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
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