Protecting groups for amines and aniline

In this section, the protections and cleavages of seven protecting groups for amines and anilines aie presented benzyl BOC Cbz Fmoc phthaloyl sulfonamide and trifluoroacetyl. 

While sulfonamides are robust protecting groups for amines and anilines, their cleavage often calls for dissolving metal chemistry. 

Trifluoroacetyl amides are an easily installed and cleaved protecting group for amines and anilines. 

An intermolecular version of the arylation of carbamates has been recently published by Hartwig et al. (Eq. (21)) [132]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P( -Bu)3 formed /V-aryl carbamates from aryl bromides or chlorides and f-butylcarbamate as substrate. Again, the reaction conditions were not as mild as those for amination, but were similar to those of the intramolecular reactions. For the intermolecular reactions, the use of sodium phenox-ide as base was crucial. Reactions using Cs2C03 showed low conversions. Those involving NaO-r-Bu as base rapidly formed a gel, presumably from the deproto-nated carbamate, and also showed little or no conversion. The products of these reactions serve as conveniently protected anilines, and r-butylcarbamate can be considered one type of ammonia surrogate. In addition, the products of these reactions are suitable for subsequent directed metalation procedures [100]. 

Donor atoms in the molecule may coordinate to the 14-electron ruthenium-catalytic species and, thereby, take up a vacant site. Basic nitrogen atoms have this effect, although there are exceptions. Nevertheless, metathesis reactions have proved very effective for the synthesis of nitrogen heterocycles, as this effect can be suppressed. One way to suppress this effect is by use of an electron-withdrawing protecting group, such as a sulfonamide, a carbamate or an amide (Scheme 8.75). Another way is to carry out the reaction in the presence of acid, so that it is the salt 8.278 with no lone pair, that cyclizes. The problem is less severe with less-basic amines, including anilines. ... 

A/ Acylated aromatic amines still direct ortho/para, but substitution is slower than for the unsubstituted aniline, and the reaction can be stopped after a single new substitution. The protecting acyl group can be removed later by treatment with acid or base. We will see the mechanisms for these reactions in Chapter 18. 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

---