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 <k2 for ArHY , but k-1 is + the same, then a larger proportion of ArDY reverts to starting compounds. That is, k2/k-1 (the partition factor) for ArDY+ is less than that for ArHY+. Consequently, the reaction is slower for ArD than for ArH and an isotope effect is observed. CHEMISTRY PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE : 28, Arenium ion mechanism in electrophilic aromatic substitution, orientation