SKO3033

ORGANIC CHEMISTRY II

CHAPTER 1
ALDEHYDES &
KETONES
ALDEHYDES AND KETONES

O
“carbonyl” functional group: C

Aldehydes Ketones

O O O
C C C
H H R H R R'

R can be Ar
NOMENCLATURE
Aldehydes, IUPAC nomenclature:
Parent chain = longest continuous carbon chain containing
the carbonyl group; alkane, drop –e, add –al. (note: no
locant, -CH=O is carbon #1.)
CH3
CH3CH2CH2CH=O CH3CHCH=O

butanal 2-methylpropanal

H2C=O CH3CH=O

methanal ethanal
CH3 O
5 2
CH3 CH2 CH CH2 C H
3 1
3-methylpentanal

 The aldehyde carbon is number 1.

 IUPAC: Replace -e with -al.

Chapter 4 4
Parent = longest continuous carbon chain containing the
carbonyl group. Alkane, drop –e, add –one. Prefix a locant
for the position of the carbonyl using the principle of lower
number.
O O O
CH3CH2CCH3 CH3CH2CCH2CH3 CH3CCH2CH2CH3

2-butanone 3-pentanone 2-pentanone

1 O

3
Br 3-bromocyclohexanone
• For cyclic ketones, the carbonyl carbon is assigned the
number 1.
Carbonyl as Substituent

 On a molecule with a higher priority functional group, a ketone is

an oxo and an aldehyde is a formyl group.
 Aldehydes have a higher priority than ketones.

O CH3 O
CH3 C CH CH2 C H
4 3 1

3-methyl-4-oxopentanal Benzaldehyde
7
PROPERTIES
Physical properties:

C O sp2 120o

C O C O

polar, no hydrogen bonding

mp/bp are relatively moderate for covalent substances
water insoluble
(except: four-carbons or less)
SYNTHESIS
ALDEHYDES, syntheses:
1. Oxidation of 1o alcohols
2. Oxidation of methylaromatics
3. Reduction of acid chlorides

KETONES, syntheses:
1. Oxidation of 2o alcohols
2. Friedel-Crafts acylation
3. Coupling of R2CuLi with acid chloride
Aldehydes synthesis
1) oxidation of primary alcohols:

RCH2-OH + K2Cr2O7  R-COOH

RCH2-OH + PCC  RCH=O
(pyridinium chlorochromate, C5H5NHCrO3Cl)
[With other oxidizing agents, primary alcohols  RCOOH]
- KMnO4, H2Cr2O4
PCC
CH2OH CH=O
pyridinium chlorochromate
benzyl alcohol benzaldehyde

CH3CH2CH2CH2CH2OH + K2Cr2O7 CH3CH2CH2CH2CO2H

1-pentanol pentanoic acid
Aromatic aldehydes only!
2) oxidation of methylaromatics:
CHO
CH3

+ CrO3, (CH3CO)2O
Br
H2O, H+
Br
p-bromobenzaldehyde

CH3 CrO3 H2O CHO

(CH3CO)2O

2-methylnaphthalene 2-naphthaldehyde

CrO3 H2O
CH3O CH3 CH3O CH=O
(CH3CO)2O

p-methylanisole p-anisaldehyde
3) reduction of acid chloride

O O
LiAlH(O-t-Bu)3
C C
R Cl lithium aluminum hydride tri-tert-butoxide R H

O O
LiAlH(O-t-Bu)3
Cl H
isovaleryl chloride isovaleraldehyde
O LiAlH(O-t-Bu)3 O
C C
Cl H
benzoyl chloride benzaldehyde

CH3 O CH3 O
LiAlH(O-t-Bu)3
CH3CHCH2C CH3CHCH2C
Cl H
isovaleryl chloride isovaleraldehyde
Ketone synthesis:
1) oxidation of secondary alcohols
H OH O
NaOCl

cyclohexanol cyclohexanone
Sodium hypochlorite - NaOCl

OH K2Cr2O7 O
CH3CHCH3 C
H3C CH3

isopropyl alcohol acetone

2) Friedel-Crafts acylation

AlCl3 O
RCOCl, AlCl3 + ArH R C Ar + HCl

O AlCl3 O
CH3CH2CH2C + CH3CH2CH2C
Cl
butyrophenone

Aromatic ketones (phenones) only!

O O
AlCl3
C Cl + C

O2N O2N

m-nitrobenzophenone

O
AlCl3
C Cl + NR

NO2

Friedel Crafts acylation does not work on deactivated

rings.
3. Coupling of R2CuLi with acid chloride
O
RCOCl + R'2CuLi C
R R'
O O

+ (CH3CH2)2CuLi
Cl
lithium diethylcuprate
Isobutyryl chloride 2-Methyl-3-pentanone
O
O
CuLi + CHCH2CH2CH3 CCH2CH2CH3
2 Cl
butyrophenone

