Objectives After completing this section, you should be able to
The Mechanism for Electrophilic Substitution Reactions of Benzene is the key to understanding electrophilic aromatic substitution. You will see similar equations written for nitration, sulphonation, acylation, etc., with the major difference being the identity of the electrophile in each case. Note that the carbocation intermediate formed has a number of resonance forms. Also, you may wish to review Section 8.2 to meet Objective 3. Halogenation is an example of electrophillic aromatic substitution. In electrophilic aromatic substitutions, a benzene is attacked by an electrophile which results in substition of hydrogens. However, halogens are not electrophillic enough to break the aromaticity of benzenes, which require a catalyst to activate.
A two-step mechanism has been proposed for these electrophilic substitution reactions. In the first, slow or rate-determining, step the electrophile forms a sigma-bond to the benzene ring, generating a positively charged benzenonium intermediate. In the second, fast step, a proton is removed from this intermediate, yielding a substituted benzene ring. The following four-part illustration shows this mechanism for the bromination reaction. Also, an animated diagram may be viewed. Preliminary step: Formation of the strongly electrophilic bromine cation Step 1: The electrophile forms a sigma-bond to the benzene ring, generating a positively charged benzenonium intermediate Step 2: A proton is removed from this intermediate, yielding a substituted benzene ring This mechanism for electrophilic aromatic substitution should be considered in context with other mechanisms involving carbocation intermediates. These include SN1 and E1 reactions of alkyl halides, and Brønsted acid addition reactions of alkenes. To summarize, when carbocation intermediates are formed one can expect them to react further by one or more of the following modes: 1. The cation may bond to a nucleophile to give a substitution or addition product. SN1 and E1 reactions are respective examples of the first two modes of reaction. The second step of alkene addition reactions proceeds by the first mode, and any of these three reactions may exhibit molecular rearrangement if an initial unstable carbocation is formed. The carbocation intermediate in electrophilic aromatic substitution (the benzenonium ion) is stabilized by charge delocalization (resonance) so it is not subject to rearrangement. In principle it could react by either mode 1 or 2, but the energetic advantage of reforming an aromatic ring leads to exclusive reaction by mode 2 (ie. proton loss).
1. What reagents would you need to get the given product? What reagents would you need to gete given product 2. What product would result from the given reagents? 3. What is the major product given the reagents below? 4. Draw the formatin of Cl+ from AlCl3 and Cl2 5. Draw the mechanism of the reaction between Cl+ and a benzene.
1. Cl2 and AlCl3 or Cl2 and FeCl3 2. No Reaction 3. 4. 5. Contributors and AttributionsLast updated: August 31st, 2022 | Electrophilic Aromatic Substitution: The Mechanism
Table of Contents 1. Electrophilic Aromatic Substitution Mechanism, Step 1: Attack of The Electrophile (E) By a Pi-bond Of The Aromatic RingLast post in this series on reactions of aromatic groups we introduced activating and deactivating groups in Electrophilic Aromatic Substitution (EAS). We learned that electron-donating substituents on the aromatic ring increase the reaction rate and electron-withdrawing substituents decrease the rate. [In the fine print, we also mentioned that evidence strongly suggests that the reaction proceeds through a carbocation intermediate, and that breakage of C-H is not the slow step.] Having established these facts, we’re now ready to go into the general mechanism of this reaction. It’s a two-step process. The good news is that you’ve actually seen both of the steps before (in Org 1) but as part of different reactions! The first step of electrophilic aromatic substitution is attack of the electrophile (E+) by a pi bond of the aromatic ring. [Note: the identity of the electrophile E is specific to each reaction, and generation of the active electrophile is a mechanistic step in itself. We’ll cover the specific reactions next. This post just covers the general framework for electrophilic aromatic substitution]. Where have we seen this type of step before? In the chapter on alkenes, we saw a whole series of reactions of pi bonds with electrophiles that generate a carbocation. A common example is the reaction of alkenes with a strong acid such as H-Cl, leading to formation of a carbocation. The reaction above is the same step, only applied to an aromatic ring. You might recall that the second step of addition of HCl to alkenes is the attack of Cl on the carbocation, generating a new C-Cl bond. That’s not what happens in electrophilic aromatic substitution. [Note 1] 2. Electrophilic Aromatic Substitution Mechanism, Step 2: Deprotonation Of The Tetrahedral Carbon Regenerates The Pi BondThe second step of electrophilic aromatic substitution is deprotonation. This breaks C–H and forms C–C (π), restoring aromaticity. You may recall that this is strongly favored – the resonance energy of benzene is about 36 kcal/mol. [This is the type of phenomenon chemists like to call a “thermodynamic sink” – over time, the reaction will eventually flow to this final product, and stay there. ] Have we seen this type of step before? Yes – it’s essentially the second step of the E1 reaction, (after loss of a leaving group) where a carbon adjacent to a carbocation is deprotonated, forming a new C-C pi bond. Just as in the E1, a strong base is not required here. A halogen atom (such as Cl– ) will usually suffice, as will any number of other weak bases, such as H2O. The exact identity of the base depends on the reagents and solvent used in the reaction. 