Heteroaromatic Chemistry- Pyrrole and friends Flashcards
Describe the structure of pyrrole
- Replace HC=CH with N
- NH is perpendicular - H is acidic
- Lone pair donates in to maintain aromaticity
What structure can pyrrole be compared to
- Looks similar to enamine- opposite of pyridine
2. Pyrroles are electron rich- nitrogen lone pair is electron donating
Can pyrrole undergo SEAr reactions
- It is electron rich so SEAr is easy
Describe regiochemistry for SEAr reactions in pyrrole
- There is a choice as to where the substitution occurs
- The stability of the intermediate is key
- Also directed by the groups on pyrrole- EWG/EDG
- Position 2 has extra resonance
What are some problems with SEAr of pyrrole
- Won’t stop at monobromination as so electron rich
2. Can’t do nitration or sulfonation as pyrrole would dimerise instead of SEAr because of acid
How can you add a formyl group to pyrrole
- SEAr Vilsmeier Formylation
- N-methylformanilide + POCl3 = chloroiminium which is added to pyrrole
- then add H2O
What positions do EDG direct
- Ortho/para
What positions do EWG direct
- Meta
Which of furan, pyrrole and thiophene are most aromatic
- Thiophene> pyrrole> furan
Which of furan, pyrrole and thiophene are most reactive
- Pyrrole> furan> thiophene
What can you view furan as
- Two enols
2. Behaves differently compared to other heteroaromatics
What does the enol characteristics of furan mean
- Under lightly acidic conditions can hydrolyse furan to produce 1,4-dicarbonyl
What are the two acidic protons in pyrrole
- N-H is most acidic- pKa= 16.5
2. H on C adjacent to N is also acidic pKa= 30
When can the less reactive proton be observed
- Only if N-H proton is protected
How can the adjacent proton be removed in furan or thiophene
- Use of strong base- nBuLi
2. Don’t need to protect as O and S instead of NH
What can you do once deprotonated pyrrole, furan or thiophene
- Can easily be trapped with electrophiles
- Or transmetallate e.g. swap the metal
- Makes them extremely versatile intermediates
Describe pyrrole construction
- Paal-Knorr synthesis
2. Treatment of 1,4-dicarbonyl’s with primary amine to form pyrroles
Describe Furan construction
- Treatment of 1,4-dicarbonyl’s with mineral acid and heat
- Paal-Knorr synthesis
- Lewis acid can be used
Describe Paal-Knorr using primary amines
- Add NH2R to 1,4-dicarbonyl
- Diketones are most favourable
- Need acid + heat
Describe Paal-Knorr using a strong mineral acid/lewis acid
- Add acid and heat
2. Causes dehydration
Describe thiophene construction
- Add P4S10 + heat and acid
- Requires preparation of thioketone intermediate
- Paal-knorr
