化学课件

5 Protective groups in organic synthesis 5.1 Introduction The selection of a protective group is an important step in synthetic methodology. 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. Many protective groups have been developed for this purpose.

The criteria for an ideal protective group:· It should be readily available.· It must react selectively in good yield to give a protected substrate.· The protective group 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.

Since few protective group can satisfy all these criteria for elaborate substrates, a large number of mutually complementary protective groups are needed and, indeed, are becoming available. 5.2 Selective removal of protective groups 5.2.1 Protective groups cleaved under basic conditions

Ester Acetate (Ac): K2CO3 or NH3/ MeOH Benzoate (Bz): K2CO3 or NH3/ MeOH Pivaloate (trimethylacetate) (Piv): NH3/ MeOH, slow Trifluoacetate: pH 7 Hydrolysis(relative rate): Acetate chloroacetate dichloroacetate trichlorocaetate 1 760 16000 100000

Amide: Stronger basic condition is required except trifluoroacetamide and phthalic imidine. O F3CCNR1R2 O C C O NHR

K2CO3/MeOH

Acyl transfer:

H2NNH2/MeOH or EtOH

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