Aldehydes

1

ALDEHYDES & KETONES

(ALKANALS & ALKANONES)

2

ALDEHYDES & KETONES (ALKANALS & ALKANONES)

The simplest aldehyde is formaldehyde (CH2O). It is the only aldehyde without an alkyl group attached to the carbonyl C.

C

O

carbonyl group

: :

R C

O

R'ketone

: :

R C

O

H

aldehyde

: :Aldehydes & ketones both contain the carbonyl group.

All other aldehydes, such as acetaldehyde (CH3CHO), have one alkyl group and one H attached to the carbonyl C.formaldehyde

C

O

HH

: :

C

O

HCH3

: :

acetaldehyde

All ketones have two alkyl groups attached to the carbonyl C.

: :

CCH3

O

methyl phenyl ketone (acetophenone)

: :

CH3C CH3

O

dimethyl ketone (acetone)

: :

CH3C CH2CH3

O

methyl ethyl ketone (MEK)

3

Aldehydes and Ketones are Electrophiles

The carbonyl group has a strong dipole.

DEN(O-C) = (3.5-2.5) = 1.0 (a polar bond) The d+ carbon is an electron acceptor,

(an electrophile). Good nucleophiles (CH3MgBr) and even fair nucleophiles (NH3)

will readily add to the carbonyl group of aldehydes and ketones.

Nu:-

E+

C

O

+

: :

The alkyl group and the H atom bonded to the carbonyl are not leaving groups. They are not displaced because hydride (H:-) and alkanides (R:-) are extremely strong bases.

pKb H:- = -21 and pKb :CH3- = -40! (:CH3

- = methide).

: :

R C

O

HNu:-

: :

R C

O

R

Nu

..

sp2 sp3

tetrahedralalkoxide

The weak p bond breaks as the Nu:- adds, so that C remains tetravalent ( 5 bonds).

4

Aldehydes and Ketones are Electrophiles Aldehydes and ketones are moderately reactive as electrophiles

(electron acceptors) among the carboxylic acid derivatives.

most

reactive

acid chloride

acid anhydride

aldehyde

ketone

ester

carboxylic acid

amide

nitrile

carboxylate

least

reactive

R C

O

Cl

: :

:....

R RC

O

O C

O: : : :....

R C

O

H

: :

R RC

O: :

R RC

O

O....

: :

R C

O

OH

: :

..

..

R N

H

HC

O: :..

R

_

C

O

O:

::....

R C N:

5

H+HSO4-: :

R C

O

R

Basicity of Aldehydes and Ketones

The d- oxygen is a weak base (pKb ca. 21)Its non bonded e’s are protonated by strong acids.

: :

R C

O

R

H

+

:

R C

O

R

H

+

The + charge is shared with the carbonyl C by resonance forming a carbocation – a very good E+.

Even weak Nu:-’s (like H2O and ROH) will donate electrons to an aldehyde or ketone in the presence of a strong acid catalyst, e.g., H2SO4 or HCl.

Nu:-

E+

C

O

+

: :

H+HSO4-: :

R C

O

R

: :

R C

O

R

H

+ CH3CH2OH..

..

: :

R C

O

R

H

CH3CH2OH..

+

6

Acidity of Aldehydes and Ketones

The a-carbon is the carbon bonded to the carbonyl, not the carbonyl carbon itself.

Hydrogens bonded to the carbonyl carbon, the a-carbon, the b-carbon, etc. are not polar and thus are not acidic hydrogens.

C

H

H

C

O: :

C

H

H

HH

-hydrogenspKa = ca. 17 in aldehydespKa = ca. 19 in ketones

pKa = ca. 55 for-hydrogens in aldehydes and ketones

The carbonyl H of analdehyde is not acidic.It's pKa is ca. 50.

The a-hydrogens can be removed by strong bases because the carbanion that forms is stabilized by resonance with the adjacent carbonyl oxygen forming an enolate.

C

H

C

O: :

C

H

H

HH..

enolate

C

H

H

C

O: :

C

H

H

HH

OH-

C

H

C

O: :

C

H

H

HH

..

7

Boiling Points and Solubility of Aldehydes and Ketones

The carbonyl group is strongly polar but does not produce hydrogen bonding (It has no polar hydrogens). As a result, the boiling points of aldehydes and ketones are higher than the nonpolar hydrocarbons and the alkyl halides but lower than those of alcohols.

