Chemical Stability 1 Flashcards
Which group is very susceptible to hydrolysis?
Esters
What are examples of common groups susceptible to hydrolysis?
Ester
Lactone (cyclic ester)
Thioester
Amide
Imide
Lactam
Sulphate/phosphate ester
What do esters undergoes hydrolysis with?
Base or acid
What is the rate of hydrolysis in esters affected by?
pH
Temperature
Moisture content
Solubility
What are the factors affecting the rate of acid catalysed hydrolysis?
Steric effects reduce
rate
Electronic effects have limited influence
What are the factors affecting the rate of base catalysed hydrolysis?
Nature of both R1 + R2 groups
EDGs reduce rate
EWGs accelerate rate
Steric effects
Describe ester hydrolysis - acid
Initial protonation
H2O act as Nu- + attack carbonyl C
sp2 - sp3 - sp2
Produce leaving group (OH)
Acid catalyst regenerated with COOH
Are all the stages reversible in hydrolysis of esters - acid?
YES
Describe hydrolysis of esters - bases
Hydroxyl ion good Nu-
Negatively charged intermediate
sp2-sp3-sp2
OR- lost as leaving group
Hydroxyl ion consumed
Carboxylate product
Are all the stages in hydrolysis of esters - base reversible?
Final stage is NOT
Describe amides
Unreactive
LP on N stabilised
Resonance stabilisation strong
Describe acid catalysed hydrolysis of amide
Nu- attack on protonated carbonyl
Loss of H+ to solvent then protonation of amine
Acid catalyst created better LG
Describe base catalysed hydrolysis of amide
Nu- attack of hydroxide on carbonyl
Loss of LG + reformation of carbonyl
LG abstracts proton from acid
Carboxylate anion
What are examples of esters?
Aspirin
Diamorphine
What are examples of amides?
Paracetamol
Lidocaine
What are beta-lactams with 5-membered rings?
Penicillins
What are beta-lactams with 6-membered rings?
Cephalosporins
What is special about the beta-lactam ring?
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
What is special about the amide in the lactam ring?
Very sensitive to acid hydrolysis
What is special about the COOH in the lactam ring?
Does not behave as a normal carbonyl group = NOT resonance expected
Why does the beta-lactam ring ring hydrolyse quite easily?
No resonance stabilisation of COOH
= no forceful conditions needed
What is the lactam ring also sensitive too?
Primary alcohols
Amines
Hydroxylamine
Amino acids
What can penicillins be inactivated by?
Metal ions
What can metal ions do to penicillins?
Open ring
= benzylpenicilloic
= further decomposition = D-penicillamine
What is a Lewis acid?
Substance that accepts e- pair
What is a Lewis base?
Substance that donates e- pair
What do “Hard acids” prefer?
“Hard bases”
What do “Soft acids”?
“Soft bases”
