Quinonemethide route

Eor an early summary of the chloromethylation route , the Claisen rearrangement route and the quinonemethide route see C. D. Gutsche, in Calixarenes A Versatile Class of Macrocyclic Compounds (Eds. J. Vicens and V. Bohmer), Kluwer, Dordrecht, 1990, p. 3. 

Alam et al. have described the synthesis of a variety of mono- and tetrasubstituted calix[4]arenes via the quinonemethide route shown in Figure 15 [26]. 

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. ... 

To the list of nucleophiles used in the p-quinonemethide route (see ref. 1, p. 142) has been added CH(C02Et)3, from which calix[4]- and -[8]arenes 196b... 

An alternative route to phenolate-like EGBs is through the cathodic reduction of quinonemethides, (36), [82, 83]. The advantage of these PBs is that they are reduced at modest potentials, which allow EGB formation to take place in situ, and they are ultimately converted into phenols that are easily reoxidized to (36) either by air or by anodic oxidation (60-70% yield) [82]. The radical anion (36a) is expected to have basicity similar to that of (35) , whereas the pK of the conjugate acid of the dianion formed by further reduction can be assumed close to that of triphenylmethane, 30.6. 

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