Six membered heterocyclic compounds with one X
N
Pyridine
Azine
Structure and Properties
The aromatic sextet is complete without participating of the lone pair of nitrogen
Molecular orbital
N
The unshared electrons is in sp2 orbital and in the same plane of the ring-------The difference between benzene and pyridine
1-Benzene symmetrical non-polar but pyridine polar
N
N
N
N
2- It is basic compound [its basicity less than aliphatic amine]
Similarity
Like that of benzene ,pyridine is resistant to oxidation, side chain can be
oxidized
Sources of Pyridine
N
Found in coal tar
CH3
CH3
N
N
CH3
CH3
N
CH3 N
picoline
picoline
picoline
CH3 H3C
N
2,4-lutidine
CH3
2,4,6-collidine
Oxidation of picolines yields the pyridine carboxylic acids
CH3
COOH
KMnO4
N
N
Synthesis of Pyridine
Hantzsch pyridine synthesis
H
EtO
O
H
EtO
O
+
+
O
O
NH3 or NH4OAc
O
O
H
H
Et
N
H
O
O
OEt
CH3
O
CH3
Reaction of Pyridine
A: Electrophilic Substitution SE
Et
OEt
FeCl3
H2O
H3C
N
CH3
Accure chiefly at the 3-position
NO2
HNO3, H2SO4
300 C
N
3- nitropyridine
SO3H
H2SO4
350 C
N
3-pyridine sulfonic acid
Br
N
Br
Br
Br2
300 C
N
3- bromopyridine
RX or RCOX
AlCl3
No Reaction
+
N
3,5-dibromopyridine
H
E
H
E
H
E
C-4 attack
N
N
N
not favoured
C-2 attack
H
N
N
H
E
H
E
N
E
N
not favoured
H
C-3 attack
H
E
N
H
E
N
E
N
Give Resone
In contast to benzene, Pyridine is very unreactive to SE reaction ?
B: Neucleophilic Substitution SN
Accure at C-2 and C-4 position
H
Nu
H
Nu
H
Nu
C-4 attack
N
N
N
specially stable
C-2 attack
H
N
N
H
Nu
H
Nu
N
Nu
N
specially stable
H
C-3 attack
H
Nu
H
Nu
Nu
N
N
N
Examples
1- Chichibabin Reaction
NaNH2
N
NH2
N
Na+
H
stabilized intrmediate
- NaH
N
2-aminopyridine
NH2
2- Alkylation or Arylation Reaction by Organolithium compounds
Ph-Li+
N
Li+
H
N
NaOH
- Cl-
Cl
Cl
N
Ph
2-phenylpyridine
stabilized intermediate
N
+ LiH
heat
heat
N
- NaH
Ph
OH
N
OH
N
H
O
2-hydroxylpyridine
stabilized intermediate
2-pyridone
enol
keto
Br
NH2
Br
Br
Br
Br
- Br-
NH3
N
NH2
N
stabilized intermediate
N
C: Reaction at N-1
1- alkylation
CH3
H3C
CH3I
Br
CH3
N
H3C
+
N
N
I
C CH2
H3C
H
CH3
N-methyl pyridinium iodide
2- Acylation
O
O-Cl
Ph-C
N
Ph S
O
Cl
N
N
O
C
Cl
Ph
benzoyl chloride
O
S
O
Cl
Ph
3- Rx with peracids and with lewis acid
AlC
-H
OO
-C O
CH 3
H+
COO
H 2O 2
N
l3
CH 3
N
N
AlCl3
O
Pyridine -N-Oxide
To activate SE
N
O
To activate SN
N
O
Examples
Electrophilic ( Nitration)
H
NO2
HNO3\H2SO4
NO2
NO2
PCl3
H+
+ POCl3
heat
N
N
N
O
O
O
N
Stabilized intermediate
Neucleophilic
NO2
H3CO
NaOCH3
NO2
OCH3
OCH3
PCl3
-NO2-
+ POCl3
heat
N
N
N
O
O
O
Stabilized intermediate
D: Oxidation and Reduction
N
Reduction
H
H
2,
N
pt
,H
l
C
C
25
N
a
tO
\E
N
H
N
H
1,4-dihydropyridine
Oxidation
??????????????????????????????????
Pipiridine
Synthesis of Quinoline
Skraup Synthesis
CH2OH
+ CHOH
NH2
NO2
+
CH2OH
H2SO4
FeSO4
+ C6H5NH2 +
H 2O
N
Describe the mechanism
Bischler Nepieralski Synthesis of isoquinoline
CH3COCl
NH2
NH
O
P2O5
heat
C
CH3
H2
+
N
N
Pd \ heat
CH3
CH3
Electrophilic Substitution
NO2
O3
c
HN
\0
O4
S
H2
N
major
Nucleophilic Substitution
H
KO
r
o OH
Na
-L
Bu
i
N
OK
N
Bu
NH 2
major
H3
Bu
1)K
2 )N
N
O
N
H
2-quinolone
N
minor
NH2
N
minor
Oxidation & Reduction
N
major
NH2
Reduction
H2\pt
H2\pt
N
N
H
LiAlH4
N
H
cis,trans- decahydro
quinoline
1,2,3,4-tetrahydro
quinoline
1,2-dihydro quinoline
N
H
Oxidation
COOH
aq K
MnO 4
alk
ali
ne
K
N
N
COOH
quinolinic acid
M
nO
4
COOH
neutral
KMnO4
COOH
O
NH
O
Other fused ring Phthalimide
phthalic acid
N
Acridine
Fused Six membered heterocyclic compounds with one X
Diazines
N
N
N
N
N
pyrimidine
pyridazine
pyrazine
O
NH2
H3C
N
N
H
Cytosine
C
Purines
N
O
O
NH
NH
N
H
Thyamine
T
O
N
H
Uracil
U
O
O
O
O
N
HN
H
N
N
HN
HN
O
N
H
N
O
Hypoxanthine
N
H
N
H
O
uric acid
Xanthine
Cl
O
H
N
HN
Cl
POCl3
Cl
N
H
N
H
NH2
N
N
O
O
N
H
N
H
N
N
Cl
N
H
N
aq. NH3
Cl
N
H
N
uric acid
HI \PH4I
1) HI
2) Zn dust
H ,
aO NH 3
N
1) aq.
