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Heterocyclic
Chemistry
1-To know types of cyclic
2-To identify Types of protein
3- To Know Heterocyclic compounds
4- To Know Nomenclatures of Heterocyclic
compounds
5-To understand methods of classification of
Heterocyclic compounds
Heterocyclic
Compounds contain ring made up of
carbon atoms and another kind of atoms.
(most commonly N, O, S)
homocyclic =( allicyclic = carbocyclic)
Compounds contain ring made up only
of carbon atoms .
Cyclic compounds
benzene
OH
cyclohexanol
cyclopentadiene
Homocyclic & Heterocyclic
Aromatic Non aromatic
To be classified as aromatic, a compound must have
1-Cyclic structure
2-Coplanar structure.
3-Each atom of the ring must have a p orbital to
form a delocalized π system i.e. no atoms in the
ring can be sp3 hybridized instead all atoms must be
sp2 hybridized (N.B. carbocation and carbanions are
sp2 hybridized
4-Fulfill Huckel rule i.e. the system must have
4n + 2= lectrons :
thus by calculating n value it will be an integral number i.e. n=0, 1, 2, 3,
Conjugated (C=C-C=C-C=C)
HETEROCYCLIC
Erich Hückel
𝜋
𝜋
Examples of aromatic compounds
Examples of non aromatic compounds
N
O
n=1 n=1 n=1 n=0 n=1 n=1
sp3 C n=1/2 n=1/2 sp3 C n=1/2
HETEROCYCLIC
What’s aheterocyclic compound?
If the ring system is made up of carbon atoms and at least one other element,
the compound can be classified as hetero cyclic(that is, hetero atoms).
As hetero atom can be N, О, S, В, Al, Si, P, Sn, As, , Cu. But The
elements that are found most commonly together with carbon in a ring system
are Nitrogen (N), Oxygen(O), and Sulfur(S).
x =N, O, S
HETEROCYCLIC
Definition: Heterocyclic compounds are organic compounds that contain a
ring structure containing atoms in addition to carbon, such as sulfur, oxygen
or nitrogen, as the heteroatom. The ring may be aromatic or non-aromatic
Significance – Two thirds of all organic compounds are aromatic heterocycles. Most
pharmaceuticals are heterocycles.
N N O S....
..
..
..
..
Pyridine Pyrrole Furan Thiophene
Excercise Apply Huckel,s rule to the following
N NH....
Naphthalene Quinoline 1H-Indole
What’s aheterocyclic compound?
If the ring system is made up of carbon atoms and at least one other element,
the compound can be classified as hetero cyclic(that is, hetero atoms).
As hetero atom can be N, О, S, В, Al, Si, P, Sn, As, , Cu. But The
elements that are found most commonly together with carbon in a ring system
are Nitrogen (N), Oxygen(O), and Sulfur(S).
x =N, O, S
HETEROCYCLIC
Definition: Heterocyclic compounds are organic compounds that contain a
ring structure containing atoms in addition to carbon, such as sulfur, oxygen
or nitrogen, as the heteroatom. The ring may be aromatic or non-aromatic
Significance – Two thirds of all organic compounds are aromatic heterocycles. Most
pharmaceuticals are heterocycles.
1- Classification according to number of ring components :-
4) six-membered hetrocycles 3) five-membered hetrocycles
HETEROCYCLIC
a. Monocyclic: One ring structure
1) Three membered
hetrocycles
2) Four membered
hetrocycles
rarer, because of the
greater difficulty of
preparing 4 member
b. Bicyclic: Two rings fused with
each other
c. Polycyclic: More than two rings,
one at least contains heteroatom
N
Isoquinoline
1
2
3
45
6
7
8N1
2
3
45
6
7
8
Quinoline
N
Acridine
HN
Carbazole
Classification
HETEROCYCLIC
Classification
3. Classification according to position of heteroatoms to each other
N N
N N
N
N
pyridine pyrimidine 1,3,5-triazine
2. Classification according to number of heteroatoms in a ring
Unsaturati
on
Saturation
Unsaturation Saturation
irene irane
ete etane
ole olane
ine ane
epine epane
O
Oxirene
O
Oxirane
OOxete
OOxetane
O
oxolefuran
O
oxolane THF
O
4H-oxine
O
2H-oxine
O
Oxane
O
Oxepine
O
Oxapane
Heterocyclic Nomenclature
Ring
size
Unsatu
ration
Saturation Unsaturation Saturation
3 irine iridine
4 ete etidine
5 ole olidine
6 ine prehydro
7 epine prehydro
NH
N1H-azirine
2H-azirine
HN
Aziridine
NAzete
NHAzetidine
NH
azolepyrrole
NH
azolidinepyrrolidine
Nazinepyridine
HN
prehydro azineprehydro pyridinepiperidine
NH
1H- azepine
N
2H- azepine
NH
Prehydro azepine
Ring containing N Ring without N
O=Oxa; S=Thia; N=Aza
There are two systems for naming heterocylic
compounds:
Heterocyclic Nomenclature
1- Trivial or Common names which convey little or no structural information but it still widely used.
