Chapter 15

AminesAmines

Structure & Classification

Amines are classified as 1°, 2°, or 3° depending on the number of carbon groups bonded to nitrogen

CH3-NH2 CH3-N-CH3

H

CH3-N-CH3

CH3

Methylamine(a 1° amine)

Dimethylamine(a 2° amine)

Trimethylamine(a 3° amine)

NH2 N-CH3

HCH2-N-CH3

CH3

Aniline(a 1° aromatic amine)

N-Methylaniline(a 2° aromatic amine)

Benzyldimethylamine(a 3° aliphatic amine)

Structure & Classification

heterocyclic amine:heterocyclic amine: an amine in which the nitrogen atom is part of a ring

PiperidinePyrrolidine Pyridine(heterocyclic aliphatic amines) (heterocyclic aromatic amines)

NH

NH

N N

N

Pyrimidine

N

N

Imidazole

N

N

N

N

HPurine

H

Nomenclature

IUPAC namesSimilar to alcoholsdrop the final -e of the parent alkane and

replace it by -amine-amineuse a number to locate the amino group on

the parent chain

CH3CHCH3

NH2

NH2

H2NNH2

1,6-HexanediamineCyclohexanamine2-Propanamine

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 usedNH2

CH3

NH2

NO2

NH2

3-Methylaniline (m-Toluidine)

Aniline 4-Nitroaniline(p-Nitroaniline)

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

NCH3

CH3

NHCH3

N,N-Dimethyl- cyclopentanamine

N-Methylaniline

Nomenclature

Common names for most aliphatic amines, list the groups

bonded to nitrogen in alphabetical order in one word ending in the suffix -amineamine

Diethylmethylaminesec-Butylamine

NNH2

NH2

Cyclohexylamine

NH2

Propylamine

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-amine (or aniline or

pyridine or the like) by -ammonium-ammonium (or anilinium or pyridinium or the like) and add the name of the anion

(CH3CH2)3NH+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 1,5-pentanediamine (cadaverine)

Physical Properties

Amines are polar compoundsboth 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

CH3OHCH3CH3 CH3NH2

-6.3 65.032.031.1MW (amu)

bp (°C)

30.1

-88.6

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

CH3-NH

HH-O-H CH3-N-H

H

HO-H

Methylammoniumhydroxide

Methylamine(a base)

++

-: :

::

::

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[CH3NH3

+][OH

- ]

[CH3NH2]Kb = = 4.37 x 10-4

pKb = - log 4.37 x 10-4 = 3.360

Basicity of Amines

aliphatic amines SS bases than NH3

aromatic amines are weaker bases

C6H5NH2

CH3CH2NH2Aliphatic

Ammonia

Aromatic

3.0 - 4.0

4.74

8.5 - 9.5

Class pKb Example Name

Ethanamine

Aniline

Stronger base

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

HO

NH2

Dopamine

HO

HO

NH3+

Conjugate acid of dopamine(the major form present

in blood plasma)

Reactions of Amines

The most important chemical property of amines is their basicityamines, whether soluble or insoluble in water,

react quantitatively with strong acids to form water-soluble salts

HO H

NH2HO

HOHCl

H2O

HO

HO NH3+Cl

-HHO

(R)-Norepinephrine hydrochloride(a water-soluble salt)

+

(R)-Norepinephrine(only slightly soluble in water)

Reactions of Amines

example:example: complete each acid-base reaction and name the salt formed

(CH3CH2)2NH HCl

NCH3COOH

+(a)

(b) +

Reactions of Amines

example:example: complete each acid-base reaction and name the salt formed

solution:solution:

(CH3CH2)2NH HCl

NCH3COOH

NH

(CH3CH2)2NH2+Cl-

CH3COO-

Diethylammoniumchloride

+Pyridinium acetate

+(a)

(b) +

Nucleophylic Substitution SN2

Displacement of a Leaving GroupLG = Weak baseLG attached to “small” tetrahedral C

NucleophileLone pair and neutralNegatively chargedOther (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 ReductionH2 plus metal catalysts (Pt, Pd, Ni, Zn, etc)

Polar ReductionH- 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

End End Chapter 15Chapter 15

Amines