Lec 2 - Electrophilic Aromatic Substitution.pdf

Organic Chemistry Lecture 2 : Electrophilic Aromatic Substitution  Electrophilic Aromatic Substitution : Because of resonance, Above and below the plane of the benzene ring there is a cloud of 𝜋 electrons. It is not surprising that in its typical reactions the benze...

Organic Chemistry Lecture 2 : Electrophilic Aromatic Substitution  Electrophilic Aromatic Substitution : Because of resonance, Above and below the plane of the benzene ring there is a cloud of 𝜋 electrons. It is not surprising that in its typical reactions the benzene ring serves as a source of electrons, that is, as a base. The compounds which it reacts are deficient in electrons, that is, are electrophilic reagents or acids.  Electrophilic Aromatic Substitution : Just as the typical reactions of the alkenes are electrophilic addition reactions, so the typical reactions of the benzene ring are electrophilic substitution reactions. These reactions are characteristic not only of benzene itself, but of the benzene ring wherever it is found and, indeed, of many aromatic rings, benzenoid and non-benzenoid.  Electrophilic Aromatic Substitution Reactions : 1. Nitration 2. Sulfonation 3. Halogenation 4. Friedel-Crafts alkylation  Electrophilic Aromatic Substitution Reactions : 5. Nitrosation 6. Diazo coupling  Effect of Substituent Groups : Like benzene, toluene undergoes electrophilic aromatic substitution: sulfonation There are three possible monosulfonation products, this reaction actually yields appreciable amounts of only two of them: the o- and p-Isomers The methyl group makes the ring more reactive than unsubstituted benzene, and directs the attacking reagent to the ortho and para positions of the ring.  Effect of Substituent Groups : Nitrobenzene has been found to undergo substitution more slowly than benzene, and to yield chiefly the meta isomer Like methyl or nitro, any group attached to a benzene ring affects the reactivity of the ring and determines the orientation of substitution.  Effect of Substituent Groups : A group that makes the ring more reactive than benzene is called an activating group. A group that makes the ring less reactive than benzene is called a deactivating group. A group that causes attack to occur chiefly at positions ortho and para to it is called an ortho, para director. A group that causes attack to occur chiefly at positions meta to it is called a meta director.  Classification of Substituent Groups : All groups fall into one of two classes:  Activating and ortho.para directing, or  Deactivating and meta-directing.  The halogens are in a class by themselves, being deactivating but ortho.para-directing. Effect of Groups on Electrophilic Aromatic Substitution  Orientation In Disubstituted Benzenes : The two substituents may be located so that the directive influence of one reinforces that of the other; for example, in I, II, and III the orientation clearly must be that indicated by the arrows. When the directive effect of one group opposes that of the other, it may be difficult to predict the major product; in such cases complicated mixtures of several products are often obtained.  Orientation In Disubstituted Benzenes : Strongly activating groups generally win out over deactivating or weakly activating groups. The differences in directive power in the sequence Orientation In Disubstituted Benzenes :  Orientation In Disubstituted Benzenes : If the two substituents have similar activating properties, neither will dominate and a mixture of products will be obtained. 58% 42%  Orientation In Disubstituted Benzenes : Three positions are activated in the following reaction, but the new substituent ends up on only two of the three positions. Steric hindrance makes the position between the substituents less accessible  Orientation and Synthesis : A laboratory synthesis is generally aimed at obtaining a single, pure compound. A goal of aromatic synthesis is control of orientation: the preparation, at will and from the same substrate, of a pure ortho, a pure meta, or a pure para isomer. First of all, we must consider the order in which we introduce these various substituents into the ring. In the preparation of the bromonitrobenzenes,  Orientation and Synthesis : for example:  Orientation and Synthesis : If our synthesis involves conversion of one group into another, For example, oxidation of a methyl group yields a carboxyl group.  General Mechanism for Electrophilic Aromatic Substitution Reactions  In an electrophilic aromatic substitution reaction, an electrophile substitutes for a hydrogen of an aromatic compound.  General Mechanism for Electrophilic Aromatic Substitution Reactions  The following are the five most common electrophilic aromatic substitution reactions: 1) Halogenation: A bromine (Br), a chlorine (Cl), or an iodine (I) substitutes for a hydrogen 2) Nitration: A nitro group substitutes for a hydrogen 3) Sulfonation: A sulfonic acid group substitutes for a hydrogen 4) Friedel–Crafts acylation: An acyl (RC=O) group substitutes for a hydrogen 5) Friedel–Crafts alkylation: an alkyl (R) group substitutes for a hydrogen General Mechanism for Electrophilic Aromatic Substitution Reactions  General Mechanism for Electrophilic Aromatic Substitution Reactions  Although benzene's pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation (electron-poor species ).  This resonance-stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond General Mechanism for Electrophilic Aromatic Substitution Reactions General Mechanism for Electrophilic Aromatic Substitution Reactions  General Mechanism for Electrophilic Aromatic Substitution Reactions  The sigma complex (also called an arenium ion) is not aromatic because the sp3-hybrid carbon atom interrupts the ring of p orbitals.  The sigma complex regains aromaticity by loss of the proton on the tetrahedral carbon atom, leading to the substitution product.  General Mechanism for Electrophilic Aromatic Substitution Reactions  In electrophilic aromatic substitution the intermediate carbonium ion is a hybrid of structures I, II, and III, in which the positive charge is distributed about the ring, being strongest as the positions ortho and para to the carbon atom being attacked.  Mechanism of Nitration :  The combination of nitric acid and sulfuric acid produces NO2+ (nitronium ion)  The reaction with benzene produces nitrobenzene  Mechanism of Nitration : Just what is the structure of this carbonium ion ?  We find that we can represent It by three structures (I, II, and III) that differ from each other only in position of double bonds and positive charge.  Mechanism of Nitration :  The Nitro group can be reduced to an Amino group if needed  Mechanism of Sulfonation :  Substitution of H by SO3 (sulfonation)  Reaction with a mixture of sulfuric acid and SO3 (“Fuming H2SO4)  Reactive species is sulfur trioxide or its conjugate acid Mechanism of Sulfonation :  Mechanism of Friedel-Crafts Alkylation:  Friedel-Crafts alkylation is an electrophilic aromatic substitution in cation acts as the eletrophile which an alkyl  Mechanism of Halogenation :  The bromination or chlorination of benzene requires a Lewis acid such as ferric bromide or ferric chloride.  In the first step of the bromination reaction, bromine donates a lone pair to the Lewis acid.  This weakens the Br-Br bond, thereby providing the electrophile necessary for electrophilic aromatic substitution. Mechanism of Halogenation :  Mechanism of Halogenation :  In the last step of the reaction, a base from the reaction mixture removes a proton from the carbocation intermediate. The following equation shows that the catalyst is regenerated:  Mechanism of Friedel-Crafts Alkylation:  Similar to alkylation  Reactive electrophile: resonance-stabilized acyl cation  An acyl cation does not rearrange  Mechanism of Friedel-Crafts Alkylation:  Can reduce carbonyl to get alkyl product