Organic Chemistry - Aldehydes and Ketones

ORGANIC CHEMISTRY: Aldehydes and Ketones

Introduction

• Textbook: John McMurry, Organic Chemistry, Ninth Edition

• Chapter 19 Focus: Aldehydes and Ketones, specifically their nucleophilic addition reactions.

Naming Aldehydes and Ketones

• General Rules for Naming Aldehydes:

  • Aldehydes are named by replacing the terminal –e of the corresponding alkane name with –al.

  • The parent chain must contain the –CHO group, which is numbered as C1.

  • If the –CHO group is attached to a ring, the suffix used is carbaldehyde.

Common Names of Some Simple Aldehydes (Table 19-1)

• Formaldehyde (HCHO) - Methanal

• Acetaldehyde (CH3CHO) - Ethanal

• Acrolein (H,C=CHCHO) - Propenal

• Crotonaldehyde (CH3CH=CHCHO) - 2-Butenal

• Benzaldehyde - Benzenecarbaldehyde (CHO)

• General Rules for Naming Ketones:

  • The terminal –e of the alkane name is replaced with –one.

  • The parent chain is determined by the longest one that contains the ketone group.

  • Numbering begins at the end nearer to the carbonyl carbon.

Retained Names for Ketones

• IUPAC retains names for some ketones.

Acyl Groups as Substituents

• An acyl group is represented as R-C=O, and the suffix -yl is derived from the root of the carboxylic acid.

• The prefix oxo- is employed if there are other functional groups present and the doubly bonded oxygen is considered a substituent on the parent chain.

Worked Example: Structures from Names

• a) 3-Methylbutanal:

  • Structure drawn with appropriate functional groups.

• b) Cis-3-tert-Butylcyclohexanecarbaldehyde:

  • Structure depicts ring with substituents appropriately placed.

Preparing Aldehydes

• Methods of Preparation:

  • Oxidization of primary alcohols using Dess-Martin pyridinium reagent in dichloromethane solvent.

  • Partial Reduction of an ester with diisobutylaluminum hydride (DIBAH).

Mechanism of Aldehyde Formation

• Step 1: Coordination of oxygen to Lewis-acidic aluminum.

• Step 2: Addition of hydride to carbonyl carbon, breaking the π bond.

• Step 3: Addition of water in acidic workup, forming a stable hemiacetal at low temperatures before reaching the final aldehyde product.

Worked Example: Preparation of Pentanal

• Starting Materials:

  • a) Primary alcohol: CH3CH2CH2CH2CH2OH

  • b) Alkene: CH3CH2CH2CH2CH=CH2

  • Solution path requires main focus on transformation methods outlined above.

Preparing Ketones

• Methods of Preparation:

  • Oxidation of secondary alcohols.

  • Ozonolysis of alkenes yields ketones when one of the unsaturated carbon atoms is disubstituted.

  • Friedel-Crafts acylation of an aromatic ring using acid chlorides and AlCl3 catalyst.

  • Certain carboxylic acid derivatives can also give ketones.

Worked Example: Reactions to Form Ketones

• Examples:

  • a) From 3-Hexyne → 3-Hexanone.

  • b) From Benzene → m-Bromoacetophenone.

Oxidation of Aldehydes and Ketones

• Aldehydes oxidize to yield carboxylic acids.

• Oxidizing Agents:

  • CrO3 in aqueous acid: Efficient for oxidizing aldehydes to carboxylic acids.

  • Slow cleavage via hot alkaline KMnO4 for breaking the C–C bond adjacent to the carbonyl, leading to carboxylic acids.

Nucleophilic Addition Reactions

• Mechanism:

  • Nucleophile adds to the electrophilic carbon of the carbonyl group.

  • Electrons from the C=O bond shift to oxygen, forming an alkoxide ion intermediate.

  • Rehybridization of the carbonyl carbon from sp² to sp³.

  • Final product formation through protonation of the alkoxide anion.

Types of Nucleophiles

• Nucleophiles can be negatively charged (:Nu-) or neutral (:Nu).

Steric Hindrance in Reactions

• Nucleophilic addition to aldehydes is less hindered due to one large substituent on the carbonyl carbon; ketones involve two large substituents, increasing steric hindrance.

Electrophilicity of Aldehydes vs. Ketones

• Aldehydes are more polarized and thus more electrophilic due to fewer alkyl groups compared to ketones, consequently stabilizing the carbonyl carbon.

Reactivity of Aromatic Aldehydes

• Less reactive towards nucleophilic addition reactions than aliphatic aldehydes, as the carbonyl carbon in aromatic structures is less positive.

Hydration Reactions

• Aldehydes and ketones react with water to yield 1,1-diols (geminal diols), and this hydration process is reversible with equilibrium dependent on the structure of the carbonyl compound.

Cyanohydrin Formation

• Reaction with HCN: Aldehydes and unhindered ketones react to form cyanohydrins:

  • Mechanism involves the generation of the nucleophilic cyanide ion (CN-).

  • Formation of a tetrahedral intermediate which resolves to the cyanohydrin adduct.

  • Equilibrium favors the cyanohydrin.

Uses of Cyanohydrins

• The nitrile group can be reduced with LiAlH4 to form primary amines or hydrolyzed to yield carboxylic acids.

Alcohol Formation via Nucleophilic Addition

• Addition of hydride reagents results in alcohols from the reduction of carbonyl compounds:

  • Aldehydes yield primary alcohols upon reduction with NaBH4.

  • Ketones yield secondary alcohols due to similar reduction methodologies.

Grignard Reagents in Reactions

• Grignard reagents and hydride reagents (LiAlH4, NaBH4) facilitate the formation of alcohols through nucleophilic addition:

  • Tetrahedral intermediate formation and irreversible protonation yield the final alcohol.

Imine and Enamine Formation

• Amines add to aldehydes and ketones to produce imines (R2C=NR) and enamines (R2N–CR=CR2) respectively, through well-defined mechanistic pathways involving nucleophilic attacks and proton transfers.

Wolff-Kishner Reaction

• Hydrazine Treatment: Converts aldehydes or ketones to alkanes via a hydrazone intermediate leading to protonation and alkane production.

Acetal Formation

• Aldehydes and ketones react with alcohols in the presence of an acid catalyst yielding acetals (R2C(OR’)2), known as ketals when derived from ketones:

  • Hydroxy ethers (hemiacetals) can form reversibly from these reactions depending on conditions.

The Wittig Reaction

• Phosphorus Ylides: Allows for conversion of aldehydes or ketones into alkenes, forming a cyclic intermediate (oxaphosphetane) that decomposes to yield alkenes and triphenylphosphine oxide:

  • Mechanism involves nucleophilic attack, formation of tetrahedral intermediates, and subsequent rearrangements to final products.

Conclusion

• This chapter provides vital insights into naming conventions, preparation methods, nucleophilic addition reactions, and the various transformations of aldehydes and ketones, establishing their foundational roles in organic chemistry.