Chapter 19: Aromatic Substitution Reactions

Transcription

1 Chem A225 Notes Page 52 Chapter 19: Aromatic Substitution Reactions Topic One: lectrophilic Aromatic Substitution I. Introduction to lectrophilic Aromatic Substitution (AS) A. eneral Reaction Pattern B. eneral Mechanism Step 1: lectrophile ( + ) reacts with bond of benzene: Intermediate carbocation is resonance stabilized. Intermediate is not aromatic, has lost the aromatic stability. Step 2: Intermediate loses a proton ( + ), bond is formed again. Prefers to reform bond in order to regain aromaticity and the resulting increase in stability.

2 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 53 Another way of writing the mechanism uses the delocalized arenium ion to represent the intermediate: + :B arenium ion C. eneralized nergy Profile Key features 1) First step is rate-determining step (RDS) and is endothermic. 2) Transition state (TS ) of RDS is similar to the intermediate, and therefore it has the properties of an electron-deficient carbocation.

3 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 54 II. Observed Reactions of lectrophilic Aromatic Substitution A. alogenation ( + = Cl + or Br + ) Observed Reaction: X 2, FeX 3 (X = Cl, Br) X Actual electrophile is a complex of the Lewis acid and the halogen: B. Nitration ( + = NO 2 + ) Observed Reaction: NO 3, 2 SO 4 NO 2 The electrophile is NO 2 + The nitro group can be reduced to an -N 2 group (amino group) Observed Reaction:

4 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 55 C. Sulfonation ( + = SO 3 ) SO 3, 2 SO 4 SO 3 The electrophile is SO 3 ; it becomes protonated after attaching to the ring. Commercially available 2 SO 4 has SO 3 in it from manufacturing: Reverse reaction is also an observed reaction (Desulfonation) SO 3 dil. 2 SO 4 Reaction is an equilibrium that can be controlled by using Le Chatelier s principle: high concentration of 2 SO 4 favors adding SO 3 to the ring low concentration of 2 SO 4, and lots of water, favors removing SO 3 from the ring

5 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 56 D. Friedel-Crafts Alkylation ( + = carbocation (R + )) Observed Reaction R Cl, AlCl 3 R Mechanism 1) Lewis Acid helps remove halide, forms carbocation 2) Carbocation reacts with aromatic ring (general AS mechanism) Problems with F-C Alkylation: 1) Rearrangement of carbocation

6 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 57 2) Polyalkylation (attaching more than one alkyl group) Alkyl groups make the ring more reactive: Can be minimized by using a large excess (> 10 eq) of the aromatic ring. 3) Carbon atom connected to halide must be sp 3 hybridized. Vinyl halides and aryl (phenyl) halides do not form carbocations under Friedel-Crafts conditions, so they will not work in the reaction. 4) F-C Alkylation (and F-C Acylation) do not work on rings that contain strong deactivating groups or -N 2 groups. (see below)

7 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 58. Friedel-Crafts Acylation ( + = R CO + (acylium ion)) Observed Reaction O R C Cl O C R AlCl 3 Mechanism 1) Formation of acylium ion 2) Acylium ion reacts with aromatic ring (follows general AS mechanism) F-C acylation avoids two of the problems of alkylation: 1) Acylium intermediate is resonance stabilized, so it doesn t rearrange. 2) Acyl groups make ring less reactive, so no poly-acylation. owever, F-C acylation still does not work on deactivated rings or rings with -N 2 attached.

8 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 59 Use F-C acylation followed by Clemmensen Reduction to attach 1 o alkyl groups to aromatic rings (see below). Clemmensen Reduction (converts C=O to C 2 ) O C R Zn(g), Cl C R Use the following sequence to attach 1 o alkyl groups to aromatic ring (using propyl as an example): III.Substituent ffects on lectrophilic Aromatic Substitution A. Classification of Substituents on Aromatic Rings Substituents are classified according to their effect on the electron density of neighboring atoms. 1) lectron donating groups (D) increase the electron density of neighboring atoms 2) lectron-withdrawing groups (W) decrease the electron density of neighboring atoms

9 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 60 Two Types of lectronic ffects 1) Inductive ffects: donation or withdrawing of electrons through bonds. Relates to electronegativities and + or charges. Bond polarity is an example of inductive effects. alogens, with their high electronegativities, are common inductive electronwithdrawing groups. Carbon groups (sp 3 alkyl) are inductive electron-donating groups. For example, alkyl groups push electrons through bonds into a carbocation, which helps stabilize the + charge on the carbocation. This is why increasing alkyl substitution stabilizes carbocations: 2) Resonance ffects: donation or withdrawing of electrons through resonance and the formation of bonds. For example, allylic carbocations are stabilized by resonance donation of the adjacent bond: Resonance effects tend to be stronger than inductive effects, especially for 2nd row atoms.

