Chapter 17 Aldehydes and Ketones. Nucleophilic Addition to the Carbonyl Group

Chapter 17Aldehydes and Ketones.Nucleophilic Additionto theCarbonyl Group

17.1Nomenclature

O O H H O O HCCHCH IUPAC Nomenclature of Aldehydes Base the name on the chain that contains the carbonyl group and replace the -e ending of the hydrocarbon by -al.

O O H H O O HCCHCH IUPAC Nomenclature of Aldehydes 4,4-dimethylpentanal 5-hexenal 2-phenylpropanedial(keep the -e endingbefore -dial)

O when named as a suffix C when named as a substituent H formyl group carbaldehyde orcarboxaldehyde IUPAC Nomenclature of Aldehydes

O O CH3CH2CCH2CH2CH3 CH3CHCH2CCH3 CH3 H3C O Substitutive IUPAC Nomenclature of Ketones Base the name on the chain that contains the carbonyl group and replace -e by -one. Number the chain in the direction that gives the lowest number to the carbonyl carbon.

O O CH3CH2CCH2CH2CH3 CH3CHCH2CCH3 CH3 H3C O Substitutive IUPAC Nomenclature of Ketones 3-hexanone 4-methyl-2-pentanone 4-methylcyclohexanone

O O CH3CH2CCH2CH2CH3 CH2CCH2CH3 O H2C CH CHC CH2 Functional Class IUPAC Nomenclature of Ketones List the groups attached to the carbonyl separately in alphabetical order, and add the word ketone.

O O CH3CH2CCH2CH2CH3 CH2CCH2CH3 O H2C CH CHC CH2 Functional Class IUPAC Nomenclature of Ketones ethylpropyl ketone benzylethyl ketone divinyl ketone

17.2Structure and Bonding:The Carbonyl Group

Structure of Formaldehyde planar bond angles: close to 120° C=O bond distance: 122 pm

very polar double bond dipole moment = 2.5D dipole moment = 0.3D The Carbonyl Group O 1-butene propanal

O H O Carbonyl group of a ketone is morestable than that of an aldehyde Alkyl groups stabilize carbonyl groups the sameway they stabilize carbon-carbon double bonds,carbocations, and free radicals. heat of combustion 2475 kJ/mol 2442 kJ/mol

O H O Spread is greater foraldehydes andketones than for alkenes Heats of combustion ofC4H8 isomeric alkenes CH3CH2CH=CH2 2717 kJ/mol cis-CH3CH=CHCH3 2710 kJ/mol trans-CH3CH=CHCH3 2707 kJ/mol (CH3)2C=CH2 2700 kJ/mol 2475 kJ/mol 2442 kJ/mol

•• – •• O O •• •• •• C C + Resonance Description ofCarbonyl Group nucleophiles attack carbon; electrophiles attack oxygen

Bonding in Formaldehyde Carbon and oxygen are sp2 hybridized

Bonding in Formaldehyde The half-filledp orbitals oncarbon andoxygen overlapto form a  bond

17.3Physical Properties

O OH Aldehydes and ketones have higher boilingthan alkenes, but lower boiling points than alcohols. boiling point More polar than alkenes, but cannot form intermolecular hydrogen bonds to other carbonyl groups –6°C 49°C 97°C

17.4Sources of Aldehydes and Ketones

Many aldehydes and ketones occur naturally

Table 17.1 Synthesis of Aldehydes and Ketones from alkenes ozonolysis from alkynes hydration (via enol) from arenes Friedel-Crafts acylation from alcohols oxidation A number of reactions alreadystudied provideefficient syntheticroutes to aldehydes and ketones.

