Aldehydes and ketones DR AKM SHAFIQUL ISLAM SCHOOL OF BIOPROCESS ENGINEERING UNIVERSITY MALAYSIA PERLIS (UniMAP)

Aldehydes and ketonesAldehydes and ketones

DR AKM SHAFIQUL ISLAMDR AKM SHAFIQUL ISLAMSCHOOL OF BIOPROCESS ENGINEERINGSCHOOL OF BIOPROCESS ENGINEERINGUNIVERSITY MALAYSIA PERLIS (UniMAP)UNIVERSITY MALAYSIA PERLIS (UniMAP)

Carbonyl groupCarbonyl group

One of the most important functional One of the most important functional groups in organic chemistry.groups in organic chemistry.

It is present in aldehydes and ketonesIt is present in aldehydes and ketones

C

O

Carbonyl CompoundsCarbonyl Compounds

AldehydesAldehydes

A compound in which the carbonyl group A compound in which the carbonyl group is connected to a hydrogen and an alkyl is connected to a hydrogen and an alkyl group or aromatic ring ( or to two group or aromatic ring ( or to two hydrogens ).hydrogens ).

C HH

O

C HR

O

C H

O

KetonesKetones

A compound in which the carbonyl group A compound in which the carbonyl group is connected to two alkyl groups or is connected to two alkyl groups or aromatic rings ( or one of each ).aromatic rings ( or one of each ).

C RR

O

C R

O

C

O

O

IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes

3-Methylbutanal 2-Propenal(Acrolein)

Hexanal

12

34H

O

H

O1

23

45

6

123

H

O

Find the longest continuous chain that includes the aldehyde group

Follow all the IUPAC naming rules for alkanes. The carbonyl carbon is always at the end of the chain, so it is

carbon number 1. Replace the final -e ending of the alkane with -al. Locate and name any other groups attached to the chain. Aldehydes containing two aldehyde groups are called dials.

IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes

The aldehyde group is abbreviated by CHO.The aldehyde group is abbreviated by CHO. The IUPAC retains the common names The IUPAC retains the common names

benzaldehyde and cinnamaldehyde, as well benzaldehyde and cinnamaldehyde, as well formaldehyde and acetaldehyde.formaldehyde and acetaldehyde.

CHO

H

OCHO

OCH3

OHtrans-3-Phenyl-2-propenal

(Cinnamaldehyde; inoil of cinnamon)

Benzaldehyde(in almonds)

Vanillin(from vanilla

beans)

IUPAC Nomenclature of IUPAC Nomenclature of KetonesKetones

CH3 C CH3

O

Because ketones have the general formula, the shortest ketone chain length is 3 carbons.

The carbonyl group cannot be at the end of the chain; it must be in the middle.

CR R

O

IUPAC Nomenclature of KetonesIUPAC Nomenclature of Ketones

Find the longest continuous chain that includes the carbonyl

group

Follow all the IUPAC naming rules for alkanes.

The chain is numbered from the end closest to the carbonyl

group.

Replace the final -e ending of the alkane with -one.

Locate and name any other groups attached to the chain.

O

Acetone 2-Methylcyclohexanone5-Methyl-3-hexanone

OO

12

34

56

12

Copyright© 2005, Michael J. Wovkulich. All rights

reserved.

CH3CCH3

O 2-propanone

dimethyl ketoneacetone

CH3CCH2CH3

O

CH3 C

O

CH2 C

CH3

CH3

C

Cl

H

CH3

2-butanone

ethyl methyl ketone ME

Kmethyl ethyl

ketone

5-chloro-4,4-dimethyl-2-hexanone1 2 3

4 56

Name the following ketones using IUPAC names and common names.

Common names - ketonesCommon names - ketones

name each alkyl group bonded to the name each alkyl group bonded to the carbonyl carbon as a separate word, carbonyl carbon as a separate word, followed by the word "ketone”followed by the word "ketone”

O

CH3CH

O

CH3COH

Acetaldehyde Acetic acid Ethyl isopropyl ketoneMethyl ethyl ketone

OO

Natural ProductsNatural Products

Physical PropertiesPhysical Properties

What kind of intermolecular forces are What kind of intermolecular forces are possible between carbonyl groups?possible between carbonyl groups?

Is H-bonding possible?Is H-bonding possible? How do you think the boiling point of How do you think the boiling point of

aldehydes and ketones compares to alkanes aldehydes and ketones compares to alkanes and alcohols?and alcohols?• Alkanes – very weak forcesAlkanes – very weak forces• Alcohols – H-bondsAlcohols – H-bonds

Physical PropertiesPhysical Properties A C=O bond is polar, with oxygen bearing A C=O bond is polar, with oxygen bearing

a a partialpartial negative charge and carbon negative charge and carbon bearing a bearing a partialpartial positive charge positive charge therefore, aldehydes and ketones are polar therefore, aldehydes and ketones are polar

moleculesmolecules

C

O

Dipole/Dipole InteractionsDipole/Dipole InteractionsThe electronegativity number (E.N.) of carbon is 2.5. The E.N. of oxygen is 3.5.

