heterocyclic compounds

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Heterocyclic Compounds

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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 Presentation

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Page 1: Heterocyclic Compounds

HeterocyclicCompounds

Page 2: Heterocyclic Compounds

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

Page 3: Heterocyclic Compounds

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

Page 4: Heterocyclic Compounds

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

Page 5: Heterocyclic Compounds

Metroindazole

b. Imidazoles as Amebicide

4. Used as Drug

Penicillin

c. Lactam as antibiotics

Page 6: Heterocyclic Compounds

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

Page 7: Heterocyclic Compounds

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

Page 8: Heterocyclic Compounds

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

Page 9: Heterocyclic Compounds

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

Page 10: Heterocyclic Compounds

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

Page 11: Heterocyclic Compounds

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.

Page 12: Heterocyclic Compounds

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

Page 13: Heterocyclic Compounds

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

Page 14: Heterocyclic Compounds

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

Page 15: Heterocyclic Compounds

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

Page 16: Heterocyclic Compounds

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

Page 17: Heterocyclic Compounds

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

Page 18: Heterocyclic Compounds

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

Page 19: Heterocyclic Compounds

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

Page 20: Heterocyclic Compounds

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).

Page 21: Heterocyclic Compounds

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

Page 22: Heterocyclic Compounds

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

Page 23: Heterocyclic Compounds

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

Page 24: Heterocyclic Compounds

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

Page 25: Heterocyclic Compounds

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

Page 26: Heterocyclic Compounds

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

Page 27: Heterocyclic Compounds

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

Page 28: Heterocyclic Compounds

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

Page 29: Heterocyclic Compounds

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

Page 30: Heterocyclic Compounds

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

Page 31: Heterocyclic Compounds

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

Page 32: Heterocyclic Compounds

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

Page 33: Heterocyclic Compounds

NH

N+

N Cl-

+NN

NH

NH

CO2MeCO2Me

NH

Br

Br2

Examples:

Page 34: Heterocyclic Compounds

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

Page 35: Heterocyclic Compounds

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..

Page 36: Heterocyclic Compounds

N+ NaNH2

N NH2

N+ PhLi

N Ph

Examples:

H2O +NaOH + H2