ALDEHYDE KETONE

AND
CARBOXYLLIC ACID
ARINDAM GOSWAMI
DELHI PUBLIC SCHOOL
GHAZIABAD
Ketones and Aldehydes
Properties
Nomenclature
Preparation
Reactions
Synthesis
Carbonyl Functional Groups
Large Dipole Controls Properties and Reactivity
 Boiling Points
Dipole-Dipole Interactions
 Classical Aldehyde Nomenclature

Prefix
form HCHO

acet CH3CHO
  
propion CHO CHO
 

butyr
CHO

valer CHO
Nomenclature for Aldehydes

7
Nomenclature for Aldehydes

8
Nomenclature for Ketones

9
Nomenclature for Ketones

10
 Nomenclature for Aldehydes

The last of these compounds is named as a

benzaldehyde rather than as a phenol because
the aldehyde
priority group
over the hasgroup in the
hydroxyl naming
IUPAC system. 32
 Preparation of Ketones and Aldehydes
Gatterman-Koch Formylation (aldehydes)

Hydration of Alkynes (ketones with oxymercuration, aldehydes with

hydroboration)

Ozonolysis of Alkenes (aldehydes and ketones depending on

substitution)

Reduction of acids, acid chlorides and nitriles (aldehydes)

From acyl chloride (acid chloride) (aldehydes)

From nitriles and esters (aldehydes)

From hydrocarbons(aldehydes)

Friedel-Crafts Acylation (ketones)

 Gatterman-Koch Formylation
From benzene or substituted benzenes(aldehydes)

O
CH
CO, HCl
AlCl3/CuCl
benzene or activated benzene needed
in situ preparation of formyl chloride
O
C O + HCl HCCl
 Oxymercuration Hydration
Hydration of Alkynes
Markovnikov

OH
HgSO4, H2SO4
CH3CH2C CH CH3CH2C=CH2
H2O
an enol

O
CH3CH2CCH3
a ketone
 Hydroboration Hydration
Anti-Markovnikov
OH
1) disiamyl borane
CH3CH2C CH CH3CH2CH=CH2
2) H2O2, NaOH
an enol

B O
H CH3CH2CH2CH
(sia)2BH an aldehyde
 Ozonolysis
Alkene Cleavage

CH3 CH3 1) O3 in CH 2Cl2 CH3 CH3

C=C C O +O C
2) CH3SCH3 + DMSO
H CH3 H CH3
or Zn/HOAc
DMS
O
O O O
O O O O
CH3 CH3
C=C H O
H
H CH3
ozonide
 DIBAH
Diisobutyl Aluminum Hydride
Reduction of an Ester to an Aldehyde
O O
COCH2CH3 CH
1) DIBAH
+ CH3CH2OH
in toluene
+
2) H3O

H
DIBAH
Al
(CH3)2CHCH2 CH2CH(CH3)2
 From acyl chloride (acid chloride)

Acyl chloride (acid chloride) is hydrogenated over catalyst, palladium

on barium sulphate. This reaction is called Rosenmund reduction.

18
 From nitriles and esters
Stephen reaction.

Nitriles are reduced to corresponding imine with stannous chloride

in the presence of hydrochloric acid, which on hydrolysis give
corresponding al dehyde.

19
 From hydrocarbons

i) By oxidation of methylbenzene

20
(ii) By side chain chlorination followed by
hydrolysis

21
(iii) By Gatterman – Koch reaction
Polarity of Organic Compounds

23
 Polarity of Organic Compounds

Principles of Polarity:
The greater the electronegativity difference between atoms in a
bond, the more polar the bond. Partial negative charges are
found on the most electronegative atoms, the others are
partially positive. In general, the presence of an oxygen is more
polar than a nitrogen because oxygen is more electronegative
than nitrogen.
The combination of carbons and hydrogens as in hydrocarbons or
in the hydrocarbon portion of a molecule with a functional group
is always NON-POLAR.

24
 Summary of Polarity

Polarity Ranking of the Functional Groups:

(most polar first)

Amide > Acid > Alcohol > Ketone ~Aldehyde

> Amine > Ester > Ether > Alkane

25
Organic Functional Group Polarity and Elect
rostatic Potential:

The molecular electrostatic potential is the potential energy of a proton

at a particular location near a molecule.

