Transcript ch13[1].

William H. Brown
Thomas Poon
www.wiley.com/college/brown
Chapter Thirteen
Aldehydes and Ketones
The Carbonyl Group
• In this and several following chapters, we study the
physical and chemical properties of classes of
compounds containing the carbonyl group, C=O.
• aldehydes and ketones (Chapter 13)
• carboxylic acids (Chapter 14)
• acid halides, acid anhydrides, esters, and amides
(Chapter 15)
• enolate anions (Chapter 16)
13-2
Structure
• The functional group of an aldehyde is a carbonyl group
bonded to a H atom.
• The functional group of a ketone is a carbonyl group
bonded to two carbon atoms.
O
HCH
Methanal
(Formaldehyde)
O
CH3 CH
Ethanal
(Acetaldehyde)
O
CH3 CCH3
Propanone
(Acetone)
13-3
Nomenclature
• IUPAC names:
• The parent chain is the longest chain that contains the
carbonyl group.
• For an aldehyde, change the suffix from -e to -al.
• For an unsaturated aldehyde, show the carbon-carbon
double bond by changing the infix from -an- to -en-; the
location of the suffix determines the numbering pattern.
• For a cyclic molecule in which -CHO is bonded to the ring,
add the suffix -carbaldehyde.
13-4
Nomenclature
O
O
3
4
1
3
H
2
2
3-Methylbutan al
HO
Cyclopen tanecarb aldehyde
5-Methyl-3h exanone
H
4
5
7
8
6
3
4
1
H
2
(2E)-3,7-D imeth yl-2,6-octad ienal
(Geran ial)
2-Propen al
(A crolein )
CHO
O
O
1
1
CHO
trans -4-Hyd roxycyclohexan ecarbald ehyde
O
2-Methylcycloh exanone
O
Acetop hen on e
O
Benzoph enone
13-5
Nomenclature
• Table 13.1 Increasing Order of Precedence of Six
Functional Groups.
13-6
Nomenclature
• Common names
• For an aldehyde, the common name is derived from the
common name of the corresponding carboxylic acid.
• For a ketone, name the two alkyl or aryl groups bonded to
the carbonyl carbon and add the word ketone.
O
H
H
Formaldehyde
O
O
H
OH
Formic acid
H
Acetaldehyde
O
Ethyl is opropyl ketone
O
OH
Acetic acid
O
O
Diethyl ketone
Dicyclohexyl ketone
13-7
Number Prefixes for Common
Names
PREFIX # C
FORM
ACET
PROPIO
BUTYR
VALER
1
2
3
4
5
PREFIX
CAPRO
CAPRYL
CAPR
LAUR
#C
6
8
10
12
SO.... BUTYRALDEHYDE IS AN ALDEHYDE OF 4
CARBONS.
….. THE SAME PREFIXES ARE USED FOR ACIDS.
13-8
Physical Properties
• Oxygen is more electronegative than carbon (3.5 versus
2.5) and, therefore, a C=O group is polar.
• Aldehydes and ketones are polar compounds and interact
in the pure state by dipole-dipole interactions.
• They have higher boiling points and are more soluble in
water than nonpolar compounds of comparable molecular
weight.
13-9
Physical Properties
• In liquid aldehydes and ketones, there are weak
intermolecular attractions are between the partial positive
charge on the carbonyl carbon of one molecule and the
partial negative charge on the carbonyl oxygen of another
molecule.
H + C O
H
O
C+
HH
H + C O
H
H
O C
- +H
• No hydrogen bonding is possible between aldehyde or
ketone molecules.
• Aldehydes and ketones have lower boiling points than
alcohols and carboxylic acids, compounds in which there
is hydrogen bonding between molecules.
13-10
Physical Properties
•Formaldehyde, acetaldehyde, and acetone are infinitely
soluble in water.
•Aldehydes and ketones become less soluble in water as the
hydrocarbon portion of the molecule increases in size.
13-11
Reactions
• The most common reaction theme of a carbonyl group is
addition of a nucleophile to form a tetrahedral carbonyl
addition compound.
13-12
Grignard Reagents
• Addition of carbon nucleophiles is one of the most
important types of nucleophilic additions to a C=O
group.
• A new carbon-carbon bond is formed in the process.
• We study addition of carbon nucleophiles called
Grignard reagents.
• Victor Grignard was awarded the Nobel Prize for
chemistry in 1912 for their discovery and application to
organic synthesis.
• Grignard reagents have the general formula RMgX,
where R is an alkyl or aryl group and X is a halogen.
