Heterocyclic Chemistry
N S O
Nomenclature of Heterocyclic compounds
Heterocyclic Chemistry
Heterocyclic Chemistry
Nomenclature of heterocyclic compounds
There are three compounds: systems for naming heterocylic
1)
The common nomenclature: which convey little or no structural information but it still widely used. The Hantzsch-Widman (IUPAC or Systematic) method which in contrast is designed so that one may deduce from it the structure of the compound. The replacement method
2)
3)
Heterocyclic Chemistry
I-Common Nomenclature
Each compound is given the corresponding trivial name (which should be memorized, see the following slides). This usually originates from the compounds occurrence, its first preparation or its special properties.
If there is more than one hetroatom of the same type numbering starts at the saturated one, e.g. imidazole.
4
N3
2 1
N H
If there is more than one type of the heteroatoms, the ring is numbered starting at the hetroatom of the higher priority (O>S>N) and it continues in the direction to give the other hetroatoms the lower numbers as possible.
Heterocyclic Chemistry
Common Nomenclature
If subsituents present, their position should be identified by the number of the atoms bearing them and then they Br should be listed in alphabetical order.
4
3 1 O
N
5
H2N
5-Amino-4-bromoisoxazole
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 trivial name.
H N
1,2-Dihydro-pyridine
Heterocyclic Chemistry
Trivial names
1) 5-membered heterocycles with one or two heteroatoms
2) 6-membered heterocycles with one or two heteroatoms
Common azines-six-membered aromatic nitorgrn heterocycles N N Pyrazine
N O 2H-Pyran O 4H-Pyran N Pyridine N N N Pyrimidine DNA/RNA bases
Pyridazine
These are tautomers Both are not aromatic
Heterocyclic Chemistry
Trivial Names
3) Fused heterocycles
O N N N NH NH2
Guanine
Heterocyclic Chemistry
Trivial Names
O O
O Chromen-4-one
O Flavone
Ph
Coumarine Chromen-2-one
6 7
8 4 3 2 7 6 5 1
1 2
9 N
H
10 N 4
H
9,10-Dihydro-acridine 9H-Carbazole
Heterocyclic Chemistry
Trivial Names
4) Saturated heterocycles
Exercise :
Give the common name of the following compounds:
N O H N
H2N
CH3
Heterocyclic Chemistry
NH
II-Replacement nomenclature
In replacement nomenclature, the heterocycles name is composed of the corresponding carbocycles 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 shown in (table 1). According to this nomenclature, tetrahydrofuran, for instance, is called oxacyclopentane.
Table 1
Atom
O
Se
Prefix
oxa
selena
Priority decreases
thia
N P
aza
phospha
Heterocyclic Chemistry
II- Replacement nomenclature
N
Benzene
N
1,4-Diazabenzene
Cyclopentadiene
O N
Oxacyclopenta-2,4-diene
Cyclopentadiene Cyclopropane
O
1-Oxa-3-azacyclopenta-2,4-diene
O
Oxacyclopropane
N O
Cyclopropene
Oxazacyclopropene
Cyclopentadiene
S
1-Thia-2-azacyclopenta-2,4-diene
Cyclohexane
1-Oxa-4-azacyclohexane
N H
Naphthalene
N
2-Azanaphthalene
Heterocyclic Chemistry
II- Replacement nomenclature
cyclohexane
S
8 7 6 5
Thiacyclohexane
8a
1 2
naphthalene
N
4a 4
2 3
4a
3 4
4H-4a-azanaphthalene
naphthalene
S
2 1
1,4-dithianaphthalene
cyclododecadiene
N O O N
7 8
1,7-Dioxa-2,8-diazacyclododeca-2,8-diene
Heterocyclic Chemistry
III-Hantzsch-Widman nomenclature (IUPAC)
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 Chemistry
Hantzsch-Widman rules for fully saturated and fully unsaturated heterocycles 1) Identify the hetroatom present in the ring and choose from (table 1 on slide 9) 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. For example:
4
N1
2
CH3
Heterocyclic Chemistry
Hantzsch-Widman rules
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 4 example: 1,3-diaza. N3
5 1 2
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 Chemistry
N H
Hantzsch-Widman rules
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). For example the prefix corresponding to the following compound is 4-Methyl-1,3Thiaza.
4
N3
2 1
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 Combine the prefix(s) and suffix together and drop the first vowel if two vowels came together.
