Transcript heterocyclic cyclic chemistry nomenclature , ring synthesis

HETEROCYCLIC CYCLIC CHEMISTRY NOMENCLATURE & RING SYNTHESIS
NOMENCLATURE OF HETEROCYCLIC COMPOUNDS
N
S
O
• DEFINITION:
• A cyclic organic compound containing all carbon atoms in ring
formation is referred to as a carbocyclic compound.
• If atleast one atom other than carbon forms a part of the ring
system then it is designated as a heterocyclic compound.
• Nitrogen , oxygen ,and sulfur are the most common
heteroatoms .
• An enormous number of heterocyclic compounds are known
and this number is increasing rapidly.
• Heterocyclic compounds may classified into
ALIPHATIC and AROMATIC.
• The Aliphatic heterocyclic's are the cyclic analogues
of amines , ethers , thioethers , amides etc. their
properties are particularly influenced by the presence
of strain in the ring. These compounds generally
consist of small(3-and 4-membered) and common(5
to 7 membered) ring systems.
• The Aromatic heterocyclic compounds in contrast are
those which have a hetero atom in the ring and
behave in similar manner to benzene in some of
their properties.
• These compounds also comply with the general rule
proposed by HUCKEL .This states that aromaticity is
obtained in cyclic conjugated and planar systems
containing (4n+2) Π electrons.
.
• The chemistry of heterocyclic compounds is as logical as
that of aliphatic or aromatic compounds. their study is of
great interest both from the theoretical as well as practical
stand point.
• Heterocyclic compounds occur widely in nature and in a
variety of non- naturally occurring compounds.
• A large number of heterocyclic compounds are essential to
life.
• Various compounds such as alkaloids, antibiotics, essential
amino acids, the vitamins, hemoglobin, the hormones and
a large number of synthetic drugs and dyes contain
heterocyclic ring systems.
• A knowledge of heterocyclic chemistry is useful in
biosynthesis and in drug metabolism.
• Nucleic acids are important in biological processes of
heredity and evolution.
NOMENCLATURE OF HETEROCYCLIC COMPOUNDS
• PREFIX FOR HETERO ATOMS
HETERO ATOM
VALENCE
PREFIX
O
2
Oxa
N
3
Aza
S
2
Thia
Se
2
Selena
Te
2
Tellura
P
3
Phospha
As
3
Arsa
Si
4
Sila
Ge
4
Germa
COMMON NAME ENDINGS FOR HETEROCYCLIC
COMPOUNDS
RING SIZE
SUFFIXES FOR FULLY
UNSATURATED COMPOUNDS
SUFFIXES FOR
SATURATED
With N
FULLY
COMPOUNDS
With N
Without N
3
-irine
-irene
-iridine
-irane
4
-ete
-ete
-etidine
-etane
5
-ole
-ole
-olidine
-olane
6
-ine
-in
-ane
7
-epine
-epin
-epane
8
-ocine
-ocin
Without N
-ocane
CLASSIFICATION OF HETEROCYCLIC COMPOUNDS
1.
Three membered heterocyclic compounds with one
hetero atom.
Aziridines
Azirines
Oxiranes
Oxirenes
Thiiranes
Thiirenes
2. Three membered heterocyclic compounds with two
hetero atoms.
Diaziridines
Diazirines
Oxaziridines
3. Four membered heterocyclic compounds with one
atom.
Azetines
Oxetanes
Thietanes
hetero
4
Five membered heterocyclic compounds with one hetero atom
Pyrroles
Furans
Thiophenes
5.
Five membered heterocyclic compounds with two hetero atoms
Pyrazole
and
Benzopyrazoles
Imidazoles and
Benzimidazoles
Isoxazoles and
Benzoisoxazoles
Oxazoles
and
Benzoxazoles
Isothiazoles and
Benzoisothiazoles
Thiazoles
and
Benzoisothiazoles
6. SIX membered heterocyclic compounds with one hetero atom
Pyridines
pyrilium salts
α and ϒ -pyrones
7. Six membered heterocyclic compounds with two hetero atoms
Pyridazines
Quinazolines
Cinnolines and Phthalazines
Pyrazines
.
Pyrimidines
Quinoxalines
8. Seven membered heterocyclic compounds .
Azepines
Oxepines
Thiepines
9. Bicyclic ring systems derived from Pyrrole , Furan , and Thiophene.
Indoles
Isoindoles
Indolizines
Dibenzopyrroles
Benzofuran , Isobenzofuran , and Dibenzofuran
Benzothiophene , Isobenzothiophene and Dibenzothiophene
10. Bicyclic ring systems derived from pyridine.
Quinolines
Acridines
Isoquinolines
Phenanthrides
Quinolizium salts
STRUCTURES OF VARIOUS HETEROCYCLIC COMPOUNDS
H
• II
S
O
N
aziridine
oxirane
thiirane
H
S
O
N
azirine
oxirene
thiirene
H
H
H
N
H
diaziridine
N
N
H
N
N
H
H
diazirine
O
oxaziridine
H
azetine
S
O
N
N
azetidine
oxetane
thietane
N
N
O
furan
N
H
pyrrole
S
thiophene
O
N
N
H
N
H
isoxazole imidazole pyrazole
N
N
N
N
N
O
H
H
benzopyrazole
benzimidazole
benzoisoxazole
N
N
N
O
benzoxazole
S
benzoisothiazole
S
benzothiazole
N
O
pyridine
+
+
S
pyrillium salt
thiopyrillium salt
O
O
O
O
pyrone
pyrone
N
N
N
pyridazine
cinnoline
N
N
quinazoline
N
N
N
N
N
pthlazine
pyrimidine
N
N
N
N
pyrazine
quinoxzline
RING SYNTHESIS FOR VARIOUS HETEROCYCLIC
COMPOUNDS
• 1. AZIRIDINE – 3 MEMBERED COMPOUND
Gabriel ring closure :
Aziridine was first obtained in 1888 by
heating ᵦ -bromoethylamine in the presence of potassium
hydroxide.
cH2
H2N
cH2
Br
KOH
etanol
N
H
aziridine
+
KBr
+
H22O
OXIRANE – 3 MEMBERED COMPOUND
• From the oxidation of Alkenes:
probably the simplest
method of preparing the parent compound Oxirane is the direct
oxidation of ethylene by air over a silver catalyst at elevated
temperatures .

