chem 2412: ch. 18 aldehydes and ketones. classes of carbonyl compounds

Chem 2412: Ch. 18

Aldehydes and Ketones

Classes of Carbonyl Compounds

© 2013 Pearson Education, Inc. Chapter 18 3

Structure of the Carbonyl Group

• Carbon is sp2 hybridized.• C═O bond is shorter, stronger, and more polar

than C═C bond in alkenes.


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.


Ketone NomenclatureKetone Nomenclature

• Select the longest continuous carbon chain that includes the carbonyl carbon.

• Number the chain so that the carbonyl carbon has the lowest number.

• Replace the alkane -e with the suffix -one.


Cyclic Ketone NomenclatureCyclic 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.

Examples of KetonesExamples of Ketones

O

butan-2-one

O

Cl

OO

but-3-en-2-one

OHO

4-hydroxybutan-2-one

O

O

octane-2,7-dione

O

3-methylcyclopentanone

O

cyclohex-2-en-1-one

Cl

O

Br

7-bromo-3-chloro-4-methylcyclooctanone

3-chloro-5-ethylheptan-4-one3,5-dimethylheptan-4-one

Cl

O

3-chloro-5-ethyloct-7-en-1-yn-4-one


Aldehydes NomenclatureAldehydes 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.

Examples of AldehydesExamples of Aldehydes

O

H

propanal

Br

O

H

4-bromo-3-methylheptanal

OH O

H

3-hydroxybutanal

O

H

(2E)-pent-2-enal

O

H

cyclohexanecarbaldehyde

O

HOH

2-hydroxycyclopentanecarbaldehyde

OH

O

H

O

H

2-(3-hydroxypropyl)pentanedial

O

H

pent-4-en-2-ynal

O

H

5-ethyl-3,6-dimethyl-4-propyloctanal

O

H

(4E)-hept-4-ene-2,6-diynal

Ketones/Aldehydes as minor FGs, benzaldehydesKetones/Aldehydes as minor FGs, benzaldehydes

If C=O is lower priority functional group•Ketone/aldehyde is oxo group•Aldehyde is formyl group (on benzene)•Aldehyde is higher priority than ketone

O O

H

3-oxopentanal

O O

OHO

3,4-dioxopentanoic acid

O O

HO

3,4-dioxopentanal

O

H

O

OH

2-formylbenzoic acid

H

O

benzaldehyde

ClH

O

3-chlorobenzaldehyde

O O

HO

methyl 3-oxopropanoate

O O

O

methyl 3-oxobutanoate

O O

HH

O

3-oxopropanoic acid

Common Names for KetonesCommon Names for Ketones

• Named as alkyl attachments to —C═O• Use Greek letters instead of numbers.

Historical Common NamesHistorical Common Names

Common Aldehydes and KetonesCommon Aldehydes and Ketones

Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011


Boiling Points

• Ketones and aldehydes are more polar, so they have a higher boiling point than comparable alkanes or ethers.

• They cannot hydrogen-bond to each other, so their boiling point is lower than the comparable alcohol.

Boiling PointsBoiling Points

CH3OH

CH3 CH3

CH3O

CH3

O

CH3 H

Ketones and aldehydes are more polar, so they have a higher boiling point than comparable alkanes or ethers.

They cannot hydrogen-bond to each other, so their boiling point is lower than the comparable alcohol.

O

R R

O

R R

δ-

δ-

δ+

δ+

Intermoleculardipolar

H HO

Hydrogen bond δ+

δ-

Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011


Solubility of Ketones and AldehydesSolubility of Ketones and Aldehydes

• 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.


Infrared (IR) SpectroscopyInfrared (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


Proton NMR SpectraProton 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.


11H NMR SpectroscopyH 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.


Carbon NMR Spectra of KetonesCarbon 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).

Mass Spectrometry (MS)Mass Spectrometry (MS)

MS for ButyraldehydeMS for Butyraldehyde


McLafferty RearrangementMcLafferty Rearrangement

• Occurs during MS analysis.• The net result of this rearrangement is the breaking of the

bond and the transfer of a proton from the carbon to the oxygen.

