Aldehydes and Ketones

Dr. Talat R. Al-Ramadhany

Introduction

Aldehydes are compounds of the general formula RCHO;Ketones are compounds of the general formula RR´CO. The groups R and R´ may be aliphatic or aromatic.

C

O

Carbonyl groupR

CH

O

AldehydeR

CR

O

Ketone

Both aldehydes and ketones contain the carbonyl group, C=O, and are often called carbonyl compounds.

An aldehyde is often written as RCHO. Remember that the H atom is bonded to the carbon atom, not the oxygen.

Likewise, a ketone is written as RCOR, or if both alkyl groups are the same, R2CO. Each structure must contain a C––O for every atom to have an octet.

The three bonds (carbon, oxygen, and the two other atoms attached to carbonyl carbon) lie in a plane; the three bond angels of carbon are very close to 120º.

NomenclatureBoth IUPAC and common names are used for aldehydes

and ketones.

Naming Aldehydes in the IUPAC System

To name an aldehyde using the IUPAC system:

[1] If the CHO is bonded to a chain of carbons, find the longest chain containing the CHO group, and change the -e ending of the parent alkane to the suffix -al. If the CHO group is bonded to a ring, name the ring and add the suffix -carbaldehyde.

[2] Number the chain or ring to put the CHO group at C1

Example:Give the IUPAC name for the compound:

Give the IUPAC name for the compound:

C

HOO2N

p-nitrobenze carbaldehyde

C

HOH3C

p-methylbenze carbaldehyde

Common Names for Aldehydes

The common names of aldehydes are derived from the names of the corresponding carboxylic acids by replacing –ic acid by –aldehyde.

Greek letters are used to designate the location of substituents in common names. The carbon adjacent to the CHO group is the ` carbon, and so forth down the chain.

Naming Ketones in the IUPAC System

To name an acyclic ketone using IUPAC rules:

[1] Find the longest chain containing the carbonyl group, and change the -e ending of the parent alkane to the suffix -one.

[2] Number the carbon chain to give the carbonyl carbon the lower number. Apply all of the other usual rules of nomenclature.

Common Names for Ketones

Most common names for ketones are formed by naming both alkyl groups on the carbonyl carbon, arranging them alphabetically, and adding the word ketone. Using this method, the common name for 2-butanone becomes ethyl methyl ketone.

H3C C CH3

O

PropanoneAcetone

H3CH2C C CH3

O

ButanoneMethyl ethyl ketone

H3CH2CH2C C CH3

O

2-Pentanone

C CH3

O

Acetophenone

C CH2CH2CH3

O

n-Butyrophenone

C

O

Benzophenone

Physical properties:

Boiling point:

Aldehydes and ketones are polar compounds due to the polarity of carbonyl group and hence they have higher boiling points than non polar compounds of comparable molecular weight.

But they have lower boiling points than comparable alcohols or carboxylic acids due to the intermolecular hydrogen bonding.

Solubility: The lower aldehydes and ketones soluble in

water, because of hydrogen bonding between carbonyl group and water, also they soluble in organic solvents.

Preparation of aldehydes & Ketones.

Preparation of aldehydes.

1. Oxidation of primary alcohols:

Primary alcohols can be oxidized to give aldehydes by using of K2Cr2O7.

RCH2OH + Cr2O7-- R C O

H+ Cr+++

1o alcohol Orange-red An aldehyde Green

K2Cr2O7

R C OOH

A carboxylic acid

2. Oxidation of Methylbenzenes:

In the case of methylbenzenes, oxidation of the side chain can be interrupted by trapping with acetic anhydride to form gem-diacetate, which on hydrolysis its return to aldehydes.

ArCH3CrO3

(AcO)2OArCH(OCCH3)2

O

hydrolysis ArCHO

A gem-diacetateNot oxidized

CH3

CHCl2 CO

H

H2O

CH(OCCH3)2

O

CO

H

H2O

3. Partial reduction of acid chlorides

Strong reducing agents (like LiAlH4) reduce acid chlorides all the way to primary alcohols. Lithium aluminum tri(t-butoxy)hydride is a milder reducing agent that reacts faster with acid chlorides than with aldehydes. Reduction of acid chlorides with lithium aluminum tri(t-butoxy)hydride gives good yields of aldehydes.

(-78ºC)

4. Partial reduction of esters

Sterically bulky reducing agents, e.g. Diisobutylaluminium hydride (DIBAH), can selectively reduce esters to aldehydes. The reaction is carried out at low temperature (-78ºC) in toluene.

