It gives the concise and complete protecting and deprotecting groups. A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis

1. Protection And Deprotection In
Organic Chemistry
Presented by Ashwani Kumar

2. Protecting groups for the amino group
Why must an amino group be protected?
N
nucleophile
acylation
O
N
O-
N
+
The most general way of masking nucleophilicity is by acylation.
it reacts with
electrophiles
because it is a
nucleophilic site
it can be deprotonated
by strong bases
because it can contain
acid protons

3. Protection of amino groups as carbamates
1) Carbobenzoxy group (CBz).
The most widely used group is the carbobenzyloxy group (Cbz).
O
OCl + RNH2
O
ORHN
O
ORHN
H2/cat
O
NR2HO
+ +PhCH3
CO2 +
HNR2
PhCH3
PROTECTION:
DEPROTECTION:
Because of the lability of the benzyl bond toward hydrogenolysis, the amine
can be regenerated from a Cbz derivative by hydrogenolysis, which is
accompanied by spontaneous decarboxylation of the resulting carbamic acid.

4. Protection of amino groups as carbamates
2) tert-butyloxycarbonyl (t-Boc)
RNH2
R2NH
O
OO
O
O
O
OO
N Ph
CN
R2N
O
O
t-butoxypyrocarbonate
2-(t-butoxycarbonyloxyimino)-2-phenylacetonitrile
BOC-ON
PROTECTION:
DEPROTECTION: CF3COOH, p-toluensulfonic acid

5. Protection of amino groups as amides
a) phtalimides
N
O
O
R
H2N NH2
RNH2 +
HN
HN
O
O
NaBH4/EtOHaq
N
O
R
HO H
H
O
RHN
O
BH4
-
HO
RHN
O
O
O
H2NR
+
PROTECTION: formation of the amide starting from the corresponding
acyl chloride or anhydride
DEPROTECTION: the use of these amides is characterized by the
possibility of a cleavage in mild conditions

6. b) trifluoroacetamides
O
AcO
OAcAcO
AcO
O
NH
COOEt
O
F3C
O
HO
OHHO
HO
O
NH2
COOH
Ba(OH)2
18h, 25°C
mild basic hydrolysis
b) trichloroacetamides, benzamides
O
CCl3N
H
R
NaBH4
ROH
O
CCl3N
H
R
BH3
RNH2 + Cl3CHO
O
PhH2N
R2AlH O
PhR2N
AlR
R2NH + PhCHO
partial
reduction

7. b) sulphonamides
NR2 S
O
O
Ar +
OMe
OMe
hν R2N
-
+ ArSO2 +
OMe
OMe
+ photochemical
cleavage
3) Allyloxy group
The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic
substitution. These reactions involve liberation of the carbamic acid by
oxidative addition to the palladium. The allyl-palladium species is
reductively cleaved by stannanes, phenylsilane, formic acid and NaBH4.

8. O
OR2N
O
OR2N
Pd
Bu3SnH
O
SnBu3R2N
RNH2 + CO2
H
Pd
Pd
0
H2O
Carbamic acid is removed by oxidative addition to palladium.
The allylpalladium is then reductively cleaved by stannane

9. Protecting groups for the carbonyl group
Why must a carbonyl group be protected?
it reacts with
nucleophiles
because it is an
electrophilic site
it reacts with
reducing agents
because it can
be reduced

10. Protection of carbonyl groups as acetals and thioacetals
PROTECTION: acid catalysed formation of acetals
O
R'R
+ HC OMe
OMe
OMe
MeO
R'
R
OMe
+
O
OMeH
O
R'R
+
OMe
OMe
MeO
R'
R
OMe
+
O
orthoester
2,2-dimethoxypropane
acid catalysed
exchange with
a ketal
+
R'O
R
R
OR'
2
O
RR
ROSiMe3
Me3SiO3SCF3 + Me3SiOSiMe3
trimethylsilyl trifluoromethylsulfonate
DEPROTECTION:
a)The carbonyl group can be deprotected by acid-
catalyzed hydrolysis by the general mechanism for
acetal hydrolysis
LiBF4/CH3CN

11. b) non hydrolityc conditions (β-haloalcohols)
DEPROTECTION (β-elimination):
H+
+
O
RR
OH
HO Br
O
BrO
R
R
3-bromo-1,2-dihydroxypropane
2,2,2-trichloroethanol
H+
+
O
RR
CCl3HO
OO
RR
CCl3Cl3C
2
PROTECTION:
+
O
RR
O
BrO
R
R
+
O
RR
HO
OO
RR
CCl3Cl3C
Cl
ClH
H
Zn
Zn
THF

12. c) non-acid conditions
DEPROTECTION:
+
O
RR
1,3-oxathiolanemercaptoethanol
SH
HO
BF3
∆/-H2O
O S
R R
PROTECTION:
O
RR
chloramine T
O S
R R
Ni-Raney
ROH
O S+
R R
CH3
S OO
-
N
ClNa+
X
H2O
X =Cl or NSO2Ar

13. Protecting groups for the carboxyl group
O
OHR
The carbonyl group
can be protected
in several ways
The hydroxy group is generally
protected as t-buthyl ester, that allows
cleavage in acid conditions, or as
2,2,2-trichloroethyl ester, that can be
cleaved in reductive conditions with Zn

14. a) oxazolidines
DEPROTECTION:
+
O
OHR HN
O
NR
O
N
H
R
(+)
N
O
R
H+
2,2-dimethylaziridine
PROTECTION:
HO
NH2
N
O
R
+
O
OHR
2-amino-2-methylpropanol
The carboxylic acid group can be regenerated by acidic hydrolysis or
converted to an ester by acid-catalyzed reaction with the appropriate
alcohol.

15. a) ortho
esters.
Ortho esters derived from simple alcohols are very easily hydrolyzed, and a
more useful ortho ester protecting group is the 4-methyl-2,6,7-
trioxabicyclo[2.2.2]octane structure. These bicyclic orthoesters can be
prepared by exchange with other ortho esters, by reaction with iminoethers,
or by rearrangement of the ester derived from 3-hydroxymethyl-3-
methyloxetan.
R
OMe
OMe
OMe CH3C(CH2OH)3
CH3C(CH2OH)3
BF3
NH
OR'R
O
O
O
R
O
O
OR
4-methyl-2,6,7-trioxabicyclo[2.2.2]octane
exchange
rearrangement

16. Protection of ester groups
•In general, the methods for protection and deprotection of carboxylic acids and
esters are not as convenient as those for alcohols, aldehydes, and ketones.
O O
O
+ Al
S
S
Al
SS
a) cyclic
b) acyclic
O
OR'
R
R
+ Al
S
S
Al
S
S
R2C
•It is, therefore, common to carry potential carboxylic acids through synthetic
schemes in the form of protected primary alcohols or aldehydes.
•The carboxylic acid can then be formed at a late stage in the synthesis by an
appropriate oxidation.
•This strategy allows one to utilize the wider variety of alcohol and aldehyde
protective groups indirectly for carboxylic acid protection.