Nomenclature of Heterocyclic Compounds.pdf

Chemistry of Heterocycles
Dr Omkulthom Al kamaly
Pharmaceutical Chemistry

Lesson Objectives
Define heterocyclic
compounds
Describe the
nomenclature systems of
heterocyclic compounds
Describe the
Classification of
Describe the
physicochemical
properties and
aromaticity of
Synthesize of heterocyclic
compounds
Define reactions of

Classification
Type and
Number of the
heteroatom
Oxygen Nitrogen Sulfur

Classification
Degree of
saturation
Aromatic
Non-
aromatic
Unsaturated
Saturated

Classification
8
7
6
Size of the
heterocyclic
compound
3
4
5

Classification
Type of
Cyclic
system
Mono Bi Tri

Introduction
o Heterocyclic compounds are those cyclic
compounds in which one or more of the ring carbon
are replaced by another atom (heteroatom).
o Heteroatoms may be: (O, N, S) this is a common
atoms and (P, As, B, Si) in some compounds.
❑ Examples:

Importance of heterocyclic compounds
Vitamins
Alkaloid
Chloro-
phyll
Amino
acids
Dyes
Drugs
Enzymes
DNA
Genetic
material
Heterocyclic
compounds
are very widely
distributed in
nature and
are particularly
important
because of
wide variety of
physiological
activities
Important
compounds
containing
heterocyclic
rings

Nomenclature
There are two systems for naming heterocyclic compounds
Nomenclature
(1)
Trivial
/Common
(2)
Systematic
/IUPAC
(A)
Hantzsch
Widman
(B)
Replacement
method

Nomenclature
❑ Trivial or common names
o They convey little or no structural information, but it still
widely used, originates from the compound's occurrence,
its first preparation or its special properties
❑ Examples:

Nomenclature
❑ Systematic/ IUPAC names
A. Replacement Method
Decrease
Priority

Nomenclature
A. Replacement Methods

Nomenclature
B. Hantzsch-Widman
➢ IUPAC name = (prefix + stem + suffix)
o According to the IUPAC system, the names of
heterocyclic compounds are made up of three parts
(if more than one heteroatom is present, they should
be listed according to the priority order):
I. Prefix describes Heteroatom
II. Stem indicates ring size
III.Suffix denotes the degree of unsaturation and
presence of nitrogen

Nomenclature (monocycle with one heteroatom)
B. Hantzsch-Widman Rules:
1. Identify the heteroatom present in the ring and choose the
corresponding prefix (N = aza, O = oxa and S = thia).
2. The position of a single heteroatom controls the numbering in a
monocyclic compound. The heteroatom is always assigned
position 1 and if substituents are present then counted around
the ring in a manner so as to take the lowest possible numbers.
❑ Example:

3. A multiplicative prefix (di, tri, etc.) is used when two or
more similar heteroatoms contained in the ring (two
nitrogen indicated by diazo) and the numbering
preferably commenced at a saturated rather than an
unsaturated atom, as depicted in the following
❑ Example:

4. If more than one type of
heteroatoms is present in the ring the
name will include more than one
prefix to indicate the relative position
of the heteroatoms
5. When combining the prefixes (e.g.
oxa and aza) two vowels may end
up together (oxaaza), therefore the
vowel on the end of the first part
should be omitted (oxaza)

6. The numbering is started from the heteroatom of the highest
priority in such a way that give the smallest possible numbers to
the other heteroatoms in the ring (the substituents are
irrelevant).
❑ Example, the prefix corresponding to the following
compound is 4-Methyl-1,3-thiaza….

7. Choose the appropriate suffix from (the following
table in slide 20 or 21) depending on whether or not
a nitrogen atom is present in the ring, the size of the
ring, and the presence or absence of any double
bonds.
8. Combine the prefix(s) and suffix together and drop
the first vowel if two vowels come together as
mentioned before.

C. Hantzsch-Widman
Nomenclature

© 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
Nomenclature (Examples)
Aziridine

© 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-
oxazaetidine), therefore the vowel on
the end of the first part should be
dropped. This gives the correct name:
1,2-oxazetidine
Nomenclature (Example)
1,2-Oxazetidine

© 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
1,2,5-Oxadiazole

© The ring is 6-membered
© Fully saturated with N
© Prefix perhydro followed
by the name of fully
unsaturated 6-
membered ring with
nitrogen azine
© Thus the full name is
perhydroazine
Perhydroazine

Nomenclature (Partial unsaturation)
C. Hantzsch-Widman Rules:
❑ Partial unsaturation in heterocyclic compounds (N or C) can
be indicated by one of the following methods:
1. The position of nitrogen or carbon atoms that 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.

2. The words dihydro, or tetrahydro are used if two 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.

2. If the cyclic system contains three saturated atoms. These
atoms are preceded by numbers indicating the position of
these saturated atoms as low as possible and followed by the
corresponding fully unsaturated Hantzsch-Widman name.

3. Alternatively, the partially unsaturated 4 and 5 rings (i.e. rings
contain one double bond) are given special Hantzsch Widman
suffixes (as in the following table) and the double bond is
specified as ∆1, ∆2, ∆3, etc.. Which indicates 1 and 2; 2 and 3; 3
and 4 atoms respectively have a double bond.
o (Name : ∆x + Prefix + special
suffix )
o (x= locant of the double
bond)

Nomenclature
❑ Exercise:
Explain how can you name the following
heterocycles.

