Nucleophilic substitution at carbonyl groups

Question 1

What types of carbonyls undergo nucleophilic Acyl substitution at the carbonyl?

Answer 1

Carboxylic acids, acyl halides, anhydrides. Esters, and amides.

Question 2

Why is nucleophilic acyl substitution subject to acid catalysis?

Answer 2

Protonation of the oxygen gives a more strongly electrophilic (+) carbon.

Question 3

What is the stereochemistry effect of nuc acrylic substitution?

Answer 3

Original stereochemistry is retained.

Question 4

What is the order of carboxylix acid derivatives in terms of reactivity and why?

Answer 4

Acid chlorides > anhydrides > esters > amides > carboxylates due to effects of basicity of leaving groups and resonance stailizationnn of of reactant (if undergoing NAcylS cause loss of res, mol is less reactive.)

Question 5

What is the expected product of and ester reacted with an organilithium/grignard?

Answer 5

A tertiary alcohol - organolith reacts twice because the ketone formed by the first addition is more reactive than the original ester.

Question 6

What type of reagent can be used to form a ketone from an acid derivative?

Answer 6

Organocuprate, only adds once

Question 7

What factors affect reactivity of acids?

Answer 7

Steric hinderence - bulky groups slow down Rxn. Electronic effects - electron-withdrawing groups increase + charge on carbonyl carbon.

Question 8

When is thionyl chloride used in nucleophilic acyl substitution?

Answer 8

When the reactant’s leaving group is a stringer base than the nucleophile - like Acids + alkoxides