Chapter 17 Aldehydes and Ketones: Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Classes of Carbonyl Compounds

© 2013 Pearson Education, Inc. Chapter 18 3 Resonance The first resonance is better because all atoms complete the octet and there are no charges. The carbonyl carbon has a partial positive and will react as an electrophile.

© 2013 Pearson Education, Inc. Chapter 18 4 Aldehydes Nomenclature The aldehyde carbon is number 1. IUPAC: Replace -e with -al. If the aldehyde group is attached to a ring, the suffix carbaldehyde is used.

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

© 2013 Pearson Education, Inc. Chapter 18 6 Ketone Nomenclature Number the chain so that the carbonyl carbon has the lowest number. Replace the alkane -e with -one.

© 2013 Pearson Education, Inc. Chapter 18 7 Cyclic Ketone Nomenclature For cyclic ketones, the carbonyl carbon is assigned the number 1. When the compound has a carbonyl and a double bond, the carbonyl takes precedence.

Functional Class IUPAC Nomenclature of Ketones CH 3 CH 2 CCH 2 CH 2 CH 3 OO CH 2 CCH 2 CH 3 CH CH 2 O H2CH2C CHC List the groups attached to the carbonyl separately in alphabetical order, and add the word ketone.

CH 3 CH 2 CCH 2 CH 2 CH 3 O ethyl propyl ketonebenzyl ethyl ketone divinyl ketone O CH 2 CCH 2 CH 3 CH CH 2 O H2CH2C CHC Functional Class IUPAC Nomenclature of Ketones

Structure and Bonding: The Carbonyl Group

planar bond angles: close to 120° C=O bond distance: 122 pm Both C and O are sp 2 hybridizes. Structure of Formaldehyde

The half-filled 2p orbitals on carbon and oxygen overlap to form a  bond. Bonding in Formaldehyde

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

2475 kJ/mol 2442 kJ/mol Alkyl groups stabilize carbonyl groups the same way they stabilize carbon-carbon double bonds, carbocations, and free radicals. heat of combustion Carbonyl Group of a Ketone is More Stable than that of an Aldehyde O O H

Nucleophiles attack carbon; electrophiles attack oxygen. Resonance Description of Carbonyl Group C O C O + –

Physical Properties

boiling point –6°C 49°C 97°C Aldehydes and Ketones have Higher Boiling Points than Alkenes, but Lower Boiling Points than Alcohols More polar than alkenes, but cannot form intermolecular hydrogen bonds to other carbonyl groups. O OH

Sources of Aldehydes and Ketones

from alkenes ozonolysis from alkynes hydration (via enol) from arenes Friedel-Crafts acylation from alcohols oxidation Table 17.1 Synthesis of Aldehydes and Ketones A number of reactions already studied provide efficient synthetic routes to aldehydes and ketones.

© 2013 Pearson Education, Inc. Chapter Ozonolysis of Alkenes The double bond is oxidatively cleaved by ozone followed by reduction. Ketones and aldehydes can be isolated as products under these conditions.

© 2013 Pearson Education, Inc. Chapter Friedel–Crafts Reaction Reaction between an acyl halide and an aromatic ring will produce a ketone.

© 2013 Pearson Education, Inc. Chapter Hydration of Alkynes The initial product of Markovnikov hydration is an enol, which quickly tautomerizes to its keto form. Internal alkynes can be hydrated, but mixtures of ketones often result.

© 2013 Pearson Education, Inc. Chapter Grignards as a Source for Ketones and Aldehydes A Grignard reagent can be used to make an alcohol, and then the alcohol can be easily oxidized.

C O R OH aldehydes from carboxylic acids RCH 2 OH 1. LiAlH 4 2. H 2 O PDC, CH 2 Cl 2 H C O R What About..?

Benzaldehyde from benzoic acid COH O CHCH O 1. LiAlH 4 2. H 2 O PDC CH 2 Cl 2 CH 2 OH (81%) (83%) Example

C O R H Ketones from aldehydes R' R C O PDC, CH 2 Cl 2 1. R'MgX 2. H 3 O + RCHR' OH What About..?

C O CH 3 CH 2 H 3-heptanone from propanal H 2 CrO 4 1. CH 3 (CH 2 ) 3 MgX 2. H 3 O + CH 3 CH 2 CH(CH 2 ) 3 CH 3 OH O CH 3 CH 2 C(CH 2 ) 3 CH 3 (57%) Example

Industrial Importance Acetone and methyl ethyl ketone are common industrial solvents. Formaldehyde is used in polymers like Bakelite  and many other polymeric products. Also used as flavorings and additives for food.

