Transcript lecture 3 - aldehydes and ketones

Aldehydes and ketones
DR AKM SHAFIQUL ISLAM
SCHOOL OF BIOPROCESS ENGINEERING
UNIVERSITY MALAYSIA PERLIS (UniMAP)
Carbonyl group
 One
of the most important functional
groups in organic chemistry.
C
O
 It
is present in aldehydes and ketones
Carbonyl Compounds
Aldehydes
 A compound
in which the carbonyl group
is connected to a hydrogen and an alkyl
group or aromatic ring ( or to two
hydrogens ).
H C H
R C H
O
O
C H
O
Ketones
 A compound
in which the carbonyl group
is connected to two alkyl groups or
aromatic rings ( or one of each ).
R C
R
C
O
O
C
O
O
R
IUPAC Nomenclature of Aldehydes
O
5
6
3
4
3
1
2
Hexanal
O
O
H
4
2
1
H
3-Methylbutan al
3
2
1
H
2-Prop enal
(Acrolein)

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 Aldehydes

The aldehyde group is abbreviated by CHO.

The IUPAC retains the common names
benzaldehyde and cinnamaldehyde, as well
formaldehyde and acetaldehyde.
O
CHO
CHO
H
OCH3
t rans-3-Phenyl-2-prop enal
(Cinn amald ehyd e; in
oil of cin namon)
Ben zaldehyde
(in almond s)
OH
Van illin
(from van illa
bean s)
IUPAC Nomenclature of
Ketones

Because ketones have the general formula,
the shortest ketone chain length is 3 carbons.
O
R

C R
The carbonyl group cannot be at the end of the
chain; it must be in the middle.
O
CH3 C CH3
IUPAC Nomenclature of Ketones
O
O
1
Acetone

O
2
3
4
5
1
6
5-Meth yl-3-h exanone
2
2-Methylcycloh exanone
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.
Name the following ketones
using
IUPAC
names
and
common names.
O
2-propanone
dimethyl ketone
acetone
CH3CCH3
O
2-butanone
methyl ethyl ketone
CH3CCH2CH3
O
CH3 C
1
2
ethyl methyl ketone
CH3 Cl
CH2 C
C CH3
4
5
3
6
CH3 H
MEK
5-chloro-4,4dimethyl-2-hexanone
Copyright© 2005, Michael J. Wovkulich. All rights reserved.
Common names - ketones
 name
COH
acid
each alkyl group bonded to the
carbonyl carbon as a separate word,
followed by the word "ketone”
O
O
Meth yl ethyl ketone Ethyl isoprop yl ketone
Natural Products
Physical Properties



What kind of intermolecular forces are
possible between carbonyl groups?
Is H-bonding possible?
How do you think the boiling point of
aldehydes and ketones compares to alkanes
and alcohols?
• Alkanes – very weak forces
• Alcohols – H-bonds
Physical Properties
 A C=O
bond is polar, with oxygen bearing
a partial negative charge and carbon
bearing a partial positive charge

therefore, aldehydes and ketones are polar
molecules
Dipole/Dipole Interactions
The 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.
dO
dO
C
d+
C
d+
dO
C
d+
dipole/dipole interaction
Lack of Hydrogen Bonding

Because aldehydes and ketones lack a hydrogen on the
oxygen, they cannot form hydrogen bonds between
other aldehyde or ketone molecules.
O
O
R
C H
Aldehyde

R
C R
Ketone
Thus, their boiling points are lower than those of alcohols
with similar molecular weights (which have extensive
hydrogen bonding).
Solubility
 Even
though it cannot H-bond with other
carbonyls, the carboxyl group can accept
H-bonds from water


formaldehyde, acetaldehyde, and acetone are
infinitely soluble in water
As the hydrocarbon portion of the molecule
increases in size, solubility in water decreases
• Larger ketones and aldehydes are soluble in
organic solvents
Water 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.
Oxidation