Negative electrostatic potential corresponds to:

partial negative charges (colored in shades of red).

Positive electrostatic potential corresponds to:

partial positive charges (colored in shades of blue).

26
 .

Preparation
of Ketones

27
1. From acyl chlorides

28
2. From nitriles

29
 3. From benzene or substituted
benzenes
Friedel-Crafts acylation reaction.

30
Friedel-Crafts Acylation

31
 Practice Exercises
Write the structures of products of the following reactions;

32
 .

Physical
Properties

33
 .

The boiling points of aldehydes and ketones are

higher than hydrocarbons and ethers of
comparable molecular masses.
It is due to weak molecular association in
aldehydes and ketones arising out of the dipole-
dipole interactions.
Also, their boiling points are lower than those of
alcohols of similar molecular masses due to
absence of intermolecular hydrogen bonding.
34
 Practice Exercises

Arrange the following compounds in increasing order of

their boiling points.

CH3CHO, CH3CH2OH, CH3OCH3, CH3CH2CH3

35
 Nucleophilic Addition Reactions:
Strong Nucleophiles


O + OH
O H 3O



Nu: Nu Nu

Basic nucleophiles: RMgX, RLi, LiAlH4, NaBH4, RC CNa

-
Nonbasic nucleophiles: CN
 Carbonyl Reactivity


 O O O O
 > > >
 C C C C
H H R H R R' R OR

decreasing rate of reaction with nucleophile

 Practice Exercises
Would you expect benzaldehyde to be more reactive or
less reactive in nucleophilic addition reactions than
propanal?

The carbon atom of the carbonyl group of benzaldehyde

is less electrophilic than carbon atom of the carbonyl
group present in propanal. The polarity of the
carbonyl group is reduced in benzaldehyde
due to resonance as shown below and hence it is less
reactive than propanal.

38
 3) Nucleophilic Addition

Nucleophilic Addition Reaction of :

a.HCN: Cyanohydrin Formation
b.NaHSO3
c.Acetal Formation
d.Grignard Reagent : Formation of
Alcohol
MECHANISM

•.

40
41
 a) Nucleophilic addition of hydrogen
cyanide

* Cyanohydrin may be formed using liquid HCN with a catalytic

amount of sodium cyanide or potassium cyanide.

O OH
HCN CN
C
C
ketone or aldehyde

MECHANISM

O O OH
+
H
CN C C CN
C CN
b) Nucleophilic addition of bisulphite

43
c) Nucleophilic addition of ROH Acetal Formation

44
d) Nucleophilic addition of RMgX
Nucleophillic addition condensation reactions

46
47
Imine Derivatives
Imine Formation
 Imines and Enamines

R
O N
o
1 amine
RNH2
+ H 2O
+
H 3O
imine
pH = 4-5
o NR2
2 amine
R2NH
+ H 2O
+
H 3O
enamine
51
52
 Practice Exercises

Ketones undergo nucleophilic addition reaction

less easily than aldehydes.
ANS:Aldehydes have only one +I effect alkyl group
whereas ketones have two alkyl group with +I effect
which decreases the electrophilicity of the carbon,
rendering it less reactive than aldehydes. Also due to
the two alkyl group present in ketones, steric
repulsions are more and therefore reactivity is less.

53
 Practice Exercises

Acid chlorides are hydrolyzed more easily than

acid amides.
ANS:Acid chlorides are easily hydrolyzed because Cl- is a
better leaving group than NH2-. Also due to the strong –I
effect of chlorine, the carbon is more electrophilic in acids
chlorides than in acid amides and therefore undergoes
hydrolysis easily. Secondly, there is double bond character
in C=N bond which has high bond dissociation energy.

