Heterocyclic compounds

the presentation contains reactivity, synthesis, mechanism and reactions of quinolines, isoquinolines and indoles.

1. Heterocyclic compounds

2. Quinolines and Isoquinolines

3. Reactivity

4. Quinoline and isoquinoline both have 1. Have basic, pyridine-like nitrogen atoms, which undergo electrophilic substitutions. 2. Are less reactive toward electrophilic substitution than benzene because of the electronegative nitrogen atom that withdraws electrons from the ring. 3. Electrophilic substitution occurs on the benzene ring rather than on the nitrogen-containing pyridine ring, and a mixture of substitution products is obtained.

5. Important method of synthesis

6. Combes Quinoline Synthesis The Combes reaction is a sequence of the following reactions: condensation of an arylamine with a 1,3-diketone, keto-aldehyde or dialdehyde providing enamine , and cyclodehydration to provide quinoline .

7. Mechanism

8. Friedlander Quinoline Synthesis The Friedliinder quinoline synthesis combines an α -amino aldehyde or ketone with another aldehyde or ketone with at least one methylene α to the carbonyl to furnish a substituted quinoline . The reaction can be promoted by acid, base, or heat.

9. Mechanism

10. Knorr Quinoline Synthesis The Knorr quinoline synthesis refers to the formation of a- hydroxyquinolines from p- ketoesters and aryl amines The intermediate anilide undergoes cyclization by dehydration with concentrated sulfuric acid

11. Mechanism

12. Skraup Reaction The Skraup reaction involves the synthesis of quinoline from the reaction of aniline and glycerol in the presence of a strong acid and an oxidant.

13. Doebner -Miller synthesis An primary arylamine with unsubstituted ortho -position is reacted with α , β -unsaturated compound in presence of an proton acid and an oxidant to give quinolines .

14. Mechanism

15. Examples

16. Bischler-Napieralski Reaction The Bischler-Napieralski ' reaction involves the cyclization of phenethyl amides in the presence of dehydrating agents such as P205 or POC13 to afford 3,4-dihydroisoquinoline products

17. Mechanism

18. Pictet -Spengler Isoquinoline Synthesis This reaction involves the condensation of a P- arylethyl amine with an aldehyde , ketone , or 1,2-dicarbonyl compound to give the corresponding tetrahydroisoquinoline

19. Mechanism

20. Pomeranz -Fritsch Reaction The Pomeranz -Fritsch reaction involves the preparation of isoquinolines via the acid- mediated cyclisation of the appropriate aminoacetal intermediate

21. Mechanism

22. General reactions

23. Indoles

24. Reactivity

25. indoles undergoes electrophillic substitution at C3 or C2 (if C3 is blocked ) indole anion is obtained at deprotonation . The indolyl anion get substituted at N to give N-substituted derivatives.

26. Important method of synthesis

27. Fischer Indole Synthesis The Fischer indole synthesis can be regarded as the cyclization of an arylhydrazone of an aldehyde or ketone by treatment with acid catalyst or effected thermally to form the indole nucleus

28. Mechanism

29. Madelung Indole Synthesis The intramolecular cyclization of N- acylated -o- alkylanilines in the presence of a strong base at elevated temperatures is known as the Madelung indole synthesis

30. Mechanism

31. Reissert Indole Synthesis The Reissert procedure involves base-catalyzed condensation of an α - nitrotoluene derivative with an ethyl oxalate which is followed by reductive cyclization to an indole-2carboxylic acid derivative

32. Mechanism

33. General reactions