This document discusses various topics related to amines including their nomenclature, properties, reactions, and synthesis. It defines primary, secondary, tertiary, and quaternary amines based on the number of alkyl or aryl groups bonded to the nitrogen atom. It also discusses the basicity of amines, noting that amines are weak bases due to their ability to donate a lone pair of electrons. Substituents on the nitrogen atom such as alkyl groups increase the basicity by stabilizing the conjugate acid. Common reactions of amines include electrophilic substitution, alkylation, acylation, oxidation, and reactions with nitrous acid to form diazonium salts. Amines can also be synthesized through reduct

1. Amina
Senyawa Organik Basa

2. Kelompok Amin
 Berdasarkan jumlah alkil/aril yang terikat dengan
atom N :
1º ( amina primer ) RNH2
2º (amina sekunder ) R2NH
3º (amina tersier ) R3N
4º (Garam amina kuartener ) R4N+

3. Penamaan amina sederhana
 Amina primer sederhanan “alkilamina”
 Contoh :
 metillamina CH3NH2
 etilamin CH3CH2NH2
 butilamin CH3CH2CH2CH2NH2
 Amina 2º atau 3º simetris “dialkilamina” atau
“trialkiamina”
 Contoh:
 dietilamina (CH3CH2)2NH; trimetilamina (CH3)3N

4. Penamaan amina lebih lanjut
 Amina dengan lebih dari satu jenis gugus alkil
dinamai N-subtituen amina primer . Rantai alkil
terpanjang menentukan nama dasar .
 Contoh
 N-methylpropylamine CH3NHCH2CH2CH3
 N,N-dimethylethylamine (CH3)2NCH2CH3

5. Penamaan lebih lanjut
 Amina yang mempunyai lebih dari satu gugus fungsi
menggunakan namanya “amino” sebagai substituen
pada molekul induknya
 Prioritas N paling rendah dibandingkan dengan gugus
fungsi lainnya : amina < etanol, maka N-amino----
 Examples:
 2-aminoethanol H2NCH2CH2OH
 4-aminobutanoic acid H2NCH2CH2CH2CO2H

6. Amina Heterosiklik
 Amina yang unsur N merupakan bagian dari
penyusun cincin . Penamaannya tidak sistemantik
(non-systematic),
NH2
N N
N
N
H
N
N
H
N
H
N
N
H
N
aniline pyridine pyrimidine pyrrole
quinoline indole imidazole benzimidazole

7. Struktur amines
 Amina mempunyai sp3
hybridized nitrogen
 In principle, tertiary amines with three different R
groups should be chiral (i.e., have a stereocenter).
 However, rapid pyramidal inversion of the amine
nitrogen prevents isolation of the enantiomers
except where the nitrogen is part of a ring or has
other geometrical constraint.
N
Y
Z
X
N
Y
Z
X
fast

8. Properties of amines
 Amines are moderately polar and are capable of
hydrogen bonding.
 Low MW amines (up to about C5) are soluble in
water; higher MW amines will dissolve in acidic
solution (as their conjugate acid).
 Many amines have foul odors.
 Amines are weak bases.

9. Contoh amina biologically active
H2NCH2CH2CH2CH2NH2 putrescine H2NCH2CH2CH2CH2CH2NH2 cadaverine
H2NCH2CH2CH2CH2NCH2CH2CH2CH2NH2
spermidineH
H2N(CH2)N(CH2)4N(CH2)3NH2
spermineH H
NHCH3
OHH
HO
HO
epinephrine
(adrenaline)
NH2
OHH
HO
HO
norepinephrine
(noradrenaline)
NH2HO
HO
dopamine

10. Lanjut …
NH2
CH3H
amphetamine
(benzadrine)
N
CH2CH2NH2
HO
H
NHCH3
CH3H
methamphetamine
(speed)
serotonin
mescaline
NH2CH3O
CH3O
OCH3
N
CO2H
nicotinic acid
(niacin)
NN
CH2CH2NH2
H
histamine

