pyrrole (o.c iv)

ORGANIC CHEMISTRYCHEMISTRY OF FIVE-MEMBERED

HETEROCYCLIC COMPOUND : PYRROLE

Mr. Srinivas R. BhairyB. Pharmacy (S.Y) (2012-2013)

StudentOrganic Chemistry- IV

Shivajirao S. Jondhle College Of PharmacyAsangaon, Tal.Shahapur, Dist.Thane

12/02/2013

SRINIVAS R. BHAIRY ORGANIC CHEMISTRY 1

OBJECTIVESIntroduction to Heterocyclic Compounds.Classification of Heterocyclic Compounds.Introduction to Pyrrole.Structure of Pyrrole.Preparation/ synthesis of Pyrrole.Properties of Pyrrole:- Physical Amphoteric ChemicalMedicinal uses/ Medicinal Compounds of Pyrrole.

2SRINIVAS R. BHAIRY ORGANIC CHEMISTRY

Introduction to Heterocyclic Compounds.Cyclic compounds with one or more other elements along with carbon atoms are heterocyclic compounds.Non carbon atoms are the hetero atoms.Common hetero atoms are the N, S, O etc.Number of drugs in pharmaceutical science are heterocyclic compounds.Hetero cyclic compounds may be of natural origin or synthetically available.


Classification of Heterocyclic Compounds

SRINIVAS R. BHAIRY ORGANIC CHEMISTRY 4

HETEROCYCLIC COMPOUNDS

5-MEMBERED HETEROCYCLIC COMPOUNDS

HETEROCYCL

IC COMPOUND

S HAVING ONE HETER

O ATOM

EXAMPLES:-1)FUR

AN2)PYRROLE3)THIOPHE

NE

HETEROCYCLI

C COMP

OUNDS

HAVING

MORE THAN ONE

HETERO

ATOMS.

EXAMPLES:-

1)PYRAZOLE

2)IMIDAZOLE3)OXAZ

OLE4)ISOXAZOLE5)THIAZOLE

6-MEMBERED HETEROCYCLIC COMPOUNDSHETER

OCYCLIC

COMPOUND

S HAVING ONE HETER

O ATOM.EXAMPLES:-1)PYRIDINE

2)PIPERIDIN

E

HETEROCYCLI

C COMP

OUNDS

HAVING

MORE THAN ONE

HETERO

ATOMS.

EXAMPLES:-

1) PYRIMI

DINE2)PYIRIDAZIN

E3)

PYRAZINE

7-MEMBERED HETEROCYCLIC COMPOUNDS.

EXAMPLES:-1) OXEPINE

2) 1-H-AZEPINE

CONDENSED HETEROCYCLIC COMPOUNDS.

EXAMPLES:-1)INDOLE

2) QUINOLINE3) ISOQUINOLINE

4) PURINE


5-MEMBERED HETEROCYCLIC COMPOUNDS HAVING ONE HETERO ATOM.

FURAN PYRROLE THIOPHENE

5-MEMBERED HETEROCYCLIC COMPOUNDS HAVING MORE THAN ONE HETERO ATOMS.

PYRAZOLE IMIDAZOLE OXAZOLE ISOXAZOLE THIAZOLE


6-MEMBERED HETEROCYCLIC COMPOUNDS HAVING ONE HETERO ATOM.

PYRIDINE PIPERIDINE

6-MEMBERED HETEROCYCLIC COMPOUNDS HAVING MORE THAN ONE HETERO ATOMS.

PYRIMIDINE PYIRIDAZINE PYRAZINE


7-MEMBERED HETEROCYCLIC COMPOUNDS.

OXEPINE 1-H-AZEPINE

CONDENSED HETEROCYCLIC COMPOUNDS.

INDOLE QUINOLINE ISOQUINOLINE PURINE

Introduction to Pyrrole.Pyrrole is an important five membered heterocyclic compound possessing a nitrogen atom as hetero atom.plays important role in the chemistry of living organisms.The essential structural feature of chlorophyll and heme is porphyrin, which consists of four Pyrrole rings held together by bridges.



