Heterocyclic Chemistry

Question 1

What are heterocyclic compounds?

Answer 1

heterocyclic compounds are ring systems with at least one heteroatom

heteroatom - oxygen, nitrogen or sulphur

Question 2

What is the structure of pyridine?

Answer 2

is a planar 6 membered aromatic ring with 5 sp2 carbons and 1 sp2 nitrogen atom

Question 3

How does the nitrogen atom affect pyridine?

Answer 3

the lone pair of the nitrogen lies in the plane of the ring but does not contribute to aromaticity
- is not included in the 6 pi electrons of the aromatic ring

is vital for the basicity of the molecule
- can act as a base and accept protons to form a pyridinium ion

Question 4

Why is pyridine less reactive than benzene?

Answer 4

the inductive effect of the nitrogen atom distorts the pi electrons towards the nitrogen atom
- makes it less reactive

Question 5

What reactions can/cannot pyridine undergo?

Answer 5

cannot
- friedal crafts = acylation/alkylation cannot occur, only occurs for reaction with anhydrides or weak lewis acids

can
- bromination, sulfonation, nitration = only under forced conditions such as high temperatures and use of a catalyst

• electrophilic substitution = at C3 and C5 due to these carbons having high electron density
• nucleophilic substitution = at C2 and C4 due to these carbons having low electron density

Question 6

At what carbons on pyridine does EAS take place?

Why does it take place at these specific carbons?

Answer 6

it takes place at C3 and C5

• these carbons have a greater electron density compared to C2, C4 and C6
• C2, C4 and C6 form the unstable nitrenium ion = has high activation energy

Question 7

Why is nucleophilic substitution possible for pyridine? At what carbons does it take place?

Answer 7

it is possible because pyridine is an electron/pi deficit compound

it takes place at C2, C4 and C6
- have low electron density so are attractive to nucleophiles

Question 8

What is a good nucleophile?

Answer 8

have a lone pair
have high basicity
have a large atomic size

Question 9

Why is nucleophilic substitution at C2,C4 and C6 favoured over reactions at C3 and C5?

Answer 9

C2, C4 and C6 form a stable nitrogen anion while C3 and C5 do not
- makes the reaction favourable

Question 10

What are the different heterocyclic five membered rings?

Answer 10

contain heteroatom which are all sp2 hybridised

pyrrole - R is NH
furan - R is O
thiophene - R is S

Question 11

What is the difference in chemistry between benzene and pyridine?

Answer 11

Benzene typically undergoes electrophilic substitution

Pyridine undergoes nucleophilic substitution and electrophilic substitution only under extreme conditions.

Question 12

Which of the five membered heterocyclic rings are electron rich?

Answer 12

pyrrole

thiophene

Question 13

What is the chemistry and structure of pyrrole?

Answer 13

is electron rich
- reacts readily with electrophiles

EAS occurs at C2 (compared to pyridine where EAS occurs at C3 and C5)

Question 14

How is pyrrole synthesised?

Answer 14

is commonly synthesised by the Paal-Knorr Synthesis

is prepared from

• 1,4-dicarbonyl compounds
• a nitrogen atom derived from either ammonia or a primary amine

Question 15

How is furan synthesised?

Answer 15

is commonly synthesised by the Paal-Knorr Synthesis

is prepared from

• 1,4-dicarbonyl compounds
• an oxygen atom derived from one of the carbonyls

is catalysed by either
- a mineral acid (sulphuric acid) OR a lewis acid (zinc chloride)

Question 16

What is the order of reactivity of furan, thiophene and pyrrole? Why is this the order?

Answer 16

order of reactivity (highest to lowest)
pyrrole, furan, thiophene

thiophene is the least reactive because its lone pair is in 3p orbital not the 2p orbital
- meaning there is less overlap with the p-orbitals of the carbon
= less delocalisation, less electron rich