Aromatic - Pyridine¶
Pyridine is:
- Unreactive to EAS
- Reactive to NAS
- Electron deficient
- Has Lewis basic/nucleophilic LPE
The LPE¶
At its most basic level, the LPE are Lewis basic and can be used catalytically, such as with bromination
Mechanism
In this exmaple, the bromine is undergoning EAS with benzene, hwich requires catalysis
PTB¶
This is actually quite common usage and is sold as pyridinium tribromide, which is a solid, stable crystalline substance, which makes it easier to handle and weigh out
PCC¶
This is also used in the oxidising agent pyridinium chlorochromate (PCC)
Acylation¶
It can also be used as a better leaving group than chlorine for acylation (or more generally, esterification), as it’s more active that it’s acyl chloride counterpart.
DMAP¶
This is further exploited by adding a dimethyl group ortho to the pyrolidinium, as the nitrogen can donate its LPE to make the new acyl group more weakly bonded.
Alkylation¶
More generally, the pyridine can be alkylated by any bromoalkyl compound
Pyridinium Ion¶
Once in its ionic form, the ring becomes so electron deficient that normal alkene chemistry can be performed, such as reducing, oxidising ans hydrogenating it
It also becomes active to simple organometallic addition and can easily be oxidised back to pyridines
Pyridine-N-oxides¶
Are a really clever way of activating pyridines, as it will activate them to EAS (since they can’t undergo EAS normally). This re-introduces Friedel-Crafts acylation, nitration and other useful EAS reactions.
Activation¶
Because the oxygen can donate an electron or the nitrogen can accept one, the n-oxides are active to both EAS and NAS
So they can undergo reactions like nitrations, with the oxygen directing o/p, facilitated by the donation of the LPE
Once the desired EAS reaction has occurred, the oxide can be removed cleanly
Warning
While this will remove the oxygen, however it will also add in a halide, meta to the nitrogen, as shown below
Another useful reaction of the N-oxides is that they can add a chloride ortho to the nitrogen. This conveniently also consumes the oxide in the process
Important Chemistry
The synthesis of the analgesic niflumic acid is another synthesis that uses the N-oxide to facilitate a chlorination that allows for NAS to be directed cleanly.