As a result of unequal sharing, the carbonyl bond is polar covalent and the oxygen acquires a partial negative charge.

Dipole/dipole interactions aren’t as strong as hydrogen bonds, but they do cause aldehydes and ketones to boil at higher temperatures than alkanes.

dipole/dipole interaction

C

O

C

O

Lack of Hydrogen BondingLack of Hydrogen Bonding

Because aldehydes and ketones lack a hydrogen on the Because aldehydes and ketones lack a hydrogen on the oxygen, they oxygen, they cannotcannot form hydrogen bonds between form hydrogen bonds between other aldehyde or ketone molecules.other aldehyde or ketone molecules.

Thus, their boiling points are Thus, their boiling points are lowerlower than those of alcohols than those of alcohols with similar molecular weights (which have extensive with similar molecular weights (which have extensive hydrogen bonding).hydrogen bonding).

Aldehyde Ketone

CR H

O

CR R

O

SolubilitySolubility

Even though it cannot H-bond with other Even though it cannot H-bond with other carbonyls, the carboxyl group can accept carbonyls, the carboxyl group can accept H-bonds from waterH-bonds from water formaldehyde, acetaldehyde, and acetone are formaldehyde, acetaldehyde, and acetone are

infinitely soluble in waterinfinitely soluble in water As the hydrocarbon portion of the molecule As the hydrocarbon portion of the molecule

increases in size, solubility in water decreasesincreases in size, solubility in water decreases

• Larger ketones and aldehydes are soluble in Larger ketones and aldehydes are soluble in organic solventsorganic solvents

Water SolubilityWater Solubility

Aldehydes and ketones form strong hydrogen bonds with water:

As a result, low-molecular weight aldehydes and ketones show appreciable solubilities in water. Acetone and ethanal are soluble in water in all proportions.

OxidationOxidation

CH3

O

H CH3

O

OH

[O ]

CH3

O

CH3

[O ]NR

Aldehydes are oxidized to Aldehydes are oxidized to carboxyliccarboxylic acidsacids Change the –H to an –OHChange the –H to an –OH

Ketones are not oxidized furtherKetones are not oxidized further

Oxidation of Primary AlcoholsOxidation of Primary Alcohols

General equation:

+ H2O

oxidizeRCH2OH

Primary alcohol

oxidize

Aldehyde(in anhydrous media)

Carboxylic acid(when water is present)

R C

OH

H

H

CR H

O

R C

O

OH

(O)

(O)

RCHO RCOOH

Oxidation of Primary AlcoholsOxidation of Primary Alcohols

Examples:

(O)CH3CH2OH

ethanol

(O)

ethanal ethanoic acid

(O)CH3(CH2)5CH2OH

1-heptanol

(O)

heptanal heptanoic acid

C

O

CH3 OHC

O

CH3 H

C

O

CH3(CH2)5 H C

O

CH3(CH2)5 OH

Tests for AldehydesTests for Aldehydes

Tollens’ reagent and Benedict’s reagent are two common chemical reagents used to test for the presence of aldehydes.

Both are mild oxidizing solutions.

Tollens’ ReagentTollens’ Reagent

+ Ag+(aq) + Ag(s)CR H

O

+1oxidation state

0oxidation state

R C OH

ONH3, H2O

heat

Tollens’ reagent is a solution of aqueous silver nitrate (AgNO3) with aqueous ammonia (NH3).

All aldehydes give a positive Tollens’ test. In general, ketones don’t react with the Tollens’ reagent except a-hydroxy ketones.

Tollens’ ReagentTollens’ Reagent(Silver Mirror Test)(Silver Mirror Test)

If the rate of reaction is slow and the test tube or flask is clean, metallic silver deposits on the sides as a mirror.

Benedict’s ReagentBenedict’s Reagent

Benedict’s reagent is a solution containing blue, Cu2+ ions.

The copper is reduced from the +2 oxidation state to the +1 oxidation state. Red Cu2O is precipitated, giving a positive test.

+ Cu2+ + Cu2OCR H

O

R C OH

O

+2oxidation state

+1oxidation state

Benedict’s ReagentBenedict’s Reagent

Aldehydes and one type of easily oxidized ketone give a positive test result. The structural features necessary are:

Aldehyde Aldehydewith adjacent alcohol group

Ketonewith adjacent alcohol group

These features are found in a number of sugars.

