C O

Propanone(Acetone)

Ethanal(Acetaldehyde)

Methanal(Formaldehyde)

O O OCH3CHHCH CH3CCH3

Aldehydes & Ketones

The Carbonyl Group:In this chapter we study the physical and chemical properties of classes of compounds containing the carbonyl group, C=O• aldehydes and ketones • carboxylic acids , • Carboxylic acid derivatives: acid halides, acid anhydrides, esters, amides.

The carbonyl group consists of • one sigma bond formed by the overlap of sp2 hybrid orbitals, and • one pi bond formed by the overlap of parallel 2p orbitals

pi bonding MOs formaldehyde

StructureThe functional group of an aldehyde is a carbonyl group bonded to a H atom and a carbon atom .The functional group of a ketone is a carbonyl group bonded to two carbon atoms.

Nomenclature: AldehydesIUPAC names:

the parent chain is the longest chain that contains the functional group for an aldehyde, change the suffix from -e to -al for an unsaturated aldehyde, show the carbon-carbon double bond by changing the

infix from -an- to -en-; the location of the suffix determines the numbering pattern for a cyclic molecule in which -CHO is bonded to the ring, name the compound by

adding the suffix -carbaldehyde

1

H

O

3-Methylbutanal 2-Propenal(Acrolein)

(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)

12

34

5

67

8H

O

H

O

2,2-Dimethylcyclo-hexanecarbaldehyde

CHOCH3

CH3

1

2

CHOC6H5CHO

trans-3-Phenyl-2-propenal(Cinnamaldehyde)

Benzaldehyde

5-Methyl-3-hexanonePropanone (Acetone)

1 3 5 6O O

1-Phenyl-1-pentanone

O1 5

-NH2

-SH-OH

C=O-CHO

-COOH

-amino-sulfanyl

oxo-

hydroxy-oxo-

-amine-thiol-ol-one-al-oic acid

Prefix If Lowerin Precedence

Suffix If Higherin Precedence

FunctionalGroup

Incr

easi

ng p

rece

denc

e

Nomenclature: KetonesIUPAC names :

select as the parent alkane the longest chain that contains the carbonyl group indicate its presence by changing the suffix -e to -one number the chain to give C=O the smaller number

Order of PrecedenceFor compounds that contain more than one functional group indicated by a suffix

2

FormaldehydeFormic acid Acetaldehyde Acetic acid

Ethyl isopropyl ketoneDiethyl ketoneDicyclohexyl ketone

O OO

H H

O

H OH

O

H

O

OH

O

C O C O –

Polarity of acarbonyl group

-+C O

+

More importantcontributing

structure

::: : :

Tetrahedral carbonyl addition compound

+ CR

RO CNu

O -

RR

Nu -: :::

:

:

Common Names• for an aldehyde, the common name is derived from the common name of the

corresponding carboxylic acid• for a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and

add the word ketone

Physical PropertiesOxygen is more electronegative than carbon (3.5 vs 2.5) and, therefore, a C=O group is polar

• aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipol interaction

• they have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

Reaction Themes One of the most common reaction themes of a carbonyl group is addition of a nucleophile

to form a tetrahedral carbonyl addition compound.

3

+fast ++C O

R

RC O

R

RH B-H-B: :: :

ether

1-Propanol(a primary alcohol)

Formaldehyde

Mg2++

++

- +-O

CH3CH2 -MgBr H-C-H

CH3CH2 -CH2 HClH2 OA magnesium

alkoxide

CH3CH2 -CH2

O- [MgBr]+ OH

A second common theme is reaction with a proton or Lewis acid to form a resonance-stabilized cation.

protonation in this manner increases the electron deficiency of the carbonyl carbon and makes it more reactive toward nucleophiles.

I. Addition of C NucleophilesAddition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group; a new carbon-carbon bond is formed in this process.We study addition of these carbon nucleophiles:

A) Grignard Reagents: Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with C- and Mg+in its reactions, a Grignard reagent behaves as a carbanion.Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge .a carbanion is a good nucleophile and adds to the carbonyl group of aldehydes and ketones.

