Transcript AMINA - Biologi 2010 Universitas Airlangga

AMINA



Senyawa yang mengandung gugus NH2
Strukrur : RNH2
Jenis
: Amina primer (1o)
Amina sekunder (2o)
Amina tersier (3o)
R
N
H
H
amina 1
R
N
R'
amina 2
H
R
N
R''
R'
amina 3
Tata Nama

Amina alifatik sederhana dinamakan
dengan gugus alkil yang terikat pada
atom N dan diberi akhiran amin.
H
CH3
CH3
CH
CH2
isobutilamin
1
CH3
CH3
NH2
CH2
N
CH
CH2 CH3
trietilamin
3
CH2
N
CH
CH3
etilisopropilamin
2
CH3
CH3
Sistem IUPAC, gugus NH2 dinamakan
gugus amino
O
NH2
CH2
CH2
OH
2-amino etanol
NH2
CH2
CH2
C
asam- 3-amino propanoat
COOH
NH2
asam -p-aminobenzoat
asam -4-aminobenzoat
OH
Tata Nama :

Jika atom N mengikat 4 gugus
hidrokarbon akan bermuatan positif
dam dikenal sebagai ion ammonium
kuartener
CH3
CH3
+
N CH3
Cl
-
CH3
tetrametil ammonium klorida
CH3
CH3
+
N CH3
-
OH
CH3
tetrametil ammonium hidroksida
Tata Nama :

Senyawa yang mengandung gugus –
NH2 pada cincin benzena dinamakan
sebagai derivat anilin.
NH2
NH2
NH2
CH3
anilin
O CH3
p-metoksianilin
(p-anisidin)
o-metilanilin
(o-toluidin)
Tata Nama :

Senyawa siklis dimana satu atom C atau
lebih diganti dengan atom nitrogen, diberi
nama khusus sebagai heterosiklik amin.
N
N
N
H
piperidin
2
N
H
pirrolidin
2
N
N
N
piridin
pirimidin
CH3
N-metilpirrolidin
3
N
H
pirrol
N
H
imidasol
Beberapa Contoh Senyawa
Heterosiklis Amin



Alkaloid : senyawa yang mengandung nitrogen
yang bersifat basa dari tumbuhan dan hewan.
Senyawa ini mempunyai struktur yang rumit dan
sifat farmakologis (faali) yang nyata
Nikotin dari tembakau
Porfirin : senyawa heterosiklis yang mengandung 4
cicin pirol yang saling berikatan. Porfirin
membentuk kompleks dengan ion logam. Apabila
membentuk kompleks dengan Fe membentuk besiporfirin yang menyebabkan warna darah merah
pada darah arteri  Hemoglobin
Contoh Senyawa Heterosiklis

Klorofil berwarna hijau adalah kompleks Mg
dengan porfirin yang termodifikasi.
HC
HC
CH2
CH3
H3C
N
C CH3
H2
N
N
CH2
Mg
Fe
N
CH3
H3C
H
C
N
CH2
N
N
CH3
H3C
N
CH3
H3C
HOOCH2CH2C
HOOCH2CH2C
CH2CH2COOH
O
H3COOC
Hemoglobin
Klorofil-a
Sifat-Sifat Fisik Amina :

Amina 1 dan 2 bersifat polar karena
mampu membentuk ikatan hydrogen



intermolekuler.

N


H
N
Larut dalam air karena mampu
membentuk ikatan hidrogen dengan
air.




Ikatan hidrogen

<
N
H
O
H
Measures of Basicity





The basicity of amines may be measured by:
1) Kb
2) pKb
3) Ka of conjugate acid
4) pKa of conjugate acid
Basicity Constant (Kb) and pKb

Kb is the equilibrium constant for the
reaction:
R3N •• + H
+
R3N
••
OH
••
Kb =
[R3NH+][HO–]
[R3N]
and pKb = - log Kb
– ••
H + ••OH
••
Ka and pKa of Conjugate Acid

Ka is the equilibrium constant for the
dissociation of the conjugate acid of the amine:
+
R3N
R3N •• + H+
H
Ka =
[R3N][H+]
[R3NH+]
and pKa = - log Ka
Relationships between acidity and basicity
constants
Ka Kb = 10-14
pKa + pKb = 14
The beverage reportedly produced using the
extract of leaves of Erythroxylon coca:
The compound: cocaine, it is an organic base:
Merck Index, #2450, 11th ed.: Caution: May be habit
forming….
Acid -Base Chemistry
(Physical Properties)
m.p. 98 oC
 b.p. (very volatile
> 90 oC)
Solubility:
 Water: 1.67 x 10-3

