Aldehydes and Ketones

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Structure and propertiesNomenclature Synthesis (some review)Reactions (some review)Spectroscopy – mass spec, IR, NMR

Structure and properties

Aldehydes and ketones are the simplest carbonyl containing compounds. R R'

The carbonyl carbon and oxygen are sp2 hybridized.

The carbon oxygen double bond is very polarized. The dipole moments of aldehydes and ketones are larger than most alkyl halides and ether.

H3C CH3

u = 2.7 D u = 2.9 D u = 1.9 D

The high polarization of the carbonyl is due to the electronegativity of oxygen and the separation of charge in the resonance form.

The large polarization of the carbonyl functional group produces dipole-dipole interaction between the molecules of aldehydes and ketones.

London dispersion Dipole-Dipole Hydrogen bonding

Hydrogen bonding does not occur between aldehyde and ketone molecules. Hydrogen bonding can occur with other molecules such as water, alcohols and amines.

Solubility

Soluble in 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. Solubility does decrease with longer chain length (> 4-5 carbons).

Naming Ketones (IUPAC)

Replace -e with -one. Indicate the position of the carbonyl with a number. For diones, don’t drop the final –e. Just add –dione.

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

For cyclic ketones the carbonyl carbon is assigned the number 1.

-CHO > RCOR > R-OH > R-NH2 > C=C > C=C

3-methyl-2-butanone3-methylbutan-2-one 3-bromocyclohexanone

4-hydroxy-3-methyl-2-butanone4-hydroxy-3-methylbutan-2-one

Cl Cl O

OCH2CH3

Common Names for Ketones

Named as alkyl attachments to -C=O. Use Greek letters instead of numbers.

(alpha, beta and gamma)

CH3 CH3CH C

methyl isopropyl ketone a-bromoethyl isopropyl ketone

Common Ketones to know:

Acetone methyl ethyl ketone (MEK)

CH3 CH3

CH3 CH2CH3

CH2CH3

Acetophenone propiophenone benzophenone

Naming Aldehydes

IUPAC: Replace -e with -al. The aldehyde carbon is number 1. If -CHO is attached to a ring, use the

suffix -carbaldehyde.

Examples

CH3 CH2 CH

CH2 C H

CHO3-methylpentanal

2-cyclopentenecarbaldehydecyclopent-2-en-1-carbaldehyde

Examples

Name as Substituent

On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl.

Aldehyde priority is higher than ketone.

CH3 C CH

CH2 C H

3-methyl-4-oxopentanal 3-formylbenzoic acid

Aldehyde Common Names

Use the common name of the acid. Drop -ic acid and add -aldehyde.

1 C: formic acid, formaldehyde 2 C’s: acetic acid, acetaldehyde 3 C’s: propionic acid, propionaldehyde 4 C’s: butyric acid, butyraldehyde.

CH3 CH

CH2 C H

O -bromobutyraldehyde

3-bromobutanal

Common Aldehyde

CH3CH2 H

CH3CH2CH2 H

Formaldehyde acetaldehyde propionaldehyde butyraldehyde

CHO CHO

Benzaldehyde p-tolualdehyde 2-naphthaldehyde

Common Aldehyde

Common forms of aldehydes.Formalin is a 40% solution of formaldehyde in water.

There are two dry forms of formaldehyde the cyclic trimer trioxane and paraformaldehyde.

O O O On

Trioxane paraformaldehyde

Heating these materials convert them to formaldehyde.

IR Spectroscopy

Very strong C=O stretch around 1710 cm-1.

Conjugation lowers C=O frequency to 1685-1690 cm-1.

Ring strain raises frequency.(Cycolpentanone 1745 cm-1, cycolpropanone 1810 cm-1 )

Additional C-H stretch for aldehyde: two absorptions at 2710 cm-1 and 2810 cm-1.

NMR Spectroscopy

1H Aldehyde protons are in the δ 9-10 range.

CH3 adjacent to a carbonyl singlet at δ 2.1.

CH2 adjacent to a carbonyl give multiple peaks at δ 2.5.

NMR Spectroscopy

13C Carbonyl carbon singlet in the 175-210 ppm range.

Carbons alpha to the carbonyl are in the 30-40 ppm range.

1H NMR Spectroscopy

13C NMR Spectroscopy

Mass Spectroscopy

Industrial Importance

Acetone and methyl ethyl ketone are important solvents.

Formaldehyde used in polymers like Bakelite.

Flavorings and additives like vanilla, cinnamon, artificial butter.

Common aldehydes and Ketones

Synthesis Review

Oxidation 2 alcohol + Na2Cr2O7 ketone 1 alcohol + PCC aldehyde

Ozonolysis of alkenes.

Synthesis Review

2 alcohol + Na2Cr2O7 ketone

OH Na2Cr2O7 , H2SO4

or H2CrO4

or KMnO4

OH Na2Cr2O7 , H2SO4

or H2CrO4

or KMnO4

Synthesis Review

1 alcohol + PCC aldehyde

HCrO3Cl-

Synthesis Review

Ozonolysis of alkenes.