2- Systematic ( IUPAC ) A )The Hantzsch-Widman (IUPAC or Systematic) method which in
contrast is designed so that one may deduce from it the structure of the
compound
B) The replacement method
• trivial names are still preferred. Some monocyclic compounds of this kind
are shown with the common (trivial) Some monocyclic compounds of this
kind are shown in the following chart, with the common (trivial) name in
bold and a systematic name
Heterocyclic Nomenclature
1-Trivial or Common names
1) 5-membered heterocycles with one or two heteroatoms
2) 6-membered heterocycles with one or two heteroatoms
O O N NN
N
N
N
N
These are tautomers
Both are not aromatic
DNA/RNA bases
Common azines-six-membered aromatic nitorgrn heterocycles
2H-Pyran 4H-Pyran Pyridine Pyridazine Pyrimidine Pyrazine
Heterocyclic Nomenclature
1-Trivial or Common names
3) Fused heterocycles
Heterocyclic Nomenclature
1-Trivial or Common names
O OO
O
Coumarine
O
O
Ph
Flavone
Chromen-2-oneChromen-4-one
4) Saturated heterocycles
Exercise :
Give the common name of the following compounds:
N
N
H2N CH3
O
NH
HN
Heterocyclic Nomenclature
1-Trivial or Common names
Heterocyclic Nomenclature
Some monocyclic compounds of this kind are shown in the following chart, with
the common (trivial) name in bold and a systematic name based on the Hantzsch-
Widman system given beneath it in blue.
In past heterocycles were given names related to their natural source, or method of
preparation
1-Trivial or Common names
• Hantzsch-Widman nomenclature is named after the German chemists Arthur Hantzsch and Oskar Widman, who proposed similar methods for the systematic naming of heterocyclic compounds in 1887 and 1888 respectively.
• According to this system three to ten-membered rings are named by combining the appropriate prefix (or prefixes) that denotes the type and position of the heteroatom present in the ring with suffix that determines both the ring size (depending on the total number of atoms in the ring) and the degree of unsaturation (note that fully saturated and fully unsaturated have certain rules for nomenclature while partially unsaturation will be indicated in certain ways).
In addition, the suffixes distinguish between nitrogen-containing heterocycles and heterocycles that do not contain nitrogen
• IUPAC name = locants +Prefix + suffix
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
Ring Size unsaturated saturated saturated ring with nitrogen
5 ole olane -olidine
6 ine inane (-ane)
O Oxa S Thia N Aza
Priority
O ox S thi N az
1. Name Prefix- Suffix – ring size - saturation
Rules for Systematic Nomenclature :
1- Generally The name consist of tow parts ,
part 1 = prefix = indicate the type of the heteroatom in the ring ( N,O,S )
part 2 = suffix = indicate the size (3,4,5,…membered) of ring
Heterocyclic Nomenclature
?
Table 1
Atom
O oxa
S thia
N aza
Priority decreases
Prefix
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman Rules for fully saturated and fully
unsaturated heterocycles
1) Identify the hetroatom present in the ring and choose from (table 1) the
corresponding prefix (e.g. thia for sulfur, aza for nitrogen and oxa for oxygen).
2) The position of a single heteroatom control the numbering in a monocyclic compound. The heteroatom is always assigned position 1 and if substituents present are then counted around the ring in a manner so as to take the lowest
possible numbers. and then they should be listed in alphabetical order.
