Hydrophilic nucleophile

Little is known about the structures of these kinetically effective complexes, or even about the aggregates of the amphiphile. Both hydrophobic and coulombic interactions are important because these aggregates are much less effective than micelles at assisting reactions of hydrophilic nucleophilic anions. These observations are consistent with the view that the aggregates are much smaller than micelles. It is probable that the structures and aggregation numbers of these aggregates depend on the nature of the solutes which bind to them and Piszkiewicz (1977) has suggested that such interactions play a role in micellar kinetics. 

Micro emulsions can be formulated with carbon dioxide in supercritical state instead of a hydrocarbon as nonaqueous solvent. Fluorinated surfactants are commonly used to prepare such microemulsions. Water-in-carbon dioxide microemulsions can be made and the droplet size has been found to be similar to the size of the droplets of water-in-hydrocarbon micro emulsions with similar composition [21]. Such a microemulsion was used for conversion of benzyl chloride to benzyl bromide using KBr as hydrophilic nucleophile. The yield was an order of magnitude higher in the carbon dioxide microemulsion than in a conventional microemulsion at similar conditions, a fact that has been ascribed to low interfacial viscosity [22]. The big advantage with these micro emulsions is the environmental friendliness and the ease of work-up associated with carbon dioxide as solvent. 

Betylates are highly reactive to nucleophiles, particularly in an aqueous medium. Betylates possibly act as phase-transfer catalysts in the displacement reaction and are of particular use in effecting reactions with hydrophilic nucleophiles."... 

The second order rate constants, A and k, for reactions in the micellar and aqueous pseudophases have the same dimensions, and can now be compared directly, and within all the uncertainties of the treatment it seems that A and k are of similar magnitudes for most reactions, and in some systems A > A . This generalization is strongly supported by evidence for reactions of relatively hydro-phobic nucleophilic anions such as oximate, imidazolide, thiolate and aryloxide, typically with carboxylate or phosphate esters [61,82-85]. These similarities of second-order rate constants in the aqueous and micellar pseudophases are consistent with both reactants being located near the micellar surface in a water-rich region. Therefore the micellar rate enhancements of bimolecular reactions are due largely to concentration of the reactants in the small volume of the micelles. Some examples are in Table 3 for reactions of or hydrophilic nucleophilic anions and in Table 4 for reactions of more hydrophobic nucleophiles. 

Hydrolysis of diphenyl phosphorochloridate (DPPC) in 2.0 M aqueous sodium carbonate is also believed to be a two-phase process. DPPC is quite insoluble in water and forms an insoluble second phase at the concentration employed (i.e. 0.10 M). It seems highly significant that the hydrophobic silicon-substituted pyridine 1-oxides (4,6,7) are much more effective catalysts than hydrophilic 8 and 9. In fact, 4 is clearly the most effective catalyst we have examined for this reaction (ti/2 < 10 min). Since derivatives of phosphoric acids are known to undergo substitution reactions via nucleophilic addition-elimination sequences 1201 (Equation 5), we believe that the initial step in hydrolysis of DPPC occurs in the organic phase. Moreover, the... 

An impressive body of evidence supports these generalizations. This evidence has been reviewed (Romsted, 1984) and it does not seem necessary to discuss it in detail here, but some examples will be given and some exceptions to these generalizations will be mentioned. Some reactions of OH- are shown in Table 3 for both inert and reactive ion surfactants, and Table 4 gives data for reactions of other hydrophilic ions. Reactions of hydrophobic nucleophiles are shown in Table 2. For all these reactions second-order rate constants in the micellar pseudophase are compared with those in water. For some reactions we also give values of krcl, i.e. the rate constant relative to that in water. These values depend upon the reactant concentration and are included merely to provide an indication of the micellar rate effects. Other examples of micellar rate effects are given in the Appendix. 

The ease of formation of hydrophobic ion pairs, and hence the rate acceleration, will be determined by the hydrophobic and electrostatic interactions between the anionic and cationic species. Lapinte and Viout (1974) found that the nucleophilic order OH- > CN > C6H50- in water was completely reversed in CTAB micelles hydrophobic phenoxide ion is activated better by the micelle. The micellar binding of phenols and phenoxides was determined by Bunton and Sepulveda (1979). Similarly, hydrophobic hydroxamates are activated much better than their hydrophilic counterparts. In the same vein, the extent of activation correlates approximately with the hydrophobic nature of aqueous aggregates as estimated by Amax of methyl orange (Table 7) and of picrate ion (Bougoin et al., 1975 Shinkai et al., 1978f Table 5). 

Displacement by cyanide works particularly well, and many other nucleophilic substitution reactions are enhanced by PTC. Most monovalent anions can be transferred, including alkoxides, phenoxides, thiocyanates, nitrates, nitrites, superoxides and all of the halides. Divalent anions are usually too hydrophilic to be transferred into the organic phase. 

A practical enzymatic procedure using alcalase as biocatalyst has been developed for the synthesis of hydrophilic peptides.Alcalase is an industrial alkaline protease from Bacillus licheniformis produced by Novozymes that has been used as a detergent and for silk degumming. The major enzyme component of alcalase is the serine protease subtilisin Carlsberg, which is one of the fully characterized bacterial proteases. Alcalase has better stability and activity in polar organic solvents, such as alcohols, acetonitrile, dimethylformamide, etc., than other proteases. In addition, alcalase has wide specificity and both l- and o-amino acids that are accepted as nucleophiles at the p-1 subsite. Therefore, alcalase is a suitable biocatalyst to catalyse peptide bond formation in organic solvents under kinetic control without any racemization of the amino acids (Scheme 5.1). 

The effect of additives betrays the intricacy of the balance of rate effects even more. The addition of cholesterol to catalytic bilayers has been found to be beneficial for the Kemp eleminiation but to inhibit the decarboxylation of 6-NBIC. In general, the effects of additives on the decarboxylation of 6-NBIC appear to subtly depend on the structure of the hydrophobic tail and hydrophilic headgroup of additives. Similarly subtle effects were found for the Kemp elimination and nucleophilic attack by Br and water on aromatic alkylsulfonates depending on the choice of additive, hydrogen bonding effects, reactivity of partially dehydrated OH , and local water concentrations all played a role and vesicular catalysis could be increased or decreased. 

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