H2C
CH2
O
Ag
oxirane
THIIRANE – 3 MEMBERED COMPOUND
• From 2- mercaptoetanol :
probably the most useful
method of preparing Thiirane is from 2-mercaptoethanol by
treating it with phosgene in ethyl acetate and pyridine to give
monothioethylene carbonate which on decarboxylation leads to
Thiirane.
O
HS
O
COCl2
200 oC
Pyridine
-CO2
OH
S
S
AZETIDINE – 4 MEMBERED COMPOUND
• Cyclization method : Azetidine and its derivatives have been
prepared by a number of methods which include intramolecular
cyclization and cycloaddition .
• In this method ϒ – bromopropylamines in the presence of base
produces Azetidine compound
+
OH
Br

NH2
NH
Azetidine
Br
-
+
H2O
THIETANES- 4 MEMBERED COMPOUND
• From 1,3- dihaloalkanes:
The earliest and common method
for the preparation of Thietane involved in the reaction of 1,3 –
dihaloalkanes with sodium or potassium sulphide .this reaction is
generally carried out in alcohol / water mixture at 70°.
Br
+
Na2S
Alcohol, water
o
Br
70 C
S
+
3,3-dimethylthietane
2NaBr
OXETANE -4 MEMBERED COMPOUND
• Cyclization reactions: It is a direct route for the preparation
of oxetane. in this reaction halohydrin in the presence of base
forms an 2,2-diethyloxetane.
OH
C2H 5
OH
H 5C2
(C2H5)2CCHCH2Br
O
-
2,2 diethyloxetane
+
Br
-
+
H 2O
PYRROLE- 5 MEMBERED COMPOUND
• From furan :
Commercially pyrrole is obtained by fractional
distillation of coal tar or bone oil. Alternatively it can be obtained
from furan by passing it over ammonia and steam and heated
(400°) in the presence of aluminium oxide catalyst. A primary
amine may be employed to prepare 1- substituted pyrrole.
O
RNH2, Al2O3
R
N