13-13
Grignard Reagents
• Grignard reagents are prepared by adding an alkyl or
aryl halide to a suspension of Mg metal in diethyl ether.
Br
+ Mg
eth er
1-Bromobutane
Br + Mg
Bromoben zene
MgBr
Butylmagn esium bromide
eth er
MgBr
Phenylmagn esium bromide
13-14
Grignard Reagents
• Given the difference in electronegativity between carbon
and magnesium (2.5 - 1.3), the C-Mg bond is polar
covalent, with C- and Mg+.
• in its reactions, a Grignard reagent behaves as a
carbanion.
• Carbanion: An anion in which carbon has an unshared
pair of electrons and bears a negative charge.
• A carbanion is a good nucleophile and adds to the
carbonyl group of aldehydes and ketones
13-15
Grignard Reagents
• Reaction with protic acids
• Grignard reagents are very strong bases and react with
proton acids to form alkanes.
- +
CH3 CH2 - MgBr + H-OH
p Ka 15.7
Stronger
Stron ger
bas e
acid
CH3 CH2 -H + Mg 2+ + OH- + BrpK a 51
Weaker
Weaker
acid
base
• Any compound containing an O-H, N-H, or S-H group
reacts with a Grignard reagent by proton transfer.
HOH
Water
ROH
A lcoh ols
ArOH
Phenols
RCOOH
Carboxylic
acids
RNH2
Amines
RSH
Thiols
13-16
Grignard Reagents
• Reaction with formaldehyde gives a 1° alcohol.
O
eth er
CH3 CH2 -MgBr + H-C-H
Formaldeh yd e
O [MgBr]+
HCl
CH3 CH2 -CH2
H2 O
A magnes ium
alkoxide
OH
CH3 CH2 -CH2 + Mg 2+
1-Propanol
(a 1° alcoh ol)
• Reaction with any aldehyde other than formaldehyde
gives a 2° alcohol.
O
Ph MgBr + CH3 -C-H
eth er
Acetaldeh yd e
O [MgBr]
Ph CHCH3
A magnes ium
alk oxid e
+
HCl
H2 O
OH
Ph CHCH3 + Mg 2+
1-Ph enyleth anol
(a 2° alcohol)
13-17
Grignard Reagents
• Reaction with a ketone gives a 3° alcohol.
O [ MgBr] +
O
Ph MgBr + CH3 -C-CH3
Acetone
eth er
OH
HCl
Ph CCH3
Ph CCH3 + Mg 2+
H2 O
CH3
CH3
A magnes ium
2-Phen yl-2-propanol
alkoxide
(a 3° alcoh ol)
• Problem: Show how to synthesize this 3° alcohol by
three different routes. OH
C-CH2 CH3
CH3
13-18
Addition of Alcohols
• Hemiacetal: A molecule containing an -OH group and an
-OR group bonded to the same carbon.
H
O
CH3 CCH3 + OCH2 CH3
OH
CH3 C-OCH2 CH3
CH3
A h emiacetal
H+
• Hemiacetals are minor components of an equilibrium
mixture except where a 5- or 6-membered ring can form.
5
3
4
O
2
1
H
OH
4-Hydroxyp entanal
redraw to show
th e OH close to
th e CHO grou p
3
5 4
2
O
H
1
H
O
3
5
2
4
O
1
OH
A cyclic h emiacetal
(major form presen t
at eq uilibrium)
13-19
Addition of Alcohols
• Acetal: A molecule containing two -OR groups bonded
to the same carbon.
OH
CH3 C-OCH2 CH3 + CH3 CH2 OH
CH3
A hemiacetal
H
OCH2 CH3
+
CH3 C-OCH2 CH3 + H2 O
CH3
A d iethyl acetal
O
H
OH
4-Hydroxypentan al
O
OH
CH3 OH
+
H
O
OCH3
+ H2 O
A cy clic acetal
13-20
Acetal Formation
1. Proton transfer from HA to the hemiacetal oxygen.
+
H
H
O
HO
R-C-OCH3 + H A
R-C-OCH3 + A
-
H
An oxonium ion
H
2. Loss of H2O gives a cation.
+
H O H
R-C-OCH3
H
+
R-C OCH3
+
R-C OCH3 + H2 O
H
H
A resonan ce-stabilized cation
13-21
Acetal Formation
3. Reaction of the cation (an electrophile) with an alcohol (a
nucleophile).
+
H
H
+
CH3 -O + R-C OCH3
H
O
CH3
R-C-OCH3
H
A p rotonated acetal
4. Proton transfer to A- gives the acetal and regenerates the
acid catalyst.