CH3 ..
N
CO2CH3
O2C
"Crack" Cocaine
What structural feature makes
cocaine a base? What simple
compound can you relate it to?
g/mL


CHCl3: 1.43 g/mL
Ether: 0.29 g/mL
“Regular” Cocaine
Conjugate Acid of Cocaine
(Physical Properties)
H
Cl
+
CH3
N
CO2 CH3
O2 C
Cocaine Hydrochloride
What accounts for the differences
in solubilities of the base and
conjugate acid?

m.p. >195 oC
Solubility:

Water: 2.5 g/mL

CHCl3: 0.08 g/mL

Ether: insoluble
Acid -Base Reactions
CH3 ..
N
CH3
CO2CH3
O2C
+
H
Cl
+
N
H Cl
-
CO2 CH3
O2 C
Cocaine Hydrochloride
Acid Base Reactions
CH3
+
N
H Cl
CH3 ..
N
-
CO2CH3
+
O2C
OH -
CO2CH3
O2C
"Crack" Cocaine
Basicity of Amines in Aqueous Solution
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
CH3CH2NH2
CH3CH2NH3+
10.8
CH3CH2NH3+ is a weaker acid than NH4+;
therefore, CH3CH2NH2 is a stronger base
than NH3.
Effect of Structure on Basicity
1.
Alkylamines are slightly stronger bases tha
ammonia.
2.
Alkylamines differ very little in basicity.
Basicity of Amines in Aqueous Solution
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
CH3CH2NH2
CH3CH2NH3+
10.8
(CH3CH2)2NH
(CH3CH2)2NH2+
11.1
(CH3CH2)3N
(CH3CH2)3NH+
10.8
Notice that the difference separating a primary,
secondary, and tertiary amine is only 0.3 pK units.
Effect of Structure on Basicity
1.
Alkylamines are slightly stronger bases tha
ammonia.
2.
3.
Alkylamines differ very little in basicity.
Arylamines are much weaker bases than
ammonia.
Basicity of Amines in Aqueous Solution
Amine
Conj. Acid
pKa
NH3
NH4+
9.3
CH3CH2NH2
CH3CH2NH3+
10.8
(CH3CH2)2NH
(CH3CH2)2NH2+
11.1
(CH3CH2)3N
(CH3CH2)3NH+
10.8
C6H5NH2
C6H5NH3+
4.6
Decreased basicity of arylamines
••
NH2 + H
+
NH3 +
••
OH
••
– ••
••OH
••


Aniline (reactant) is
stabilized by
conjugation of
nitrogen lone pair
with ring p system.
This stabilization is
lost on protonation.
Decreased basicity of arylamines
Increasing
delocalization makes diphenylamine a
weaker base than aniline, and triphenylamine a
weaker base than diphenylamine.
Kb
C6H5NH2
(C6H5)2NH
(C6H5)3N
3.8 x 10-10
6 x 10-14
~10-19
Effect of Substituents on Basicity of Arylamines
1.
Alkyl groups on the ring increase basicity, but
only slightly (less than 1 pK unit).
2.
Electron withdrawing groups, especially ortho
and/or para to amine group, decrease basicity
and can have a large effect.
Basicity of Arylamines
X
X
H
CH3
CF3
O2N
NH2
pKb
9.4
8.7
11.5
13.0
X
NH3+
pKa
4.6
5.3
2.5
1.0
p-Nitroaniline
••
O ••
+
N
••O ••
– ••
Lone
••
NH2
– ••
••O ••
+
N
+
NH2
••O ••
– ••
pair on amine nitrogen is conjugated with
p-nitro group—more delocalized than in aniline
itself. Delocalization lost on protonation.
Effect is Cumulative
Aniline
is 3800 times more basic than
p-nitroaniline.
Aniline is ~1,000,000,000 times more
basic than 2,4-dinitroaniline.
Heterocyclic Amines
••
N
is more basic than
N
••
H
piperidine
pyridine
Kb = 1.6 x 10-3
Kb = 1.4 x 10-9
(an alkylamine)
(resembles an
arylamine in
basicity)
Preparation and Reactions
of Amines
The Gabriel Synthesis of Primary Amines
Reductive Amination
Synthesis of Amines via Reductive Amination
In reductive amination, an aldehyde or ketone
is subjected to catalytic hydrogenation in the
presence of ammonia or an amine.
R
fast
C
R'
The
O
R
+ NH3
C
NH + H2O
R'
aldehyde or ketone equilibrates with the
imine faster than hydrogenation occurs.
Synthesis of Amines via Reductive Amination
The imine undergoes hydrogenation faster
than the aldehyde or ketone. An amine is
the product.
R
fast
C
O
R'
+ NH3
C
H
C
NH + H2O
R'
R
R'
R
NH2
H2, Ni
Example: Ammonia gives a primary amine.
O + NH3
H2, Ni
H
ethanol
NH2
(80%)
via:
NH
Example: Primary amines give secondary amines
O
CH3(CH2)5CH
+ H2N
H2, Ni
ethanol
CH3(CH2)5CH2NH
(65%)
Example: Primary amines give secondary amines
O
CH3(CH2)5CH
+ H2N
H2, Ni
ethanol
CH3(CH2)5CH2NH
via:
CH3(CH2)5CH
N
(65%)
Example: Secondary amines give tertiary amines
O
CH3CH2CH2CH
+
N
H
H2, Ni, ethanol
N
CH2CH2CH2CH3
(93%)
Reductive Amination Is
Versatile