2) at
he
NH2
I
O
N
HN
I
H2N
N
N
N
N
N
H
N
N
H
N
N
adinine
Zn dust
guanine
N
N
N
H
N
purine
Miscellaneous
S
N
N
H
N
Hypnotic, Sedative, Anxiolytic Anticonvulsant,
Muscle relaxant Properties
N
1,4-benzodiazepine
CH3
O
N
Valium
Preparation of Valium
Cl
N
O
NH2
+
Cl
H
N
O
Cl
C
C O
CH2
C O
Cl
NH3
H
CH3
N
N
Valium
O
N
O
Cl
Cl
Amino Acids
C
CH2Cl
CH3I
N
Cl
Characteristics and Structures
Amino acids contain both a carboxyl group (COOH) and an
amino group (NH2). The general formula for an amino acid is
given below. Although the neutrally-charged structure is
commonly written, it is inaccurate because the acidic COOH
and basic NH2 groups react with one another to form an
internal salt called a zwitterion. The zwitterion has no net
charge; there is one positive (COO-) and one negative (NH3+)
charge.
There are 20 amino acids derived from proteins. While there are several methods
of categorizing them, one of the most common is to group them according to the
nature of their side chains.
1-Nonpolar Side Chains
2-Polar, Uncharged Side Chains
3-Charged Side Chains
Name
Abbreviation
Linear Structure
Alanine
ala A
CH3-CH(NH2)-COOH
Arginine
arg R
HN=C(NH2)-NH-(CH2)3-CH(NH2)-COOH
Asparagine
asn N
H2N-CO-CH2-CH(NH2)-COOH
Aspartic Acid
asp D
HOOC-CH2-CH(NH2)-COOH
Cysteine
cys C
HS-CH2-CH(NH2)-COOH
Glutamic Acid
glu E
HOOC-(CH2)2-CH(NH2)-COOH
Glutamine
gln Q
H2N-CO-(CH2)2-CH(NH2)-COOH
Glycine
gly G
NH2-CH2-COOH
Histidine
his H
NH-CH=N-CH=C-CH2-CH(NH2)-COOH
Isoleucine
ile I
CH3-CH2-CH(CH3)-CH(NH2)-COOH
Leucine
leu L
(CH3)2-CH-CH2-CH(NH2)-COOH
Lysine
lys K
H2N-(CH2)4-CH(NH2)-COOH
Methionine
met M
CH3-S-(CH2)2-CH(NH2)-COOH
Phenylalanine
phe F
Ph-CH2-CH(NH2)-COOH
Proline
pro P
NH-(CH2)3-CH-COOH
Serine
ser S
HO-CH2-CH(NH2)-COOH
Threonine
thr T
CH3-CH(OH)-CH(NH2)-COOH
Tryptophan
trp W
Ph-NH-CH=C-CH2-CH(NH2)-COOH
Tyrosine
tyr Y
HO-Ph-CH2-CH(NH2)-COOH
Valine
val V
(CH3)2-CH-CH(NH2)-COOH
The 20 Amino Acids
The twenty amino acids commonly found in proteins include:



nonpolar amino acids: glycine (gly), alanine (ala), valine (val), leucine
(leu), isoleucine (ile), methionine (met), phenylalanine (phe), tryptophan
(trp), and proline (pro)
polar amino acids: serine (ser), threonine (thr), cystein (cys), tyrosine
(tyr), asparagine (asn), and glytamine (gln)
charged amino acids: aspartic acid (asp), glutamic acid (glu), lysine (lys),
arginine (arg), and histidine (his)
Importance of Amino Acids
- Amino acids are the building blocks of protein
-you get protein from your diet
- 'condensation reactions
- polypeptide chains
- the individual amino acids are called petides
- complex structures know as proteins
Essential and Nonessential Amino Acids
Nonessential amino acids are those that are synthesized by mammals,
while the essential amino acids must be obtained from dietary sources
The Ten "Nonessential" Amino Acids
Alanine
Asparagine
Aspartate
Cysteine (requires sulfhydryl group from
methionine)
Glutamate
Glutamine
Glycine
Proline
Serine
Tyrosine
(synthesized from phenylalanine)
The Ten "Essential" Amino Acids
Arginine (see below)
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Threonine
Tryptophan
Valine
Strecker amino acid synthesis