Arenes Mannich reaction

Oxyiminium cations formed from iV,0-diaIkyhydroxylamines and formaldehyde are sufficiently reactive for Mannich reactions with activated arenes. Mannich reactions of oxyiminium cations with indoles (e.g. 74, equation 48) " as well as pyrroles and furans but not phenol and thiophene have been reported. 

The p-quinonemethide route, introduced in the late 1980s,starts with the reaction of a p-H-calixarene with HCHO and a dialkylamine to produce a Mannich base, followed by methylation of the Mannich base to give the quaternary salt, and treatment with two equivalents of a nucleophile to produce a p-CH2Nu-calixarene, as illustrated by the conversion of 194 to 196. The Mannich reaction appears to occur with greater facility with the fully hydroxylated calixarenes than with their partial ethers, perhaps a consequence of the greater acidity of the former. For example, 4 reacts smoothly at room temperature (24 h) to afford the tetrakis(dimethylaminomethyl)calix[4]arene, whereas its A,C-dimethyl ether fails to react under these conditions and requires 66 h reaction time in refluxing dioxane. The A,C-dibenzoate and the A,C-diallyl ether of 4 both fail to undergo the Mannich reaction even at 140°C. ... 

Another example is the dimeric capsule (L-26a)2 that is made of simple amino acids connected using the Mannich reaction to the resorcin[4]arene scaffold... 

In our discussion, many calixarens have been mentioned in number of chemical reactions as catalyst, however out of these, quaternary ammonium-terminated calixarenes calix[4]arene 4 and calix[6]arene 2 catalysts were used in one-pot Mannich reaction of benzaldehyde, acetophenone and aniline in aqueous media to produce p-aminocarbonyl compounds (see Fig. 27.7) [19]. These calix[n]arene catalysts emphasized not only the high catalytic activity but also have an outstanding reusability with high yield, at low loading amoxmt. Advantages of that were, short reaction times, high yields, and easy work-up that make them great candidate for Mannich-type reactions (see Table 27.5). 

Some of calix[ ]arene sulfonic acids were also developed as Bronsted acid catalysts for Mannich-type reactions [23]. Because of their water-solubility, the reaction can be performed in water with obvious advantages from an environmentally point of view. As depicted in Fig. 27.8, two water soluble calixarene bearing a sulphonic acid group are suitably employed in the Mannich reaction in water as a catalyst. 

Because of the water solubility of calixarene sulfonic acids, they have been used in many organic reactions other than Mannich reaction outlined in above. In a study, p-sulfonic acid calix[4]arene (calix[4]arene 5) was employed as... 

Fig. 27.7 Three component Mannich reaction in the presence of calix[n]arene catalysts Table 27.5 Mannich reaction in the presence of calix[4]arene 4 or calix[6]arene 2 catalyst [22]...

Fig. 27.8 Three component Mannich reaction in the presence of Bronsted-type calix[n]arene catalysts...

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