N
CH3
1
23
4
O
N1
2
34
5
Br
H2N
5-Amino-4-bromoisoxazole
O=Oxa; S=Thia; N=Aza
1,4-dithiane
1,2-dithiane 1,3-dithiane 1,4-dithiine 1,2-dithiine
1,2,3-triazole 1,3,5-Triazine
1,3,5-trioxane 1,2-dioxolane
1,4-dioxine
Rules for fully saturated and fully
unsaturated heterocycles
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
3) A multiplicative prefix (di, tri, ect.) and locants are used when two or more similar heteroatoms contained in the ring( two nitrogen indicated by diaza) and the numbering preferably commenced at a saturated rather than an unsaturated atom, as depicted in the following example: 1,3-diaza….
O
S
1,2-oxathiolane
O
N
IUPAC name: 1,2-oxazole
Common name: isoxazole
O
N
IUPAC name: 1,3-oxazole
Common name: oxazole
4) If more than one type of hetroatoms present in the ring the name will include more than one prefix with locants to indicate the relative position of the heteroatoms.
Atom prefixes have a strict order of priority (preference) in which they are to be listed. For example,‘’Oxa’’(for oxygen) always comes before ‘’aza’’ (for nitrogen) in a name (see table 1).
When combining the prefixes (e.g. oxa and aza) two vowels may end up together, therefore the vowel on the end of the first part should be omitted (oxaza).
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
Rules for fully saturated and fully
unsaturated heterocycles
The numbering is started from the heteroatom of the highest priority in such a way so as to give the smallest possible numbers to the other heteroatoms in the ring (the substituents are irrelevant).
12
34
N
S
5
4-Methyl-1,3-Thiaza….
Old Soldiers Never Cry (O > S > N > C)
Unsat Unsat sat sat
N-present N-absent
irine iridine irene irane
ete ete etidine etane
ole olidine ole olane
ine a
in ane
epin
Table 2
a
Ring size
epine epane
a: means use the prefix perhydro followed by the fully unsaturated name
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
Rules for fully saturated and fully
unsaturated heterocycles
5) Choose the appropriate suffix from (table 2) depending on whether or not nitrogen atom is present in
the ring, the size of the ring and presence or absence of any double bonds
This ring contains (N) Prefix is aza
The ring is 3-membered and fully saturated suffix is iridine
By combining the prefix and suffix, two vowels ended up together (azairidine),therefore
the vowel on the end of the first part should be dropped. This gives the correct name:
Aziridine
HN
6) Combine the
prefix(s) and suffix
together and drop the
first vowel if two
vowels came together.
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
Rules for fully saturated and fully
unsaturated heterocycles
• This ring contains (O ,N) and (o) has higher priority than (N) and by starting
numbering the ring at (O) Prefix is 1,2-Oxaaza, but the first vowel must
be omitted to give
1,2-Oxaza
• The ring is 4-membered and fully saturated suffix is etidine
• By combining the prefix and suffix, two vowels
ended up together (1,2-oaxazaetidine), therefore the vowel on the end of the first
part should be dropped. This gives the correct name:1,2-oxazetidine
HN O
N
O
N
1
2
34
5
This ring contains (O) prfix1 (oxa), and two (N) prfix2 diaza
Locants, since (O) is higher priority than (N) so it is in position 1 by default and the
two (N) are therefore at positions 2 and 5, this gives the combined prefixes as 1,2,5-
oxadiaza (note that the a in oxa is not dropped)
It is 5-membered,fully unsaturated ring with (N) the suffix is ole
By combining the prefixes and the suffix and dropping the appropriate vowels we
get the correct name as : 1,2,5-Oxadiazole
The ring is 6-memberd, fully saturated with N Prefix
perhydro followed by the name of fully unsaturated 6-
memberd ring with nitrogen azine
Thus the full name is perhydroazine NH
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
Rules for fully Partial unsaturation in
heterocyclic compounds
Partial unsaturation in heterocyclic compounds can be indicated by one of the
following methods:
1) The position of nitrogen or
carbon atoms which bear extra
hydrogen atoms must be indicated
by numbers and italic capital H
(e.g. 1H, 2H, etc.) followed by the
name of maximally unsaturated
ring.