CH C H

O

R

OH

CH C R

O

R

OH

CR H

O

Benedict’s ReagentBenedict’s Reagent

Benedict’s reagent is the key material in a test kit available from drugstores that permits individuals to monitor the glucose levels in their urine.

Nucleophilic ReactionNucleophilic Reaction Reagents that attack the electron-rich d- end of the C=O Reagents that attack the electron-rich d- end of the C=O

bond are called electrophiles (literally, "lovers of electrons"). bond are called electrophiles (literally, "lovers of electrons"). Electrophiles include ions (such as HElectrophiles include ions (such as H++ and Fe and Fe3+3+) and neutral ) and neutral molecules (such as AlClmolecules (such as AlCl33 and BF and BF33) that are Lewis acids, or ) that are Lewis acids, or electron-pair acceptors.electron-pair acceptors.

Reagents that attack the electron-poor d+ end of this bond Reagents that attack the electron-poor d+ end of this bond are nucleophiles (literally, "lovers of nuclei"). Nucleophiles are nucleophiles (literally, "lovers of nuclei"). Nucleophiles are Lewis bases (such as NHare Lewis bases (such as NH33 or the OH- ion). or the OH- ion).

Nucleophilic AdditionNucleophilic Addition A strong nucleophile attacks the carbonyl carbon, A strong nucleophile attacks the carbonyl carbon,

forming an alkoxide ion that is then protonated.forming an alkoxide ion that is then protonated.

A weak nucleophile will attack a carbonyl if it has A weak nucleophile will attack a carbonyl if it has been protonated, thus increasing its reactivity.been protonated, thus increasing its reactivity.

Aldehydes are more reactive than ketones.Aldehydes are more reactive than ketones.

=>

Reaction Themes, Nu attack at CReaction Themes, Nu attack at C

One of the most common reaction themes of a carbonyl One of the most common reaction themes of a carbonyl group is addition of a nucleophile to form a tetrahedral group is addition of a nucleophile to form a tetrahedral carbonyl addition compound.carbonyl addition compound.

Tetrahedral carbonyl addition compound

+ CR

R

O CNu

O -

RR

Nu -

Reaction Themes, O attack at HReaction Themes, O attack at H

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

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

B -

C OR

R

H-Nu

H-B

C OR

RH

B -

C OR

RH

CNu

O-H

RR

C OR

RH

H-B

+fast +

++

+slow

Tetrahedral carbonyl addition compound

++ +

Addition of C NucleophilesAddition of C Nucleophiles

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

RMgX RLi - C RC C - NA Grignard

reagentAn organolithium

reagentAn alkyne

anionCyanide ion

A. A. GrignardGrignard Reagents Reagents

Given the difference in electronegativity between carbon Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Ccovalent, with C-- and Mg and Mg++..

in its reactions, a Grignard reagent behaves as a in its reactions, a Grignard reagent behaves as a carbanion.carbanion.

CarbanionCarbanion: an anion in which carbon has an unshared : an anion in which carbon has an unshared pair of electrons and bears a negative charge.pair of electrons and bears a negative charge.

a carbanion is a good nucleophile and adds to the a carbanion is a good nucleophile and adds to the carbonyl group of aldehydes and ketones.carbonyl group of aldehydes and ketones.

Grignard Reagents, 1Grignard Reagents, 1oo alcohols alcohols

addition of a Grignard reagent to formaldehyde addition of a Grignard reagent to formaldehyde followed by Hfollowed by H33OO++ gives a 1° alcohol. gives a 1° alcohol.

these reactions require two steps.these reactions require two steps.

CH3CH2-MgBr

O

H-C-H

O -[MgBr]

+

CH3CH2-CH2 HClH2O

OH

CH3CH2-CH2 Mg2+

ether

1-Propanol(a 1° alcohol)

Formaldehyde

+

+

A magnesiumalkoxide

Grignard Reagents, 2Grignard Reagents, 2oo alcohols alcohols

addition to any other aldehyde, RCHO, gives a addition to any other aldehyde, RCHO, gives a 2° alcohol (two steps).2° alcohol (two steps).

MgBr

H

O

O -[MgBr]

+

HClH2O

OH

Mg2+

+ether

Acetaldehyde(an aldehyde)

+

A magnesiumalkoxide

1-Cyclohexylethanol(a 2° alcohol;

(racemic)

Grignard Reagents, 3Grignard Reagents, 3oo alcohols alcohols

addition to a ketone gives a 3° alcohol (two addition to a ketone gives a 3° alcohol (two steps).steps).

Ph-MgBrO

Ph

O -[MgBr]

+HClH2O Ph

OHMg2+

+

Acetone(a ketone)

ether

+

A magnesiumalkoxide

2-Phenyl-2-propanol(a 3° alcohol)

Phenyl-magnesium bromide

B. Organolithium CompoundsB. Organolithium Compounds Organolithium compounds, RLi, give the same C=O Organolithium compounds, RLi, give the same C=O

addition reactions as RMgX but generally are more addition reactions as RMgX but generally are more reactive and usually give higher yields.reactive and usually give higher yields.

