1. Six membered heterocyclic compounds with one X
Structure and Properties
The aromatic sextet is complete without participating of the lone pair of nitrogen
Molecular orbital
The unshared electrons is in sp2 orbital and in the same plane of the ring but other
P orbital (including N) is ┴ and has one electron, where it overlapped making the
aromatic system

2. Six membered heterocyclic compounds with one X
The difference between benzene and pyridine
1- Benzene symmetrical non-polar but pyridine polar
It resist electrophilic substitution only in N-atom or at meta-position
It is highly susceptible to neucleophilic substitution

3. Six membered heterocyclic compounds with one X
The difference between benzene and pyridine
2- It is basic compound [its basicity less than aliphatic amine]

4. Six membered heterocyclic compounds with one X
Similarity
Like that of benzene ,pyridine is resistant to oxidation, side chain can be oxidized

5. Six membered heterocyclic compounds with one X
Sources of Pyridine
Found in coal tar
Oxidation of picolines yields the pyridine carboxylic acids α β γ

6. Six membered heterocyclic compounds with one X

7. Six membered heterocyclic compounds with one X
The 3- isomer is Vitamin
The 4- isomer has been used in the form of its hydrazide in treatment of T.B

8. Six membered heterocyclic compounds with one X
Synthesis of Pyridine
Hantzsch pyridine synthesis

9. Six membered heterocyclic compounds with one X
Reaction of Pyridine
Pyridine behave as both
Tertiary amine with protonation, alkylation's, acylation,
and N-oxidation
Aromatic compounds with Neocleophilic substitution
and Electrophilic substitution

10. Six membered heterocyclic compounds with one X
Reaction of Pyridine
A: Electrophilic Substitution SE
Pyridine resemble highly deactivated benzene derivatives
It undergo nitration , sulfonation, and halogenation
only under very vigrous condition
chiefly at the 3-position

11. Six membered heterocyclic compounds with one X
Why mainly at c-3 ?

12. Six membered heterocyclic compounds with one X
In contrast to benzene, Pyridine is very unreactive to SE reaction ?
1- due to electron withdrawing effect of N in the ring
2- the intermediate is destabilized by electro negativity effect of N
3- rapid formation of pyridinium cation …. So resist further SE reaction

13. Six membered heterocyclic compounds with one X
B: Neucleophilic Substitution SN

14. Six membered heterocyclic compounds with one X
Example
1- Chichibabin Reaction

15. Six membered heterocyclic compounds with one X
Example
2- Alkylation or Arylation Reaction by Organolithium compounds

16. Six membered heterocyclic compounds with one X
C: Reaction at N-1
Alkylation

17. Six membered heterocyclic compounds with one X
C: Reaction at N-1
Acylation

18. Six membered heterocyclic compounds with one X
C: Reaction at N-1
Rx with lewis acid
Rx with peracids

19. Pyridine N-oxide

20. Six membered heterocyclic compounds with one X
Electrophilic ( Nitration)

21. Six membered heterocyclic compounds with one X
Neucleophilic

22. As before oxidation of Picolines
Reduction
Oxidation
D: Oxidation and Reduction
As before oxidation of Picolines

23. Fused Six membered heterocyclic compounds with one X
Quinoline
Benzo[b]pyridine
1-azanaphthaline
Isoquinoline
Benzo[c]pyridine
2-azanaphthaline
Both are weak bases
Both undergo SE more easly than pyridine in position 5 and 8
on benzoid ring, no on the deactivated N-ring Why?
Like pyridine , N-ring of quinoline and isoquinoline undergo SN
at α position

24. Fused Six membered heterocyclic compounds with one X

25. Fused Six membered heterocyclic compounds with one X

26. Fused Six membered heterocyclic compounds with one X
Synthesis of Quinoline Skraup Synthesis
Describe the mechanism

27. Fused Six membered heterocyclic compounds with one X
Bischler Nepieralski Synthesis

28. Fused Six membered heterocyclic compounds with one X
Electrophilic Substitution
Nitration
Sulfonation
Halogenation

29. Fused Six membered heterocyclic compounds with one X
Nucleophilic Substitution
Hydroxylation
Alkylation
Or Arylation
with organo-
Amination

30. Fused Six membered heterocyclic compounds with one X
Oxidation & Reduction
Reduction
Oxidation

31. Fused Six membered heterocyclic compounds with one X
Other fused ring

32. Fused Six membered heterocyclic compounds with one X Diazines
Used only in research
as building block for
more complex comp.
Three neucleobases
found in nucleic acid
cytosine
thyamine
uracil
-Found in folic acid
& cigarette der.
- Less basic than
the other two

33. Six membered heterocyclic compounds with two N Diazines
In DNA & RNA, these bases form H-bonds with their complementary Purines
DNA A________ T
G________ C
RNA A________ U
Chemical properties of Pyrimidines
in common with pyridine, as number of N-atoms in the ring increase
the ring π- electrons become less energetic
So SE gets more difficult while SN gets easier

34. Fused Six membered heterocyclic compounds with two X
Purines
Contain pyrimidine fused to imidazole ring

35. Fused Six membered heterocyclic compounds with one X

36. Miscellaneous Dibenzothiazine or Thiodiphenylamine
Drugs containing this nucleus used as antipsychotic and adrenergic blocker
H.W find 2 drugs and draw their structures

37. Miscellaneous Hypnotic, Sedative, Anxiolytic
Anticonvulsant, Muscle relaxant
Properties
Valium

38. Miscellaneous
Preparation of Valium