6 11
2
3
O
2H, 3H-Oxole
4
5
N
1H-Azepine
12
3N
SO
4
5
5H-1,2,3-Oxathiazole
1O
2
34
5
4H-Oxin
H
2)The words dihydro, or
trihydro, or tetrahydro are used
if two or three or four atoms are
saturated. These words are
preceded by numbers indicate the
position of saturated atoms as
low as possible and followed by
the corresponding fully
unsaturated Hantzsch-Widman
name
12
3
NH
1,2-Dihydroazine
NH
1,4-Dihydroazine
Isomers have the same M.F.but differ in the position of the double bond
N
2,3,4,5-Tetrahydroazine
111222
333
444
555
666
O
2,3-Dihydrooxole
4
5
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
A) Hantzsch-Widman
Rules for fully Partial unsaturation in
heterocyclic compounds
Ring size
3) Alternatively, the partially unsaturated 4 and 5 rings (i.e. rings contain one double bond) are given special Hantzsch-Widman suffixes as in table 3 and the double bond is specified as ∆1, ∆2, ∆3, etc.. Which indicates 1 and ; 2 and 3; 3 and 4 atoms respectively have a double bond
(i.e. Name : ∆x + Prefix + special suffix )
( x= locant of the double bond)
Table 3
With N Without N
-etine
-oline
-etene
-olene
HN HN
2
-Azetine
1 1
2
O1
2
2
-Oxetene
NH
O
3
-Azoline 2-Oxolene
12 2
3 34 4
5 51
S
NH
12
3
5
4
-1,3-Thiazoline
4
NH
N
2
34
51
2-1,3-Diazoline
Definitions:
Fusion: This term is used to describe the process of joining
two separate rings with the maximum number of non-
cumulative double bonds via two atoms and one common bond.
Ortho-fused rings: are those rings that have only two common
atoms and one bond, example; naphthalene
Ortho-and peri-fused rings: are those found in a polycyclic
compound with a ring that is ortho- fused to different sides of two
other rings that are themselves ortho-fused together (i.e. there are
three common atoms between the first ring and the other two).
Naphthalene
1H-Phenalene
1H-phenalene is considered as being composed of three benzene rings, each is ortho-peri-
fused to the other two.
Polycyclic compounds incorporating one heterocyclic ring or fused heterocylic
system fused to benzene are known benzoheterocycles.
Also bicyclic compounds with two fused heterocyclic rings are well known.
Both types can be named according to certain rules
Heterocyclic Nomenclature
Nomenclature of Fused Systems
A. Nomenclature of benzofused compounds:
Polycyclic compounds incorporating one heterocyclic ring or fused heterocylic
system fused to benzene are known benzoheterocycles and is named by:
1. prefix: the word benzo
2. letter in square brackets: indicating the position of fusion
3. name of heterocyclic ring: (common or IUPAC name).
Name= Benzo[letter]name of heterocyclic ring
(the connected bond take letter ( a,b,c …)
Heterocyclic Nomenclature
Nomenclature of Fused Systems
O
2
1
34
5 a
bc
d
e
O
Benzo[b]oxole
HN
Benzo[b]azole
Indole
Benzo[c]pyridine
Isoquinoline
N
1. Numbering the H.C.R
a. When numbering a ring with one heteroatom, the heteroatom is #1 and continues in the
direction that is closer to the fused bond.
b. When numbering a ring with more than one heteroatom, the highest priority atom is #1 and
continues in the direction that gives the next priority atom the lowest number.
2. The bonds of the heterocyclic ring are assigned by alphabetical letters staring with the 1,2-bond
Heterocyclic Nomenclature
Nomenclature of Fused Systems
For designating the position of fusion the following rule is followed
O
1
2
34
5
a
b
Benzo[b]furan
S1
23
4
5
67
a
bc
d
Benzo[d]thiepine
NH
1
2
34
5
ab
Benzo[b]pyrrole Indole
N
1
N
1
2
2
3
45
6
7
8
4a
8a
Benzo[b]pyidine Qunioline
a
ab
bcdef
Benzo[f]qunioline
S1
23
45
ab
c
Benzo[c]thiophene
The name is formed of :
name of substituent ring (minor ring)[number, number-letter] name of base ring (major ring
B. Nomenclature of fused heterocylic compounds:
The name of the minor ring is derived by writing a contracted prefix for the substituent ring present
Naming a fused heterocyclic systems composed of two monoheterocyclic units or benzoheterocycles (e.g. chromene) fused with anotehr hetrocycle ring is based upon considering one system as the parent (base) and the second is considered as subsitituent
Heterocyclic Nomenclature
Nomenclature of Fused Systems
The numbers indicate which atoms in the minor ring are common to the major ring (fusion sites in minor ring).
