This document discusses retrosynthetic analysis approaches for aromatic compounds. It covers aromatic electrophilic and nucleophilic substitution reactions, including addition of cationic synthons, Friedel-Crafts alkylation and acylation, and substitution of diazonium salts. It also discusses aromatic side chain transformations through functional group interconversion and nucleophilic aromatic substitution of halides.

1. RETROSYNTHETIC APPROCH TO ORGANIC SYNTHESIS Dr. Shaikh S. Nizami Department of Chemistry University of Karachi

2. RETROSYNTHESIS OF AROMATIC COMPOUNDS

3. CONTENTS 1.Aromatic Eletrophilic Substitution Reactions 2.Aromatic Nucleophilic Substitution Reactions

4. Retrosynthesis of Aromatic Electrophilic Substitution Reactions Addition of cationic synthons to the aromatic ring

5. Reagents for Aromatic Electrophilic Substitution

6. Reagents for Aromatic Electrophilic Substitution

7. Friedel-Crafts Alkylation

8. Retrosynthesis of BHT & Synthesis

9. Friedel-Crafts Acylation

10. Friedel-Crafts Acylation

11. One-carbon electrophile for aromatic synthesis

12. Retrosynthesis of Piperonol (perfumery compound) & Synthesis

13. AROMATIC SIDE CHAINS BY Function Group Interconversion Y X Reagent Reduction -NO 2 -NH 2 H 2 , Pd, C Sn, conc.HCl -COR -CH(OH)R NaBH 4 -COR -CH 2 R Zn/Hg/conc.HCl

14. AROMATIC SIDE CHAINS BY Functional Group Interconversion Oxidation Y X Reagent - CH 2 Cl -CHO hexamine - CH 2 R -CO 2 H KMnO 4 -CH 3 - COR -OCOR R’CO 3 H

15. Aromatic Side Chains by Functional Group Interconversion Substitution Y X Reagent -CH 3 -CCl3 Cl 2 ,PCl 5 - CCl 3 -CF3 SbF 5 -CN -COOH HO-, H 2 O

16. Nucleophilic Aromatic Substitution Reactions Addition of an oxygen atom to an aromatic ring Add anionic reagents RO - to an Aromatic compound with a leaving Group .

17. Nucleophilic Aromatic Substitution Nucleophilic aromatic substitution works best when the leaving groups is N 2 (diazonium salts) The synthetic sequence is nitration, reduction,diazotisation and substitution

18. Nucleophilic Aromatic Substitution

19. Retrosynthesis of Phenol

20. Synthesis HNO 3 H 2 SO 4 Sn/H + HOAc Br 2 NaOH NaNO 2 /HCl H 2 O

21. Aromatic compounds made by nucleophilic displacement of daizonium salts Reagent_____ HO H 2 O RO ROH CN Cu(I)CN Br/Cl Cu(I)Br/Cu(I)Cl I KI H H 3 PO 2 or EtOH/H + ____Z_____

22. Retrosynthetic analysis & synthesis Subst. FGI

23. SYNTHESIS HNO 3 H 2 SO 4 H 2 Pd,c NaNO 2 ,HCl Cu(I)CN

24. NUCLEOPHILIC SUBSTITUTION OF HALIDES Direct displacement of halide from an aromatic ring is possible only if : There are ortho and para nitro groups OR Similar electron-withdrawing groups

25. NUCLEOPHILIC SUBSTITUTION OF HALIDES HNO 3 H 2 SO 4 Nu -

26. Retrosynthetic analysis Trifluralin B- a herbicide

27. SYNTHESIS HNO 3 H 2 SO 4 base N-Pr 2 NH