Basicity, alkylamines amides

Alkylamines (RNH2) are more basic than amides (RCONH2), which have a delocalized lone pair from the N atom (25.1 OC). 

Sulfonamides are prepared from an amine and a sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Most arylsulfonamides are stable to alkaline hydrolysis and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, as well as by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than those of the more basic alkylamines. 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 property of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Intriguingly, the scope of amines is complementary in the former case, strongly basic alkylamines are applicable whereas the latter conditions accommodate less basic arylamines and amides. 

The nitrogen that reacts is the one that is a tertiary alkylamine. Of the other two nitrogens, is attached to an aromatic ring and is much less basic and less nucleophilic. The third nitrogen, , is an amide nitrogen amides are less nucleophilic than amines. 

Amines are weak bases. Alkylamines and ammonia are of comparable basicity, but aromatic amines are much weaker as a result of delocalization of the unshared electron pair on nitrogen to the ortho and para carbons of the aromatic ring. Amides are much weaker bases than amines because of delocalization of the unshared electron pair on nitrogen to the adjacent carbonyl oxygen. Amides are stronger Bronsted acids than amines because of the partial positive charge on the amide nitrogen and resonance in the amidate anion. 

The amination of aryl halides and triflates catalyzed by palladium complexes is suitable for use in complex synthetic problems. Many substrates will produce high yields of mixed arylamines with one of the existing catalyst systems. Nevertheless, there are many combinations of substrates for which the amination chemistry may be substantially improved. For the most part, these reactions involve nitrogen centers, such as those in pyrroles, indoles, amides, imidazoles and other heterocyclic groups that are less basic than those in standard alkylamines. Although mild reaction conditions have been developed for many substrates, the harsh conditions used in many of the applications indicate that continued studies on developing mild condi-... 

To compare the basicity of an alkylamine (RNH2) and an amide (RCONH2), we must once again compare the availability of the nonbonded electron pair on nitrogen. With RNH2, the electron pair is localized on the N atom. With an amide, however, the electron pair is delocalized on the carbonyl oxygen by resonance. This decreases the electron density on N, making an amide much less basic than an alkylamine. 

---