Nomenclature
❑ Exercise:
heterocycles.
Oxirene 4-Bromo-1,3-thiazole
1,3-Oxathiolane 1,3,5-Triazine

Nomenclature
❑ Exercise:
heterocycles.
Aziridine 2H-Azirine
Oxirane Oxirene
Thiiridine Thiirene

Nomenclature
❑ Exercise:
heterocycles.
Azetidine Azete
Oxetane Oxet-1-ium
Thetane Thiet-1-ium

Nomenclature
❑ Exercise:
heterocycles.
Azolidine Azole
Oxolane Oxole
Thiolane Thiole

Nomenclature
❑ Exercise:
heterocycles.
Perhydroazine Pyridine
(Piperidine)
Perhydroxin Pyrilium
(Tetrahydropyran)
Thiane Thiopyran

Nomenclature
❑ Exercise:
heterocycles.
Azepane Azepine
Oxepane Oxepime
Thiepane Thiepine

● Such compounds are defined by the prefixes bi,
ter, quarter, etc. according to the number of
systems, and the bonding is indicated as follows:
Nomenclature (Identical systems connecting by single bond)

● 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.
Nomenclature (Fused rings)
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). (1H-
Phenalene)

1. Heterocycle + Benzene ring
● When naming such compounds, the side of the
heterocyclic ring is labeled by the letters a, b, c, etc.,
starting from the atom numbered 1.
● Therefore side ‘a’ is between atoms 1 and 2, side ‘b’
is between atoms 2 and 3, and so on as shown below
for pyridine.

● The name of the heterocyclic ring is chosen as the
parent compound and the name of the fused ring is
attached as a prefix.
● The prefix in such names has the ending ‘O’, i.e.,
benzo, naphtho, and any other compound not listed
is named by removing the (e) at the end of name.

❑ Examples
Parent Parent Parent

Notice that the saturated position take a number lower than the
unsaturated one

● The letters for the faces of the monocycle are placed
inside the ring, and the numbers for ring positions of the
bicycle taken as a whole are shown on the outside.
● The final numbering always begins at a position next to
the benzo group and that the heteroatoms are given
the lowest numbers possible, observing the O>S>N>P
rule.
● The positions of ring fusion bear the number of the
preceding ring atom with the letter “a” attached.
● Brackets are used around the face letter, and the name
is put together without spaces, except that a dash
separates the bracket from ring numbers if present, as in
benzo[d]-1,3- thiazole

● A convention frequently followed is to write the
structure with the hetero ring on the right and with
its heteroatom at the bottom
● If two heterocyclic rings are fused, additional
rules are required.
● A parent ring is selected, and the other ring is
considered fused on, as was observed for benzene
fusion. Some rules are as follows:
● If one ring contains N, it is considered the
parent, and its name is placed last in the
compound’s name.

2. Heterocycle + Heterocycle
● If both rings contain N, the larger ring is the parent.
● If both rings are of the same size, that with the most N
atoms is the parent, or if the same number of N atoms
is present, that fusion of the rings that gives the smallest
numbers for N when the bicycle is numbered is
chosen.
● If no N is present, O has priority over S over P, and then
the above rules are applied.
● The ring fused onto the parent has the suffix “o”;
common names are used (with modification) where
possible to simplify the name.

● Some examples are pyrido for pyridine, pyrrolo for pyrrole,
thieno for thiophene, furo for furan, imidazo for imidazole,
pyrimido for pyrimidine, pyrazino for pyrazine, among
others
● The face letter of the parent ring where the fusion
occurs is placed in brackets preceding the name of
that ring.
● The position numbers of the fused ring are placed inside
the brackets before the face letter of the parent ring,
separated by a comma.
● The proper numbers for the fused ring are those that are
encountered as one goes around the ring in the same
direction as going alphabetically around the faces of the
parent.

● Consider the examples below
● Fusing the 2,3-bond of furan onto the b-face of
pyrrole, taken as the parent, results in the name
6H-furo[2,3-b]pyrrole.

● Similarly, fusing the 2,3-bond of pyrrole
onto the b-face of pyridine results in a 1H-
pyrrolo[2,3-b]pyridine.

Multicyclic systems (Fused rings)

Examples of drugs(Five membered with one heteroatom)
Furan derivatives
Pyrrole derivatives
Pyrrolidine derivatives
Thiophene derivatives

Examples of drugs (Five membered with two heteroatoms)
Imidazole derivatives
Oxazoles
Imidazoline derivatives
Imidazolidines

Examples of drugs (Five membered with two heteroatoms)
1, 3 thiazoles

Examples of drugs (Five membered with three heteroatoms)
1, 2, 5-thiadiazoles
1, 3, 4-thiadiazoles

Examples of drugs (Six membered hetero compounds With one heteroatom)
Chromanes
Pyridines
Piperidines

Examples of drugs (Six membered hetero compounds With one heteroatom)
Quinolines
Isoquinolines
Thioxanthenes

Examples of drugs (Six membered hetero compounds With two heteroatoms)
Pyrimidines
Pyrazines

Piperazines
Examples of drugs (Six membered hetero compounds With two heteroatoms)
Phenothiazines

1, 2, 4-benzothiadiazines
Examples of drugs (Six membered hetero compounds With three heteroatoms)
Thiazide diuretics
Oxazaphosphorines

5H-Dibenzo [b,f] azepine
Examples of drugs (Seven membered hetero compounds With one heteroatoms)

Examples of drugs (Seven membered hetero compounds With two heteroatoms)
1, 5-benzodiazepines
1, 4-Benzodiazepines

Examples of drugs (Poly heterocyclic systems)
Purines
Pteridines

Nomenclature of Heterocyclic Compounds.pdf

Nomenclature of Heterocyclic Compounds.pdf

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Nomenclature of Heterocyclic Compounds.pdf

Similar to Nomenclature of Heterocyclic Compounds.pdf (20)

Recently uploaded

Recently uploaded (20)

Nomenclature of Heterocyclic Compounds.pdf