1) Addition of a Grignard reagent to: formaldehyde followed by H3O+ gives a 1° alcohol

2) Addition to any other RCHO gives a 2° alcohol

4

ether

A magnesium alkoxide

Acetaldehyde(an aldehyde)

1-Cyclohexylethanol(a secondary alcohol)

+ Mg2+

+-+

+-

MgBrO

CHCH3

O- [MgBr]+

OHCHCH3

CH3-C-H

HClH2 O

Mg2+

ether

2-Phenyl-2-propanol (a tertiary alcohol)

Acetone

+

+

A magnesium alkoxide

C6H5 MgBrO

C6H5 CCH3CH3

O-[MgBr]+ OH

CH3

C6H5 CCH3

CH3-C-CH3

HClH2O

1-Ethynyl-cyclohexanol

+

O

C -HC Na+

HClH2 O

C OHHC

Cyclohexanol

A sodium alkoxide

C O-Na+HC

:

3) Addition to a ketone gives a 3° alcohol

B)Addition of an acetylide anion:Addition of an acetylide anion followed by H3O+ gives an -acetylenic alcohol.

5

2-Hydroxypropanenitrile(Acetaldehyde cyanohydrin)

+ HC N CH3C-C NCH3CHOH

H

O

-••+H3C

CH3C

CO:-

H3C

H3C

CN

NC

CO:-

H3C

H3C

CH C C

C

H3C

H3C

O-H

NN-:C++

O

NN

Propenenitrile(Acrylonitrile)

+ acidcatalyst

2-Hydroxypropanenitrile(Acetaldehyde cyanohydrin)

CH3CHC N NCH2=CHC H2 OOH

Oxidation of terminal alkyne:

C) Addition of HCN : HCN adds to the C=O group of an aldehyde or ketone to give a cyanohydrin Cyanohydrin: a molecule containing an -OH group and a -CN group bonded to the same

carbon

Mechanism of cyanohydrin formation:

The value of cyanohydrins acid-catalyzed dehydration of the 2° or 3° alcohol

6

CHCOH

NOHCHCH2NH22H2

Benzaldehyde cyanohydrin 2-Amino-1-phenylethanol

Ni+

32

1+

A 1,3-dithiane (a cyclic thioacetal)

+

An aldehyde

SC

S

R

HRCH

H+H2 OHS SH

1,3-Propane-dithiol

O

An imine(a Schiff base)

AmmoniaCyclohexanone

++ NH3 H2 OO NHH+

CH3CH H2N H+CH3CH=N H2 O+ +

Acetaldehyde Aniline An imine(a Schiff base)

O

• catalytic reduction of the cyano group gives a 1° amine

II.Addition of S NucleophilesThiols, like alcohols, add to the C=O of aldehydes and ketones to give tetrahedral carbonyl addition products.The sulfur atom of a thiol is a better nucleophile than the oxygen atom of an alcohol .A common sulfur nucleophile used for this purpose is 1,3-propanedithiolthe product is a 1,3-dithiane.

III.Addition of N Nucleophiles Ammonia, 1° aliphatic amines, and 1° aromatic amines react with the C=O group of

aldehydes and ketones to give imines (Schiff bases).

Formation of an imine occurs in two steps :Step 1: carbonyl addition followed by proton transfer

7

:

CO

H2 N-R N-RH

CO:- H

N-RH

CO H

+

A tetrahedral carbonyl addition compound

+

:O H

H

HN-RH

CO H

N-RH

CO HH

OH

H

C N-R H2 O

An imine

+

+

++

:

+

Dicyclohexylamine

Cyclohexanone

(An imine)

Cyclohexylamine

O

N NH

-H2O

H2 / Ni

H+H2N

O H-N H+N H2 O

An enaminePiperidine(a secondary amine)

++

Cyclohexanone

Step 2: loss of H2O and proton transfer to solvent

A value of imines is that the carbon-nitrogen double bond can be reduced to a carbon-nitrogen single bond

