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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 δ2.1-2.4 Carbon NMR Spectra Mass Spectrometry (MS) Mass Spectrometry (MS) 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(tbutoxy)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 O O O H O 1) NaBH4 2) H3O+ H OH • 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 • NaBH4 can reduce ketones and aldehydes, not esters, carboxylic acids, acyl chlorides, or amides Reducing Reagents- Lithium Aluminum Hydride • LiAlH4 can reduce any carbonyl OH O R R(H) aldehyde or ketone LiAlH4 ether R H R(H) 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)