The order of the numbers indicates which atom of the minor ring is encountered closest to atom 1 in the major numbering system (i.e. these numbers may be written in ascending or descending order e.g.2,3 or 3,2 )
The letter defines the position of attachment of the minor ring to the major ring (fusion sites in base component)
Finally a suffix indicate the name of the base ring is written.
The numbering system for the whole fused system is not the same as the numbers in the square brackets (i.e. there are three numbering systems; one for minor ring, one for major ring and the third is for the system as a whole)
Heterocyclic Nomenclature
Nomenclature of Fused Systems
B. Nomenclature of fused heterocylic compounds:
Selection of a parent or base ring is based on the following rules which are applied in order
Rule 1: A heterocyclic ring containing the heteroatom
occurring earliest in the order N, O, S,
(i.e. ring containing N preferred to the rings does not
contain N or containing O, or S)
O
N
O
N
Substituent ringpyrano
Base or parent ringbecause it has Npyrrole
12
3 1
2
3
4
5
a
b
c
pyrano[2,3-c]pyrrole
Priority order of component ring systems:
Heterocyclic Nomenclature
Nomenclature of Fused Systems
O
S
Parent ringO preferred to SFuran
1
2
3
4
1
2
3
4
5
6
7
12
3a
b
S
O
7H-Thiopyrano[3,2-b]furan
Note: The numbering system for the whole
fused system is not the same as the numbers in
the square brackets (i.e. there are three
numbering systems; one for parent ring, one for
substituent ring and the third is for the system
as a whole)
B. Nomenclature of fused heterocylic compounds:
Priority order of component ring systems:
Heterocyclic Nomenclature
Nomenclature of Fused Systems
B. Nomenclature of fused heterocylic compounds:
O
N
O
N
Substituent ringChromeno
Base or parent ringbecause it has Npyrrole
12
3 1
2
3
4
5
a
b
c
Chromeno[2,3-c]pyrrole
Rule 1: more example
Rule 2: A heterocyclic component containing the
largest possible individual ring
O
O
2H-Furo[3,2-b]pyran(pyran [6] preferred to furan [5])
a
b1
2
3
Indicated H
Heterocyclic Nomenclature
Nomenclature of Fused Systems Priority order of component ring systems:
Rule 3: A heterocyclic component
containing the greater number of
heteroatom of any kind
N
O
N
5H-Pyrido[2,3-d][1,2]oxazine
(Oxazine preferred to pyridine)
ab c
d
12
3
5
1
2
3
4
6
7
8
4a
8a
Note: The whole molecule is numbered
starting from pyridine ring to give the
three heteroatom the lowest possible
number (1,6,7), however, stating from
oxazine ring will give them (2,3,5) or
(2,3,8).
Note: The whole molecule is numbered starting from pyrazole ring to give the four heteroatom the lowest possible number (1,2,4,6). While starting from oxazole ring give them (1,3,4,5) or (1,3,5,6).
O
N
N
NH
1H-Pyrazolo[4,3-d]oxazole
(O & N preferred to N only)
a
b
c
d 1
3 2
45
Rule 4: A heterocyclic component containing
the greater variety of heteroatom
Heterocyclic Nomenclature
Nomenclature of Fused Systems Priority order of component ring systems:
Rule 5: A heterocyclic component containing
the greater number of heteroatoms most
preferred when considered in order O, S,N,
O
N
N
S
[1,3]Thiazolo[5,4-d][1,3]oxazole
(N & O preferred to N & S)
ab
c
d
12
34
5
Rule 6: A heterocyclic component with the lower possible number for heteroatoms
N
N
N
N
Pyrazino[2,3-d]pyridazine
(pyridazine [2N-1,2] preferred to pyrazine [2N-1,4]
a
b c
d
12
3
Rule 7: If a position of fusion is occupied by a heteroatom the name of the component
rings to be used are so chosen as both to contain the heteroatom.