Secondary amines react with the C=O group of aldehydes and ketones to form enamines

8

Hydrazine++

A hydrazoneO NNH2H2NNH2 H2O

Hydroxylamine PhenylhydrazineH2N-OH H2N-NH

+

Formaldehyde Formaldehyde hydrate (>99%)

O

H

OHHCH H2O HCOH

2,2-Propanediol (0.1%)

Acetone (99.9%)

+H3C

CH3C

O COH

H3C

H3C

OHH2O

The mechanism of enamine formation involves formation of a tetrahedral carbonyl addition compound followed by its acid-catalyzed dehydration

The carbonyl group of aldehydes and ketones reacts with hydrazine and its derivatives in a manner similar to its reactions with 1° amines

• hydrazine derivatives include

IV. III.Addition of OucleophilesA) Addition of H 2O:Addition of water (hydration) to the carbonyl group of an aldehyde or ketone gives a gem-diol, commonly referred to as a hydrate.when formaldehyde is dissolved in water at 20°C, the carbonyl group is more than 99% hydrated

The equilibrium concentration of a hydrated ketone is considerably smaller.

9

A hemiacetal

+H

CH3CCH3 OCH2CH3 CH3COCH2CH3

OH

CH3

O

B - + H OR B + - ORH: :

OCH3-C-CH3

– :O-RO:–

CH3-C-CH3OR

+

OR

OHCH3-C-CH3

–:O-R++ H–ORO:–

CH3-C-CH3OR

b) Addition of AlcoholsAddition of one molecule of alcohol to the C=O group of an aldehyde or ketone gives a hemiacetalHemiacetal: a molecule containing an -OH and an -OR or -OAr bonded to the same carbon

Formation of a hemiacetal is base catalyzed

Step 1: proton transfer from HOR gives an alkoxide

Step 2: Attack of RO- on the carbonyl carbon

Step 3: proton transfer from the alcohol to O- gives the hemiacetal and generates a new base catalyst

10

OCH3-C-CH3 H-A

OCH3-C-CH3

H

:A-+

+ +:

OCH3-C-CH3

H

H-O-RO

OH

RH

CH3-C-CH3++

+:

:

O

OH

RH

CH3-C-CH3OR

OHCH3-C-CH3 H-A

++

A - ::

A diethyl acetal

+

+

A hemiacetal

OH

CH3

CH3

OCH2CH3

CH3COCH2CH3 CH3CH2OH H+

CH3COCH2CH3 H2O

A cyclic acetalO CH2

CH2O

+O HOCH2CH2OH H+

+ H2O

Formation of a hemiacetal is also acid catalyzed Step 1: proton transfer to the carbonyl oxygen

Step 2: attack of ROH on the carbonyl carbon

Step 3: proton transfer from the oxonium ion to A- gives the hemiacetal and generates a new acid catalyst

Hemiacetals react with alcohols to form acetalsAcetal: a molecule containing two -OR or -OAr groups bonded to the same carbon

With ethylene glycol, the product is a five-membered cyclic acetal.

11

Acetophenone

++CCH3

O OCCH2BrBr2 CH3COOH HBr

RCCH3O 3Br2

3NaOHRCCBr3O NaOH RCO-Na+

OCHBr3+

Tribromomethane (Bromoform)

:ORC-CBr3

-:OHO-

RC-CBr3OH

ORC

OH-:CBr3+ +

Conjugate baseof bromoform

-:CBr3

ORC-O:-

ORC-O-H + + H-CBr3

Bromoform

V. -Halogenation: -Halogenation: aldehydes and ketones with at least one -hydrogen react at -carbon with Br2 and Cl2 reaction is catalyzed by both acid and base

Haloform ReactionIn the presence of base, a methyl ketone reacts with three equivalents of halogen to give a 1,1,1-trihaloketone, which then reacts with an additional mole of hydroxide ion to form a carboxylic salt and a trihalomethane

+

5-Methyl-3-hexen-2-one 4-Methyl-2-pentenoicacid

Trichloromethane(Chloroform)

