hapter 18 Ketones and Aldehydes arbonyl ompounds hapter 18: Aldehydes and Ketones Slide 18-2 1
arbonyl Structure arbon is sp 2 hybridized. = bond is shorter, stronger, and more polar than = bond in alkenes. hapter 18: Aldehydes and Ketones Slide 18-3 IUPA 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. hapter 18: Aldehydes and Ketones Slide 18-4 2
Examples 3 3 3 3-methyl-2-butanone 3-methylbutan-2-one Br 3-bromocyclohexanone 3 2 3 4-hydroxy-3-methyl-2-butanone 4-hydroxy-3-methylbutan-2-one hapter 18: Aldehydes and Ketones Slide 18-5 Naming Aldehydes IUPA: Replace -e with -al. The aldehyde carbon is number 1. If - is attached to a ring, use the suffix -carbaldehyde. hapter 18: Aldehydes and Ketones Slide 18-6 3
Examples 3 3 2 2 3-methylpentanal 2-cyclopentenecarbaldehyde cyclopent-2-en-1-carbaldehyde hapter 18: Aldehydes and Ketones Slide 18-7 Name as Substituent n a molecule with a higher priority functional group, = is oxo- and - is formyl. Aldehyde priority is higher than ketone. 3 3 2 3-methyl-4-oxopentanal 3-formylbenzoic acid hapter 18: Aldehydes and Ketones Slide 18-8 4
ommon Names for Ketones Named as alkyl attachments to -=. Use Greek letters instead of numbers. 3 3 3 3 Br 3 3 methyl isopropyl ketone α bromoethyl isopropyl ketone hapter 18: Aldehydes and Ketones Slide 18-9 istorical ommon Names 3 3 3 acetone acetophenone benzophenone hapter 18: Aldehydes and Ketones Slide 18-10 5
Aldehyde ommon Names Use the common name of the acid. Drop -ic acid and add -aldehyde. 1 : formic acid, formaldehyde 2 s: acetic acid, acetaldehyde 3 s: propionic acid, propionaldehyde 4 s: butyric acid, butyraldehyde. 3 Br 2 β-bromobutyraldehyde 3-bromobutanal hapter 18: Aldehydes and Ketones Slide 18-11 Boiling Points More polar, so higher boiling point than comparable alkane or ether. annot -bond to each other, so lower boiling point than comparable alcohol. hapter 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 - or N-. Acetone and acetaldehyde are miscible in water. hapter 18: Aldehydes and Ketones Slide 18-13 IR Spectroscopy Very strong = stretch around 1710 cm -1. onjugation lowers frequency. Ring strain raises frequency. Additional - stretch for aldehyde: two absorptions at 2710 cm -1 and 2810 cm -1. hapter 18: Aldehydes and Ketones Slide 18-14 7
1 NMR Spectroscopy hapter 18: Aldehydes and Ketones Slide 18-15 13 NMR Spectroscopy hapter 18: Aldehydes and Ketones Slide 18-16 8
MS for 2-Butanone hapter 18: Aldehydes and Ketones Slide 18-17 MS for Butyraldehyde hapter 18: Aldehydes and Ketones Slide 18-18 9
McLafferty Rearrangement Loss of alkene (even mass number) Must have γ-hydrogen hapter 18: Aldehydes and Ketones Slide 18-19 UV Spectra, π π* = conjugated with another double bond. Large molar absorptivities (> 5000) hapter 18: Aldehydes and Ketones Slide 18-20 10
UV Spectra, n π* Small molar absorptivity. Forbidden transition occurs less frequently. hapter 18: Aldehydes and Ketones Slide 18-21 Synthesis Review xidation 2 alcohol Na 2 r 2 7 ketone 1 alcohol P aldehyde zonolysis of alkenes. hapter 18: Aldehydes and Ketones Slide 18-22 11
Synthesis Review (2) Friedel-rafts acylation Acid chloride/all 3 benzene ketone l All 3 /ul benzene benzaldehyde (Gatterman-Koch) ydration of terminal alkyne Use gs 4, 2 S 4, 2 for methyl ketone Use Sia 2 B followed by 2 2 in Na for aldehyde. hapter 18: Aldehydes and Ketones Slide 18-23 Synthesis Using 1,3-Dithiane Remove with n-butyllithium. Alkylate with primary alkyl halide, then hydrolyze. hapter 18: Aldehydes and Ketones Slide 18-24 12
Ketones from 1,3-Dithiane After the first alkylation, remove the second, react with another primary alkyl halide, then hydrolyze. BuLi S S 2 3 S 3 Br S _ 2 3 S S 3 2 3, gl 2 2 3 2 3 hapter 18: Aldehydes and Ketones Slide 18-25 Ketones from arboxylates rganolithium compounds attack the carbonyl and form a dianion. Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone. hapter 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. 3 2 MgBr N ether N MgBr 2 3 3 2 3 hapter 18: Aldehydes and Ketones Slide 18-27 Aldehydes from Acid hlorides Use a mild reducing agent to prevent reduction to primary alcohol. Bulk of reagent helps also. 3 2 2 l LiAl(-t-Bu) 3 3 2 2 hapter 18: Aldehydes and Ketones Slide 18-28 14