R C OR

O

R C H

Oi. DIBAH , -78oC

ii. H2O

(H3C)2HCH2C Al

H

CH2CH(CH3)2

Ester Aldehyde

Diisobutylaluminium hydride(mild reducing agent)

5. Reduction of Nitriles

Reduction of nitrile with a less powerful reducing reagent, e.g. DIBAH, produces aldehyde. The reaction is carried out at low temperatures (-78ºC) in toluene.

R C N i. DIBAHii. H2O

R C H

O

Nitrile Aldehyde

R C

O

H

RH2C OHK2Cr2O7, H2SO4

warm

ArCH3i. CrO3 , (AcO)2O

ii. hydrolysis

1o Alcohol

Methylbenzene

R C

O

Cl

R C

O

OR

Acid chloride

Ester

i. LiAlH(O-t-But)3

ii. H3O+

ii. H3O+

i. DIBAH

i. DIBAHii. H2O

C NRNitrile

Preparation of Ketones

1. Oxidation of Secondary alcohols:Secondary alcohols are oxidized to ketones by chromic

acid (H2CrO4) in a form selected for the job at hand: aqueous K2Cr2O7, CrO3 in glacial acetic acid, CrO3 in pyridine, etc. Hot permanganate also oxidizes alcohols; it is seldom used for the synthesis of ketones.

R CH

R-

OHK2Cr2O7 or CrO3 R C

R-

O

A 2o alcohol A ketone

2. Cleavage of Carbon–Carbon double bond by Ozone:

Oxidative cleavage of an alkene breaks both the σ and π bonds of the double bond to form two carbonyl groups. Depending on the number of R groups bonded to the double bond, oxidative cleavage yields either ketones or aldehydes.

3. Friedel-Crafts acylation.

The Friedel-Crafts reaction involves the use of acid chlorides rather than alkyl halides. An acyl group (RCO–) becomes attached to the aromatic ring. Thus forming a ketone; the process is called acylation.

Ar H + R CCl

OAlCl3 Ar C R

O

+ HClor other

Lewis acid

4. Synthesis of Ketones from Nitriles.

A Grignard or organolithium reagent attacks a nitrile to give the magnesium salt of an imine. Acidic hydrolysis of the imine leads to the ketone.

5. Hydration of alkynes.

Alkynes undergo acid-catalyzed addition of water across the triple bond in the presence of mercuric ion as a catalyst. A mixture of mercuric sulfate in aqueous sulfuric acid is commonly used as the reagent.

Reactions of aldehydes and Ketones

Aldehydes and Ketones undergo many reactions to give a wide variety of useful derivatives. There are two general kinds of reactions that aldehydes and ketones undergo:

[1] Reaction at the carbonyl carbon (Nucleophilic addition reactions).

[2] Reaction at the α carbon.A second general reaction of aldehydes and ketones involves

reaction at the α carbon. A C–H bond on the α carbon to a carbonyl group is more acidic than many other C–H bonds, because reaction with base forms a resonance-stabilized enolate anion.

[1] Nucleophilic addition reaction.

Two general mechanisms are usually drawn for nucleophilic addition, depending on the nucleophile (negatively charged versus neutral) and the presence or absence of an acid catalyst.

With negatively charged nucleophiles, nucleophilic addition follows the two-step process first (nucleophilic attack) followed by protonation.

Step [1]: The nucleophile attacks the carbonyl group, cleaving the π bond and moving an electron pair onto oxygen. This forms a sp3 hybridized intermediate with a new C–Nu bond.

Step [2]: protonation of the negatively charged O atom by H2O forms the addition product.

Absence of an acid catalyzed nucleophilic addition

Acid-catalyzed nucleophilic addition

Step [1] Protonation of the carbonyl group

The general mechanism for this reaction consists of three steps (not two), but the same product results because H and Nu- add across the carbonyl π bond. In this mechanism protonation precedes nucleophilic attack.

Steps [2]–[3] Nucleophilic attack and deprotonation

In Step [2], the nucleophile attacks, and then deprotonation forms the neutral addition product in Step [3].

a) Addition of Alcohols (Acetal Formation):

Aldehydes and ketones react with two equivalents of alcohol to form acetals. In an acetal, the carbonyl carbon from the aldehyde or ketone is now singly bonded to two OR" (alkoxy) groups.

b) Nucleophilic Addition of H- (Reduction reaction)

Treatment of an aldehyde or ketone with either Sodium borohydride (NaBH4) or Lithium hydride (LiAlH4) followed by protonation forms a 1° or 2° alcohol.

Hydride reduction of aldehydes and ketones occurs via the two-step mechanism of nucleophilic addition, that is, nucleophilic attack of H:– followed by protonation.

