The document discusses protecting groups in organic synthesis. It provides characteristics that a good protecting group should have such as being selectively introduced and removed in good yields without affecting other functional groups. Common protecting groups for amino groups are discussed, including carbamates like Boc and Cbz which are installed under mild conditions and removed under acidic or basic conditions. Other protecting groups for amines mentioned are amides, formamides, acetamides, and sulfonamides which are stable but removed under strong acidic or basic conditions. The document provides examples of protecting group introduction and removal in peptide and amine synthesis.

1. PRESENTED TO:
Pushpendra Soni
M.Pharm 1st sem
1900101072
Dr. Kuldeep Singh
Professor
FOP, IUL
PRESENTED BY:

2. Characteristics of a Good Protecting
Group in Organic Synthesis
It must react selectively in good yield to give a protected substrate is stable to the
projected reactions.
The protective group must be selectively removed in good yield by readily available,
preferably nontoxic reagents that do not attack the regenerated functional group.
The protective group should form a derivative (without the generation of new
stereogenic centers) 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.

3. R-FG
Free Functional group
(Reactive)
R-FG-PG
Masked Functional group
(Unreactive)
What are protecting groups ?
It plays an important role in multistep organic synthesis.
A protecting group is introduced into a molecule by chemical modification of a functional
group to obtain chemo selectivity in a chemical reaction.
When a chemical reaction is to be carried out selectively at one reactive site in a
multifunctional compound, other reactive sites must be temporarily blocked.
(PG)

4. PROTECTION FOR AMINO
GROUP
Amino groups easily undergoes reactions with oxidizing reagents, alkylating
reagents, and many carbonyl compounds.
In order to prevent the amino group from undergoing such reaction it must be
suitably protected.
Many methods are available for protecting amino groups.
It is due to peptide synthesis has become very important.
It is not possible to build a peptide of specific structure from it component amino
acids unless the amino groups can be suitably protected

5. Why protection group are required
in amines
Primary and secondary (1° and 2° ) amine are deprotonate easily with some groups
(specially alcohol)
Organometallic group easily remove hydrogen from primary and secondary amines
Basic group are also responsible for removal of hydrogen
Protecting group is required to avoid all of these type of reaction during process.
Protection is required for longer period of time but it is easy to cleaved after product
formation ........

6. METHODS
OF PROTECTING
AMINO GROUP

7. 04
METHODS OF PROTECTING
AMINO GROUP
01 02
03

8. 1. Carbamate as Protecting group for amines
Protecting group for amines
Formation
• t-Butyl carbamate (Boc group):-
"Boc-protection"
Amine
( can be primary
or secondary)
Carbamate
"Boc- protected
amine"
Carbamates are practical protecting groups for amines. They can be installed and removed under
relatively mild conditions.

9. referred to as
"Boc₂O" or "Boc anhydride"
L-phenylalanine
methyl ester N-Boc) L-phenylalanine
methyl ester
Specific Example:-
Removal of the Boc group: acidic conditions

10. Mechanism

11. Application
Synthesis of dipeptide, glycine-alanine

12. Base
L-phenylalanine
methyl ester
(N-Cbz) L-phenylalanine
methyl ester
Specific
Example:-
• Cbz or Z corboxybenzyl
Carbamate
Amine
(can be primary
or secondary )
"Cbz-protected" amine
Formation
Cbz - protection

13. • Cbz or Z corboxybenzyl
Removal of the cbz group: acidic conditions

14. 2. AMIDE AS PROTECTING GROUP FOR
AMINE
Amides are readily prepared from an amine and an acid
chloride or anhydride. These are relatively more stable
compounds that, classically, are cleaved by heating in
strongly acidic or basic solutions.

15. FORMAMIDE
Formation
Cleavage - Removed with strong acid
Secondary amine react with ethylformate to form formamide (HCOONH2)

16. Formation
ACETAMIDE
Cleavage - Removed with strong acid
Secondary amine react with acetic anhydride to form acetamide (CH3CONH2)

17. Formation
Cleavage: - base (K2CO3, MeOH, reflux)- NH3, MeOH
TRIFLUOROACETAMIDE
Secondary amine react with tri floroacetic anhydride to form Trifluoroacetamide
(CF3CONH2)

18. Formation
Cleavage: - - Strong acid, sodium Naphthalide , Na(Hg)
SULFONAMIDE p-Toluenesulfonyl

19. Refrence
• March, J; Smith, M.B.; March's Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure; Wiley Publication; Sixth Edition; pp 1271-1279
• Hanson, J.R.; Protecting Groups in Organic Synthesis; Sheffield Academic Press; pp
8-80
• Organic chemistry .org
https://www.organic-chemistry.org/protectivegroups/amino.shtm
• Master organic chemistry ( protecting group for amine)
https://www.masterorganicchemistry.com/2018/06/07/protecting-groups-for-amines-
carbamates

20. Refrence
• Protective groups in organic synthesis, third edition, theodora.W.Greene, Peter
G.M. Wuts
• John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic
Chemistry, second edition. W. A. Benjamin, Inc., Menlo Park, CA. ISBN 0- 8053-8329-
8.
• Protection of Carboxyl Groups E. Haslam Department of Chemistry University
of Sheffield, Sheffield, England
• Theodora W. Greene, Peter G. M. Wuts (1999). Protecting Groups in Organic
Synthesis (3 ed.). J. Wiley