Reactions of Aldehydes and Ketones: A Review and a Preview Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Already covered in earlier chapters: Reduction of C=O to CH 2 Clemmensen reduction Wolff-Kishner reduction Reduction of C=O to CHOH Addition of Grignard and organolithium reagents Table 17.2 Reactions of Aldehydes and Ketones

© 2013 Pearson Education, Inc. Chapter Catalytic Hydrogenation Widely used in industry Raney nickel is finely divided Ni powder saturated with hydrogen gas. It will attack the alkene first, then the carbonyl.

© 2013 Pearson Education, Inc. Chapter Deoxygenation of Ketones and Aldehydes The Clemmensen reduction or the Wolff– Kishner reduction can be used to deoxygenate ketones and aldehydes.

Clemmensen Reduction

© 2013 Pearson Education, Inc. Chapter Wolff–Kishner Reduction Forms hydrazone, then heat with strong base like KOH or potassium tert-butoxide Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO. A molecule of nitrogen is lost in the last steps of the reaction.

© 2013 Pearson Education, Inc. Chapter Sodium Borohydride NaBH 4 can reduce ketones and aldehydes, but not esters, carboxylic acids, acyl chlorides, or amides.

© 2013 Pearson Education, Inc. Chapter Lithium Aluminum Hydride LiAlH 4 can reduce any carbonyl because it is a very strong reducing agent. Difficult to handle

Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones

© 2013 Pearson Education, Inc. Chapter In an aqueous solution, a ketone or an aldehyde is in equilibrium with its hydrate, a geminal diol. With ketones, the equilibrium favors the unhydrated keto form (carbonyl). Hydration of Ketones and Aldehydes

© 2013 Pearson Education, Inc. Chapter Acid-Catalyzed Hydration of Carbonyls Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile.

© 2013 Pearson Education, Inc. Chapter The hydroxide ion attacks the carbonyl group. Protonation of the intermediate gives the hydrate. Base-Catalyzed Hydration of Carbonyls

© 2013 Pearson Education, Inc. Chapter Cyanohydrin Formation The mechanism is a base-catalyzed nucleophilic addition: Attack by cyanide ion on the carbonyl group, followed by protonation of the intermediate. HCN is highly toxic.

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

Example CH 3 CCH 3 O NaCN, water then H 2 SO 4 CH 3 CCH 3 OH CN (77-78%) Acetone cyanohydrin is used in the synthesis of methacrylonitrile.

Acetal Formation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Some reactions of aldehydes and ketones progress beyond the nucleophilic addition stage Acetal formation Imine formation Enamine formation Compounds related to imines The Wittig reaction

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

Alcohols Under Analogous Reaction with Aldehydes and Ketones R”OH C O R R' R"O C O H R R' Product is called a hemiacetal.

R”OH, H + Hemiacetal reacts further in acid to yield an acetal R"O C O H R R' R"O C OR” R R' Product is called an acetal.

HCl 2CH 3 CH 2 OH + + H 2 O Benzaldehyde diethyl acetal (66%) Example CH O CH(OCH 2 CH 3 ) 2

HOCH 2 CH 2 OH + CH 3 (CH 2 ) 5 CH O p-toluenesulfonic acid benzene + H2OH2O (81%) H (CH 2 ) 5 CH 3 H2CH2C CH 2 O O C Diols Form Cyclic Acetals

In general: Position of equilibrium is usually unfavorable for acetal formation from ketones. Important exception: Cyclic acetals can be prepared from ketones.

HOCH 2 CH 2 OH + O p-toluenesulfonic acid benzene + H2OH2O H2CH2C CH 2 O O C (78%) C 6 H 5 CH 2 CCH 3 CH 3 C 6 H 5 CH 2 Example

© 2013 Pearson Education, Inc. Chapter Mechanism for Hemiacetal Formation Must be acid-catalyzed. Adding H + to carbonyl makes it more reactive with weak nucleophile, ROH.

Acetal Formation

C R R' O 2R"OH + OR" R R' C OR" + H 2 O mechanism: reverse of acetal formation; hemiacetal is intermediate application: Aldehydes and ketones can be "protected" as acetals. Hydrolysis of Acetals

Acetals as Protecting Groups

The conversion shown cannot be carried out directly... CH CH 3 CCH 2 CH 2 C O CCH 3 CH 3 CCH 2 CH 2 C O 1. NaNH 2 2. CH 3 I Example

because the carbonyl group and the carbanion are incompatible functional groups. C:C: CH 3 CCH 2 CH 2 C O –

1) protect C=O 2) alkylate 3) restore C=O Strategy

HOCH 2 CH 2 OH + p-toluenesulfonic acid benzene H2CH2C CH 2 O O C CH 3 CH 3 CCH 2 CH 2 C O CH CH 2 CH 2 C CH Example: Protect

H2CH2C CH 2 O O C CH 3 CH 2 CH 2 C CH 1. NaNH 2 2. CH 3 I H2CH2C CH 2 O O C CH 3 CH 2 CH 2 C CCH 3 Example: Alkylate

H2CH2C CH 2 O O C CH 3 CH 2 CH 2 C CCH 3 H2OH2O HCl HOCH 2 CH 2 OH (96%) CCH 3 CH 3 CCH 2 CH 2 C O + Example: Deprotect

Reaction with Primary Amines: Imines Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

© 2013 Pearson Education, Inc. Chapter Formation of Imines Ammonia or a primary amine reacts with a ketone or an aldehyde to form an imine. Imines are nitrogen analogues of ketones and aldehydes with a C ═ N bond in place of the carbonyl group. Optimum pH is around 4.5.