O O C C R H R OH 1. LiAlH4 PDC, CH2Cl2 2. H2O RCH2OH What about..? aldehydes from carboxylic acids

O O COH CH 1. LiAlH4 PDCCH2Cl2 2. H2O CH2OH (83%) (81%) Example benzaldehyde from benzoic acid

O O C C R R' R H 1. R'MgX OH PDC, CH2Cl2 2. H3O+ RCHR' What about..? ketones from aldehydes

O CH3CH2C(CH2)3 CH3 1. CH3(CH2)3MgX H2CrO4 OH 2. H3O+ CH3CH2CH(CH2)3 CH3 Example 3-heptanone from propanal O C CH3CH2 H (57%)

17.5Reactions of Aldehydes and Ketones:A Review and a Preview

Table 17.2 Reactions of Aldehydes and Ketones Already covered in earlier chapters: reduction of C=O to CH2 Clemmensen reduction Wolff-Kishner reduction reduction of C=O to CHOH addition of Grignard and organolithium reagents

17.6Principles of Nucleophilic Addition to Carbonyl Groups:Hydration of Aldehydes and Ketones

O C •• •• •• •• HO O H C •• •• Hydration of Aldehydes and Ketones H2O

OH O + C H2O R R' C R' R OH Substituent Effects on Hydration Equilibria compared to H electronic: alkyl groups stabilize reactants steric: alkyl groups crowd product

Table 17.3 Equilibrium Constants and Relative Ratesof Hydration C=O hydrate K % Relative rate CH2=O CH2(OH)2 2300 >99.9 2200 CH3CH=O CH3CH(OH)2 1.0 50 1.0 (CH3)3CCH=O (CH3)3CCH(OH)2 0.2 17 0.09 (CH3)2C=O (CH3)2C(OH)2 0.0014 0.14 0.0018

When does equilibrium favor hydrate? when carbonyl group is destabilized • alkyl groups stabilize C=O • electron-withdrawing groups destabilize C=O

O Substituent Effects on Hydration Equilibria OH + C H2O R R C R R OH R = CH3: K = 0.000025 R = CF3: K = 22,000

H – – •• •• HO O C O O C •• •• •• •• •• •• •• •• Mechanism of Hydration (base) Step 1: +

– •• •• HO O C •• •• •• H H O H •• – •• •• •• + HO OH C O •• •• •• •• •• Mechanism of Hydration (base) Step 2:

H H O O C •• •• + •• H H + O + OH C •• •• •• H Mechanism of Hydration (acid) Step 1: +

H H •• O OH C O •• •• •• + •• H H Mechanism of Hydration (acid) Step 2: + + OH C ••

H H •• O H H + •• O •• H + H •• O OH C •• •• •• + •• O OH C •• H •• H Mechanism of Hydration (acid) Step 3:

17.7Cyanohydrin Formation

•• N C C O O H C •• •• •• •• Cyanohydrin Formation + HCN

– C O N C •• •• •• •• Cyanohydrin Formation

H – •• O H N C O C •• •• •• + •• H H •• O H N C O C •• •• •• •• H Cyanohydrin Formation

Cl Cl O OH Cl Cl CH CHCN Example NaCN, water then H2SO4 2,4-Dichlorobenzaldehyde cyanohydrin (100%)

OH O CH3CCH3 CH3CCH3 CN Example NaCN, water then H2SO4 (77-78%) Acetone cyanohydrin is used in the synthesis of methacrylonitrile (see problem 17.7).

Amygdaline: vitamine B17

17.8Acetal Formation

R O C •• •• R' HOH R •• •• HO O H C •• •• R' Recall Hydration of Aldehydes and Ketones

R R •• •• R"O OR C •• O •• C •• •• R' R' R"OH R •• •• R"O O H C •• •• R' Alcohols Under Analogous Reactionwith Aldehydes and Ketones Product is called an acetal. ketalfrom ketone acetal from aldehyde ROH, H+ + H2O hemiacetal.

H •• O O H C •• •• + R Mechanism of Acetal Formation First stage is analogous to hydration andleads to hemiacetal acid-catalyzed nucleophilic addition of alcohol to C=O H •• + O O C •• •• H R pKa = -7 pKa = - 2.5

Chapter 17 Aldehydes and Ketones. Nucleophilic Addition to the Carbonyl Group