11. Lanjut-----
H2N C OCH2CH3
O
benzocaine
(a topical anesthetic)
Cl
N
N
H
O
O
diazepam (Valium)
N
N
O
N
N
CH3
CH2CH2CH3
H
SO
O
N
N
CH3
CH3CH2O
Sildenafil (Viagra)

12. Lanjut-----
R'O
O
RO
NCH3
codeine (R = CH3, R' = H)
morphine (R and R' = H)
heroin (R and R' = COCH3)
mepiridine
(Demerol)
N
N
N
N
O
O
CH3
H3C
CH3
caffeine
N
N
CH3
H
nicotine
N
H3C
C
O
H
O
C
O
H
OCH3
cocaine
NCH3C
O
CH3CH2O
Methadone
C6H5 NCH3C
O
CH3CH2
CH3
CH3

13. Lanjut -----
N
HO
H
N
H
H
quinine
N
O
N
O
H
H
strychnine
N
N
H
C
O
(CH3CH2)2N
CH3
lysergic acid diethylamide (LSD)
N
H
CH2CH2CH3
H
coniin (the poison from
hemlock used to kill Socrates)

14. Kebassan amina
 Amin sedikit basa, karena mempunyai pasangan
elektron bebas dapat mendonorkan ke proton,
bersifat nucleophiles.
 Amina mempunyai nilai Kb = 10-3
to 10-4
RNH2 + H OH RNH3 + OH
Kb =
[RNH3 ] [OH ]
[RNH2]

15. Kebasaan amina -------
 Biasa digunakan nilai Ka asam konjugat amina
 Asam konjugat lebih lemah, lebih basa (amina)
 Amina sejenis mempunyai Ka values (conjugate
acids) dari 10-10
sampai 10-11
(nilai pKa 10 sampai
11.)
RNH3 RNH2 + H Ka =
[RNH3 ]
[RNH2] [H ]

16. Nilai pKa asam konjugat amina
CH3NH2 10.7
CH3CH2NH2 10.8
(CH3)2NH 10.7
(CH3CH2)2NH 10.5
(CH3)3N 9.8
(CH3CH2)3N 11.0
pKa = 14 – pKb atau pKb = 14 - pKa
Semua nya mempunyai nilai
yang sama .
Efek substituen sama
menstabilkan karbokation,
maka .
Gugus pelepas elektron
(alkil) , pada nitrogen
menaikkan kebasaan
N nya lebih banyak mengikat
substituen gugs alkil nilai
pKa lebih rendah (kurang
asam atau lebih basa)

17. Kebasaan amina
 1. Jika amina bebas terstabilkan terhadap
kationnya, maka amina merupakan basa
yang lebih lemah
 2. Jika kation itu relatf terstabilkan terhadap
amina bebasnya , maka aminanya basa lebih
kuat

18. Amina basanya lemah
(conj. acid)
 Anilin basa lemah karena adanya delokalisasi
elektron melalui resonansi
 Pyridine is weaker because it is an imine (C=N).
 Pyrrole is much weaker because the lp of electrons is
delocalized with the other π electrons to make 6 π e-.
Therefore, the lp is unavailable to act as a base.
aniline pyridine pyrrole
pKa = 4.6 5.2 0.4
NH2
N
N
H

19. Efek Substituent pada kebasaan anilin
Resonance stabilizes free base, destabilizes its protonated form (see next slide)
2 Penjelasan mengenai kebasaan :
NH2 NH2
OCH3
NH2
NO2pKa of
conj. acid: 5.3 1.04.6
(much weaker base)
NH2
NO2
NH2
N
OO
NH2
N
OO
NH2
N
OO
NH3
NO2

20. Pengaruh Substituent pada kebassan
Anilin
NH3
NH3CH3O
NH3O2N
Reaction progress (protonation)
Energy

21. Amina yang tingkat kebasan lebih kuat
 Hanya satu jenis amine : basanya lebih kuat
 Basa guanidin Guanidine basa kuat karena asam
konjugatnya terstabilkan melalui resonansi
guanidine
pKa = 13.6
(conj. acid)
A guanidine group is part of the structure of the amino acid arginine.
NH
C
H2N NH2
NH2
C
H2N NH2
NH2
C
H2N NH2
NH2
C
H2N NH2
NH2
C
H2N NH2

