Chapter 18: Ketones and Aldehydes

Classes of Carbonyl Compounds

Carbonyl C=O bond is shorter, stronger and more polar than C=C bond in alkenes

Nomenclature: Ketone Number chain so the carbonyl carbon has the lowest number Replace “e” with “one”

Nomenclature: Cyclic Ketone Carbonyl carbon is #1

Nomenclature: Aldehydes Carbonyl carbon is #1 Replace “e” with “al” If aldehyde is attached to ring, suffix “carbaldehyde” is used

Nomenclature With higher-priority functional groups, ketone is “oxo” and an aldehyde is a “formyl” group Aldehydes have higher priority than ketones

Nomenclature- Common Names: Ketones Name alkyl groups attached to carbonyl Use lower case Greek letters instead of numbers

Nomenclature

Boiling Points Ketones and aldehydes are more polar. Have higher boiling point that comparable alkanes or ethers

Solubility: Ketones and Aldehydes Good solvent for alcohols Acetone and acetaldehyde are miscible in water

Formaldehyde Gas at room temperature

IR Spectroscopy Strong C=O stretch around 1710 cm -1 (ketones) or 1725 cm -1 (simple aldehydes) C-H stretches for aldehydes: 2710 and 2810 cm -1

IR Spectroscopy Conjugation lowers carbonyl frequencies to about 1685 cm -1 Rings with ring strain have higher C=O frequencies

Proton NMR Spectra Aldehyde protons normally around δ9-10 Alpha carbon around δ

Carbon NMR Spectra

Mass Spectrometry (MS)

McLafferty Rearrangement Net result: breaking of the  bond and transfer of a proton from the  carbon to oxygen

Ultraviolet Spectra of Conjugated Carbonyls Have characteristic absorption in UV spectrum Additional conjugate C=C increases max about 30 nm, additional alkyl groups increase about 10nm

Carbonyl Electronic Transitions

Industrial Uses Acetone and methyl ethyl ketone are common solvents Formaldehyde is used in polymers like Bakelite and other polymeric products  Used as flavorings and additives for food

Industrial Uses

Synthesis of Aldehydes and Ketones The alcohol product of a Grignard reaction can be oxidized to a carbonyl

Synthesis of Aldehydes and Ketones Pyridinium chlorochromate (PCC) or a Swern oxidation takes primary alcohols to aldehydes

Synthesis of Aldehydes and Ketones Alkenes can be oxidatively cleaved by ozone, followed by reduction

Synthesis of Aldehydes and Ketones Friedel-Crafts Acylation

Synthesis of Aldehydes and Ketones Hydration of Alkynes Involves a keto-enol tautomerization Mixture of ketones seen with internal alkynes

Synthesis of Aldehydes and Ketones Hydroboration-oxidation of alkyne Anti-Markovnikov addition

Synthesis Problem

Synthesis of Aldehydes and Ketones Organolithium + carboxylic acid  ketone (after dehydration)

Synthesis of Aldehydes and Ketones Grignard or organolithium reagent + nitrile  ketone (after hydrolysis)

Synthesis of Aldehydes and Ketones Reduction of nitriles with aluminum hydrides will afford aldehydes

Synthesis of Aldehydes and Ketones Mild reducing agent lithium aluminum tri(t- butoxy)hydride with acid chlorides

Synthesis of Aldehydes and Ketones Organocuprate (Gilman reagent) + acid chloride  ketone

Nucleophilic Addition Aldehydes are more reactive than ketones

Wittig Reaction Converts the carbonyl group into a new C=C bond Phosphorus ylide is used as the nucleophile

Wittig Reaction Phosphorus ylides are prepared from triphenylphosphine and an unhindered alkyl halide Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus

Wittig Reaction- Mechanism Betaine formation Oxaphosphetane formation

Wittig Reaction- Mechanism Oxaphosphetane collapse

How would you synthesize the following molecule using a Wittig Reaction

Hydration of Ketones and Aldehydes In aqueous solution, a ketone or aldehyde is in equilibrium with it’s hydrate Ketones: equilibrium favors keto form

Hydration of Ketones and Aldehydes Acid-Catalyzed

Hydration of Ketones and Aldehydes Base-Catalyzed

Cyanohydrin Formation Base-catalyzed nucleophilic addition HCN is highly toxic

Formation of Imines Imines are nitrogen analogues of ketones and aldehydes Optimum pH is around 4.5

Formation of Imines- Mechanism

Condensations with Amines

Acetal Formation

Hemiacetal Formation- Mechanism Must be acid-catalyzed

Acetal Formation- Mechanism Must be acid-catalyzed

Hydrolysis of Acetals Acetals can be hydrolyzed by addition of dilute acid Excess of water drives equilibrium towards carbonyl formation

Cyclic Acetals Addition of diol produces cyclic acetal Reaction is reversible Used as a protecting group Stable in base, hydrolyze in acid

Cyclic Acetals- Protecting Group Acetals are stable in base, only ketone reduces Hydrolysis conditions protonate the alkoxide and restore the aldehyde

Oxidation of Aldehydes Easily oxidized to carboxylic acids

Tollens Test Involves a solution of silver-ammonia complex to the unknown compound If an aldehyde is present, its oxidation reduces silver ion to metallic silver

Reducing Reagents- Sodium Borohydride NaBH 4 can reduce ketones and aldehydes, not esters, carboxylic acids, acyl chlorides, or amides

Reducing Reagents- Lithium Aluminum Hydride LiAlH 4 can reduce any carbonyl

Reducing Reagents- Catalytic Hydrogenation Widely used in industry Raney nickel is finely divided Ni powder saturated with hydrogen gas Will attack alkene first, then carbonyl

Deoxygenation of Ketones and Aldehydes Clemmensen reduction or Wolff-Kishner reactions can deoxygenate ketones and aldehydes

Clemmensen Reduction Uses Zinc-Mercury amalgam in aqueous HCl

Wolff-Kishner Reduction Forms hydrazone, then needs heat with strong base like KOH or potassium tert-butoxide Use high-boiling solvent (ethylene glycol, diethylene glycol, or DMSO)