Transcript Amines

Chapter 15
Amines
Structure & Classification

Amines are classified as 1°, 2°, or 3°
depending on the number of carbon groups
bonded to nitrogen
CH3 -NH2
Methylamine
(a 1° amine)
NH2
Anilin e
(a 1° aromatic amine)
H
CH3 -N-CH3
Dimethylamine
(a 2° amine)
H
N-CH3
N -Methylan iline
(a 2° aromatic amine)
CH3
CH3 -N-CH3
Trimethylamine
(a 3° amine)
CH3
CH2 -N-CH3
Ben zyldimethylamine
(a 3° aliph atic amin e)
Structure & Classification

heterocyclic amine: an amine in which the
nitrogen atom is part of a ring
N
N
N
H
N
H
Pyrrolidin e Pip eridin e
(h eterocyclic aliph atic amin es)
N
N
N
N
H
H
Pyridin e Pyrimidin e Imid azole Purine
(heterocyclic aromatic amines )
N
N
N
Nomenclature

IUPAC names
Similar to alcohols
 drop the final -e of the parent alkane and
replace it by -amine
 use a number to locate the amino group on
the parent chain

NH2
CH3 CHCH3
2-Propanamine
NH2
H2 N
Cyclohexanamine
NH2
1,6-Hexanediamine
Nomenclature

IUPAC names (cont’d)



IUPAC nomenclature retains the common name
aniline for C6H5NH2, the simplest aromatic amine
use numbers to locate substituents or, alternatively,
use the prefixes ortho (o), meta (m), and para (p)
common names are still widely used
NH2
NH2
NH2
CH3
A niline
NO2
4-N itroaniline
(p-N itroan iline)
3-Methylaniline
(m-Tolu idine)
Nomenclature

IUPAC names (cont’d)



name unsymmetrical secondary and tertiary amines
as N-substituted primary amines
take the largest group bonded to nitrogen as the
parent amine
smaller group(s) are substituents indicated by using
the prefix N
CH3
NHCH3
N-Meth ylan ilin e
N
CH3
N,N -D imethylcyclopentan amin e
Nomenclature

Common names

for most aliphatic amines, list the groups
bonded to nitrogen in alphabetical order in
one word ending in the suffix -amine
NH2
Propylamine
NH2
NH2
N
sec-Butylamin e D ieth ylmethylamin e
Cyclohexylamine
Nomenclature

Amine salts
when four things are bonded to a nitrogen
atom, the nitrogen bears a positive charge
 name the compound as a salt
 replace the ending -amine (or aniline or
pyridine or the like) by -ammonium (or
anilinium or pyridinium or the like) and add the
name of the anion

+
-
( CH3 CH2 ) 3 NH Cl
Triethylammonium chloride
Physical Properties

Like ammonia, low-molecular-weight
amines have very sharp, penetrating
odors
trimethylamine, for example, is the pungent
principle in the smell of rotting fish
 two other particularly pungent amines are
1,4-butanediamine (putrescine) and 1,5pentanediamine (cadaverine)

Physical Properties

Amines are polar compounds

both 1° and 2° amines have N-H bonds, and
can form hydrogen bonds with one another
Physical Properties
an N-H---N hydrogen bond is weaker than
an O-H---O hydrogen bond
 compare the boiling points of ethane,
methanamine, and methanol

MW (amu)
bp (°C)
CH3 CH3
CH3 NH2
CH3 OH
30.1
-88.6
31.1
-6.3
32.0
65.0
Physical Properties
all classes of amines form hydrogen bonds
with water and are more soluble in water
than are hydrocarbons of comparable
molecular weight
 most low-molecular-weight amines are
completely soluble in water
 higher-molecular-weight amines are only
moderately soluble in water or are insoluble

Basicity of Amines

Like ammonia, amines are weak bases,
and aqueous solutions of amines are
basic

the acid-base reaction between an amine
and water involves transfer of a proton from
water to the amine
H
+
CH3 -N-H :O-H
H
Meth ylammoniu m
hydroxide
: :
: :
H
CH3 -N: + H-O-H
H
Methylamin e
(a bas e)
Basicity of Amines

The base dissociation constant, Kb, for
the reaction of an amine with water has
the following form, illustrated for the
reaction of methylamine with water to
give methylammonium hydroxide

pKb is defined as the negative logarithm of
+
Kb
[CH3 NH3 ][ OH ]
-4
Kb =
= 4.37 x 10
[ CH3 NH2 ]
pKb = - log 4.37 x 10-4 = 3.360
Basicity of Amines
aliphatic amines SS bases than NH3
 aromatic amines are weaker bases

Clas s
Aliph atic
Ammonia
Aromatic
pKb
Example
3.0 - 4.0 CH3 CH2 NH2
N ame
Ethan amin e Stron ger bas e
4.74
8.5 - 9.5 C6 H5 NH2
Anilin e
Weaker base
Basicity of Amines

We can determine which form of an
amine exists in body fluids, pH 7.40

if an aliphatic amine is dissolved in blood, it
is present predominantly as its protonated
(conjugated acid) form
HO
NH 2
HO
D opamine
HO
NH3 +
HO
Con jugate acid of d op amine
(the major form p res ent
in b lood p lasma)
Reactions of Amines

The most important chemical property of
amines is their basicity

amines, whether soluble or insoluble in water,
react quantitatively with strong acids to form
water-soluble salts
HO H
HO
HO
NH2
+ HCl
HO
(R)-N orepinep hrin e
(on ly s ligh tly solub le in w ater)
H2 O
HO
H
+
-
NH3 Cl
HO
(R)-N orep ineph rine h yd roch loride
(a w ater-soluble s alt)
Reactions of Amines

example: complete each acid-base reaction
and name the salt formed
(a) ( CH3 CH2 ) 2 NH + HCl
+ CH3 COOH
(b )
N
Reactions of Amines
example: complete each acid-base reaction
and name the salt formed
 solution:

(a) (CH3 CH2 ) 2 NH + HCl
+
-
(CH3 CH2 ) 2 NH2 Cl
D ieth ylammoniu m
chloride
-
+ CH3 COOH
(b)
N
CH3 COO
N+
H
Pyridinium acetate
Nucleophylic Substitution SN2

Displacement of a Leaving Group
LG = Weak base
 LG attached to “small” tetrahedral C


Nucleophile
Lone pair and neutral
 Negatively charged
 Other (Later)

Synthesis of Amines

1) Alkyl halides react with ammonia to
make primary amines – SN2


This can lead to multiple amination products
Example
Reduction

Non-polar Reduction


H2 plus metal catalysts (Pt, Pd, Ni, Zn, etc)
Polar Reduction

H- source
LiAlH4 or NaBH4)
 Biochem NaDH or NaDPH2

Cyanide SN2 and Reduction

2) Alkyl halides may be reacted with
cyanide and then hydrogenated to form
the primary amine exclusively.
Reactions of Amines

3) Aldehydes and ketones can condense
with primary amines and then be
hydrogenated to for secondary amines
Ketone to Amine - Biochem

Biological Application
Transamination - Biochem

Amine Transfer
Amines
End
Chapter 15