We shall start by looking at the dissolving metal reduction of aromatic rings, known as the Birch reduction. The margin shows the reaction of benzene with lithium in liquid ammonia. At first sight this reaction looks improbable, with an aromatic ring ending up as an unconju gated diene. The mechanism will explain why we get this regiochemistry, and also why the reaction stops there—in other words, why the dissolving lithium reduces an aromatic ring more readily than an alkene. The fi rst thing to note is that when lithium or sodium dissolve in ammonia they give an intense blue solution. Blue is the colour of solvated electrons: these group 1 metals ionize to give Li+ or Na+ and e−(NH₃) n. With time, the blue colour fades, as the electrons reduce the ammonia to NH₂ − and H₂. Birch reductions use those blue solutions, with their solvated electrons, as reducing agents. The reduction of NH3 to NH₂ − and H₂ is quite slow, and a better electron acceptor will get reduced in preference. With benzene, the electrons go into the lowest lying antibonding orbital (benzene’s LUMO). The species we get can be represented in several ways, all of them radical anions (molecules with one excess unpaired electron). The radical anion is very basic, and it picks up a proton from the ethanol that is in the reaction mixture.

The molecule is now no longer anionic, but it is still a radical. It can pick up another electron, which pairs with the radical to give an anion, which is quenched again by the proton source (ethanol). Overall we have arrived at two additional H atoms by sequentially adding two electrons plus two protons.

More questions of regioselectivity arise when there are substituents around the aromatic ring. Here are two examples.

These examples serve to illustrate a general principle:

• Electron-withdrawing groups promote ipso, para-Birch reduction.

• Electron-donating groups promote ortho, meta-Birch reduction.

The explanation must lie in the distribution of electron density in the intermediate radical anions. Electron-withdrawing groups stabilize electron density at the ipso and para positions, and protonation occurs para,

while electron-donating groups stabilize ortho and meta electron density:

If you want the conjugated dienes as products, it is quite a simple matter to isomerize them using an acid catalyst. In fact, a small amount (about 20%) of the conjugated product is pro duced anyway in the reaction of anisole above. With anilines, it is impossible to stop the isomerization taking place during the reaction, and Birch reduction always gives conjugated dienamines.

مواضيع ذات صلة

The Boc protecting group—gastrin and aspartame

The Cbz protecting group—oxytocin

Peptide synthesis

A survey of protecting groups

How to react the less reactive group (II): protecting groups

Chemoselectivity in the reactions of dianions

How to react the less reactive group (I): react both then ‘unreact’ one

Competing reactivity: choosing which group reacts

How to oxidize primary alcohols to aldehydes

How to oxidize secondary alcohols to ketones

Dissolving metal reductions

Getting rid of functional groups