The document discusses the role of protecting groups in organic synthesis, emphasizing their importance in selective reactions amidst more reactive functional groups. It outlines various protective strategies for hydroxyl, carbonyl, carboxyl, and amino groups, detailing specific reagents and methods for their formation and cleavage. The properties of effective protecting groups are also highlighted, ensuring stability and selective reactivity during multi-step syntheses.

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.