Structure and Classification of Amines

• Classification• 1°, 2°, or , 3° amines: Amines in which 1, 2,

or 3 hydrogens of NH3 are replaced by alkyl or aryl groups.

Amines

• Amines are further divided into aliphatic, aromatic, and heterocyclic amines.• Aliphatic amine: An amine in which nitrogen is

bonded only to alkyl groups.• Aromatic amine: An amine in which nitrogen is

bonded to one or more aryl groups.

• Heterocyclic amine: An amine in which nitrogen is one of the atoms of a ring.

• An acyclic sp3 nitrogen atom with three different groups and a lone pair of electrons is asymmetric.

• Even so, an amine with an asymmetric nitrogen atom is rarely a stereocenter, leading to enantiomers.

sp3 Nitrogens as Stereocenters

• Acyclic amines interconvert into their own mirror images billions of times per second in a process called pyramidal inversion.

• Thus acyclic amines are not chiral.

• Cyclic amines and quaternary ammonium salts can be chiral since they are unable to undergo pyramidal inversion.

• When the Cahn-Ingold-Prelog rules are used to priorize groups to determine stereoisomers, the electron lone-pair is last.

Nomenclature of Amines• Aliphatic amines: replace the suffix -e of the

parent alkane by -amine.

• To name a secondary or tertiary amine, the alkyl branches need to be named and “numbered” using “N” to designate the branching.

N-ethyl-2-propanamine

H3C

CH

CH3

HN

H2C

CH3

CH2

C

CH2

N

CH3

H3C CH3

H2C

H3C

CH2

HC

C

CH3

NH

H3C

H3C

CH3

3,N-dimethyl-2-butanamine

N,N-dimethyl-3-ethyl-3-pentanamine

• For aromatic amines, the IUPAC system retains the common name aniline.

• Among the functional groups, -NH2 has one of the lowest priorities.

• Thus –NH2 is often referred to as an amino group and is given the amino- prefix.

• Common names for most aliphatic amines are derived by listing the alkyl groups bonded to nitrogen in one word ending with the suffix -amine.

• Alkyl groups are listed alphabetically.

• When four groups are bonded to the nitrogen atom, we name the compound as a salt (with cation and anion) of the corresponding amine.

• Use the suffix –ium to name tetraalkyl amine cation.• i.e., ammonium, pyridinium, anilinium, etc…

• Include the counterion (chloride, bromide, etc…) in the name.

Physical Properties of Amines• Amines are polar compounds, and both 1° and 2°

amines form intermolecular hydrogen bonds.• N-H- - - -N hydrogen bonds are weaker than O-H- - - -O

hydrogen bonds because the difference in electronegativity between N and H (3.0 - 2.1 = 0.9) is less than that between O and H (3.5 - 2.1 = 1.4).

• Amines generally smell bad.• Trimethylamine is responsible for the smell of rotting

fish.

Applications of Amines

• Amines are used as precursors to make dyes.

• Mauveine• The first synthetic

dye invented by William Perkin when he was 18.

• Acid Orange 7• It is used in hair

coloring formulations.

• Aniline Yellow• It is used in inkjet

printer inks.

nicotine

• Alkaloids are naturally occurring amines many with medicinal properties. Many are 3o heterocyclic amines.

• Many important neurotransmitters are amines.

Basicity of Amines

• All amines are weak bases; thus, aqueous solutions of amines are basic.

• The reaction of the weak base with water is quantified with the base-dissociation constant, Kb.

3 3

b3 2

CH NH OHK

CH NH

• It is also common to discuss the basicity of amines by reference to the acid-dissociation constant of its corresponding conjugate acid.

• For any conjugate acid-base pair, the pKa and pKb are deeply connected to each other.

• Using values of pKa, we can predict the position of equilibrium in acid-base reactions.

• Acetic acid is the stronger acid and, therefore, the position of this equilibrium lies to the right.

• Aliphatic amines have about the same base strength, pKb 3.0 – 4.0 and are slightly stronger bases than NH3.

• Aromatic amines are considerably weaker bases than aliphatic amines.

• Aromatic amines are weaker bases than aliphatic amines because the resonance stabilization of the base is lost on protonation.

• That is, the conjugate acid of an aromatic amine is a stronger acid than the conjugate acid of the aliphatic amine.

• Electron-withdrawing groups, such as halogen atoms, the nitro group, and the carbonyl group, decrease the basicity of aromatic amines by decreasing the availability of the electron pair on nitrogen.

• Guanidine (pKb = 0.4) is the strongest base among neutral organic compounds.

• Its basicity is due to the resonance delocalization of the positive charge over the three nitrogen atoms.

Reactions of Amines (Summary)

• Formation of ammonium salts with strong acids.• Reduction of nitro group to form amino group.

(Formation of primary amine)• Reagent in nucleophilic substitution.• Formation of benzenediazonium salt from aniline

with HNO2.

• Reaction of benzenediazonium salt with various reagents to make substituted benzenes.

Formation of Ammonium Salts

• All amines, whether soluble or insoluble in water, react quantitatively with strong acids to form water-soluble salts.• Many drugs that are water-insoluble are made soluble

through the reaction with hydrochloric acid.

Norepinephrine is used to treat hypotension (low blood pressure).

Synthesis of 1° Amines

• Most 1° aromatic amines are synthesized by nitration of an aromatic ring followed by catalytic reduction of the nitro group to an amino group.

Amines in Nucleophilic Substitution

• Reaction of an amine with an alkyl halide can be used to form a new covalent bond.

• Step 1: Reaction of a nucleophile with an electrophile to form a new covalent bond.

• Step 2: Take a proton away. Unreacted base deprotonates the substrate, converting the amine salt to a free amine.

• In Step 2, a new 2° amine was produced.• The new amine can then also act as a

nucleophile.• Thus the final reaction mixture will consist of

varying ratios of RNH2, R2NH, R3N, and R4N+Cl–.

• These ratios are difficult to control and, therefore, amines are avoided as nucleophiles in nucleophilic substitutions reactions.

Formation of the Benzenediazonium Salt

NH2 NaNO2 HClH2O

N N Cl- H2O0°C

++

Benzenediazoniumchloride

+ +

Aniline(a 1° aromatic

amine)

Sodiumnitrite

• Aniline reacts with sodium nitrite and hydrochloric acid to produce an important intermediate substrate, benzenediazonium salt.

• Once formed, the benzenediazonium salt can further react with a large variety of reagents to yield a substituted benzene compound.

N N Cl- H2O OH N2

Benzenediazoniumchloride

++

+

Phenol

Reactions of the Benzenediazonium Salt

• Benzenediazonium salt reacts with water and an acid catalyst when heated to form phenol.

• Benzenediazonium salt reacts with tetrafluoroboric acid when heated to form fluorobenzene.

N NH2O

H+, heat

OH

N NHBF4, heat

F

Reactions of the Benzenediazonium Salt

• Benzenediazonium salt reacts with potassium iodide to form iodobenzene.

• Benzenediazonium salt reacts with copper(I) chloride, copper(I) bromide or copper(I) cyanide to form chloro-, bromo-, or cyanobenzene.

• Chemists sometimes think of cyanide as an honorary halogen ion.

• Recall that R – C ≡ N is called a nitrile.

N NCuCl, CuBr, CuCN

X

N NKI

I

Reactions of the Benzenediazonium Salt

• Benzenediazonium salt reacts with hypophosphorous acid, H3PO2, to replace the diazonium group with hydrogen to form benzene.

N NH3PO2

H

O

P

OH

H

H

Reactions of the Benzenediazonium Salt