Interfacial deprotonation

The interfacial mechanism provides an acceptable explanation for the effect of the more lipophilic quaternary ammonium salts, such as tetra-n-butylammonium salts, Aliquat 336 and Adogen 464, on the majority of base-initiated nucleophilic substitution reactions which require the initial deprotonation of the substrate. Subsequent to the interfacial deprotonation of the methylene system, for example the soft quaternary ammonium cation preferentially forms a stable ion-pair with the soft carbanion, rather than with the hard hydroxide anion (Scheme 1.8). Strong evidence for the competing interface mechanism comes from the observation that, even in the absence of a catalyst, phenylacetonitrile is alkylated under two-phase conditions using concentrated sodium hydroxide [51],... 

Figure 11. Interfacial deprotonation of indanone 5 in toluene/aqueous NaOH.

Fig. 5.10 Carbanion formation and alkylation via interfacial deprotonation using concentrated aqueous hydroxide solution.

The interfacial mechanism is confirmed by stirring rates around 700-800, necessary to obtain reproducible results [29]. Moreover, a number of interfacial deprotonations and further reactions of carbanions are described in the absence of catalysts. For example, phenylacetonitrile is alkylated by 1-iodobutane and 50% aqueous NaOH at 80°C. Under these conditions the concentration of phenylacetonitrile in the aqueous phase and its carbanion sodium salt in the organic phase were less than 2 and 5 ppm, respectively [30]. 

Another important feature of PTC alkylation of carbanions is inhibitory effect of iodide anions on the catalytic process. The rationalization of this phenomenon presented in the Introduction for reactions of inorganic anions is not sufficient for PTC reactions of carbanions, carried out in the presence of concentrated NaOH solution, because carbanions are as a rule more lipophilic than iodide anions. There are also numerous papers describing the successful PTC alkylation of various CH acids with alkyl iodides. It seems that this fact is connected with inhibition of the interfacial deprotonation of the carbanion precursors by iodide anions. Because of their low hydration energy, iodide anions occupy mostly the interfacial region between the organic phase and concentrated NaOH solution, where the deprotonation takes place. One can assume that fraction of the surface occupied by the carbanions and iodide anions in the equilibrated systems... 

In some cases, the Q ions have such a low solubility in water that virtually all remain in the organic phase. ° In such cases, the exchange of ions (equilibrium 3) takes place across the interface. Still another mechanism the interfacial mechanism) can operate where OH extracts a proton from an organic substrate. In this mechanism, the OH ions remain in the aqueous phase and the substrate in the organic phase the deprotonation takes place at the interface. Thermal stability of the quaternary ammonium salt is a problem, limiting the use of some catalysts. The trialkylacyl ammonium halide 95 is thermally stable, however, even at high reaction temperatures." The use of molten quaternary ammonium salts as ionic reaction media for substitution reactions has also been reported. " " ... 

FIG. 4 Thermodynamic equilibria for the interfacial distribution of a solute X which can be ionized n times, and X being its most acidic (or deprotonated) and its most basic (or protonated) forms, respectively. X and are the dissociation constants in the aqueous and organic phase, respectively, and P is the partition coefficient of the various species between the two phases. 

The acidity of amides (pKa 23) is such that it is reasonable to postulate that, in contrast with the analogous reactions of the amines, the phase-transfer catalysed N-alkylation proceeds by way of the initial generation of the amidic anion under basic conditions. It has been demonstrated that the preformed sodium salt of benzamide can be solubilized in toluene upon the addition of Aliquat [1 ] and further evidence [2] has been provided for the postulated deprotonation under the two-phase conditions in which it is assumed that the deprotonation occurs by an interfacial mechanism (see Chapter 1). 

It can be assumed that the azoles are deprotonated by the interfacial exchange mechanism, but it is noteworthy that it has been suggested that the rate of alkylation of indole under liquiddiquid two-phase conditions decreases with an increase in the concentration of the sodium hydroxide [8]. The choice of catalyst appears to have little effect on the reaction rate or on the overall yields of alkylated azole. Benzyltriethylammonium chloride, Aliquat, and tetra-n-butylammonium hydrogen sulphate or bromide have all been used at ca. 1-10% molar equivalents (relative to the concentration of the azole) for alkylation reactions, but N-arylation of indole with an activated aryl halide requires a stoichiometric amount of the catalyst [8]. 

The polymer described here is prepared through interfacial polymerization using a variation of the well-known Schotten-Baumann reaction. The reaction is shown in Scheme 4. To work effectively, the aromatic OH groups must be deprotonated by treatment with base, and the phenolate ions produced from the monomers 10 and 11 then react with sebacoyl chloride 12. In fact, in the example chosen, the polymer formed was found to have a rather low molecular weight. 

Charles Liotta modified the Makosza interfacial mechanism. In this modification deprotonation takes place at the interfacial region and is assisted by the quaternary cation. 

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