After completing this section, you should be able to
- write an equation to represent the reduction of a substituted benzene to a substituted cyclohexane.
- identify the catalyst and reagents used to reduce aromatic rings.
- compare the ease of reduction of alkenes with the difficulty in reducing benzene rings, and show how this difference in reactivity can be used in organic synthesis.
- write an equation to illustrate the reduction of an aromatic ketone to an arene.
- explain why Friedel-Crafts acylation, followed by reduction, provides a better route to primary alkylbenzenes than does direct alkylation.
- show how a specified alkylbenzene may be prepared by a Friedel-Crafts acylation, followed by reduction. Specify all reagents, the structure of the intermediate ketone, and the necessary starting material.
Catalytic hydrogenation of aromatic rings requires forcing conditions (high heat and hydrogen pressure).
Under milder conditions it is possible to reduce the double-bond of an alkene without reducing the aromatic ring.
Notice in the above equation that H2/Pd does not reduce the keto-carbonyl group. Remember, however, that H2/Pd will reduce a keto-carbonyl group when it is directly attached to an aromatic ring (see equations 4 and 5 under Carbonyl Reductions).
This reduction of the (C=O) group next to an aromatic ring is an important synthetic tool. Recall the Friedel-Crafts alkylation from Section 16.3. When attaching larger alkyl groups to arenes there is a possibility of rearrangement of the alkyl group structure.
To generate the target compound (in this case n‑propylbenzene) in a more controlled fashion, one can simply use the equivalent Friedel-Crafts acylation and then reduce the keto-carbonyl group next to the ring as a final step.
Although it does so less readily than simple alkenes or dienes, benzene adds hydrogen at high pressure in the presence of Pt, Pd or Ni catalysts. The product is cyclohexane and the heat of reaction provides evidence of benzene's thermodynamic stability. Substituted benzene rings may also be reduced in this fashion, and hydroxy-substituted compounds, such as phenol, catechol and resorcinol, give carbonyl products resulting from the fast ketonization of intermediate enols. Nickel catalysts are often used for this purpose, as noted in the following equations.
Benzene is more susceptible to radical addition reactions than to electrophilic addition. We have already noted that benzene does not react with chlorine or bromine in the absence of a catalyst and heat. In strong sunlight or with radical initiators benzene adds these halogens to give hexahalocyclohexanes. It is worth noting that these same conditions effect radical substitution of cyclohexane, the key factors in this change of behavior are the pi-bonds array in benzene, which permit addition, and the weaker C-H bonds in cyclohexane. The addition of chlorine is shown below on the left; two of the seven meso-stereoisomers are displayed to the right.
Reduction of Nitro Groups and Aryl Ketones
Electrophilic nitration and Friedel-Crafts acylation reactions introduce deactivating, meta-directing substituents on an aromatic ring. The attached atoms are in a high oxidation state, and their reduction converts these electron withdrawing functions into electron donating amino and alkyl groups. Reduction is easily achieved either by catalytic hydrogenation (H2 + catalyst), or with reducing metals in acid. Examples of these reductions are shown here, equation 6 demonstrating the simultaneous reduction of both functions. Note that the butylbenzene product in equation 4 cannot be generated by direct Friedel-Crafts alkylation due to carbocation rearrangement. The zinc used in ketone reductions, such as 5, is usually activated by alloying with mercury (a process known as amalgamation).
Several alternative methods for reducing nitro groups to amines are known. These include zinc or tin in dilute mineral acid, and sodium sulfide in ammonium hydroxide solution. The procedures described above are sufficient for most cases.
The Birch Reduction
Another way of adding hydrogen to the benzene ring is by treatment with the electron rich solution of alkali metals, usually lithium or sodium, in liquid ammonia. See examples of this reaction, which is called the Birch Reduction. The Birch reduction is the dissolving-metal reduction of aromatic rings in the presence of an alcohol.
Limitations of Friedel-Crafts Alkylation
- Carbocation Rearrangement - Only certain alkylbenzenes can be made due to the tendency of cations to rearrange.
- Compound Limitations - Friedel-Crafts fails when used with compounds such as nitrobenzene and other strong deactivating systems.
- Polyalkylation - Products of Friedel-Crafts are even more reactive than starting material. Alkyl groups produced in Friedel-Crafts Alkylation are electron-donating substituents meaning that the products are more susceptible to electrophilic attack than what we began with. For synthetic purposes, this is a big dissapointment.
To remedy these limitations, a new and improved reaction was devised: The Friedel-Crafts Acylation, also known as Friedel-Crafts Alkanoylation.
The goal of the reaction is the following:
The very first step involves the formation of the acylium ion which will later react with benzene:
The second step involves the attack of the acylium ion on benzene as a new electrophile to form one complex:
The third step involves the departure of the proton in order for aromaticity to return to benzene:
During the third step, AlCl4 returns to remove a proton from the benzene ring, which enables the ring to return to aromaticity. In doing so, the original AlCl3 is regenerated for use again, along with HCl. Most importantly, we have the first part of the final product of the reaction, which is a ketone. Thie first part of the product is the complex with aluminum chloride as shown:
The final step involves the addition of water to liberate the final product as the acylbenzene:
Because the acylium ion (as was shown in step one) is stabilized by resonance, no rearrangement occurs (Limitation 1). Also, because of of the deactivation of the product, it is no longer susceptible to electrophilic attack and hence, is no longer susceptible to electrophilic attack and hence, no longer goes into further reactions (Limitation 3). However, as not all is perfect, Limitation 2 still prevails where Friedel-Crafts Acylation fails with strong deactivating rings.
How would you make the following from benzene and an acid chloride?
Contributors and Attributions
Prof. Steven Farmer (Sonoma State University)
- Mario Morataya (UCD)
- James Kabrhel (University of Wisconsin - Green Bay, Sheboygan Campus)