CH 3 NH 2 CH O + CH=NCH 3 + H 2 O N-Benzylidenemethylamine (70%) Example

CH 3 NH 2 CH O + CH=NCH 3 + H 2 O N-Benzylidenemethylamine (70%) Example CH OHOH NHCH 3 CH 3

© 2013 Pearson Education, Inc. Chapter Mechanism of Imine Formation Acid-catalyzed addition of the amine to the carbonyl compound group Acid-catalyzed dehydration

© 2013 Pearson Education, Inc. Chapter Other Condensations with Amines

CH 3 (CH 2 ) 5 CH+ H 2 NOH O CH 3 (CH 2 ) 5 CH+ H 2 O NOH (81-93%) Example

+ H 2 NNH 2 + H 2 O (73%) Example O C NNH 2 C

CCH 3 Example O + H 2 NNH phenylhydrazine + H 2 O CCH 3 NNH a phenylhydrazone (87-91%)

CH 3 (CH 2 ) 9 CCH 3 O H 2 NNHCNH 2 O + H2OH2O CH 3 (CH 2 ) 9 CCH 3 NNHCNH 2 O + Example semicarbazide a semicarbazone (93%)

17.11 Reaction with Secondary Amines: Enamines

R2NHR2NH + H 2 O (enamine) C R2NR2N C Enamine Formation C O R2NR2N H H C C O H C

+ (heat in benzene) Example O NHNH via OHOHOHOH N (80-90%) N

© 2013 Pearson Education, Inc. Chapter The Wittig Reaction  The Wittig reaction converts the carbonyl group into a new C═C double bond where no bond existed before.  A phosphorus ylide is used as the nucleophile in the reaction.

© 2013 Pearson Education, Inc. Chapter Preparation of Phosphorus Ylides  Prepared from triphenylphosphine and an unhindered alkyl halide.  Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus.

© 2013 Pearson Education, Inc. Chapter Mechanism of the Wittig Reaction Betaine formation Oxaphosphetane formation

© 2013 Pearson Education, Inc. Chapter Mechanism for Wittig  The oxaphosphetane will collapse, forming alkene and a molecule of triphenyl phosphine oxide.

Retrosynthetic Analysis There will be two possible Wittig routes to an alkene. Analyze the structure retrosynthetically. Disconnect the doubly bonded carbons. One will come from the aldehyde or ketone, the other from the ylide. CC R R' A B

Retrosynthetic Analysis of Styrene C 6 H 5 CH CH 2 HCH O + (C 6 H 5 ) 3 P CHC 6 H 5 + – C 6 H 5 CH O + (C 6 H 5 ) 3 P CH 2 + – Both routes are acceptable.

© 2013 Pearson Education, Inc. Chapter Oxidation of Aldehydes Aldehydes are easily oxidized to carboxylic acids.

© 2013 Pearson Education, Inc. Chapter Infrared (IR) Spectroscopy  Very strong C═O stretch around 1710 cm -1 for ketones and 1725 cm -1 for simple aldehydes  Additional C—H stretches for aldehyde: Two absorptions at 2710 cm -1 and 2810 cm -1

© 2013 Pearson Education, Inc. Chapter IR Spectra  Conjugation lowers the carbonyl stretching frequencies to about 1685 cm -1.  Rings that have ring strain have higher C═O frequencies.

© 2013 Pearson Education, Inc. Chapter Proton NMR Spectra  Aldehyde protons normally absorb between  9 and  10.  Protons of the α carbon usually absorb between  2.1 and  2.4 if there are no other electron-withdrawing groups nearby.

© 2013 Pearson Education, Inc. Chapter H NMR Spectroscopy  Protons closer to the carbonyl group are more deshielded.  The , and  protons appear at values of  that decrease with increasing distance from the carbonyl group.

© 2013 Pearson Education, Inc. Chapter Carbon NMR Spectra of Ketones  The spin-decoupled carbon NMR spectrum of 2-heptanone shows the carbonyl carbon at 208 ppm and the α carbon at 30 ppm (methyl) and 44 ppm (methylene).

© 2013 Pearson Education, Inc. Chapter Mass Spectrometry (MS)

© 2013 Pearson Education, Inc. Chapter MS for Butyraldehyde