Protecting groups
- 1. PROTECTING GROUPS Presented by, Vikas R. Mathad I M. Pharm. Dept. of Pharmachemistry SJMCP
- 2. Contents ▪ Introduction ▪ Role of protection in organic synthesis ▪ Protection for the Hydroxyl group ▪ Protection for the Carbonyl group ▪ Protection for the Carboxyl group ▪ Protection for the Amino group
- 3. Introduction ▪ A group, the use of which makes possible to reactive functional group selectivity in presence of a more reactive group is known as protecting group. ▪ It plays an important role in multistep organic synthesis. ▪ In many preparations of delicate organic compounds, some specific parts of their molecules cannot survive the required reagents or chemical environments.
- 4. Properties ▪ It must react selectively in good yield to give a protected substrate that is stable to the projected reactions. ▪ The protective group must be selectively removed in good yield by readily available, preferably non toxic reagents that do not attack the regenerated functional group. ▪ The protective group should form a derivative (without the generation of new stereo genic centres) that can easily be separated from side products associated with its formation or cleavage. ▪ The protective group should have a minimum of additional functionality to avoid further sites of reaction.
- 5. Protection of Hydroxyl group ▪ Principle – The lone pairs of electrons on the hydroxyl oxygen of alcohols impart nucleophilicity to them. Therefore, alcohols react readily with oxidizing agents to give carbonyl compounds and with other electrophiles, alkyl halides and acyl halides they give ethers and esters, respectively.
- 6. Ethers as protecting groups for alcohols
- 7. Esters as protecting groups for alcohols ▪ Formate esters: HCOOR Formation- Cleavage-
- 8. Cyclic acetals and ketals ▪ Ethylidene acetals: Formation- Cleavage-
- 9. Cyclic acetals and ketals ▪ Acetonides: Formation- Cleavage- A variety of acid – catalysed hydrolysis conditions can cleavage an acetonide- i. 1N HCl / THF (1:1), 20ºC ii. 2N HCl, 80ºC
- 10. Cyclic acetals and ketals ▪ Cyclic carbonates: Formation- Cleavage-
- 11. Protection of Carbonyl group ▪ Dimethyl acetals and ketals: RR₁C(OCH₃)₂ Formation- Cleavage-
- 12. Protection of Carboxylic acids ▪ Esters Methyl ester: RCOOCH₃ Formation- Cleavage-
- 13. Protection of Carboxylic acids ▪ Amides – Formamide: Formation- Cleavage-
- 14. Protection of Carboxylic acids ▪ Hydrazides Formation- Cleavage-
- 15. Protection of Amino group ▪ Carbamates: RR₁NCOOCH₃ – Methyl Carbamate Formation- Cleavage-
- 16. Protection of Amino group ▪ Amides – Formamide: RR₁NCHO Formation- Cleavage-
- 17. Protection of Amino group ▪ Amides – Acetamide: RR₁NCOCH₃ Formation- Cleavage-
- 18. Reference ▪ Organic synthesis, Dr. Jagdamba Singh and Dr. L.D.S. Yadav, Eleventh edition 2015, Chapter 7, Page No., 696-736.