Chapter 19: Aldehydes and Ketones: Nucleophilic Addition Reactions

Carbonyl Group

The C=O bond is polar, as oxygen is electronegative and withdrawing electrons. So, a carbonyl carbon is an electrophile, and the oxygen is electron rich. Nucleophiles attack carbonyl carbons

Aldehyde Naming

1. Find longest chain containing the Aldehyde

2. Your aldehyde carbon is carbon #1

3. Ends in -al

Ketone Naming

1. Find the longest Carbon chain containing C=O

2. Number closes to carbonyl

3. Ends in -one

Preparing Aldehydes (Alcohol Oxidation: Primary alcohol —> Aldehyde )

Primary alcohol —> Aldehyde

Reagents: PCC & Dess-Martin Periodinane

It stops at aldehyde and does not overoxidize.

DIBAL Reduction (preparing an aldehyde)

makes an ester into an aldehyde. This is a partial reduction

Preparing Ketone (Alcohol Oxidation: Secondary alcohol —> Ketone)

see image

Friedel-Crafts Acylation

makes an aromatic ketone from Benzene + Acyl chloride

Gilman Reagents (used to make ketones)

Reagent: R2CuLi

Similar to Grignard but: Less reactive and does a substitution

Oxidations of Aldehydes

Aldehydes oxidize easily, and become carboxylic acids

Reagents:

• KMnO4

• CrO3/H +

• Na2Cr2O7/ H +

(PCC and Dess-Martin do not make carboxylic acids, they stop at aldehyde.)

Ketone Oxidation

Ketones are harder to oxidize. A strong oxidation with KMnO4 causes oxidative cleavage, which breaks C-C bonds. It produces Ketones & carboxylic acids.

Nucleophilic Addition

Aldehydes and Ketones undergo nucleophilic addition, not substitution, because aldehydes and ketones do not have leaving groups.

Nucleophilic Addition Mechanism

1. Nucleophile attacks carbonyl carbon (The C=O electrons move onto oxygen) This produces an alkoxide intermediate.

2. Protonation: O- grabs H+, produces an alcohol

Acid Conditions:

1. Carbonyl oxygen gets protonated first

2. Nucleophile attacks

Basic Conditions:

1. Nucleophile attacks first

2. Protonation second

A nucleophilic addition reaction to an aldehyde or ketone. The nucleophile approaches the carbonyl group from an angle of

approximately 75° to the plane of the sp2 orbitals, the carbonyl carbon rehybridizes from sp2 to sp3, and an alkoxide ion is

formed. Protonation by addition of acid then gives an alcoho

Why are aldehydes more reactive than ketones?

1. Sterics: Aldehydes have only one large group, making it less crowded. While ketones have 2 large groups, making it more crowded.

2. Electronegativity: Ketones have 2 electron donating alkyl groups, making the carbonyl carbon less positive (less reactive).

Aldehyde > Ketone reactivity

Nucleophilic Addition

see image

Nucleophile strength

Strong nucleophiles are:

• Negatively charged

• Atoms with lone pairs

Anions > neutral molecules

Aldehydes and Ketones can be electron withdrawing groups (meta-director deactivators) when

attached to a benzene ring (see image)

Hydration (adding water)

Reaction: Carbonyl + H2O —> Geminal Diol (Two OH groups on the same carbon)

Hydrates are geminal diols. Hydrates are favored when electron withdrawing groups are nearby

Cyanohydrin Formation

Reagent: HCN

Adds: CN + OH

Product: Cyanohydrin

Nitriles can become:

• Carboxylic acids

• amines

Alcohol Formation: Hydride Reduction

Reagents: NaBH4 or LiAlH4

Both add hydride (H-) to carbonyl.

Products: Aldehyde (primary alcohol) & Ketone (secondary alcohol)

LiAlH4 and NaBH4 do not reduce C=C bonds

Alcohol Formation: Hydride Reduction mechanism is a

Nucleophilic Addition

Note: Reductions maintain carbon skeleton

Alcohol Formation: Grignard Reactions

Reagent: RMgX

The carbon behaves like a nucleophile.

Grignard increases carbon skeleton

Alcohol Formation: Grignard Reactions Mechanism

1. Carbon attacks Carbonyl

2. Alkoxide forms

3. Acid workup protonates Oxygen

Product is an alcohol

Grignard increases carbon skeleton

Amine Reactions (Imines)

Primary amines making Imines

Reagent: RNH2

Product: C=N

Mechanism:

1. N attacks Carbonyl

2. Carbinolamine forms

3. Water leaves

4. Imine forms

Amine Reaction (Enamines)

Secondary amines make Enamines

Reagent: R2NH

Forms C=C-N (Enamine)

(Cannot make C=N because Nitrogen has no H to remove)

Oximes and Hydrazones

Carbonyl + Substituted amine forms derivatives

Used for identifying aldehydes/ketones and melting point analysis

Wolff-Kishner Reaction

Purpose: Carbonyl —> Alkane

Reagents: Hydrazine + Strong base

This removes Oxygen completely

Acetyl Formation

Carbonyl + Alcohol —> Acetal (two OR groups on the same Carbon, OR + OR)

Acetals are protecting groups. Used when you want to protect a carbonyl from reactions like an LiAlH4 reduction

Wittig Reaction

Purpose: Carbonyl —> Alkene

Reagent: Phosphorus Ylide

Changes a C=O to a C=C, driving force, phosphorus loves oxygen.

Cannizzaro Reaction

An aldehyde can oxidize and reduce itself with base catalysis

Conjugate Addition

For: α,β-unsaturated carbonyls

Two possible additions:

1,2 Addition

Direct attack at carbonyl carbon

Favored by:

Grignards (RMgBr)

1,4 Addition

Attack at β carbon

Favored by:

Gilman reagents

R₂CuLi

Product forms:

enolate → enol → ketone/aldehyde

Spectroscopy

IR:

Carbonyl C=O has a strong peak at 1700 cm-1

1 H NMR:

Aldehyde protons: 9-10 ppm

Carboxylic acid: 10 ppm

13 C NMR:

Carbonyl Carbon: 160-220 ppm

Mass Spec:

Alpha Cleavage: Major fragmentation near Carbonyl

McLafferty rearrangement: Occurs when Carbonyl compound has suitable hydrogen arrangement.

summary

see image