Heteroaromatic Chemistry- Indoles Flashcards
What is an indole
- A fused bicyclic heteroaromatic compound
- 10 pi-electron system
- Similarities to pyrrole Pka around 17
What do indoles look like and what that means
- C=C-NH looks like an enamine
- Indoles are electron rich
- Nitrogen lone pair unit is electron donating
Can indoles carry out SEAr
- Yes
- They are electron rich
- Only with C3 regiochemistry
Describe regiochemistry of SEAr indole reactions
- Only C3
2. Resonance for C3 only has 2 but both maintain the aromatic ring which is much more stable than resonance on C2
When can SEAr reactions occur on C2 position of indoles
- If the C3 position is already substituted
- But can’t occur directly
- Need 2 eq of electrophile
What are the consequences of the benzenoid ring system of an indole undergoing SEAr
- Would break the aromatic ring
2. Not favourable even with a lot of resonance
What are the two acidic protons in indole
- NH is most acidic
2. Adjacent H is also acidic, only observed if N-H is protected
How can you deprotonate the C-H bond
- Use of strong base- nBuLi and cold temp
2. Need to protect N
What can happen once the C-H bond has been deprotonated
- Easily trapped with electrophiles
2. Or transmetallate - swap with metal
How does disconnection of indoles work
- Two disconnections
- Between NH and adjacent CH and between C3 and aromatic
- Produces ketone and aromatic- aryl hydrazone(NH-NH2)
What is Fisher-Indole synthesis
- Preparation of indoles via treatment of aryl hydrazones with ketones
- Requires either Bronsted acid or Lewis acid
What is the Bartoli reaction
- Reaction of 2-substituted nitro arenes with excess vinyl grignards to prepare indoles
- Quick reactions
- Need ortho-substituent to ensure good yields
What is Leimgruber-Batcho
- Preparation of indoles from o-nitrotoluenes
