1. Aromaticity of heterocyclic compounds

2. Characteristics of aromatic compounds:
The structure must be cyclic with conjugated π bonds.
All atoms must be sp2 hybridized (i.e. double bond, cation or anion)
The compound must follow Hückel's Rule (4n + 2) π, where n = 0, 1, 2, 3, and so on).
Coplanar structure, with all the contributing atoms in the same plane.
Antiaromatic compound: They are cyclic, conjugated, with sp2 orbitals and follows 4n p rule.
Nonaromatic compound: All atoms are not sp2 hybridized.

5. The π-excessive heterocyclic compounds
They are Planar, fully conjugated, monocyclic systems with 6p electrons [i.e. follow (4n + 2)p electrons ,(n is an integer 0, 1, 2, etc.)]
In benzene each carbon corner has one unit of pi-electron, but this system (p-excessive) has in each corner more than one p-electron.
As a result of such a situation these molecules are generally more reactive toward electrophiles than benzene itself and generally have reactivity similar to that of electron rich benzene derivatives e.g. phenol or aniline.

6. In terms of valence bond theory these compounds are resonance hybrids
In terms of valence bond theory these compounds are resonance hybrids. However, resonance structures have charge separation.

7. The π-difficient heterocyclic compounds
They are Fully unsaturated six membered heterocycles, the heteroatom lone pair of electron does not contribute to this electronic configuration, in fact it is out of plane.
As a result the reactivity pattern toward electrophiles similar to that of p-deficient benzene derivatives e.g. nitrobenzene.
Moreover, having p-deficient carbon these molecules are reactive towards nucleophiles.

8. Reactivity of Five membered pi-Excessive Heterocyclic ring
Reactivity towards electrophilic substitution
Pyrrole, furan and thiophene are all much more reactive than benzene toward electrophilic substitution.
Thiophene is 100 times more reactive than benzene and pyrrole is the most reactive. Furan is less reactive than pyrrole because oxygen is more electronegative than nitrogen.

9. There are two position for electrophilic attack, C-2 and C-3.
Attack at C-2 is preferred because it yields a more stable carbocation (3 resonance structures, while attack at C-3 gives only 2 resonance structures(
E+ substitution occurs predominately at the 2-position (and if that position is already substituted, substitution occurs at the C-5).
If 2- and 5-position are already occupied, electrophilic substitution takes place at 3-position.

10. Although furan is the least aromatic (R. E
Although furan is the least aromatic (R.E. = 16 Kcal / mol), pyrrole (R.E. = 21 Kcal / mol) is most reactive. Thiophene which is the most aromatic with (R.E. = 29 Kcal / mol) is least reactive in electrophilic reactions.
This inverted reactivity pattern is due to the excessive participation of nitrogen lone pair is stabilising reactive intermediate for substitution at C-2.
21 Kcal/mol Kcal/mol Kcal/mol
Resonance energy
Reactivity sequence

11. Energy needed to go from the more aromatic pyrrole to its reactive intermediate is less than energy needed for a similar step with furan

12. 1- It was found that pyrrole reacts readily with some weak electrophiles, while thiophene and furan did not react

13. 2- Halogenation. Just as is true for aniline, the pyrrole ring is reactive toward bromine or chlorine, giving polysubstituted products
3- On the other hand, Due to the low aromaticity of furan, it reacts differently towards bromine

14. 4. Due to the sensitivity to acids nitration is conducted in aprotic media.
5- Only thiophene (least acid reactive can be nitrated by mixed acid nitration.

15. 6-Due to the low aromaticity of furan, its reactions in presence of a nucleophile gives in many cases adducts in which intermediate instead of undergoing proton loss reacts with nucleophile, e. g.

16. 7. Acylation of -excessive molecules can be made either in complete absence of a Lewis acid or in presence of ZnCl2. Pyrrole is acylated at N and not at C-
Furan and thiophene undergo Friedel –Craft reaction while pyrrole did not?

18. Reactions of Furan

19. Reactions of Thiophene

20. Reactions of Pyrrole

21. Acidic character of pyrrole
Unlike furan and thiophene, pyrrole is weakly acidic in nature. Thus, on reaction with metallic potassium or potassium hydroxide it forms a potassium salt, which is hydrolyzed back to pyrrole on treatment with water.

22. The acidic character of pyrrole is due to
Pyrrole is a resonance hybrid of various structures carrying a positive charge on nitrogen.
The greater stability of pyrrole anion compared to pyrrole.
The higher stability of the anion is due to resonance.

23. The acidic character is also reflected in the formation of pyrrolyl magnesium halide when reacted with alkylmagnesium halide.

24. The action of acids pyrrole, thiophene and furan

25. The mechanism of trimerization of pyrrole in acid medium

26. Nucleophilic Substitutions in Pyrrole, Furan and Thiophene
We have seen that the reactivity of pyrrole, furan and thiophene towards electrophilic substitution is in the following order
The reactivity of these rings towards nucleophilic substitution is in the opposite order

27. Pyrroles: the pyrrole ring is the least reactive and both 2-halo- and 3-halopyrroles behave like aryl halides in nucleophilic displacement. Thus, 2-chloropyrrole does not react with potassium tert-butoxide or with lithium aluminum hydride

28. Furans are more reactive towards nucleophilic displacement than pyrrole. 2-bromo- and 2-chloro react with piperidine at 200oC as follows:

29. The presence of electron-withdrawing groups on the furan ring facilitates nucleophilic displacement. Thus, 2-bromo-5-nitrofuran and methyl 2-bromo-5-carboxylate react readily with nucleophiles

30. It is of considerable interest that in these reactions the furans react about 10 times faster than the corresponding benzene analogues. This strong behavior has also been observed in theiophene series

31. Thiophenes
Nucleophilic substitution occurs much more readily within the thiophene series than it does for the corresponding benzene compounds. The thiophenes are at least 1000 times more reactive than corresponding benzene analogues (This increased reactivity has also been noticed in the electrophilic substitution of thiophenes compared to the corresponding benzene analogues).
The increased reactivity of thiophene ring nucleophilic substitution can be explained by Wheland intermediates involved in nucleophilic substitution of bromine in 2-bromo-5-nitrothiophene.

32. It is suggested that the sulfur atom causes additional stabilization by involvement of its d-orbitals "Structure III"

33. It must be noted that the lone pair of the sulphur atom also enters into resonance with the  electrons. X-ray studies indicate that the valency angle of C-S-C in thiophene is nearly 91o and not 105o as expected. This can be explained by assuming that the 3d orbital of sulphur are also used in resonance and following additional contributing structures may be written.

34. Copper-meditated nucleophilic substitutions of halo thiophenes are also of great synthetic utility. Examples of some transformation follow

35. Condensed Five-Membered Heterocycles
Fusing benzene ring with 2,3-positions of furan, pyrrole and thiophene leading to benzo[b]furan, indole and benzo[b]thiophene, respectively.

36. The molecular orbital description of benzofused heterocycles with one heteroatom is very similar to that furan, pyrrole and thiophene, the only added feature being distribution of - electrons. The reactivity of these fused heterocycles is lower than that of the parent heterocycle but still higher than that of benzene.
Position 3- is preferred position for electrophilic attack in indole, since it results in two more stable resonance structures in the aromatic sixtet of the benzene ring is preserved, which attack at position 2-yield one structure only in which the aromatic sixtet is preserved.

37. Attack at position 2-
Attack at position 3-

39. Electrophilic substitution in benzo[b]furan occurs mainly at C-2.