Aldehydes, Ketones & Carboxylic Acids - Nucleophilic Addition Reaction

Slide 1: Aldehydes, Ketones & Carboxylic Acids - Nucleophilic Addition Reaction

Introduction to nucleophilic addition reactions of aldehydes, ketones, and carboxylic acids
Nucleophile: A species that donates a pair of electrons to form a new covalent bond
Addition reaction: A reaction in which two reactant molecules combine to form a new product molecule
Nucleophilic addition reaction: A reaction in which a nucleophile adds to the carbon atom of a carbonyl group

Slide 2: Nucleophilic Addition Reactions of Aldehydes

Aldehydes have a carbonyl group (-C=O) at the end of the carbon chain
They undergo nucleophilic addition reactions due to the presence of a polar carbonyl group
The oxygen atom of the carbonyl group is partially negatively charged, attracting nucleophiles
Examples of nucleophilic addition reactions of aldehydes:
- Addition of hydrogen cyanide (HCN) to form a cyanohydrin
- Addition of sodium bisulfite (NaHSO3) to form a bisulfite adduct

Slide 3: Nucleophilic Addition Reactions of Ketones

Ketones have a carbonyl group (-C=O) in the middle of the carbon chain
They undergo nucleophilic addition reactions similar to aldehydes
The carbonyl group provides a partial positive charge on the carbon atom, attracting nucleophiles
Examples of nucleophilic addition reactions of ketones:
- Addition of Grignard reagents (RMgX) to form alcohols
- Addition of organolithium compounds (RLi) to form alcohols

Slide 4: Nucleophilic Addition Reactions of Carboxylic Acids

Carboxylic acids have a carbonyl group (-C=O) and a hydroxyl group (-OH)
They undergo nucleophilic addition reactions involving the carbonyl group or the -OH group
Examples of nucleophilic addition reactions of carboxylic acids:
- Addition of nucleophiles to the carbonyl group to form esters or amides
- Addition of strong reducing agents to reduce the carboxylic acid to an alcohol

Slide 5: Mechanism of Nucleophilic Addition Reactions

Nucleophilic addition reactions follow a specific mechanism
Step 1: Nucleophile attacks the carbonyl carbon atom, forming a tetrahedral intermediate
Step 2: Proton transfer or elimination of a leaving group occurs, regenerating the carbonyl group
The mechanism can involve acid catalysis, base catalysis, or be uncatalyzed

Slide 6: Acid-Catalyzed Nucleophilic Addition Reactions

Acid-catalyzed nucleophilic addition reactions involve an acidic catalyst, such as H2SO4 or HCl
The acid protonates the carbonyl oxygen, making it more susceptible to nucleophilic attack
Examples of acid-catalyzed nucleophilic addition reactions:
- Addition of water (hydration) to form geminal diols
- Addition of alcohols (acetal formation) to form acetals or ketals

Slide 7: Base-Catalyzed Nucleophilic Addition Reactions

Base-catalyzed nucleophilic addition reactions involve a basic catalyst, such as NaOH or KOH
The base deprotonates the nucleophile, making it more reactive towards the carbonyl group
Examples of base-catalyzed nucleophilic addition reactions:
- Addition of primary amines to form imines or enamines
- Addition of alcoholates (alkoxides) to form hemiacetals or acetals

Slide 8: Nucleophilic Addition of Cyanide (HCN) to Aldehydes and Ketones

Addition of HCN to aldehydes and ketones forms cyanohydrins
Cyanohydrins have a hydroxyl group (-OH) and a cyano group (-CN) on the same carbon atom
This reaction is catalyzed by acid, typically HCN in the presence of concentrated sulfuric acid (H2SO4)
Example: Addition of HCN to propanal produces (2-hydroxypropanenitrile) cyanohydrin

Slide 9: Nucleophilic Addition of Grignard Reagents to Aldehydes and Ketones

Grignard reagents (RMgX) are strong nucleophiles that add to the carbonyl group of aldehydes and ketones
The carbon atom of the carbonyl group is attacked by the alkyl or aryl group of the Grignard reagent
The resulting alcohol product contains the added group from the Grignard reagent
Example: Addition of phenylmagnesium bromide (C6H5MgBr) to benzaldehyde produces (1-phenylethanol)

