Protection & deprotection for the AMINE

1. PROTECTION FOR THE AMINE
GROUP
PRESENTED BY- INDRAJIT SAMANTA
M.PHARM ( PHARMACEUTICAL CHEMISTRY), 1ST SEM, 1ST YEAR
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY,
SPER, JAMIA HAMDARD, NEW DELHI

2. CONTENTS
INTRODUCTION
Qualities of a Good Protecting Group
Protecting Groups for Amino Groups
Carbamates as Protecting Groups for Amines
Amides as Protecting groups for Amines
Cyclic Imides As Protecting Group
REFERENCE:

3. INTRODUCTION
CHEMO SELECTIVITY
Which functional groups will
react
REGIO SELECTIVITY
Where it will react

4. INTRODUCTION
 Which functional group reacts first 1. Reaction
2. Condition
3. reagents

5. INTRODUCTION
 WHAT IS A PROTECTING GROUP?
A protecting group (PG) is a molecular framework that is introduced onto a specific functional
group (FG) in a poly-functional molecule to block its reactivity under reaction conditions needed
to make modifications elsewhere in the molecule.
R-FG PG R-FG-PG
Free functional group (reactive) MUSK FUNCTIONAL GROUP(
Unreactive)

6. QUALITIES OF A GOOD PROTECTING GROUP IN ORGANIC
SYNTHESIS
 (a) It should be readily, but selectively introduced to the desired functional group in a poly-
functional molecule.
 (b) It should be stable / resistant to the reagents employed in subsequent reaction steps in
which the group being masked (protected) is desired to remain deactivated (protected).
 (c) It should be capable of being selectively removed under mild conditions when its
protection is no longer required
TACTICAL CONSIDERATIONS
Easy & efficient
introduction
stable throughout
reaction, work up &
purification
efficient and
selective removal
under mild
conditions
should not create any
stereo-genic centre

7. PROTECTING GROUPS FOR AMINO GROUPS
 The basic problem of peptide synthesis is one of protecting the amino group.
 In bringing about interaction between the carboxyl group of one amino acid
and the amino group of a different amino acid, one must prevent interaction
between the carboxyl group and the amino group of the same amino acid.
 In preparing glycyl alanine, for example, one must prevent the simultaneous
formation of glycylglycine.
 Reaction can be forced to take place in the desired way by attaching to one
amino acid a group that renders the NH, unreactive

8. PROTECTING GROUPS FOR AMINO GROUPS

9. PROTECTING GROUPS FOR AMINO GROUPS
 Carbamates as Protecting Groups for Amines:
 Formation:-
 CLEAVAGE:

10. CARBAMATES AS PROTECTING GROUPS FOR AMINES:
 t-Butyl carbamate (Boc group):-
 FORMATION:
RR’NH + Me3COCOCl Base RR’NCOOCMe3
 CLEAVAGE:
RR’NCOOCMe3 3M HCl RR’NH

11. CARBAMATES AS PROTECTING GROUPS FOR AMINES:
 9-Fluorenylmethyl carbamate (Fmoc or 9-fluorenylmethyloxycarbonyl): 9-
Fluorenylmethyloxycarbonyl protection is used for an alcohol or amine and it is carried out
with an Fmoc-X reagent (X-CI or Nj) in the presence of pyridine or NaHCO3
 FORMATION:
 CLEAVAGE:

12. BENZYL CARBAMATE [BENZYLOXY-CARBONYL OR
CBZ GROUP (RRNCOOCH2PH)]:-
FORMATION:
CLEAVAGES:

13. AMIDES AS PROTECTING GROUPS FOR AMINES:-
 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.
 FORMAMIDE:
 FORMATION:
RR’NH + HCOOH DCC, Pyridine RR’NCHO
CLEAVAGE:

14. AMIDES
 AMIDES
 Amide condensation of phenylacetic acid and benzylamine with various catalysts under sealed conditions
 FORMATION
 Direct amide condensation of various carboxylic acids and amines by 8a ( SiO2

15. CYCLIC IMIDES AS PROTECTING GROUP FOR
PRIMARY AMINES:-
 Phthalimide:-
 FORMATION:

16. CYCLIC IMIDES AS PROTECTING GROUP FOR
PRIMARY AMINES:-
 CLEAVAGE:

17. OTHER PROTECTION FOR AMINE

18. SYNTHETIC APPLICATIONS
 1) synthesis of dipeptide (glycine alanyl )

19. APPLICATION:
 YU’s synthesis of Paroxetine:

20. SYNTHETIC APPLICATIONS
 Romero synthesis of HIV-I protease inhibitor:

21. SYNTHETIC APPLICATIONS
 Synthesis of beta- lactam in preparation of carpetimycin A:

22. SYNTHETIC APPLICATIONS
 SYNTHESIS OF BETA LACTUM ANTIBIOTIC:

23. SYNTHETIC APPLICATIONS
 SYNTHESIS OF 4- HYDROXYPHOSPHONINE :

24. SYNTHETIC APPLICATIONS
 SYNTHESIS OF AZASUGAR:

25. SYNTHETIC APPLICATIONS
 SYNTHESIS OF OTHER DURGS:

26. REFERENCES:
 Hanson, J.R.; Protecting Groups in Organic Synthesis; Sheffield Academic Press; pp 8-80.
 Morrison, R.T.; Boyd R.N.; Organic Chemistry; Prentice-Hall of India Private Limited; Sixth Edition- 2002;
pp. 1147.
 2,2,6,6-Tetramethylpiperidin-1-yloxycarbonyl: A Protecting Group for Primary, Secondary, and Heterocyclic Amines,
Joseph R. Lizza, Maximilian Bremerich, Stephanie R. McCabe, Peter Wipf,
Org. Lett. 2018. https://doi.org/10.1021/acs.orglett.8b02874