Protecting group

A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction.

Quotes

• The protecting group reagent must react selectively (kinetic chemoselectivity) in good yield to give a protected substrate that is stable to the projected reactions.
  The protecting group must be selectively removed in good yield by readily available reagents.
  The protecting group should not have additional functionality that might provide additional sites of reaction.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 3 : The Concept of Protecting Functional Groups

• Protection of the amino group in amino acids plays a crucial role in peptide synthesis. N-Benzyl groups (N-Bn) are especially useful for replacing the N-H protons in primary and secondary amines when exposed to organometallic reagents or metal hydrides. … Acylation of primary and secondary amines with acetic anhydride or acid chlorides furnishes the corresponding amides in which the basicity of the nitrogen is reduced, making them less susceptible to attack by electrophilic reagents. … Treatment of primary and secondary amines with methyl or ethyl chloroformate in the presence of a tertiary-amine furnishes the corresponding methyl and ethyl carbamates, respectively. The protected amines behave like amides; hence, they no longer act as nucleophiles. … The benzyloxycarbonyl group (abbreviated as Cbz or Z) is one of the most important nitrogen-protecting groups in organic synthesis, especially in peptide synthesis. … The t-butoxycarbonyl group (Boc) is another widely used protecting group for primary and secondary amine.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 3 : The Concept of Protecting Functional Groups

• The most important protecting groups for alcohols are ethers and mixed acetals. … Methyl ethers are readily accessible via the Williamson ether synthesis, but harsh conditions are required to deprotect them. … t-Butyl ethers are readily prepared and are stable to nucleophiles, hydrolysis under basic conditions, organometallic reagents, metal hydrides, and mild oxidations. … Benzyl ethers are quite stable under both acidic and basic conditions and toward a wide variety of oxidizing and reducing reagents. Hence, they are frequently used in organic syntheses as protecting groups. … The PMB ether, also referred to as an MPM ether [(4-methoxyphenyl)methyl], is less stable to acids than a benzyl ether. … Trityl ethers have played an important role in the selective protection and manipulation of -CH₂OH groups in carbohydrate chemistry. … The popularity of silicon protecting groups stems from the fact that they are readily introduced and removed under mild condition. Moreover, a wide variety of silylating agents are available for tailor-made protection of ROH groups. The THP group is a widely used protecting group; it is readily introduced by reaction of the enol ether dihydropyran with an alcohol in the presence of an acid catalyst. … The use of carboxylic acid esters as protective groups for alcohols is limited since they may undergo acyl substitution, hydrolysis or reduction.
  • George S. Zweifel and Michael H. Nantz, Modern Organic Synthesis (2006), Ch. 3 : The Concept of Protecting Functional Groups