54
 Practice Exercises
Why the pH of the reaction is carefully controlled while preparing
ammonium derivatives of carbonyl compounds?
ANS:While preparing ammonium derivatives of carbonyl
compounds, the pH is maintained around 3-4 because in the
acidic medium the oxygen of the carbonyl group gets
protonated, which by resonance increases the positive charge
on the carbonyl carbon due to which weak nucleophiles like
ammonia derivatives readily attack the carbonyl carbon.
If the pH is further lowered the acid combines with the basic
ammonia derivatives thus, preventing the protonation. Also at a
higher pH the protonation does not occur and no reaction takes
place.

55
 Practice Exercises
There are two -NH2 groups in semicarbazide, however only one is
involved in the formations of semicarbazones. Explain.

Ans: - Semicarbazide is NH2NHCONH2. Inspite of having

two NH2- groups, only one is involved in the formation
of semicarbazones because the lone pair of electrons
on nitrogen is involved in resonance with the carbonyl
group and is not available for reaction with aldehydes
or ketones.

56
 2. Reduction
Clemmensen Reduction

The carbonyl group of aldehydes

and ketones is reduced to CH2 group on treatment with
.
zincamalgam and concentrated hydrochloric acid
 2. Reduction
Wolff-Kishner Reduction

The carbonyl group of aldehydes and ketones is reduced to

CH2 group on treatment with hydrazine followed by heating
with sodium or potassium hydroxide in high boiling solvent
such as ethylene glycol (Wolff-Kishner reduction).
 3. Oxidation

Tollens’ test: On warming an aldehyde with freshly prepared

ammoniacal silver nitrate solution (Tollens’ reagent), a bright
silver mirror is produced due to the formation of silver metal.
The aldehydes are oxidised to corresponding carboxylate anion.
The reaction occurs in alkaline medium.

59
 3. Oxidation

(ii) Fehling’s test: Fehling reagent comprises of two solutions,

Fehling solution A and Fehling solution B. Fehling solution A is
aqueous copper sulphate and Fehling solution B is alkaline
sodium potassium tartarate (Rochelle salt). These two solutions
are mixed in equal amounts before test. On heating an aldehyde
with Fehling’s reagent, a reddish brown precipitate is obtained.

60
 What is the order of ease of oxidation for aldehydes, ketones
and alcohols?

Aldehydes are the easiest to oxidize because they contain the highly
polarized carbonyl group. The partial positive charge on the carbon
makes it very reactive toward a hydride source such as sodium
borohydride.
Ketones and tertiary alcohols are the hardest to oxidize because doing
so requires breaking carbon-carbon bonds.
The remaining types of compounds, namely primary and secondary
alcohols, are intermediate between these two extremes.

61
 6) Haloform Reaction
• Iodoform test is useful for the methyl ketone group (CH3C=O) in
ethanal and methyl ketones.
• If an alkaline solution of iodine is warmed with an organic
compound and a yellow precipitate of triiodomethane is produced,
the organic compound is likely to be one of the following:

OH O
ethanol CH3 ethanal CH3 C H
H
C OH
a secondary alcohol with the CH3 group
H
CH
O
group
a ketone with the CH3
C
 Haloform Reaction

.
(iii) Oxidation of methyl ketones by haloform reaction:

64
 4. Reactions due to α-hydrogen

Aldol condensation: Aldehydes and ketones having at least one

α-hydrogen undergo a reaction in the presence of dilute alkali
as catalyst to form β-hydroxy aldehydes (aldol) or β-hydroxy
ketones (ketol), respectively. This is known as Aldol reaction.

65
Cross aldol condensation:

66
 5. Other reactions

(i) Cannizzaro reaction: Aldehydes which do not have an

α-hydrogen atom, undergo self oxidation and reduction
(disproportionation) reaction on heating with concentrated alkali.
In this reaction, one molecule of the aldehyde is reduced to
alcohol while another is oxidised to carboxylic acid salt.

67
 Electrophilic substitution reaction:

Carbonyl group acts as a deactivating and meta-

directing group.

68
 .

Carboxylic Acids
 Session Objectives
1. Introduction to carboxylic acids
2. Physical properties and structure
3. General method of preparation
By oxidation
Carbonation of grignard reagent
Hydrolysis of acid derivatives
From nitriles
4. Reactions of the carboxylic acids
 Introduction

The functional group of carboxylic acids

consists of a C=O with -OH bonded to the
same carbon.
Carboxyl group is usually written -COOH.
Aliphatic acids have an alkyl group bonded
to -COOH.
Aromatic acids have an aryl group.
Fatty acids are long-chain aliphatic acids.
Structure

72
 Common Names

Many aliphatic acids have historical

names.
Positions of substituents on the chain
are labeled with Greek letters.