Heterocyclic Nomenclature
Nomenclature of Fused Systems
Priority order of component ring systems:
Imidazo[2,1-b]thiazole
1
23
a
b
N
N
S
Order of preference between alternative numbering system of
the whole molecule
a)Give low numbers for the heteroatoms as
a set
HN
NO
1H-Furo[2,3-d]imidazole
(heteroatoms 1,3,4 is preferred to 1,3,6 or 1,4,6)
4HN
NO
HN
NO
1
1
223
34
4
55
6
6
1
2
3
5
6
Heterocyclic Nomenclature
Nomenclature of Fused Systems
Numbering the whole fused system should start from the first atom after fusion in
any direction to fulfill the following rules in order:
b)Give low numbers for heteroatoms
of higher priority O,S, N
OS
4,5-Dihydro-thieno[2,3-b]furan
1
2
34
5
6
c) Give low numbers to fusion carbon atom
N
N
N
N
N
N
N
N
N
N
N
N
6,7-dihydroimidazo[1,2-b][1,2,4]triazine
Fusion carbon 4a is preferred to 7a
D) Give low numbers to indicate hydrogen atom
2
O
O
N
NH
1
2
3
5
6
O
O
N
NH
1
4 3
5
6
4
Not4H-[1,3]dioxolo[4,5-d]imidazole
Heterocyclic Nomenclature
Nomenclature of Fused Systems
B)- If there is a heteroatom at the position of the fusion …)
divide the components such that the common heteroatom is a member of both component
parts
NH
N
N
O
N
N
O = +
imidazo[2,1-b]oxazole
Summary of Nomenclatures Rules
Scheme for deriving the base component of' a fused ring system
1. Is there only one ring which contains nitrogen?
(YES:. choose this as base component)
2. Are the two rings have the same heteroatoms but their size is different ?
(Yes: choose the larger one )
3. Are the two rings of the same size but have different heteroatoms?
(YES: choose the ring containing a heteroatom of the highest priority i.e. O
>S)
4. Are the rings of the same size but contain different numbers of heteroatoms?
(Yes: choose the ring with the greater number )
5. Are the two rings of the same size and the same number of different
heteroatoms?
(Yes: choose the ring with the greatest variety of heteroatoms
7-Are the two rings have the same size and the same number and type of
heteroatoms?
(yes: choose the ring with the lower numbers for heteroatoms )
Heterocyclic Nomenclature
• In replacement nomenclature, the heterocycle’s name is composed of the corresponding
carbocycle’s name and an elemental prefix for the heteroatom introduced (if more than one
heteroatom is present they should be listed according to the priority order According to this
nomenclature, tetrahydrofuran, for instance, is called oxacyclopentane.
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
B-Replacement nomenclature
S
O
N
N
O
S
S
N
cyclohexane
naphthalene
naphthalene
cyclododecadiene
Thiacyclohexane
1,4-dithianaphthalene
1,7-Dioxa-2,8-diazacyclododeca-2,8-diene
4H-4a-azanaphthalene
12
3
44a
12
8a1
2
3
45
6
7
8
4a
7 8
Heterocyclic Nomenclature
2-Systematic ( IUPAC )
B-Replacement nomenclature
O
N
O
NS
N
O
N
N
O
NH
Benzene
Cyclopentadiene
Cyclopentadiene
Cyclopropene
Cyclopentadiene
Cyclohexane
1,4-Diazabenzene
Oxacyclopenta-2,4-diene
1-Oxa-3-azacyclopenta-2,4-diene
Oxazacyclopropene
1-Thia-2-azacyclopenta-2,4-diene
1-Oxa-4-azacyclohexane
NNaphthalene
O
Cyclopropane Oxacyclopropane
2-Azanaphthalene
Importantce and uses of Heterocyclic compounds:-
•Biosynthesized
•Essential for life ( haem, chlorophyll)
•Their metabolitis used as
- toxin towords off predators
- colouring agents to attact mates
In general various important compounds such as:-
alkaloids, vitamins, antibiotics, essential amino acids,
hormones, drugs and dyes contain heterocyclic
structure.
in general: nucleic acids, amino acids (proteins),
• feeding: proteins, carbohydrates, vitamins
• alkaloids: nicotine, caffeine
Application:
• antibiotics (penicillins, sulfonamides)
• insecticides (triazoles)
• herbicides (triazines, pyridines)
HETEROCYCLIC
Heterocyclic Nomenclature
Hetero-atom is to be counted as 1 or as low as possible
When there is more than one hetero-atom (and they are different), preference is
given to O, then S, then N, then C. Also N-H presides over –N=.Mnemonic: Old
Soldiers Never Cry (O > S > N > C) the first one in periodic take number 1
if the 2 element are the same we use; di ,tri, tetra before the prefix
When there is more than one hetero-atom, numbering should be as direct as
possible from one to the other
Substituents are numbered as low as possible
Acceptable prefixes include O=Oxa; S=Thia; N=Aza
Common suffixes for N- and non-N-heterocycles For partially unsaturated
systems, H is(are) are used to indicate the location of saturation
Hantzsch-Widman System of systematic name of heterocyclic compounds
final of prefixes is dropped when followed by a vowel ( a,e,i,o and u)
2. IUPAC (systemic) Names
?