1. Cl2 / NaOH2. HCl/ H2 O CHCl3

O

OH

O

The final stage is divided into two stepsStep 1: addition of OH- to the carbonyl group gives a tetrahedral carbonyl addition intermediate and is followed by its collapse

Step 2: proton transfer from the carbonyl group to the haloform anion

12

CHO H2CrO4 COOHHexanal Hexanoic acid

Vanillic acidVanillin

++CH

HO

CH3OO O

CH3O

HO

COHAg2OTHF, H2O

NaOHAgHCl

H2O

Benzoic acidBenzaldehyde

+CHO O

COH2O22

Hexanedioic acid (Adipic acid)

Cyclohexanone(keto form)

Cyclohexanone(enol form)

HNO3

O

HO OH

OO OH

VI. a)Oxidation of Aldehydes Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents, including

H2CrO4

They are also oxidized by Ag(I) in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a

slurry of silver oxide

Aldehydes are oxidized by O2 in a radical chain reactionliquid aldehydes are so sensitive to air that they must be stored under N2

b)Oxidation of Ketones• ketones are not normally oxidized by chromic acid• they are oxidized by powerful oxidants at high temperature and high concentrations of

acid or base

13

+ 25oC, 2 atmPt

Cyclohexanone Cyclohexanol

O OH

H2

1-Butanol trans-2-Butenal(Crotonaldehyde)

2H2NiH

OOH

Hydride ionLithium aluminum hydride (LAH)

Sodium borohydride

H

H H

HH-B-H H-Al-HLi +Na+ H:

VII. Reduction• aldehydes can be reduced to 1° alcohols• ketones can be reduced to 2° alcohols • the C=O group of an aldehyde or ketone can be reduced to a -CH2- group

AldehydesCan BeReduced to Ketones

Can BeReduced to

O OOH

RCHRCH2 OH

RCH3RCR'

RCHR'

RCH2 R'

a)Catalytic ReductionCatalytic reductions are generally carried out at from 25° to 100°C and 1 to 5 atm H2

A carbon-carbon double bond may also be reduced under these conditions• by careful choice of experimental conditions, it is often possible to selectively reduce a

carbon-carbon double in the presence of an aldehyde or ketone.

b) Metal Hydride ReductionThe most common laboratory reagents for the reduction of aldehydes and ketones are NaBH4

and LiAlH4 .Both reagents are sources of hydride ion, H:-, a very powerful nucleophile

14

4RCHO

NaBH4

(RCH2O)4B- Na+ H2O 4RCH2OHA tetraalkyl borate

borate salts

+

+ methanol

from water

from the hydride reducing agent

+H

H O O BH3

OH

H

HH-B-HNa+ R-C-R' R-C-R'

Na+

H2 O

R-C-R'

4RCR LiAlH4

(R2CHO)4Al- Li+ H2O4RCHR

OH+

+ aluminum salts

ether

A tetraalkyl aluminate

O

O OHRCH=CHCR' RCH=CHCHR'

1. NaBH42. H2O

+ RhO

RCH=CHCR' RCH2 CH2CR'H2

O

• reductions with NaBH4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol

• one mole of NaBH4 reduces four moles of aldehyde or ketone

The key step in metal hydride reduction is transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound

LiAlH4 Reduction• unlike NaBH4, LiAlH4 reacts violently with water, methanol, and other protic solvents• reductions using it are carried out in diethyl ether or tetrahydrofuran (THF)

Metal Hydride Reduction• metal hydride reducing agents do not normally reduce carbon-carbon double bonds, and

selective reduction of C=O or C=C is often possible

15

Zn(Hg), HClOH O OH

Clemmensen Reduction• refluxing an aldehyde or ketone with amalgamated zinc in concentrated HCl converts the

carbonyl group to a methylene group

Wolff-Kishner Reduction• in the original procedure, the aldehyde or ketone and hydrazine are refluxed with KOH in

a high-boiling solvent• the same reaction can be brought about using hydrazine and potassium tert-butoxide in

DMSO

16