RC

R

OH2 + Ni, Pt

LiAlH4 orNaBH4 then H+

R C

H

OH

Ror Pd

O

i) LiAlH4

ii) H+

OHH

CyclopentanolCyclopentanone

CH

CH

C H

Oi) NaBH4

ii) H+CH

CH

CH

H

OH

Cinnamyl alcohol3-Phenylacrylaldehyde(Cinnamaldehyde)

Examples:

c) Reduction to alkane (Deoxygenation of Ketones and Aldehydes):

i) Clemmensen reduction.

ii) Wolff–Kishner reduction.

Clemmensen reduction: The Clemmensen reduction is most commonly used to

convert acylbenzenes (from Friedel-Crafts acylation) to alkylbenzenes, but it also works with other ketones or aldehydes that are not sensitive to acid. The carbonyl compound is heated with an excess of amalgamated zinc (zinc treated with mercury; Zn (Hg), and concentrated hydrochloric acid (HCl). The actual reduction occurs by a complex mechanism on the surface of the zinc.

CH3CH2CH2COCl

AlCl3

n-Butyrophenone

Zn(Hg),

conc. HCl

n-Butylbenzene

CCH2CH2CH3

O

CCH2CH2CH3

H H

The Clemmensen reduction uses zinc and mercury in the presence of strong acid.

H3C (CH2)5 CZn(Hg)

HCl, H2OH3C (CH2)5 CH3

O

H

Heptanal n-Heptane (72%)

Zn(Hg)

HCl, H2O

OH

H

Cyclohexane (75%)Cyclohexanone

CCH3

O

Zn(Hg), conc. HClC

CH3

Acetophenone

HH

1-Ethylbenzene

Compounds that cannot survive treatment with hot acid can be deoxygenated using the Wolff–Kishner reduction. The ketone or aldehyde is converted to its hydrazone, which is heated with Hydrazine (NH2NH2), and strong base such as KOH. Ethylene glycol, diethylene glycol, or another high-boiling solvent is used to facilitate the high temperature (140-200°C) needed in the second step.

Wolff–Kishner reduction:

C

O

+ H2N NH2 C

N NH2

+ H2O KOHHeat C

HH+ H2O + N N

Hydrazone

O

N2H4

NNH2

Hydrazone

KOH, 175oC

HOCH2CH2OCH2CH2OH(Diethylene glycol)

H H

+ N2

CC(CH3)3

O

NH2NH2 + OH-C

C(CH3)3

HH

O

i) NH2NH2

ii) base

HH

CyclopentaneCyclopentanone

O

Zn(Hg), conc. HCl

NH2NH2, base

C

H

H

C

H

H

Clemmensen reductionfor compounds sensitive to base

for compounds sensitive to acidWolff-Kishner reduction

Summary:

d) Nucleophilic Addition of CN– :Treatment of an aldehyde or ketone with NaCN and a strong

acid such as HCl adds the elements of HCN across the carbon–oxygen π bond, forming a cyanohydrin.

CH

ONaCN

NaHSO3

CH

CNOH

MandelonitrileBenzaldehyde

H3C C CH3

O

Acetone

+ NaCNH2SO4 H3C C CN

CH3

OHAcetone cyanohydrin

H2O, H2SO4 H3C C COOH

CH3

OH

H2C C COOH

CH3

Methacrylic acid

- H2O

e) Addition of Bisulfate.Sodium bisulfate adds to most aldehydes and to many ketones

(especially methyl ketones and cycloketones) to form bisulfate addition products:

C

O+ Na+ HSO3

- C

OH

SO3- Na+

A bisulfateaddition product

C

O

C

O-

SO3-

:SO3H-

C

OH

SO3-H+

Nucleophilicreagent

Examples:

C HO

+ Na+ HSO3- C

OH

SO3- Na+

H

+ Na+ HSO3-H3CH2C C CH3

O

H3CH2C C SO3- Na+

OH

CH3

H2O

n-Butanone

+ Na+ HSO3-H

C CHC

OH2O

CH3

CH3

H3C

CH3

Isopropyl ketone2,4-Dimethyl-3-pentanone

No reaction ?

Ketones containing bulky groups usually fail to react with bisulfate, because of steric effect.

f) Addition of organometallic reagents (R–)

The addition of Grignard reagents to aldehydes and ketones yields alcohols. The organic group, transferred with a pair of electrons from magnesium to carbonyl carbon, is a powerful nucleophile. 

C

O

+ R: MgX

CR

OMgXH2O

CR

OH + Mg(OH)X

H+

Mg++ + X- + H2O

g) Addition of derivatives of Ammonia (Formation of imine).

Treatment of an aldehyde or ketone with a 1° amine affords an imine (also called a Schiff base).

Nucleophilic attack of the 1° amine on the carbonyl group forms an unstable carbinolamine, which loses water to form an imine. The overall reaction results in replacement of C=O by C=NR.