Ketones from Acid hlorides Use lithium dialkylcuprate (R 2 uli), formed by the reaction of 2 moles of R-Li with cuprous iodide. 2 3 2 2 Li ui ( 3 2 2 ) 2 uli ( 3 2 2 ) 2 uli 3 2 l 3 2 2 2 3 hapter 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. hapter 18: Aldehydes and Ketones Slide 18-30 15
Wittig Reaction Nucleophilic addition of phosphorus ylides. Product is alkene. = becomes =. hapter 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 3 P 3 2 Br Ph 3 P 2 3 Br Ph 3 P 2 3 BuLi _ Ph 3 P 3 ylide hapter 18: Aldehydes and Ketones Slide 18-32 16
Mechanism for Wittig The negative on ylide attacks the positive of carbonyl to form a betaine. xygen combines with phosphine to form the phosphine oxide. _ Ph 3 3 P Ph 3 P 3 3 Ph 3 Ph Ph 3 P _ 3 3 Ph Ph 3 P 3 3 Ph Ph 3 P 3 3 Ph hapter 18: Aldehydes and Ketones Slide 18-33 Phosphonate Modification hapter 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. 2 K = 2000 3 3 2 3 3 K = 0.002 hapter 18: Aldehydes and Ketones Slide 18-35 Addition of N (yanohydrins) N is highly toxic. Use NaN or KN in base to add cyanide, then protonate to add. Reactivity formaldehyde > aldehydes > ketones >> bulky ketones. 3 2 N 3 N 3 2 3 hapter 18: Aldehydes and Ketones Slide 18-36 18
Formation of Imines Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule. = becomes =N-R RN 2 3 Ph R 2 N 3 _ Ph R N 3 Ph 3 R 3 R N N Ph Ph hapter 18: Aldehydes and Ketones Slide 18-37 p Dependence Loss of water is acid catalyzed, but acid destroys nucleophiles. N 3 N 4 (not nucleophilic). ptimum p is around 4.5. hapter 18: Aldehydes and Ketones Slide 18-38 19
ther ondensations hapter 18: Aldehydes and Ketones Slide 18-39 Addition of Alcohol hapter 18: Aldehydes and Ketones Slide 18-40 20
Mechanism Must be acid-catalyzed. Adding to carbonyl makes it more reactive with weak nucleophile, R. emiacetal forms first, then acid-catalyzed loss of water, then addition of second molecule of R forms acetal. All steps are reversible. hapter 18: Aldehydes and Ketones Slide 18-41 Mechanism for emiacetal xygen is protonated. Alcohol is the nucleophile. is removed. hapter 18: Aldehydes and Ketones Slide 18-42 21
emiacetal to Acetal 3 3 3 3 3 3 3 3 3 3 hapter 18: Aldehydes and Ketones Slide 18-43 yclic Acetals Addition of a diol produces a cyclic acetal. Sugars commonly exist as acetals or hemiacetals. 2 2 2 2 hapter 18: Aldehydes and Ketones Slide 18-44 22
Acetals as Protecting Groups ydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones. 2 2 hapter 18: Aldehydes and Ketones Slide 18-45 Selective Reaction of Ketone React with strong nucleophile (base). Remove protective group. _ MgBr 3 3 MgBr 3 3 hapter 18: Aldehydes and Ketones Slide 18-46 23
xidation of Aldehydes Easily oxidized to carboxylic acids. hapter 18: Aldehydes and Ketones Slide 18-47 Tollens Test Add ammonia solution to AgN 3 solution until precipitate dissolves. Aldehyde reaction forms a silver mirror. Mild, basic way to make carboxylic acids. R 2 Ag(N 3 ) 2 3 _ 2 2 Ag R _ 4 N 3 2 2 hapter 18: Aldehydes and Ketones Slide 18-48 24
Reduction Reagents Sodium borohydride, NaB 4, reduces =, but not =. Lithium aluminum hydride, LiAl 4, much stronger, difficult to handle. ydrogen gas with catalyst also reduces the = bond. hapter 18: Aldehydes and Ketones Slide 18-49 atalytic ydrogenation Widely used in industry. Raney nickel, finely divided Ni powder saturated with hydrogen gas. Pt and Rh also used as catalysts. Raney Ni hapter 18: Aldehydes and Ketones Slide 18-50 25
Deoxygenation Reduction of = to 2 Two methods: lemmensen reduction if molecule is stable in hot acid. Wolff-Kishner reduction if molecule is stable in very strong base. hapter 18: Aldehydes and Ketones Slide 18-51 lemmensen Reduction 2 3 Zn(g) 2 2 3 l, 2 2 Zn(g) l, 2 2 3 hapter 18: Aldehydes and Ketones Slide 18-52 26
Wolff-Kisher Reduction Form hydrazone, then heat with strong base like K or potassium t-butoxide. Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMS. 2 2 N N 2 2 NN 2 K heat 2 3 hapter 18: Aldehydes and Ketones Slide 18-53 End of hapter 18 omework: 40, 46, 47, 49, 51, 52, 56, 61, 62, 66, 68, 70, 74, 75 hapter 18: Aldehydes and Ketones Slide 18-54 27