Heterocyclic Compounds

Assis.prof.Dr. Athraa Hameed

Mekky

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 Heterocyclic Compounds
Heterocyclic chemistry is a very important branch of organic chemistry accounting
for nearly one-third of modern publications. They are an important class of
compounds, making up more than half of all known organic compounds. A cyclic
organic compound containing all carbon atoms in ring formation is referred to as a
carbocyclic compound. If at least one atom other than carbon forms a part of the
ring system (i.e. where one or more atom(s) of the ring are heteroatoms) then it is
designated as a heterocyclic compound.

A ring atom that is not carbon is called a heteroatom. The name comes from the
Greek word heteros, which means “different.” The most common heteroatoms
found in heterocyclic compounds are N, O, S, P, As, Se, B, and so on. Heterocyclic
compounds may be classified into aliphatic and aromatic. The aliphatic heterocyclics
are the cyclic analogues of amines, ethers, thio ethers, amides, etc.
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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 heteroatom in the ring and behave in a manner similar to
benzene in some of their properties

Besides the vast distribution of heterocycles in natural products, they are also the
major components of biological molecules such as DNA and RNA. DNA is without
doubt the most important macromolecule of life. Nucleotides, the building blocks of
our genes are derivatives of pyrimidine and purine ring structures. Chlorophyll and
heme, the oxygen carriers in plants and animals respectively are derivatives of large
porphyrin rings.

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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, haemoglobin , the hormones and a large number of synthetic drugs and
dyes contain heterocyclic ring systems

Common structural types of heterocycles

The heterocycles with the structures analogous to that of benzene but with a
heteroatom replacing at least one carbon atom of the benzene ring are called
aromatic heterocycles, for example, pyridine.
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There are other analogous heterocycles where more than one carbon
atom of the benzene ring are replaced by heteroatoms, for example ,
pyridazine , pyrimidine, pyrazine , 1,2,3-triazine, 1,2,4-triazine, 1,3,5-
triazine, and 1,2,4,5-tetrazine.

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All of the above heterocycles are six-atom, six--electron aromatic heterocycles.
There are five-atom, six--electron aromatic heterocycles, for example, pyrrole ,furan,
and thiophene contain only one heteroatom in the ring system, and oxazole, thiazole,
isothiazole, 1H-pyrazole, 1H-imidazole, and 1H-tetrazole contain two heteroatoms in
the ring

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There are fused-ring system aromatic heterocycles. For example,
quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline,
phthalazine, indole, isoindole, and benzimidazole.

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Besides the above fully unsaturated aromatic heterocycles, there are
other nonaromatic small-ring heterocyclic compounds that may be
either partially or fully saturated. In these heterocyclic compounds,
there is no possibility of cyclic delocalization of p-electrons for
which they lack any aromatic character and these small-ring
heterocycles suffer from considerable angle strain. For example,
pyrrolidine, tetrahydrofuran, thiolan, pyran, aziridine, oxiran,
azetidine, oxetan, and so on, are fully saturated heterocycles and
dihydropyrrole, azirine, oxetene, and so on, are partially saturated
heterocycles.

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I. Type of the heteroatom
Monocyclic compounds are named by prefixing the name that indicates the nature of the
heteroatom. The type of heteroatom is indicated by a prefix as shown below for common heteroatoms

Heteroatom SYMBOL prefix coordination

Nitrogen N aza 3
sulphur S thia 2
Oxygen O oxa 2
silicon Si sila, 4
phosphorus P phospha 3

boron B bora. 4
Selenium Se Selena 2
arsenic As arsa 3, 5
Tellurium Te Tellura 2

Ge Ge Germa 4
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II. Ring size (n)
The size of the ring of monocyclic compounds is indicated by appropriate
suffixing for each ring size.

