Aromatic Compounds and

Their Reactions 1

Based on Organic Chemistry, T.W. GRAHAM SOLOMONS and CRAIG B. FRYHLE 10e. & Organic Chemistry, DAVID KLEIN, 2nd e.

Organic Chemistry II 1st Semester, Year 2 (2015-2016) Lectures 1 & 2

Nomenclature of Benzene Derivatives

Monosubstituted Derivatives of Benzene: Monosubstituted derivatives of benzene are named systematically using benzene as the parent and listing the substituent as a prefix. Below are several examples.

The following are some monosubstituted aromatic compounds that have common names accepted by IUPAC. You must commit these names to memory, as they will be used extensively throughout the remaining chapters.

If the substituent is larger than the benzene ring (i.e., if the substituent has more than six carbon atoms), then the benzene ring is treated as a substituent and is called a phenyl group.

The presence of phenyl groups is often indicated with the letters Ph or with the Greek letter phi (ᵩ)

Phenyl groups bearing substituents are sometimes indicated with the letters Ar, indicating the presence of an aromatic ring.

Disubstituted Derivatives of Benzene Dimethyl derivatives of benzene are called xylene, and there are three constitutionally isomeric xylenes.

These isomers differ from each other in the relative positions of the methyl groups and can be named in two ways: (1) using the descriptors ortho, meta, and para or (2) using locants (i.e., 1,3 is the same as meta). Both methods can be used when the parent is a common name:

Polysubstituted Derivatives of Benzene

The descriptors ortho, meta, and para cannot be used when naming an aromatic ring bearing three or more substituents.

When naming a polysubstituted benzene ring, we will follow the same four-step process used for naming alkanes, alkenes, alkynes, and alcohols. 1. Identify and name the parent. 2. Identify and name the substituents. 3. Assign a locant to each substituent. 4. Arrange the substituents alphabetically. When identifying the parent, it is acceptable (and common practice) to choose a common name.

Homework: Provide a systematic name for each of the following compounds:

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• In 1825, Michael Faraday isolated benzene from the oily residue left by illuminating gas in London street lamps. Further investigation showed that the molecular formula of this compound was C6H6: a hydrocarbon comprised of six carbon atoms and six hydrogen atoms.

• August Kekulé proposed that benzene was a rapidly equilibrating mixture of two compounds, each containing a six-membered ring with three alternating bonds.

• In the Kekulé description, the bond between any two carbon atoms is sometimes a single bond and sometimes a double bond.

• These structures are known as Kekulé structures.

The Kekulé Structure for Benzene:

A problem soon arose with the Kekulé structure, however. The Kekulé structure predicts that there should be two different 1,2-dibromobenzenes, but there are not. In one of these hypothetical compounds (below), the carbon atoms that bear the bromines would be separated by a single bond, and in the other they would be separated by a double bond.

To accommodate this objection, Kekulé proposed that the two forms of benzene (and of benzene derivatives) are in a state of equilibrium and that this equilibrium is so rapidly established that it prevents isolation of the separate compounds. Thus, the two 1,2-dibromobenzenes would also be rapidly equilibrated, and this would explain why chemists had not been able to isolate the two forms:

Stability of Benzene

An energy diagram comparing the heats of hydrogenation for cyclohexene, cyclohexadiene, and benzene.

The difference between the expected value (-360) and the observed value (-208) is 152 kJ/mol, which is called the stabilization energy of benzene. This value represents the amount of stabilization associated with aromaticity.

Hückel’s Rule

We might expect the following two compounds to exhibit aromatic stabilization like benzene:

After all, they are similar to benzene in that each compound is comprised of a ring of alternating single and double bonds. The reactivity of cyclooctatetraene (C8H8) suggests that cyclooctatetraene does not exhibit the same stability exhibited by benzene. For example, the compound readily undergoes addition reactions, such as bromination.

Cyclobutadiene (C4H4) also does not exhibit aromatic stability. It is extremely unstable and resisted all attempts to prepare it until the second half of the twentieth century. Cyclobutadiene is so unstable that it reacts with itself at -78°C in a Diels-Alder reaction.

The Diels-Alder reaction generates an initial tricyclic product that is also unstable and rapidly rearranges to form cyclooctatetraene.

The presence of a fully conjugated ring of p electrons is not the sole requirement for aromaticity; the number of π electrons in the ring is also important. Specifically, we have seen that an odd number of electron pairs is required for aromaticity.

The requirement for an odd number of electron pairs is called Hückel’s rule. Specifically, a compound can only be aromatic if the number of π electrons in the ring is 2, 6, 10, 14, 18, and so on. This series of numbers can be expressed mathematically as 4n + 2, where n is a whole number.

Homework: Predict whether each of the following compounds should be aromatic:

The Criteria for Aromaticity

Benzene is not the only compound that exhibits aromatic stabilization. A compound will be aromatic if it satisfies the following two criteria: 1. The compound must contain a ring comprised of continuously overlapping p orbitals. 2. The number of p electrons in the ring must be a Hückel number. Compounds that fail the first criterion are called nonaromatic. Below are three examples, each of which fails the first criterion for a different reason.

