The now-banned diet drug fen-phen is a mixture of two synthetic substituted benzene: fenfluramine and phentermine.

The now-banned diet drug fen-phen is a mixture of two synthetic substituted benzene: fenfluramine and phentermine.

Chemists have synthesized compounds with structures similar to adrenaline, producing amphetamine.

Compounds like benzene that have relatively few hydrogens in relation to the number of carbons, are typically found in oils produced by trees and other plants. Early chemists called such compounds aromatic compounds because of their fragrances.

Benzene is a particularly stable compound because its delocalization energy -the extra stability it gains from having delocalized electron. Compounds with unusally large delocalization energies are called aromatic compounds. To be classified as aromatic, a compound must meet both of the following criteria: Must be cyclic and planar. Must have an uninterupted cloud of of electrons. The clound must contain an odd number of pairs of electrons.

Not aromatic aromatic Not aromatic

Not aromatic Not aromatic aromatic Cyclopentadiene is not aromatic. It does not have an uninterupted ring of p orbital-bearing atoms. One of its ring atoms is sp 3 hybridized. Cyclopentadienyl cation also is not aromatic because, although it is planar and has an uninterupted ring of p orbitalbearing atoms, its clouds has two (even number) of pairs of electrons.

All the carbon in the cyclopentadienyl anion are equivalent. Each carbons has exactly one-fifth of the negative charge associated with the anion.

Naphthalene (five pair of electrons), phenanthrene (seven pairs of electrons), and chrysene (nine pairs of electrons) are aromatics. All are aromatic

A heterocyclic compound is a cyclic compound in which one or more of the ring atoms is an atom other than carbon. A ring atom that is not carbon is called a heteroatom. Pyridine is an aromatic heterocyclic compound. It contains three pairs of electrons.

Pyrrole has three pairs of electrons and it is aromatic.

Furan and thiophene are stable aromatic compounds.

Some monosubstituted benzenes are named simply by attaching benzene to the name of the substituent.

Some monosubstituted benzenes have names that incorporate the name of the substituent. Unfortunately, such names have to be memorized.

When a benzene ring is a substituent, it is called a phenyl group. A benzene ring with a methylene group is called a benzyl group.

An aryl group (Ar) is the general term for either a phenyl group. ArOH could be used to desinate any of the following phenols.

Aromatic compounds such as benzene undergo electrophilic aromatic substitution reactions.

The cloud of electrons above and below the plane of its ring causes benzene to be a nucleophile. It will react with an electrophile (Y + ). Then, a carbocation intermediate is formed.

If the carbocation intermediate were to react similarly with a nucleophile (as path b), the product of the reaction would not be aromatic.

Because the aromatic substitution product is much more stable than the nonaromatic addition product, benzene undergoes electrophilic substitution reactions that preserve aromaticity rather than electrophilic addition reaction. The substitution reaction is more accurately called an electrophilic aromatic substitution reaction.

Mechanism for electrophilic aromatic substitution In an electrophilic aromatic substitution reaction, an electrophile (Y + ) is put on a ring carbon, and the H + comes off the same ring carbon.

Requires a Lewis acid catalyst such as ferric bromide or ferric chloride.

Mechanism of bromination

Mechanism of chlorination

Requires sulfuric acid as a catalyst. Structure of nitric acid To generate the necessary electrophile.

Mechanism of nitration

Forming the + SO 3 electrophile.

Mechanism of sulfonation

The electrophile (an acylium ion) is formed by the reaaction of the acyl chloride with AlCl 3, a Lewis acid. Mechanism for Friedel-Crafts acylation

Formation of electrophile

Mechanism for Friedel-Crafts alkylation

Alkylation of benzene by an alkene

Because benzene is an unusually stable compound, its double bonds do not react with H 2 under these condition.

An alkyl group bonded to a benzene ring can be oxidized to a COOH group. When an organic compound is oxidized, either the number of C-O bonds increase or the number of C-H bonds decrease. Regardless of the length of the alkyl substituent, it will be oxidized to a COOH group.

