Chem 150
Unit 7 - Organic Molecules II
Carboxylic Acids, Phenols & Amines
In this unit and the next we look at the chemical and
physical properties of a variety of organic families, all of
which play important roles in biochemistry. These
include the carboxylic acids, phenols, amines and
amides. We also look at a new type of stereoisomer
that figures predominantly in biological chemistry; the
optical isomer.
Introduction
The organic groups covered in this Unit all have important
biological roles
• Carboxylic acids
• Fatty acids
• Amino acids and proteins
• Phenols
• Colors and flavorings
• Amino acids and proteins
• Signal molecules
• Amines
• Amino acids and proteins
• Signal molecules
• Drugs
• Amides
• Amino acids and proteins
2
Carboxylic Acids
Naming carboxylic acids
• The IUPAC ending is -oic acid.
4
Question
Give the IUPAC names for the following carboxylic acids:
O
A)
CH3 CH2 CH2 CH2 C
O
B)
HO
C
CH3
CH2 CH
CH3
5
OH
CH2 CH
CH3
Carboxylic Acids
•
•
6
Carboxylic acid have high melting points
Small carboxylic acids are quite soluble in water
Carboxylic Acids
Small (volatile) carboxylic acids have noticeable odors.
• Ethanoic acid (acetic acid) vinegar
O
CH3 C
•
OH
Butanoic acid (butyric acid) vomit, dirty socks
O
CH3 CH2 CH2 C
•
OH
Hexanoic acid (caproic acid) goats, ripe cheese
O
CH3 CH2 CH2 CH2 CH2 C
7
OH
Phenols
Simplest phenol is phenol.
• A hydroxyl group attached to a benzene ring.
OH
8
Phenols
All phenols contain hydroxyl groups attached to aromatic
rings.
9
Phenols
All phenols contain hydroxyl groups attached to aromatic
rings.
10
These have
2 hydroxyl
groups
attached to a
benzene ring
11
Carboxylic Acids & Phenols as Weak Acids
Both carboxylic acids and phenols are weak acids
pKa ≈ 5
O
CH3 C
OH
+
acid
O
CH3 C
H2O
base
O
+
base
H3O+
acid
pKa ≈ 10
OH
acid
12
+
H2O
base
O
base
+
H3O+
acid
Carboxylic Acids & Phenols as Weak Acids
The acidity of hydroxyl groups depend on what they are
connected to:
carboxylic
acids
phenols
alcohols
O
C
O
acidic
13
H
O
weakly acidic
H
C
O
H
non-acidic
Carboxylic Acids & Phenols as Weak Acids
•
•
At pH 7, the carboxylate ion of carboxylic acids predominate
At pH 7, the phenol of phenol predominate
O
CH3 C
O
OH
+
acid
CH3 C
H2O
base
pKa ≈ 5
OH
acid
pH = 7
14
+
H2O
O
base
pH = 7
base
pKa ≈ 10
H3O+
acid
O
base
+
+
H3O+
acid
Carboxylic Acids & Phenols as Weak Acids
Strong bases can be used to convert carboxylic acids and
phenols to their corresponding carboxylate and phenoxide
ions
15
Carboxylic Acids & Phenols as Weak Acids
Fatty acids are carboxylate ions at pH 7
• Fatty acids with less that 12 carbons are soluble in water
• Fatty acids with greater than 12 carbons are amphipathic,
and form micelles when mixed with water.
16
Carboxylic Acids & Phenols as Weak Acids
IUPAC names for carboxylate ions:
• Remove the “-ic acid” from the corresponding conjugate
acids name and replace it with “-ate ion”.
17
Carboxylic Acids & Phenols as Weak Acids
Examples:
18
Carboxylic Acids & Phenols, Other Reactions
We have already seen how carboxylic acids and
carboxylate ions can be made from from the hydrolysis of
esters.
