heterocyclic compounds
DESCRIPTION
Heterocyclic Compounds. Cyclic compounds. Homocyclic Compounds contain ring made up only of carbon atoms . Heterocyclic Compounds contain ring made up of carbon atoms and another kind of atoms. (most commonly N, O, S) . Importance of Heterocyclic Compounds. 1. Used as solvents. - PowerPoint PPT PresentationTRANSCRIPT
HeterocyclicCompounds
HeterocyclicCompounds contain ring made up of carbon atoms and another kind of atoms.(most commonly N, O, S)
HomocyclicCompounds contain ring made up only of carbon atoms .
Cyclic compounds
NH
pyrroleO
O
1,4-dioxane
S
benzothiophene
benzene
OH
cyclohexanol
cyclopentadiene
Importance of Heterocyclic Compounds
1 .Used as solvents
OO
1,4-dioxane
N
pyridine
O
tetrahydrofuran (THF)
2. Found as natural product
N N
CH3
Nicotine in tobacco
sucrose (table sugar)
OOO
OH
OH
OH
OH
OH
OH
OH
OH
3. Found in Biomolecules:
N
NN
NH N
NN
NH
NH2
N
NHN
NH
NH2
O
purineadenine guanine
Nitrogen bases in DNA and RNA
4. Used as Drug
Quinine
a. Quinoline as Anti malaria for 400 years
Metroindazole
b. Imidazoles as Amebicide
4. Used as Drug
Penicillin
c. Lactam as antibiotics
N - Heterocyclic rings
Five-membered rings
UnsaturatedNH
NNHN
NNH
N
NNH
NNH
N N
NNH
pyrrole pyrazole imidazole 1,2,3-triazole1,2,4-triazole tetrazole
NH
NH O
NHNH
lactampyrrolidine pyrazolidine
Most common Heterocyclic rings
Saturated
Six-membered rings
N N
N
NN
N
N
pyridine pyrimidine pyridazine pyrazine
NH
NH
NH
piperazinepiperidine
NH
NH
O
O
uracil
NH
NH
O
O
CH3
thymidine
NH
N
NH2
O
cytosine
Unsaturated
Saturated
DNA bases
N - Heterocyclic rings
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
N - Heterocyclic rings
O- Heterocyclic rings
furan
O O
O
tetrahydrofuran lactone
O
OOO
O
O
O
O+
2-pyrone 4-pyrone 1,4-dioxane pyrilium cation
O
benzofuranO O
coumarin
O
O
chromone
Five- membered
Six- membered
Benzene fused
O4H-pyran
O2H-chromene
S - Heterocyclic rings
S
thiopheneS
benzothiophene
Unsaturated
Heterocyclic rings with two different heteroatoms
NO
NN
O
N
O
N
NO
N
NO
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
NS
N
N
N1,3-thiazole 1,2-thiazole 1,2,3-thiadiazole 1,3,4-thiadiazole 1,2,4-thiadiazole 1,2,3,4-thiatriazole
Naming monoheterocyclic compounds with more than one heteroatoms
Prefix- Suffix – ring size - saturationName:
Nomenclature of Heterocyclic Compounds
Ring Size unsaturated saturated saturated ring with nitrogen
5 ole olane -olidine 6 ine inane (-ane)
O Oxa
S Thia
N Aza
Prio
rity
O ox
S thi
N az
1.
O
S
1,2-oxathiolane
O
N
IUPAC name: 1,2-oxazoleCommon name: isoxazole
O
N
IUPAC name: 1,3-oxazoleCommon name: oxazole
6H-1,2,5-thiadiazine
S
N
N
2H-1,5,2-dithiazine
S
NH
S
3.Indication of the position of saturated atoms: When a ring is partially saturated , the location of saturated atoms, may be designated by a "#H "
2. Indication of the position of hetero atoms: the highest priority atom is #1 and continues in the direction that gives the next priority atom the lowest number
A. Nomenclature of benzofused compounds:
• a benzene ring fused to a heterocycle 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
Nomenclature of Fused Systems
For designating the position of fusion the following rule is followed:
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
ExamplesO1
2
34
5
a
b
Benzo[b]furan
S 1
23
4
5
67
abc
d
Benzo[d]thiepine
NH
12
34
5
ab
Benzo[b]pyrrole Indole
N1
N1
2
2
3
45
6
7
8
4a
8aBenzo[b]pyidine Qunioline
a
ab
b cdef
Benzo[f]qunioline
S1
23
45
ab
c
Benzo[c]thiophene
The name is formed of : name of substituent ring [number, number-letter] name of base ring
B. Nomenclature of fused heterocylic compounds:
Note: The name of the substituent ring is derived by writing
Priority order of component ring systems:
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
45
ab
c
pyrano[2,3-c]pyrrole
Example 1
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)
Example 2
Substituent ring
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])
ab
12
3
Indicated H
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
d1
2
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).
Rule 4: A heterocyclic component containing the greater variety of heteroatom
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)
ab
cd 1
3 2
4 5
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
cd
12
34
5
Rule 6: A heterocyclic component with the lower possible number for heteroatoms
N
NN
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.
Imidazo[2,1-b]thiazole
1
23a
bN
N
S
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:
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
35
6
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 atoms
1
2
3
44a
5
6
7 N
N
N
N
N
N
N
N
N
N
N
N1
2
3
45
6
77a
1
2
3 4
5
6
77a
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
Not
4H-[1,3]dioxolo[4,5-d]imidazole
Summary of Nomenclatures Rules
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 )
Scheme for deriving the base component of' a fused ring system
NN
S
NO N
S
N O
O NH
N NNH
O
N S
O
SNH
N
NH
O
O
4H-pyrano[2,3-b]pyridine
5,7-dihydrothieno[3,4-d]pyridazine
[1,2]thiazolo[4,5-d][1,2]oxazole
4,7-dihydropyrano[2,3-b]pyrrole
1H-imidazo[1,2-b]pyrazole
4,6-dihydrothieno[3,4-d][1,3]oxazole
4H-[1,3]oxathiolo[4,5-b]pyrrole
4H-[1,3]dioxolo[4,5-d]imidazole
NNH
N
O1H-pyrazolo[4,3-d][1,3]oxazole
examples
pyrrole
Aromaticity Aromatic It has 6 delocalized electrons
.
..
.
NH..
Basicity It has not basic properties because the nitrogen lone pair electrons are involved in aromaticity of the ring
Resonance Structures of Pyrrole
Reactions of Pyrrole: Resonance structures show that carbon atoms in pyrrole ring are rich of Electrons. That means Pyrrole like to undergo Electrophilic substitution reaction
Position 2
Position 3
NH
N+
N Cl-
+NN
NH
NH
CO2MeCO2Me
NH
Br
Br2
Examples:
pyridine
AromaticityAromatic
It has 6 delocalized electrons
N ..
...
.
. .
Basicity It has basic properties because the nitrogen lone pair electrons are free and available for sharing as base
Resonance Structures of Pyridine
Reactions of Pyridine: Resonance structures show that carbon atoms at ortho and para are deficient of Electrons. That means Pyridine like to undergo Nucleophilic substitution reaction at ortho and para positions
N..
N NuNu
Nu
..
+ 3 Nu..
N+ NaNH2
N NH2
N+ PhLi
N Ph
Examples:
H2O +NaOH + H2