Heteroaromatic Chemistry- Pyrrole and friends

Question 1

Describe the structure of pyrrole

Answer 1

1. Replace HC=CH with N
2. NH is perpendicular - H is acidic
3. Lone pair donates in to maintain aromaticity

Question 2

What structure can pyrrole be compared to

Answer 2

1. Looks similar to enamine- opposite of pyridine

2. Pyrroles are electron rich- nitrogen lone pair is electron donating

Question 3

Can pyrrole undergo SEAr reactions

Answer 3

1. It is electron rich so SEAr is easy

Question 4

Describe regiochemistry for SEAr reactions in pyrrole

Answer 4

1. There is a choice as to where the substitution occurs
2. The stability of the intermediate is key
3. Also directed by the groups on pyrrole- EWG/EDG
4. Position 2 has extra resonance

Question 5

What are some problems with SEAr of pyrrole

Answer 5

1. 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

Question 6

How can you add a formyl group to pyrrole

Answer 6

1. SEAr Vilsmeier Formylation
2. N-methylformanilide + POCl3 = chloroiminium which is added to pyrrole
3. then add H2O

Question 7

What positions do EDG direct

Answer 7

1. Ortho/para

Question 8

What positions do EWG direct

Answer 8

1. Meta

Question 9

Which of furan, pyrrole and thiophene are most aromatic

Answer 9

1. Thiophene> pyrrole> furan

Question 10

Which of furan, pyrrole and thiophene are most reactive

Answer 10

1. Pyrrole> furan> thiophene

Question 11

What can you view furan as

Answer 11

1. Two enols

2. Behaves differently compared to other heteroaromatics

Question 12

What does the enol characteristics of furan mean

Answer 12

1. Under lightly acidic conditions can hydrolyse furan to produce 1,4-dicarbonyl

Question 13

What are the two acidic protons in pyrrole

Answer 13

1. N-H is most acidic- pKa= 16.5

2. H on C adjacent to N is also acidic pKa= 30

Question 14

When can the less reactive proton be observed

Answer 14

1. Only if N-H proton is protected

Question 15

How can the adjacent proton be removed in furan or thiophene

Answer 15

1. Use of strong base- nBuLi

2. Don’t need to protect as O and S instead of NH

Question 16

What can you do once deprotonated pyrrole, furan or thiophene

Answer 16

1. Can easily be trapped with electrophiles
2. Or transmetallate e.g. swap the metal
3. Makes them extremely versatile intermediates

Question 17

Describe pyrrole construction

Answer 17

1. Paal-Knorr synthesis

2. Treatment of 1,4-dicarbonyl’s with primary amine to form pyrroles

Question 18

Describe Furan construction

Answer 18

1. Treatment of 1,4-dicarbonyl’s with mineral acid and heat
2. Paal-Knorr synthesis
3. Lewis acid can be used

Question 19

Describe Paal-Knorr using primary amines

Answer 19

1. Add NH2R to 1,4-dicarbonyl
2. Diketones are most favourable
3. Need acid + heat

Question 20

Describe Paal-Knorr using a strong mineral acid/lewis acid

Answer 20

1. Add acid and heat

2. Causes dehydration

Question 21

Describe thiophene construction

Answer 21

1. Add P4S10 + heat and acid
2. Requires preparation of thioketone intermediate
3. Paal-knorr