Catalytic two-phase reactions

These were discovered by Makosza who has reviewed the scope of the reaction [21]. Alkylation of weak acids of pKa 22 is carried out using 

In contrast to alkylation in liquid ammonia/sodamide, only the mono-alkylated product is formed. A variety of carbanion reactions can be carried out. Ketones undergo the Knoevenagel reaction. The Wittig reaction is successful with aldehydes, and olefines can be transformed into halocyclopropanes via carbene addition (e.g. equation 12.14). 

The catalytic two-phase reaction technique, in addition to permitting the use of water insoluble, readily recoverable solvents, actually widens the scope of the available chemistry. Makosza s review [21] is a mine of interesting chemistry. 

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If pore diffusion affects the reaction rate and Rj in Equation 6.14 is replaced by r ejRp the effectiveness factor, ejy can be obtained the same way as in the case of catalytic two-phase reactions (Section 5.2.2). Equations developed for two-phase reactions in Section 5.2.2 are also valid for three-phase cases, provided that the catalyst particles are completely wetted by the liquid. In this case, we only have one phase a liquid present inside the catalyst pores. Using the formulae introduced in Section 5.22, the diffusion and mass transfer coefficients of the gas phase are, of course, replaced by those of the liquid phase. 

Higher selectivity, easier processing, use of inexpensive solvents, use of cheaper chemicals, and ease of heat removal have been realized through phase-transfer catalysis (PTC). It appears that no catalytic method has made such an impact as PTC on the manufacture of fine chemicals (Sharma, 1996). Many times we benefit by deliberately converting a single-phase reaction to a two-phase reaction. Consider catalysis by. sodium methoxide in a dry organic. solvent. This can invariably be made cheaper and safer by using a two-pha.se. system with a PT catalyst. 

Other liquid-ligand two-phase reactions mediated by polyethers include anion promoted C-alkylations, oxidations, and (borohydride) reductions. In such cases, the organic substrate and a catalytic amount of polyether in an organic phase are shaken with a saturated aqueous solution of the required anionic reagent. 

Figure 21.1 Fixed-bed catalytic reactors (FBCR) for two-phase reactions modes of operation (each rectangle or shaded area represents a bed of catalyst each circle represents a...

These two phase reactions summarized in Scheme 1 are strongly promoted by catalytic amounts of the quaternary onium salts which will transfer between aqueous and organic phases, as shown in Scheme 2 for the substitution of halides with cyanides. The effect was termed by Starks... 

The problems encountered in the catalytic transfer of highly hydrophilic anions from aqueous solutions into the organic phase can be countered by the use of anhydrous solid salts the organic reactant is dissolved in the organic solvent or, if liquid, may be used neat. Solid liquid two-phase reactions using ammonium salts have widespread application (see, for example, the many examples cited in later chapters) frequently with shortened reaction times, lower reaction temperatures, and higher yields [e.g. 66, 67] and are generally superior to solidrliquid reactions catalysed by crown ethers [68]. The process is particularly useful in base-initiated reactions with fluorides, hydroxides or carbonates. 

One-pot conversions of 2-hydroxy(acylbenzenes) with anhydrides or acid chlorides to produce coumarins [52-54] and flavones [54-58] under mild liquiddiquid or solidtliquid two-phase conditions via a Baker-Venkataraman type reaction (Scheme 6.19) are catalysed by quaternary ammonium salts. 3-Substituted coumarins are produced from salicylaldehyde and malonodinitrile, or substituted acetonitriles, in high yield (>85%) in a one-pot catalysed sequential aldol-type reaction and cycliza-tion in the absence of an added organic solvent [59]. When 2 -hydroxychalcones are reduced under catalytic two-phase conditions with sodium borohydride, 2,4-cis-flavan-4-ols are produced [60] (see Section 11.3). 

The increase in the rate of reactions catalysed by quaternary ammonium salts is often proportional to the concentration of the catalyst used. When I started to collect data for their use in organic synthesis, it rapidly became obvious that it was difficult to make a clear distinction between purely catalytic reactions and those using stoichiometric amounts of the ammonium salt this was because the practical techniques often varied (e.g., liquidiliquid two-phase reactions vs liquid solid two-phase reactions). Consequently, I have presented a general practical overview of the use quaternary ammonium salts, categorised according to specific bond formations or reaction types. I have tried to be as comprehensive as possible, but in order to keep the text concise, some abstruse experimental variations have been omitted, as has a complete citation of the patent literature. 

Even in an excess of ligands capable of stabilizing low oxidation state transition metal ions in aqueous systems, one may often observe the reduction of the central ion of a catalyst complex to the metallic state. In many cases this leads to a loss of catalytic activity, however, in certain systems an active and selective catalyst mixture is formed. Such is the case when a solution of RhCU in water methanol = 1 1 is refluxed in the presence of three equivalents of TPPTS. Evaporation to dryness gives a brown solid which is an active catalyst for the hydrogenation of a wide range of olefins in aqueous solution or in two-phase reaction systems. This solid contains a mixture of Rh(I)-phosphine complexes, TPPTS oxide and colloidal rhodium. Patin and co-workers developed a preparative scale method for biphasic hydrogenation of olefins [61], some of the substrates and products are shown on Scheme 3.3. The reaction is strongly influenced by steric effects. 

Because hydroformylation is a gas-liquid two-phase reaction under mostly high pressure, various special methods have been used for direct observation of the catalytic reactions. Here, we focus on the techniques recently developed for this purpose. 

