Addition of a Grignard reagent to an aldehyde or ketone gives a stable alkoxide, which can be protonated with acid to produce an alcohol (you met this reaction in Chapter 9). The same is not true for addition of an alcohol to a carbonyl group in the presence of base—in Chapter 6 we drew a reversible, equilibrium arrow for this transformation and said that the product, a hemiacetal, is formed to a significant extent only if it is cyclic. The reason for this instability is that RO− is easily expelled from the molecule. We call groups that can be expelled from molecules, usually taking with them a negative charge, leaving groups. We’ll look at leaving groups in more detail later in this chapter and again in Chapter 15.

●Leaving groups Leaving groups are anions such as Cl⁻, RO⁻, and RCO₂ ⁻ that can be expelled from molecules taking their negative charge with them.

So, if the nucleophile is also a leaving group, there is a chance that it will be lost again and that the carbonyl group will reform—in other words, the reaction will be reversible. The energy released in forming the C=O bond (bond strength 720 kJ mol⁻¹) makes up for the loss of two C–O single bonds (about 350 kJ mol⁻¹ each), one of the reasons for the instability of the hemiacetal product in this case. The same thing can happen if the starting carbonyl compound contains a potential leaving group. The unstable negatively charged intermediate in the red box below is formed when a Grignard reagent is added to an ester.

Again, it collapses with loss of RO− as a leaving group. This time, though, we have not gone back to starting materials: instead, we have made a new compound (a ketone) by a substitu tion reaction—the OR group of the starting material has been substituted by the Me group of the product. In fact, the ketone product can react with the Grignard reagent a second time to give a tertiary alcohol. Later in this chapter we’ll discuss why the reaction doesn’t stop at the ketone.

مواضيع ذات صلة

Oxidation of alcohols

?Secondary and tertiary alcohols: which organometallic, which aldehyde, which ketone

Making primary alcohols from organometallics and formaldehyde

Making carboxylic acids from organometallics and carbon dioxide

Using organometallics to make organic molecules

Halogen–metal exchange

Making organometallics by deprotonating alkynes

Organometallics as bases

How to make organolithium reagents

Making organometallics, How to make Grignard reagents

Organometallic compounds contain a carbon–metal bond

Lewis acids and bases