heterocyclic compounds. heterocyclic compounds contain ring made up of carbon atoms and another kind...
TRANSCRIPT
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HeterocyclicCompounds
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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
pyrrole
O
O
1,4-dioxane
S
benzothiophene
benzene
OH
cyclohexanol
cyclopentadiene
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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
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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
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Metroindazole
b. Imidazoles as Amebicide
4. Used as Drug
Penicillin
c. Lactam as antibiotics
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N - Heterocyclic rings
Five-membered rings
UnsaturatedNH
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
Most common Heterocyclic rings
Saturated
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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
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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
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O- Heterocyclic rings
furan
O O
O
tetrahydrofuranlactone
O
OOO
O
O
O
O+
2-pyrone 4-pyrone 1,4-dioxane pyrilium cation
O
benzofuran
O O
coumarin
O
O
chromone
Five- membered
Six- membered
Benzene fused
O
4H-pyran
O
2H-chromene
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S - Heterocyclic rings
S
thiopheneS
benzothiophene
Unsaturated
Heterocyclic rings with two different heteroatoms
N
O
NN
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
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
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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.
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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
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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
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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
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Examples
O
1
2
34
5
a
b
Benzo[b]furan
S 1
23
4
5
67
abc
d
Benzo[d]thiepine
NH
1
2
34
5
ab
Benzo[b]pyrrole Indole
N1
N1
2
2
3
45
6
7
8
4a
8aBenzo[b]pyidine Qunioline
a
ab
bcdef
Benzo[f]qunioline
S1
23
45
ab
c
Benzo[c]thiophene
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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
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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
4
5
ab
c
pyrano[2,3-c]pyrrole
Example 1
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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
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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
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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).
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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
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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
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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
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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
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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
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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
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c) Give low numbers to fusion carbon atoms
1
2
3
4
4a5
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
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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
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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
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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
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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
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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
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NH
N+
N Cl-
+NN
NH
NH
CO2Me
CO2MeNH
Br
Br2
Examples:
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pyridine
AromaticityAromatic
It has 6 delocalized electrons
N ..
...
.
. .
BasicityIt has basic properties because the nitrogen lone pair electrons are free and available for sharing as base
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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..
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N
+ NaNH2
NNH2
N
+ PhLi
NPh
Examples:
H2O +NaOH + H2