Heterocyclic Chemistry
6)
Hantzsch-Widman rules
Table 2
Ring size N-present N-absent
Unsat irine ete ole ine epine ocine 9 10 onine ecine
sat
iridine etidine olidine
a a
Unsat irene ete
ole in epin ocin
sat
irane
etane
olane ane epane ocane
a a
onin
ecin
onane ecane
Heterocyclic Chemistry a: means use the prefix perhydro followed by the fully
Hantzsch-Widman rules
Examples
H N
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
Heterocyclic Chemistry
Hantzsch-Widman rules
HN O
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: Heterocyclic Chemistry 1,2-oxazetidine
Hantzsch-Widman rules
4 3
N O
1
N2
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
Heterocyclic Chemistry
Hantzsch-Widman rules
N H
The ring is 6-memberd, fully saturated with N Prefix perhydro followed by the name of fully unsaturated 6memberd ring with nitrogen azine Thus the full name is perhydroazine
Heterocyclic Chemistry
Hantzsch-Widman rules
Exercise:
Explain how can you name the following heterocycles.
Br N O O S N N N S
Heterocyclic Chemistry
Hantzsch-Widman rules for partially unsaturated heterocycles
a)
Partial unsaturation in heterocyclic compounds can be indicated by one of the following methods: 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.
4 5 6 1 O 3 2
4 5 O 1
3 2
1 N H 1H-Azepine
3N 4 2S 1 5 O 5H-1,2,3-Oxathiazole
2H, 3H-Oxole
4H-Oxin
Heterocyclic Chemistry
Hantzsch-Widman rules for partially unsaturated heterocycles
b) 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.
4 5 3 5 4 3 5 4 3 4 3
N H
N H
1,2-Dihydroazine
1,4-Dihydroazine
2,3,4,5-Tetrahydroazine
2,3-Dihydrooxole
Isomers have the same M.F. but differ in the position of the double bond
Heterocyclic Chemistry
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 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 Ring size With N Without N
-etine -oline
-etene
-olene
Heterocyclic Chemistry
Hantzsch-Widman rules for partially unsaturated heterocycles
Examples
2 1 1 1 4 3 4 3
HN
HN
O
2
5 1
5 1
-Azetine
-Oxetene
3
N H
-Azoline
4 3
2 -Oxolene
NH
2 1 5
2 1
-1,3-Thiazoline
N H
2 -1,3-Diazoline
Heterocyclic Chemistry
Nomenclature of Fused Systems 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
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).
Heterocyclic Chemistry
Nomenclature of Fused Systems
For example : 1H-phenalene is considered as being composed of three benzene rings, each is ortho-perifused to the other two.
1H-Phenalene
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 Chemistry
I-Nomenclature of Fused Heterocyles
A. Nomenclature of benzofused compounds:
Unless listed as a trivially named heterobicycle (see slide 6), a benzene ring fused to a heteromonocycle of five or more members or a heterobicylcle is named by prefixing the word benzo to a letter indicating the position of fusion in square brackets by the name of heterocyclic ring (common or IUPAC or modified replacement name). Name= Benzo[letter]name of heterocyclic ring For designating the position of fusion, the peripheral bonds of the heterocyclic ring are consecutively assigned alphabetical letters staring with the 1,2-bond as a side and the labeling is continued around the ring to give the common bond the lowest order.