If the alkyl group lacks a benzylic hydrogen, the oxidation reaction will not occur because the first step in the oxidation reaction is removal of a hydrogen from the benzylic carbon.

If the two substituents are different, they are listed in alphabetical order.

If one of the substituents can be incorporated into a name, that name is used and the incorporated substituent is given the 1- position.

Substituents that donate electrons into the benzene ring stabilize both the carbocation intermediate and the transition state leading towards its formation, thereby increasing the rate of electrophilic aromatic substitution: these are called activating substituents. In contrast, substituents that withdraw electrons from the benzene ring disstabilize the carbocation intermediate and the transition state leading towards its formation, thereby decreasing the rate of electrophilic aromatic substitution: these are called deactivating substituents.

There are two ways substituents can donate electrons : inductively or by resonance. The + NH 3 group is an example of a substituent that withdraws electrons inductively because it is more electronegative than a hydrogen.

Substituents such as NH 2, OH, OR, and Cl donate electrons by resonance. These substituents also withdraw electrons inductively because the atom attached to the benzene ring is more electronegative than a hydrogen.

Substituents such as C=O, C N, SO 3 H, and NO 2 withdraw electrons by resonance.

All activating substituents and the weakly deactivating halogens are ortho-para directors, and all substituents that are more deactivating than the halogens are meta directors. The substituents can be divided into three groups. 1. All activating substituents direct an incoming electrophile to the ortho and para positions.

2. The weakly deactivaing halogens also direct an incoming electrophile to the ortho and para positions.

3. All moderately deactivating and strongly deactivating substituents direct an incoming electrophile to the meta position.

When the substituent is one that can denote electrons by resonance, the carbocations formed by putting the incoming electrophile on the ortho and para positions have a fourth resonance contributor (very stable, atoms have complete octets). It is obtained only by directing an incoming substituent to the ortho and para positions. Therefore, all substituents that donate electrons by resonance are ortho and para director.

When the substituent is an alkyl group, the resonance contributors that are highlight in Fig 8.4 are the most stable. The alkyl group is attached directly to the positively charged carbon and can stabilize it by inductive electron donation. A relatively stable resonance contributor is obtained only when the incoming group is directed to an ortho or para position. Therefore, alkyl substituents are ortho-para diractors.

Substituents with a positive charge or a partial positive charge on the atom attached to the benzene ring will withdraw electrons inductively from the benzene ring, and most will withdraw electrons by resonance as well. The resonance contributors highlighted in Fig 8.5 are the least stable. The most stable carbocation is formed when the incoming electrophile is directed to the meta position. Therefore, all substituents that withdraw electrons (except for halogens, which are ortho-para directors because they donate electrons by resonance) are meta directors.

All substituents that donate electrons into the ring either inductively or by resonance are ortho-para directors. All substituents that cannot donate electrons into the ring either inductively or by resonance are meta directors.

If you want to systhesize meta-bromobenzenesulfonic acid, the sulfonic acid group has to be placed on the ring first, because that group will direct the bromo substituent to the desired meta position.

If the desired product is para-bromobenzenesulfonic acid, the order of the two reactions must be reversed because only the bromo substituent is an ortho-para director.

The methyl group is oxidized after it directs the chloro substituent to the para position. In the synthesis of meta-chlorobenzoic acid, the methyl group is oxidized before chlorination because a meta director is needed to obtain the desired product.

The friedel-crafts acylation reaction must be carried out first because if the ring were nitrated first, the benzene ring of nitrobenzene would be too deactivated to undergo a Fridel- Crafts reaction.

The pka of phenol in H 2 O is 9.95. the pka of para-nitrophenol is lower (7.14) because the nitro substituent withdraws electrons from the ring, whereas the pka of para-methyl phenol is higher (10.19) because the methyl substituent donates electrons into the ring.

The more deactivating (electron withdrawing) the substituent, the more it increases the acidity of a COOH, an OH, or an + NH 3 group attached to a benzene ring. The more activating (electron donating) the substituent, the more it decreases the acidity of a COOH, an OH, or an + NH 3 group attached to a benzene ring.