nomenclature of heterocyclic compounds. cyclic compounds with at least two different atoms in the...
TRANSCRIPT
Nomenclature of
Heterocyclic compounds
Cyclic compounds with at least two different atoms in the ring
are known as heterocyclic compounds. The ring itself is called
a heterocycle
A hetero atom is an atom other than carbon. The name comes from
the Greek word heteros, which means "different."
The N-atom is the most common heteroatom. Next in the importance
are O- and S-atoms. Heterocycles with Se-, Te-, P-, As-, Sb-, Bi-, Si-,
Ge-, Sn-, Pb- or B-atoms are less common.
It has been found that the introduction of hetero-atom in carbocyclic
molecules makes predictable changes in their physical and chemical
characteristics.
These changes are not only in the behavior of the parent ring but also
in the chemical behavior of the functional groups attached to these
rings X
N N X N
X
N
X
monosubstituted rings
There are several methods to nominate heterocycles
which can be summarized as follow:
I)Trivial names
These names are given to heterocycles and usually
arising from the origin of compounds or of their utility
and they are approved by the IUPAC
O NH
NH
NH
S
Furan1H-Pyrrole
PyrrolidinePyrroline
Thiophene
Five membered rings containing two heteroatoms
NH
N
N
NH
N
O
N
S
N
O
N
S
NH
NH
NH
NH
O
NH
O
NH
S
NH
S
NH
1H-Pyrazole isoxazole isothiazole
oxazole thiazoleImidazole
Pyrazoline
pyrazolidine
isoxazoline
isoxazolidine
isothiazoline
isothiazolidine
Un
satu
rate
dP
arti
ally
Un
s at u
rate
dS
atu
rat e
d
Six membered rings
N
N
N
N
NN
NH
NH
O
NH
HN
N OO
PyrazinePyrimidinePyridazine
Piperidine MorphilinePiperazine
Pyridine 2H-Pyran4H-Pyran
The basis for this system were introduced independently by A. Hantzsch
and O. Widman .
This system was suggested at the beginning for six and five membered
rings and then was extended to include rings from 3 to 10 atoms.
The names of the rings is derived by combining a prefix and a suffix
)i.e Name = prefix + suffix)
According to this system a prefix is used to indicate the nature of
heteroatom in the ring (O, N, S, P,……)
a suffix is used to indicate the size and the degree of saturation in the
ring .
)i) Prefix: is used to indicate the nature of heteroatom in the ring
(O, N, S, P,……)
When different heteroatom is present the highest priority will be as follow:
ElementsValencePrefix
5) Oxygen (O)2oxa
6) Sulphur (S)2thia
9) Nitrogen (N)3aza
The Latin numbers (di, tri, tetra,….) are used to indicate the number of
heteroatoms.
Ex: Tetra + aza ► tetraza
When different heteroatom is present the highst periority will be as follow:
O > S > N
For a ring has O + N ► Oxaza
For a ring has S + N ► thiaza
For a ring has O + S ► oxathia
Suffix is used to indicate the size and the degree of
saturation in the ring
Suffix = Stem + end
Ring sizeStem
3ir
4et
5ol
6*in
7ep
The end refers to the degree of unsaturation in the ring
) as shown in the next table)
2 :System for Hantzsch-Widman names
Ring size
Rings containing NitrogenRings containing no Nitrogen
Unsaturated SaturatedUnsaturatedSaturated
3irineiridineIreneIrane
4eteetidineeteetane
5oleolidineoleolane
6*ineane**ineane***
7epine****epineepane
8ocine****ocineocane
9onin****onineonane
10ecin****ecineecane
Ring size
Rings containing NitrogenUnsaturated Saturated
Rings containing no NitrogenUnsaturated Saturated
3IrineIridineIreneIrane
azirineAziridineOxirene
thiirene
oxirane
thiirane
4eteetidineEteetane
AzeteAzetidineThiete
oxete
Thietane
oxitane
HNH
NO
O
NNH S S
O O
S SO
NH
Oxaziridine
O
NH
2H-[1,2]Oxazete
O
NH
[1,2]Oxazetidine
O
N
Oxazirine
5OleOlidineOleOlane
oxole
thiole
Oxolane
thiolane
6*ineane**ineane***
Oxine
thiine
Oxane
thiane
O O
S S
OO
S S
NH
Azole
N
O
[1,3]-Oxazole
O
NH
[1,3]-Oxazolidine
NH
Azolidine
N
Azine
O
N
2H-[1,3]Oxazine
NH
Azane
NH
O
[1,3]Oxazinane
SO1
2
3
5
4
NH
N
1
2
3
5
4 N
NH
Oxole Thiole 1,2-Diazole 1,3-Diazole
1
2
3
5
4 N
S1
2
3
5
4 N
O 1
2
3
5
4
NNH
N
1,3-Thiazole 1,3-Oxazole 1,2,3-Triazole
N1
NN
N
N
Azine 1,2-Diazine 1,3-Diazine
1
2
3
5
4
ON
1,2-Oxazole
N
N
1,4-Diazine
The rings that have one heteroatom, the rings are numbered so that
the heteroatom is given number 1.