Formaldehyde is a gas at room temperature (b.p. = -21 C) but heavier aldehydes are liquids. Acetone, the simplest ketone, is a liquid at room temperature (b.p. = 56 C).

Lower molecular weight aldehydes and ketones are water soluble. Acetone, formaldehyde and acetaldehyde are miscible in water.

8

IUPAC Nomenclature of Aldehydes

Aldehydes: in open chains: alkane+al “alkanal”

Aldehydes: attached to rings: ring+carbaldehyde “ringcarbaldehyde”

1234

3-bromobutanal 4-hydroxypentanal 12345

2-phenylethanal 12

The parent chain must contain the CHO- group, and this group is numbered as carbon 1 (because it is always at a chain end).

C

O

H C

O

HHO CHO

benzenecarbaldehyde 3-hydroxycyclopentanecarbaldehyde

cyclohexanecarbaldehyde

CH3CHBrCH2C

O

H CH3CHCH2CH2C

O

H

OH

CH2C

O

H

9

Functional Group Precedence in Nomenclature Functional Group Name as Suffix Name as Prefix

Principal Groups

Carboxylic Acids -oic acid –carboxylic acid

carboxy

Acid Anhydrides -oic anhydride -carboxylic anhydride

Esters -oate -carboxylate

alkoxycarbonyl

Acid Halides -oyl halide -carbonyl halide

halocarbonyl

Amides -amide -carboxamide

amido

Nitriles -nitrile -carbonitrile

cyano

Aldehydes -al -carbaldehyde

oxo

Ketones -one oxo

Alcohols -ol hydroxy

Phenols -ol hydroxy

Thiols -thiol mercapto

Amines -amine amino

Imines -imine imino

Alkenes -ene alkenyl

Alkynes -yne alkynyl

Alkanes -ane alkyl

10

Common Names of Aldehydes

In the common system, aldehydes are named from the common names of the corresponding carboxylic acid.

The ‘ic acid’ ending is replaced with ‘aldehyde’.

Substituents locations are given using Greek letters (, , , , , .) beginning with the carbon next to the carbonyl carbon, the a-carbon.

Structure IUPAC name Common name Structure IUPAC Common name

HCO2H methanoic acid HCHO methanal

CH3CO2H ethanoic acid CH3CHO ethanal

CH3CH2CO2H propanoic acid CH3CH2CHO propanal

CH3(CH2)2CO2H butanoic acid CH3(CH2)2CHO butanal

CH3(CH2)3CO2H pentanoic acid CH3(CH2)3CHO pentanal

CH3(CH2)4CO2H hexanoic acid CH3(CH2)4CHO hexanal

formic acid

acetic acid

propionic acid

butyric acid

valeric acid

caproic acid

formaldehyde

acetaldehyde

propionaldehyde

butyraldehyde

valeraldehyde

caproaldehyde

-bromobutyraldehyde -hydroxyvaleraldehyde -phenylacetaldehyde

CH3CHBrCH2C

O

H CH3CHCH2CH2C

O

H

OH

CH2C

O

H

11

IUPAC Nomenclature of Ketones

Ketones are just below aldehydes in nomenclature priority. A ketone group is named as an ‘oxo’ substituent in an aldehyde.

Ketones: in both open chains and rings: alkane+one “alkanone”

The parent chain must contain the C=O group , and this chain is numbered to give the carbonyl group as low a number as possible. In cyclic ketones, the carbonyl group is assigned the number ‘1’.

CH3CCH2CH3

OCH3CHCCHCH3

O

Cl CH3

C CH2CH2CH3

O

1 2 3 4

2-butanone 2-chloro-4-methyl-3-pentanone

1 2 4 5

1 2 3 4

1-phenyl-1-butanone

12345

3-oxopentanal

An olefinic ketone is named as an ‘enone’, literally: “#-alken-#-one”.

1

23

4

4-methyl-2-cyclohexen-1-one

CH3CH2CCH2CHO

O

OH3C

12

Common Names of Ketones

The two alkyl groups attached to the carbonyl are named and the word ‘ketone’ is added as a separate word. It is literally ‘alkyl alkyl ketone’.

The alkyl groups are listed alphabetically or in order of increasing size.

