Chemical Stability 1

Question 1

Which group is very susceptible to hydrolysis?

Answer 1

Esters

Question 2

What are examples of common groups susceptible to hydrolysis?

Answer 2

Ester
Lactone (cyclic ester)
Thioester
Amide
Imide
Lactam
Sulphate/phosphate ester

Question 3

What do esters undergoes hydrolysis with?

Answer 3

Base or acid

Question 4

What is the rate of hydrolysis in esters affected by?

Answer 4

pH
Temperature
Moisture content
Solubility

Question 5

What are the factors affecting the rate of acid catalysed hydrolysis?

Answer 5

Steric effects reduce
rate
Electronic effects have limited influence

Question 6

What are the factors affecting the rate of base catalysed hydrolysis?

Answer 6

Nature of both R1 + R2 groups
EDGs reduce rate
EWGs accelerate rate
Steric effects

Question 7

Describe ester hydrolysis - acid

Answer 7

Initial protonation
H2O act as Nu- + attack carbonyl C
sp2 - sp3 - sp2
Produce leaving group (OH)
Acid catalyst regenerated with COOH

Question 8

Are all the stages reversible in hydrolysis of esters - acid?

Answer 8

YES

Question 9

Describe hydrolysis of esters - bases

Answer 9

Hydroxyl ion good Nu-
Negatively charged intermediate
sp2-sp3-sp2
OR- lost as leaving group
Hydroxyl ion consumed
Carboxylate product

Question 10

Are all the stages in hydrolysis of esters - base reversible?

Answer 10

Final stage is NOT

Question 11

Describe amides

Answer 11

Unreactive
LP on N stabilised
Resonance stabilisation strong

Question 12

Describe acid catalysed hydrolysis of amide

Answer 12

Nu- attack on protonated carbonyl
Loss of H+ to solvent then protonation of amine
Acid catalyst created better LG

Question 13

Describe base catalysed hydrolysis of amide

Answer 13

Nu- attack of hydroxide on carbonyl
Loss of LG + reformation of carbonyl
LG abstracts proton from acid
Carboxylate anion

Question 14

What are examples of esters?

Answer 14

Aspirin
Diamorphine

Question 15

What are examples of amides?

Answer 15

Paracetamol
Lidocaine

Question 16

What are beta-lactams with 5-membered rings?

Answer 16

Penicillins

Question 17

What are beta-lactams with 6-membered rings?

Answer 17

Cephalosporins

Question 18

What is special about the beta-lactam ring?

Answer 18

Planar square ring = should be 90 degrees bond angle
BUT C is sp2 = 120 degrees
= very reduced
= LP cannot be pushed on to the O

Question 19

What is special about the amide in the lactam ring?

Answer 19

Very sensitive to acid hydrolysis

Question 20

What is special about the COOH in the lactam ring?

Answer 20

Does not behave as a normal carbonyl group = NOT resonance expected

Question 21

Why does the beta-lactam ring ring hydrolyse quite easily?

Answer 21

No resonance stabilisation of COOH
= no forceful conditions needed

Question 22

What is the lactam ring also sensitive too?

Answer 22

Primary alcohols
Amines
Hydroxylamine
Amino acids

Question 23

What can penicillins be inactivated by?

Answer 23

Metal ions

Question 24

What can metal ions do to penicillins?

Answer 24

Open ring
= benzylpenicilloic
= further decomposition = D-penicillamine

Question 25

What is a Lewis acid?

Answer 25

Substance that accepts e- pair

Question 26

What is a Lewis base?

Answer 26

Substance that donates e- pair

Question 27

What do “Hard acids” prefer?

Answer 27

“Hard bases”

Question 28

What do “Soft acids”?

Answer 28

“Soft bases”