When different heteroatom is present the highest priority will be
O > S > N and move in the direction that gives the other heteroatoms
the nearest possible numbers.
NH1
2
34
5
O
1
2
34
5
O
N
1
2
3
4 5
NS1
2
3
45
For partially saturated 5-membered rings containing
Nitrogen
For partially saturated rings we must designate the location of the nearest
unsaturated atom by Δn )where n = the number of the first unsaturated atom).
NH
NH
NH
azole azoline azolidine
NH
O
N
O
N
O
1
2
34
5
-1-oxa-3-azoline
4
-1-oxa-3-azoline3
-1-oxa-3-azoline2
For full unsaturated rings which contain extra hydrogens, the
positions of extra hydrogens are indicated as nH in the prefix
1
2
3 5
6
4
NH
O1
2
3 5
6
4N
S1
2
3 5
6
4
NH
S
4H-1,4-Oxazine 2H-1,4-thiazine 4H-1,4-thiazine
N
NS
N
NS
N
NHS
1
2
3
4
5
6
4H-1-thia-2,5-diazine 6H-1-thia-2,5-diazine 2H-1-thia-2,5-diazine
When a heterocycle contains two similar
atoms, the one carrying the heavier
substituent is numbered first.
When a heterocycle contains two or more N atoms, we begin numbering
from SP3 nitrogen without deviation from the priority
N
N
H3C
1
23
4 5
1-Phenyl-2-methyl-1,2-diazolidine
N
NH
NH
1
2
34
5
1. Heterocyclic systems are named by considering
them to be derived from cyclic hydrocarbons by
replacing a carbon corner by heteroatom.
2. The heteroatoms are indicated by the same
prefixes used in the Hantzsch-Widman
nomenclature.
3. When more than one heteroatom is present
citation numbers are used (O>S>N).
NH
O
1-Oxa-4-azacyclohexane
O
Oxacyclopent-2,4-diene
N
Azabenzene
S
N
1-Thia-2-azacyclopent-2,4-diene
O
N
Oxazacyclopropene
S
1-thiacyclohexa-2,5-diene
N
O N
O
1,7-Dioxo-2,8-diazacyclododeca-2,8-diene
2,3-Dihydro-1,4-dithianaphthalen
N
S
S
N
O
N
2-Azanaphthalene
11
2
3
4
1
2
3 4
5
1
2
3
44a
5
6
7
4H-4a-Azanaphthalene 1-Oxa-3-azacyclopenta-2,4-diene
2
)iv )Naming substituted monocyclic compounds In case of heterocycles with one heteroatom the hetero atom is given No. 1.
Numbers are then given in the way that gives substituents least possible
numbers.
(When more than one heteroatom is present the heteroatom of highest priority is
numbered 1. Numbering is then made in the way that gives other heteroatoms
least possible numbers. This means least difference between the first two atoms
and not least algebraic sum of numbers.