• Base-catalyzed hydrolysis of esters:
•
19
Acid-catalyzed hydrolysis of esters:
Carboxylic Acids & Phenols, Other Reactions
The acid-catalyzed hydrolysis of esters is reversible and can
be used to make esters from carboxylic acids and alcohols:
• Synthesis of esters from carboxylic acids and alcohols:
20
Carboxylic Acids & Phenols, Other Reactions
A biologically important reaction involving carboxylic acids is
the decarboxylation of α-keto and β-keto acids:
21
Carboxylic Acids & Phenols, Other Reactions
The decarboxylation of β-keto acids produces ketones
The decarboxylation of α-keto acids produces aldehydes
22
Carboxylic Acids & Phenols, Other Reactions
The oxidation of
hydroquinones is also
an important biological
reaction.
• A chemical oxidation
of hydroquinones
can be carried out
the oxidizing agent
K2Cr2O7 (potassium
dichromate)
23
Carboxylic Acids & Phenols, Other Reactions
Example:
• Coenzyme Q and the Electron Transport Chain
24
Carboxylic Acids & Phenols, Other Reactions
Example:
• Coenzyme Q and the Electron Transport Chain
25
Amines
Amines are a nitrogen with one or more carbons attached:
• Amines are classified based on the number of carbons that
are attached to the nitrogen.
• Primary amine (1°): 1 carbons
• Secondary amine (2°): 2 carbons
• Tertiary amine (3°): 3 carbons
N
26
Amines
It is possible for a fourth carbon to attach to the nitrogen
• The nitrogen will take on a positive charge to become an
ion.
• Quaternary (4°) ammonium ions: 4 carbon atoms
N
27
Amines
28
Amines
The IUPAC names for 1°, 2°, and 3° amines.
• Create the parent name by picking the longest chain of
carbons that is attached to the nitrogen.
• Replace the “-e” in the parent with the ending “-amine”.
• Number the longest chain from the end that gets you to the
the carbon to which the nitrogen is attached in the fewest
number of carbons.
• Use a numbered prefix to indicate which the carbon in the
longest chain the nitrogen is bonded to.
• If other substituents are attached to the nitrogen, list them
and use the prefix “N-” to indicate that they are attached to
the nitrogen.
29
Questions
Give the IUPAC names for the following amines:
CH3
A)
CH3 CH2 CH
CH3 CH2 CH
NH2
N
CH2 CH3
CH3 CH2 CH2 CH3
30
Questions
Give the IUPAC names for the following amines:
CH3
A)
CH3 CH2 CH
NH2
2-butanamine
2-butanamine
CH3 CH2 CH
N
CH2 CH3
CH3 CH2 CH2 CH3
N-ethyl-N-propyl-2-butanamine
31
N-ethylN-propyl
Amines
For heterocyclic amines the nitrogen is part of a ring.
• The ring can be either aromatic or not.
• The nucleic acid nucleotide bases are good examples of
hetoercyclic amines
32
Amines
Hydrogen Bonding
• 1° and 2° amines can serve as both a hydrogen bond
donor and acceptor.
• 3° amines can server as a hydrogen bond acceptors, but
not donors.
33
Amines
Hydrogen Bonding
• 4° ammonium ion cannot form hydrogen bonds, but
because they are charged, form ionic bonds:
CH3
CH3
N
CH3
34
CH3
Cl
Amines
The ability to hydrogen bond give amines moderately high
boiling points and high solubilities in water.
35
Amines
Another notable property of amines is their odor.
• Like carboxylic acids, they can also produce foul odor.
• The produce a “fishy” smell.
• Examples of amines, whose names imply their odoriferous
properties, include
H2N
putrescine
36
NH2
H2N
NH2
cadaverine
Amines as Weak Bases
In Unit 6, while discussing the definitions of acids and bases,
we saw that ammonia, NH3, is operationally a base
• That is, when added to water ammonia causes the pH to
rise above pH 7.
NH3 (aq)
•
+
H2O (l)
NH4+ (aq)
+
Ammonia was the example we used to demonstrate the need for the
Brønsted-Lowry definition of acids and bases.
