Organic Chemistry

Organic Chemistry Jin Hongwei College of Chemical Engineering and Materials Science jhwei828@zjut.edu.cn

Chapter Five Aromatic Hydrocarbons and Aromaticity • Isomerism and Nomenclature of Aromatic Hydrocarbons. • Structure and Stability of Benzene. • Physical Properties of Monocyclic Aromatic Hydrocarbons. • Chemical Properties of Monocyclic Aromatic Hydrocarbons. • Chemical Properties of Polycyclic Aromatic Hydrocarbons. • Aromaticity and the Huckel Rule.

Introduction(1) • In 1834 the German chemist Eilhardt Mitscherlich (University of Berlin) firstly synthesized benzene by heating benzoic acid with calicum oxide. Using vapor density measurements, Mitscherlich further showed that benzene has the molecular formula C6H6: • The molecular formula itself was surprising. Benzene hasonly as many hydrogen atoms as it has carbon atoms, it should be a highly unsaturated compound. Eventually, chemists began to recognize that benzene does not show the behavior expected of a highly unsaturated compound.

Introduction(2) • During the latter part of the nineteenth century the Kekule –Couper-Butlerov theory of valence was systematically applied to all known organic compounds. Organic compounds were classified as being either aliphatic or aromatic. • To be classified as aliphatic meant that the chemical behavior of a compound was “fatlike”. • To be classified as aromatic meant that the compound had a low hydrogen-carbon ratio and that it was “fragrant”.

Isomerism and Nomenclature of Aromatic Hydrocarbons(2) • Disubstituted benzenes are named using one of the prefixesortho(o), meta(m), or para(p). • An ortho-disubstituted benzene has its two substituents in a 1,2 relationship on the ring; a meta-disubstituted benzene has its two substituents in a 1,3 relationship; and a para-disubstituented benzene has its substituents in a 1,4 relationship. For example: BACK

Isomerism and Nomenclature of Aromatic Hydrocarbons(1) • Monosubstituted benzene are systematically named in the same manner as other hydrocarbons, with –benzene as the parent name. For example: • If the alkyl substituent has more than six carbons, or has carbon-carbon double bond and triple bond, the compound is named as a phenyl-substituted alkane, alkene or alkyne. For example:

Structure and Stability of Benzene(1) • In 1865, August Kekule, the originator of the structual theory, proposed the first definite structure for benzene, a structure that is still used today. Kekule suggested that the carbon atoms of benzene are in a ring, that they are bonded to each other by alternating single and double bonds, and that one hydrogen atom is attached to each carbon atom. • The fact that the bond angles of the carbon atoms in the benzene ring are all 120o strongly suggests that the carbon atoms are sp2 hydridized.

Structure and Stability of Benzene(2) • Although benzene is clearly unsaturated, it is much more stable than other alkenes, and it fails to undergo typical alkene reactions. For example: • We can get a quantitative idea of benzene’s stability from the heats of hydrogenation.

Chemical Properties of Monocyclic AromaticHydrocarbons(1) • Chemistry of Benzene: Electrophilic Aromatic Substitution. • The most common reaction of aromatic compounds iselectrophilic aromatic substitution. That is, an electrophile (E+) react with an aromatic ring and substitutes for one of the hydrogens: • Many different substituents can be introduced onto the aromatic ring by electrophilic substitution reactions. By choosing the proper reagents, it’s possible to halogenate the aromatic ring, nitrate it, sulfonate it, alkylate it, or acylate it. • Halogenation • Nitration Sulfonation • Alkylation Acylation

Chemical Properties of Monocyclic Aromatic Hydrocarbons(2) • Aromatic Halogenation: • A. Bromination of Aromatic Rings • A benzene ring , with its sixπelectrons in a cyclic conjugated system, is a site of electron density. Thus, benzene acts as an electron donor (aLewis base, ornucleophile) in most of its chemistry, and most of its reactions take place with electron acceptors (Lewis acids, orelectrophiles). For example, benzene react with Br2 in the presence of FeBr3 as catalyst to yield the substitution product bromobenzene.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(3) • The mechanism of the electrophilic bromination of benzene.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(4) • Aromatic Halogenation: • B. Chlorination and Iodination of Aromatic Rings • Chlorine and iodine can be introduced into aromatic rings by electrophilic substitution reactions, but fluorine is too reactive, and only poor yields of monofluoroaromatic products are obtained by direct fluorination. For example:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(5) • Aromatic Nitration • Aromatic rings can be nitrated by reaction with a mixture of concentrated nitric and sulfuric acids. The electrophile in this reaction is the nitronium ion, NO2+, which is generated from HNO3 by protonation and loss of water. The nitronium ion react with benzene to yield a carboncation intermediate in much the same way as Br+. Loss of H+ from this intermediate gives the product, nitrobenzene.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(6) • Aromatic Sulfonation • Aromatic rings can be sulfonated by reaction with fuming sulfuric acid, a mixture of H2SO4 and SO3. The reactive electrophile is either HSO3+ or SO3, depending on reaction conditions. Substitution occurs by the same two-step mechanism seen previously for bromination and nitration.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(7) • Alkylation of Aromatic Rings: The Friedel-Crafts Reaction • One of the most useful of all electrophilic aromatic substitution reactions isalkylation, the attachment of an alkyl group to the benzene ring. • For example: • TheFriedel-Crafts alkylation reactionis an electrophilic aromatic substitution in which the electrophile is a carbocation, R+. Aluminum chloride catalyzes the reaction by helping the alkyl halide to ionize in much the same way that FeBr3 catalyzes aromatic brominations by polarizing Br2 . Loss of a proton then completes the reaction.

