Heterocyclic - Psau · Heterocyclic Nomenclature 2-Systematic ( IUPAC ) A) Hantzsch-Widman 3) A multiplicative prefix (di, tri, ect.) and locants are used when two or more similar

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

8

10

6

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.

Pyrrole Is Aromatic

Furan Is Aromatic

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

• Exercise:

Explain how can you name the following heterocycles.

O S N N

N

O

N S

Br

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

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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