According to IUPAC rules the organic compounds are arranged in order of
decreasing priority as follow:
a. Cation and anions
b. Acids: Carboxylic, peroxycarboxylic, thiocarboxylic, sulfonic, sulfinic,… Etc.
c.Derivatives of acids: anhydrides, esters, acyl halides, amides, hydrazides,
imides, amidines, …… etc.
d. Nitriles: cyanides, isocyanides.
e. Aldehydes, thioaldehydes and their derivatives
f.Ketones, thioketones and their derivatives.
g. Alcohols, phenols, thioles, and their esters derivatives with inorganic acids.
h. hydroperoxides.
i. Amines, imines and hydrazines.
j. Ethers, thioethers.
k. Peroxides.
All other functional groups, which are included in one of these classes,
are then written as prefixes in form of the name in alphabetic order.
O
Cl
NH
NH2
NH
N
N
COCH3
CN
N
N
HN
C2H5
Ph
N
O
NH2
C2H5O2C
S
NN
SCNNH
N
NH2NC
N
NH
NH2NC
3-furanyl chloride 3-Amino-1H-pyrrole
5-Actyl-4H-1,2,4-triazole-3-carbonitrile 2-Ethyl-1-phenyl-1,2,4-triazolidine
Ethyl 5-aminoisoxazol-3-carboxylate
1,3,4-thiadiazol-2-ylthiocyanate 3-Amino-1H-pyrazole-4-carbonitrile 5-amino-1H-pyrazole-4-carbonitrile
B) Polycycles
)A) Trivial names
Trivial names approved to be utilized are given below.
These were drawn from the IUPAC (Blue Book).
N
N
Quinoline Isoquinoline
4
3
2
18
7
6
5
1
2
3
45
6
7
8
N
N
N
N
Peteridine
1
2
3
45
6
7
845
6
7
Phthalazine
N
N
8 1
N
N
Quinoxaline
2
3
45
6
7
8
N
N
N
N
QuinazolineCinnoline
1
2
3
45
6
7
81
2
3
45
6
7
8
1
2
3
NH
1
2
3456
7
8
9
4a4b
8a 9a
Carbazole
1H-Indole 1H-Indazole
NH
N1
2
34
5
6
7
NH
12
34
5
6
7
1
2
34
56 7
8
9
Purine
N
HN
N
NN
Indolizine
N
3
2
18
7
6
5
2
1
5
1H-Pyrrolizine
434
6
7
NH
2H-Isoindole
1
2
34
5
6
7
Fusion names When a heterocyclic ring is fused to a carbocyclic ring, the hetero ring is
chosen as the parent or base component. Then the systematic name is
formulated from the prefix benzo- and the trivial name of the heterocyclic
component as follows:
The bonds between the ring atoms are denoted according to the successive
numbers of the ring atoms by the letters a, b, c, etc.
The letter must be as early as possible and hence benzo[d]thiophene is
incorrect.
12
3
5
4
S S
+a
b
c
d
e
benzo[b]thiophene
b
Base component
O
NH
Benzo[b]furanBenzo[b]pyrrole
or Indole
12
3
b
1
2
3
5 4
SS
+a
b
c
d
e
naphtho[2,3-b]thiophenebase component
•Polycyclic systems with two or more heterocycles
The base component is chosen as that in the Hantzsch-Widman nomenclature except that of nitrogen is given the highest priority.
Prefixes are formed by changing the terminal )e) of the trivial or the Hantzsch-Widman names of the components into )o)
Chose of the base component.
i- Is there only one component which contains nitrogen?
No Yes: choose this as base component
O
N
Base component pyrrole
ii- Is nitrogen absent from all the rings?
NO Yes: choose the ring containing a heteroatom Which occurs
highest?
S OBase component furan
iii- Are there more than two rings presents?
No Yes: choose the component containing the greater
number of rings
N N
N
Base component quinoline
iv- Are the two rings of different size?
No Yes: choose the larger one
O
N
Base component azepine
V- Do the rings contain different numbers oh heteroatoms?