Aldehydes are oxidized to carboxylic acids


Change the –H to an –OH
Ketones are not oxidized further
O
O
[O]
H3C
H3C
H
O
[O]
H3C
NR
CH3
OH
Oxidation of Primary Alcohols
General equation:
RCH2OH
oxidize
Primary alcohol
RCOOH
Aldehyde
Carboxylic acid
(in anhydrous media)
(when water is present)
OH
O
(O)
R C H
oxidize
RCHO
R
C H
+
H2O
H
O
(O)
R C OH
Oxidation of Primary Alcohols
Examples:
O
CH3CH2OH
(O)
ethanol
O
CH3 C H
(O)
ethanal
ethanoic acid
O
CH3(CH2)5CH2OH
1-heptanol
(O)
CH3(CH2)5 C H
heptanal
CH3 C OH
O
(O)
CH3(CH2)5 C OH
heptanoic acid
Tests 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’ Reagent

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.
O
R
C H
O
+ Ag+(aq)
NH3, H2O
R C OH
+ Ag(s)
heat
+1
oxidation state
0
oxidation state
Tollens’ Reagent
(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 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.
O
R
C H
O
+ Cu2+
+2
oxidation state
R C OH
+ Cu2O
+1
oxidation state
Benedict’s Reagent
Aldehydes and one type of easily oxidized ketone give a positive test result. The
structural features necessary are:
O
R
C H
O
R CH C H
OH
Aldehyde
Aldehyde
with adjacent
alcohol group
O
R CH C R
OH
Ketone
with adjacent
alcohol group
These features are found in a number of sugars.
Benedict’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 Reaction

Reagents that attack the electron-rich d- end of the C=O
bond are called electrophiles (literally, "lovers of electrons").
Electrophiles include ions (such as H+ and Fe3+) and neutral
molecules (such as AlCl3 and BF3) that are Lewis acids, or
electron-pair acceptors.

Reagents that attack the electron-poor d+ end of this bond
are nucleophiles (literally, "lovers of nuclei"). Nucleophiles
are Lewis bases (such as NH3 or the OH- ion).
Nucleophilic Addition

A strong nucleophile attacks the carbonyl carbon,
forming an alkoxide ion that is then protonated.

A weak nucleophile will attack a carbonyl if it has
been protonated, thus increasing its reactivity.

Aldehydes are more reactive than ketones.
=>
Reaction Themes, Nu attack at C

One of the most common reaction themes of a carbonyl
group is addition of a nucleophile to form a tetrahedral
carbonyl addition compound.
O
R
Nu
-
C
+
R
O
Nu
-
C
R
R
Tetrahedral carbonyl
addition compound
Reaction Themes, O attack at H

A second common theme is reaction with a proton or
other Lewis acid to form a resonance-stabilized cation.

protonation increases the electron deficiency of the carbonyl
carbon and makes it more reactive toward nucleophiles.
R
C O
+ H-B
B +
R
+
C O H
-
+ H-Nu +
+
C O H
R
slow
+
C O H
R
R
B
R
fast
R
R
O-H
Nu
+
C
H-B
R
R
Tetrahedral carbonyl
addition compound
Addition of C Nucleophiles

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 these carbon nucleophiles.
RMgX
A Grignard
reagent
RLi
RC C An organolithium An alkyne
reagent
anion
-
C N
Cyanide ion
A. Grignard Reagents

Given the difference in electronegativity between carbon
and magnesium (2.5 - 1.3), the C-Mg bond is polar
covalent, with Cd- and Mgd+.


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.
Grignard Reagents, 1o alcohols

addition of a Grignard reagent to formaldehyde
followed by H3O+ gives a 1° alcohol.
 these reactions require two steps.
O
CH3 CH2 -MgBr + H-C-H
ether
Formaldehyde
-
O [ MgBr]
CH3 CH2 -CH2
A magnesium
alkoxide
+
HCl
H2 O
OH
CH3 CH2 -CH2 + Mg2 +
1-Propanol
(a 1° alcohol)
Grignard Reagents, 2o alcohols