As with aldehydes, substituents locations are given in common names using Greek letters (, , , , , .) beginning with the a-carbon.

: :

R C

O

R'

alkyl alkyl ketone

methyl isobutyl ketone (MIBK)

-chloroethyl isopropyl ketone g-methoxypropyl phenyl ketone

C CH3

O

C H

O

C

O

acetophenone benzophenone benzaldehyde

Some historic names persist:

CH3CHCCHCH3

O

Cl CH3

C CH2CH2CH2

OOCH3

CH3CCH2CHCH3

O CH3

13

Nomenclature Practice

Name these in IUPAC and, where possible, common nomenclature.

CH2 C

O

CH3

F

C

O

H C

O

H

(I) 1-phenyl-2-propanone

(c) methyl benzyl ketone

(I) 4-fluorocyclohexane-1-carbaldehyde

(I) 3-cylcopentene-1-carbaldehyde

Draw the structures of the following compounds.butanedial bromomethyl b-bromoethyl ketone 2,4-pentanedione

And these:

(I) 2-butenal (I) 3-buten-2-one(c) methyl vinyl ketone

HCCH2CH2CH

OO

C

O

CH2CH2BrBrCH2

C

O

H3C CH2 C

O

CH3

CH3CH CH C

O

H

C

O

CH3 CH2 CH

14

Preparation of Aldehydes (2 Methods)

1. Mild oxidation of 1° Alcohols: (with anhydrous oxidants, PCC in CHCl2 or Collins reagent (CrO3 in pyridine). 1,3-cyclobutanedicarbaldehyde

2. Reduction of acid chlorides,esters, and nitriles.

1 DIBAH

2 H3O+

: :

R C

O

H

aldehyde

C

O

R Cl

: :

:....

C

O

R OR

: :

..

..

R C N:

-78°C1equiv.

acid chloride

ester

nitrile

Only 1 equivalent of very cold DIBAH is used to avoid further reduction of the aldehyde to an alcohol.

Dry ice (solid CO2) sublimes at

–78°C.

HOCH2 CH2OHPCC in CH2Cl2

HC CH

OO

15

1 LiAlH4

2 H3O+


Recall that 1° alcohols are readily oxidized to carboxylic acids by most oxidants in aqueous media.

moderate tostrong oxidation

In non aqueous media, moderate to strong oxidants become mild, oxidizing 1° alcohols only as far as the aldehyde.

PCC in CH2Cl2

CrO3 in N

or

: :

R C

O

H

aldehyde

R OH

1° alcohol

mild oxidationC

O

R OH

: :

..

..

carboxylic acid

moderate tostrong oxidation

Jones reagentCrO3 in H2SO4

Carboxylic acids can be reduced to 1° alcohols with LiAlH4, but no reagent has been found that will stop the reduction at the aldehyde.

(Cr+6, HNO3, KMnO4, etc.)

16


Carboxylic acids are difficult to reduce and any reducing agent strong enough to reduce them, e.g., LiAlH4, will not stop at the aldehyde but always produces the 1° alcohol.

Several ‘derivatives’ of carboxylic acids can be reduced to aldehydes under carefully controlled conditions.

Acid chlorides, esters, and nitriles are reduced to aldehydes using very cold conditions (-78°C) and only 1 equivalent of a mild reducing agent, ‘diisobutylaluminum hydride’ = DIBAH (usually in toluene).

CH3CHCH2

CH3

CH2CHCH3

CH3

Al

H

CH3CHCH2

CH3

CH2CHCH3

CH3

Al+ H:

_

diisobutyl aluminum hydride (DIBAH)

+

DIBAH is weaker than LiAlH4. DIBAH is neutral; LiAlH4 is ionic.

DIBAH is similar to AlH3 but is hindered by its bulky isobutyl groups. Only one mole of H:- is released per mole of DIBAH.

Al

H

H H

aluminumhydride

17

1.

2. H3O+

DIBAH -78ºCtoluene

CH3CH2 C

O

H + CH3OH

CH3CH2 C

O

Cl

propanoyl chloride

CH3CH2 C

O

O CH3

methyl propanoateCH3CH2C N

propanenitrileNH3

_HCl

_

propanal


Study the following examples and note which groups are displaced by the hydride (H:-) from DIBAH.