No Yes: chose the one with the greater number
NO
Base component isoxazole
HN
Vi- Are there differences between the numbers of each kind of
heteroatom in the two rings?
No Yes: choose the ring with the greater number of atoms
listed first
O
N
Base component oxazole
N
S
Vii- In case of the two rings are of the same size and contains
the same heteroatoms, how to select the base component?
Rule is to select the base ring to be the one in which
heteroatoms has less separation between the heteroatoms.
Thus:
N
NN
NN
NN
N
NH
N
Base component Pyrazole
N
HN
Base component Pyridazine Base component Pyridazine
Viii- The ring containing the greatest Varity of heteroatom
arranged according to their order priority
Base component Oxazole
N
O
N
HN N
N
S
Base component Thiazole
1- When a heterocyclic ring is fused to a carbocyclic
ring (choose the hetero ring as the parent or base
component
2- One ring only contains N (choose the ring
containing N)
3- No, Nitrogen ( choose according to the priority O
˃ S )
Sbenzo[b]thiophene
b
Base component is thiophene
How to Choose of the base component )Summary)
O
N
Base component pyrrole
S OBase component furan
4- One consists of two or more rings
(Choose one with the greater number of rings)
5- Two rings of different size (choose the larger)
6- Choose the one with more heteroatoms
N N
N
Base component quinoline
O
N
Base component azepine
NO
Base component isoxazole
HN
7- Same number of heteroatoms (choose O > S > N)
8- Same type and number of heteroatoms, and same
ring size (choose lower separation between atoms)
9- Choose the ring containing the greatest Varity of
heteroatom.
O
N
Base component oxazole
N
S
NH
N
Base component Pyrazole
N
HN
Base component Oxazole
N
O
N
HN
Bridge Specification
Adding prefixes to the name of a base component
The base component is chosen as before
Prefixes are formed by changing the terminal e of the trivial name into <O>
)e.g. pyrazole is converted to pyrazolo)
Some prefixes are formed as in the following table
AcenaphthyleneAcenaphthoNaphthaleneNaphtho
AnthraceneAnthraPerylenePerylo
BenzeneBenzoPyridinePyrido
FuranFuroPyrimidinePyrimido
ImidazoleImidazoQuinolineQuino
IsoquinolineIsoquinoThiopheneThieno
The position of fusion between the prefix and the base is indicated
by inserting )in square brackets) number for the prefix and italic
letter for the base component.
Name = prefix[number, letter]base
N
O
+
NN
O
N
11
2
3
4
1
2
3
4
5
6
Base component 5H-pyrido[2,3-d][1,2]oxazine
a
b c
de
ab
c
d2
3
O
N+
HN
N
1
2
34
5
a
b
c
d
e
N
O
N
HN
1H-pyrazolo[4,3-d]oxazoleBase component
1
2
3
4
N
NN
N
N
NN
N
+
pyrazino[2,3-d]pyridazine
c
d
1
2
3
4
1
2
3
4
5
6
a
b 2
3
a
b c
d
Base component
Pref ix
Pref ix
a
bc
d 1
23
4
1
N
N
N
4H-pyrimido[1,2-b]pyridazine
N
N
N
N
Pyrazino[2,3-d]pyrimidineor
pteridine
N
NN
N
Pyrazino[2,3-c]pyridazine
ON
N
O
oxazolo[5,4-d]isoxazole
SN
N
S
thiazolo[5,4-d]isothiazole
N
NN
N
Pyrimido[4,5-c]pyridazine
If a position of fusion is occupied by a heteroatom, the names of
the two component rings are chosen in a way that both contain
this heteroatom.
