PYRROLE

• Occurs in coal tar. Colourless liquid with odour of chloroform, mp -24C, bp 131C, slightly soluble in water. It has resonance energy of 100KJ per mole. It is found in proline and nicotine.

RETROSYNTHESIS OF PYRROLE

NNOH

NH2O

OH2

NH2

H

O

X

OH2

-NH3

O O

OH2

N

OH

N

OH

OH

NH2

OH

O

NH2

O

O

+

+

Acid-base rxns of pyrrole

• Protonation occurs at C-2

N N

N

NaH

NNa

N

BuLi

NLi

+ H+

+

POLYMERS

protonation on C2

+

+

_

+

• Electrophilic substitution rxns

NH

SO2Cl

NH

Cl

NH

Br2/acetic anhydrideNH

Br

+ heat

+

2

NH

HNO3/acet anhNH

NO2

NH

NH

SO3HSO3/pyri

+

+100C

NH

NH

O O

H2O2

NH

H2/NiNH

OXIDATION

REDUCTION

or high pressure

high temp

• COMPOUNDS CONTAINING PYRROLE OR PYRR• OLIDINE

NH

CO2HN

N

CH3

PROLINE NICOTINE

• IMIDAZOLEN

N

N

N N

N

4H-IMIDAZOLE

WEAKER BASE THAN PYRROLE DUE TO ADDITIONAL N

SUBST OCCURS AT POSITIONS 4,5

+ HCl +

RETROSYNTHESIS OF IMIDAZOLE

N

NH

N

NHOH

H

N

NHOH

H

OH

OH2

-NH3

NH

OO

NH3

H O2

+

N

NH

N

NHOH

H

O

X NH

NH2

H O2

+

• COMPOUNDS CONTAINING IMIDAZOLE

NH

NNH2

HO2C

NH

NNH2

HISTIDINE HISTAMINE

Vasodilator, high level causes allergic rxnssuppressed by anti-histamines-blocks allegy causing H-receptors

PYRAZOLE CONT’D

N

N

2H-PYRAZOLE

subst occurs at C-4Elec

analgesic, anti-inflammatory

PYRAZOLE

This is a weaker base than imidazole

PYRAZOLE CONT’D

N

NOH2

NH

NHOH

OH2

NH

NHOH

OH

O

O

NH2NH2

+

RETROSYNTHESIS OF OXAZOLE

N

O

OH2N

OOH

N

OHO

NH

OO

OXAZOLE CONT’D

NH

OO

NH2

OO

X

X

OO

NH2

OR

A

BA

B

OXAZOLE CONT’D

• OXAZOLE IS COLOURLESS LIQ, SMELLS LIKE PYRIDINE, SOL, IN WATER, ARYL-SUBSTITUTED STRONGLY FLUORESCENT. SUITABLE AS LUMINOUS SUBSTANCES (LIQ SCINTILLATION COUNTERS OR USED AS BRIGHTENING AGENTS)

SUMMARY-RXNS

O NH

S

O

N

N

N

S

NE EE

N N

EE E

1,3-benzoxazole

• Colourless liq, sol. In water. Aroma constituent in cocoa, coconuts, walnuts and beer. Derivative occurs in fireflies.

S

N

Benzothiazole or 1,3-benzothiazole

• Colourless crystals, moderately sol in water, very soluble in ethanol

NH

N

Benzoimidazole

BENZO[b]THIPHENE

• Benzo[b]thiophene occurs in coal tar and roasted coffee beans

S

Benzo[b]thiophene

• Derivative used as antibacterial drug(with nitrophenyl side chain), colourless, oily liq, water insoluble, occurs in coal tar

O

Benzo[b]furan or 1-benzofuran

O

Isobenzo[b]furan or 2-benzofuran

• Colourless, fluorescent crystals,occurs in coal tar

O

Dibenzo[b,d]furan

• Electro subs occurs at C-3. Colourless solid leaflet crystals, mod. Sol in water. Occurs in coal tar and jasmine oil

NH

benzo[b]pyrrole or

1H-indole

• Bufotein-poison on frog skin; psilocin-causes hallucinations

NH

OHN(CH3)2

NH

N(CH3)2

OH

bufotein

psilocin

NOMENCLATURE SIX MEMB.