Slide 10: Nucleophilic Addition of Organolithium Compounds to Ketones

Organolithium compounds (RLi) are strong nucleophiles that add to the carbonyl group of ketones
The carbon atom of the carbonyl group is attacked by the alkyl group of the organolithium compound
The resulting alcohol product contains the added alkyl group from the organolithium compound
Example: Addition of n-butyllithium (C4H9Li) to acetone produces (4-methyl-2-pentanol)

Slide 11: Nucleophilic Addition of Sodium Bisulfite (NaHSO3) to Aldehydes

Sodium bisulfite (NaHSO3) can add to the carbonyl group of aldehydes
This reaction generates a bisulfite adduct
The bisulfite adduct is used for the identification and purification of aldehydes
Example: Addition of sodium bisulfite to formaldehyde produces sodium hydroxymethanesulfonate

Slide 12: Nucleophilic Addition of Nucleophiles to Carboxylic Acids

Nucleophiles can add to the carbonyl group of carboxylic acids
This reaction forms esters or amides
The nucleophile replaces the hydroxyl group of the carboxylic acid
Examples: Addition of an alcohol to a carboxylic acid forms an ester
Addition of an amine to a carboxylic acid forms an amide

Slide 13: Reduction of Carboxylic Acids to Alcohols

Strong reducing agents can reduce carboxylic acids to alcohols
The carboxylic acid is converted to an aldehyde intermediate, which is further reduced to an alcohol
Examples of reducing agents: LiAlH4 (lithium aluminum hydride), NaBH4 (sodium borohydride)
Example: Reduction of ethanoic acid to ethanol using NaBH4

Slide 14: Mechanism of Acid-Catalyzed Nucleophilic Addition Reactions

In acid-catalyzed reactions, the acid donates a proton to the carbonyl oxygen
This protonation increases the electrophilicity of the carbonyl carbon atom
The nucleophile attacks the carbonyl carbon, forming an intermediate
Example: Acid-catalyzed hydration of an aldehyde to form a geminal diol

Slide 15: Mechanism of Base-Catalyzed Nucleophilic Addition Reactions

In base-catalyzed reactions, the base deprotonates the nucleophile, making it more reactive
The nucleophile attacks the carbonyl carbon, forming an intermediate
Example: Base-catalyzed addition of a primary amine to form an imine

Slide 16: Nucleophilic Addition of Water (Hydration) to Aldehydes and Ketones

Addition of water to aldehydes and ketones is called hydration
In the presence of an acid catalyst, a geminal diol is formed
The carbonyl oxygen is protonated by the acid catalyst, facilitating nucleophilic attack by water
Example: Hydration of propanal to form propan-2-ol (isopropanol)

Slide 17: Nucleophilic Addition of Alcohols (Acetal Formation) to Aldehydes and Ketones

Addition of alcohols to aldehydes and ketones is called acetal formation
In the presence of an acid catalyst, an acetal or ketal is formed
The carbonyl oxygen is protonated by the acid catalyst, facilitating nucleophilic attack by the alcohol
Example: Acetal formation of propanal with ethanol to form diethyl acetal

Slide 18: Nucleophilic Addition of Primary Amines to Aldehydes and Ketones

Addition of primary amines to aldehydes and ketones forms imines or enamines
The carbonyl oxygen is protonated by an acid catalyst, enhancing nucleophilic attack by the amine
The resulting imine or enamine retains the nitrogen substituent from the amine
Example: Addition of ammonia to propanal forms N-propyl propan-2-imine (propylamine)

Slide 19: Nucleophilic Addition of Alcoholates (Alkoxides) to Aldehydes and Ketones

Alcoholates or alkoxides (formed from alkoxides) can add to aldehydes and ketones
The carbonyl oxygen is deprotonated by a base catalyst, creating a more nucleophilic carbonyl group
The alcoholate attacks the carbonyl carbon, forming a hemiacetal or acetal
Example: Addition of sodium methoxide (NaOCH3) to propanal forms 1-methoxypropan-2-ol

Slide 20: Summary of Nucleophilic Addition Reactions

Nucleophilic addition reactions involve the addition of a nucleophile to the carbonyl group
Aldehydes, ketones, and carboxylic acids exhibit nucleophilic addition reactions
Acid-catalyzed and base-catalyzed mechanisms are commonly observed
Different nucleophiles can be used, such as HCN, Grignard reagents, organolithium compounds, etc.
These reactions are important in organic synthesis and can create a wide range of functional groups