N
NH
S
N
+
1
2
3
a
b
N
N
S
1
23
7
imidazo[2,1-b]thiazolebase component
a
b
Symmetric and Asymmetric Heterocycle
N N
N
N
pyrazolo[1,5-a][1,3,5]triazine
N
N
N
N
pyrazolo[5,1-c][1,2,4]triazine
12
3
45
a
a bc
12
3
45
N N
N
O
N
N
N
O
8aH-isoxazolo[2,3-a][1,3,5]triazine
8aH-isoxazolo[3,2-c][1,2,4]triazine
a
a
12
3
b
c
12
3
Other examples for Bridge Specification
1
2
3
ab
c
O
N
pyrano[2,3-c]pyrrole
1
2
3 a
b
S
O
thieno[3,2-b]furan
1
2
3
ab
N N
N
pyrazino[2,3-b]quinoline
12
3a
b
N
O
oxazolo[3,2-a]azepine
1
2
3a
b
c
NO
HN
4H-pyrrolo[2,3-d]isoxazole
d
1
2
3ab
c
dN
O
NS
isothiazolo[5,4-d]oxazole
4
5
N
N
N
pyrido[3,2-d]pyrimidine
1
2
3a
bcd
eN
NH
NN
abc
12
3 4
5
imidazo[4,5-c]pyrazole
N N
N
pyrido[2,3-d]pyrimidine
1 2
3a
bcd
e
N
N
NN
1
2
3
a
bcd
e
N
NN
N1
2
3a
b c
d
pyrazino[2,3-d]pyridazine
4
5N
NN
N 1
23
ab c
d
pyrimido[4,5-d]pyridazinenot
pyrimido[5,4-d]pyridazine
pyrido[3,2-e][1,2,4]triazine
NN
HN
1H-imidazo[1,2-b]pyrazole
N
N
N
4H-pyrimido[1,2-b]pyridazine
N S
NS
thiazolo[5,4-d]isothiazole
N
O
furo[3,4-c]quinoline
ab
c
2
3
4
1
a)- Give low numbers to the heteroatoms
O
Benzo[b]furan
NH O
S
4H-[1,3]oxathiolo[5,4-b]pyrrole
(N.B: 1,3,4 is lower than 1,3,6)
1
2
3 4
5
61
2
3
b) Give low number to heteroatoms in the order O> S> N
SO
Thieno[2,3-b]furan
1
2
34
5
6
N
O
N
HN
6H-imidazo[4,5-d]oxazole
N
O
N
HN
Me
5-methyl-6H-imidazo[4,5-d]oxazole
1
2
3 4
5
6
1
2
3 4
5
6
c) Give hydrogen atom the lowest numbers
O
O
6
4H-cyclopenta[d][1,3]dioxole
N
NH O
O
5
6
4H-[1,3]dioxolo[4,5-d]imidazole
1
2
34
5
1
2
34
A carbon atom common to two or more rings is given a lower case
letter after the numeral of the atom immediately proceeding. A
heteroatom common to two or more rings receives an individual
locant.
N
N
N
N
1
2
3
45
6
7 8
4a
Imidazo[1,2-b][1,2,4]triazine
1
2
3
45
6
1
2
3a
b
c
N
N
N
N
6-methylimidazo[1,2-b][1,2,4]triazine
H3C
7 8
N
N
NN
N4a
12
3
45
6
1
2
3
a
b
7
N
N
NN N
N
N
CN
NH2
6-Aminopyrazolo[1,5-a]pyrimidine-5-carbonitrile
CN
NH2
4
5
8
12
3
456
N
O
3,9-dimethylfuro[3,4-c]quinoline
75a
CH3
CH3
3a8
99a
9b 1
2
3 N
N
N
7-methyl-4H-pyrimido[1,2-b]pyridazine
CH345 6
7
8
9
1
2 3 4
5
67
7a
4a
NN
S
NH2
thieno[3,4-d]pyridazin-5-amine
1
2
3
4
5 6
7
NNH
O
NH2NC
6-amino-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
NN
N
CH3
3,6-dimethyl-3H-imidazo[1,2-b]pyrazole
H3C
1
2 3
4
5
67
8
NS NH2
COOC2H5NC
Ethyl 5-amino-8-cyano-7H-thiazolo[3,2-a]pyridine-6-carboxylate
N O
NN
Pyrrolo[3,2-e][1,3,4]oxadiazine
Pyrrolo[2,3-e][1,3,4]oxadiazine
O
NNN