Chapter 19 – Amines

Nomenclature
o Classification of amines
 Amines are classified as 1°, 2°, or 3° based on how many R groups are
attached to the nitrogen
R
R
R
R
R
R
primary
secondary
tertiary

When there are four R groups attached to a nitrogen, it is called a
quaternary ammonium salt.
o Common names
 Say the alkyl groups attached and then say “amine”
ethyl isopropyl amine
o IUPAC names
 Find the longest carbon chain with the nitrogen attached.



Name that as the parent, remove the –e, and replace it with amine
 Heptane → 3-heptanamine
Whatever else is on the nitrogen is named as a substituent, with N as the
locant.
N-methyl-3-heptanamine
If the amine is not the high-priority group, then the nitrogen is named as
an amino substituent.
5-amino-N-methyl-2-heptanol



Structure of amines
o Trigonal pyramidal
o Chirality
 Amines can be chiral, but the lone pair flips from side to side of the
nitrogen, changing them from R to S.
 There are two times when chirality is locked.
 Quaternary ammonium salts
 Sometimes sterics can prevent the lone pair from flipping.
Physical properties
o Strongly polar
o Can hydrogen-bond if they are 1° or 2°
 Remember that the hydrogen bonding of nitrogen is not as strong as that
with oxygen, so boiling points will be lower than similarly sized alcohols.
o Small amines will be water-soluble. Larger ones will not.
Basicity of amines
o The pKb of ammonia is 4.74.
o Amines are slightly stronger bases because the alkyl groups are electron
donating groups, as we have seen in previous chapters.
 Amines have pKb’s around 3-4.
 Aniline has a pKb around 10 because the lone pair is conjugated with the
aromatic system.
-

-
Pyridine also has a pKb around 10, because the lone pair is less available
in the sp2 orbital than it would be in a sp3 orbital.
 Pyrrole is even less basic, with a pKb around 16, because its lone pair is
involved in aromaticity.
o EDGs will increase basicity, while EWGs will decrease basicity.
o My weird way of thinking about basicity:
 The lone pair of a base is like teeth that want to bite a proton.
 The bigger the teeth, the stronger the base.
 EDGs make the teeth bigger, EWGs suck the teeth back into the gums.
 When the teeth are involved with aromaticity, that’s like they’re already
chewing something, so they’re not available to bite a proton.
 This is why pyrrole has a pKb around 15.


When the teeth are in sp2 orbitals, they are held closer in to the mouth,
and aren’t as available.
 This is why pyridine has a pKb of 8.75
Amine salts and extraction
o By protonating an amine, you make it more water-soluble.
o Mr. Baker likes to ask questions about what would be left in the organic or
aqueous layer after adding either an acid or base.
 If on a test or quiz he doesn’t specifically say that you drain off the
aqueous phase, make sure to ask.
 Below, you are not draining in between.
hexane
phenol
dipropyl amine
phenol
phenol
decanoic acid
dipropyl amine
dipropyl amine
decanoic acid
diethyl ether
diethyl ether
diethyl ether
diethyl ether
HCl
NaHCO3
dipropyl
ammonium Cl
NaOH
decanoate
decanoate
phenoxide
H2O
o Here’s an example with draining in between. Remember that he can change up
when you drain, which would change the answer.
hexane
phenol
dipropyl amine
phenol
decanoic acid
decanoic acid
diethyl ether
diethyl ether
1)HCl
2) Drain
phenol
diethyl ether
1)NaHCO3
diethyl ether
NaOH
2) Drain
phenoxide
H2O

Phase transfer catalysts
o Large 4° ammonium salts are somewhat soluble in both organic and aqueous
phases. As such, they can move ionic reagents into the organic phase so that
they can react.

o Crown ethers also make good phase transfer catalysts.
Substitution of aniline
o In chapter 17 we said that NH2 was a strong ortho-, para-director, but is it?
NH2
CH3Cl
NH2
AlCl3
H3C

All the electrophilic aromatic substitution conditions were acidic, so the
nitrogen would become positive, and thus now a meta-director.
_
AlCl3
NH2
+NH
2
CH3Cl
AlCl3

