The very first conjugate addition reaction in this chapter depended on the conditions of the reaction. Treating an enone with cyanide and an acid catalyst at low temperature gives a cyanohydrin by direct attack at C=O, while heating the reaction mixture leads to conjugate addition. What is going on?

We’ll consider the low-temperature reaction first , it is quite normal for cyanide to react with a ketone under these conditions to form a cyanohydrin. that cyanohydrin formation is reversible. Even if the equilibrium for cyanohydrin formation lies well over to the side of the products, there will always be a small amount of starting enone remaining. Most of the time, this enone will react to form more cyanohydrin and, as it does, some cyanohydrin will decompose back to enone plus cyanide—such is the nature of a dynamic equilibrium. But every now and then—at a much slower rate—the starting enone will undergo a conjugate addition with the cyanide.

Now we have a different situation: conjugate addition is essentially an irreversible reaction, so once a molecule of enone has been converted to conjugate addition product, its fate is sealed: it cannot go back to enone again. Very slowly, therefore, the amount of conjugate addition product in the mixture will build up. In order for the enone–cyanohydrin equilibrium to be maintained, any enone that is converted to conjugate addition product will have to be replaced by reversion of cyanohydrin to enone plus cyanide. Even at room temperature, we can therefore expect the cyanohydrin to be converted bit by bit to conjugate addition product. This may take a very long time, but reaction rates are faster at higher temperatures, so at 80 °C this process does not take long at all and, after a few hours, the cyanohydrin has all been converted to conjugate addition product. The contrast between the two products is this: the cyanohydrin is formed faster than the conjugate addition product, and is known as the product of kinetic control (or the kinetic product), but the conjugate addition product is the more stable compound and is the product of thermodynamic control (or the thermodynamic product). Typically, kinetic control involves lower temperatures and shorter reaction times, which ensures that only the fastest reaction has the chance to occur. And, typically, thermodynamic control involves higher temperatures and long reaction times to ensure that even the slower reactions have a chance to occur, and all the material is converted to the more stable compound.

● Kinetic and thermodynamic control

• The product that forms faster is called the kinetic product.

• The product that is the more stable is called the thermodynamic product. Similarly,

 • Conditions that give rise to the kinetic product are called kinetic control.

• Conditions that give rise to the thermodynamic product are called thermodynamic control.

Why is direct addition faster than conjugate addition? Well, although the carbon atom β to the C=O group carries some positive charge, the carbon atom of the carbonyl group carries more, and so electrostatic attraction for the charged nucleophiles will encourage it to attack the carbonyl group directly rather than undergo conjugate addition. And why is the conjugate addition product the more stable? In the conjugate addition product, we gain a C–C σ bond, losing a C=C π bond, but keeping the C=O π bond. With direct addition, we still gain a C–C bond, but we lose the C=O π bond and keep the C=C π bond. C=O π bonds are stronger than C=C π bonds, so the conjugate addition product is more stable. Practically, then, to get conjugate addition to occur you just have to give the reaction plenty of energy and maybe plenty of time to find its way to the most stable product. Here’s an example: note the temperature!

مواضيع ذات صلة

Conjugated alkenes can be electrophilic

Alkenes conjugated with carbonyl groups

Two reasons to avoid a Friedel–Crafts alkylation

Two or more substituents may cooperate or compete

Phenols react rapidly with bromine

Alkyl and acyl substituents can be added to a benzene ring by the Friedel–Crafts reaction

Sulfonation of benzene

Nitration of benzene

Benzene and its reactions with electrophiles

enols and phenols

Reactions of silyl enol ethers with halogen and sulfur electrophiles

Reactions of enol ethers Hydrolysis of enol ethers