as fast as at position 3. In the gas phase, when using acids of moderate strength, such as C 4 H 9 + and NH 4 + , pyrrole is protonated exclusively at carbon atoms , and the propensity to attach a proton at position 2 is higher than at position 3. The most thermodynamically stable cation, the 2H-pyrrolium ion, is formed upon addition of a proton at position 2, and the pKa value determined for pyrrole is associated precisely with this cation. The weak N-basicity of pyrrole is due to the absence of mesomeric delocalization of the positive charge in the 1H-pyrrolium cation.
