Protecting Groups

by James

Sometimes, having multiple functional groups on a molecule can interfere with a reaction we wish to perform. So we need some chemical means of “putting it out of the way”. Kind of like when you’re painting a wall and you come to an electrical outlet. The painter’s solution is to cove the outlet with tape, paint the wall, and then remove the tape when the job is done. It’s more effective than just being “really, really careful”.

In chemistry we have equivalents of painter’s tape. They’re called “protecting groups”.

There are two common situations that arise when protecting groups are necessary, although this is by no means exhaustive.

The first situation is when we have a species with an acidic hydrogen (such as OH or COOH) in the presence of an electrophilic carbon (such as an alkyl halide or carbonyl). Acid base reactions are fast, relative to attack at carbon (due to steric hindrance), and they will occur first. So if a nucleophile is basic, the first equivalent of nucleophile will be used just deprotonating the acidic hydrogen. Sometimes, that can itself cause problems (see the example below). In cases like this, we can simply protect the alcohol (with trimethylsilylchloride (TMSCl)  for example) – do the reaction, and then remove the TMS when we are finished.

A second important functional group that occasionally needs protection is the carbonyl. Carbonyl carbons can be attacked by strong nucleophiles (such as Grignard reagents) as well as by oxidants and reductants. Sometimes that will lead to undesired byproducts, such as when we are trying to make a Grignard reagent from a molecule containing a ketone. In cases like these, it is best to protect the ketone as an acetal, using alcohol and acid. Then, we can make the Grignard reagent without worrying about it reacting with the ketone. When our Grignard is done, then we can deprotect the acetal with aqueous acid, and we’re done.

Thanks for reading!

James

 

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