N - Heterocyclic rings
Five-membered rings
NH
NNHN
N
NH
N
N
NH
N
NH
N N
N
NH
pyrrole pyrazole imidazole 1,2,3-triazole1,2,4-triazole tetrazole
NH
NH
O
NH
NH
lactampyrrolidine pyrazolidine
Saturated
Heterocyclic (Most common )
Six-membered rings
Unsaturated
Unsaturated
N N
N
NN
N
N
pyridine pyrimidine pyridazine pyrazine
NH
NH
NH
piperazinepiperidine
saturated
NH
NH
O
O
uracil
NH
NH
O
O
CH3
thymidine
NH
N
NH2
O
cytosine
DNA bases
Fused rings
N
NN
NH N
NN
NH
NH2
N
NHN
NH
NH2
O
purineadenine guanine
Pyrimidine –imidazole
(DNA bases)
NH
1H-indole
N
quinoline
N
isoquinoline
Benzene fused
Heterocyclic (Most common )
N - Heterocyclic rings
O- Heterocyclic rings
furan
OO
O
tetrahydrofuranlactone
O
OOO
O
O
O
O+
2-pyrone 4-pyrone 1,4-dioxanepyrilium cation
O
benzofuran
O O
coumarin
O
O
chromone
Five- membered
Six- membered
Benzene fused
O
4H-pyran
O
2H-chromene
Heterocyclic (Most common )
S - Heterocyclic rings
S
thiophene
S
benzothiophene
Unsaturated
Heterocyclic rings with two different heteroatoms
N
O
N
N
O
N
O
N
N
O
N
N
O
oxazole isoxazole 1,2,3-oxadiazole 1,3,4-oxadiazole 1,2,4-oxadiazole
NH
O
morpholine
N and O
N and S
S
4H-thiopyran
S
thiepine
S
N
SN
SN
N
S
N N
S
N
N
S
N
N
N
1,3-thiazole 1,2-thiazole 1,2,3-thiadiazole 1,3,4-thiadiazole 1,2,4-thiadiazole 1,2,3,4-thiatriazole
Heterocyclic (Most common )
Heteroatom Saturated Unsaturated
Nitrogen Aziridine Azirine
Oxygen (ethylene Oxirane
oxide, epoxides) Oxirene
Sulfur Thiirane Thiirene
1-Common 3-membered
Those with two heteroatoms
Heteroatom Saturated Unsaturated
Nitrogen ------ Diazirine
Nitrogen/oxygen Oxaziridine ------
Oxygen Dioxirane ------
2-Common 4-membered rings
Heteroatom Saturated Unsaturated
Nitrogen Azetidine Azete
Oxygen Oxetane Oxete
Sulfur Thietane Thiete
Those with one heteroatoms
Those with one heteroatoms
Heterocyclic Nomenclature
Those with two heteroatoms
Heteroatom Saturated Unsaturated
Nitrogen Diazetidine -----
Oxygen Dioxetane Dioxete
Sulfur Dithietane Dithiete
Heteroatom S Unsaturated
3 × Nitrogen Triazoles
2 × Nitrogen / 1 ×
oxygen
Furazan
Oxadiazole
2 × Nitrogen / 1 × sulfur Thiadiazole
1 × Nitrogen / 2 × sulfur Dithiazole
Heterocyclic Nomenclature
Heteroatom Saturated Unsaturated
Nitrogen
Pyrrolidine
(Azolidine is
not used)
(Azole Pyrrole
is not used)
Oxygen
Tetrahydrofura
is Oxolane(n
rare)
is Oxole( Furan
not used)
Sulfur Thiolane
Thiophene
(Thiole is not
used)
Those with two heteroatoms
Those with one heteroatoms
Heteroato
m Saturated
Unsaturated (and
partially
unsaturated)
Nitrogen/n
itrogen
Imidazolidine
Pyrazolidine
Imidazole
)Imidazoline(
)Pyrazoline( Pyrazole
Nitrogen/o
xygen
Oxazolidine
Isoxazolidine
)Oxazoline( Oxazole
Isoxazole
Nitrogen/s
ulfur
Thiazolidine
Isothiazolidin
e
)Thiazoline( Thiazole
Isothiazole
Oxygen/ox
ygen
Dioxolane
Sulfur/sulf
ur
Dithiolane
Those with three heteroatoms