Write equations showing the preparation of:a) pentanal from 1-pentanol

b) butanal from an ester

c) benzaldehyde from a nitrile

CH3CH2CH2CH2CH2OH

PCC in CH2Cl2or

CrO3 in N

CH3CH2CH2CH

O

1 DIBAH

2 H3O+

-78°C1equiv.

C N

1 DIBAH

2 H3O+

-78°C1equiv.

C

O

H

CH3CH2CH2CH2CH

O

CH3CH2CH2COCH3

O

18

Preparation of Ketones (4 Methods)

1. Oxidation of 2° Alcohols: with mild (anhydrous) oxidants, moderate, or strong oxidants, e.g., H2CrO4, HNO3, KMnO4, NaOCl, etc.

OH(CH3 )3 CPCC

or Jones reagent

O(CH3 )3 C

4-t-butylcyclohexanone

2. Friedel Crafts Acylation of Aromatics: yields ketones when an acid chloride is used as the electrophile.

HO CH3CH2 C

O

Cl+AlCl3

EASpropanoyl chloride 1-(4-hydroxyphenyl)propanone

3. Hydration of Alkynes: with Hg+2 and H3O+ yields an enol, that ‘tautomerizes’ to a ketone.

CH3 (CH2)3 C CH

Hg(OAc)2

H3O+

1-hexyne

CH3 (CH2)3 C CH

H

OH

an enol

CH3 (CH2)3 C CH

H

O H

2-octanone

CHO

O

CH2CH3

19

Preparation of Ketones (4 Methods)

4. Acid Chlorides + Lithium Dialkyl Copper (Gilman Reagent): produces ketones.

The reaction is unique to these two reagents and the mechanism is uncertain. As with DIBAH for aldehyde reductions, a low temperature (-78 C) solvent (ether) is used to prevent further alkyl addition to the ketone to form an alcohol. (Acid chlorides are very good electrophiles).

Carboxylic acids, esters, anhydrides and amides are not reduced by diorganocopper reagents. They are not as reactive as acid chlorides.

CH3 (CH2)4 C

O

Cl

hexanoyl chloride

+ (CH3)2 Cu- Li+

dimethyl copper lithiumGilman reagent

78ºC

ether

-

CH3 (CH2)4 C

O

CH3

2-heptanone

Recall that a stronger reducing reagent, such as a Grignard (RMgBr) will also reduce an acid chloride to a ketone, but reduction cannot be stopped here. The ketone is further reduced to an alcohol.

C

O

R Cl

: :

:....

CH3MgBr

acid chlorideC

O

R CH3

: :CH3MgBr

ketone

C

O

R CH3

:

CH3

..:

2 H3O+

alkoxide 3° alcohol

C

O

R CH3

:

CH3

..H

20

Preparation of Ketones Problems

Write equations to show how the following transformations can be carried out. Show all reagents and intermediate products.

a) 3-hexyne 3-hexanone

b) benzene m-bromoacetophenone

c) bromobenzene acetophenone

d) 1-methylcyclohexene 2-methylcyclohexanone

CH3CH2C CCH2CH3

3-hexyne Hg+2, H3O+

AlCl3C

O

H3C Cl

: :

:....

acetyl chloride

+Br2

FeBr3 C

OBr

+

CH3

HBr

m-bromoacetophenone

Br MgBr

CH3CH2C CCH2CH3

O

H

H

3-hexanone

CH3CH2C CCH2CH3

OH

H

C

O

CH3

acetophenone

Mg in ether

C

O

H CH3

: :

CH

O: :..

CH3 H3O

+ CH

OH:..

CH3

C

O

CH3

acetophenone

Cr+6, H+

CH3 BH3, THFNaOH, H2O2, pH8

12

CH3

OH

Cr+6, H+CH3

O

21

NH2

OH

CH3OCH3 F

Cl

Br

I

C OH

O

C CH3

O

C H

O

NH C CH3

O

SO3H NO2

N+R3C N

COCH3

OH

Reactivity Reactivity

o- and p- directing

activators

o- and p- directing

deactivatorsdeactivators

m-directing

Preparation of Ketones Problems

Recall the effects of substituents on aromatic rings. They affect both the reactivity of aromatics and the position at which Electrophilic Aromatic Substitution (EAS) will occur.

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Aldehydes