The ring size is indicated by a suffix according to Table I below. Some of the
syllables are derived from Latin numerals, namely ir from tri, et from tetra, ep
from hepta, oc from octa, on from nona , ec from deca. Ring size Suffix Ring size
Suffix.
Table2: Stems to indicate the ring size of heterocycles

Ring size Suffix Ring size Suffix

3 ir 7 ep
4 et 8 oc
5 Ol 9 on
6 in 10 ec
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The endings indicate the size and degree of unsaturation
of the ring.
The suffixing depends on the nature of the heteroatom-

nitrogen-containing heterocycles and heterocycles

without nitrogen are suffixed in different but distinct ways.

The suffixing of aromatic (fully unsaturated) and

nonaromatic (fully or partially saturated) heterocycles

have different but related suffixes.

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 Ring Nitrogen present Nitrogen obsent
size Un Saturated saturated Unsaturated Saturated

irine -iridine -iren (e) -iran or irane

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4 ete -etidine -et(e) -etan or -etane

5 ole -olidine -ole -olan or olane

6 ine perhydro.......ine -in - ane

7 epine -epin -epane

-
8 ocine -ocin -ocane
-
9 onine - -onin -onane
10 ecine - -ecin -ecane

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a: means use the prefix perhydro followed by the fully unsaturated name
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Notice : According to this system heterocyles are named by combining appropriate
prefix/prefixes with a stem from Table II. The letter “a” in the prefix is omitted where
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NOTE : It is important to recognize that the saturated suffix applies

only to completely saturated ring systems, and the unsaturated

suffix applies to rings incorporating the maximum number of

noncumulated double bonds.

In a monocyclic compound, numbering starts from the

heteroatom and moves in the direction where the substituent

gets lower location. For example,

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Partial Unsaturation Use fully unsaturated name with dihydro, tetrahydro, etc

When numbering give priority to saturated atoms

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II. Common Names
There are a large number of important ring systems which are named widely known with
their non-systematic or common names.

Aromatic

Non aromatic

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 III. The Replacement Nomenclature

In replacement nomenclature, the heterocycle's name is composed of the carbocycle's

name and a prefix that denotes the heteroatom
Thus, "aza", "oxa", and "thia" are prefixes for a nitrogen ring atom, an oxygen ring atom,
and asulfur ring atom, respectively.
that heterocyclic rings are numbered so that the heteroatom has the lowest possible
number

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 Rings With More Than One Heteroatom.
For having more than one heteroatom, the priority of the heteroatoms is decided as
follows:
If more than one hetero atom occur in the ring (monocyclic compounds ) the
heterocycle is named by combining the appropriate prefixes with the ending in
order of their preference,

If there is more than one hetroatom of the same type numbering

starts at the saturated one.
Two or more similar atoms contained in a ring are indicated by the
prefixes ‘di-’, ‘tri’, tetra etc.
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If substituents present, their position should be identified by the number of the
atoms bearing them and then they should be listed in alphabetical order.

IUPAC name = locants+ prefix + suffix

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Hantzsch-Widman rules for partially unsaturated heterocycles

c) 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 1Δ , 2Δ , 3Δ etc.. Which indicates 1 and 2; 2 and 3; 3 and 4 atoms respectively

have a double bond

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Naming Heterocycles with fused rings
Fused heterocycles are systems constructed by combining two or
more rings.

The rings are fused if they are linked in such away that each ring
has one common bond(fusion bond)to each other.

Moreover, each of the fused ring units should contain a maximum

number of non-cumulative double bonds.
•There are two broad types of fused heterocycles.They involve either a
aromatic carbocycle linked to a heterocycle or a heterocycle linked
to an other heterocycle

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To generate this name, it is necessary to identify the fused or

attached ring and the base ring that will be the parent ring that

will provide the suffix of the molecule

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To derive the name of the fused heterocycle,the attached component is
added as a prefix to the name of the base component.
The prefix in such names is generated by replacing the terminal„e‟in the name
of the attached component by„ o‟,i.e.benzo,naphtho and soon.
•The prefixes for the common aromatic heterocycles are listed below:

benzene = benzo
Naphthalene = naphtho
Furan = furo
Thiophene = thieno
Pyridine = pyrido
Pyrrole = pyrrolo
Imidazole = imidazo
Quinoline = quino
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Naming a Carbocycle Fused to Heterocycle
•To name a fused heterocycle ,derived from the fusion of a
carbocycle to a heterocycle:

i. Derive the parent name (written at the end)from the name of the
heterocyclic ring (base component).

