Nucleophilic substitution at carbonyl Flashcards
What can esters be formed from?
Acid chlorides
Acid anhydrides
How can acid anhydrides be made from acid chlorides?
If carboxylate is the nucleophile
What nucleophile is required for the formation of amides?
Amine
What does the stability of the tetrahedral intermediate depend on?
How good a leaving group X- is
What makes a good leaving group?
Most electronegative is the most stable as a negative charge
What can the leaving group ability of X- be judged by?
How strong an acid HX is
How does acid strength affect leaving group ability?
Strong acids HX readily dissociate to give X-, so X- must be relatively stable and a good leaving group
How does pKaH relate to leaving group ability?
The lower the pKaH, the better the leaving group
What tends to be the best leaving group?
Cl-
pKaH = -7
How does pKaH relate to the strength of the molecule as a nucleophile?
The higher the pKaH, the better the nucleophile
What is the most electrophilic carboxylic acid derivative and why?
Acid chloride
Most electronegative Cl- makes C=O more delta positive
What is the least electrophilic carboxylic acid derivative and why?
Amide
Inductive electron withdrawal is less as nitrogen is less electronegative
What effect does protonation of the C=O have?
Makes the carbon more delta positive
What effect does protonation of the leaving group have?
Lowers pKaH and makes it a better leaving group
What type of reaction is acid catalysed ester hydrolysis?
Reversible
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