Synthesis Topic 5 Flashcards
Why pyridine generally does not readily undergo elkectrophilic aromatic substitution?
Becasue if double bond breaks by reacting it will form a positive intermediate and using resonance positive charge can move on nitrogen that is electronegative. This destebalises positive charge.
Why pyridine usually reacts with Nitrogen lone pair?
When electrophile attackes at N them cationic intermediate is formed that is inert to further electrophilic attack. Also the N in the ring lowers the HOMO compares to benzene, making the ring electro deficient and less nucleophilic.
When pyridine does undergo electrophilic aromatic substitution. what is the favourable position?
Substitution is going to occur on the position that has the least electron-density drawn away from it. For pyridine it is meta position away from nitrogen
How can we make pyridine more active for electrophilic substitution?
By adding electron- donating groups to pyridine which would push electron density into the aromatic π system and increases nucleophilicity.
Or by converting pyridine to N-oxide. Oxygen acts as protecting group as it blocks reaction on nitrogen and as activating group as O electrons are delocalised around the ring: raises HOMO, increases nucleophilicity. Substutution will occur on para- and ortho- positions.
What can you use to turn pyridine into puridine N-oxide?
mCPBA or H2O2
Draw a reaction mechanism of pyridine N-oxide with HNO3 and H2SO4
How to remov O from pyridine N-oxide?
By reacting it with PPh3, and O=PPh3, strong O=P bong is formed
When quinoline and isoquinoline undergo electrophilic aromatic substitution on the more electron-rich benzene ring, which positions substituents usually take?
5 and 8
Suggest which products will be formes and provide a reaction mechanism.
Suggest which products will be formes and provide a reaction mechanism.
N readilly react with empty p orbital in Al.
Why reactivity rates are: pyrrole>furan> thiophene?
Because there is difference in electronegativities O> N> S
Why for 5-membered heteroaromatics attack on position 2 is prefered?
As at position 2 we can have 3 resonance forms amd at position 3 we can have just 2 resonance forms.
How pyrrole self polymerises?
Pyrrole in strong acid forms positive intermediate that can react with other pyrrole molecules.
What are the steps for Vilsmeier-Haak reaction?
1a. formation of the carbon electrophile
1b. electrophilic aromatic substitution
2. hydrolysis of the imine
What is the use of Vilsmeier-Haak reaction?
Pyrridine can be very reactive and substitute every H or polymerise itself, to prevent that we do a reaction without acid to form mono-formylate electron rich aromatics.
What is the reaction with pyrrole and POCl2 with Na2CO3, H2O?
How can we make reaction with pyrrole occur on the N?
By first reacting it with basic molecules to remove H, like K, KOH or DMSO.
Draw a reaction mechanism of furans reacting with Br2 and MeOH.
What happens when indole ring undergoes electrophilic substitution?
Pyrrole ring is more reactive than benzene ring. Thus pyrrole is attacking electrophile favouring 3-position not bresking the arromaticity of the benzene ring.
