Ketones and Aldehydes: Structure, Synthesis, and Reactivity

Ketones and Aldehydes

Introduction and Structure

Aldehydes and ketones are important classes of organic compounds containing the carbonyl group (C=O). Aldehydes have at least one hydrogen attached to the carbonyl carbon, while ketones have two carbon groups attached.

• Aldehyde: $RCHO$

• Ketone: $RCOR'$

• Both are classified as carbonyl compounds.

• They exhibit similar reactivity due to the polar nature of the carbonyl group.

Preparation of Ketones and Aldehydes

Oxidation of Alcohols

Alcohols can be oxidized to form aldehydes and ketones. The outcome depends on the type of alcohol and the oxidizing agent used.

• Primary alcohols ($1^ ext{o}$) oxidize to aldehydes:

$RCH_2OH \xrightarrow{PCC/CH_2Cl_2} RCHO$

• Secondary alcohols ($2^ ext{o}$) oxidize to ketones:

$R_2CHOH \xrightarrow{PCC} R_2CO$

• Common oxidizing agents: PCC (pyridinium chlorochromate), $H_2SO_4$ (Jones reagent), $Na_2Cr_2O_7$.

• Primary alcohols can be further oxidized to carboxylic acids under strong conditions.

Ozonolysis of Alkenes

Ozonolysis cleaves alkenes to yield aldehydes or ketones, depending on the substitution pattern.

$R_2C=CR_2 \xrightarrow{1. O_3, 2. (CH_3)_2S} R_2C=O + R_2C=O$

• Both sides of the double bond are oxidized to carbonyl groups.

Friedel–Crafts Acylation

This reaction introduces a ketone group onto an aromatic ring via acylation.

$Ar-H + RCOCl \xrightarrow{AlCl_3} ArCOR$

• Forms aryl ketones (e.g., acetophenone from benzene and acetyl chloride).

Reactivity of Ketones and Aldehydes

General Reactivity

The carbonyl carbon is electrophilic due to the polarization of the C=O bond, making it susceptible to nucleophilic attack.

• Aldehydes are generally more reactive than ketones due to less steric hindrance and greater partial positive charge on the carbonyl carbon.

• Reactions can proceed under acidic or basic conditions, affecting the mechanism and intermediates.

Reactions with Strong Nucleophiles (Basic Conditions)

Strong nucleophiles (e.g., $R-MgX$, $R-Li$, $LiAlH_4$, $NaBH_4$) attack the carbonyl carbon directly, forming a tetrahedral alkoxide intermediate, which is then protonated to yield an alcohol.

General Mechanism:

• Nucleophilic addition to the carbonyl group

• Formation of a tetrahedral intermediate

• Protonation to yield the alcohol

$R_2C=O + Nu^- \rightarrow R_2C(ONu)^- \xrightarrow{H_2O} R_2C(OH)Nu$

Reactions with Weak Nucleophiles (Acidic Conditions)

Under acidic conditions, the carbonyl oxygen is first protonated, increasing the electrophilicity of the carbonyl carbon. Weak nucleophiles (e.g., water, alcohols) then attack, followed by deprotonation.

General Mechanism:

• Protonation of the carbonyl oxygen

• Nucleophilic attack

• Deprotonation to yield the product

Types of Strong Nucleophiles

• Organometallic reagents: Grignard reagents ($R-MgX$), organolithium reagents ($R-Li$)

• Hydride donors: $LiAlH_4$ (lithium aluminum hydride), $NaBH_4$ (sodium borohydride)

Examples:

• $R-MgX$ adds to aldehydes and ketones to form alcohols after hydrolysis.

• $LiAlH_4$ and $NaBH_4$ reduce aldehydes to primary alcohols and ketones to secondary alcohols.

Reactions of Metal Hydrides (LiAlH4 and NaBH4)

These reagents deliver hydride ($H^-$) to the carbonyl carbon, reducing aldehydes and ketones to alcohols.

$RCHO \xrightarrow{LiAlH_4/H_2O} RCH_2OH$

$RCOR' \xrightarrow{NaBH_4/H_2O} RCH(OH)R'$

• Mechanism involves nucleophilic addition of hydride, followed by protonation.

Grignard Reagents ($R$-MgX)

Grignard reagents are highly nucleophilic and react with aldehydes and ketones to form alcohols after aqueous workup.

$R-MgX + R'CHO \xrightarrow{1. ether, 2. H_2O} R'CH(OH)R$

• Preparation: $R-Br + Mg \rightarrow R-MgBr$ (in ether)

• React with formaldehyde to give primary alcohols, with other aldehydes to give secondary alcohols, and with ketones to give tertiary alcohols.

Mechanism of Grignard Addition

• Nucleophilic attack by $R^-$ on the carbonyl carbon

• Formation of a tetrahedral intermediate

• Protonation during aqueous workup yields the alcohol

Examples in Synthesis

• Sequential use of oxidation and Grignard addition allows for the construction of complex alcohols.

• Example: Oxidation of a primary alcohol to an aldehyde, followed by Grignard addition to form a secondary alcohol.

Summary Table: Reactions of Aldehydes and Ketones with Nucleophiles

Reagent	Type	Product with Aldehyde	Product with Ketone
LiAlH4 / NaBH4	Hydride donor	Primary alcohol	Secondary alcohol
R-MgX (Grignard)	Organometallic	Secondary alcohol	Tertiary alcohol
R-Li	Organometallic	Secondary alcohol	Tertiary alcohol
H2O (acidic)	Weak nucleophile	Geminal diol	Geminal diol

Additional info: The notes also reference the use of Wittig reagents ($R_2C=PPh_3$) for the conversion of carbonyls to alkenes, and the importance of reaction conditions (acidic vs. basic) in determining the mechanism and outcome of nucleophilic addition reactions.