Protection for the Sulfonamide —NH

In the presence of a 3-hydroxy group the benzyl group can be removed by hydrogenolysis with Pd(OH)2, but in its absence it is inert unless the nitrogen is acyl-ated.2  

Ceric ammonium nitrate is used to cleave the PMB group from a sulfonamide 

The Tmob group is introduced by reaction of the sulfonyl chloride with 2,4,6-trimethoxybenzylamine.  

The MP group is introduced on a sulfonamide through a Cu(OAc)2 catalyzed coupling with 4-methoxyphenylboronic acid. It can in principle be cleaved oxidatively with DDQ. 

When the benzylic position was protected, an indole could be prepared without side products. 

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Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Miller s biomimetic approach inspired Ishihara [234] to develop a minimal artificial acylase for the KR of mono-protected cw-l,2-diols and A-acylated 1,2-amino alcohols. Derived from (S)-histidine, Ishihara s organocatalyst contains only one stereogenic centre and incorporates a sulfonamide linkage in place of a polypeptide chain to allow the NH group to engage as an H-bond donor with the substrates (Fig. 13) [234]. 

Alkylation of N-Anions. This is an important process of wide application in organic synthesis and manufacturing of pharmaceuticals, plant protection agents, etc. PTC is an efficient way to execute this process for relatively strong NH acids such as sulfonamides, imides, or cyanamide as well as for less acidic diarylamines, amides, and a variety of heterocycles. Depending on acidity of the precursors, anhydrous K2CO3, diluted or concentrated aqueous NaOH, or solid NaOH in liquid-liquid or liquid-solid systems were applied in these reactions (eqs. 25-29). 

Protective group chemistry for these amines has been separated from the simple amines because chemically they behave quite differently with respect to protective group cleavage. The increased acidity of these aromatic amines makes it easier to cleave the various amide, carbamate, and sulfonamide groups that are used to protect this class. A similar situation arises in the deprotection of nucleoside bases (e.g., the isobutanamide is cleaved with methanolic ammonia ), again, because of the increased acidity of the NH group. 

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