This document discusses aromatic heterocyclic compounds. It begins with an introduction to aromatic heterocycles and aromaticity. Aromatic heterocycles contain a cyclic structure with both carbon and heteroatoms that satisfy the rules of aromaticity. Approximately two-thirds of organic compounds are aromatic heterocycles. The document then focuses on the structures, syntheses and reactions of pyridine and pyrrole as examples of important aromatic heterocyclic compounds. It describes the structures and mechanisms of common syntheses for these compounds. It also outlines some characteristic reactions including electrophilic substitution, oxidation, and addition reactions. The document references several textbooks and online sources for further information.

1. Contents:
1) Introduction to aromatic Heterocycles
2) Aromaticity
3) Structure, Synthesis and reactions of
some common aromatic heterocyclic
compounds

2. 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

3. 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

4. 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

5. Page no:74 and 27 Heterocyclic Chemistry, 2nd Edition, By Joule And Smith
Synthesis Of Pyridine:

6. Mechanism of that reaction is shown on next slide
Page no: 912. Organic Chemistry By Mehta Mehta

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

8. Hantzsch Dihydropyridine Synthesis:
http://jpkc.zju.edu.cn/k/146/Organic_Chemistry_Level_1/Presentations/Hantzsch_Dihydropyridine_Synthesis.pdf

9. http://jpkc.zju.edu.cn/k/146/Organic_Chemistry_Level_1/Presentations/Hantzsch_Dihydropyridine_Synthesis.pdf
The reaction can be
visualized as proceeding
through a Knoevenagel
Condensation product as a
key intermediate

10. http://jpkc.zju.edu.cn/k/146/Organic_Chemistry_Level_1/Presentations/Hantzsch_Dihydropyridine_Synthesis.pdf
a second key
intermediate is an
ester enamine,
which is produced
by condensation
of the second
equivalent of the
β- ketoester with
ammonia

11. Further condensation between the two fragments gives the
dihydropyridine derivative.

14. SOME REACTIONS OF PYRIDINE
PYRIDINE AS A CATALYST:

15.  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 alkylation
Reaction with nitrobenzene
Reaction 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:

18. 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 Chemistry
Page no:53 Heterocyclic Chemistry, 2nd Edition, By Joule And Smith

19. As per given on previous slide
NUCLEOPHILIC SUBSTITUTION REACTION OF PYRIDINE

20. REACTION WITH REDUCING AGENT:

21. 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

22. SYNTHESIS OF PYRROLE
PAAL-KNORR SYNTHESIS:

23. HANTZSCH SYNTHESIS:

24. MECHANISM:

25. 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:

26. 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

27. FORMATION OF N-SUBSTITUTED PYRROLE

28. REFERENCES:
Clayden, Greeves, Warren and Wothers Organic Chemistry
Hawley’s Condensed Chemical Dictionary, 11th Edition, Revised By Irving And
Richard
 Organic Chemistry By Mehta Mehta
Heterocyclic Chemistry, 2nd Edition, By Joule And Smith
 Hydrogen Storage Technology: Materials and Applications
www.chem.ucla.edu/harding/tutorials/aromaticity.pdf
jpkc.zju.edu.cn/k/146/Organic_Chemistry_Level_1/Presentations/Hantzsch_Dihydropyridin
e_Synthesis.pdf
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