Synthesis Review

Predict the products of the following reactions.

2) (CH3)2S

Synthesis Review

Friedel-Crafts acylation of aromatic rings Acid chloride/AlCl3 + benzene

ketone

Gatterman-Koch CO + HCl + AlCl3/CuCl + benzene

benzaldehyde

Synthesis Review

Z = H , halogen or donor group

1) R Cl

2) H2O

1) H3C Cl

2) H2O

Predict the products.

Synthesis Review

Z = H , activating group

CO, HCl, AlCl3 / CuCl

Synthesis Review

Hydration of alkyne Use HgSO4, H2SO4, H2O : a methyl ketone is

obtained with a terminal alkyne.

Use Sia2BH followed by H2O2 in NaOH for aldehyde.

Synthesis Review

Hydration of alkyne

CH3CH2CH2C CH

Hg2+ , H2SO4

H2OCH3CH2CH2CCH3

CH3CH2CH2C CCH3

Hg2+ , H2SO4

Synthesis Review

Hydration of alkyne to an aldehyde

CH3CH2CH2C CH1) Sia2BH

2) H2O2 , NaOHCH3CH2CH2CH2C

Synthesis Using 1,3-Dithiane

Remove H+ with n-butyllithium.

• Alkylate with primary alkyl halide, then hydrolyze.

R-X is a primary halide or tosylate.

Ketones from 1,3-Dithiane

After the first alkylation, the second H can be removed using BuLi and the resulting anion react with another primary alkyl halide. Giving a ketone upon hydrolyze.

CH3 CH2CH3

CH3BrS S

CH2CH3

CH2CH3H2O

H+, HgCl2

H CH2CH3

Examples of using 1,3-Dithiane

1) BuLi

S S 2) C6H5CH2Cl

3) H+ , HgCl2 , H2O

2) (CH3)2CHCH2Cl

3) H+ , HgCl2 , H2O

1) BuLi

Ketones from Carboxylates

Organolithium compounds attack the carbonyl and form a dianion.

Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone.

The reaction can be done by first treating with one eq. of LiOH followed by a alkyl/aryl lithium reagent. Consider what is happening in each step (mechanistically how does the reaction work?).

Ketones from Carboxylates

O1) LiOH

2) CH3Li

3) H3O+

1) LiOH

2) C6H5Li

3) H3O+

Ketones from Nitriles

A Grignard or organolithium reagent attacks the nitrile carbon.

The imine salt is then hydrolyzed to form a ketone.

CCH2CH3

CH2CH3

N MgBr

+CH3CH2MgBr H3O+

1) CH3Li

2) H3O+

CN2) H3O

1) C6H5Li

Aldehydes from Acid Chlorides

A mild reducing agent can reduce an acid chloride to an aldehyde.

CH3CH2CH2C

HLiAlH(O-t-Bu)3CH3CH2CH2C

What would happen if you used LAH?

Acid Chlorides are prepared by treating an acid with thionyl chloride (SOCl2).

Show the synthesis of benzaldehyde from toluene.

Ketones from Acid Chlorides

Treatment of an acid chloride with lithium dialkylcuprate (R2CuLi) can also be used to synthesize ketones.

CH3CH2CH2Li2CuI

(CH3CH2CH2)2CuLi

(CH3CH2CH2)2CuLi + CH3CH2C

Cl CH3CH2C

CH2CH2CH3

Reagent preparation:

Ketones from Acid Chlorides

How it the lithium reagent made?

(CH2=CHCH2)2CuLi

(C6H5CH2)2CuLi

Nucleophilic Addition

Note: The carbonyl carbon is an electrophilic center.

The addition of a nucleophile to the carbonyl carbon is the most common reaction of aldehydes and ketones.

There two general types of addition reactions.

Strong nucleophiles attack the carbonyl carbon, forming an alkoxide ion. The resulting alkoxide is then protonated to give an alcohol. (see previous slide)

Weak nucleophiles attack a carbonyl if it has been protonated (acid conditions). Protonation of the carbonyl increases the reactivity of the carbonyl carbon toward nucleophilic attack. The final step is deprotonation of the nucleophile.

Strong nucleophile addition.

If the carbonyl carbon becomes a stereo center in the product, both enantiomer are produced.

Weak nucleophile addition.

R'NucR

H-NucO-

R'NucR

+ Nuc-

R'NucR

H-NucOH

R'NucR

Grignard reactionGrignard reagents add to aldehydes to give secondary alcohols and

ketones to give tertiary alcohols. (one exception: CH2O)R X

etherR Mg X

"Grignard"

R Mg X1)R'CHO

2) H3O+

1)C6H5CHOR Mg X R

Addition of Water hydration

In acid, water is the nucleophile. In base, hydroxide is the nucleophile. Aldehydes are more electrophilic since they have

fewer e--donating alkyl groups. (more reactive)

H+ H2O C

K = 2000

+ H2O CCH3 CH3

K = 0.002

Classify the products?