Compounds that satisfy the first criterion but have 4n electrons (rather than 4n + 2) are antiaromatic.

Reactions of Aromatic Compounds

Electrophilic Aromatic Substitution Reactions:

Mechanism of Electrophilic Aromatic Substitution

For brevity, we can show the mechanism using the hybrid formula for benzene:

There is firm experimental evidence that the arenium ion is a true intermediate in electrophilic substitution reactions. It is not a transition state. This means that in a free-energy diagram the arenium ion lies in an energy valley between two transition states.

The reaction leading from benzene and an electrophile to the arenium ion is highly endothermic, because the aromatic stability of the benzene ring is lost. The reaction leading from the arenium ion to the substituted benzene, by contrast, is highly exothermic because it restores aromaticity to the system.

Of the following two steps, step 1 (the formation of the arenium ion) is usually the rate determining step in electrophilic aromatic substitution because of its higher free energy of activation:

Step 2, the removal of a proton, occurs rapidly relative to step 1 and has no effect on the overall rate of reaction.

Halogenation of Benzene:

The purpose of the Lewis acid is to make the halogen a stronger electrophile.

The mechanism of the chlorination of benzene in the presence of ferric chloride is analogous to the one for bromination. Fluorine reacts so rapidly with benzene that aromatic fluorination requires special conditions and special types of apparatus. Even then, it is difficult to limit the reaction to monofluorination. Fluorobenzene can be made, however, by an indirect method. Iodine, on the other hand, is so unreactive that a special technique has to be used to effect direct iodination; the reaction has to be carried out in the presence of an oxidizing agent such as nitric acid.

Nitration of Benzene: Benzene undergoes nitration on reaction with a mixture of concentrated nitric acid and concentrated sulfuric acid.

Sulfonation of Benzene:

Benzene reacts with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is sulfuric acid that contains added sulfur trioxide (SO3). Sulfonation also takes place in concentrated sulfuric acid alone, but more slowly. Under either condition, the electrophile appears to be sulfur trioxide.

In concentrated sulfuric acid, sulfur trioxide is produced in an equilibrium in which H2SO4

acts as both an acid and a base (see step 1 of the following mechanism).

All of the steps in sulfonation are equilibria, which means that the overall reaction is reversible. The position of equilibrium can be influenced by the conditions we employ.

If we want to sulfonate the ring (install a sulfonic acid group), we use concentrated sulfuric acid or—better yet—fuming sulfuric acid. Under these conditions the position of equilibrium lies appreciably to the right, and we obtain benzenesulfonic acid in good yield. If we want to desulfonate the ring (remove a sulfonic acid group), we employ dilute sulfuric acid and usually pass steam through the mixture. Under these conditions—with a high concentration of water—the equilibrium lies appreciably to the left and desulfonation occurs. We sometimes install a sulfonate group as a protecting group, to temporarily block its position from electrophilic aromatic substitution, or as a directing group, to influence the position of another substitution relative to it. When it is no longer needed we remove the sulfonate group.

Friedel–Crafts Alkylation

Friedel–Crafts alkylations are not restricted to the use of alkyl halides and aluminum chloride. Other pairs of reagents that form carbocations (or species like carbocations) may be used in Friedel–Crafts alkylations as well. These possibilities include the use of a mixture of an alkene and an acid:

Friedel–Crafts Acylation

The group is called an acyl group, and a reaction whereby an acyl group is introduced into a compound is called an acylation reaction.

The Friedel–Crafts acylation reaction is often carried out by treating the aromatic compound with an acyl halide (often an acyl chloride). Unless the aromatic compound is one that is highly reactive, the reaction requires the addition of at least one equivalent of a Lewis acid (such as AlCl3) as well. The product of the reaction is an aryl ketone:

Friedel–Crafts acylations can also be carried out using carboxylic acid anhydrides.

In most Friedel–Crafts acylations the electrophile appears to be an acylium ion formed from an acyl halide in the following way:

Limitations of Friedel–Crafts Reactions

1- When the carbocation formed from an alkyl halide, alkene, or alcohol can rearrange to one or more carbocations that are more stable, it usually does so, and the major products obtained from the reaction are usually those from the more stable carbocations.

2- Friedel–Crafts reactions usually give poor yields when powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an NH2, NHR, or NR2 group. This applies to both alkylations and acylations.

3- Aryl and vinylic halides cannot be used as the halide component because they do not form carbocations readily

4- Polyalkylations often occur.

Polyacylations are not a problem in Friedel–Crafts acylations, however. The acyl group (RCO ) by itself is an electron-withdrawing group, and when it forms a complex with AlCl3 in the last step of the reaction, it is made even more electron withdrawing. This strongly inhibits further substitution and makes monoacylation easy.

Synthetic Applications of Friedel–Crafts Acylations: The Clemmensen Reduction 1- Rearrangements that happen in the Friedel–Crafts alkylations can be avoided by using Friedel–Crafts acylations

2- When cyclic anhydrides are used as one component, the Friedel–Crafts acylation provides a means of adding a new ring to an aromatic compound. One illustration is shown here. Note that only the ketone is reduced in the Clemmensen reduction step. The carboxylic acid is unaffected