Ph
Cl O
CH3CH2CH2CHCH2COOH
CH3CH2CHC OH
-phenylcaproic acid
-chlorobutyric acid
=>
Physical properties

74
 Boiling Points

Higher boiling points than similar alcohols, due

to dimer formation.

Acetic acid, b.p. 118C

 Melting Points
Aliphatic acids with more than 8 carbons are solids at
room temperature.
Double bonds (especially cis) lower the melting point.
Note these 18-C acids:
Stearic acid (saturated): 72C
Oleic acid (one cis double bond): 16C
Linoleic acid (two cis double bonds): -5C
 Solubility
 Water solubility decreases with the length
of the carbon chain.
 Up to 4 carbons, acid is miscible in water.
 More soluble in alcohol.
 Also soluble in relatively nonpolar solvents
like chloroform because it dissolves as a
dimer.
 Preparation Reactions

 Oxidation of Primary Alcohols

 Oxidation of Aldehydes
 Oxidation of Substituted Aromatics
 Carbonation of Grignard reagents
 Hydrolysis of Acid derivatives and Nitriles
 Haloform reaction
 Periodic acid Cleavage of Vicinal Dials/Diketones
 Oxidative Cleavage of Alkenes/Alkynes
 Carboxylic Acids via Oxidation

From Primary Alcohols

From Aldehydes
From Substituted Aromatics
From Substituted Aromatics examples

80
 Oxidative Cleavage Reactions

Alkene Cleavage
Hot Potassium Permanganate
Alkyne Cleavage
Hot Potassium Permanganate
Ozonolysis

KMnO
KMnO44
RR CH CH R'
CH CH R' ²² RCOOH ++R'COOH
RCOOH R'COOH

ozonolysis
ozonolysis RCOOH + R'COOH
RR CC CC R'
R' RCOOH + R'COOH
or
or
KMnO
KMnO44
²²
 Grignard Synthesis
Grignard reagent + CO2 yields a carboxylate salt.


O
R C + O O
H+
Mg O R C OMgX R C OH
H 2O
X
 Hydrolysis of acid derivatives
+
H
R C G R C OH + HG
H 2O
O O
OH - - -
R C G R C O + G
H 2O
O O

where G = -X,- OR, - NH2 , - NHR, - NR2 , &- O C R

O
+ -
H or OH
RC N R C NH 2 R C OH ( R C O- )
H 2O
O O O
 Hydrolysis of Nitriles

Basic or acidic hydrolysis of a nitrile produces a carboxylic acid.

Br CN + COOH
NaCN H
H2O
 Haloform Reaction
Cleavage of methyl carbinols
Cleavage of methyl carbonyls

H
X2 -
CH 3 C R - RCOO + HCX 3
OH /H 2O
OH
X2 -
CH 3 C R - RCOO + HCX 3
OH /H 2O
O
 Practice exercises
Write chemical reactions to affect the
following transformations:
(i)Butan-1-ol to butanoic acid
(ii) Benzyl alcohol to phenylethanoic acid
(iii) 3-Nitrobromobenzene to 3-nitrobenzoic acid
(iv)4-Methylacetophenone to benzene-1,4-dicarboxylic acid
(v)Cyclohexene to hexane-1,6-dioic acid
(vi)Butanal to butanoic acid.
86
 .
Chemical Reactions

87
Reactions Involving Cleavage
of O–H Bond

88
Acidity

89
Resonance Stabilization
 Substituent Effects on Acidity

COOH COOH COOH COOH COOH

NO 2

NO 2
OCH3 NO 2
p-methoxy benzoic acid m-nitro p-nitro o-nitro
pKa = 4.46 pKa = 4.19 pKa = 3.47 pKa = 3.41 pKa = 2.16
 Effect of substituents on the acidity of
carboxylic acids:

Electron withdrawing group (EWG)

stabilises the carboxylate anion
and strengthens the acid

Electron donating group (EDG)

destabilises the carboxylate
anion and weakens the acid

92
93
94
Direct attachment of groups such as phenyl or
vinyl to the carboxylic acid, increases the
acidity of corresponding carboxylic acid

95
This is because of greater electronegativity of sp2 hybridised
carbon to which carboxyl carbon is attached.

The presence of electron withdrawing group on the phenyl of aromatic carboxylic

acid increases their acidity while electron donating groups decrease their acidity.