• An alkene is formed as a product of this rearrangement through the tautomerization of the enol.


Review: Grignards as a Source for Ketones and Review: Grignards as a Source for Ketones and AldehydesAldehydes

• A Grignard reagent can be used to make an alcohol, and then the alcohol can be easily oxidized.

• Aldehyde Ketone

Review: Oxidation of Primary Alcohols to AldehydesReview: Oxidation of Primary Alcohols to Aldehydes

• PCC is selectively used to oxidize primary alcohols to aldehydes.• The Swern oxidation could also be used.

Review: Ozonolysis of AlkenesReview: Ozonolysis of Alkenes

• Double bond is oxidatively cleaved by ozone followed by reduction.• Ketones and aldehydes can be isolated as products under these conditions.


FriedelFriedel––Crafts ReactionCrafts Reaction

• Reaction between an acyl halide and an aromatic ring will produce a ketone.


Review: Hydration of AlkynesReview: 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.


Review: HydroborationReview: Hydroboration––Oxidation of AlkynesOxidation of Alkynes

• Hydroboration–oxidation of an alkyne gives anti-Markovnikov addition of water across the triple bond.


Synthesis of Ketones from Carboxylic AcidsSynthesis of Ketones from Carboxylic Acids

• Organolithiums will attack the lithium salts of carboxylate anions to give dianions.

• Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone.

• Product different than addition of R to esters, acid chlorides (Chapter 10).


Ketones and Aldehydes from Nitriles

• A Grignard or organolithium reagent can attack the carbon of the nitrile.

• The imine is then hydrolyzed to form a ketone.


Reduction of Nitriles to Aldehydes

• Aluminum hydrides can reduce nitriles to aldehydes.• Diisobutylaluminum hydride, abbreviated (i-Bu)2AlH or

DIBAL-H, is commonly used for the reduction of nitriles.


Aldehydes from Acid ChloridesAldehydes from Acid Chlorides

• Lithium aluminum tri(t-butoxy)hydride is a milder reducing agent that reacts faster with acid chlorides than with aldehydes.

• Similar to LAH, which adds H- as nucleophile to carbonyls, producing primary or secondary alcohols (chapter 10).


Lithium Dialkyl Cuprate ReagentsLithium Dialkyl Cuprate Reagents

• A lithium dialkylcuprate will transfer one of its alkyl groups to the acid chloride.

• Grignards and organolithiums cannot do this reaction.


Nucleophilic AdditionNucleophilic Addition

• A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated.

• Aldehydes are more reactive than ketones.


The Wittig ReactionThe 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.


Preparation of Phosphorus YlidesPreparation of Phosphorus Ylides

• Prepared from triphenylphosphine and an unhindered alkyl halide.

• Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus.


Mechanism of the Wittig ReactionMechanism of the Wittig Reaction

Betaine formation

Oxaphosphetane formation


Mechanism for WittigMechanism for Wittig

• The oxaphosphetane will collapse, forming carbonyl (ketone or aldehyde) and a molecule of triphenyl phosphine oxide.


• 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 AldehydesHydration of Ketones and Aldehydes


Hydration of CarbonylsHydration of Carbonyls

• Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile.

Acid catalyzed

Base catalyzed

• The hydroxide ion attacks the carbonyl group. • Protonation of the intermediate gives the hydrate.


Cyanohydrin FormationCyanohydrin 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.


Formation of IminesFormation 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.

Mechanism of Imine FormationAcid-catalyzed addition of the amine to the carbonyl compound group

Acid-catalyzed dehydration

Formation of AcetalsFormation of Acetals

Addition of alcohol to aldehydes and ketonesAddition of alcohol to aldehydes and ketones

Hemiacetal is unstable, hard to isolate (see next slide). With excess alcohol and an acid catalyst, a stable acetal is formed.

