Subject Chemistry
Paper No and Title 5, Organic Chemistry-II (Reaction Mechanism-1)
Module No and Title 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams Module Tag CHE_P5_M28
CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
TABLE OF CONTENTS
1. Learning Outcomes 2. Introduction: Electrophilic Aromatic Substitution
3. Arenium Ion Mechanism
3.1 Steps involved in Arenium Ion Mechanism
3.2 Energy Profile Diagram of the Arenium Ion Mechanism of Electrophilic Aromatic Substitution
3.3 Generation of Electrophiles (E+)
4. Evidence of Arenium Ion Mechanism
5. Orientation and Reactivity
7. Summary
CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
1. Learning Outcomes
After studying this module, you shall be able to
Understand why aromatic compounds undergo electrophilic aromatic substitution Mechanism of electrophilic aromatic substitution and arenium ion intermediate/ Wheland intermediate involved Isolation of the arenium ion intermediate as a proof of arenium ion mechanism The orientation and reactivity of benzene and related aromatics towards electrophilic aromatic substitution The energy profiles or the free energy diagrams associated with electrophilic aromatic substitution
2. Introduction
There are two main classes of aromatic substitution. One is electrophilic substitution and the other nucleophilic substitution. There are many types of aromatic systems. Among them, the chemistry of benzene and its simple derivatives has been studied in most detail. Thus, this modules concerns with reaction on a benzene ring and in particular electrophilic aromatic substitution.
The attacking electrophile is a positive ion (or positive end of a dipole or induced dipole). After the reaction the “leaving group” must depart without its electrons. The most common departing group is the proton, H+.
3. Electrophilic Aromatic Substitution
One of the characteristics of benzene derivatives is that they tend to undergo substitution at aromatic carbon rather than to undergo substitution at aromatic carbon rather than
CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
addition (to the double bonds). This property aromatic compounds is mainly due to their ‘aromaticity’. Some common examples of electrophilic aromatic substitution reactions are shown in the given figure.
Fig. 1: Some examples of most commonly occurring electrophilic aromatic substitution These questions are usually important in aromatic substitution reactions: 1. What is the attaching agent? 2. How does it carry out the substitution? 3. How is the reaction influenced by other groups on the benzene ring? We shall discuss these concerns in detail now.
4. Arenium Ion Mechanism and Energy Profile Diagrams
4.1 Steps involved in Arenium Ion Mechanism The mechanism aromatic electrophilic substitution is known as the arenium ion mechanism and has two main steps. Step 1: The initial step is the attack of an electrophile creating a resonance stabilized carbocation/intermediate called arenium ion, which is also known as the Wheland CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
Intermediate. Although the Wheland intermediate or σ-complex or now popularly known as arenium ion is stabilized by resonance (with charge dispersal over the carbons ortho and para to the site of attachment of the electrophile), this step is accompanied by loss of aromaticity, so the energy of activation is high. This is also the rate-determining step of the reaction because of the disruption of aromaticity.
Fig. 2: Rate determining slow step which leads to generation of arenium ion and its resonance stabilized forms
Step 2: In the second step the leaving group departs. This leads to regeneration of aromatic stabilization. The second step is nearly always faster than the first, making the first rate determining, and the reaction is second order.
Fig. 3: Formation of product and regeneration of aromaticity
Note: There is some resemblance of this mechanism to the attack of nucleophiles on the carbonyls of esters or amides to give tetrahedral intermediates, except that the charges are reversed. If the electrophilic species is not an ion but a molecule with a polarized covalent bond, the product must have a negative charge unless part of the dipole, with its
CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
pair of electrons, is broken off somewhere in the process, as in the conversion of A to B. Note that when the aromatic ring attacks X, Z may be lost directly to give B.
A B Fig. 4: When the attacking electrophile is a molecule instead of an ion
4.2 Energy Profile Diagram of the Arenium Ion Mechanism of Electrophilic Aromatic Substitution
Fig. 5: Free energy diagram of electrophilic aromatic substitution The energy diagram of this reaction shows that step 1 is highly endothermic and has a ‡ large ∆G (1) The first step requires the loss of aromaticity of the very stable benzene ring, which is highly unfavourable The first step being a slow step, is rate-determining ‡ Step 2 is highly exothermic and has a small ∆G (2) The ring regains its aromatic stabilization, which is a highly favorable process
4.3 Generation of Electrophiles (E+) CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
The electrophiles can be generated in various ways, examples are shown below:
Fig. 6: Generation of electrophiles for electrophilic aromatic substitution
CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
5. Evidence for Arenium Ion Mechanism
The direct evidence for proposed reaction intermediate in aromatic substitution has been obtained by Dr. Olah using NMR spectroscopy. A mixture of mesitylene (1) with an alkyl halide and a good lewis acid at low temperatures yielded the intermediate (2). This (2) went on to the final product (3) at higher temperature.