+
CH3
H
CH
O
3
O
A
+
R-C-OCH3
H
A p rotonated acetal
HA + R-C-OCH3
H
An acetal 13-22
Acetals
• Draw a structural formula for the acetal formed in each
reaction.
(a)
OH
O + HO
Eth ylen e
glycol
OH
(b)
O
+
H2 SO4
H2 SO4
OH
13-23
Acetals as Carbonyl -Protecting
Groups
• One way to synthesize the ketoalcohol on the right is by a
Grignard reaction.
O
Ph
O
H
+
Benzaldehyde
Br
H
4-Bromobu tanal
OH
??
O
Ph
H
5-Hyd roxy-5-p henylpen tanal
• But first the aldehyde of the bromoaldehyde must be
protected; one possibility is as a cyclic acetal.
O
Br
H +
OH
HO
Eth ylene glycol
H
O
+
Br
+ H2 O
O
A cyclic acetal
13-24
An Acetal as a Carbonyl -Protecting
Group
• Now the Grignard reagent can be prepared and the new
carbon-carbon bond formed.
O
O
Br
O
A cyclic acetal
O
Ph
BrMg
+ Mg
ether
O
A Grignard reagent
-
H + BrMg
O MgBr
O
+
O
O
Ph
A magnesiu m alk oxid e
O
• Hydrolysis gives the hydroxyaldehyde.
-
+
O MgBr
Ph
OH
O
O
HCl, H2 O
Ph
O
H + HO
OH
13-25
Imines
• Imine: A compound containing a C=N bond; also called
a Schiff base.
• Formed by the reaction of an aldehyde or ketone with
ammonia or a 1° amine.
O
+
H+
NH3
Cycloh exanone A mmonia
O
An imine
+
CH3 CH + H2 N
Ethanal
NH + H2 O
Aniline
H
CH3 CH=N
+ H2 O
An imine
13-26
Formation of Imines
1. Addition of the amine to the carbonyl carbon followed by
proton transfer gives an aminoalcohol.
O
C
+ H2 N-R
O- H
+
C N-R
H
O
C
H
N-R
H
A tetrah edral carb on yl
ad dition intermediate
2. Two proton-transfer reactions and loss of H2O.
H
+
O H +
H
O
C
H
N-R
H
H
+
H
O
C
H
C N-R + H2 O + H O H
N-R
H
O
H
H
An imine
13-27
Rhodopsin
• Reaction of vitamin A aldehyde (retinal) with an amino
group on the protein opsin gives rhodopsin.
11
12
+ H2 N-Opsin
11-cis -Retinal
H
C=O
Rhodopsin
(Vis ual purple)
H
C= N-Opsin
13-28
Reductive Amination
• Reductive amination: The formation of an imine followed by its
reduction to an amine.
+
O + H2 N
Cyclohexanone
Cyclohexylamine
(a 1° amine)
H
-H2 O
N
H2 / Ni
An imine
(n ot isolated)
H
N
D icyclohexylamin e
(a 2° amine)
• Reductive amination is a valuable method for the conversion of
ammonia to a 1° amine, and a 1° amine to a 2° amine.
13-29
Keto-Enol Tautomerism
• Enol: A molecule containing an -OH group bonded to a
carbon of a carbon-carbon double bond.
O
CH3 -C-CH3
Acetone
(keto form)
OH
CH3 -C=CH2
Aceton e
(enol form)
The keto form
predominates
for most
simple
aldehydes and
ketones
13-30
Keto-Enol Tautomerism
• Problem: Draw two enol forms for each ketone.
O
O
(b)
(a)
• Problem: Draw the keto form of each enol.
O
OH
CHOH
(a)
(b)
OH
(c)
OH
13-31
Keto-Enol Tautomerism
• Interconversion of keto and enol forms is catalyzed by
both acid and base.
• Following is a mechanism for acid catalysis
1. Proton transfer to the carbonyl oxygen.
2. Proton transfer from the a-carbon to A:-
13-32
Racemization an at a-Carbon
• When an enantiomerically pure aldehyde or ketone with
at least one a-hydrogen is treated with a trace of acid or
base, it gradually becomes a racemic mixture; it loses all
optical activity.
Ph
O
C
C
H
OH
Ph
+
C
-
or OH
H3 C
CH3
H
(R)-3-Phenyl-2butanone
H3 C
C
CH3
An ach iral en ol
H
+
or OH-
Ph
O
C
C
H
CH3
H3 C
(S)-3-Ph enyl-2b utanone
13-33
a-Halogenation
• Aldehydes and ketones with an a-hydrogen react with
Br2 and Cl2 to give an a-haloaldehyde or an ahaloketone.