Lithium is monovalent and does not insert between C Lithium is monovalent and does not insert between C and X like Mg.and X like Mg.

Like the Grignard this requires two steps.Like the Grignard this requires two steps.

LiO

O- Li+

HClH2O

OH

3,3-Dimethyl-2- butanone

3,3-Dimethyl-2-phenyl-2-butanol(racemic)

+

Phenyl-lithium

A lithium alkoxide(racemic)

C. Salts of Terminal AlkynesC. Salts of Terminal Alkynes

Addition of an alkyne anion followed by Addition of an alkyne anion followed by HH33OO++ gives an acetylenic alcohol. gives an acetylenic alcohol.

C:- Na+HC

OC O -Na+HC

HClH2O

C OHHC

1-Ethynyl-cyclohexanol

A sodiumalkoxide

+

CyclohexanoneSodiumacetylide

Salts of Terminal AlkynesSalts of Terminal Alkynes

Addition of water or hydroboration/oxidation of Addition of water or hydroboration/oxidation of the product gives an enol which rearranges.the product gives an enol which rearranges.

H2O

HO C CHH2SO4, HgSO4

1. (sia)2BH

2. H2O2, NaOH

O

HO CCH3

HO CH2CH

O

An -hydroxyketone

A -hydroxyaldehyde

D. Addition of HCND. Addition of HCN

HCN adds to the C=O group of an aldehyde or HCN adds to the C=O group of an aldehyde or ketone to give a cyanohydrin.ketone to give a cyanohydrin.

CyanohydrinCyanohydrin: a molecule containing an -OH : a molecule containing an -OH group and a -CN group bonded to the same group and a -CN group bonded to the same carbon.carbon.

2-Hydroxypropanenitrile(Acetaldehyde cyanohydrin)

+ HC N CH3C-C NCH3CH

OH

H

O

Addition of HCNAddition of HCN

Mechanism of cyanohydrin formation:Mechanism of cyanohydrin formation: Step 1: nucleophilic addition of cyanide to the Step 1: nucleophilic addition of cyanide to the

carbonyl carbon.carbonyl carbon.

Step 2: proton transfer from HCN gives the Step 2: proton transfer from HCN gives the cyanohydrin and regenerates cyanide ion.cyanohydrin and regenerates cyanide ion.

-• •

+H3C

CH3C

O CO -

H3C

H3C

CN

NC

CO -

H3C

H3C

C NNH C C

C

H3C

H3C

O-H

NC N++

-• •

CyanohydrinsCyanohydrins

The value of cyanohydrins:The value of cyanohydrins: 1. acid-catalyzed dehydration of the alcohol gives an 1. acid-catalyzed dehydration of the alcohol gives an

alkene.alkene.

2. catalytic reduction of the cyano group gives a 1° 2. catalytic reduction of the cyano group gives a 1° amine.amine.

Propenenitrile(Acrylonitrile)

+

acidcatalyst

2-Hydroxypropanenitrile(Acetaldehyde cyanohydrin)

CH3CHC N NCH2=CHC H2 O

OH

CHC

OH

N 2H2Ni

OH

CHCH2NH2

2-Amino-1-phenylethanol(racemic)

+

Benzaldehydecyanohydrin

(racemic)

CyanohydrinsCyanohydrins

The value of cyanohydrins:The value of cyanohydrins: 3. acid-catalyzed hydrolysis of the nitrile gives 3. acid-catalyzed hydrolysis of the nitrile gives

a carboxylic acid.a carboxylic acid.

2-Hydroxypropanoic acid

acidcatalyst

2-Hydroxypropanenitrile(Acetaldehyde cyanohydrin)

CH3CHC N CH3- CHCOOH H 2O

OHOH

Mechanism of Aldol ReactionsMechanism of Aldol Reactions

Aldol reactions, like all carbonyl condensations, occur by Aldol reactions, like all carbonyl condensations, occur by nucleophilic addition of the enolate ion of the donor nucleophilic addition of the enolate ion of the donor molecule to the carbonyl group of the acceptor moleculemolecule to the carbonyl group of the acceptor molecule

The addition intermediate is protonated to give an The addition intermediate is protonated to give an alcohol productalcohol product

Conditions for CondensationsConditions for Condensations

A small amount of base is used to generate a A small amount of base is used to generate a small amount of enolate in the presence of small amount of enolate in the presence of unreacted carbonyl compoundunreacted carbonyl compound

After the condensation, the basic catalyst is After the condensation, the basic catalyst is regeneratedregenerated