There are numerous studies which show that such salts like this intermediate can exist as stable species under favourable conditions. Even the simplest benzonium ion (4) could be prepared and studied. These types of charged units are sometimes called as σ complexes.
The evidence for the arenium ion mechanism is mainly of two kinds:
1. Isotope Effects: If the hydrogen ion departs before the arrival of the electrophile (SE1 mechanism) or if the arrival and departure are simultaneous, there should be a substantial isotope effect (i.e., deuterated substrates should undergo substitution more slowly than CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams
non-deuterated compounds) because, in each case, the C ̶ H bond is broken in the rate- determining step. However, in the arenium ion mechanism, the C ̶ H bond is not broken in the rate-determining step, so no isotope effect should be found. Many such studies have been carried out and, in most cases, especially in the case of nitrations, there is no
isotope effect. This result is incompatible with either the SE1 or the simultaneous mechanism. However, in many instances, isotope effects have been found. Since the
values are generally much lower than expected for either the SE1 or the simultaneous
mechanisms (e.g., 1–3 for kH/kD instead of 6–7), there must be another explanation. For the case where hydrogen is the leaving group, the arenium ion mechanism can be summarized:
Fig. 7: When hydrogen is the leaving group in electrophilic aromatic substitution reaction The small isotope effects found most likely arise from the reversibility of step 1 by a partitioning effect. The rate at which ArHY+ reverts to ArH should be essentially the same as that at which ArDY+ (or ArTY+) reverts to ArD (or ArT), since the Ar ̶ H bond is not cleaving. However, ArHY+ should go to ArY faster than either ArDY+ or ArTY+,
since the Ar ̶ H bond is broken in this step. If k2»k-1, this does not matter; since a large majority of the intermediates go to product, the rate is determined only by the slow step + (k21[ArH][Y ]) and no isotope effect is predicted. However, if k2≤ k-1, reversion to + + + starting materials is important. If k2 for ArDY (or ArTY ) is 2. Isolation of Arenium Ion Intermediates: The isolation of arenium ions in many cases provides for a very strong evidence for the arenium ion mechanism. When 10 was heated, the normal substitution product (11) was obtained. Even the simplest such ion, the benzenonium ion (12) has been prepared in HF ̶ SbF5 ̶ SO2ClF ̶ SO2F2 at -134 °C, where it could be studied spectrally. Fig. 8: Isolation of arenium ion intermediates 6. Orientation and Reactivity When an electrophilic substitution reaction is performed on a monosubstituted benzene, the new group may be directed primarily to the ortho, meta, or para position. Also, sometimes, a fourth type of substitution may be encountered viz., ipso substitution, a special case of electrophilic aromatic substitution where the leaving group is not hydrogen but the original substituent itself. Fig. 9: Four possibilities of attack on monosubstituted benzene CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams Note that the substitution may be slower or faster than with benzene itself. Thus, the formation of four possible intermediates is dependent not on the thermodynamic stability of the products, but on the activation energy necessary to form each of the four intermediates. Considering the Hammond postulate, we assume that the geometry of the transition state also resembles that of the intermediate and that anything that increases the stability of the intermediate will also lower the activation energy necessary to attain it. Fig. 10: Reaction coordinate for the first step in various electrophilic substitutions in monosubstituted benzene The group already on the ring determines which position the new group will take and whether the reaction will be slower or faster than with benzene. Groups that increase the reaction rate are called activating and those that slow it are deactivating. The groups, R/Z, according to their influence on both reactivity and orientation are classified into different categories. Two properties of R/Z have a major influence, namely, inductive (I) effects and resonance (sometimes known by the older term, mesomeric) (Re or M) effects. The groups, R/Z, fall into the following categories: - O , NR2, NHR, NH2, OH, OR, NHCOR, OCOR NO2, CN, SO3H, CHO, COR, CO2H, CONH2 CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams R - CO2 + + NR3, NH3, CCl3, CF3 F, Cl, Br, I Fig. 11: Ortho, meta and para substitution in monosubstituted benzene and the possible structures of the corresponding arenium ions formed. Six common electrophilic aromatic substitution reactions are listed below: 1. Halogenation: This is done by replacing hydrogen with a bromine or chlorine. Both processes bromination and chlorination require a Lewis acid, which accepts a pair of electrons to create a permanent bond dipole of the Br-Br bond or the Cl- Cl bond. This dipole allows the bromine or chloride to have a formal positive charge and therefore allows the group to be electrophilic enough to overcome the activation energy caused by the loss of aromaticity of the benzene ring. a. Bromonation b. Chloronation CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams Consider