The Physical and Chemical

Properties, and Reactions of

Amines

Chem-261

IntroductionOq.

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Classes of Amines

OPrimary (1): one C-N bond, 2 N-H bonds.

OSecondary (2): two C-N bonds, 1 N-H bond.

OTertiary (3): three C-N bonds, no N-H bond.

OQuaternary (4): four C-N bonds, nitrogen has a + formal charge. 04/19/23Dr Seemal Jelani 3

Classify:

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N

H

CH3 C

CH3

CH3

NH2

NCH3

CH3

CH3CH2 N

CH3

CH2CH3+

Br_

=>

Common NamesName the alkyl or aryl groups bonded to

nitrogen, then add suffix -amine.

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(CH3CH2)2NCH3

NHCH3

NH

diethylmethylamine

cyclopentylmethylamine

Diphenylamine =>

Amine as SubstituentOOn a molecule with a higher priority

functional group the amine is named as a substituent.

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NH2CH2CH2CH2COOH

NHCH3

OH

-aminobutyric acid or4-aminobutanoic acid

2-methylaminophenol =>

IUPAC NamesO Name is based on longest carbon chain.O -e of alkane is replaced with -amine.O Substituents on nitrogen have N- prefix.

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NH2CH2CH2CHCH2CH3

BrCH3CH2CHCH2CH2CH3

N(CH3)2

3-bromo-1-pentanamine N,N-dimethyl-3-hexanamine

=>

Aromatic AminesAmino group is bonded to a benzene ring. Parent compound is called aniline.

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NH2

aniline

NCH3

CH3

N,N-dimethylaniline

=>

NH2

H3C

4-methylanilineor p-toluidine

Heterocyclic AminesThe nitrogen is assigned the

number 1.

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N

H

N

H

N

HN N CH3

aziridinePyrrole

PyrrolidinePyridine

2-methylpyridine

Structure of AminesNitrogen is sp3 hybridized with a lone pair of

electrons in an sp3 orbital.

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Chirality of AminesNitrogen may have 3 different groups and a lone pair, but enantiomers cannot be isolated due to inversion around N.

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Boiling PointsO N-H less polar than O-H.O Weaker hydrogen bonding.O Tertiary amines cannot hydrogen bond.

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Solubility and Odor

OSmall amines (<6 C) soluble in water.OAll amines accept hydrogen bonds from

water and alcohol.OBranching increases solubility.OMost amines smell like rotting fish.

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NH2CH2CH2CH2CH2CH2NH2

1,5-pentanediamine or cadaverine=>

Basicity of AminesOLone pair of electrons on nitrogen can

accept a proton from an acidOAqueous solutions are basic to litmus.OAmmonia pKb = 4.74

OAlkyl amines are usually stronger bases than ammonia

O Increasing the number of alkyl groups decreases solvation of ion, so 2 and 3 amines are similar to 1 amines in basicity. 04/19/23Dr Seemal Jelani 14

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OAlkyl Amine is more basic than ammonia because of the +I effect of the Alkyl group present

O It donates its electron cloud to the nitrogen group therefore nitrogen has a greater tendency to donate it lone pair of electrons

O This makes it more basic than ammonia where such a positive inductive effect is absent.

Why is alkyl amine more basic than ammonia?

Resonance EffectsAny delocalization of the electron pair weakens

the base.

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Amine Salts

OIonic solids with high melting points OSoluble in water ONo fishy odor

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Reactions of AminesChem-261

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Reaction of AminesO Amines are BASES!

O React with acids and accept a proton (H+) to Form alkyl ammonium salts

methylamine

NH2H3C + HCl

methylammonium chlorideNH3

+ Cl-H3C

diethylamine

NH CH2 CH3CH2CH3 + HCl

diethylammonium chloride

NH2CH2 CH3CH2CH3+

Cl-

N,N-dimethylaniline

N CH3CH3

+ HCl

NH CH3CH3

N,N-dimethylanilinium chloride

+Cl-

Reaction of AminesO Amines are BASES!

?

Electrophilic Substitution of Aniline

O-NH2 is strong activator, o-,p-directing.

OMay trisubstituted with excess reagent.OH+ changes -NH2 to -NH3

+, a meta-directing deactivator.

OAttempt to nitrate aniline may explode.

