Chapter 7: Nucleophilic Addition

Learning Objectives
By the end of this section, you should be able to apply concepts related to basic organic techniques
such as:

• Explain the chemical reactivity of carbonyl compounds and predict the products of the reactions they
undergo
• Outline the reaction mechanism of nucleophilic addition of hydrides and cyanides on carbonyl
compounds
• Predict the products/ starting materials of the reactions of carbonyl compounds with hydrides and
cyanides.

Chemical reactivities of carbonyl compounds

 There are two kinds of reactions that carbonyl compounds undergo:

Reactions at the carbonyl carbon Reactions at the α carbon (Not in syllabus)

- The carbonyl carbon (C=O) is electrophilic as it is
electron deficient (unsaturated), due to the highly
electronegative oxygen atom
- Therefore it is susceptible to nucleophilic addition by
hydrides (H-) and cyanides (CN-)
- Involves the C-H bond at the α-carbon which is more
acidic than many other C-H bonds.
- A carbanion (enolate) is formed when an α-H is
abstracted, which can then attack an electrophile

General mechanism:

1. Nu (H- or CN-) attacks the electrophilic C of the

carbonyl (C=O) group and breaks the π bond
2. The intermediate alkoxide is formed
3. Protonation of the alkoxide intermediate to give an
alcohol derivative

Addition of hydride H- (Reduction)
Nucleophile:
- H- nucleophiles from reducing agents metal hydrides to carbonyl compounds
Sodium borohydride (NaBH4)
Mechanism for nucleophilic addition of aldehydes / ketones:
Step 1
- NaBH4 is weaker than LiAlH4
- Nucleophilic attack: H- from NaBH4 selectively
attacks electrophilic C of C=O in:
- Aldehydes  primary alcohols
- Ketones  secondary alcohols
- Results in the breakage of π bond and a new
C-H bond is formed
NOTE: H- alone does NOT exist, you have to write
it as NaBH4/ LiAlH4
Step 2
- Acid/ water/ alcohol is added as a source of H +
for protonation
- Protonation: O- of alkoxide intermediate
accepts a proton from acid/(H2O/H+) / alcohol
Electrophilic Addition
Addition of cyanide
Nucleophile:
- Cyanide (CN-) nucleophile from NaCN/KCN to carbonyl
compounds
Lithium aluminium hydride (LiAlH4)
Mechanism for nucleophilic addition of carbonyl compounds:
Step 1 Step 1
- Nucleophilic attack: CN- from NaCN is added and is able to
attack electrophilic C of C=O
- Results in the breakage of π bond and a new C-H bond is
formed
- LiAlH4 is stronger than NaBH4
Step 2
- Nucleophilic attack: H- from LiAlH4 is able to attack
- HCN or any acid is added as a source of H+ for protonation
electrophilic C of C=O in:
- Protonation: O- of alkoxide intermediate accepts a proton
- Aldehydes  primary alcohols
from HCN results in the cyanohydrin product
- Ketones  secondary alcohols
- Carboxylic acids  primary alcohols (no need Step 3 (Possible)
to know mechanism) - The cyanohydrin formed can further react with:
- Amides  amines (no need to know - H2O/ H+ and heat to give -COOH
mechanism) - 1) LiAlH4 2)H2O or H2/ Ni to give CH2NH2
- Results in the breakage of π bond and a new C-H
bond is formed
Step 2
- Acid/ water/ alcohol is added as a source of H + for
protonation
- Protonation: O- of alkoxide intermediate accepts a
proton from acid/ (H2O/H+) / alcohol