Hemoglobin

Structure of Pyrrole.Pyrrole has 3 pairs of delocalized ∏ electrons. Two of the pars are shown as bonds and third pair is shown as a pair of nonbonding electrons on the hetero atom (nitrogen). These non bonding electrons are in a SP2hybrid orbital perpendicular to the p-orbitals. Since it is cyclic, planar molecule with three pairs of delocalized electrons, fulfils the criteria for aromaticity.


SOME DIFFERENT REPRESENTATION MODELS OF PYRROLE:-


Continuous…..

EXPLICIT STRUCTURE OF PYRROLE, WITH AROMATICITY INDICATED BY DASHED BONDS

NUMBERED SKELETAL STRUCTURE OF PYRROLE

BALL & STICK MODEL OF PYRROLE MOLECULE

SPACE- FILLING MODEL OF PYRROLE MOLECULE ( 3D- MODEL)

Continuous…..

Pyrrole is less aromatic than thiophene and more aromatic than furan. Therefore the total orbital diagram of Pyrrole is:


Continuous…..According to the resonance theory Pyrrole is considered as a resonance hybrid of the following contributing structures.

Among the resonance contributing structures 1. 2, and 3 are the main contributing structures to the resonance hybrid and hence resonance hybrid has a larger electron density at positions 2 and 5 than at 3 and 4.


Preparation/ synthesis of Pyrrole.Parrole is obtained commertially by distillation of coal tar. It is synthesized in the laboratory by the following methods:a. From Furan.b. From Distillation of Succinimide. c. From Acetylene and Ammonia. d. Paal - Knorr Synthesis.


a. From FuranFuran on heating with Ammonia in presence of Alumina (Al2O3) gives Pyrrole.


FURAN PYRROLE

b. From distillation of succinimide

Pyrrole is also obtained by the Distillation of Succinimide with Zinc dust.


SUCCINIMIDE PYRROLE ZINC OXIDE

c. From acetylene and ammonia Pyrrole can also be prepared by passing Acetylene and Ammonia through a Red-hot tube.


Red- hot tube

ACETYLENE AMMONIA ACETYLENE PYRROLE

d. Paal - Knorr Synthesis Pyrrole derivatives are synthesized by treating 1,4-diketone with Primary amine.


1,4-DIKETONE

PRIMARY AMINE

1,2,5- TRIALKYL PYRROLE WATER

Properties of PyrrolePhysical Properties :--


CHARECTERISTICS INFORMATION

Compound name pyrroleIUPAC name 1H-Pyrrolesynonym AzoleState Liquid/ solidAppearance colourlessSolubility Water- sparingly

Organic solvents- easily solubleMolecular formula C4H5NMolar mass 67.09 g mol−1

Melting point 23 °C, 250 K, -9 °FBoiling point 129-131 °C, 402-404 K, 264-268 °FDensity 967.00 kg/m³Vapour pressure 7 mmHg at 23 °Cviscosity 0.001225 Pa sChemical nature Weak acid & weak base ( amphoteric)

pyrrole is weak base because the lone pair of electrons of nitrogen atom contributes to the (4n+2) π-electron cloud (aromatic sextet). Hence the availability of these electrons is decreased and consequently it is a very weak base.Pyrrole also exhibit weak acidic properties. The weak acidic property is due to its formation of potassium pyrrole with potassium hydroxide.


Amphoteric Properties :--

KOH

PYRROLE POTASSIUM PYRROLE


Chemical Properties :--Pyrrole behaves both as a weak acid and exhibits the following chemical reactions.a. Reduction reaction.b. Oxidation reaction.c. Ring expansion reaction.d. Reimer-Tiemann reaction.e. Ring opening reaction.f. Electrophilic aromatic substitution reaction. (Nitration, Sulphonation, Chlorination, Iodination, Acetylation)

a. Reduction reaction.

Pyrrole on reduction with Zinc and Acetic acid gives 2,5-dihydropyrrole which on reduction with HI and Red phosphorus gives Pyrrolidine.


