Chapter 18 Ketones and Aldehydes Carbonyl Compounds => Chapter 18: Aldehydes and Ketones Slide 18-2 1 Carbonyl Structure • Carbon is sp2 hybridized. • C=O bond is shorter, stronger, and more polar than C=C bond in alkenes. => Chapter 18: Aldehydes and Ketones Slide 18-3 IUPAC Names for Ketones • Replace -e with -one. Indicate the position of the carbonyl with a number. • Number the chain so that carbonyl carbon has the lowest number. • For cyclic ketones the carbonyl carbon is assigned the number 1. => Chapter 18: Aldehydes and Ketones Slide 18-4 2 Examples O O CH3 C CH CH3 CH3 Br 3-methyl-2-butanone 3-methylbutan-2-one 3-bromocyclohexanone O CH3 C CH CH2OH CH3 4-hydroxy-3-methyl-2-butanone 4-hydroxy-3-methylbutan-2-one => Chapter 18: Aldehydes and Ketones Slide 18-5 Naming Aldehydes • IUPAC: Replace -e with -al. • The aldehyde carbon is number 1. • If -CHO is attached to a ring, use the suffix -carbaldehyde. => Chapter 18: Aldehydes and Ketones Slide 18-6 3 Examples CH3 O CH3 CH2 CH CH2 C H 3-methylpentanal CHO 2-cyclopentenecarbaldehyde cyclopent-2-en-1-carbaldehyde => Chapter 18: Aldehydes and Ketones Slide 18-7 Name as Substituent • On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl. • Aldehyde priority is higher than ketone. COOH O CH3 O CH C CH CH C H 3 2 CHO 3-methyl-4-oxopentanal 3-formylbenzoic acid => Chapter 18: Aldehydes and Ketones Slide 18-8 4 Common Names for Ketones • Named as alkyl attachments to -C=O. • Use Greek letters instead of numbers. O O CH3 C CH CH3 CH3CH C CH CH3 Br CH CH3 3 methyl isopropyl ketone α−bromoethyl isopropyl ketone => Chapter 18: Aldehydes and Ketones Slide 18-9 Historical Common Names O C O CH3 CH3 C CH3 acetone acetophenone O C benzophenone => Chapter 18: Aldehydes and Ketones Slide 18-10 5 Aldehyde Common Names • Use the common name of the acid. • Drop -ic acid and add -aldehyde. 1 C: formic acid, formaldehyde 2 C’s: acetic acid, acetaldehyde 3 C’s: propionic acid, propionaldehyde 4 C’s: butyric acid, butyraldehyde. Br O β-bromobutyraldehyde CH3 CH CH2 C H 3-bromobutanal => Chapter 18: Aldehydes and Ketones Slide 18-11 Boiling Points • More polar, so higher boiling point than comparable alkane or ether. • Cannot H-bond to each other, so lower boiling point than comparable alcohol. => Chapter 18: Aldehydes and Ketones Slide 18-12 6 Solubility • Good solvent for alcohols. • Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H or N-H. • Acetone and acetaldehyde are miscible in water. => Chapter 18: Aldehydes and Ketones Slide 18-13 IR Spectroscopy • Very strong C=O stretch around 1710 cm-1. • Conjugation lowers frequency. • Ring strain raises frequency. • Additional C-H stretch for aldehyde: two absorptions at 2710 cm-1 and 2810 cm-1. => Chapter 18: Aldehydes and Ketones Slide 18-14 7 1H NMR Spectroscopy => Chapter 18: Aldehydes and Ketones Slide 18-15 13C NMR Spectroscopy => Chapter 18: Aldehydes and Ketones Slide 18-16 8 MS for 2-Butanone => Chapter 18: Aldehydes and Ketones Slide 18-17 MS for Butyraldehyde => Chapter 18: Aldehydes and Ketones Slide 18-18 9 McLafferty Rearrangement • Loss of alkene (even mass number) • Must have γ-hydrogen => Chapter 18: Aldehydes and Ketones Slide 18-19 UV Spectra, π → π* • C=O conjugated with another double bond. • Large molar absorptivities (> 5000) => Chapter 18: Aldehydes and Ketones Slide 18-20 10 UV Spectra, n → π* • Small molar absorptivity. • “Forbidden” transition occurs less frequently. => Chapter 18: Aldehydes and Ketones Slide 18-21 Synthesis Review • Oxidation 2° alcohol + Na2Cr2O7 → ketone 1° alcohol + PCC → aldehyde • Ozonolysis of alkenes. => Chapter 18: Aldehydes and Ketones Slide 18-22 11 Synthesis Review (2) • Friedel-Crafts acylation Acid chloride/AlCl3 + benzene → ketone CO + HCl + AlCl3/CuCl + benzene → benzaldehyde (Gatterman-Koch) • Hydration of terminal alkyne Use HgSO4, H2SO4, H2O for methyl ketone Use Sia2BH followed by H2O2 in NaOH for aldehyde. => Chapter 18: Aldehydes and Ketones Slide 18-23 Synthesis Using 1,3-Dithiane • Remove H+ with n-butyllithium. • Alkylate with primary alkyl halide, then hydrolyze. => Chapter 18: Aldehydes and Ketones Slide 18-24 12 Ketones from 1,3-Dithiane After the first alkylation, remove the second H+, react with another primary alkyl halide, then hydrolyze. + O BuLi CH3Br H , HgCl2 S S S S C S S _ H2O CH3 CH2CH3 CH3 CH2CH3 H CH2CH3 CH2CH3 => Chapter 18: Aldehydes and Ketones Slide 18-25 Ketones from Carboxylates • Organolithium compounds attack the carbonyl and form a dianion. • Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone. => Chapter 