Nitrogen Containing Heterocycles 3 Membered Ring 12272021 1

Nitrogen Containing Heterocycles ü 3 -Membered Ring 12/27/2021 1

Nitrogen Containing Heterocycles ü 3 -Membered Ring in our system? ü How do these work? 12/27/2021 2

Higher Heterocycles Containing Nitrogen ü Basic Ring Systems ü Acid – Base Properties Ist p. KA ? IInd p. KA ? ü Stability to Water, Acid and Base Without substituents ? With substituents ? 12/27/2021 3

Higher Heterocycles Containing Nitrogen ü Examples of Drugs … 4 -membered ring ü Importance of b-lactam ring in activity …… generation of resistance!! 12/27/2021 4

Higher Heterocycles Containing Nitrogen ü Examples of Drugs … 5 -membered ring (anti-hyperlipidemic agent) (anti-histaminic) 12/27/2021 5

Higher Heterocycles Containing Nitrogen and Another Heteroatom ü Five membered Rings ü Acid – Base Properties Ist p. KA ? IInd p. KA ? Why is imidazole not basic ? p. KA with greater substitution ? ü Stability to Water, Acid and Base Without substituents ? With substituents ? 12/27/2021 6

Higher Heterocycles Containing Nitrogen and Another Heteroatom ü Examples of such heterocycles in Drugs (anti-biotic agent) 12/27/2021 (anti-biotic agent) (pain medication) 7

Heterocycles Containing Sulfur ü Basic Ring Systems ü Examples in Drugs (Antihistamine) 12/27/2021 (Antibiotic) (Antimalarial) 8

Complex Heterocycles ü Examples in Drugs (Antibiotic) (Antihypertensive) (for pneumonia) (Anti-infectious) 12/27/2021 (Antihypertensive) (Anti-seizure) 9

6 Membered Nitrogen Containing Heterocycles ü Examples in Drugs 12/27/2021 10

Barbiturates / Barbituric Acids (Keto form) p. KA = ~4 (Enol form) 12/27/2021 Phenytoin (anti-psychotic) 11

Heterocycles ü More Complex Unsaturated Ring Systems Ø 6 -membered and higher heterocycles 12/27/2021 12

Heterocycles ü More Complex Unsaturated Ring Systems Ø 6 -membered and higher heterocycles Azepine 12/27/2021 diazepine oxazepine 13

7 and 8 Membered Nitrogen Containing Heterocycles 12/27/2021 14

Heterocycles ü Electrophilic Aromatic Substitution in Heterocycles Ø heterocycles generally react well with electrophiles; better than benzene (except for pyridines) Ø their stability to metabolic enzymes is generally lower than their carbocyclic analogs Ø EAS occurs at the 2 -position of 5 -membered heterocycles Ø EAS occurs at the 3 -position of 6 -membered heterocycles 12/27/2021 15