96
97
98
Reactions Involving Cleavage of C–OH Bond

99
. Formation of anhydride

Esterification
Reaction with ammonia

Reactions with PCl5 , PCl3

and SOCl2
100
anhydride

101
ester

102
Acid chloride

103
Reactions Involving –COOH Group

104
 Reduction
Decarboxylation

105
106
 Reduction of Carboxylic Acids

 Lithium Aluminum Hydride reduction

 Diborane reduction

+
LiAlH
LiAlH44 H
H
+
RCOOH
RCOOH RCH
RCH22OH
OH
ether
ether H
H2OO
2
(selective
(selectivereduction
reductionof
of
BB2H
RCOOH 2 H66 RCH OH carboxyl
carboxylgroup
groupinin
RCOOH diglyme RCH22OH preference
preferencetotocarbonyl
diglyme of
carbonyl
ofaldehydes/ketones)
aldehydes/ketones)
 Substitution in the hydrocarbon part

Hell-Volhard-Zelinsky reaction

Acids having an -hydrogen are halogenated at the -position

on treatment with chlorine or bromine in the presence of
small amount of red phosphorus to give -halocarboxylic
acids.
X2 / P4, H2O
RCH2COOH   RCH(X)COOH
 Ring substitution in aromatic acids

—COOH group is deactivating and meta directing.

Aromatic carboxylic acids do not undergo Friedel-Crafts reaction.

Nitration

COOH COOH
H N O 3 (co n c.)

H 2S O 4(co nc.) NO2

Bromination
COOH COOH
B r2 /F e B r3

Br
 IMPORTANT
do not undergo Friedel-Crafts
reaction

110
because the carboxyl group is
deactivating and the catalyst
aluminium chloride (Lewis acid)
gets bonded to the carboxyl group

111
 Some commercially important carboxylic acids

Methanoic acid; (HCOOH)

473 K, 10 atm H
+
NaO H + CO HCOONa HCOOH

It is colourles, pungent smelling liquid.

It is powerful reducing agent. It reduces Tollen’s reagent and
Fehling solution.
Used in rubber, textile, dyeing, leather and electroplating
industries.
 Ethanoic acid(acitic acid, CH3COOH)

Main constituent of vinegar and is obtained by fermentation of

molasses in presence of air.

Industrially, it is obtained in pure form by oxidation of ethanal with air

in the presence of cobalt acetate catalyst or by carbonylation of
methanol in the presence of rhodium catalyst.

CH3CHO + CO  CH3COOH
CH3OH + CO  CH3COOH

Colourless liquid with pungent odour.

Freezes at 289 K forming ice like crystal.
Water free acetic acid, obtained by melting of the crystals is called
glacial acetic acid.
Thank you
114
Thank you
115
Thank you
116
Acidity

117
Acidity
 Session - 3

Carboxylic acid derivatives

 Session objectives
1. Nomenclature
2. Structures of the functional groups
3. Physical properties
4. Preparation of acyl halides and reactions
5. Preparation of acid anhydrides and reactions
6. Preparation of esters and their reactions
7. Preparation of amides and their reactions
 Introduction
Acyl group bonded to Y, an electronegative atom or
leaving group
Includes: Y = halide (acid halides), acyloxy
(anhydrides), alkoxy (esters), amine (amides), thiolate
(thioesters), phosphate (acyl phosphates)
 Naming Carboxylic Acid Derivatives

Acid Halides, RCOX

Derived from the carboxylic acid name by replacing the -ic
acid ending with -yl or the -carboxylic acid ending with –
carbonyl and specifying the halide
 Naming Acid Anhydrides, RCO2COR‘

