[PDF] Chapter 9 Aldehydes and Ketones: Nucleophilic Addition Reactions PDF Chapter%209%20-%20Aldehydes%20and%20Ketones.pdf

1 Chapter 9 Aldehydes and Ketones: Nucleophilic Addition Reactions Carbonyl group, C=O: the most important and widely occurring functional group

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[PDF] Chapter 9 Aldehydes and Ketones: Nucleophilic Addition Reactions

1 Chapter 9 Aldehydes and Ketones: Nucleophilic Addition Reactions Carbonyl group, C=O: the most important and widely occurring functional group

[PDF] Reactions of Ketones and Aldehydes Nucleophilic Addition

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Oxidation of secondary alcohols yields ketones Aldehydes are very easily oxidized to carboxylic acids Nucleophific addition reactions to the carbon- oxygen

9.1 Chemistry of the Carbonyl Group

Carbonyl compounds are planar about the double bond and have bond angles of approximately 120 o Carbon-oxygen double bonds are polarized because of the high electronegativity of oxygen relative to carbon. Carbonyl carbon () - electrophilic (a Lewis acid), reacts with nucleophile. Carbonyl oxygen () - nucleophilic (a Lewis base), reacts with electrophile or acid.

9.2 Naming Aldehydes and Ketones

Aldehydes

1. Acyclic case:

Aldehydes are named by replacing the terminal -e of the corresponding alkane name with -al. The parent chain must contain the -CHO group, and the -CHO carbon is always numbered as carbon #1.

2. Cyclic case:

Attach the suffix -carbaldehyde to the name of cyclic structure.

Ketones

Ketones are named by replacing the terminal -e of the corresponding alkane name with -one. The parent chain is the longest one that contains the ketone group, and numbering begins at the end nearer the carbonyl carbon. ଖCarbonyl groups can be referred to as substituents using the general term acyl. RCO

An acyl group

CH 3 CO

Acetyl

H CO

Formyl

Ar CO Aroyl Ph CO

Benzoyl

9.3 Synthesis of Aldehydes and Ketones

1. Oxidation of alcohols

Primary alcohols are oxidized to give aldehydes by PCC in CH 2 Cl 2 Secondary alcohols are oxidized to give ketones. PCC, CrO 3 , and Na 2 Cr 2 O 7 can be used.

2. Hydration of a terminal alkyne

CH 3 (CH 2 3 CCHH 3 O

Hg(OAc)

2 CH 3 (CH 2 3 CCH 3 O 78%

3. Friedel-Crafts acylation

+ClO AlCl 3 O 95%

9.4 Oxidation of Aldehydes

Aldehydes are easily oxidized to carboxylic acids, but ketones are unreactive towards oxidation. This reactivity difference is a consequence of structure: aldehydes have a -CHO proton that can be removed during oxidation, but ketones do not. Tollen's test: to detect the presence of an aldehyde functional group in a molecule by oxidizing it with Ag in dilute aqueous ammonia. A shiny mirror of silver metal is deposited on the walls of the test tube. Oxygen in air can also convert aldehyde into carboxylic acids. Sunlight promotes this reaction.

9.5 Nucleophilic Addition Reactions of Aldehydes and Ketones

A nucleophile adds to the electrophilic carbon of the carbonyl group.

Nucleophiles - hydride (H:

, reduction), H 2

O (hydration), ROH (acetal formation),

RMgX (Grignard addition), RNH

2 (imine formation).

Mechanism

Acidic condition

OHA OH A

Nu HOH

Nu H AOH NuHA Step 1. The carbonyl group is protonated by an acid, H-A. Step 2. A neutral nucleophile NuH attacks the electrophilic carbon, pushing electrons from the C=O bond onto oxygen and neutralizing the positive charge.

Step 3. A base removes H

from the nucleophile to give a neutral addition product.

2. Basic condition

O Nu NuOHA OH Nu

Step 1. A negatively charged nucleophile Nu

attacks the electrophilic carbon and pushes electrons from the C=O bond onto oxygen. Step 2. The alkoxide ion is protonated, either by solvent or by added acid, to give a neutral addition product.

9.6 Reduction

Reducing agents: NaBH

4 , LiAlH 4 , NADH, NADPH etc. , NADPH: reduced nicotinamide adenine dinucleotide phosphateN O NH 2 H NAD NADP LiAlH

Mechanism

O HO OH H HMM H 3 O

9.7 Nucleophilic Addition of Water: Hydration

A nucleophilic addition reaction of H

O to yield 1,1-diols, geminal (gem) diols.

reversible, and the position of the equilibrium depends on the structure of the carbonyl compound. Equilibrium strongly favors the carbonyl The nucleophilic addition of water to aldehydes and ketones is slow in pure water but is catalyzed by both acid and base.