Ammonia, primary amines, and secondary amines
yield primary, secondary, and tertiary amines,
respectively
Mechanism of Reductive
Amination

Imine is intermediate
Hofmann and Curtius
Rearrangements

Carboxylic acid derivatives can be converted into
primary amines with loss of one carbon atom by both
the Hofmann rearrangement and the Curtius
rearrangement
Hofmann Rearrangement


RCONH2 reacts with Br2 and base
Gives high yields of arylamines and alkylamines
Curtius Rearrangement


Heating an acyl azide prepared from substitution an
acid chloride
Migration of R from C=O to the neighboring
nitrogen with simultaneous loss of a leaving group
COPE REACTION

H2O2
NR2
_
+
NR2
O
N-OXIDE
-
O
R2N

H
- HO-NR2
45
LESS HINDERED BETA HYDROGEN
SYN ELIMINATION
Amine Oxides Undergo a
Cope Elimination Reaction
46
COPE EXAMPLE
NMe
2
H3C
H2O2
Mild conditions
47
-O
H +NMe
2
H2C
-HONMe2
Reactions of Amines

Alkylation and acylation have already been presented
Arylamines Are Not Useful for
Friedel-Crafts Reactions


The amino group forms a Lewis acid–base complex
with the AlCl3 catalyst, preventing further reaction
Therefore we use the corresponding amide
Diazonium Salts: The
Sandmeyer Reaction

Primary arylamines react with HNO2, yielding stable
arenediazonium salts
NaNO2 + HCl
HONO
Uses of Arenediazonium
Salts

The N2 group can be replaced by a nucleophile
Diverse Reactions of Arenediazonium Salts

Sequence of (1) nitration, (2) reduction, (3)
diazotization, and (4) nucleophilic substitution leads
to many different products
Preparation of Aryl Halides


Reaction of an arenediazonium salt with CuCl or CuBr
gives aryl halides (Sandmeyer Reaction)
Aryl iodides form from reaction with NaI without a
copper(I) salt
Aryl Nitriles and Carboxylic Acids

An arenediazonium salt and CuCN yield the nitrile,
ArCN, which can be hydrolyzed to ArCOOH
Formation of Phenols (ArOH)

From reaction of the arenediazonium salt with
copper(I) oxide in an aqueous solution of copper(II)
nitrate
Reduction to a Hydrocarbon

By treatment of a diazonium salt with
hypophosphorous acid, H3PO2
Mechanism of Diazonium Replacement

Through radical (rather than polar or ionic) pathways
Diazonium Coupling Reactions

Arenediazonium salts undergo a coupling reaction
with activated aromatic rings, such as phenols and
arylamines, to yield brightly colored azo compounds,
ArN=NAr
How Diazonium Coupling Occurs


The electophilic diazonium ion reacts with the
electron-rich ring of a phenol or arylamine
Usually occurs at the para position but goes ortho if
para is blocked
Azo Dyes

Azo-coupled products have extended p conjugation
that lead to low energy electronic transitions that
occur in visible light (dyes)