addition to any other aldehyde, RCHO, gives a
2° alcohol (two steps).
MgBr
O
+
ether
H
Acetaldehyde
(an aldehyde)
-
O [ MgBr]
+
OH
HCl
H2 O
A magnesium
alkoxide
+ Mg2 +
1-Cyclohexylethanol
(a 2° alcohol;
(racemic)
Grignard Reagents, 3o alcohols

addition to a ketone gives a 3° alcohol (two
steps).
O
Ph-MgBr
Phenylmagnesium
bromide
ether
+
Acetone
(a ketone)
-
O [ MgBr]
Ph
A magnesium
alkoxide
+
HCl
H2 O
OH
+ Mg2+
Ph
2-Phenyl-2-propanol
(a 3° alcohol)
B. Organolithium Compounds



Organolithium compounds, RLi, give the same C=O
addition reactions as RMgX but generally are more
reactive and usually give higher yields.
Lithium is monovalent and does not insert between C
and X like Mg.
Like the Grignard this requires two steps.
O
Li
O- Li+
HCl
H2 O
+
Phenyl- 3,3-Dimethyl-2lithium
butanone
OH
A lithium alkoxide
(racemic)
3,3-Dimethyl-2-phenyl2-butanol
(racemic)
C. Salts of Terminal Alkynes
 Addition
of an alkyne anion followed by
H3O+ gives an acetylenic alcohol.
O
HC C O - Na+
HCl
H2 O
-
HC C: Na+ +
Sodium
acetylide
Cyclohexanone
HC C OH
A sodium
alkoxide
1-Ethynylcyclohexanol
Salts of Terminal Alkynes

Addition of water or hydroboration/oxidation of
the product gives an enol which rearranges.
O
H2 O
HO
C CH
HO

CCH3
H2 SO4 , HgSO4
An -hydroxyketone
HO
1 . (sia) 2 BH
2 . H2 O2 , NaOH

O

CH2 CH
A -hydroxyaldehyde
D. Addition of HCN

HCN adds to the C=O group of an aldehyde or
ketone to give a cyanohydrin.
 Cyanohydrin: a molecule containing an -OH
group and a -CN group bonded to the same
carbon.
O
CH3 CH + HC N
OH
CH 3 C- C N
H
2-Hydroxypropanenitrile
(Acetaldehyde cyanohydrin)
Addition of HCN

Mechanism of cyanohydrin formation:

Step 1: nucleophilic addition of cyanide to the
carbonyl carbon.
H3 C
•
•
H3 C
C O + C N
H3 C

O
-
C
H3 C
C N
Step 2: proton transfer from HCN gives the
cyanohydrin and regenerates cyanide ion.
H3 C
O
-
C N
H C N
O-H
+
C
H3 C
C N
-
•
•
+
C
H3 C
H3 C
C N
Cyanohydrins

The value of cyanohydrins:

1. acid-catalyzed dehydration of the alcohol gives an
alkene.
OH
CH3 CHC N
acid
catalyst
CH2 = CHC N + H2 O
2-Hydroxypropanenitrile
(Acetaldehyde cyanohydrin)

Propenenitrile
(Acrylonitrile)
2. catalytic reduction of the cyano group gives a 1°
amine.
OH
OH
CHC N + 2 H2
Benzaldehyde
cyanohydrin
(racemic)
Ni
CHCH2 NH2
2-Amino-1-phenylethanol
(racemic)
Cyanohydrins
 The

value of cyanohydrins:
3. acid-catalyzed hydrolysis of the nitrile gives
a carboxylic acid.
OH
CH3 CHC N
acid
catalyst
H2 O
2-Hydroxypropanenitrile
(Acetaldehyde cyanohydrin)
OH
CH3 - CHCOOH
2-Hydroxypropanoic acid
Mechanism of Aldol Reactions


Aldol reactions, like all carbonyl condensations, occur by
nucleophilic addition of the enolate ion of the donor
molecule to the carbonyl group of the acceptor molecule
The addition intermediate is protonated to give an
alcohol product
Conditions for Condensations

A small amount of base is used to generate a
small amount of enolate in the presence of
unreacted carbonyl compound
 After the condensation, the basic catalyst is
regenerated