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Simon Muller
Simon Muller

 “Stop using protection, it’s producing way too much waste!” What a sentence to start with, right? But no worries, I don’t mean to start questionable arguments against contraceptives-

I’m talking organic synthesis here.

Protecting groups are groups used in organic chemistry that protect a part of a molecule that would otherwise be vulnerable to the conditions of a reaction. They are however a bit like the huge amounts of plastic used for packing items in supermarkets. They’re there for a good reason, but you’d really prefer to avoid them. In organic chemistry protecting groups are also useful, but they produce waste, take time and consume energy (in a huge chemistry factory an important aspect!).

 

It’s not that bad with protecting groups ;)

In organic synthesis chemists produce complex molecular structures by putting one piece onto another. It is a bit like playing Lego back when you were a child. Put one brick on another until you produce huge and beautiful structures.

This is also why organic chemistry is so much fun ;)

 

In this process protecting groups work like this: you have a molecule with several reactive features (say, a blue and a red Lego brick) and you want to add a yellow brick  onto the red brick.  However, in chemistry you cannot just take one molecule and put it on another; it’s more like letting the yellow brick fall down  50 metres  from  the sky and hoping  it will attach  onto  the red brick  and not to blue one. One possible solution is to put a cap on the blue brick,  so that the yellow brick  cannot dock onto the blue brick  anymore.

In organic chemistry such a cap is called Boc, Fmoc, MOM or more generally: a protecting group.

 

Organic chemistry in Lego-style! Many bricks;  how do you connect the right ones?

Why are protecting groups a problem then?

In principle they are great: they give access to the desired transformation while keeping other functionalities intact. In a research lab this is actually all right. You’ll need a bit more time for the protection and deprotection step (you have to take the cap away after the reaction so that your blue brick is free to be used again) but they won’t be a major concern. However, when you do real chemistry on an industrial scale, the amount of waste produced and energy consumed in the necessary protection and deprotection steps are enormous.

So what’s a more sustainable solution to the problem of having two (or more) reactive functional groups but desiring a specific reaction with just one of them?

 

There are several strategies to avoid the use of protecting groups.

1.)    Plan your synthetic route

(the plan in what order you put your Lego pieces together) in a manner in which you introduce highly reactive, vulnerable parts as late as possible. So you don’t have to protect them.

2.)    Find methods which are mild and selective.

This means developing  methods in which the yellow brick  can only dock onto the red one, maybe by making the red brick  more accessible than the blue one. Catalysts are being designed for this very purpose, bringing in new selectivity u under mild reaction conditions.

3.)    Tune these catalysts

so that they even react with the red brick  if they would normally always prefer to react with the blue one.

Why did I choose to put the third aspect aside from the second although they are very similar? I decided to put it apart because for an organic chemist it has very counter-intuitive consequences.

During all the time of our studies we learn why some functional parts are more reactive than others. But  recently researchers have shown on several beautiful examples that you can turn the reactivity around with some smart tricks. It’s like convincing the Lego playing child who loves fries (or chips, as we call them in the UK) more than anything else that actually peas and carrots would be a much better lunch today.

 

For those of you who have already had some insights into organic chemistry check out this microreview -it’s  a very beautiful example.

 

Protecting groups will surely stick around for a while. In  some areas there is no proper replacement for them so far. However, the deeper understanding of catalyst design and versatile reactivity can provide new, creative strategies to avoid protecting groups and with them, a lot of chemical waste.