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Aniline Substitution

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Electrophilic Substitution of Pyridine

OStrongly deactivated by electronegative N.OSubstitutes in the 3-position.OElectrons on N react with electrophile.

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N

fuming H2SO4

HgSO4, 230oC

N

SO3H

=>

Alkylation of Alkylation of AmmoniaAmmonia

Desired reaction is:Desired reaction is:

2 NH2 NH33 ++ R—XR—X R—NHR—NH22++ NHNH44XX

Alkylation of Alkylation of AmmoniaAmmonia

Desired reaction is:Desired reaction is:

2 NH2 NH33 ++ R—XR—X R—NHR—NH22++ NHNH44XX

via:via:

HH33NN ••••••••

••••RR XX••••

HH33NN RR++ ••••

••••XX••••

••••––

++ ++

then:then:

HH33NN •••• ++

HH NN

HH

HH

RR++

HH33NN HH++

++ NN

HH

HH

RR••••

Alkylation of Alkylation of AmmoniaAmmonia

But the method doesn't work well in practice.But the method doesn't work well in practice.Usually gives a mixture of primary, secondary,Usually gives a mixture of primary, secondary,and tertiary amines, plus the quaternary salt. and tertiary amines, plus the quaternary salt.

NNHH33

RRXXRRNNHH22

RRXXRR22NNHH

RRXX

RR33NNRRXX

RR44NN++

XX––

ExampleExample

CHCH33(CH(CH22))66CHCH22BrBrNHNH33

CHCH33(CH(CH22))66CHCH22NHNH22

(45%)(45%)

++

CHCH33(CH(CH22))66CHCH22NHNHCHCH22(CH(CH22))66CHCH33

(43%)(43%)

OAs octylamine is formed, it competes with ammonia for the remaining 1-bromooctane. Reaction of octylamine with 1-bromooctane gives N,N-dioctylamine.

Ogives primary amines without formation ofsecondary, etc. amines as byproducts

Ouses an SN2 reaction on an alkyl halide to formthe C—N bond

Othe nitrogen-containing nucleophileis N- potassiophthalimide

Gabriel SynthesisGabriel Synthesis

Othe pKa of phthalimide is 8.3

ON- potassiophthalimide is easily prepared by

the reaction of phthalimide with KOH

N-PotassiophthalimideN-Potassiophthalimide OO

OO

NN•••• ••••––

KK++

OO

OO

NNHH••••KOHKOH

N-Potassiophthalimide as a N-Potassiophthalimide as a nucleophilenucleophile OO

OO

NN•••• ••••–– ••••

••••RR XX••••

++

OO

OO

NN RR••••

+ + ••••

••••XX••••

••••––

SSNN22

Cleavage of Alkylated Cleavage of Alkylated PhthalimidePhthalimide

OO

OO

NN RR•••• ++ HH22OO

HH22NN RR++

COCO22HH

COCO22HH

acid or baseacid or base

Oimide hydrolysis is imide hydrolysis is nucleophilic acyl nucleophilic acyl substitutionsubstitution

Formation of Sulfonamides

OPrimary or secondary amines react with sulfonyl chloride.

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R NH2 S

O

O

R' Cl S

O

O

R' NH R

H

+Cl

_base S

O

O

R' NH R

• Sulfa drugs are sulfonamides that are antibacterial agents.

NH2

S OO

NH2=>

Oxidation of AminesOAmines are easily oxidized, even in air.OCommon oxidizing agents: H2O2 , MCPBA.OMeta chloroperoxybenzoic acidO2 Amines oxidize to hydroxylamine (-NOH)O3 Amines oxidize to amine oxide (-N+-O-)

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Reduction

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CH3 C

O

ClNH3

CH3 C

O

NH2

LiAlH4

H2O

1)

2)CH3 CH2 NH2

primary amine

LiAlH4

H2O

1)

2)C

O

ClHN(CH3)2

C

O

N(CH3)2CH2 N(CH3)2

tertiary amine =>

Reduction of Nitro Compounds (1)

O -NO2 is reduced to -NH2 by catalytic hydrogenation, or active metal with acid.

O Commonly used to synthesize anilines.

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CH3

NO2

Zn, HCl

CH3CH2OH

CH3

NH2

=>

Hofmann Rearrangement of

Amides (1)In the presence of a strong base, primary amides react with chlorine or bromine to form amines with one less C.

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C

O

NH2H2O

Br2, OH_

NH2

=>