Base-catalyzed hydration

O OHOOH OH OHH 2 O+OH

Acid-catalyzed hydration

OHO OH OH 2 OH OOH OHH 3 O+HH H H OH 2 chap_09_01.ppt

9.8 Nucleophilic Addition of Alcohols: Acetal Formation

Aldehydes and ketones react with alcohols in the presence of an acid catalyst to yield acetals, R 2

C(OR')

2 Formation of hemiacetal - a carbon bearing both an OR group and an OH group. S N 1 All of the steps during acetal formation are reversible, and the reaction can be made to go either forward or backward, depending on reaction conditions following the Le

Chatelier principle.

The forward reaction is favored by conditions that remove water from the medium and thus drive the equilibrium to the right. The backward reaction is favored in the presence of an excess of water, which drives the equilibrium to the left.

9.9 The Importance of Hemiacetals and Acetals: Nature and the Laboratory

Hemiacetals and acetals in nature

Sugars (or carbohydrates) - Glucose, Cellulose, and Starch

Acetals in laboratory as protecting groups

Acetals are stable to bases, reducing agents, and various nucleophiles, but they can be cleaved by treatment with acid. OCH 3 OH 2 CH 3 OH H 3

CO OCH

1. LiAlH

4 2. H 2 OCH 2 OHH 3

CO OCH

3 H 3 O

9.10 Addition of Amines to Form Imines

Ammonia and primary amines, R'NH

2 , add to aldehydes and ketones to yield imines, R 2

C=NR',

Imines are formed by addition of the nucleophilic amine to the carbonyl group, followed by loss of water from the amino alcohol addition product. Bacillus subtilis prepares alanine from pyruvic acid and ammonia.

9.11 Nucleophilic Addition of Grignard Reagents: Alcohol Formation

The carbon-magnesium bond of a Grignard reagent is polarized so that the carbon atom is both nucleophilic and basic (carbanions: R

Grignard reagent

The reaction of Grignard reagents with aldehydes and ketones first produces a tetrahedral magnesium alkoxide intermediate, which is then protonated to yield the neutral alcohol on treatment with aqueous acid (irreversible process).

Primary alcohols from formaldehyde

MgBr HHO H 3 OCH 2 OH

65%Ether

Secondary alcohols from aldehydes

HO MgBr +H 3

OEtherOH

73%

Tertiary alcohols from ketones

CH 3 CH 2

MgBr+OH

OEtherOH

CH 2 CH 3 89%

Some limitations of the Grignard reaction

Grignard reagent reacts with the following groups: -CHO, -COR, -CO 2

R, -CONR

2 , -CN, -NO 2 , -SO 2 R Grignard reagent is destroyed by the acidic hydrogen from the following groups: -OH, -NH, -SH, -CO 2 H

9.12 Conjugate Addition Reactions

Conjugate (1,4) addition

-Unsaturated ketoneO NuO Nu O NuH 3 O NuO

HHSaturated ketone

134
21
4

Enolate ion

The initial product of conjugate addition is a resonance stabilized enolate ion, which typically undergoes protonation on the carbon to give a saturated ketone product. Nu: for the conjugate addition: RS , CN , R 2

CuLi, and stabilized carbanions.

chap_09_02.pptquotesdbs_dbs17.pdfusesText_23

[PDF] [PDF] Chapter 9 Aldehydes and Ketones: Nucleophilic Addition Reactions

9.1 Chemistry of the Carbonyl Group

9.2 Naming Aldehydes and Ketones

Aldehydes

1. Acyclic case:

2. Cyclic case:

Ketones

An acyl group

Acetyl

Formyl

Benzoyl

9.3 Synthesis of Aldehydes and Ketones

1. Oxidation of alcohols

2. Hydration of a terminal alkyne

Hg(OAc)

3. Friedel-Crafts acylation

9.4 Oxidation of Aldehydes

9.5 Nucleophilic Addition Reactions of Aldehydes and Ketones

Nucleophiles - hydride (H:

O (hydration), ROH (acetal formation),

RMgX (Grignard addition), RNH

Mechanism

Acidic condition

Nu HOH

Step 3. A base removes H

2. Basic condition

Step 1. A negatively charged nucleophile Nu

9.6 Reduction

Reducing agents: NaBH

Mechanism

9.7 Nucleophilic Addition of Water: Hydration

A nucleophilic addition reaction of H

O to yield 1,1-diols, geminal (gem) diols.

Base-catalyzed hydration

Acid-catalyzed hydration

9.8 Nucleophilic Addition of Alcohols: Acetal Formation

C(OR')

Chatelier principle.

9.9 The Importance of Hemiacetals and Acetals: Nature and the Laboratory

Hemiacetals and acetals in nature

Acetals in laboratory as protecting groups

CO OCH

1. LiAlH

CO OCH

9.10 Addition of Amines to Form Imines

Ammonia and primary amines, R'NH

C=NR',

9.11 Nucleophilic Addition of Grignard Reagents: Alcohol Formation

Grignard reagent

Primary alcohols from formaldehyde

65%Ether

Secondary alcohols from aldehydes

OEtherOH

Tertiary alcohols from ketones

MgBr+OH

OEtherOH

Some limitations of the Grignard reaction

R, -CONR

9.12 Conjugate Addition Reactions

Conjugate (1,4) addition

HHSaturated ketone

Enolate ion

CuLi, and stabilized carbanions.