Basic rganic hemistry ourse code: EM 12162 (Pre-requisites : EM 11122) hapter 06 hemistry of Aldehydes & Ketones Dr. Dinesh R. Pandithavidana ffice: B1 222/3 Phone: (+94)777-745-720 (Mobile) Email: dinesh@kln.ac.lk
arbonyl ompounds
arbonyl Structure arbon is sp 2 hybridized. = bond is shorter, stronger, and more polar than = bond in alkenes.
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.
Examples 3 3 3 3-methyl-2-butanone Br 3-bromocyclohexanone 3 2 3 4-hydroxy-3-methyl-2-butanone
Naming Aldehydes Replace -e with -al. The aldehyde carbon is number 1. If - is attached to a ring, use the suffix - carbaldehyde. 3 3 2 2 3-methylpentanal 2-cyclopentenecarbaldehyde
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
istorical ommon Names 3 3 acetone acetophenone 3 benzophenone
Aldehyde - ommon Names Use the common name of the acid. Drop -icacid and add -aldehyde. 1 : formic acid, formaldehyde 2 s: acetic acid, acetaldehyde 3 s: propionic acid, propionaldehyde 4 s: butyric acid, butyraldehyde.
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. Formaldehyde Gas at room temperature. Formalin is a 40% aqueous solution. heat formaldehyde, b.p. -21 2 formalin trioxane, m.p. 62
xidation Synthesis Review 2 alcohol + Na 2 r 2 7 ketone 1 alcohol + P aldehyde zonolysis of alkenes. R R' R'' 1) 2) 3 ( 3 ) 2 S R + R' R'' ydration of terminal alkynes Use gs 4, 2 S 4, 2 for methyl ketone Use Sia 2 B followed by 2 2 in Na for aldehyde.
Synthesis Using 1,3-Dithiane Remove + with n-butyllithium. S S BuLi S _ S Alkylate with primary alkyl halide, then hydrolyze. S _ S 3 2 Br S S 2 3 +, gl 2 2 2 3
Ketones from 1,3-Dithiane After the first alkylation, remove the second +, react with another primary alkyl halide, then hydrolyze. S S BuLi S S _ 3 Br S S +, gl 2 2 3 2 3 2 3 2 3 3 2 3
Ketones from arboxylates rganolithium compounds attack the carbonyl and form a diion. Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone. _ Li+ 3 Li _ + Li _ Li + 3 + 3 3 _ 2 3
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
Aldehydes from Acid hlorides Use a mild reducing agent to prevent reduction to primary alcohol. 3 2 2 l LiAl(-t-Bu) 3 3 2 2
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
Reactions of 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.
Wittig Reaction Nucleophilic addition of phosphorus ylides. Product is alkene. = becomes =.
ow to Prepare 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
Mechanism for Wittig Reaction The negative on ylide attacks the positive of carbonyl to form a betaine. xygen combines with phosphine to form the phosphine oxide. + _ Ph 3 P + 3 Ph 3 P 3 3 Ph 3 Ph + _ Ph 3 P 3 3 Ph Ph 3 P 3 Ph 3 Ph 3 P 3 3 Ph
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
N is highly toxic. Addition of N 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
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 R 3 _ N Ph Ph R N 3 Ph R N 3 Ph
Addition of Alcohol
Must be acid-catalyzed. Mechanism 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.
Mechanism for emiacetal + + + 3 3 + + 3 3 + + 2 3
emiacetal to Acetal + 3 + 3 + 3 + + 3 3 3 3 3 3 3 +
yclic Acetals Addition of a diol produces a cyclic acetal. Sugars commonly exist as acetals or hemiacetals. 2 2 + 2 2
Acetals as Protecting Groups ydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones. 2 2 +
Selective Reaction of Ketone React with strong nucleophile (base) Remove protective group. + _ MgBr 3 3 MgBr 3 + 3
xidation of Aldehydes Easily oxidized to carboxylic acids.
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.
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
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.
lemmensen Reduction 2 3 Zn(g) 2 2 3 l, 2 2 Zn(g) l, 2 2 3
Wolff-Kishner 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