You need to protect the –NH2, often by acylating it.
NH2
H3O+
H2SO4
HO3S
HO3S

That said, when aniline is not protonated, it is a strong ortho-, paradirecting activator.
 In fact, it’s so active that you can halogenate without the metal
Lewis-acid catalyst.
NH2

Br2
Alkylation of amines by alkyl halides
o Just SN2 followed by deprotonation.
NH2
NH2

o The problem with this reaction is that it’s difficult to control how many alkyl
groups add.
 This works if you want a 4° ammonium salt.
 This also works if you add excess ammonia, so that you get one addition.
Acylation of amines by acid chlorides
o This is a nucleophilic substitution at the carbonyl
NH3
o The acid chloride is more reactive than ketones and aldehydes, and amines are
not nucleophilic enough to add to the amide formed in the substitution.
o Acylating aniline is a way to maintain the ortho-, para-directingness of the –NH2
and the acyl group is easily removed by acid hydrolysis.
H3O+
HNO3
H2SO4
NO2

Formation of sulfonamides
o Just like Acylation, but with sulfonyl chlorides
 Is it me, or did all the colors make this one exciting?
NO2

Hofmann Elimination
o An E2-like reaction where 4° nitrogen is the leaving group, and you get the lesssubstituted alkene.
 First, excess of an alkyl halide (usually CH3X) is added to give quaternary
ammonium salt.
excess CH3I
NH2

Then, a strong base abstracts a proton to give a carbanion intermediate.
_
-OH


This carbanion intermediate explains why you get the anti-Zaitsev
product with Hoffman elimination.
Elimination occurs to expel the amine, giving an alkene product.
_

o Sometimes Ag2O (aq) is the base used.
 It generates O2-, to a small extent.
 This is the conjugate base of hydroxide. Yikes!
 But remember that because it’s aqueous, it just deprotonates the water,
forming hydroxide.
 You cannot have a base stronger than hydroxide in an aqueous
environment.
o For those of you going on to take inorganic, you’ll see that
this is called “solvent leveling.”
Diazonium salts
o Formation
 Reaction of HNO2 (nitrous acid) with 1° alkyl amines
 Often formed in situ with NaNO2 with HCl
HNO2

Reaction of HNO2 with aryl amines
HNO2

The last step of the N2 gas falling off doesn’t happen because the
aryl cation would be unstable.
o Reactions of aryl diazonium salts
 You don’t need to know any mechanisms here.
HBF4
CuCl
CuBr
KI
CN
CuCN
H2O
heat
H3PO2
or ethanol
o Now we can do even more synthesis!
?

Step 1:
CH3Cl
AlCl3

Step 2:
HNO3
H2SO4
NO2

Step 3:
Sn/HCL
NH2
NO2

Step 4:
AlCl3
NH2

Step 5:
AlCl3

Step 6:
H3O+
NH2

Step 7:
HNO2
N2+
NH2

Step 8:
ethanol
N2+


Synthesis of amines by acylation-reduction
o Just what it sounds like
o Acylate
o LiAlH4 completely chops off the oxygen of an amide instead of reducing the
carbonyl to an alcohol
Gabriel synthesis – always makes 1° amines
o Phthalimide is deprotonated by a strong base

The pKa is 8.3.
-
OH
o The anion is a good nucleophile (but weak base) which performs an S N2 on a
suitable alkyl halide or tosylate.
o Hydrolysis gives you the amine
H3O+

Reduction of azides and nitriles
o Once an azide has been used as a nucleophile in an SN2 reaction, it can be
reduced to the amine by either LiAlH4 or catalytic hydrogenation.
N3
LiAlH4
N3-
Nitriles are also reduced to the amine by the same conditions.
H2
CN
Pt

Be sure not to lose a carbon here.


Reduction of nitro groups to NH2
o LiAlH4
o Catalytic hydrogenation
o Fe, Zn, or Sn in acid
Removing the oxygen from amides to form amines
LiAlH4

Hofman rearrangement
o 1° amide + bromine or chlorine in base → amine where the whole carbonyl is
gone.
Br2
-
OH
o You are not responsible for the mechanism.