10 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 61 B. Substituent ffects on Reactivity Compare the rate of reaction of benzene with the rate of reaction when a hydrogen has been replaced by a group : If the substituted aromatic ring reacts faster than benzene, then group is an activating group. Activating groups make the aromatic ring react faster than benzene. If the substituted aromatic ring reacts slower than benzene, then group is a deactivating group. Deactivating groups make the ring react slower than benzene. So how can a group change the rate of reaction? By changing the energy of the transition state (TS ), which changes the energy of activation ( a ).

11 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 62 The rate determining step of the AS reaction is endothermic. According to the ammond postulate, the transition state should be similar (in structure and properties) to the delocalized carbocation intermediate. Substituent groups can be either electron-donating or electron-withdrawing (when compared to a hydrogen). lectron-donating groups will stabilize the carbocation intermediate; therefore, they should also stabilize the TS. This will lower a, and the reaction will go faster (when compared with the rate of reaction of benzene). Thus, electron-donating groups are activating groups. lectron-withdrawing groups will make the carbocation intermediate less stable; therefore, they should also destabilize the TS. This will raise a, and the reaction will go slower (when compared with the rate of reaction of benzene). Thus, electronwithdrawing groups are deactivating groups. C. Regioselectivity ffect of Substituent roups When a substituent group is attached to the aromatic ring, there are three possible regioisomeric products of the electrophilic aromatic substitution: Compare the relative energies of the TS for the three pathways that lead to the three different regioisomers. The pathway with the lowest energy TS (and therefore the lowest a) will be fastest and will produce the most product. Use the intermediate to guess the structure of the TS since they are similar

12 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 63 xample One: Resonance-Donating Substituents Carbocation falls on carbon adjacent to the group in the ortho and para intermediates. It skips over carbon adjacent to the group in the meta intermediate. The electron-donating group can stabilize the carbocation when it is on the adjacent carbon, which occurs in the ortho and para intermediates. The electron-donating group doesn t stabilize the carbocation in the meta intermediate. All pathways are lower energy than benzene (donating groups are activating groups) benzene meta Ortho/para intermediates are lower energy than meta because group stabilizes the adjacent carbocation potential energy or + + ortho/para Therefore, ortho/para products are preferred. reaction coordinate (RC)

13 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 64 xample Two: lectron-withdrawing Substituents Carbocation falls on carbon adjacent to the group in the ortho and para intermediates. It skips over carbon adjacent to the group in the meta intermediate. The electron-withdrawing group destabilizes the carbocation when it is on the adjacent carbon, which occurs in the ortho and para intermediates. The electron-withdrawing group doesn t destabilize the carbocation in the meta intermediate. All pathways are higher energy than benzene (withdrawing groups are deactivating groups) Ortho/para intermediates are higher energy than meta because group destabilizes the adjacent carbocation potential energy or + + ortho/para meta benzene Therefore, meta products are preferred. reaction coordinate (RC)

14 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 65 ACTIVATIN ROUPS (more reactive than benzene) DACTIVATIN ROUPS (less reactive than benzene) Summary of Substituent roup ffects Reactivity Strength Site Selectivity lectronic Properties Structural Characteristics xamples Strong Activating Weak Activating Ortho / Para Directing Ortho / Para Directing Resonance Donating Inductive Donating Lone pair or pi bond on atom attached to ring Alkyl group Alkyl roups -N 2, -NC(=O)R, -O, -OR, -OC(=O)R, -C=C-, -Ph Benzene Weak Deactivating Ortho / Para Directing Strong Deactivating Meta Directing Inductive Withdrawing, Resonance Donating Inductive and Resonance Withdrawing alogens -F, -Cl, -Br, -I Positive formal charge on atom attached to ring in at least one resonance form -NO 2, -SO 3, -CN, -CF 3, -C(=O), -C(=O)R, -C(=O)O, -C(=O)OR, -C(=O)NR 2

15 Chem A225 Notes Ch 19: Aromatic Substitution Reactions Page 66 D. Regioselectivity with Two or More Substituents Predicting products when 2 or more directing groups are on the aromatic ring: 1) The regiochemistry effect of the most strongly activating group takes preference. Strong activating groups take preference over all others, weak activating groups take preference over halogens and deactivating groups, and halogens take preference over strong deactivating groups. 2) The electrophile will not attach between two meta-related groups unless there is no other choice. Problem-solving strategy: Circle each directing group in a different color (or shape), draw labeled arrows to show preferred site of attack for each group, then eliminate arrows using rules 1-2 above. Any remaining arrows indicate preferred products. C 3 NO 3, 2 SO 4 NO 2 C 3 NO 3, 2 SO 4 NO 2