CH3 O
O
CH3CH2CH2C + CH3CH CuLi CH3CH2CH2CCHCH3
Cl 2 CH3

2-methyl-3-hexanone
SUMMARY

K2Cr2O7, or
1 alcohol
o

C5H5NHCrO3Cl

CrO3 H2 O
Ar-CH3 aldehyde
(AcO)2O

LiAlH(O-t-Bu)3
acid chloride
NaOCl, etc.
2 alcohol
o

AlCl3
acid chloride + ArH ketone
EXERCISE

1. outline three different syntheses for benzaldehyde

2. outline three different syntheses for benzophenone

3. outline a different synthesis for each of the following

compounds:

• Cyclohexanone
• 4-bromobenzaldehyde
• 2-pentanone
• Valeraldehyde
• Acetophenone
• Isobutyraldehyde
ANSWER

1. Synthesize benzaldehyde three different ways.

CH2OH
K2Cr2O7

CH3 CH(OOCCH3)2 CH=O

CrO3 H2O
(CH3CO)2O

O benzaldehyde
C Cl
LiAlH(O-t-Bu)3
2. Synthesize benzophenone three different ways.

OH NaOCl
CH

O AlCl3 O
C + C
Cl

O
C + CuLi
Cl 2
3. Cyclohexanone, 4-bromobenzaldehyde, valeraldehyde,
acetophenone, isobutyraldehyde, using a different method for each
one.

O
Br CHO

oxidation of 2o alcohol oxidation of Ar-CH3

O
CH3CH2CH2CCH3 CH3CH2CH2CH2CHO
R2CuLi + R'COCl oxidation of 1o alcohol

O CH3
CH3C CH3CHCHO

Friedel-Crafts acylation reduction of acid chloride

H O
OH K2Cr2O7

O O
(CH3CH2CH2)CuLi + CH3 C CH3CH2CH2CCH3
Cl

O AlCl3 O
CH3 C + CH3C
Cl
CrO3 H2O
Br CH3 Br CHO
(CH3CO)2O

K2Cr2O7
CH3CH2CH2CH2CH2-OH CH3CH2CH2CH2CHO
special conditions

CH3 O LiAlH(O-t-bu)3 CH3

CH3CHC CH3CHCHO
Cl
REACTIONS

Aldehydes & ketones, reactions:

1) Oxidation
2) Reduction
3) Nucleophilic addition
• Addition of cyanide
• Addition of derivatives of ammonia
• Addition of alcohols
• Cannizzaro reaction
• Addition of Grignard reagents
alkane alcohol

reduction

aldehyde addition
ketone nucleophilic product
addition
oxidation

carboxylic acid
1) Oxidation
a) Aldehydes (very easily oxidized!)

CH3CH2CH2CH=O + KMnO4, etc.  CH3CH2CH2COOH

carboxylic acid

CH3CH2CH2CH=O + Ag+  CH3CH2CH2COO- + Ag

Silver mirror

Tollen’s test for easily oxidized compounds like aldehydes.

(AgNO3, NH4OH(aq))
b) Ketones

Ketones only oxidize under vigorous conditions via the enol.

+ KMnO4 No reaction

Cyclohexanone

+ KMnO4, heat HOOCCH2CH2CH2CH2COOH

adipic acid

OH

enol
c) Methyl ketones:

test for methyl ketones

O
CH3CH2CH2CCH3 + (xs) NaOI CH3CH2CH2CO2- + CHI3
2-pentanone excess

**sodium hypoiodite - NaOI

O O
C + OI- C - + CHI3
R CH3 R O
iodoform
Yellow ppt
2) Reduction
O H2, Ni OH
a) Ketone to secondary alcohol C C
H

NaBH4 or LiAlH4
then H+

H2, Pt H
O
OH
cyclopentanol
cyclopentanone

O 1. NaBH4 OH
C CH3 CHCH3
2. H+
acetophenone 1-phenylethanol
b) Aldehyde to primary alcohol

O H2, Pt
C CH2OH
H

benzaldehyde benzyl alcohol

CH3 LiAlH4 CH3

H+
CH3CHCH=O CH3CHCH2OH

isobutyraldehyde isobutyl alcohol

hydride reduction
mechanism: nucleophilic addition; nucleophile = hydride

O RDS O
1) C + H: Al C + Al
H

O
2) C + Al H C O Al
H
Then + H+  alcohol
c) Ketone/aldehyde to hydrocarbons

O NH2NH2, OH-
CH2
C
Wolff-Kishner

O Zn(Hg), HCl
C CH2
Clemmensen
O 1. CN- OH
3) Addition of cyanide
C C
2. H+ CN
cyanohydrin

OH
O + NaCN; then H+
CN

mechanism for addition of cyanide

nucleophilic addition

RDS O
O
1) C + C N C
C
N

O ONa
C + Na+ C then + H+
2) C C
N N
Cyanohydrins have two functional groups plus one additional carbon.
Nitriles can be hydrolyzed to carboxylic acids in acid or base:

OH OH
H2O, OH-
CH2CH C N CH2CH COO-
heat

OH
H2O, H+
CH2CH C N C C COOH
heat H H
4) Addition of derivatives of ammonia

O (H+)
+ H2N G + H2O
N G
O
H2N NH2 H2N OH
H2N N NH2
hydrazine hydroxylamine H
semicarbazide