chlorination of nitrobenzene which gives rise to the meta substituted product as nitro is an electron withdrawing group. Fig. 12: Halogenation of nitrobenzene as an example of EAS 2. Nitration: This happens by the replacement of a hydrogen with a nitro (NO2) group. Nitration process requires the presence of sulfuric acid (H2SO4) as a catalyst. Just like we had to take extra steps to create the electrophile in bromination and chlorination (with the help of a Lewis acid), we must use the sulfuric acid to protonate the nitric acid, resulting in the formation of a nitronium ion. The nitronium ion can then proceed as a general electrophilic aromatic substitution. Nitration of toluene gives a para product predominantly as alkyl groups are o-/p- directing. Fig. 13: Nitration of toluene as an example of EAS CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams 3. Sulfonation: This occurs by replacing a hydrogen with a sulfonic acid (SO3). The sulfonation process is quite similar to nitration because in general, we create the electrophile by protonating the SO3 with H2SO4 to make a stronger electrophile. The mechanism can then proceed as an electrophilic aromatic substitution reaction. The sulphonation of acetophenone gives a meta substituted reaction. Fig. 14: Sulphonation of acetophenone as an example of EAS 4. Friedel-Crafts Acylation: Friedel-Crafts acylation occurs by replacing a hydrogen with an acyl group (RC=O). In Friedel-Crafts Acylation, we form the acylium ion (the electrophile in the reaction) by using a lone pair from the chlorine (of the H3COCl) to fill the open octet of the aluminium (of the AlCl3). As a result, the chlorine carbon bond is weakened and Cl+-Al-Cl3 leaves. The acylium ion acts as an electrophile in the electrophilic aromatic substitution mechanism. The hydroxyl group hers is an o-/p- directing group thus a para substituted product is formed henceforth. CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams Fig. 15: Friedel-Crafts acylation of phenol as an example of EAS 5. Friedel-Crafts Alkylation: Friedel-Crafts alkylation replacing a hydrogen with an alkyl group (R). In Friedel-Crafts Alkylation, we use the lone pair of the chlorine (of the CH3Cl) to fill the open octet of aluminium (of the AlCl3). As a + result, the ClAl-Cl3 leaves. The (CH3)3C acts as the electrophile in the electrophilic aromatic substitution mechanism. Alkyl group here is an o-/p- directing group in toluene, thus a para substituted product is formed henceforth. Fig. 16: Friedel-Crafts alkylation of toluene as an example of EAS + 6. Diazotization of a Primary Amine: In this reaction, we react an acid (like H3O ) - + with NO2 to form a nitrosonium cation (O=N ) which behaves as an electrophile. CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams Then, we form the N-N bond with the electrophilic attack of the nitrosonium cation to the Ph-NH2. Then, through a series of protonation and deprotonation steps by water (the proton shuttle) a diazonium cation is formed. Fig. 17: Diazotization of phenol as an example of EAS These conclusions are correct as far as they go, but they do not lead to the proper results in all cases. In many cases, there is resonance interaction between Z and the ring; this also affects the relative stability, in some cases in the same direction as the field effect, in others differently. 7. Summary SN2 reactions observed with alkanes do not occur with aromatic compounds as they are stabilized by ‘aromatic stabilization’ energy. The concentration of negative charge above and below the plane of the ring carbon atoms make the aromatic systems susceptible to attack by electrophiles. Arenium ion/ Wheland intermediate/ σ-complex is the name of the intermediate involved in the electrophilic susbstitution of aromatic compounds. Arenium ion mechanism and has two main steps. CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams The first step is the rate determining step, involves the attack of electrophile and loss of aromaticity. The second step involves departure of the leaving group leading to regain of aromaticity. ‡ The first step is highly endothermic and has a large ∆G (1) while the latter step is ‡ highly exothermic and has a small ∆G (2). The isotope effects and the isolation of the arenium ion using various techniques and their spectral studies form the main evidences for the arenium ion mechanism When an electrophilic substitution reaction is performed on a monosubstituted benzene, the new group may be directed primarily to the ortho, meta, or para position. Also, sometimes, a fourth type of substitution may be encountered viz., ipso substitution, a special case of electrophilic aromatic substitution where the leaving group is not hydrogen but the original substituent itself. The group already on the ring determines which position the new group will take and whether the reaction will be slower or faster than with benzene. Groups that increase the reaction rate are called activating (o-/p- directing) and those that slow it are deactivating (m- directing). In many cases, there is resonance interaction between Z and the ring; this also affects the relative stability, in some cases in the same direction as the field effect, in others differently. CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation and reactivity, energy profile diagrams