22. Amina terprotonasi pada pH Physiological
 Persamaan Henderson-Hasselbalch :
 Consider the neurotransmitter dopamine, a typical amine (having a pKa of its
conjugate acid = 10.6) in a living cell (buffered at pH = 7.3):
 That is, the concentration of the protonated amine is 2000x that of the
neutral amine! Typical amines are >99.9% protonated at physiological pH.
pH = pKa + log
[RNH2]
[RNH3
+
]
7.3 = 10.6 + log
[RNH2]
[RNH3
+
]
log
[RNH2]
[RNH3
+
]
-3.3 =
[RNH2]
[RNH3
+
]
2 x 10
3
=
;
;
[RNH2]
[RNH3
+
]
5 x 10
- 4
=

23. Sintesis Amina
 Sintesis amina, melalui :
reaksi Substitusi, reaksi reduksi dan
penataan ulang
a. Substitusi Nu :
SN2 OH-
a. RX + NH3 RNH3
+
X-
RNH2
b. Reduksi
c. Penataan ulang amida :

24. Chapter 19 24
Electrophilic Substitution
of Aniline
 -NH2 is strong activator, o-,p-directing.
 May trisubstitute with excess reagent.
 H+
changes -NH2 to -NH3
+
, a meta-directing
deactivator.
 Attempt to nitrate aniline may explode.
=>

25. Chapter 19 25
Aniline Substitution
=>

26. Chapter 19 26
Electrophilic Substitution
of Pyridine
 Strongly deactivated by electronegative N.
 Substitutes in the 3-position.
 Electrons on N react with electrophile.
N
fuming H2SO4
HgSO4, 230
o
C
N
SO3H
=>

27. Chapter 19 27
Nucleophilic Substitution
of Pyridine
 Deactivated toward electrophilic attack.
 Activated toward nucleophilic attack.
 Nucleophile will replace a good leaving
group in the 2- or 4-position.
N Cl
OCH3
_
N OCH3
+ Cl
_
=>

28. Chapter 19 28
Alkylation of Amines
 Amines react with 1° alkyl halides via the SN2
mechanism.
 Mixtures of the mono-, di-, and tri-alkylated
products are obtained.
=>

29. Chapter 19 29
Useful Alkylations
 Exhaustive alkylation to form the
tetraalkylammonium salt.
CH3CH2CHCH2CH2CH3
N(CH3)3
CH3CH2CHCH2CH2CH3
NH2
3 CH3I
NaHCO3
+ _
I
• Reaction with large excess of NH3 to
form the primary amine.
CH3CH2CH2Br
NH3 (xs)
CH3CH2CH2NH2 + NH4Br
=>

30. Chapter 19 30
Acylation of Amines
by Acid Chlorides
 Amine attacks C=O, chloride ion leaves.
 Product is amide, neutral, not basic.
 Useful for decreasing activity of aniline toward
electrophilic aromatic substitution.
NH2
CH3 C
O
Cl
N
H
C
O
CH3
N
to remove HCl
=>

31. Chapter 19 31
Formation of Sulfonamides
 Primary or secondary amines react with
sulfonyl chloride.
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
=>

32. Chapter 19 32
Oxidation of Amines
 Amines are easily oxidized, even in air.
 Common oxidizing agents: H2O2 , MCPBA.
 2° Amines oxidize to hydroxylamine (-NOH)
 3° Amines oxidize to amine oxide (-N+
-O-
)
=>

33. Chapter 19 33
Nitrous Acid Reagent
 Nitrous acid is produced in situ by mixing
sodium nitrite with HCl.
 The nitrous acid is protonated, loses water
to form the nitrosonium ion.
H O N O
H
+
H O N O
H
+
H2O + N O
+
N O
+
=>

34. Chapter 19 34
Reaction with Nitrous Acid
 1° Amines form diazonium salts, R-N+
≡N.
 Alkyldiazonium salts are unstable, but
arenediazonium salts are widely used for
synthesis.
 2° Amines form N-nitrosoamines, R2N-N=O,
found to cause cancer in laboratory animals.
=>