O2N

H2N HN H2N HN NO2

phenylhydrazine

2,4-dinitrophenylhydrazine
acid catalyzed nucleophilic addition mechanism followed by dehydration

1) O OH
+
C + H C

OH
OH
+ H2N G C RDS
2) C
NH2 G

OH
C + H2O + H+
C
3) N
NH2 G G
CH2 CHO + H2NOH CH2 CH NOH
hydroxylamine
phenylacetaldehyde an oxime

O H+ O
O + H2NHNCNH2 NHNCNH2
semicarbazide
cyclohexanone a semicarbazone

CH3CH2CH2CH2CHO + NH2 NH CH3CH2CH2CH2CH N NH

pentanal a phenylhydrazone
phenylhydrazine
O OR
5) Addition of alcohols + ROH, H +
C C
excess acetal
OR

OH
C
OR hemiacetal

Mechanism = nucleophilic addition, acid catalyzed

(xs) EtOH, H+ OEt
CH2CHO CH2 CH
O OH
OEt
1) + H C
C acetal

RDS OH OCH3
OH2 ROH C O (xs) CH3OH, dry HCl
2) + OCH3
C HOR
ketal

OH OH
3) C C + H
HOR OR
6) Cannizzaro reaction (self oxidation/reduction)

CHO CH2OH COO-

conc. NaOH
+
Br Br Br

conc. NaOH
H2C=O CH3OH + HCOO-
7) Addition of Grignard reagents.
O O MgBr
C + RMgX C
R

O MgBr OH
C + H2O C + Mg(OH)Br
R R
larger alcohol
HX Mg
ROH RX RMgX

H2O larger
alcohol

ox.
R´OH -C=O
mechanism = nucleophilic addition

1) O RDS O
C + RMgBr C + MgBr
R

O OMgBr
C + MgBr C
2) R
R

#3 synthesis of alcohols. Used to build larger molecules from smaller organic

compounds.
O
H+
RMgX + C RCH2OMgX RCH2OH
H H
1o alcohol + 1 C
formaldehyde

O H+
RMgX + R'CHOMgX R'CHOH
C
R' H R
R
other aldehydes 2o alcohol + Carbon
R' R'
O H+
R-MgX + C R-COMgX R-COH
R' R" R"
R"
ketone
3o alcohol + Carbons

O H+
RMgX + RCH2CH2OMgX RCH2CH2OH
H2C CH2
ethylene oxide 1o alcohol + 2 Carbons
EXERCISE
Planning a Grignard synthesis of an alcohol:
a) The alcohol carbon comes from the carbonyl compound.
b) The new carbon-carbon bond is to the alcohol carbon.

O OH
H+
C + RMgX C
R
New carbon-carbon bond

CH3 O
H2O
CH3CH2CH2CH2 C CH3 CH3CH2CH2CH2MgBr + CH3CCH3
OH
2-Methyl-2-hexanol
or

CH3 O
H2O
CH3CH2CH2CH2 C CH3 CH3CH2CH2CH2CCH3 + CH3MgBr
OH
2-Methyl-2-hexanol
EXERCISE

Grignard synthesis of 4-methyl-2-pentanol from alcohols of four-

carbons or less:
Step one: determine the carbonyl compound and Grignard
reagent that you would use:

CH3 H2O CH3

CH3CHCH2MgBr + CH3CH=O CH3CHCH2CHCH3
OH

Step two: show the syntheses of the Grignard reagent and the
carbonyl compound from alcohols…
CH3 HBr CH3 Mg CH3
CH3CHCH2OH CH3CHCH2Br CH3CHCH2MgBr

H+

K2Cr2O7 CH3
CH3CH2OH CH3CH=O CH3CHCH2CHCH3
special cond. 4-methyl-2-pentanol OH

Br2,Fe Mg
Br MgBr

H2O OH
C CH3
CH3

OH CrO3 O 2-phenyl-2-propanol
CH3CHCH3 CH3CCH3
HBr Mg
CH3OH CH3Br CH3MgBr
H3C OH
H2O
O
H OH
NaOCl
1-Methylcyclohexanol

Cyclohexanol Cyclohexanone

H OH H Br H MgBr
HBr Mg

H CH2OH
H2O

K2Cr2O7
CH3OH H2C=O Cyclohexylmethanol
special cond.
EXERCISE

Using the Grignard synthesis of alcohols we can make any alcohol that
we need from a few simple alcohols. From those alcohols we can
synthesize alkanes, alkenes, alkynes, alkyl halides, ethers, aldehydes,
ketones, carboxylic acids…

eg. Outline all steps in a possible laboratory synthesis of

3-methyl-1-butene from alcohols of four carbons or less.

CH3
CH3CHCH=CH2
CH3 PBr3 CH3 Mg CH3
CH3CHCH2-OH CH3CHCH2Br CH3CHCH2MgBr

K2Cr2O7
CH3OH H2C=O
special cond. H2 O

CH3
CH3CHCH2CH2-OH

HBr

CH3 KOH(alco) CH3

CH3CHCH=CH2 CH3CHCH2CH2-Br
SUMMARY

ketone aldehyde RCOOH

ROR ROH

alkene

RX

Alcohols are central

to organic syntheses RH alkyne