1

is pyridinium chlorochromate, PCCC5H5NH CrO3Cl

C5H5NH CrO 3ClRCH

O

RCH2OH

R1 C

R2

H

O HK 2Cr2O 7

R1 C

R2

O

Aldehydes and Ketones

Preparation of Aldehydes —

Oxidation of primary alcohols –

The aldehyde that is the product is very easily oxidized toa carboxylic acid, RCOOH.

Preparation of Ketones —

Oxidation of secondary alcohols –

Unlike aldehydes, ketones are not easily oxidized.

2

C C R2R1

H2SO4, HgSO4

H2O

C C R2R1

O

H

H

C C R2R1

H

HO

+

H2O

H2SO4, HgSO4C C RH C C RH

O

H

H

Owing to the formation of mixtures ifR1 R2, this reaction is most usefulwhen R1 = R2 ...

...or when the alkyne has a terminal triple bond.

≠

Hydration of an alkyne –

An enol initially forms in this reaction, but it tautomerizesto the more stable ketone. Terminal alkynes, followingMarkovnikov’s rule, give methyl ketones rather thanaldehydes.

3

H R C

O

ClAlCl3

C

O

R+

C O sp2 orbitals π

δ+ δ−

Friedel-Crafts acylation for aryl ketones –

The aromatic ring cannot have, as a substituent, anamino group or a meta director.

Structural Features of Aldehydes and Ketones

Both contain the carbonylgroup and only carbons orhydrogens bonded to thisgroup. In aldehydes atleast one hydrogen isjoined to the carbonylcarbon (formaldehyde has two). In ketones, only carbonsare bonded to the carbonyl carbon.

Since the carbon has a partial positive charge it is likely tobe a site that is attacked by nucleophiles. And, since theoxygen bears a partial negative charge, it is likely to be asite of electrophilic attack. Since ordinary carbanions (R:−)and hydride ions (H:−) are very poor leaving groups (unlikehalide ions, X−) nucleophilic substitution does not usuallyoccur at the carbonyl carbon of aldehydes or ketones.

4

C O

R2

R1

Nu:- C O

R2

NuR1:-+∅∅

5

Aldehydes

R C H

O(Ar)

O2 or CrO3 or K2Cr2O7

or KMnO4, etc. R C OH

O(Ar)

Tollen's test for aldehydes:

R C H

O(Ar)

+ Ag(NH3)2+

-OHRCO-

O

+ Ago

(Ar)

Fehling's test, Benedict's test:

R C H

O(notAr)

+ 2 CuO RCOH

O

+ Cu2Ocomplexedwith citrateor tartarate,in solution

redprecipitate

Ketones

RCH2 C CH2R'

O

RCOH

O

R'COH

O

+hot KMnO4

or hot HNO3Vigorous conditionsrequired for reaction.

R'CH2COH

O

+RCH2COH

O

Reactions of Aldehydes and Ketones —

Oxidation —

Aldehydes are easily oxidized to carboxylic acids, ketonesare not.

6

RC O

R'

:Nu-

δ−δ+

RC OR'

Nuδ−

δ−becoming tetrahedral:sp2 sp3

RC

OR'

NuH+

RC

OHR'

Nu

R, R' = alkyl, aryl, H

Nucleophilic Additions —

:Nu or :Nu- is a generic nucleophile.

Since there is an increase in crowding on going fromreactant to transition state (~120o to ~109o), some stericeffects might be expected. This is one reason aldehydes(less crowded) are more reactive than ketones.

7

C O

R'

R

+ H+ C O

R'

R

H C O

R'

R

H

More easily attacked by nucleophilethan unprotonated carbonyl.

C O H2O C

OH

OH+acid or base

catalyst

Nucleophilic additions may be acid catalyzed —

However, when acid catalysis is employed one shouldusually be careful to avoid completely converting thenucleophile to its conjugate acid (which would be muchless nucleophilic).

Nucleophilic Addition of Water: Hydration —

The product here is known as a geminal diol. In mostcases the equilibrium greatly favors the carbonylcompound. Formaldehyde and chloral(trichloroacetaldehyde) are two common exceptions.

8

C O C OHOHO

H O H

C OHO H

O H+

The mechanism for this reaction under basic conditions isas follows –

In this case – basic catalysis – a powerful nucleophileattacks the substrate. In acidic catalysis, as we shall seebelow, the nucleophile will be much weaker – water. Butthe substrate has been activated by protonation and ismore susceptible to attack.