35. Chapter 19 35
Arenediazonium Salts
 Stable in solution at 0°–10°C.
 The -+
N≡N group is easily replaced by
many different groups.
 Nitrogen gas, N2, is a by-product.
HBF4 (KI)
H3O
+
CuCl (Br)
CuCN
H3PO2
H Ar'
Ar N N
+
Ar OH
Ar Cl
Ar C N
Ar F
Ar H
Ar N N Ar'
(Br)
(I)
phenols
aryl halides
benzonitriles
aryl halides
benzene
azo dyes =>

36. Chapter 19 36
Synthesis by
Reductive Amination
 To produce a 1° amine, react an aldehyde
or ketone with hydroxylamine, then reduce
the oxime.
 To produce a 2° amine, react an aldehyde
or ketone with a 1° amine, then reduce the
imine.
 To produce a 3° amine, react an aldehyde
or ketone with a 2° amine, then reduce the
imine salt. =>

37. Chapter 19 37
Examples
primary amine
CH3CH2CH2 CH
NH2
CH3
Ni
H2
CH3CH2CH2 C
N
CH3
OH
H
+
NH2 OH
CH3CH2CH2 C
O
CH3
secondary amine
CH3 CH
NHCH3
CH3
2)
1)
H2O
LiAlH4
CH3 C
NCH3
CH3
H
+
CH3NH2
CH3 C
O
CH3
tertiary amine
=>
C
N
H
CH3H3C
H
Na(CH3COO)3BHC
N
H
CH3H3C
+
H
+
HN(CH3)2C
O
H
CH3COOH

38. Chapter 19 38
Acylation-Reduction
 An acid chloride reacts with ammonia or a 1°
amine or a 2° amine to form an amide.
 The C=O of the amide is reduced to CH2
with lithium aluminum hydride.
 Ammonia yields a 1° amine.
 A 1° amine yields a 2° amine.
 A 2° amine yields a 3° amine.
=>

39. Chapter 19 39
Examples
CH3 C
O
Cl
NH3
CH3 C
O
NH2
LiAlH4
H2O
1)
2)
CH3 CH2 NH2
primary amine
LiAlH4
H2O
1)
2)
C
O
Cl
HN(CH3)2
C
O
N(CH3)2
CH2 N(CH3)2
tertiary amine
=>

40. Chapter 19 40
Direct Alkylation (1°)
 Use a large excess (10:1) of ammonia with
a primary alkyl halide or tosylate.
 Reaction mechanism is SN2.
CH3CH2CH2 Br
NH3
+CH3CH2CH2 NH2 NH4Br
=>

41. Chapter 19 41
Azide Reduction (1°)
 Azide ion, N3
-
, is a good nucleophile.
 React azide with unhindered 1° or 2° halide
or tosylate (SN2).
 Alkyl azides are explosive! Do not isolate.
Br
NaN3
N3
LiAlH4
H2O
1)
2)
NH2
=>

42. Chapter 19 42
Nitrile Reduction (1°)
 Nitrile, -C≡N, is a good SN2 nucleophile.
 Reduction with H2 or LiAlH4 adds -CH2NH2.
Br
NaCN
CN
LiAlH4
H2O
1)
2)
CH2NH2
=>

43. Chapter 19 43
Reduction of Nitro Compounds
(1°)
 -NO2 is reduced to -NH2 by catalytic
hydrogenation, or active metal with acid.
 Commonly used to synthesize anilines.
CH3
NO2
Zn, HCl
CH3CH2OH
CH3
NH2
=>

44. Chapter 19 44
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.
C
O
NH2
H2O
Br2, OH
_
NH2
=>

45. Chapter 19 45
Gabriel Synthesis (1°)
 Use the phthalimide anion as a form of
ammonia that can only alkylate once.
 React the anion with a good SN2 substrate,
then heat with hydrazine.
+N
O
O
_
R X
N
O
O
R H2N NH2
heat
NH
NH
O
O
R NH2
=>