Functional groups can be useful for putting a molecule together, but they aren’t always needed in the final product. We need ways of getting rid of them. Hydrogenation of alkenes is one way that you have seen. Hydrogenation of alkynes to alkanes is very useful because we can build long chains of carbon atoms by alkylating alkynes, then hide the evidence by hydrogenation:

Alcohols can be got rid of either by elimination to alkenes and then hydrogenation or by tosylation and substitution using borohydride to provide a nucleophilic hydrogen atom.

Removal of carbonyl groups is harder, although there are several possible methods. C–O bonds are strong, but C–S bonds are much weaker and are often easily reduced with Raney nickel. We can get rid of aldehyde and ketone carbonyl groups by making them into thioacetals, sulfur analogues of acetals, formed in a reaction analogous to acetal formation (see Chapter 11) but using a dithiol with a Lewis acid catalyst. Freshly prepared Raney nickel carries enough H₂ to reduce the thioacetal without added hydrogen.

A slightly more vigorous method, known as the Wolff–Kishner reduction, is driven by the elimination of nitrogen gas from a hydrazone. Hot concentrated sodium hydroxide solution deprotonates the hydrazone, which can then lose nitrogen to form an alkyl anion, which is immediately protonated by water.

The third method is the simplest to do, but has the most complicated mechanism. The Clemmensen reduction is also rather violent, and really reasonable only for compounds with just the one functional group. It uses zinc metal dissolving in concentrated hydrochloric acid. As the metal dissolves, it gives up two electrons—in the absence of something else to do, these electrons would reduce the H+ in the acid to H₂, and give ZnCl₂ and H₂. But in the presence of a carbonyl compound, the electrons go to reduce the C=O bond.

The mechanism has a good deal in common with a whole class of reductions, of which the Clemmensen is a member, known as dissolving metal reductions. We shall now look at these as our third (after metal hydrides and catalytic hydrogenation) important class of reducing agents.

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

Birch reduction of arenes

Dissolving metal reductions