aromatic heterocycles

Contents:1) Introduction to aromatic

Heterocycles2) Aromaticity3) Structure, Synthesis and reactions

of some common aromatic heterocyclic compounds

Aromatic Heterocycles

Heterocycles that have aromatic character or that fulfil basic rules of aromaticity are known as Aromatic Heterocycles.Probably about two-third of organic compounds belong to this class!They number among some most significant compounds for human beings especially in medicinal field.

Page no 1147, Ch 43

Clayden, Greeves, Warren and Wothers Organic Chemistry

AROMATICITY:

RULE 1: An aromatic compound is cyclic and planar

RULE 2: compounds should have parallel p-orbitals

for continuous overlapping around the ring

RULE 3: It must follow Hückel rule

http://www.chem.ucla.edu/harding/tutorials/aromaticity.pdf

PYRIDINE ______Structure, Synthesis And Some Reactions

Lone pair of nitrogen does not take part in delocalization because it is perpendicular to the plane

Pyridine have 5 carbon atoms and one nitrogen atom.

All are sp² hybridized.

The p-orbital of nitrogen and all carbon atoms lie in the same plane.

Overlapping of p-orbitals result in delocalization of six π-electrons in the cyclic ring, following Hückel rule, imparts aromatic character to pyridine.

Page no: 912 Organic Chemistry By Mehta Mehta

Page no:74 and 27 Heterocyclic Chemistry, 2nd Edition, By Joule And Smith

Synthesis Of Pyridine:

Mechanism of that reaction is shown on next slide

Page no: 912. Organic Chemistry By Mehta Mehta

Page no: 309 & 310 Hydrogen Storage Technology: Materials and Applications

Hantzsch Dihydropyridine Synthesis:

http://jpkc.zju.edu.cn/k/146/Organic_Chemistry_Level_1/Presentations/Hantzsch_Dihydropyridine_Synthesis.pdf


The reaction can bevisualized as proceedingthrough a KnoevenagelCondensation product as akey intermediate


a second key intermediate is an ester enamine,which is produced by condensation of the secondequivalent of the β- ketoester with ammonia

Further condensation between the two fragments gives the dihydropyridine

derivative.

SOME REACTIONS OF PYRIDINE

PYRIDINE AS A CATALYST:

In most cases electrophilic substitution of pyridine occurs very much less readily than in the case of a correspondingly substituted benzene. some of typical electrophilic substitution reactions do not occur at all

Friedal- Crafts acylation and alkylationReaction with nitrobenzeneReaction with acetophenone

Milder electrophilic reagents such as diazonium salts, nitrous acid etc, which do not react with benzene, likewise fail to effect C-substitution. Usual nitration and sulphonation can not occur but may occur if and only if providing some special conditions.

ELECTROPHILIC SUBSTITUTION REACTIONS OF PYRIDINE:

Reactions with Oxidizing Agents:

This pyridine N-Oxide is a very useful synthetic intermediate, yields about 95% from this reaction

Page no:1153 Clayden, Greeves, Warren and Wothers Organic ChemistryPage no:53 Heterocyclic Chemistry, 2nd Edition, By Joule And Smith

As per given on previous slide

NUCLEOPHILIC SUBSTITUTION REACTION OF PYRIDINE

REACTION WITH REDUCING AGENT:

PYRROLE _____ Structure, Synthesis And Some Reactions

Pyrrole have 4 carbon atoms and one nitrogen atom.

All are sp² hybridized.

The p-orbital of nitrogen and all carbon atoms lie in the same plane.

Overlapping of p-orbitals result in delocalization of 6π-electrons in the cyclic ring, following Hückel rule, imparts aromatic character to pyrrole.

Page no: 912 Organic Chemistry By Mehta Mehta

SYNTHESIS OF PYRROLEPAAL-KNORR SYNTHESIS:

HANTZSCH SYNTHESIS:

MECHANISM:

Orientation of Electrophilic Substitution in Pyrrole Electrophilic substitution normally occurs at a carbon atoms instead of at the nitrogen. Also it occurs preferentially at C-2 (the position next to the heteroatom) rather than at C-3 (if position 2- is occupied it occurs at position 3). This is due to attack at C-2 gives more stable intermediate (it is stabilized by three resonance structure) than the intermediate resulted from C-3 attack (it is stabilized by two resonance structure) .

SOME REACTIONS OF PYRROLE:

Pyrrole is sensitive to strong acids.This is due to protonation occurs at one of C-3 and the resulting protonated molecule will add to another unprotonated pyrrole molecule this continues to give pyrrole trimer. This reaction is considered as electrophilic addition to pyrrole

http://www.copharm.uobaghdad.edu.iq/uploads/%D9%85%D8%AD%D8%A7%D8%B6%D8%B1%D8%A7%D8%AA/%D9%85%D8%AD%D9%85%D8%AF%20%D8%AD%D8%B3%D9%86/2nd%202s/H.C.4.pdf

FORMATION OF N-SUBSTITUTED PYRROLE

REFERENCES:Clayden, Greeves, Warren and Wothers Organic ChemistryHawley’s Condensed Chemical Dictionary, 11th Edition, Revised By Irving And Richard Organic Chemistry By Mehta MehtaHeterocyclic Chemistry, 2nd Edition, By Joule And Smith Hydrogen Storage Technology: Materials and Applicationswww.chem.ucla.edu/harding/tutorials/aromaticity.pdfjpkc.zju.edu.cn/k/146/Organic_Chemistry_Level_1/Presentations/Hantzsch_Dihydropyridine_Synthesis.pdfwww.copharm.uobaghdad.edu.iq/uploads/%D9%85%D8%AD%D8%A7%D8%B6%D8%B1%D8%A7%D8%AA/%D9%85%D8%AD%D9%85%D8%AF%20%D8%AD%D8%B3%D9%86/2nd%202s/H.C.4.pdf

aromatic heterocycles

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