3. Putting Two Steps Together: The General MechanismLet’s combine both steps to show the full mechanism. Again, we won’t go into the details of generating the electrophile E, as that’s specific to each reaction. Note that attack could have occurred at any one of the six carbons of benzene and resulted in the same product. 4. The Reaction Energy Diagram of Electrophilic Aromatic SubstitutionWhat might the reaction energy diagram of electrophilic aromatic substitution look like? First, the overall appearance is determined by the number of transition states in the process. Recall that transition states always have partial bonds and are at the “peaks” of a reaction energy diagram, and intermediates such as carbocations are in the “valleys” between peaks. Intermediates can be observed and isolated (at least in theory); in contrast, transition states have a lifetime of femtoseconds, and although they may fleetingly be observed in certain cases, they can never be isolated. Electrophilic aromatic substitution has two steps (attack of electrophile, and deprotonation) which each have their own transition state. There is also a carbocation intermediate. This means that we should have a “double-humped” reaction energy diagram. Second, the relative heights of the “peaks” should reflect the rate-limiting step. What’s the slow step? In other words, which of the two steps has the highest activation energy? One clue is to measure the effect that small modifications to the starting material have on the reaction rate. We showed in the last post that electron-donating substitutents increase the rate of reaction (“activating”) and electron-withdrawing substituents decrease the rate of reaction (“deactivating”). [Conversely, substitution of hydrogen for deuterium has very little effect on the reaction rate, which leads us to conclude that the second step is not rate-determining. ] Since electron-donating and electron-withdrawing substitutents affect the nucleophilicity of the pi bond (through pi-donation and pi-acceptance) as well as the stability of the intermediate carbocation, the logical conclusion is that attack on the electrophile (step 1) is the rate-determining step. We therefore should depict it with the higher “hump” in our reaction energy diagram, representing its higher activation energy. Note that this reaction energy diagram is not to scale and is more of a sketch than anything else. A truly accurate reaction energy diagram can be modelled if one had accurate energies of the transition states and intermediates, which is sometimes available through calculation. 5. Beyond Benzene: Formation Of Ortho, Meta, and Para Disubstituted BenzenesSo that’s all there is to electrophilic aromatic substitution? Yes and no. Yes, this addresses electrophilic aromatic substitution for benzene. But, as you’ve no doubt experienced, small changes in structure can up the complexity a notch. Imagine we start not with benzene, but with a mono-substituted derivative, such as methylbenzene (toluene). What are the possible products of electrophilic aromatic substitution on a mono-substituted benzene derivative? Unlike with benzene, where only one EAS product is possible due to the fact that all six hydrogens are equivalent, electrophilic aromatic substitution on a mono-substituted derivative can yield three possible products: the 1,2- isomer (also called “ortho“), the 1,3-isomer (“meta“) and the 1,4-isomer (“para“). If we assume that the reaction obeys the laws of statistics, we might therefore expect that the product distribution should be 40% ortho. 40% meta, and 20% para. So is that what happens? No! Two important examples are illustrative. 6. EAS On Monosubstituted Benzenes: The Distribution Of Ortho, Meta and Para Isomers Is NOT Random!In the nitration of toluene, the product distribution is far from statistical. We get much less meta (5%) than expected, and more ortho (57%) and para (37%) than expected. In this sense we can say that the methyl group tends to act as an ortho- para- director: it “directs” the electrophile to these positions at the expense of the meta position. Is this the case for all substituents? No. In the nitration of nitrobenzene, the opposite result is obtained. Much less ortho and para is produced than expected, and the meta product is major (93%). In this case the nitro group is said to be acting as a meta- director. Substituents on benzene tend to fall into one of two categories: ortho–para directors, or meta directors. If you’re sharp, you might have already made an intuitive leap: the ortho- para- directing methyl group is an activating group, and the meta- directing nitro group is deactivating. So, therefore, are all activating groups ortho- para- directors and all deactivating groups meta- directors? It’s a good guess – and almost accurate! The fly in the bourbon is the halogens (F, Cl, Br, I) which are deactivating ortho-para directors. Why? What leads some substituents to be ortho-para directors, and others to be meta-directors? That’s going to have to wait until the next post for a full discussion. But here’s a hint: it has to do with our old friend, “pi-donation”. Thanks to Mattbew Knowe for valuable assistance with this post. NotesNote 1 – Why can’t the counterion attack the aromatic ring carbocation? Does that happen? Yes, but it’s a dead end. Let’s say we form the carbocation, and it’s attacked by a weak nucleophile (which we’ll call X). This gives us the addition product. However, it’s rarely a very stable product. X is typically a weak nucleophile, and therefore a good leaving group. Furthermore, loss of the leaving group will result in a highly resonance-stabilized carbocation. (Think of the first step in the SN1 or E1 reaction). This would re-generate the carbocation, which could then undergo deprotonation to restore aromaticity. Once that aromatic ring is formed, it’s not going anywhere. : – ) To make a long story short, yes, addition could occur, but the addition product will eventually undergo E1 to form the aromatic product. (figure below) (Advanced) References and Further ReadingThe EAS mechanism covers a variety of reactions – Friedel-Crafts substitutions, halogenation, nitration, and many others.
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