If symmetrical replace “acid” with “anhydride”

based on the related carboxylic acid (for
symmetrical anhydrides)
From substituted monocarboxylic acids: use
bis- ahead of the acid name
Unsymmetrical anhydrides— cite the two acids
alphabetically
 Naming Amides, RCONH2

With unsubstituted NH2 group. replace -oic acid or -ic acid with -amide,
or by replacing the -carboxylic acid ending with –carboxamide
If the N is further substituted, identify the substituent groups (preceded
by “N”) and then the parent amide
 Naming Esters, RCO2R
Name R’ and then, after a space, the carboxylic acid
(RCOOH), with the “-ic acid” ending replaced by “-ate”
Summary of nomenclature
Relative Reactivity of Carboxylic Acid Derivatives

Nucleophiles react more

readily with unhindered
carbonyl groups

More electrophilic carbonyl

groups are more reactive to
addition (acyl halides are most
reactive, amides are least)
The intermediate with the best
leaving group decomposes
fastest
 Conversion to acid derivatives

The group bonded to the acyl carbon determines the class of

compound:
-OH, carboxylic acid
-Cl, acid chloride
-OR’, ester
-NH2, amide
These interconvert via nucleophilic acyl substitution.
 Fischer Esterification
Acid + alcohol yields ester + water.
Acid catalyzed for weak nucleophile.
All steps are reversible.
Reaction reaches equilibrium.

O
COOH + COCH2CH3
H
+ CH3CH2OH + HOH
 Conversion to Acid Chlorides

An activated form of the carboxylic acid.

Chloride is a good leaving group, so undergoes acyl
substitution easily.
To synthesize acid chlorides use thionyl chloride or oxalyl
chloride with the acid.

O O
O O C Cl
C OH
+ C C + HCl + CO + CO2
Cl Cl
 Conversion to Amides
Amine (base) removes a proton from the
carboxylic acid to form a salt.
Heating the salt above 100C drives off steam
and forms the amide.

O O O
C OH CH NH C O- +NH CH C NHCH
+ 3 3 3
3 2
heat
+ H2O
 Reduction to 1 Alcohols

Use strong reducing agent, LiAlH4.

Borane, BH3 in THF, reduces carboxylic acid to
alcohol, but does not reduce ketone.
 Decarboxylation of RCOOH

 Thermolysis of beta-diacids
 Thermolysis of beta-keto acids

COOH H
C C + CO 2
²
COOH COOH

COOH H
C C + CO 2
²
C C
O O
 Substitution in Synthesis
We can readily convert a more reactive acid
derivative into a less reactive one
Reactions in the opposite sense are possible
but require more complex approaches
Nucleophilic Acyl Substitution

Carboxylic acid derivatives have an acyl carbon

bonded to a group Y that can leave
A tetrahedral intermediate is formed and the
leaving group is expelled to generate a new
carbonyl compound, leading to substitution
 General Reactions of Carboxylic Acid Derivatives

With water  carboxylic acid

With alcohols  esters
With ammonia or an amine  an amide
With hydride source  an aldehyde or an alcohol
With Grignard reagent  a ketone or an alcohol
 Boiling Points

Even 3 amides have strong attractions.

 Melting Points
Amides have very high melting points.
Melting points increase with increasing number of N-
H bonds.

O O O H
C H3 H
H C N C H3 C N C H 3C H 2 C N
C H3 C H3 H

m.p. -61C m.p. 28C m.p. 79C

 Solubility

Acid chlorides and anhydrides are too reactive to

be used with water or alcohol.
Esters, 3 amides, and nitriles are good polar
aprotic solvents.
Solvents commonly used in organic reactions:
– Ethyl acetate
– Dimethylformamide (DMF)
– Acetonitrile
 Preparation of acid derivatives

Must enhance reactivity

Convert OH into a better leaving group
Specific reagents can produce acid chlorides, anhydrides,
esters, amides
 From carboxylic acids into acid Chlorides
Reaction with thionyl chloride, SOCl2.
Reaction with PBr3.
 Reactions of Acid Halides
Nucleophilic acyl substitution
Halogen replaced by OH, by OR, or by NH2
Reduction yields a primary alcohol
Grignard reagent yields a tertiary alcohol
 Hydrolysis: Conversion of Acid Halides
into Acids

