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PROTECTION OF HYDROXYL GROUPS

Protection of hydroxyl groups  are ways to minimize if not eliminate the reactivity of hydroxyl groups in an organic synthesis. By now it should be apparent that hydroxyl groups are very reactive to many reagents. This is both an advantage and a disadvantage in synthesis. To avoid interference by hydroxyl groups, it often is necessary to protect (or mask) them by conversion to less reactive functions. The general principles of how functional groups are protected were outlined and illustrated in “PROTECTING GROUPS IN ORGANIC SYNTHESIS” post. In the case of alcohols the hydroxyl group may be protected by formation of an ether, an ester, or an acetal.

 Protection of Hydroxyl Groups by Ether Formation

A good protecting group is one that does everything you want it to do when you want it to. It must be easily put into place, stable to the reagents from which protection is required, and easily removed when desired. For this reason simple ethers such as methyl or ethyl ethers usually are not suitable protecting groups because they cannot be removed except under rather drastic conditions.


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More suitable ethers are phenylmethyl and trimethylsilyl ethers:

Both of these ethers are prepared easily by nucleophilic displacements (Equations 15-7 and 15-8) and can be converted back to the parent alcohol under mild conditions, by catalytic hydrogenation for phenylmethyl ethers (Equation 15-9), or by mild acid hydrolysis for trimethylsilyl ethers (Equation 15-10):

Protection of Hydroxyl Groups by Ester Formation

Esters are formed from the alcohol and acyl halide, anhydride, or acid (Section 15-4D). The alcohol can be regenerated easily by either acid or base hydrolysis of the ester:

Protection of Hydroxyl Groups by Acetal Formation

We have seen the reversible conversion of alcohols  to acetals under acidic conditions. The acetal function is a very suitable protecting group for alcohols under basic conditions, but is not useful under acidic conditions because acetals are not stable to acids:

An excellent reagent to form acetals is the unsaturated cyclic ether, 16. This ether adds alcohols in the presence of an acid catalyst to give the acetal 17:

The 3-oxacyclohexene (dihydropyran) protecting group can be removed readily by treating the acetal, 17, with aqueous acid:

An example of the use of 16 in protection of hydroxyl groups is given in PROTECTING GROUPS IN ORGANIC SYNTHESIS post.

Thanks for reading “Protection of Hydroxyls Groups”

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