3-Common 5-membered rings
Those with one heteroatoms Those with two heteroatoms
Heterocyclic Nomenclature
4-Common 6-membered rings
Heteroatom Saturated Unsaturated
Nitrogen
Piperidine
(Azinane is not
used)
Pyridine
is not Azine(
used)
Oxygen Oxane
-H2( Pyran
is not Oxine
used)
Sulfur Thiane
Thiopyran
(2H-Thiine is
not used)
:
Heteroatom Saturated Unsaturate
d
Nitrogen/nitrogen Piperazine Diazines
Oxygen / nitrogen Morpholine Oxazine
Sulfur / nitrogen Thiomorpho
line Thiazine
Oxygen / oxygen Dioxane Dioxine
Sulfur / sulfur Dithiane Dithiine
Those with three heteroatoms
Heteroatom Saturated Unsaturated
Nitrogen Triazine
Oxygen Trioxane
Sulfur Trithiane
Heteroatom Saturated Unsaturated
Nitrogen Tetrazine
Those with four heteroatoms
Those with one heteroatoms Those with two heteroatoms
Heterocyclic Nomenclature
5-Common 7-membered rings
Heteroatom Saturated Unsaturated
Nitrogen Azepane Azepine
Oxygen Oxepane Oxepine
Sulfur Thiepane Thiepine
Heteroatom Saturated Unsaturated
Nitrogen Homopipe
razine Diazepine
Nitrogen/sulfur Thiazepine
Heterocyclic Nomenclature
Saturated Unsaturated
Heteroatom Nitrogen Oxygen Sulfur Nitrogen Oxygen Sulfur
3-Atom
Ring
Aziridine Oxirane Thiirane Azirine Oxirene Thiirene
4-Atom
Ring
Azetidine Oxetane Thietane Azete Oxete Thiete
5-Atom
Ring
Pyrrolidine Oxolane Thiolane Pyrrole Furan Thiophene
6-Atom
Ring
Piperidine Oxane Thiane Pyridine Pyran Thiopyran
7-Atom
Ring
Azepane Oxepane Thiepane Azepine Oxepine Thiepine
Unsaturati
on
Saturation
Unsaturation Saturation
irene irane
ete etane
ole olane
ine ane
epine epane
O
Oxirene
O
Oxirane
OOxete
OOxetane
O
oxolefuran
O
oxolane THF
O
4H-oxine
O
2H-oxine
O
Oxane
O
Oxepine
O
Oxapane
Heterocyclic Nomenclature
Ring
size
Unsatu
ration
Saturation Unsaturation Saturation
3 irine iridine
4 ete etidine
5 ole olidine
6 ine prehydro
7 epine prehydro
NH
N1H-azirine
2H-azirine
HN
Aziridine
NAzete
NHAzetidine
NH
azolepyrrole
NH
azolidinepyrrolidine
Nazinepyridine
HN
prehydro azineprehydro pyridinepiperidine
NH
1H- azepine
N
2H- azepine
NH
Prehydro azepine
Ring containing N Ring without N
Hantzsch – Widman Nomenclature (adopted by IUPAC)
Ring
Size
Saturat
ed
Partly
Saturated
Unsatura
ted
3 -irane - -irene
4 -etane (dihydro) -ete
5 -olane (dihydro) -ole
6 -inane (di or
tetrahydro)
-ine
7 -epane (di or
tetrahydro)
-epine
8 -ocane (di, tetra, or
hexahydro)
-ocine
O Common name : ethylene oxide
Systematic name : Oxa + irane …Oxirane
OCommon name : furan
Systematic name : Oxa + ole …. Oxole
Common name : pyrrole
Systematic name : H at 1 position + Aza +
ole …. 1H-Azole
NH
Common name : piperidine
Systematic name : Aza + inane …. 1H-
Azinane
HN
Common name : pyrimidine
Systematic name : two aza at 1, 3
positions + ine …. [1,3]-diazine N
N
S
thiacyclobutane
ONH
1-oxa-3-azacyclopentane
Heterocyclic Nomenclature