O

R H+ H

R

O

RO

HO

R H

H+, RO-H

RO

RO

R H + H-O-H

Hemiacetal Hemiacetal intermediateintermediate

acetalacetal

O

R R+ H

R

O

RO

HO

R R

H+, RO-H

RO

RO

R R + H-O-H

Hemiketal Hemiketal intermediateintermediate

ketalketal


Mechanism for Stable Hemiacetal FormationMechanism for Stable Hemiacetal Formation

• Must be acid-catalyzed.• Adding H+ to carbonyl makes it more reactive with

weak nucleophile, ROH.

Acetal FormationAcetal Formation

Hydrolysis of acetals and ketalsHydrolysis of acetals and ketals

“Cutting by water” is essentially the reverse of the addition of alcohol to either aldehyde or ketone.

aldehydealdehydeacetalacetal

RO

RO

R H +H

H

O H+ O

R H

2 R-OH+

alcoholalcohol

ketoneketoneketalketal alcoholalcohol

RO

RO

R R +H

H

O H+ O

R R

2 R-OH+


Cyclic AcetalsCyclic Acetals

• Addition of a vicinal diol produces a cyclic acetal.• The reaction is reversible.• This reaction is used in synthesis to protect carbonyls from

reaction.


Acetals as Protecting GroupsAcetals as Protecting Groups

O

H

O

HOOH

H+ H

O

OO

• Hydrolyze easily in acid; stable in base• Aldehydes are more reactive than ketones.


Reaction and DeprotectionReaction and Deprotection

H

O

OO1) NaBH42) H3O+

O

H

OH

• The acetal will not react with NaBH4, so only the ketone will get reduced.

• Hydrolysis conditions will protonate the alcohol and remove the acetal to restore the aldehyde.


Review: Oxidation of AldehydesReview: Oxidation of Aldehydes

Aldehydes are easily oxidized to carboxylic acids.

Summary of Reduction ReagentsSummary of Reduction Reagents

• Sodium borohydride, NaBH4, can reduce ketones to secondary alcohols and aldehydes to primary alcohols.

• Lithium aluminum hydride, LiAlH4, is a powerful reducing agent, so it can also reduce carboxylic acids and their derivatives.

• Hydrogenation with a catalyst can reduce the carbonyl, but it will also reduce any double or triple bonds present in the molecule.


Review: Sodium BorohydrideReview: Sodium Borohydride

• NaBH4 can reduce ketones and aldehydes, but not esters, carboxylic acids, acyl chlorides, or amides.


Review: Lithium Aluminum HydrideReview: Lithium Aluminum Hydride

R R(H)

OH

HR R(H)

OLiAlH4ether

aldehyde or ketone

• LiAlH4 can reduce any carbonyl because it is a very strong reducing agent.

• Difficult to handle


Catalytic HydrogenationCatalytic 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.


Deoxygenation of Ketones and AldehydesDeoxygenation of Ketones and Aldehydes

• The Clemmensen reduction or the Wolff–Kishner reduction can be used to deoxygenate ketones and aldehydes.

Clemmensen ReductionClemmensen Reduction


WolffWolff––Kishner ReductionKishner 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.

Intramolecular addition of alcohols to aldehydeIntramolecular addition of alcohols to aldehyde

C1 is hemiacetal carbon. Attached to it you will find: H, OH, OR and R, just like non-cyclical compounds.

Intramolecular Intramolecular hemiacetalhemiacetalglucoseglucose

C

C

C

C

CH2

C

OH

OH

OH

OH

HO H

H

H

H

H O1

2

3

4

5

6

* CH2OH

C

C

C C

O

C

6

5

4

3 2

1

OH

H

OH

OH

OH

H

H

H

H

Aldehyde Rxns – Testing for AldehydesAldehyde Rxns – Testing for Aldehydes

Tollens’ reagent reduces silver ions to metallic silver Benedict’s Reagent reacts with ketones that have an alcohol on the adjacent carbon (e.g., glucose) Products include a red precipitate of copper (I) oxide

Tollens’ Reagent (reacts with all aldehydes)Tollens’ Reagent (reacts with all aldehydes)

Benedict’s Reagent (reacts with aldehydes, some ketones)Benedict’s Reagent (reacts with aldehydes, some ketones)

chem 2412: ch. 18 aldehydes and ketones. classes of carbonyl compounds

Documents