Oxidation reaction

Aldehydes are readily oxidized to yield carboxylic acids; but ketones are generally inert toward oxidation.

The difference is a consequence of structure: aldehydes have a –CHO proton that can be abstracted during oxidation, but ketones do not.

RC

H

OHydrogen here

RC

OH

O[O]

An aldehyde Carboxylic acidR

CR

O No hydrogen here

A ketone

Many oxidizing agents, including KMnO4 and hot HNO3, convert aldehydes into carboxylic acid.

But CrO3 in aqueous acid is a more common choice in the laboratory. The oxidation occurs rapidly at room temperature and results in good yields.

RCHO or ArCHO KMnO4

K2Cr2O7

RCOOH or ArCOOH

hot HNO3

Tollen's reagent

In the laboratory, oxidation of an aldehyde can be carried out using a solution of silver oxide (Ag2O) in aqueous ammonia, the so-called Tollen's reagent. Oxidation of aldehyde is accompanied by reduction of silver ion to free silver (in the form of a mirror under the proper conditions).

H3CC

H

O

+ Ag(NH3)2+ + 3OH- 2Ag + CH3COO- + 4NH3 + 2H2O

Colorlesssolution

Silvermirror

CH

O

Ag2O

NH4OH, H2O,Ethanol

Benzaldehyde

COH

O

Benzoic acid

+ 2Ag

Methyl ketones:Oxidation of ketones required breaking of C–C bond next to

the carbonyl group and takes place only under vigorous conditions, except for methyl ketones which oxidized smoothly by mean of hypohalite (NaOX) to form Haloform (Haloform reaction).

Reactions of aldehydes and Ketones

Aldehydes and Ketones undergo many reactions to give a wide variety of useful derivatives. There are two general kinds of reactions that aldehydes and ketones undergo:

[1] Reaction at the carbonyl carbon (Nucleophilic addition reactions).

[2] Reaction at the α carbon.A second general reaction of aldehydes and ketones involves

reaction at the α carbon. A C–H bond on the α carbon to a carbonyl group is more acidic than many other C–H bonds, because reaction with base forms a resonance-stabilized enolate anion.

[2] Reaction involving acidic α-hydrogen

The carbonyl strengthens the acidity of the hydrogen atoms attached to the α-carbon and, by doing this, gives rise to a whole set of chemical reactions.

Ionization of an α-hydrogen, yields a carbanion (I) that is a resonance hybrid of two structures: Keto form and Enol form.

C C

H

+ :B C C + B:H

OO

(I)

C C C C

OO

(I)

C C

H O

keto form Enol form

equivalent to

a) Halogenation of ketones:

When a ketone is treated with a halogen and base, an α-halogenation reaction occurs.

b) Aldol condensation

Under the influence of or , two molecules of an aldehyde or a ketone, which , may combine to form a β-Hydroxy aldehyde or β-Hydroxy ketone. This reaction is called the .

Aldehyde alcohol

dilute base dilute acidcontained α-hydrogen

Aldol condensation

Mechanism:

If aldehyde or ketone does not contain an α-hydrogen, a simple Aldol condensation cannot take place.

For example:

ArCHOHCHO(CH3)3CCHOArCOArArCOCR3

No-hydrogenatoms

dilute OH-No reaction

Cannizzaro reaction.

In the presence of concentrated alkali, aldehydes containing no α-hydrogen undergo self-oxidation and reduction to yield a mixture of an alcohol and a salt of a carboxylic acid. This reaction is known as the Cannizzaro reaction.

C

H

O2 strong baseCOO- + CH2OH

An aldehyde withno hydrogen

Acidsalt

Alcohol

Examples:

H C

H

O250% NaOH

room temp.H COO- + CH3OH

Formaldehyde Formate ion Methanol

CHO

Clm-Chlorobenzaldehyde

250% KOH

COO-

Cl

+

CH2OH

Clm-Chlorobenzyl

alcoholm-Chlorobenzoate

ion

O2N CHO

p-Nitrobenzaldehyde

35% NaOHO2N CH2OH O2N COO- Na++

Sodium p-nitrobenzoatep-Nitrophenyl alcohol

2

If two different aldehydes with no α-hydrogen undergo Cannizzaro reaction yield a mixture of products. This reaction is called crossed Cannizzaro reaction.

ArCHO + HCOH ArCH2OH +HCOO- Na+conc. NaOH

CHO

conc. NaOH

CH2OH

+ HCOO- Na+

OCH3

+ HCOH

OCH3

Anisaldehydem-Methoxybenzaldehyde

m-Methoxybenzyl alcohol

Crossed Cannizzaro reaction