Organic Chemistry 101, Part IV

In Part II of my Organic Chemistry series, I talked about the Mitsunobu reaction (For a refresher please check it out here Mitsunobu ). Now, in the example I talked about, they used pthalimide to displace an alcohol. Now the main reason that you would do this type of reaction, is so that you can convert an alcohol to a primary amine (a primary amine is only bonded to one carbon species and has two free hydrogens, a secondary amine is bonded to two carbons and a tertiary amin is bonded to three carbon species).

The way you go about this is you take your newly formed Phthalimide product and react it with hydrazine (rocket fuel, very explosive, also very nucleophilic) usually in ethanol and it reacts with your Pthalimide to give you a primary amine. (see below)



Well, I also thought that I would show you just how this process works. In organic chemistry, we draw arrows to show how the reaction takes place mechanistically (This is what we call a mechanism) . What I've drawn below is most likely what is happening within the reaction mixture. Hydrazine is very nucleophilic (which means that it has a lot of electron density) and will attack places that are very electrophilic (places that lack electron density). As you can see from the diagram below, hydrazine attacks the carbonyl carbon (carbonyl carbons are fairly electrophilic and you can add a variety of nucleophiles to them) forcing the electrons onto the oxygen. After a quick hydrogen transfer the electrons on the oxygen force the five membered ring open and then the other nitrogen in hydrazine can swing down and react with the other carbonyl, finally forcing out our desired primary amine.



Using this hydrazine reduction of Pthalimide to give you a primary amine is a fairly common method employed in Organic Chemistry. It's actually very hard to generate primary amines in other ways because they themselves are very nucleophilic and reactive. Once you have your primary amine in hand there are a variety of transformations that a medicinal chemist will employ to generate a variety of analogues. Such as reductive amination, carbonylation, sulfonylation, alkylation and a variety of others, perhaps in my next Organic Chem 101 I'll talk about the different things you can do with amines.

Anyway, I'm going to be doing this reaction today on my material so that I can generate a primary amine as a starting scaffold, to generate a variety of amine analogues.

Anyway, I hope you enjoyed todays Chemisty update. Any questions?