Nomenclature for amines
t Common names are widely used, named as alkylamines
t Systematic (IUPAC) nomenclature replaces the - e of the
Chapter 20
corresponding parent alkane with -amine
Amines
t Simple secondary and tertiary amines are named by designating
the organic groups separately in front of the word amine
t In systematic nomenclature, the smaller groups on the amine
nitrogen are designated as substituents and given the locant N
Aryl amines
t In IUPAC nomenclature the substitutent -NH2 is called the amino group
N H2
C HO
Cl
N O2
3-chloro-4-nitroaniline
N (C H 3)2
p-dimethylaminobenzaldehyde
1
Heterocyclic Amines
t The important heterocyclic amines have common names
t In IUPAC nomenclature the prefixes aza-, diaza- and triaza-
are used to indicate that nitrogen has replaced carbon in
the corresponding hydrocarbon
H The nitrogen is assigned position 1 and the ring is numbered to give the lowest
overall set of locants to the heteroatoms
DNA base pairs are a purine with a pyrimidine
Physical Properties and Structure of Amines
l Primary and secondary amines can form hydrogen bonds to
each other and water
l Tertiary amines cannot hydrogen bond to each other but can
form hydrogen bonds to hydrogen bond donors such as water
l Tertiary amines have lower boiling points than primary or
secondary amines of comparable molecular weights
l Low molecular weight amines tend to be water soluble whether
they are primary, secondary or tertiary
l Amines smell fishy (or worse)
2
Structure of Amines = sp3 hybridized
Organophosphorus analogs can be resolved
t The unshared electron pair around nitrogen - along with the
..
three groups results in a tetrahedral geometry
t The shape of the amine itself is trigonal pyramidal
P
CH3
Chiral: racemizes at 200o C
t Quaternary ammonium salts can be resolved into enantiomers
l Nitrogen inversion not possible with 4 substituents
t It is usually impossible to resolve amine enantiomers that are
chiral at nitrogen because they interconvert rapidly
l Nitrogen inversion of the unshared electron pair
Basicity of Amines
t Amines are weak bases
t Relative basicitydefined by pK a of its conjugate acid
t In the gas phase, basicityin the family of methylamines increases with
increasing methyl substitution
l More alkyl substitution = more stabilization of the alkylaminium ion
l The more basic the amine, the higher the pKa of its conjugate acid
t In aqueous solution, trimethylamine is less basic than dimethyl- or
t Primary alkyl amines are more basic than ammonia
methylamine
l An alkyl group helps to stabilize the alkylaminium ion
t Solvation of the ion becomes important
t The trimethylaminium ion is solvated less well than the dimethylaminium
ion, which has two hydrogen atoms for hydrogen bonding
3
t Arylamines are weaker bases than the corresponding
t Greater resonance stabilization of aniline than its anilinium
ion means a larger ∆ Ho for protonation, as compared with
∆ Ho for protonation of an amine that is not aromatic
nonaromatic cyclohexylamines
t The unshared electron pair on nitrogen of an arylamine is
delocalized to the ortho and para positions of the ring
l Lone pair is less available for protonation, i.e., it is less basic
t Less resonance stablization available to the anilinium ion
Amines versus Amides
Basicity of Heterocyclic Amines
t Nonaromatic heterocyclic amines have comparable basicity
to acyclic counterparts
t Aromatic heterocyclic amines (in aqueous solution) are
much weaker bases than nonaromatic amines
t
Amides are much less basic than amines
1.
Amide is stabilized by resonance and protonated amide is not
2.