Acid chlorides react with water to yield

carboxylic acids
HCl is generated during the hydrolysis: a
base is added to remove the HCl
 Conversion of Acid Halides to Esters

Esters are produced in the reaction of acid chlorides react

with alcohols in the presence of pyridine or NaOH
The reaction is better with less steric bulk
 Aminolysis: Conversion of Acid Halides into Amides

Amides result from the reaction of acid chlorides with NH 3,

primary (RNH2) and secondary amines (R2NH)
The reaction with tertiary amines (R3N) gives an unstable
species that cannot be isolated
HCl is neutralized by the amine or an added base
Reduction: Conversion of Acid Chlorides into Alcohols

LiAlH4 reduces acid chlorides to yield aldehydes and then

primary alcohols
 Reaction of Acid Chlorides with Organometallic Reagents

Grignard reagents react with acid chlorides to

yield tertiary alcohols in which two of the
substituents are the same
 Formation of Ketones from Acid Chlorides

Reaction of an acid chloride with a lithium diorganocopper

(Gilman) reagent, Li+ R2Cu
Addition produces an acyl diorganocopper intermediate, followed
by loss of RCu and formation of the ketone
 Preparation of acid anhydrides
Heat cyclic dicarboxylic acids that can form
five- or six-membered rings

from acid chlorides and carboxylic acids

 Reactions of Acid Anhydrides
Similar to acid chlorides in reactivity
 Acetylation
Acetic anhydride forms acetate esters from alcohols and N-
substituted acetamides from amines
 Chemistry of Esters
Many esters are pleasant-smelling liquids: fragrant
odors of fruits and flowers
Also present in fats and vegetable oils
 Preparation of Esters
Esters are usually prepared from carboxylic acids
 Preparation of esters

Methods include reaction of a carboxylate

anion with a primary alkyl halide
 Fischer Esterification
Heating a carboxylic acid in an alcohol solvent
containing a small amount of strong acid produces an
ester from the alcohol and acid
 Reactions of Esters
Less reactive toward nucleophiles than are acid
chlorides or anhydrides
Cyclic esters are called lactones and react
similarly to acyclic esters
 Hydrolysis: Conversion of Esters into Carboxylic Acids

An ester is hydrolyzed by aqueous base or

aqueous acid to yield a carboxylic acid plus
an alcohol
 Acid Catalyzed Ester Hydrolysis

The usual pathway is the reverse of the Fischer esterification

 Aminolysis of Esters

Ammonia reacts with esters to form amides

 Reduction: Conversion of Esters into
Alcohols

Reaction with LiAlH4 yields primary alcohols

 Partial Reduction to Aldehydes

Use one equivalent of diisobutylaluminum

hydride (DIBAH = ((CH3)2CHCH2)2AlH)) instead of
LiAlH4
Low temperature to avoid further reduction to
the alcohol
 Reaction of Esters with Grignard Reagents

React with 2 equivalents of a Grignard reagent to

yield a tertiary alcohol
 Chemistry of Amides
Prepared by reaction of an acid chloride with ammonia,
monosubstituted amines, or disubstituted amines
 Reactions of Amides

Heating in either aqueous acid or aqueous base produces a

carboxylic acid and amine.
Acidic hydrolysis by nucleophilic addition of water to the
protonated amide, followed by loss of ammonia.
 Basic hydrolysis of amides

Addition of hydroxide and loss of amide ion

 Reduction: Conversion of Amides into
Amines

Reduced by LiAlH4 to an amine rather than an alcohol

Converts C=O  CH2
 Mechanism of Reduction

Addition of hydride to carbonyl group

Loss of the oxygen as an aluminate anion to give an
iminium ion intermediate which is reduced to the amine
Thank you!
Negative electrostatic potential corresponds to:
partial negative charges (colored in shades of red).
Positive electrostatic potential corresponds to:
partial positive charges (colored in shades of blue).