Addition of Alcohols

The addition of alcohols to the carbonyl is similar to the addition of water.

Mechanism

The formation of acetals and ketals is acid catalyzed.

Adding H+ to carbonyl makes it more reactive with weak nucleophile, ROH.

The addition of a single alcohol produces a hemiacetal. Under the acidic reaction conditions water is loss, followed by addition of a second molecule of ROH forming the acetal.

All steps are equilibrium processes (reversible) .

Mechanism for Hemiacetal

The acid catalyst protonates the carbonyl. Alcohol (a weak nucleophile) then adds to the

carbonyl. Loss of H+ gives the hemiacetal.

Hemiacetal to Acetal

OCH3HO OCH3

HO OCH3

OCH3CH3OOCH3CH3O

Cyclic Acetals

Formation of cyclic acetals is used as a way of protecting the carbonyl group from under going nucleophilic attack in subsequent reactions. The protecting group can be remove by treatment with dilute acid.

Cyclic acetals are made by reacting the aldehyde or ketone with a diol

O OCH2

+CH2 CH2

Sugars commonly exist as acetals or hemiacetals.

Acetals as Protecting Groups

Hydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones.

+ CH2CH2

Selective Reaction of Ketone

React with strong nucleophile (base). Remove protective group.

CH3MgBr

H+ / H2O

Selective Reaction of aldehydes and Ketones

CH2CH2

How could the following synthesis be done.

Addition of HCN

CN- adds to the carbonyl group to give cyanohydrin. The order of reactivity is: formaldehyde > aldehydes > ketones >>

bulky ketones.

CH3CH2C

CH3 + CCH3CH2 CH3

The nitrile group can be convert to an acid group by acid hydrolysis.

α-hydroxy acid

Formation of Imines

The formation of an imine involves an initial nucleophilic attack by ammonia or a primary amine on the carbonyl carbon. Followed by subsequent loss of a water molecule.

The C=O becomes a C=N-R group where R= H, alkyl or aryl

“imine” also called a Schiff base when R is an alkyl group

C OH3C

H H2N R

H2OR N C

+ H3O+

HR N C

H2OR N C

Important N-containing derivatives

Formation of N derivatives

NH2NHCONH2

Loss of water is acid catalyzed, but acid deactivates the nucleophiles. NH3 + H+ NH4

+ (not nucleophilic). Optimum pH is around 4.5.

Wittig Reaction

This reaction involves the nucleophilic addition of a phosphorus ylides to the carbonyl carbon.

The product of a Wittig reaction is an alkene.

Phosphorus Ylides

The ylide is prepared by first reacting triphenylphosphine with an unhindered alkyl halide (methyl or primary halide) to form a phosphonium salt.

Treatment with butyllithium then abstracts a hydrogen from the carbon attached to phosphorus to produce the ylide.

Ph3P + CH3CH2Br Ph3P CH2CH3

Ph3P CH2CH3

Ph3P CHCH3BuLi

Mechanism for Wittig

The negative C on ylide attacks the positive C of carbonyl to form a betaine.

Oxygen combines with phosphine to form the phosphine oxide.

Ph3P O

C CCH3

_+Ph3P

Ph3P CHCH3

Wittig Reaction

Purpose are synthetic route for the preparation of the following compounds.

Oxidation of Aldehydes

Aldehydes are easily oxidized to carboxylic acids.

Tollens Test

Tollens reagent is prepared by adding ammonia to a AgNO3 solution until the precipitate dissolves.

Addition of Tollens reagent to a solution containing an aldehyde results in the formation of a silver mirror.

H + 2 + 3 + 2+ 4+Ag(NH3)2+ OH

_ H2O2 Ag R C

NH3 H2O

H + 2 + 3 + 2+ 4+Ag(NH3)2+ OH

_ H2O2 Ag R C

NH3 H2O

Reduction Reagents

Sodium borohydride, NaBH4, reduces C=O, but not C=C.

Lithium aluminum hydride, LiAlH4, much stronger, difficult to handle.

Hydrogen gas with catalyst also reduces the C=C bond.

Catalytic Hydrogenation

Catalytic hydrogenation is widely used in industry.

Raney nickel, finely divided Ni powder saturated with hydrogen gas.

Pt and Rh also used as catalysts.

ORaney Ni

Deoxygenation

Reduction of C=O to CH2

Two methods: Clemmensen reduction if molecule is stable in

hot acid. Wolff-Kishner reduction if molecule is stable in

very strong base.

Clemmensen Reduction

CH2CH3 Zn(Hg)

HCl, H2O

CH2CH2CH3

H HCl, H2O

Zn(Hg)CH2 CH3

Wolff-Kisher Reduction

Form hydrazone, then heat with strong base like KOH or potassium t-butoxide.

Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO.

HH2N NH2

H KOHheat

CH2 CH3

Aldehydes and Ketones

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