18: Aldehydes and Ketones Slide 18-26 13 Ketones from Nitriles • A Grignard or organolithium reagent attacks the nitrile carbon. • The imine salt is then hydrolyzed to form a ketone. MgBr N O C N C CH2CH3 + C CH CH MgBr + H O CH2CH3 3 2 ether 3 => Chapter 18: Aldehydes and Ketones Slide 18-27 Aldehydes from Acid Chlorides Use a mild reducing agent to prevent reduction to primary alcohol. Bulk of reagent helps also. O O LiAlH(O-t-Bu)3 CH3CH2CH2C Cl CH3CH2CH2C H => Chapter 18: Aldehydes and Ketones Slide 18-28 14 Ketones from Acid Chlorides Use lithium dialkylcuprate (R2CuLi), formed by the reaction of 2 moles of R-Li with cuprous iodide. CuI 2 CH3CH2CH2Li (CH3CH2CH2)2CuLi O O (CH3CH2CH2)2CuLi + CH3CH2C Cl CH3CH2C CH2CH2CH3 => Chapter 18: Aldehydes and Ketones Slide 18-29 Nucleophilic Addition • A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated. • A weak nucleophile will attack a carbonyl if it has been protonated, thus increasing its reactivity. • Aldehydes are more reactive than ketones. => Chapter 18: Aldehydes and Ketones Slide 18-30 15 Wittig Reaction • Nucleophilic addition of phosphorus ylides. • Product is alkene. C=O becomes C=C. => Chapter 18: Aldehydes and Ketones Slide 18-31 Phosphorus Ylides • Prepared from triphenylphosphine and an unhindered alkyl halide. • Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus. + _ Ph P CH CH Br 3 + 3 2 Ph3P CH2CH3 Br _ + + BuLi Ph3P CH2CH3 Ph3P CHCH3 ylide => Chapter 18: Aldehydes and Ketones Slide 18-32 16 Mechanism for Wittig • The negative C on ylide attacks the positive C of carbonyl to form a betaine. • Oxygen combines with phosphine to form the phosphine oxide. + Ph P O _ H C 3 + 3 CH C O H C C 3 Ph3P CHCH3 Ph Ph CH3 _ + Ph3P O Ph3P O Ph3P O H CH3 H C C CH3 H C C CH3 C C H C Ph CH Ph CH Ph 3 3 3 => Chapter 18: Aldehydes and Ketones Slide 18-33 Phosphonate Modification Chapter 18: Aldehydes and Ketones Slide 18-34 17 Addition of Water • In acid, water is the nucleophile. • In base, hydroxide is the nucleophile. • Aldehydes are more electrophilic since they have fewer e-- donating alkyl groups. OH O HO C C + H2O H H H H K = 2000 OH O HO + H O C C 2 K = 0.002 CH3 CH3 CH3 CH3 => Chapter 18: Aldehydes and Ketones Slide 18-35 Addition of HCN (Cyanohydrins) • HCN is highly toxic. • Use NaCN or KCN in base to add cyanide, then protonate to add H. • Reactivity formaldehyde > aldehydes > ketones >> bulky ketones. O CN HO C C CH3CH2 CH3 + HCN CH3CH2 CH3 => Chapter 18: Aldehydes and Ketones Slide 18-36 18 Formation of Imines • Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. • C=O becomes C=N-R CH3 CH3 H3C R R C O C _ C RNH2 H2N O N OH Ph + Ph H Ph CH CH3 R 3 R C N C OH N H Ph Ph => Chapter 18: Aldehydes and Ketones Slide 18-37 pH Dependence • Loss of water is acid catalyzed, but acid destroys nucleophiles. + + • NH3 + H → NH4 (not nucleophilic). • Optimum pH is around 4.5. Chapter 18: Aldehydes and Ketones Slide 18-38 19 Other Condensations => Chapter 18: Aldehydes and Ketones Slide 18-39 Addition of Alcohol => Chapter 18: Aldehydes and Ketones Slide 18-40 20 Mechanism • Must be acid-catalyzed. • Adding H+ to carbonyl makes it more reactive with weak nucleophile, ROH. • Hemiacetal forms first, then acid-catalyzed loss of water, then addition of second molecule of ROH forms acetal. • All steps are reversible. => Chapter 18: Aldehydes and Ketones Slide 18-41 Mechanism for Hemiacetal • Oxygen is protonated. • Alcohol is the nucleophile. • H+ is removed. => Chapter 18: Aldehydes and Ketones Slide 18-42 21 Hemiacetal to Acetal H + OCH3 HO OCH3 HO OCH3 + H+ + HOH HOCH3 H OCH + 3 CH3O OCH3 CH3O OCH3 + HOCH3 => Chapter 18: Aldehydes and Ketones Slide 18-43 Cyclic Acetals • Addition of a diol produces a cyclic acetal. • Sugars commonly exist as acetals or hemiacetals. CH CH2 2 O O O CH CH + 2 2 HO OH => Chapter 18: Aldehydes and Ketones Slide 18-44 22 Acetals as Protecting Groups • Hydrolyze easily in acid, stable in base. • Aldehydes more reactive than ketones. O O CH2 CH2 HO OH + O H H C C O O => Chapter 18: Aldehydes and Ketones Slide 18-45 Selective Reaction of Ketone • React with strong nucleophile (base). • Remove protective group. + _ MgBr O CH3 O CH3 HO + CH3MgBr H3O H O O C C C O O O => Chapter 18: Aldehydes and Ketones Slide 18-46 23 Oxidation of Aldehydes Easily oxidized to carboxylic acids. => Chapter 18: Aldehydes and Ketones Slide 18-47 Tollens Test • Add ammonia solution to AgNO3 solution until precipitate dissolves. • Aldehyde reaction forms a silver mirror.