Protecting group

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A Protecting group or protective group is introduced into a molecule by chemical modification of a functional group in order to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.

Acetal protection for LAH reduction

In many preparations of delicate organic compounds, some specific parts of their molecules cannot survive the required reagents or chemical environments. Then, these parts, or groups, must be protected. For example, lithium aluminum hydride is a highly reactive but useful reagent capable of reducing esters to alcohols. It will always react with carbonyl groups, and this cannot be discouraged by any means. When a reduction of an ester is required in the presence of a carbonyl, the attack of the hydride on the carbonyl has to be prevented. For example, the carbonyl is converted into an acetal, which does not react with hydrides. The acetal is then called a protecting group for the carbonyl. After the step involving the hydride is complete, the acetal is removed (by reacting it with an aqueous acid), giving back the original carbonyl. This step is called deprotection.

Protecting groups are more commonly used in small-scale laboratory work and initial development than in industrial production processes because their use adds additional steps and material costs to the process.

[edit] Common protecting groups

[edit] Alcohol protecting groups

Acetyl (Ac) - Removed by acid or base.
Tetrahydropyran (THP) - Removed by acid.
Methoxymethyl ether (MOM) - Removed by acid.
β-Methoxyethoxymethyl ether (MEM) - Removed by acid.
p-Methoxybenzyl ether (PMB) [1] - Removed by acid, hydrogenolysis, or oxidation.
Methylthiomethyl ether - Removed by acid.
Pivaloyl (Piv) - Removed by acid, base or reductant agents. It is stronger than other acyl protecting groups.
Silyl ether (most popular ones include trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS), and triisopropylsilyl (TIPS) ethers) - Removed by acid or fluoride ion.

[edit] Amine protecting groups

Carbobenzyloxy (Cbz) group - Removed by hydrogenolysis
tert-Butyloxycarbonyl (BOC) group (Common in solid phase peptide synthesis) - Removed by concentrated, strong acid. (such as HCl or CF₃COOH)
9-Fluorenylmethyloxycarbonyl (FMOC) group (Common in solid phase peptide synthesis) - Removed by base, such as piperidine.
Benzyl (Bn) group - Removed by hydrogenolysis
p-methoxyphenyl (PMP) group - Removed by Ammonium cerium(IV) nitrate (CAN)

[edit] Carbonyl protecting groups

Acetals and Ketals - Removed by acid. Normally, the cleavage of acyclic acetals is easier than of cyclic acetals.
Acylals - Removed by lewis acid.
Dithianes - Removed by metal salts or oxidizing agents