Nucleophilic Substitution @ Carbonyl

Question 1

3 major factors determining mechanism operation

Answer 1

1. strength of incoming nucleophile (Nu: identity and pKa of conjugate acid)
   good nucleophiles are poor leaving groups (high pKa, species readily forms new bonds to hydrogen and readily form bonds to carbon, won’t lose a proton easily)
2. carbonyl group reactivity (C ∂+ strength)
   - inductive effect - WITHDRAWAL
   O (3.5) > Cl (3.0) = N (3.0)
   conjugation effect means acyl chloride and amide aren’t same reactivity
   - conjugative effect - DONATION
3. LGA (X- identity and pKa of conjugate acid (pKaH))

Question 2

hydride reducing agents

Answer 2

earlier discussed NaBH4 used to reduce ketones/aldehydes

sodium borohydride not universally possible with all carbonyl derivatives

Question 3

acid chloride/anhydride reduction to alcohol with NaBH4

Answer 3

use mildest possible reagent in lab
more reactive than ketones
need 2 EQUIVALENTS of hydride overall to furnish alcohol products

Question 4

acids speed up hydrolysis by…

Answer 4

protonating carbonyl oxygen making it more susceptible to nucleophilic attack
protonating leaving group, lowering its pKa and making it a better leaving group

Question 5

bases speed up hydrolysis by…

Answer 5

being/ creating a negatively charged nucleophile (more reactive)
deprotonating carboxylic acid product - pulls eqbm irreversibly over towards hydrolysis products