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Nomenclature of Heterocyclic Compounds
pharmaceutical chemistry (The University of Mustansiriyah)
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Nomenclature of Heterocyclic Compounds
What are heterocyclic compounds?
• These are considered to be derived from the carbocyclic compounds by the
replacement of one or more carbon atoms by the heteroatom(s) such as N, O, S etc.
• In earlier days of organic chemistry, names were given to compounds as a means of
identifying them, usually before their structure were known.
• A systematic nomenclature is necessary so that the structure of the compound can
be deduced from its name.
• Several different systems of nomenclature have been devised for heterocyclic
compounds.
• But, normally, particularly for aromatic heterocycles, a hybrid of trivial and Hantzsch-
Widman systems is used.
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Trivial names of Common ring systems
• These were given before their structural identification.
• Trivial names of the heterocycles were given on the basis of their characteristic
properties (or) on the sources from which they are obtained. Eg: Picoline, Furfurol,
Pyrrole.
• Therefore the trivial names hardly provide any structural information.
• There are about 49 ‘recognized’ trivial names.
• Eg: Pyrole, Pyrazole, Pyran, Purine, Pyrimidine, Quinoline, Isoquinoline, Xanthene,
Perimidine.
Trivial Names
1) 5-membered heterocycles with one or two heteroatoms
2) 6-membered heterocycles with one or two heteroatoms
C o m m o n a z in e s -s ix -m e m b e r e d a r o m a tic n ito r g r n h e te r o c y c le s
N
N
N
O O N N N N
2 H -P y ra n 4 H -P y ra n P y r id in e P y rid a z in e P y rim id in e P y ra z in e
T h e s e a r e ta u to m e r s D N A /R N A b a s e s
B o th a r e n o t a r o m a tic
3) Fused heterocycles
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O
N
N H
N N N H 2
G u a n in e
O O
O O
O O
Ph
C o u m a r in e C h ro m e n -4 -o n e F la v o n e
C h ro m e n -2 -o n e
8 9 1
5
6 4
7 2
3
7
6 10 3
2
N
8 9 5 4
N
1
H
H
9 ,1 0 - D ih y d r o - a c r id in e
9 H - C a r b a z o le
4) Saturated heterocycles
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Systematic (Hantzsch-Widman) nomenclature system.
• 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.
• This is the most widely used systematic method and is used for naming three- to ten-
membered heterocyclic systems with various degrees of unsaturation.
• This nomenclature specifies the ring size, nature, type and position(s) of the
heteroatom(s).
• For partially saturated heteromonocycles, the prefixes ‘dihydro’, ‘tetrahydro’ etc
should be used.
Stems for 3-10 membered heterocycles
Ring size N-present N-absent
Unsat sat Unsat sat
irine iridine irene irane
ete etane
ete etidine
ole olidine ole olane
ine a in ane
a
epine epin epane
ocine a ocin ocane
9 onine a onin onane
10 ecine a ecin ecane
a: means use the prefix perhydro followed by the fully unsaturated name
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Combination of prefix(es) with stem
• The heteromonocyclic system is named by combining one or more ‘a’ prefixes for the
heteroatom(s) with a stem indicating the size of the ring. If the stem begins with
vowel, the terminal letter ‘a’ of the ‘a’ prefix is dropped.
• Prefixes: The prefixes indicate the heteroatoms present in the heterocyclic systems.
The prefixes for different heteroatoms are presented in the table in the order of
preference.[position, no. of heteroatoms (di, tri,…etc.), heteroatom(s)].
• Stems: The stems are used to indicate the size of the ring and the
saturation/unsaturation in the heteromonocyclic systems. (Ring size, sat. or unsat.
ring)
• IUPAC name = Prefix + stem
• When two or more heteroatoms of the same type are present, then the prefixes, di-,
tri-, etc. are used and placed before the prefix used for the heteroatom.
• When two or more different heteroatoms are present in the same ring, the
prefixes of heteroatoms are combined in the order of preference.
Numbering
• With one heteroatom: The numbering starts from the heteroatom giving the
position-1 and proceeds in such a way as to give the lowest possible locate to the
substituent if present.
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With two or more identical heteroatoms: The ring is numbered in such a way that the
heteroatoms are assigned the lowest possible set of number of locates.
• With two or more different heteroatoms: The numbering starts from the heteroatom
with the highest preference as in the table (O>S>N…). The remaining heteroatoms
are given lowest number locates.
Presence of saturated atom (indicated hydrogen) in compound not
complete saturated
• When heterocyclic ring with maximum number of noncumulative double bonds
contains a saturated atom, its position is given the lowest possible locate and is
numerically indicated by an italic capital H before the name of heterocyclic ring
system.
• However, the indicated hydrogen is normally cited as an italic capital H in
parenheterocyclic system in which a carbon atom of the ring is involved in
the carbonyl prosthesis after the locate of the additional structural features.
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Presence of saturated atom (indicated hydrogen) in compound not complete saturated
1 position (H)
2 position (dihydro)
3 position (dihydro- H)
4 position (tetrahydro)
5 position (tetrahydro- H)
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Naming of fused ring systems
• The fused heterocyclic system is considered to be constructed by the combination of
two or more cyclic structural units.