Slide 21: Nucleophilic Addition of Amines to Carboxylic Acids

Primary and secondary amines can add to carboxylic acids to form amides
The carbonyl oxygen is protonated by an acid catalyst, enhancing nucleophilic attack by the amine
The resulting amide retains the nitrogen substituent from the amine
Example: Addition of ethylamine to ethanoic acid forms N-ethylacetamide

Slide 22: Nucleophilic Addition of Alcohols to Carboxylic Acids

Alcohols can add to carboxylic acids to form esters
The carbonyl oxygen is deprotonated by a base catalyst, creating a more nucleophilic carbonyl group
The alcohol attacks the carbonyl carbon, forming an ester
Example: Addition of methanol to ethanoic acid forms methyl ethanoate (ethyl acetate)

Slide 23: Example: Nucleophilic Addition of Sodium Bisulfite (NaHSO3) to Aldehydes

Sodium bisulfite (NaHSO3) reacts with aldehydes via nucleophilic addition
The bisulfite ion (HSO3-) attacks the carbonyl carbon, forming a bisulfite adduct
Addition of concentrated sulfuric acid (H2SO4) catalyzes the reaction
This reaction is used for the identification and purification of aldehydes
Example: Addition of sodium bisulfite to benzaldehyde forms hydroxymethylphenylsulfonate

Slide 24: Example: Nucleophilic Addition of Hydrogen Cyanide (HCN) to Ketones

Ketones react with hydrogen cyanide (HCN) via nucleophilic addition
The cyanide ion (CN-) attacks the carbonyl carbon, forming a cyanohydrin
This reaction is catalyzed by acid, typically HCN in the presence of H2SO4
Example: Addition of HCN to propanone forms 2-hydroxy-2-methylpropanenitrile

Slide 25: Example: Nucleophilic Addition of Grignard Reagents to Aldehydes

Grignard reagents (RMgX) react with aldehydes via nucleophilic addition
The alkyl or aryl group of the Grignard reagent attacks the carbonyl carbon, forming an alcohol
This reaction is typically carried out in anhydrous conditions
Example: Addition of phenylmagnesium bromide to propanal forms 1-phenylpropan-1-ol

Slide 26: Example: Nucleophilic Addition of Organolithium Compounds to Ketones

Organolithium compounds (RLi) react with ketones via nucleophilic addition
The alkyl group of the organolithium compound attacks the carbonyl carbon, forming an alcohol
This reaction is typically carried out in anhydrous conditions
Example: Addition of n-butyllithium to propanone forms 2-methylbutan-2-ol

Slide 27: Example: Nucleophilic Addition of Water (Hydration) to Ketones

Ketones undergo hydration when water is added in the presence of acid
The carbonyl oxygen is protonated by the acid catalyst, making it more susceptible to nucleophilic attack by water
This reaction forms a geminal diol
Example: Hydration of propanone forms 2,2-dimethyl-1,3-propanediol

Slide 28: Example: Acid-Catalyzed Nucleophilic Addition of Alcohols (Acetal Formation) to Ketones

Ketones undergo acetal formation when alcohols are added in the presence of acid
The carbonyl oxygen is protonated by the acid catalyst, facilitating nucleophilic attack by the alcohol
This reaction forms an acetal
Example: Acetal formation of propanone with ethanol forms 1,1-diethoxypropane

Slide 29: Example: Base-Catalyzed Nucleophilic Addition of Primary Amines to Ketones

Ketones react with primary amines in the presence of a base catalyst to form imines
The carbonyl oxygen is deprotonated by the base catalyst, enhancing nucleophilic attack by the amine
This reaction forms an imine and water
Example: Addition of ethylamine to propanone forms N-ethylpropan-2-imine

Slide 30: Example: Base-Catalyzed Nucleophilic Addition of Alcoholates to Ketones

Ketones undergo nucleophilic addition with alcoholates in the presence of a base catalyst
The carbonyl oxygen is deprotonated by the base catalyst, creating a more nucleophilic carbonyl group
This reaction forms a hemiacetal or acetal
Example: Addition of sodium ethoxide to propanone forms 1,1-diethoxypropane