Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 328

Brief Organic Chemistry

Summer 2004

Lecture Notes: 22 June (lecture 2)

© R. Paselk 2004
 
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Benzene Chemistry

Oxidation

Benzene is very resistant to oxidation, being unaffected by strong oxidizing agents such as chromic acid (H2CrO4) and potassium permanganate (KMnO4). However, carbons attached to the benzene ring (benzyl groups) can frequently be oxidized.

Benzyl group oxidation: In general we can say that if there is a hydrogen attached to a benzylic carbon (the carbon attached directly to the benzene ring), then the benzylic carbon can be oxidized. These reactions are rather surprizing at first sight, for example, in both of the oxidations below, the benzylic carbon is oxidized to the carboxylic acid while the benzene ring is untouched!:

The oxidation of alkyl substituted rings is even more surprizing, with the remainder of the alkane chain going to carbon dioxide:

On the other hand, a t-butyl group, with no benzylic hydrogen, is unreactive, again demonstrating the relative stability of carbon-carbon bonds.

 

Electrophilic Aromatic Substitution

Electrophilic attack on the ring is the most important type of aromatic reaction, as we might expect. After all the aromatic ring has electron rich 'clouds' above and below the ring. Many different substituents can be introduced onto the ring using proper reagents: -X, -NO2, -SO3H, -R (alkyl grps).

Bromination of Benzene: However, the reactions are not always what one would expect based on an alkene model. For example, bromination gives a single, mono-substituted product:

So why don't we see the di-substituted product? What mechanism accounts for the mono-substitution? A look at the possible carbocation intermediates helps in understanding this process:

A reaction coordinate diagram for this reaction is shown below (note that it has the same shape and general characteristics as the halogenation of ethylene we saw earlier).

So looking at the mechanism and the diagram, why don't we see the formation of the dibromo-product? It turns out that due to the loss of the delocalized electron system represented by the resonance forms, the dibromo-product, 5,6-dibromo-1,3-cyclohexadiene, has an energy close to that of the intermediate. Thus any 5,6-dibromo-1,3-cyclohexadiene formed in the reaction would be in rapid equilibrium with this intermediate because of the relatively low activation energy, and it would all go to the final product, bromobenzene.

Chlorination of Benzene: This reaction is like the bromination reaction, using ferric chloride as catalyst. It is used in a variety of synthess reactions including pharmaceuticals and (more commonly in the past) for herbacide (e.g. 2,4,5-T, 2,4-D etc.) and insecticide (e.g. DDT, alare, etc.) synthesis:

Nitration of Benzene: In this reaction the nitronium ion, NO2+, is the electrophilic species, as seen for Br+ above. Concentrated nitric acid asts as a source for this ion, while concentrated sulfuric acid acts as a catalyst. Nitration is important for the production of explosives (TNT = TriNitroToluene), dyes, pharmaceuticals, etc.:

Sulfonation of Benzene: In this reaction the bisulfite ion, HSO3+, is the electrophilic species. Fuming sulfuric acid (sulfuric acid saturated with sulfur trioxide) serves as the catalyst and source of HSO3:

Friedel-Crafts Alkylation and Acylation Reaction: This reaction allows alkyl and acyl groups to be attached to benzene rings via an electrophilic substitution reaction. Here the problem is how to make alkyl or acyl groups into electrophiles. In each case a halide derivative is involved.

For the Friedel-Crafts alkylation an alkyl chloride reacts with a benzene ring in the presence of an aluminum chloride catalyst:

The mechanism for this substitution occurs in two parts. First the AlCl3 catalyst reacts with the alkyl chloride to give AlCl4- and a carbocation electrophile:

The carbocation can then undergo electrophilic attack by the benzene ring:

This reaction is very useful, but is limited: 1) only alkyl halides will work, and 2) aromatic rings with -NO2, -SO3H, -CN, or -COR substituents are unreactive.

In the Friedel-Crafts acylation an acyl chloride reacts with a benzene ring in the presence of an aluminum chloride catalyst:

 

Substituent Effects in Electrophilic Aromatic Substitution Reactions

When one attempts to put a second substituent onto an aromatic ring it is found that the first substituent has two effects on this second substitution:

The initial substituent has an effect on the reactivity of the aromatic ring. Thus some groups activate it (make it more reactive). Compared to hydrogen, the following groups increase the ring's reactivity (in order, H2N- gives the greatest activation): C6H5- (phenyl), CH3- (alkyl), CH3CONH-, CH3O-, HO-, and H2N-. Other groups deactivate the ring, making it less reactive. Compared to hydrogen the following groups deactivate (in order, -N+R3 gives the least reactive): -F, -Cl, -Br, -I, -CHO, -COOCH3, -COOH, -COCH3, -SO3H, -CN, -NO2, -N+R3.

The initial substituent also has an orientation effect. That is some substituents direct additional substituents toward the ortho- and para- positions while others direct toward the meta- position. This can occur in three different ways:

 
 

Theory of Substituent Effects

 
Activation vs. Deactivation:

 

Orienting Effects

Ortho & Para Directors: In general ortho and para directors have lone pairs of electrons on the atom directly attached to the ring. These lone pairs have the possibility of forming a double bond to the ring, transferring the positive charge of the carbocation intermediate from the ring to the substituent, delocalizing the charge over a larger atomic system:

But of course for predicting the final products we have said that what is important is the relative stability of the final products. However, in these reactions there is such a difference in the transition state energies that we just don't see equilibrium being achieved, so from a practical point of view it is the transition state energy which determines final product.

Meta Directors: Note in this case that although the substituent makes all of the intermediates less stable (so the reaction goes slower), the direction is due to making the ortho and para intermediates and derivatives less stable than the meta intermediate set and derivatives:

 

Reduction of Aromatic Compounds: Benzene and its derivatives are resistant to reduction as well. Only at high temperatures and pressures does reduction occur.

Polycyclic Aromatic Compounds: Napthalene (two rings), Anthracene (three rings fused in a line). Polycyclic rings can be much more complicated, such as Benzo(a)pyrene. They are important carcinogens, since they are produced during pyrolysis (burning) and thus are present in smoke and tar from fires, including cigarettes. (Tar was one of the first postulated carcinogens, associated with high testicular cancer in chimney sweeps in 1775.) Like many carcinogens, the molecule itself is not the active substance, rather it must be activated by the host organism, as for example in Benzo(a)pyrene:


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Last modified 22 June 2004