See the Unit 6 Elaboration Definitions of Acids and Bases - Part III:
Brønsted-Lowry Definition
37
OH- (aq)
Amines as Weak Bases
Like ammonia, 1°, 2° and 3°, act as Brønsted-Lowry bases.
H
CH3 N
H (aq)
H
methanamine
(base)
38
+
H2O (l)
CH3 N
H (aq)
H
methylammonium ion
(acid)
+
OH- (aq)
Amines as Weak Bases
The conjugate acids are called ammonium ions
• When placed in water, these ammonium ions will behave
like acids.
H
CH3 N
pKa - 10
H (aq)
H
methylammonium ion
(acid)
39
+
H2O (l)
CH3 N
H (aq)
H
methanamine
(base)
+
H3O+ (aq)
Amines as Weak Bases
Because it is charged, the conjugate acid is even more
soluble that the amine.
• Many drugs are amines and are sold the ammonium salts,
which are more readily absorbed, due to their increased
solubility.
• Ephedrine is used as a decongestant.
CH3
CH
CH
OH
N
+
CH3
HCl
H
CH
OH
ephedrine
40
CH
CH
N
CH3
Cl-
H
ephedrine HCl
CH3
CH
H
OH
ephedrine
2
CH3
N
H
CH3
+
H2SO4
CH
CH3
H
CH
N
OH
ephedrine sulfate
H
CH3
SO422
Amines as Weak Bases
Ephedrine is an example of an alkaloid.
• Alkaloids are alkaline molecules that are derived from
plants.
• “alkaline” and another name for basic.
• Ephedrine is isolated from the Chinese ma huang
plant(Ephedra sinica)hyperlink
CH3
CH
CH
OH
ephedrine
41
CH3
N
H
CH3
CH2
CH
N
H
methamphetamine
CH3
Amides
•
•
42
When a carboxylic acid reacts with an amine it also
produces and ammonium salt
If the ammonium salt is then heated, an amide is
produced.
Amides
Amides are important in
biochemistry.
• For example, amino
acids are connected
together to form
proteins using amide
groups.
amino acid
43
Amides
Amides can be hydrolyzed back to carboxylic acids and
amines by heating them in the presence of an acid
44
Stereoisomers
So far we have encountered two different types of isomers.
• Constitutional Isomers
• Stereoisomers
• cis/trans isomers with alkenes and cycloalkanes, that arise from
restricted rotation about bonds.
There is one more type of stereoisomer, which is important in
biochemistry.
• optical isomers
45
Stereoisomers
Optical isomers arise when a carbon atom has four different
things attached to it.
• These carbons are called chiral carbons.
• The a molecule containing a chiral carbon is non
superimposable on its mirror image.
• The molecule and its mirror image are referred to as enantiomers
46
Stereoisomers
47
Stereoisomers
48
Stereoisomers
49
Stereoisomers
50
Stereoisomers
51
Stereoisomers
When developing drugs that are chiral, it is important to look
at the effects of both the enantiomers.
O
O
H
H
N
O
NH
O
O
O
N
NH
O
O
R-thalidomide
S-thalidomide
is effective in
treating morning
sickness in pregnant
women
is a teratogen,
causing birth
defects
R and S are another way of distinguishing enantiomers; R is
the rectus (right) isomer, while S is the sinister (evil) isomer!
52
Stereoisomers
When chiral molecules contain more than one chiral carbon,
it is possible for two molecules to be stereoisomers without
being mirror images.
• Such molecules are referred to as diastereomers.
CH3
C
OH
CH
H
ephedrine
53
CH3
N
H
C
CH3
H
CH
OH
N
H
pseudoephedrine
CH3
Stereoisomers
Each chiral carbon that a chiral molecule contains doubles
the number of stereoisomers for that molecule.
• Ephedrine has two chiral carbons, it therefore has 2 x 2 = 4
stereoisomers.
• pseudoephedrine is one of 4 stereoisomers.
CH3
C
OH
CH
H
ephedrine
54
CH3
N
H
C
CH3
H
CH
OH
N
H
pseudoephedrine
CH3
The End