ARYNES (BENZYNES) PharmD ppt by dr farhat sagir

benzenes

1. ARYNES (BENZYNES) By: Dr. Farhat Saghir

2. introduction Benzynes or Arynes are highly reactive uncharged chemical species derived from an aromatic ring by removal of two hydrogens or groups from adjacent carbon atoms. Thus they are 1,2-didehydrobenzenes or 1,2-didehydroarenes. Benzynes or arynes are commonly described as having a strained triple bond. However they possess some diradical character as well.

3. Structure Structure of benzynes can be represented by following resonance contributing structures…

4. The alkyne representation is the most widely accepted. However the cumulene and the diradical structures are also significant resonance contributors. The alkyne structure calls for sp -hybridized carbon atoms at the two bond termini of the triple bond. The rest of the ring skeleton consists of sp2 -hybridized carbon atoms. Thus, the aromatic character of the ring is still retained in the benzyne. Geometric constraints on the triple bond result in a reduced overlap of in-plane p-orbitals and thus a weaker triple bond than in an unstrained alkyne. In a chemical reaction, benzynes behave as electrophiles.

5. GENERATION (Formation): Benzynes may be generated in a chemical reaction in following ways… a) From aryl halides: Aryl halides can be treated with a strong base to remove an aromatic proton and generate benzyne via elimination.

6. b) From o-amino benzoic acid (anthranilic acid): This method involves diazotization of o-amino benzoic acids. After diazotization, loss of nitrogen and carbon dioxide generates benzyne.

7. c) From 1-amino benzotriazole: This method involves oxidative decomposition of 1-amino benzotriazole. The oxidized intermediate decomposes with elimination of two molecules nitrogen.

8. d) From o- dihalo aromatic precursors: o- dihalo aromatic compounds generate benzyne when treated with lithium amalgam (Li/Hg) or alkyl lithium (R–Li).

9. Reactions: Benzynes or arynes are very reactive reaction intermediates and show electrophilic character. They undergo nucleophilic addition, pericyclic and radical reactions. Following are the important reactions of benzynes…

10. a) Nucleophilic additions: Benzynes react with nearly all nucleophiles especially nitrogen bearing nucleophiles and carbanions to give addition product. For example…

11. b) Pericyclic cycloaddition reactions: They can be of various types such as… i . [4+2]-cycloadditions: Benzynes can undergo [4+2]-cycloaddition reactions. For example, Diels-Alder reaction between benzyne and butadiene occurs as follows…

12. Cycloaddition between benzyne and furan

13. ii. [2+2]-cycloadditions: Benzynes undergo [2+2]-cycloaddition reactions with a wide range of olefins especially with olefins bearing electron-donating substituents. For example, benzynes react with a ketene acetal to give benzocyclobutanones .

14. c) σ- bond insertion reactions: Benzynes can undergo carbon-carbon σ-bond insertion reactions. For example…

15. d) Metal catalyzed reactions: Metal catalyzed aryne chemistry is highly underdeveloped and involves complex reactions. An example is the palladium catalyzed [2+2+2]-cyclization of aryne and diyne in total synthesis of taiwanin -C (an antiviral drug).