Aromatic HYdroxylation

Question 1

What is Phase 1 metabolism?

Answer 1

Chemically diverse small molecules are converted generally to more polar compounds

Question 2

What will Phase 1 metabolism generally be for a compound with a full benzene ring?

Answer 2

Aromatic Hydroxylation: The addition of OH to the benzene ring

Question 3

What are the enzymes involved in Aromatic Hydroxylation?

Answer 3

CYP family

Question 4

Describe the selectivity of Aromatic Hydroxylations:

Answer 4

The more electron rich the aromatic ring, the faster the aromatic hydroxylation.
Electron withdrawing groups on the benzene ring will decrease how electron rich the aromatic ring is, therefore decreasing the chance of Aromatic Hydroxylation taking place.

Question 5

Give examples of some electron withdrawing groups that could be attached to the benzene ring:

Answer 5

COOH, CN, Sulfonic acid (SOOOH), NH3+

weakly withdrawing: Cl, I, Br

Question 6

What would electron donating groups do to effect the selectivity of Aromatic Hydroxylations?

Answer 6

Electron donating groups would make the benzene ring more electron rich, and therefore more likely to undergo Aromatic Hydroxylation.

Question 7

Give some examples of Electron Donating Groups

Answer 7

OH, NH2, O-.

Weakly activating: CH3.

Question 8

What happens to a compound with more than one Benzene ring?

Answer 8

Generally, the more electron rich ring will undergo Aromatic Hydroxylation

Question 9

How would you slow down or block Aromatic Hydroxylation?

Answer 9

Substitute the aromatic ring with a ‘para-chlorine’ or ‘para-fluorine’ which will deactivate the ring.

Question 10

What are the positions including ‘para’ on a benzene ring?

Answer 10

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