Pyrrole
+
H2O
FURAN – 5 MEMBERED COMPOUND
• From furfural : The most important source of furan is furfural.
The latter is available by acid hydrolysis of polysaccharides
present in oat, husks and corn cobs. these are degraded to
pentose's which are subsequently converted to furfural on further
treatment with acid.
• Furfural can also be converted directly to furan by its gas phase
.decarbonylation in the presence of palladium and charcoal.
O
CHO
200 oC, Pd/C
O
-CO
Furfural
Furan
THIOPHENE – 5 MEMBERED COMPOUND
• From sodium succinate : The classical method for preparing
Thiophene in the laboratory consists of heating a mixture of
sodium succinate in the presence of phosphorous trisulphide.
+ -
Na O OC
-
+
COO Na
P2S3
S
180 oC
Thiophene
PYRIDINE – 6 MEMBERED COMPOUND
• 6- benzyl -3,5-dichloro-2H,1,4-oxazin-2- one on refluxing with
phenyl acetylene in Toluene yields a highly substituted pyridine.
H2CH5C6
Cl
O
O
Phenylacetylene
Cl
80 oC, toluene
15-16 hr
C6H 5
H2CH5C6
Cl
N
Cl
2,6-dichloro-3-benzyl-5-phenyl pyridine
AZEPINE – 7 MEMBERED COMPOUND
• From nitrobenzene : Nitrobenzene by its deoxygenation with
tributylphosphine
initially forms an arylnitrene .this is
accomplished with an primary alcohol leads to the formation of
2-alkoxy -3H – azepines.
NO2
:N:
Bu3P
OR
ROH
N
2-alkoxy-3H-azepine
OXEPIN - 7 MEMBERED COMPOUND
• Oxepin was first prepared by the treatment of 1,2-epoxy-4,5dibromo cyclohexane with a mild dehdrohalogenating agent
O
Br2
Br
O
Br
CH3O-Na+
ether, reflux
-2HBr
O
O
Oxepin
THIEPIN - 7 MEMBERED COMPOUND
• Wynberg
and
Helder
reported
that
2,3,4,5tetramethylthiophene and dicyanoacetylene in the presence of
aluminium chloride yielded Thiepin derivative.
CN
CN
AlCl3, CH2Cl2
+

S
CN
S
CN
CN
CN
S
Thiepin derivative
INDOLE – BICYCLIC RING SYSTEMS DERIVED FROM PYRROLE
• The Reissert synthesis : This procedure also offers a convenient
method for the preparation of indole and its derivatives. It involves
a base – catalysed condensation of
0-nitrotoluene with oxalic
acid ester in the presence of sodium ethoxide forms 0- nitrophenylpyruvate this on hydrolysis gives a corresponding acid ,this
on reductive (zn/CH3COOH) cyclization yields Indole.
COOC2H5
+
NO2
COOH
COOC2H5
O
NO2
COOC2H5
H2O, H+

C2H5O-Na+
Zn, CH3COOH
COOH
O
NO2
N
H
220 oC
-CO2
N
H
Indole
BENZOFURAN – BICYCLIC RING SYSTEM DERIVED FROM FURAN
• From coumarin: This method involves initially the bromination
of coumarin to 3,4- dibromocoumarin followed by treatment with
alkali to coumarillic acid. The acid decarboxylates to benzofuran.
Br
Br
Br2, CHCl3
O
O
O
-Br-
H+
O
-
KOH
-HBr
O
Distill with CaO
-CO2
O
Benzofuran
-
CHCOO
Br
BENZOTHIOPHENE-BICYCLIC RING SYSTEM DERIVED FROM
THIOPHENE
• From o-mercapto ᵦ -chlorostyrene : The o- mercapto ᵦ chlorostyrene on refluxing with an alcoholic solution of alkali
cyclizes to benzothiophene.
H
-
CH Cl
SH
Alc kOH
reflux
S
Benzothiophene
ACRIDINE- BICYCLIC RING DERIVED FROM PYRIDINE
• From Diphenylamine-2-Carboxylic Acid: o-chlorobenzoic
acid is first condensed with aniline in the presence of a base to
yield diphenylamine-2-carboxylic acid. The acid is cyclized in the
presence of sulphuric acid to acridone whereas reaction with
phosphorous oxychloride gives 9-chloroacridine.reaction of
acridone and 9-chloroacridine with appropriate reagents provide
acridan.this on oxidation by air or ferric chloride leads to
ACRIDINE.
COOH
COOH
Cl
Base
+
N
H
H2N
O
Cl
N
H
N
H
N
H
oxidation
N
Acridine
PHENANTHRIDINE-BICYCLIC RING DERIVED FROM PYRIDINE
• Cyclodehydration of an acyl o- aminodiphenyl in the presence of
phosphorous oxychloride.
POCl3,boil
NH
C=O
R
N
Cl-C
R
-HCL
N
R
Phenanthridine
REFERENCES
• TEXT BOOK OF HETEROCYCLIC CHEMISTRY BY RAJ
K.BANSAL.
• TEXT BOOK OF THE CHEMISTRY OF HETEROCYCLIC
COMPOUNDS BY R.MORRIN ACHESON.
• WWW . GOOGLE .COM
• WWW.WIKIPEDIA .COM
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