9

C O

O

H

HH

HO

H

C O H C O H

H O H

HO

HC O H

HO

H

HO C O H

HO

H

H+

Under acidic conditions the following mechanism applies –

10

C OROH

C OHROROH

C ORRO H2O+

H H

hemiacetal acetal

Acetal Formation —

Under acidic conditions an aldehyde or ketone will reactwith an alcohol to form a hemiacetal. The hemiacetal, inturn, will react with more alcohol to form an acetal.

11

C O

O

H

HR

RO

H

C O H C O H

R O H

RO

HC O H

RO

H

RO C O H

RO

H

H+

hemiacetal

The mechanism is as follows –

OK. Now we have to get from the hemiacetal to theacetal.

12

O

H

HR

RO

H

R O H

RO C O H

RO C O H

H RO C O H

H

RO

HRO C

RO

H

RO

RO C

RO

HH

acetal

Acetals are used to “protect” the carbonyl groups ofaldehydes and ketones when one wants to have someother part of the molecule react without affecting thealdehyde or ketone functional group. They can be usedthis way because they are fairly unreactive and thecarbonyl functional group can be regenerated from theacetal. For example if you wanted to convert a ketoacidto a ketoalcohol you could do the following: (1) convertthe keto group to an acetal, (2) reduce the acid withLiAlH4, and (3) regenerate the keto group from the acetal.

13

R-Xor Ar-X

+ Mg

anhydrousC2H5OC2H5

or

O

R-Mg-Xor Ar-Mg-X

X = I, Br, Cl

Addition of Grignard Reagents —

A powerful method for synthesis of alcohols. In the Grignard Synthesis smaller molecules —> largermolecules.

Formation of Grignard reagent —

14

3o alcoholketone

2o alcoholaldehyde

1o alcoholformaldehyde

R'' C

R'

OH

R

H2OH3O+C O

R'

R''+

H C

R'

OH

R

H2OH3O+C O

R'

H+

H C

H

OH

R

H2OH3O+C O

H

H+RMgX

or ArMgX

+ Mg(OH)XR C O HH2O

magnesium salt of an alcohol

XR C O MgMg XR C O

δ+ δ−C O

R Mg Xδ− δ+

Grignards react with aldehydes and ketones to givealcohols —

A pseudo-mechanism for this reaction —

15

Synthesize 2-phenyl-2-butanol using a Grignardsynthesis —

The figure below shows three possible routes by whichthis synthesis can be accomplished. In practice, theroute chosen would likely depend on the startingmaterials that may be at hand in the laboratory (all ofthese compounds could be purchased).

In the scheme below, CH3MgBr could be made fromCH3Br and Mg, but methyl bromide is not convenient tohandle. It boils at 4oC, so it is a gas at room temperature. [Large quantities of methyl bromide are used as a soiland grain fumigant. Its use is quite controversial since itis somewhat toxic and an ozone depleting chemical. See,for example:http://www.epa.gov/docs/ozone/mbr/mbrqa.html]

16

O

H3CC

CH3CH2MgBr

+

CH3CH2Br

Mg anhydrous ether

CH3CH2CCH3

O

+MgBr

Mg anhydrous ether

Br

CCH3CH2

O

+ CH3MgBr

CH3

OH

CH3CH2 C

not commonly available

17

alcohol 1 alkyl halide Grignard reagent

alcohol 2 aldehydeor ketone

more complicated alcoholwhich may become alcohol 1 or 2 in a subsequentGrignard synthesis, etc.

It is possible to extend the Grignard synthesis to makequite complex alcohols from simple ones (you don’t winthe Nobel prize for nothing). The basic scheme is asfollows –

18

C O

R'

R

+ K+ -C N H3O

+

R' C

OH

CN

R

H3O+CH3CH2CH2 C

OH

CN

H

H2Oheat

CH3CH2CH C COOH

H

H2O,KOH heat

CH3CH2CH2 C

OH

COO- K+

H

H2OHCl CH3CH2CH2 C

OH

COOH

H

+ KCl

Formation of Cyanohydrins —

These compounds can be hydrolyzed by base or acid togive α-hydroxyacids or α,β-unsaturated acids, respectively.

19

C

O+ R NH2

weak acidcatalyst

C

NR

an iminea primaryamine

C

O+ NH2OH weak acid

catalystC

NOH

an oximehydroxyl-amine

C

ONO2

O2N

NH2NH+ weak acidcatalyst

NO2

O2N

NHN

C

a 2,4-dinitrophenylhydrazone

Oximes, 2,4-DNPs,and semicarbazonesare used as derivatives in identifying aldehydesand ketones.

Addition of Ammonia and Its Derivatives —