The document discusses protecting groups, focusing on protecting alcohols. It defines protecting groups as functional groups that are stable to reaction conditions but can be easily removed to regenerate the original functional group. The document outlines criteria for protecting groups and then discusses various methods for protecting alcohols, including using acetals, ethers, and silyl ethers. It provides examples of specific protecting groups like THP, MEM, benzyl ethers, and trialkylsilyl ethers.

1. PROTECTING GROUPS
Prepared By :
MAHENDRA G S
M-Pharm,Pharmaceutical
Chemistry
JSSCP, MYSURU

2. Definition of Protecting Groups
Criteria for Protecting Groups
Protection of alcohols
Protection of amines
Protection of aldehydes & ketones
CONTENTS

3. Definition
OEt
O O
OEt
OOH
NaBH4
OH OH
LiAlH4
The ester cannot be directly reduced leaving
the ketone unaffected

4. The problem may be circumvented
in two ways:
a) By the use of protecting groups
b) By changing the synthetic
strategy to theTM
Solution of problem

5. If it is necessary to reduce an ester in
presence of a ketone then
First the ketone must be converted to
a function which is stable to the
reducing agent/
The ester then be reduced and
ketone subsequently regenerated.
Solution of problem

6. Protection of a ketone during reduction
of an ester
OEt
O O
OH
O
OEt
O
OO
OH
OO
overall
HOCH2CH2OH/H+
LiAlH4
H3O+

7. Simple to introduce in a molecule, in
good yield
Stable to the reaction conditions for
the next step
Easy to remove to get back same
functional group, in good yield
Criteria for protecting groups

8. Following methods have been used
to protect alcoholic group
1. Use of acetals
2. Use of alkyl ethers
3. Use of silyl ethers
PROTECTION OF ALCOHOLS

9. It includes
Tetrahydropyranyl (THP)
derivatives
Methoxyethoxymethyl (MEM)
derivatives
PROTECTION OF ALCOHOLS
1. Use of acetals

10. Acetals as protecting groups for
alcohols (THP)
R OH +
O OOR
Tetrahydropyran
(THP)
H+
or
OTHPR
RCH2OTHP is stable to oxidation, reduction
& base
H2O/H+
R OH
Deprotection
Protection

11. Acetals as protecting groups for
alcohols (MEM)
R OH
+
Cl O
O
or
OMEMR
R OH
Methoxethoxymethyl (MEM)
RCH2OMEM is stable to
oxidation, reduction & base
H+
Protection
Deprotection
O O
O
R

12. It includes
benzyl ethers
t-butylethers
PROTECTION OF ALCOHOLS
2. Use of ethers

13. Benzyl ethers as protecting groups for
alcohols
R OH+Cl Ph R O Ph
pyridine
R OH
H2/P
d
Benzyl ether is stable to base,
mild acid, oxidation & reduction
Protection
Deprotection

14. t- Butyl ethers as protecting groups for
alcohols
R OH +
OH R O
or
H+
Protection
R OH
H3O+
Deprotection
t-Butyl ether is stable to base,
mild acid, oxidation & reduction

15. PROTECTION OF ALCOHOLS
3. Use of silyl ethers
R OH + Me3SiCl R O
SiMe3pyridine
Protection
R OH
or R OTMS
H+Deprotection
Trimethylsilyl ether is stable
to base, oxidation & reduction

16. PROTECTION OF ALCOHOLS
3. Use of silyl ethers
Trimethylsilyl ethers are attacked by
certain nucleophiles.
To overcome this problem a number
of more bulky trialkylsilyl protecting
groups have been developed

17. Bulky trialkylsilyl protecting
groups
OR
Si
OR
Me
Me
Si Si
Ph
Ph
OR
I II III
I, Triisopropylsilyl ether (TIPSOR)
II, t-Butyldimethylsilyl ether (TBDMSOR)
III, t-Butyldiphenylsilyl ether (TBDPSOR)