O O

2H-PYRAN 4H-PYRAN

NO

N

O

6H-1,2-OXAZINE 2H-1,3-OXAZINE

N N

PYRIDINE 3,4-DIHYDROPYRIDINE

NN

N

N

PYRIDAZINEPYRIMIDINE

N N

QUINOLINE ISOQUINOLINE

Si Sisiline silinane

P P

PHOSPHININE PHOSPHINANE

PYRILIUM ION

• Planar and slightly distorted hexagon. It is aromatic. Positive charge at 2,4,6.Hence nucleophilic attack at 2,4,6

O+

RING OPENING

• OH adds at pos 2 and with heating ring opens

O OOHOH O

+ +

OH-

• Ring opens to form 1,5-diketone or 1,5-dialdehyde

O O

RING OPENING CON’D

• Grignard reagent can also add at pos 2. Heating opens up the ring to form dienone

O O R O RRMgX

+

2H-PYRAN

• The parent compd has not yet been isolated. However, 2,2-disubstituted derivatives have been isolated

O Oparent

disubstituted derivative

THERMAL RING OPENING OF 2H-PYRAN DERIVATIVE

• This compd undergoes thermal ring opening

O Oheat

2H-PYRAN-2-ONE

• Bp of 208C, colourless liq. It behaves like 1,3-dienes and also like lactones

O O

2H-PYRAN-2-ONE

RXN OF 2H-PYRAN-2-ONE

O O

RMgX

O

2H-PYRAN-2-ONE

SYNTHESIS OF TETRAHYDROPYRAN

• Dehydration rxn catalyzed by acid. Loss of water with subsequent cyclization

OHOH O

heat

2H-CHROMENE

• It is found in natural products like plants

O

2H-CHROMENE

OR 2H-1-BENZOPYRAN

2H-CHROMEN-2-ONE or coumarin

• Occurs in plants (lavender), mp 68C, colourless crystalline solid. Reacts like lactone.

O O

2H-CHROMENE-2-ONE

OR 2H-1-BENZOPYRAN-2-ONE

OR COUMARIN

LACTONE RING OPENING

• Ring opens to form free carboxylic acid

O O

OH

CO2HO -

1-BENZOPYRILIUM ION

• The derivative of this compd is found in leaves and flowers. It gives various colours to leaves and flowers

O+

BENZOPYRILIUM ION CONT’D

• Numerous red, blue and violet pigments of blossom and leaves are made of this derivative. Occurs as glycosides(anthocyanins)

O

OH

OH

OH

+

4H-PYRAN

• Unlike 2H-Pyran, the parent compd is known. It is synthesized from 1,5-diketone or 1,5-dialdehyde

O4H-PYRAN

SYNTHESIS OF 4H-PYRAN

O O O

_ H O2

heat

4H-PYRAN-4-ONE

• Mp 32C, colourless, crystalline. Occurs in the bark of larch tree; also formed by dry distillation of starch and cellulose. Also found in opium

O

O

4H-PYRAN-4-ONE

4H-1-BENZOPYRAN(4H-CHROMENE)

• Derivatives found in plants

O

4H-1-BENZOPYRAN

4H-CHROMENEOR

4H-CHROMEN-4-ONE(4H-1-BENZOPYRAN-4-ONE)

• Mp 59C, colourless needles. Also known as chromone. Derivative found in plants

O

O

4H-1-BENZOPYRAN-4-ONE

4H-CHROMENE-4-ONEOR

OTHER DERIVATIVES OF 4H-CHROMEN-4-ONE

• Phenyl at pos 2 gives FLAVONES, eg apigenin, leteolin. Occurs in yellow pigments in plants

O

OOH

OH

OHFLAVONE(APIGENIN)

FLAVONES CONT’D

• Flavones have a wide spectrum of biological activity-anti-tumor, anti-inflammatory. Also used as dyes in textile industry

O

OOH

OH

OH

OH

OH

FLAVONOL(QUERCETIN)

FLAVONES CONT’D

• Quercetin found in apples. Major constituent of red wine. Found to reduce incidences of cardiovascular diseases

O

OH

OH

OH

OH

OH

FLAVANOL eg catechin

Chroman, flavan, flavanol etc

• Constituent of vitamin E

O

3,4-Dihydro-2H-1-benzopyranCHROMANOR

Vitamin E

O

vitamin E

Flavan, flavanol

O

OH

O

FLAVANOLFLAVAN

DIBENZOPYRAN DERIVATIVES

O

HNO3

O

O

XANTHENE XANTHONE