• The cyclic structural units contain maximum number of non-cumulative double bonds
and are fused in such a way that each structural unit has one bond common with
other.
Nomenclature of fused heterocylic compounds:
v Naming a fused heterocyclic systems composed of two
monoheterocyclic units or benzoheterocycles fused with
anotehr hetrocycle ring is based upon considering one system
as the parent (base) and the second is considered as
subsitituent
v The name is formed of :
name of minor ring [ number, number-letter] name of major ring
( base component)
v The name of the minor ring is derived by writing a contracted
prefix(o) for the substituent ring present
Furo from Furan
Imidazo from Imidazole
pyrido from Pyridine
Pyrimido from Pyrimidine
Thieno from Thiophene
Pyridazino from pyridazine
Pyrazino from pyrazine
Chromeno from chromene
Benzeo from benzene
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Rules for naming fused heterocyclic rings:
• The fused heterocyclic system is dissected into its components in which one is base
component and the other(s) is attached component(s).
• The components are given their recognized trivial names (if possible) else, systematic
name is used.
• The base component should always be a heterocyclic system. If there is a choice, it is
determined by order of preference.
Selection of base component (Seven rules):
1. Nitrogen containing component: a nitrogen containing component is selected as base
component.
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2. If nitrogen is absent, then ring with other heteroatom(s) is selected as base component
(order of preference as in the table)
3. Component with greatest number of rings is selected and named with recognized trivial
name if possible.
4. If rings of unequal size are present, then the one with largest size of the ring is selected.
5. If rings or equal size with different number of heteroatoms are present, then the ring
with greater number of heteroatoms of any kind is considered as a base component.
6. If rings of equal size with equal number of different heteroatoms are present, then the
component containing ring with greatest variety of heteroatoms is selected.
7. If rings of same size with same numbers and same kinds of heteroatoms are
present, then the component containing the ring with heteroatoms which have
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lowest locate numbers is preferred.
Numbering of fused systems:
• The attached component is added as a prefix to the name of the base component.
The terminal ‘e’ is replaced by ‘o’.
• The bonds of the base component are alphabetized with consecutive italic letters
starting with ‘a’ for 1,2-bond…..
• The atoms are other prefix component are numbered in the normal way 1,2,3….in
the principle of lowest possible numbering.
• Go in the same direction.
Numbering the outer group (s) or atom(s)of fused systems:
• Use rectangular coordinate.
• As many rings as possible lie in a horizontal raw.
• A no. of rings are in the upper right quadrant.
• The system is numbered in clockwise direction commencing with that atom which is
not engaged in the ring fusion and is furthest to the left
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• In the upper most ring or in the furthest to the right in the upper row.
• Carbon atoms which belong to more than one ring are omitted.
• Hetero atoms in such position are however, includes.
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Nomenclature of Benzofused systems:
• If a benzene is fused to the heterocyclic ring, the compound is named by placing
number(s) indicating position(s) of the heteroatom(s) before the prefix benzo- (from
benzene) followed by the name of the heterocyclic component.
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However, the heterocyclic system in which two benzene rings are orthofused to a six-
membered 1,4-diheteromonocycle containing the same heteroatoms are named by adding
the replacement prefix for the heteroatom to the term ‘-anthrene’ replacing ‘a’.
• If two benzene rings are ortho-fused to a six membered 1,4-dihetero monocyclic ring
containing different atoms, then it is named by adding the prefix ‘pheno-’ to the H-W
name of heterocycle.
Replacement Nomenclature System
• This system is based on the fact that the heterocyclic compounds are derivatives of
carbocyclic compounds. Therefore the rules of nomenclature are similar to those
applied for the carbocyclic compounds.
• It is used for the heterocycles containing Spiro heterocyclic systems.
Spiro Heterocycles
• The compounds in which two rings are fused at a common point are known as spiro
compounds and the common atom which is quaternary in nature is designated as
spiro atom.
• Spiro heterocycles with one sprio atom consisting of one or both heterocyclic rings
are named by prefixing spiro to the name of normal alkane with same number of
carbon atoms. The number of atoms in each ring are indicated by Arabic numbers
separated by a full stop and enclosed in a square bracket in ascending order and are
placed between spiro prefix and the name of hydrocarbon. The heteroatoms are
indicated by the prefixes and are prefixed with their positions to the name of spiro
hydrocarbon.
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• The numbering starts from the ring atom of the smaller ring (if rings are of unequal
size) attached to the spiro atom and proceeds first around the smaller ring and then
around the larger ring through the spiro atom. The heteroatoms are assigned the
lowest possible number locates.
• If there is a choice between two different heteroatoms, the preferential numbering is
decided according to the appearance of the heteroatoms in the table.
• The heterocyclic ring is preferred over the carbocyclic ring of the same size. If both
the rings are heterocyclic, the preference is given to the heterocyclic ring with the
heteroatom appearing in the table.
• If unsaturation is present in a ring, the pattern of numbering remains the same but
the direction around the ring remains in such a way that the multiple bond is given
number as low as possible. However, the heteroatom is preferred over the multiple
bond.
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