Heterocyclic Chemistry
I-Nomenclature of Fused Heterocyles Examples
1 2
a O b
5
3 4
c d
a
S
1
b a
2
5 1
5 7 6
N H
Benzo[b]furan
Benzo[d]thiepine
Benzo[b]pyrrole Indole
b
2
f
1 6
4 4a
d a
c
3
b c
a
S
5 1
N
7 1 8a 8
b
2
Benzo[b]pyidine Qunioline
Benzo[f]qunioline
Benzo[c]thiophene
Heterocyclic Chemistry
I-Nomenclature of Fused Heterocyles
B. Nomenclature of fused heterocylic compounds: 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 The name is formed of : The name of the minor ring is derived by writing a contracted prefix 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
Heterocyclic Chemistry
name of minor ring [number, number-letter] name of major ring
I-Nomenclature of Fused Heterocyles
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)
Selection of a parent component or attached component is based on the following rules which are applied in order
Heterocyclic Chemistry
Priority order of component ring systems:
I-Nomenclature of Fused Heterocyles
Rule 1: A heterocyclic ring containing the heteroatom occuring
earlist in the order N, F, Cl. Br, I, O, S, Se,.. (i.e. ring containing N preferred to the rings does not contain N or containing O, or S)
N O
5 3 4
c
2 1 3
Substituent ring Chromeno
b 2 Base or parent ring because it has N pyrrole
Chromeno[2,3-c]pyrrole
Heterocyclic Chemistry
I-Nomenclature of Fused Heterocyles
1
O
2
7 6
S
4
a
2 3
2 1
Parent ring O preferred to S Furan
Substituent ring Thiopyrano with one satrated C that take locant 7 when the system is numbered as a whole (starting from O to give the two heteroatoms locants 1,4 while starting from S gives them locants 1,5)
7H-Thiopyrano[3,2-b]furan
Heterocyclic Chemistry
I-Nomenclature of Fused Heterocyles Rule 2: A heterocyclic component containing the largest possible individual ring
O 1
Indicated H
b a
O
2 3
2H-Furo[3,2-b]pyran (pyran [6] preferred to furan [5]) Numbering the whole system is started from O in furan ring to give the two heteroatoms locants 1,4 while starting from O in pyran ring gives them locants 1,5, thus the indicated H takes locant 2
Heterocyclic Chemistry
I-Nomenclature of Fused Heterocyles
Rule 3: A heterocyclic component containing the greater number of hetroatoms of any kind
8 7N 1 8a
b c a d
5
2 3
4a
N 1
6 O
3 4
5H-Pyrido[2,3-d][1,2]oxazine (Oxazine preferred to pyridine)
N.B. The whole molecule is numbered starting from pyridine ring to give the three heteratoms the lowest locants (1,6,7), however, stating from oxazine ring will give them locants (2,3,5) or (2,3,8).
Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 4: A heterocyclic component containing the greater variety of hetroatoms
a b
O
d c
3
4 5
NH
1N
1H-Pyrazolo[4,3-d]oxazole (O & N preferred to N only)
N.B. The whole molecule is numbered starting from pyrazole ring to give the four heteratoms the lowest locants (1,2,4,6). While starting from oxazole ring give them locants (1,3,4,5) or (1,3,5,6).
Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 5: A heterocyclic component containing the greater number of heteroatoms most preferred when considered in order F, Cl, Br, I, O, S, Se, Te, N, P, As, Sb, Bi, Si, Ge, Sn Pb, B, Hg
S N c
5
1 4 2
b a
O
[1,3]Thiazolo[5,4-d][1,3]oxazole (N & O preferred to N & S)
Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES Rule 6: A heterocyclic component with the lower locants for heteroatoms
b
N
c
2
N
1
a
N
Pyrazino[2,3-d]pyridazine (pyridazine [2N-1,2] preferred to pyrazine [2N-1,4]
Exercise: Name the following compound.
O
N H Heterocyclic Chemistry
NOMENCLATURE OF FUSED HETEROCYCLES 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.
S N 3
2 1
a b
N
Imidazo[2,1-b]thiazole
Heterocyclic Chemistry
Order of preference between alternative numbering system of the whole molecule
Numbering the whole fused system should start from the first atom after fusion in any direction to fulfill the following rules in order: Give low numbers for the heteroatoms as a set
6 5
O H N1
a)
4 2 5
O
H3 N
2
N
3 2
O
H N N
4 5
6 1H-Furo[2,3-d]imidazole
(heteroatoms 1,3,4 is preferred to 1,3,6 or 1,4,6)
b)
Give low numbers for heteroatoms of higher priority i.e. O,S, N
1
O
5 4
3 Heterocyclic Chemistry 4,5-Dihydro-thieno[2,3-b]furan
Order of preference between alternative numbering system of the whole molecule
c) Give low numbers to fusion carbon atoms
1 7 6 3
N
4 6 2
Not 7
5 3 3
Not
8
N
5
N
4
N
6 7
N
2
N
4a
8a
2
N
8a
Imidazo[1,2-b][1,2,4]triazine fusion C -4a is preferred to 8a
d)
Give low numbers to indicated hydrogen atom
6
N O
4
N
3
O
4N
H
2
O
Not
N H
6
2H,4H-[1,3]dioxol[4,5-d]imidazole Indicated hydrogens 2,4 not 2,6
Heterocyclic Chemistry
NOMENCLATURE OF HETEROCYCLES
Exercise Q1. Name the following compounds (a-d):
N S N N H N N O S
(a)
(b)
(c)
(d)
Heterocyclic Chemistry
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 Chemistry
