Aldehydes and Ketones I: Electrophilicity and Oxidation-Reduction

Aldehydes and Ketones I: Electrophilicity and Oxidation-Reduction section provides High Yield information for College Students, Medical Students to succeed in the MCAT exam and Medical School.

Aldehydes and Ketones I: Description and Properties

• Ketone: two alkyl groups bonded to the carbonyl
• Aldehyde: one alkyl group and one hydrogen
• Characterized by strong smell (found in many spices)

Nomenclature

• Aldehydes are named by replacing the –e at the end of an alkane with the suffix –al
  • When named as substituents, use the prefix oxo-
• Common names for first five aldehydes:
  • -formaldehyde
  • -acetaldehyde
  • -propionaldehyde
  • -butyraldehyde
  • -valeraldehyde
• If an aldehyde is attached to a ring, the suffix –carbaldehyde is used
• Ketones are named by replacing the –e with the suffix –on
  • When naming ketones by common name, the two alkyl groups are named alphabetically followed by –ketone.
  • When names as substituents, use either oxo- or keto-
  •                    

Physical Properties

•   Governed by the presence of the carbonyl group. Dipole is stronger than the dipole of an alcohol since the double-bonded oxygen is more electron-withdrawing.
• Even though aldehydes and ketones have dipoles that are more polar, the boiling point of alcohols is higher due to the presence of hydrogen bonding in an alcohol.
• Both usually act as electrophiles due to the electron withdrawing properties of the carbonyl oxygen, which leaves a partial positive charge on the oxygen.
• Generally, aldehydes are more reactive towards nucleophiles since they have less steric hindrance and fewer electron donating groups than ketones.

Formation

• An aldehyde can be formed from the partial oxidation of a primary alcohol, but only with PCC.
• A ketone can be obtained from the oxidation of a secondary alcohol. Range of reagents can be used (from dichromate, chromium trioxide to PCC).
  • No concern for oxidizing too far since the reactants will stop at the ketone stage.

Nucleophilic Addition Reactions

• Carbonyl carbon has a partial positive charge and carbonyl oxygen has a partial negative charge, which make it prime for a nucleophilic attack.
• Nucleophile forms a covalent bond to the carbon which break the pi bond associated with carbonyl.
  • The electrons from the pi bond are pushed onto the oxygen atom.
  • This bond breaking forms a tetrahedral intermediate
• Any time a carbonyl is opened, should ask: Can I reform the carbonyl?
  • Carbonyl will not reform if no good leaving group is present (aldehydes/ketones)
    • O^– will simply accept a proton form the solvent to form a hydroxyl group (alcohol)
  • Carbonyl double bond reforms if good leaving groups are present (carboxylic acid and its derivatives)
    • Double bond pushes off the leaving group
    • 

Hydration

• In presence of water, aldehydes/ketones react to form germinal diols (1,1- diols)
• Nucleophilic oxygen in water attacks the electrophilic carbonyl carbon
  • • 

Acetals and Hemiacetals

• Hemiacetal: when one equivalent of alcohol (acts as the nucleophile) is added to an aldehyde
• Hemiketal: when one equivalent of alcohol (acts as the nucleophile) is added to a ketone
  • Recognized by the retention of the hydroxyl group
• Hemi is known as the halfway point and is the endpoint in basic conditions
  • • 
• When two equivalents of alcohol are added, the reaction proceeds to completion which results in the formation of an Acetal and a ketal.
  • Reaction proceeds by the substitution reaction S_N1 and is catalyzed by anhydrous acid
  • Hydroxyl group of a hemiacetal or hemiketal is protonated under acidic conditions and lost as a molecule of water. Which leads to the formation of a carbocation.
  • Another equivalent of alcohol attacks the carbocation which results in the formation of an Acetal or ketal.
  • Are relatively inert, so they are often used as protecting groups for carbonyl functionalities.
    • Can be converted back to carbonyls with aqueous acid and heat
  • 

Imines and Enamines

• Nitrogen and nitrogen based functional groups act as good nucleophiles since nitrogen has a lone pair of electrons
• Imine: simplest case. Ammonia adds to a carbon atom and water is lost
  • Compound with a nitrogen atom double bonded to a carbon atom
  • Condensation reaction: small molecule is lost in the formation of the bond
  • Nucleophilic substitution since nitrogen replaces carbonyl oxygen
• Common ammonia derivatives: hydroxylamine, hydrazine, semicarbazide
• Enamines: contain both a double bond and a nitrogen-containing group
  • Imines can undergo tautomerization to form these
  • 

Cyanohydrins

• Hydrogen cyanide is a classic nucleophile on the MCAT
  • Has both triple bonds and an electronegative nitrogen atom which makes it relatively acidic (pKa of 9.2).
• After the hydrogen atom dissociates, the nucleophilic CN^– can attack the carbonyl carbon atom.
• Reaction with aldehydes and ketones produces stable compounds called cyanohydrins
  • Gains stability from newly formed C-C bond.
  • 

Oxidation-Reduction Reactions

• Aldehydes are in the middle of the redox spectrum since they are more oxidized than alcohols but less oxidized than carboxylic acid
• Ketones are as oxidized as secondary carbons can get.

Oxidation of Aldehydes

• When aldehydes are oxidized further they from carboxylic acid.
  • Facilitated through any oxidizing agent that is stronger than PCC
    • 

Reduction by Hydride Reagents

• Can also undergo reduction to form alcohols
• Often performed by hydride reagents (lithium aluminum hydride & sodium borohydride)
  •