O
O
+ Br2
A cetophenone
CH3 COOH
Br
+ HBr
a-Bromoacetophen on e
13-34
a-Halogenation
• The key intermediate in a-halogenation is an enol.
1. Formation of the enol.
OH
O
+
H
Keto form
En ol form
2. Nucleophilic attack of the enol on the halogen.
H
O
O
+ Br Br
Br
+ H-Br
13-35
a-Halogenation
• A value of a-halogenation is that the carbon adjacent to
the aldehyde or ketone now bears a good leaving group
and is susceptible to nucleophilic attack.
O
O
Br
N
+ H N
A n a-bromok eton e
D iethylamine
+ HBr
An a-dieth ylaminoketone
13-36
Oxidation
• Aldehydes are one of the most easily oxidized of all
functional groups.
CHO
H2 CrO4
Hexan al
MeO
HO
Van illin
2
COOH
Hexanoic acid
CHO
+ Ag2 O THF, H2 O
NaOH
CHO + O2
Benzald ehyde
HCl
H2 O
2
COOH
+ Ag
MeO
HO
V anillic acid
COOH
Benzoic acid
13-37
Oxidation
• Ketones are not normally oxidized by H2CrO4; in fact this
reagent is used to oxidize 2° alcohols to ketones.
• They are oxidized by HNO3 at higher temperatures.
• Oxidation is via the enol.
O
OH
O
HNO3
Cycloh exanone
(k eto form)
Cyclohexan one
(enol form)
HO
OH
O
Hexan edioic acid
(Ad ipic acid )
• Adipic acid is one of the starting materials for the
synthesis of nylon 66.
13-38
Oxidation
• Tollens’ reagent: Prepared by dissolving AgNO3 in
water, adding NaOH to precipitate Ag2O and then adding
aqueous ammonia to redissolve silver ion as the silverammonia complex ion. Tollens’ reagent is specific for
the oxidation of aldehydes. If done properly, silver
deposits on the walls of the container as a silver mirror.
O
+
R-C-H + 2 Ag( NH3 ) 2 + 3 OH
A ldehyde Tollens'
reagen t
O
R-C-O + 2 Ag + 4 NH3 + 2 H2 O
Carboxylic Silver
an ion
mirror
13-39
Reduction
• Aldehydes are reduced to 1° alcohols.
• Ketones are reduced to 2° alcohols.
O
reduction
R-CH
A n aldehyde
R-CH2 OH
A p rimary
alcohol
O
OH
reduction
R-C-R'
R-CH-R'
A second ary
A k eton e
alcohol
13-40
Catalytic Reduction
• Catalytic reductions are generally carried out from 25°
to 100°C and 1 to 5 atm H2.
OH
O
+
H2
Pt
25 o C, 2 atm
Cyclohexanone
Cyclohexanol
• A carbon-carbon double bond may also be reduced under
these conditions.
O
H
trans- 2-Butenal
(Crotonaldehyde)
2 H2
Ni
OH
1-Butanol
13-41
Metal Hydride Reductions
• The most common laboratory reagents for the reduction
of aldehydes and ketones are NaBH4 and LiAlH4.
• Both reagents are sources of hydride ion, H:-, a very
strong nucleophile.
H
Na
+
H- B- H
H
Sodium
borohydride
H
Li
+
H- A l- H
H
Lithium aluminum
hydride (LAH)
H:
Hydride ion
13-42
NaBH 4 Reductions
• Reductions with NaBH4 are most commonly carried out in
aqueous methanol, in pure methanol, or in ethanol.
• One mole of NaBH4 reduces four moles of aldehyde or
ketone.
O
methanol
4 RCH + NaBH4
-
+
( RCH2 O) 4 B Na
A tetraalkyl borate
H2 O
4 RCH2 OH + borate
salts
13-43
NaBH 4 Reductions
• The key step in metal hydride reductions is transfer of a
hydride ion to the C=O group to form a tetrahedral
carbonyl addition compound.
H
O
+
Na H-B-H + R-C-R'
H
O BH3 Na
+
R-C-R'
H
from the hydride
reducing agent
H2 O
from
w ater
O-H
R-C-R'
H
13-44
Metal Hydride Reductions
• Metal hydride reducing agents do not normally reduce
carbon-carbon double bonds, and selective reduction of
C=O or C=C is often possible.
O
RCH= CHCR'
1 . Na BH 4
2 . H2 O
O
RCH= CHCR'
+
H2
Rh
OH
RCH= CHCH R'
O
RCH2 CH 2 CR'
13-45
Aldehydes and
Ketones
End Chapter 13
13-46