Zn/CH3COOH HI / P

PYRROLE 2,5 -DIHYDROPYRROLE

PYRROLIDINE

Pyrrole is oxidized to Maleinimide (Imide of acetic acid) with chromium tri oxide in Acetic acid.


b. Oxidation reaction.

CrO3 / CH3COOH

PYRROLE NASANT OXYGEN ATOM

Maleinimide (Imide of acetic acid)

Pyrrole ring expands on heating Potassium Pyrrole with Chloroform and Sodium Ethoxide.


c. Ring expansion reaction.

CHCl3 / C2H5ONa

POTASSIUM PYRROLE 3-CHLORO PYRIDINE

In presence of a strong base and Chloroform Pyrrole undergoes Reimer- Tiemann reaction to form Pyrrole-2-aldehyde.


d. Reimer-Tiemann reaction.

CHCl3 / KOH

PYRROLE PYRROLE-2-ALDEHYDEINTERMIDIATE

Pyrrole ring structure opens and forms Succinaldehyde dioxime (addition product) on Refluxing with Ethanolic Hydroxylamine.


e. Ring opening reaction.

NH2OH / C2H5OH

REFLUX

PYRROLE SUCCINALDEHYDE DIOXIME

pyrrole undergoes electrophilic aromatic substitution more readily at C-2 than C-3 position. Mechanism of electrophilic aromatic substitution : electrophilic aromatic substitution of pyrrole, involves the following steps:


f. Electrophilic aromatic substitution reaction.


Step-01) Generation of electrophile :

ELECTROPHILE

Step-02) Attachment of electrophile to the aromatic ring to form intermediate carbocation :

PYRROLE ELECTROPHILE INTERMEDIATE CARBOCATION


Step-03) Elimination of proton from carbocation to form substitution product :

INTERMEDIATE CARBOCATION

SUBSTITUTION PRODUCT

PROTON


In Pyrrole Electrophilic Substitution takes place at 2 or 5 positions. If these positions are filled substitution takes place at 3 or 4 positions. This can be explained as follows :

Substitution occurs preferentially at C–2 because the intermediate carbocation obtained by putting a substituent at this position is more stable than the intermediate carbocation obtained by placing a substituent at C-3. The intermediate resulting from C-2 substitution has 3 resonance contributors; they both have a positive charge on a relatively stable secondary allylic carbon. The intermediate resulting from c-3 Substitution has only 2-resonance contributors and has positive charge on a primary carbon, which is unstable. Thus substitution at C-2 predominates.


Continuous…..


HNO3/(CH3CO)2O10* NITRATION

SO3, PYRIDINE,100*CSULPHONATION

SO2Cl2 0*CCHLORINATION

I2 / Aq. KIIODINATION

(CH3CO)2O /SnCl4200*c

PYRROLE

2-NITRO PYRROLE

2-PYRROLE SULPHONIC ACID

2,3,4,5TETRACHLORO PYRROLE

2,3,4,5TETRAIODO PYRROLE

2-ACETYL PYRROLE

Medicinal uses/ Compounds.


Chemically procyclidine is α-cyclohexyl, α- phenyl-l-pyrrolidinepropanol.It is an anti-muscarinic drug used in the treatment of parkinsonism.

The following medicinal compounds possess pyrrole heterocyclic ring system.

PROCYCLIDINE

Anti-muscarionic Drugs are the agents that blocks the activity of muscarinic Acetylcholine receptors.Acetylcholine receptors are of two types :-I. Muscarinic receptors which

responds to muscarin neurotransmitters.

II. Nicotinic receptors which responds to nicotine.


PROCYCLIDINE

Continuous…..

BIBLIOGRAPHYI. A text book of Heterocyclic Chemistry, Rama Rao.II. Heterocyclic Chemistry, J. A. Joule and K. Mills, 4

th Ed., Blackwell Publishing, 2005.III. Wikipedia, the free encyclopedia.

(file:///G:/under%20cop/PYRROLE/Pyrrole.htm)IV. Graphical Images from www.google.com/pyrrole.



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pyrrole (o.c iv)

Health & Medicine