Chemical Properties of Monocyclic AromaticHydrocarbons(8) • The mechanism of the Friedel-Crafts alkylation reaction: • Give the structures of the major products of the following reactions: • How to prepare propylbenzene by Friedel-Crafts reaction?

Chemical Properties of Monocyclic Aromatic Hydrocarbons(9) • An acyl group, -COR, is introduced onto the ring when an aromatic compound reacts with a carboxylic acid chloride, RCOCl, in the presence of AlCl3. For example, reaction of benzene with acetyl chloride yields the ketone, acetophenone. • The mechanism ofFriedel-Crafts acylation:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(10) • How to prepare propylbenzene by Friedel-Crafts reaction? • By contrast, the Friedel-Crafts acylation of benzene with propanoyl chloride produces a ketone with an unrearranged carbon chain in excellent yield. • This ketone can then be reduced to propylbenzene by several methods. One general method-called the Clemmensen reduction-consists of refluxing the ketone with hydrochloric acid containing amalgamatedzinc.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(11) • Substituent Effects in Substituted Aromatic Rings • Only one product can form when an electrophilic substitution occurs on benzene, but when what would happen if we were to carry out a reaction on an aromatic ring that already has a substituent? • A substituent already present on the ring has two effects: • 1. A substituent affects thereactivity of the aromatic ring. Some substituentsactivatethe ring, making it more reactive than benzene, and somedeactivatethe ring, making it less reactive than benzene. • For example: Reactive rate 1000 1 0.033 6╳10-8 of nitration

Chemical Properties of Monocyclic Aromatic Hydrocarbons(12) • Substituent Effects in Substituted Aromatic Rings • 2.Substituents affect theorientationof the reaction. The three possible disubstituted products-ortho, meta, and para-are usually not formed in equal amounts. Instead, the nature of the substituent already present on the benzene ring determines the position of the second substitution. For example:Orientation of Nitration in Substitued Benzenes • Product (%) Product(%) • Ortho Meta Para Ortho Meta Para • Meta-directing deactivatorsOrtho- and para-directing deactivators • -+N(CH3)3 2 87 11 -F 13 1 86 • -NO27 91 2 -Cl 35 1 64 • -COOH 22 76 2 -Br 43 1 56 • -CN 17 81 2 -I 45 1 54 • -COOCH328 66 6 Ortho- and para-directing activators • -COCH326 72 2 -CH3 63 3 34 • -CHO 19 72 9 -OH 50 0 50 • -NHCOCH3 19 2 79

Chemical Properties of Monocyclic Aromatic Hydrocarbons(13) • Substituent Effects in Substituted Aromatic Rings • Substituents can be classified into three groups: • Ortho-and para-directing activators, ortho-and para-directing deactivators, and meta-directing deactivators. • Ortho-and para- ortho-and para- Meta-directing • directing activators directing deactivators deactivators