169
Negative electrostatic potential corresponds to:
partial negative charges (colored in shades of red).
Positive electrostatic potential corresponds to:
partial positive charges (colored in shades of blue).

170
 Boiling Point
Definition:

In a liquid the molecules are packed

closely together with many random
movements possible as molecules slip past
each other.
As a liquid is heated, the temperature is
increased. As the temperature increases,
the kinetic energy increases which causes
increasing molecular motion (vibrations
and molecules slipping pas each other).

Eventually the molecular motion becomes

171
so intense that the forces of attraction
 Polarity and Boiling Point:

The polarity of the molecules determines the forces of

attraction between the molecules in the liquid state.
Polar molecules are attracted by the opposite charge
effect (the positive end of one molecule is attracted to
the negative end of another molecule.
Molecules have different degrees of polarity as
determined by the functional group present

172
Principle: The greater the forces of
attraction the higher the boiling point or
the greater the polarity the higher the
boiling point.

173
 Functional Group Ranking by Boiling Points
Functional Boiling Polar Name Brief Explanation
Group Point Rank
Name (most
to
least)

(1) AMIDE:The reason is that it can

both hydrogen bond and accept
Amide
222o 1 ethanamide hydrogen bonds on both the oxygen
and the nitrogen.

(2) ACID: These compounds are second

ethanoic acid in the polarity because of hydrogen
Acid 118o 2 or bonding capabilities and the presence
acetic acid of two oxygen atoms.

(3) ALCOHOL: These compounds are

third in the polarity because of
hydrogen bonding capabilities and the
Alcohol 117o 3 propanol
presence of only one oxygen vs. the
two in the acid functional group.174
 Functional Group Ranking by Boiling Points

Functional Boiling Polar Name Brief Explanation

Group Point Rank
Name (most
to
least)

propanone
Ketone (4) KETONE and (5) ALDEHYDE: A comparison
56o 4, 5 or
of the boiling points of aldehyde and ketone
acetone
with the corresponding alcohol shows that
the alcohol is more polar due to its ability to
hydrogen bond. Since ketones and aldehydes
lack hydroxyl groups, they are incapable of
intermolecular hydrogen bonds. But due to
the presence of the oxygen, they can accept
hydrogen bonds from water molecules which
account for the complete solubility of low
molecular weight compounds.
175
 Functional Group Ranking by Boiling Points

Functional Boiling Polar Name Brief Explanation

Group Point Rank
Name (most
to
least)

On the other hand, their boiling points are

considerable higher than the ether or
alkane, indicating the presence of weak
intermolecular dipole-dipole forces. The
carbonyl group ("carbon double bond
Aldehyde 49o 4, 5 propanal oxygen") is polar since oxygen is more
electronegative than carbon and forms a
partially charged dipole.

176
 Functional Group Ranking by Boiling Points

Functional Boiling Polar Name Brief Explanation

Group Point Rank
Name (most
to
least)

(6) AMINE : The polarity of the amine

nitrogen is shown to be much less than the
oxygen in alcohol group. The nitrogen in the
Amine amine is much less electronegative than
49o 6 propylamine
oxygen in the alcohol. Therefore, the dipole
on N-H is much weaker than the dipole on O-
H.
(7) ESTER: The ester functional group has a
similar character to the ketone and aldehyde
methyl
Ester 32o 7 functional group. The boiling point indicates
ethanoate
that it is the least polar of the three.
177
 Functional Group Ranking by Boiling Points
Functional Boiling Polar Name Brief Explanation
Group Point Rank
Name (most
to
least)

8) ETHER : The carbon-oxygen-carbon bond

in ethers is much like the carbon-carbon
bond in alkanes. The lack of any oxygen-
hydrogen bond makes hydrogen bonding
Ether methyl ethyl
11o 8 impossible. There is very little intermolecular
ether
association. Therefore, the properties of
ethers are much like alkanes. Ethers are
essentially non-polar and insoluble in water.

(9) HYDROCARBON: There is very little

intermolecular association because the
carbon-hydrogen bond is non-polar. Alkanes,
Alkane -42o 9 propane
alkenes, and alkynes are essentially non-
polar and insoluble in water.
178