Amines

Bettelheim, Brown, Campbell and Farrell

Chapter 16

Amines – Amines contain a nitrogen atom that is bonded to

at least one carbon group– Can think of amines as derivatives of ammonia,

NH3

– aliphatic amine:aliphatic amine: all carbons bonded to nitrogen are derived from alkyl groups

– aromatic amine:aromatic amine: one or more of the groups bonded to nitrogen are aryl groups

CH3-NH2 CH3-N-CH3

H

CH3-N-CH3

CH3

Methylamine(a 1° amine)

Dimethylamine(a 2° amine)

Trimethylamine(a 3° amine)

Classification of Amines

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

– Aliphatic amine:Aliphatic amine: Only alkyl groups bonded to the nitrogen

– Aromatic amine:Aromatic amine: One or more aromatic (or aryl) groups bonded to the nitrogen

NH2 N-CH3

HCH2-N-CH3

CH3

Aniline(a 1° aromatic amine)

N-Methylaniline(a 2° aromatic amine)

Benzyldimethylamine(a 3° aliphatic amine)

Heterocyclic Amines– Heterocyclic amine:Heterocyclic amine: Amine in which the nitrogen

atom is part of a ring– Heterocyclic aliphatic amine:Heterocyclic aliphatic amine: Heterocyclic amine

in which the ring is saturated (has no C=C bonds) – Heterocyclic aromatic amine:Heterocyclic aromatic amine: Amine nitrogen is

part of an aromatic ring• Important in nature

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

NH

NH

N N

N

Pyrimidine

N

N

Imidazole

N

N

N

N

HPurine

H

Common Names (easier)

• Aliphatic amines: List the groups bonded to nitrogen in alphabetical order followed by the suffix –amineamine

• Entire name given in one word

Diethylmethylaminesec-Butylamine

NNH2

NH2

Cyclohexylamine

NH2

Propylamine

IUPAC Nomenclature

• IUPAC names – IUPAC names for aliphatic amines derived in

similar way as alcohol names– Drop the final -e of the parent alkane and

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

the parent chain

CH3CHCH3

NH2

NH2

H2N NH2

1,6-HexanediamineCyclohexanamine2-Propanamine

IUPAC Nomenclature– Uses common name aniline for C6H5NH2, the

simplest aromatic amine– Use numbers to locate substituents OR– Use the prefixes ortho (o), meta (m), and para (p)– Several aniline derivatives have common names

that are still widely used

NH2

CH3

NH2

NO2

NH2

3-Methylaniline (m-Toluidine)

Aniline 4-Nitroaniline(p-Nitroaniline)

IUPAC Nomenclature– Name unsymmetrical secondary and tertiary

amines as N-substituted primary amines– Take the largest group bonded to nitrogen as the

parent amine– Name the smaller group(s) bonded to nitrogen– Show their location on nitrogen by using the

prefix N (indicating that they are bonded to nitrogen)

NCH3

CH3

NHCH3

N,N-Dimethyl- cyclopentanamine

N-Methylaniline

Ammonium salts

N is group 5

5 valence electrons

NH3 has an unshared pair

that can form a fourth bond

but with a + charge on N

Nomenclature of Amine Salts• Amine salts

– Have four atoms or groups of atoms bonded to a nitrogen atom i.e., CH3NH3

+ – Nitrogen bears a positive charge– Ion is a quaternary ion-4 bonds to N with + charge – Positive ion is associated with an anion as a salt– Compound named as a salt of the corresponding

amine• Replace the ending -amine-amine (or aniline or pyridine etc.) by

-ammonium-ammonium (or anilinium or pyridinium etc.)• Add the name of the anion (CH3CH2)3NH

+Cl-

Triethylammonium chloride

Physical Properties

• Small amines have very nasty, sharp, penetrating odors– Trimethylamine smells like rotting fish– Names sometimes reflect their odors:

• 1,4-butanediamine is putrescine • 1,5-pentanediamine is cadaverine

Physical Properties• Amines are polar compounds

– 1° and 2° amines have N-H bonds and can form hydrogen bonds with one another

– 3° amines have no N-H bond and cannot form hydrogen bonds with one another

Physical Properties– Hydrogen bonds between amines are weaker than

hydrogen bonds between alcohols, because O is more electronegative than N

– Boiling points of amines lower than those of comparable alcohols

– Boiling points of amines higher than those of comparable alkanes

– Compare ethane, methanamine and methanol:

CH3OHCH3CH3 CH3NH2

-6.3 65.032.031.1MW (amu)

bp (°C)

30.1

-88.6

Physical Properties

– Amines form hydrogen bonds with water and are more soluble in water than are hydrocarbons of comparable molecular weight

– Most small amines are completely soluble in water– Larger amines are only moderately soluble in

water or are insoluble

Basicity of Amines• Amines are weak bases

• Aqueous solutions of amines are basic– 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)

++

-: :

::

::

Base Conjugate acid

Reactions of Amines

• Basicity is most important chemical property of amines – Amines, 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)

Basicity of Amines

• Aliphatic amines– Weak base– Basicity similar to ammonia– Stronger than aromatic amines

• Aromatic or Heterocyclic aromatic amines– Very weak base– Weaker than aliphatic amines

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

• Which form of an amine exists in blood?– pH of blood is approximately 7.40, which is slightly

basic– Thus an aliphatic amine dissolved in blood exists

predominantly in its protonated (conjugate acid) form

HO

HO

NH2

Dopamine

HO

HO

NH3+

Conjugate acid of dopamine(the major form present

in blood plasma)

Physical Properties of Quaternary Ammonium Salts

• Unlike 1o, 2o and 3o amines, quaternary nitrogens have 4 bonds and a +1 charge

• They are associated with an anion• Melting and Boiling points much higher than amines

(held together by charges)• Salts are much more soluble in water

– Many drugs are made as hydrochloride salts rather than just free amines

– Cocaine exists as “free base” or “crack” (smoked) and as HCl salt (injected)

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) +

Aminoalcohols found in Lipids

• Ethanolamine

• Choline

• Sphinogosine

Alkaloids

• Alkaloids are basic compounds obtained from plants

• Alkaloids contain nitrogen

• Alkaloids frequently have physiological effects

• Alkaloids are often poisonous

• Common names often end in “ine”

Alkaloids

Cocaine

Coniine (from hemlock)

Caffeine

Properties of Cocaine

Property Free Base

freebase/crack

HCl Salt

Melting point oC 98 195

Solubility in H2O Low high

Solubility in fats/oils

High none

Volatility High

Smoked

Low

Injected/inhaled

Related Alkaloids• Many compounds are related

– Heroin: H’s replaced by acetate– Codeine: Blue H replaced by methyl

• Codeine• Heroin • Demerol• Methadone

morphine

N

HO

O

HO

CH3

Common Drugs

• Amphetamine

• Methamphetamine