The nitrogen lone pair is delocalized to the carbonyl oxygen
è The pKa of a protonated amide is typically about zero
l
l
Amides are actually protonated at the oxygen atom
Allows resonance stabilization of the positive charge
4
Aminium Salts and Quaternary Ammonium Salts
t Protonation of amines with acids leads to aminium salts
l Aminium salts are formed from 1o, 2 o or 3o amines
l An aminium ion bears at least one hydrogen
t Quaternary ammonium halides are not basic because they
do not have an unshared electron pair on nitrogen and are
not acidic because they have no H to donate
t Quaternary ammonium hydroxides are very basic because
they contain the very strong base hydroxide
t Quaternary ammonium salts have four groups on the nitrogen
l The nitrogen atom is positively charged but has no hydrogen atom
These ions can be soluble in water because they are charged
They can also be soluble in organic solvents if alkyl groups are larger
Phase Transfer Catalysis (Solomons , p.504)
t General problem: anionic nucleophiles tend to be soluble in
Purple benzene??
water, but not organic solvents
Herriott and Picker, Journal of the American Chemical Society, 97, 2345 (1975)
Herriott, Journal of Chemical Education, 54, 229 (1977)
Q+
= (Bu)4
N+
5
Solubility of Amines in Aqueous Acid
t Most aminium salts are water soluble
l Amines in soluble in water usually dissolve in dilute aqueous acid
Amines as Resolving Agents
t A chiral amines can be used to resolve a racemic mixture of
carboxylic acids by formation of diastereomeric salts
l Diastereomers = different physical properties (solubility, m.p .)
l Acidification of the separated diastereomeric salts gives the resolved
carboxylic acids
t Used as a chemical test to distinguish amines
t Extraction : water-insoluble amines can be separated from other
water-insoluble organic compounds
l The amine is extracted into aqueous acid
l The amine is recovered by making the solution basic and extracting
the amine into an organic solvent
t Amides are not basic and are not soluble in aqueous acids
Preparation of Amines
t Nucleophilic Substitution Reactions
l Alkylation of Ammonia with an alkyl halide
è Initial aminium salt is treated with base to give the primary amine
è The method is limited because multiple alkylations usually occur
l Using an excess of ammonia helps to minimize multiple alkylations
6
Amines via Nucleophilic Substitution Reactions
Amines via Nucleophilic Substitution Reactions – Gabriel Synthesis
t Primary amines can also be made cleanly by the Gabriel Synthesis
t Alkylation of Azide Ion followed by Reduction
l A primary amine is prepared more efficiently by reaction of azide anion with
an alkyl halide and subsequent reduction of the alkylazide to the amine
t First step in the Gabriel synthesis is alkylation of potassium phthalimide
t Reaction of the N-alkylphthalimide with hydrazine in boiling ethanol gives
the primary amine
Amines through Reductive Amination
t Preparation of Aromatic Amines by Reduction of Nitro Compounds
t
Aldehydes and ketones react with ammonia, primary or secondary amines to yield
imines or iminium ions
l
These are then be reduced to alkylated amines
Useful way to introduce an amino group on a benzene ring:
1.
Nitration
2.
Reduction
[H ]
7
t The reduction can be accomplished using catalytic hydrogenation
or a hydride reducing reagent
l NaBH3 CN and LiBH 3 CN are especially effective in reductive
aminations (milder; added sequentially, but one pot)
Amines through Reduction of Nitriles, Oximes, and Amides
t Reduction of nitriles or oximes yield primary amines
t Reduction of amides can yield primary, secondary or tertiary
amines
t Reduction can be accomplished by dissolving metal reduction,
catalytic hydrogenation, or LiAlH4
t Reductive amination can be used for monoalkylation of an amine
l Acylation the amine with an acid chloride
l Reduction of the resulting amide
8
Primary Amines by the Hofmann and Curtius Rearrangements
The N-bromo amide losses a second proton and then a bromide ion, and
rearranges to an isocyanate
t An unsubstituted amide can be converted with bromine in
base to a primary amine by formal loss of the amide carbonyl
Isocyanates readily hydrolyzed to a carbamate and lose CO2 to
yield the primary amine
t The initial steps of the mechanism result in N-bromination of
the amide
t The Curtius rearrangement occurs similarly through the
Converts a carboxylic acid to an amine
with one fewer carbons
intermediacy of an acyl azide
l The acyl azide is obtained from an acid chloride with sodium azide
l Rearrangement of the acyl azide occurs with loss of N2 , a very
stable leaving group
l In the last step, the isocyanate is hydrolyzed by adding water
CO 2H
NH 2
CO2NH2
Br 2
NaOH
9