Latent biphasic system

Figure 4.2 Schematic representation of dendrimer catalyst recycling via (a) solvent precipitation (b) membrane filtration and (c) phase separation (latent biphasic system [24]).

A latent biphasic system is a miscible solvent mixture that will become biphasic by the addition of a small amount of an additive. For example, a mixture of 10 mL of heptane, 9.2 mL of ethanol, and 0.8 mL of water would be miscible near room temperature. However, addition of a small amount (200 ]iL) of water or the addition of some salt would make this mixture biphasic. Such solvent mixtures that are at the cusp of immiscibility are useful as homogeneous media for catalysis and, after perturbation, as biphasic systems for separation. If a soluble polymer-immobilized catalyst is present that is by design phase-selectively soluble in one or the other phases of the biphasic mixture, it is possible to design recoverable reusable homogeneous catalysts with such latent biphasic systems. 

The first reported example using macromolecule-supported catalysts in latent biphasic systems was work by Chan s group that employed a dendrimer-bound BINAP 127 that was used to form a chiral ruthenium hydrogenation catalyst [164]. The dendritic Ru-BINAP complex formed from the reaction of [RuCl2(benzene)2]2 and 127 was successfully used in four cycles in the hydrogenation of 2-phenylacrylic acid (Eq. 65) in a 1 1 (vol/vol) ethanol/hexane mixture. Addition of 2.5 vol% water to this mixture produced a biphasic mixture where >99% of the dendritic catalyst was in the hexane phase. Addition of a fresh ethanolic substrate solution to this hexane phase produced another miscible solution of catalyst and substrate. The second and subsequent cycles of hydrogenation carried out in this manner led to consistent conversions of substrate with synthetic yields of >91% with e.e. values of 90%. 

Our work on latent biphasic systems has focused on linear polymers [165]. Initially these studies focused on poly(JV-alkylacrylamide)s like PNODAM because we had earlier shown that these lipophilic materials are very phase-selectively soluble in heptane [158,165]. This initial work used the PNODAM-bound SCS-Pd catalyst 116 in a DMA-heptane mixture with iodobenzene and acrylic acid as substrates and triethylamine as a base. This catalyst mixture was initially homogeneous at 25 On heating, Heck chemistry occurred to form cinnamic acid. Subsequent cooling of this reaction mixture formed a biphasic mixture even without addition of water because the reaction had formed some triethyl ammonium iodide, and this ammonium salt functioned as the perturbant. 

While nonpolar poly(JV-alkylacrylamide)s would be most suitable for catalyst isolation in a latent biphasic system comprised of polar/nonpolar solvents, polar polymers can be designed that quantitatively separate into the most polar phase of a polar/polar biphasic solvent mixture. Specifically, while both the dye-labeled poly(AT-hydroxyethylacrylamide) 128 (PNHEAM) and PNIPAM 110 both dissolve in a 5 3 2 (vohvohvol) mixture of tert-hutyl methyl ether (TBME), ethanol, and water, these polymers that contain dyes as surrogates for immobilized catalysts end up in different phases after 10 vol% of water is added to perturb this solvent mixture. The PNIPAM 110 ends up in the less polar TBME-rich phase after water perturbation of this latently biphasic mixture. In contrast, the more polar PNHEAM 128 ends up in the more polar water-rich phase. 

The addition of water to hydrophobic ionic liquids can result in the formation of a triphasic system consisting of the ionic liquid + catalyst/water/organic product. The aqueous phase eventually contains the inorganic salt formed during the reaction. This approach has been applied in Pd-catalyzed cross-coupling reactions [84]. The products can also separate after the reaction by perturbation (of a latent biphasic system). This can be realized by tuning the temperature to crystallize the ionic liquid. But the refrigeration cost may be problematic, and some ILs may remain in the product. 

A second example of latent biphasic catalysis used the polymer-bound trifunctional base catalyst 129 as a dimethylaminopyridine analog in acylation of 2,6-dialkylphenols by (Boc)20 in a 1 1 heptane-ethanol solvent mixture. After acylation of the phenol was complete, the addition of 10 vol% H2O perturbed the system. The yields of product carbonate from Eq. 66 were 35,66,89,99%, 99, and 99% through the first six cycles. 

A second nucleophilic catalyst supported by PtBS is the polymer-bound di-methylaminopyridine analog that was also used in latent biphasic catalysis with the poly(JV-alkylacrylamide) support 129 [131]. This example of a nucleophilic catalyst (133) was used to catalyze formation of a t-Boc derivative of 2,6-di-methylphenol (Eq. 70). In this case, the extent of recovery of the catalyst and the yields of product were directly comparable to those seen with thermomorphic systems. The isolated yield for the first five cycles of this reaction were 34.3, 60.9,82.2,94.6, and 99%. In this case we reused catalyst 133 through 20 cycles. Yields after the first few cycles were essentially quantitative (ca. 93% average for each of 20 cycles). Separation of the polymer from the aqueous ethanol phase was quantitative as judged by either visual observation or UV-visible spectroscopic analysis. 

Figure 4.2 Schematic depiction of recycling methods for immobilized catalysts, (a) Solvent precipitation, (b) membrane filtration,(c) latent biphasic catalytic system, and (d) thermo-morphic catalytic system.

Biphasic oligomerization with ionic liquids is not restricted to chloroaluminate systems. Especially in those cases where the - at least - latent acidity or basicity of the chloroaluminate causes problems, neutral ionic liquids with wealdy coordinating anions can be used with great success. 

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