ii. Generate the attached name (written first) from the name of the
attached benzene (i.e Benzo).
iii.The bond of fusion of the parent ring with the attached benzene
ring is indicated using alphabetical lletters (a ,b ,cetc) placed in
square brackets between the prefix and parent name
.
iv.To determine the alphabet for the bond of fusion, number the
parent ring from the heteroatom to the fusion bond such that
side1,2,takes letter(a), side2,3 takes letter (b),side3,4
takesletter(c)etc.
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Identifying the Fused Components
•To identify the fused components of afused heterocycle ,dissect it
along the fusion bond in to its component rings to set one as its base
component and the other will be designated as the attached component

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Worked Example: Indole

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Note :that when the fused heterocycles are partially saturated or

substituted, the total numbering of the complete fused system is done

to determine the positions of saturations or substitutions.

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Heterocycle Fused to Another Heterocycle

The IUPAC nomenclature of such systems is based on:

i.The parent name(suffix)of the base component is given by the higher priority heterocycle.

ii.The attached component is the ring name of the lower priority ring and is used as the prefix.

•The bond of fusion is indicated by numbers and an appropriate letter enclosed in a square

bracket and placed immediately after the prefix.

•The numbers (positions of attachment) of the attached component are placed in the sequence in

which they are attached to the base component.

•For substituted systems ,the total numbering of the fused heterocycle is in the usualway

1,2,3….based on the principle of lowest possible numbering

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If there is a choice between different heterocyclic
components, nitrogen-containing components take
singular precedence over all other heterocycles as the
base component
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If nitrogen is absent, then the ring with other
heteroatom(s) is selected as base component based on the
order of preference (oxygen > sulphur). 47
 Thieno[2,3-b]furan
If components have the same heteroatom, but rings of unequal size

are present, then the one with largest size of the ring is selected.

2H-furo[3,2-b]pyran
If rings of 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.

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For fused heterocycles containing a heterocycle with a similar number and
type of heteroatoms, the ring containing the greater number of carbon atoms
adjacent to the bond of fusion is the parent ring.

For fused heterocycles containing a heterocycle with a multiplicity of

heteroatoms ,the ring containing the greatest number of heteroatoms
or greatest varieties of heteroatoms is the parent ring

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Note in these examples that the number for the obligatory
saturated carbon is determined by the numbering that
gives the two heteroatoms the lowest combination of
location numbers.

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For fused-ring heterocycles, the heterocyclic ring having maximum number of rings with a

simple name is chosen. If more than one heterorings are present, then the nitrogen containing

ring is given preference. For heterorings having no nitrogen, the order of preference is decided

by the above mentioned two rules (1) and (2). When the parent heteroring is chosen, its name

is prefixed by the name of the ring fused with it, for example, benzo-, naphtho-.

The structure is now written with the greatest number of rings in horizontal position, and the

other nonhorizontal rings are written at the right of the horizontal row and above it. To

distinguish isomers, the peripheral sides of the parent compound are lettered as a, b, c . . . ,

and so on, beginning with “a” for the side C1—C2, “b” for C2—C3 . . . , and so on. The

numbering of the parent ring is done in such a way that the side undergoing fusion gets the

lowest alphabet. For example heterocycle isoquinoline ring should be numbered as follows:

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The naphthalene ring is numbered as follows:

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Therefore, the name of the isomer

is naphtho[3,2-h]isoquinoline. Another example is given below.

In the above compound, the heteroring is

which is called 1,3-Thiazole.

The compound is, therefore, naphthothiazole. To identify the fused

side, the lettering is done as follows:

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The fused face is d. The naphthalene ring is numbered as follows:

So, the name of the compound

is 2-ethanoyl naphtho[2,1-d]-1,3-thiazole.

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