Chemical Properties of Monocyclic Aromatic Hydrocarbons(14) • An Explanation of Substituent Effects(1) • Activation and Deactivation of Aromatic Rings • The common feature of all activating groups is that they donate electrons to the ring, thereby stabilizing the carbocation intermediate from electrophilic addition and causing it to form faster. • The common feature of all deactivating groups is that they withdraw electrons from the ring, thereby destabilizing the carbocation intermediate from electrophilic addition and causing it to form more slowly.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(15) • An Explanation of Substituent Effects(2) • Ortho- and Para- Directing Activators: Alkyl Groups • Inductive and resonance effects account for the directing ability of substituents as well as for their activating or deactivating ability. Take alkyl groups, for example, which have an electron-donating inductive effect and behave as ortho and para directors. The results of toluene nitration are shown as below:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(15) • An Explanation of Substituent Effects(3) • Ortho- and Para- Directing Activators: OH and NH2 • Hydroxyl, alkoxyl, and amino groups are also ortho-para activators, but for a different reason than for alkyl groups. Hydroxyl, alkoxyl, and amino groups have a strong, electron-donating resonance effect that is most pronounced at the ortho and para positions and outweighs a weaker electron-withdrawing inductive effect. When phenol is nitrated, only ortho and para attack is observed:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(16) • An Explanation of Substituent Effects(4) • Ortho- and Para- Directing Deactivators: Halogens • Halogens are deactivating because their stronger electron-withdrawing inductive effect outweighs their weaker electron-donating resonance effect. Though weak, that electron-donating resonance effect is felt only at the ortho and para positions.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(17) • An Explanation of Substituent Effects(5) • Meta- Directing Deactivators • Meta-directing deactivators act through a combination of inductive and resonance effects that reinforce each other. Inductively, both ortho and para intermediates are destabilized because a resonance form places the positive charge of the carbocation intermediate directly on the ring carbon atom that bears the deactivating group. At the same time, resonance electron withdrawal is also felt at the ortho and para positions. Reaction with an electrophilic therefore occurs at the meta position.

Chemical Properties of Monocyclic Aromatic Hydrocarbons(18) • Trisubstituted Benzenes: Additivity of Effects • Further electrophilic substitution of a disubstituted benzene is governed by the same resonance and inductive effects just discussed. The only difference is that it’s necessary to consider the additive effects of two different groups. In practice, three rules are usually sufficient: • Rule 1. If the directing effects of the two groups reinforce each other, there is no problem. • Rule 2. If the directing effects of the two groups oppose each other, the more powerful activating group has the dominant influence, but mixtures of products often result. • Rule 3. Further substitution rarely occurs between the two groups in a meta- disubstituted compound because this site is too hindered. • Some examples:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(19) • Synthesis of Substituted Benzenes • One of the surest ways to learn organic chemistry is to work synthesis problems. The ability to plan a successful multistep synthesis of a complex molecule requires a working knowledge of the uses and limitations of many hundreds of organic reactions. Not only must you know which reactions to use, you must also know when to use them. The order in which reactions are carried out often critical to the success of the overall scheme. • The ability to plan a sequence of reactions in the right order is particularly valuable in the synthesis of substituted aromatic rings, where the introduction of a new substituent is strongly affected by the directing effects of other substituents. Planning synthesis of substituted aromatic compounds is therefore an excellent way to gain facility withthe many reactions learned in the past few chapters. Some examples:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(20) • Reduction of Aromatic Compounds • To hydrogenate an aromatic ring, it’s necessary to use a platinum catalyst with hydrogen gas at several hundred atmospheres pressure. For example: • Oxidation of Benzene:

Chemical Properties of Monocyclic Aromatic Hydrocarbons(21) • Oxidation of Alkylbenzene Side Chains • Alkyl side chains are readily attacked by oxidizing agents and are converted into carboxyl groups, -COOH. For example: • Bromination of Alkylbenzene Side Chains BACK

Chemical Properties of Polycyclic Aromatic Hydrocarbons(1) • Polycyclic aromatic hydrocarbons have two or more benzene ringsfused together. For example: • Naphthalene Anthracene Phenanthrene • Reactions of Naphthalene:

Chemical Properties of Polycyclic Aromatic Hydrocarbons(2) • Substituent Effects in Substituted Naphthalene

Aromaticity and the Huckel Rule • In 1931 the Germen physicist Erich Huckel carried out a series of mathematical calculations based on the theory of molecular orbital.Huckel’s ruleis concerned with compounds containingone planar ring in which each atom has a p orbitalas in benzene. His calculations show that planar monocyclic rings containing4n+2πelectrons, where n=0, 1, 2, 3,……, and so on,delocalized electrons should be aromatic.For example:

Additional problems of chapter five (1) • 3.1 Give IUPAC names for the following compounds: • (a) (b) • (c) (d) • 3.2 Predict the major product(s) of the following reactions: • (a) • (b) • (c)

Additional problems of chapter five (2) • 3.3 At what position, and on what ring, would you expect the following substances to undergo electrophilic substitution? • (a) (b) (c) • (d) (e) (f) • (g) (h) (i) • 3.4 How would you synthesize the following substances starting from benzene? • (a) (b) (c) (d)

Additional problems of chapter five (3) • 3.4 Which would you expect to be aromatic compounds according to Huckel 4n+2 rule? • (a) (b) (c) (d) (e) • (f) (g) (h) (i)

Organic Chemistry