This document discusses protecting groups in organic chemistry. Protecting groups are atoms or groups that are temporarily attached to functional groups to prevent undesirable side reactions from occurring. The document defines protecting groups and lists advantages and disadvantages. It provides examples of common protecting groups for alcohols, amines, carbonyls, and carboxylic acids. Guidelines for selecting protecting groups include being inert, easily removed, allowing desired reactions while preventing undesired ones, not introducing new stereocenters, and being easily and selectively removed under mild conditions. References for further information are provided.

1. Organic Chemistry
“Protective groups”
DEC 17 , 2015
Raed H. AL- Hweiyyan

2. 1- Definition of protecting groups.
2- Most common group protected.
3- Most common protecting group.
4- Mechanisms of the reaction of protecting group.
5- Know why and when do you need to protect a functional group.
6- References.
Outline

3. - Protecting groups are groups of atoms that are attached to (and later
removed from) a functional group to mask it from competitive
undesired reactions.
- Advantages: Allows reactions that otherwise would not be possible.
- Disadvantages: extra steps (at least 2 - protection and de protection),
lowered yield, low atom economy, added mass of PG on substrate.
- Considerations: protecting group and both protection / de protection
sequences must be compatible with all other desired steps and other
functional groups.
Definition

4. 1- Are inert and small compared to the mass of what you are trying to make.
2- Can be applied and removed in great yield.
3- Allow the functionality to survive the reaction conditions necessary, BY MASKING THE
REACTIVITY OF PROTECTED GROUP.
4- Do not introduce stereo-centers. Uncontrolled stereo centers in the protecting group
complicate the manipulation and handling of the material because the amount of dia
stereomers increases.
5- Allow selective and easily de protected under mild conditions.
6- Cheap & commercially available Easy & efficient introduction.
7- Protecting groups add extra steps to your synthesis more steps cost time and money.
Protecting groups

5. Ether protectionEther silyl protectionEster protection
Acetoxy (AC) Methyl (Me)Trimethylsilyl (TMS)
Alcohol Protecting Groups

6. boring is good!
Ether protecting group
need very harsh
condition to break ,
how to cleave them with
very strong acid (e.g.
with hydroiodic acid, HI)
ethers are inert to pretty
much any other reaction
condition you can name.
……………………. So

7. The Si-F bond
,steric
hindrance

8. • Also note: TMS is
not a protecting
group for 1°
alcohols. Too
unstable! !(TBDPS)

9. Amine Protecting Groups
?

10. Amide protectionAmine protection
Benzyl (Bn) Acetyl (Ac)

11. Sulfonamide protectionCarbamate Protection
(tert-Butyloxycarbonyl (BOC (Tos).Tosyl

12. Carbonyl Protecting Groups
1- Ketones and aldehydes have π* orbitals as the lowest unoccupied molecular
orbitals.
2- Nucleophiles interact with this orbital by doing addition.
3- Bases interact with this orbital by deprotonation at the alpha position.
3- Two things can happen to: Addition and Deprotonation / polymerization. Both
are governed by π*.

13. Carbonyl Protecting Groups
-Dimethyl acetal
-1,3-Dioxane
1,3--Dioxolanes
Dithiane - 1,3-
Dithiolanes - 1,3-

14. O,O-acetals
1- Preparation: diol react with aldehydes or ketones in the presence of acid
catalyst.
- Acetal is prepared easier than ketal.
- Cyclic is easier than acyclic.
- Bulky carbonyl react slowly.
- Electron-withdrawing group of aromatic ring promotes the reaction.
2- Deprotection by acidic hydrolysis:
1) 1,3-dioxolane > 1,3-dioxane.
2) 1,3-dioxane of ketones > 1,3-dioxane of aldehyde.

15. Carboxylic Acid Protecting Groups
Methyl ester Benzyl ester
tert-Butyl Ester

16. Silyl ester
Oxazoline

17. Protect the aldehyde selectively in the presence of ketones
1 MeOH, dry HCl, 2 min, reflux, 12 min
2 deprotection 2N H2SO4, MeOH, H2O, reflux
Reference: J. Chem. Soc. 1953, 3864.

18. TMSCl, Pyr
CH2Cl2

22. 1. Comprehensive Synthetic Organic Chemistry, 6, 631-701.
2. Protective Groups in Organic Synthesis 2nd ed. Greene, T.W.; Wuts, P.G.M
3. Synthetic Organic Chemistry Michael B. Smith, 629-672. A very smart discussion.
2.4. Advanced Organic Chemistry part B: Reactions and Synthesis 3rd ed. Carey, F.A.; Sundberg,
R.J. pp. 677-92
References
-Oxazoline