Aromatic heterocycles

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 H ückel 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, 2 nd 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.

12. SOME REACTIONS OF PYRIDINE PYRIDINE AS A CATALYST:

13. 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:

14. 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, 2 nd Edition, By Joule And Smith

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

16. REACTION WITH REDUCING AGENT:

17. 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 6 π -electrons in the cyclic ring, following Hückel rule, imparts aromatic character to pyrrole. Page no: 912 Organic Chemistry By Mehta Mehta

18. SYNTHESIS OF PYRROLE PAAL-KNORR SYNTHESIS:

19. HANTZSCH SYNTHESIS:

20. MECHANISM:

21. 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:

22. 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

23. FORMATION OF N-SUBSTITUTED PYRROLE

24. REFERENCES: Clayden, Greeves, Warren and Wothers Organic Chemistry Hawley’s Condensed Chemical Dictionary, 11 th Edition, Revised By Irving And Richard Organic Chemistry By Mehta Mehta Heterocyclic Chemistry, 2 nd 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_Dihydropyridine_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