The pH-neutral ionic liquids are highly polar and noncoordinating. These liquids have potential applications as solvents for metallic and organometallic reagents in two-phase reactions, and as replacements for polar, aprotic solvents like dimethyl-foimamide. The Lewis-acidic and superacidic ionic liquids are being investigated for use as catalytic solvents. 

Reactions of carbanions, anions of weak organic acids (e.g., indole or carbazole), and dihalocarbenes may be carried out in liquid-liquid systems, in which concentrated aqueous sodium hydroxide is the aqueous phase. The term phase transfer catalysis is mechanistically incorrect these are often referred to as catalytic two-phase systems. Numerous reactions of carbanions including alkylation, nitroarylation, addition, the Darzens condensation, cyclopropanation, and also a variety of reactions of dihalocarbenes are conveniently carried out in this way. 

Sample integrations similar to pharmaceutical approaches were already examined in 1997 [39]. Here, a chip-like microsystem was integrated into a laboratory automaton that was equipped with a miniaturized micro-titer plate. Microstructures were introduced later [40] for catalytic gas-phase reactions. The authors also demonstrated [41] the rapid screening of reaction conditions on a chip-like reactor for two immiscible liquids on a silicon wafer (Fig. 4.8). Process conditions, like residence time and temperature profile, were adjustable. A third reactant could be added to enable a two-step reaction as well as a heat transfer fluid which was used as a mean to quench the products. 

Makosza, M. (1975) Two-phase reactions in the chemistry of carbanions and halocarbenes. A useful tool in organic synthesis. Pure Appl. Chem., 43, 439. Mason, D., Magdassi, S. and Sasson, Y. (1990) Interfacial activity of quaternary salts as a guide to catalytic performance in phase-transfer catalysis./. Org. Chem., 55, 2714. 

What is the specific feature in the reaction at the liquid/liquid interface The catalytic role of the interface is of primary importance in solvent extraction and other two-phase reaction kinetics. In solvent extraction kinetics, the adsorption of the extractant or an intermediate complex at the liquid/liquid interface significantly increased the extraction rate. Secondly, interfacial accumulation or concentration of adsorbed molecules, which very often results in interfacial aggregation, is an important role played by the interface. This is because the interface is available to be saturated by an extractant or mehd complex, even if the concentration of the extractant or metal complex in the bulk phase is very low. Molecular recognition or separation by the interfacial aggregation is the third specific feature of the interfacial reaction and is thought to be closely related to the biological functions of cell membranes. In addition, molecular diffusion of solute and solvent molecules at the liquid/liquid interface has to be elucidated in order to understand the molecular mobility at the interface. In this chapter, some examples of specific... 

The stoichiometric asymmetric dihydroxylation obeys a rate law which is first order in osmium tetroxide and aikene, but shows saturation behavior in ligand (cf Fig. 2). The kinetic behavior of the reaction is shown in Scheme 7 and Eq. (2). This kinetic scheme is also vahd for a discussion of the factors governing the enantioselectivity in the catalytic asymmetric dihydroxylation, since the hydrolysis and reoxidation steps does not affect the selectivity of the AD reactions under the normal two-phase reaction using KjFelCNlg as cooxidant. 

The technique of aqueous catalytic reactions has had such an impact on the field of more general two-phase reactions that scientists have now also proposed and tested other solutions. Fluorous systems (FBS, perfluorinated solvents cf. Section 7.2) and nonaqueous ionic liquids (NAILs, molten salts cf. Section 7.3) meet the demand for rapid separation of catalyst and product phases and, owing to the thermoreversibility of their phase behavior, have advantages in the homogeneous reaction and the heterogeneous separation. However, it is safe to predict that the specially tailored ligands necessary for these technologies will be too expensive for normal applications. Compared to the cheap and ubiquitous solvent water, with its unique combination of properties (cf. Table 1), other solvents may well remain of little importance, at least for industrial applications. Other ideas are mentioned in Section 7.6. 

This reaction mechanism described by Starks [28,33] is widely accepted for a catalyst transferring between the two phases. Reactions occurring in such systems involve (1) the reactant reacting with catalyst in the normal phase to form an intermediate catalytic reactant, (2) transfer of the intermediate catalytic reactant from its normal phase into the reaction phase, (3) transferred intermediate catalytic reactant reacting with untransformed reactant in the reaction phase to produce the product and catalyst, and (4)... 

Polymers, with [//] = 0.30—0.56 dl/g, containing methyl sulfonyl groups have been synthesized by copolymerization of methyl-4-vinylphenyl sulfoxide with styrene [92]. These copolymers are soluble in toluene but are insoluble in water. Their catalytic activity has been studied in Sf 2-type reactions of alkyl halides with different nucleophiles in water-toluene solutions at 100°C for 20 h. The copolymers effectively catalyze two-phase reactions of octyl bromide with KSCN, NaSCN and KI and of butyl bromide with NaOPh and NaSPh with a 11-78% yield of respective reaction products. These reactions, however, are not catalyzed by DMSO, methylphenyl-sulfoxide and benzyl methyl sulfoxide. The copolymer catalytic activity is higher than that of the monomer analogues and increases with an increment in the number of styrene units in the copolymer. These copolymeric catalysts are easily extracted from the reaction medium. The influence of the hydrophobic environment of active centers on the catalytic activity of polymeric catalysts has already been discussed. 

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