Thermomorphic separation

While polyethylene oligomers complete insolubility cold and solubility hot as a function of temperature provides a thermomorphic way to separate a catalyst and product, it should be noted that polymers are not the only vehicle for thermomorphic separations that involve a quantitative temperature-dependent solid/liquid separation. This is most evident in fluorous systems. For example, Gladysz has described several examples of fluorinated catalysts that are insoluble in organic solvents cold but soluble hot [74]. Qualitatively, these catalysts behave as if they were attached to a piece of Teflon that had temperature-vari-able solubility like the polyethylene oligomers above. Similar temperature-dependent solubility has been noted with other fluorous catalysts too [75-77]. 

Dendrimers too can be used in thermomorphic systems. In a report describing dendrimer-bound Pd(0) catalysis [163], Kaneda compared the liq-uid/liquid thermomorphic separation scheme with more established membrane and solvent precipitation procedures. Starting with commercially available third-, fourth-, and fifth-generation poly(propylene imine) dendrimers, the primary amine groups at the periphery were converted into chelating phosphines. The resulting phosphines were in turn allowed to react with Cl2Pd(PhCN)2 to form Pd(II) complexes that were reduced by hydrazine in the presence of triphenylphosphine to form the Pd(0) catalyst 126 (Eq. 63). This catalyst was successfully used in the allylic amination shown in Eq. 64. In this example, solvent precipitation, membrane filtration, and thermomorphic liq-uid/liquid separation were all used to recycle 126. The latter procedure proved to be simplest with the best recovery of active catalyst. 

Palladium nanoparticles, stabilized in micelles formed by polystyrene-co-poly(ethylene oxide) copolymer (PS-PEO) and acetylpyridinium chloride (CPC) as a surfactant, have been used to catalyze heterocyclization of N-methylsulfonyl-o-iodoaniline with phenylacetylene leading to formation of a substituted indole. The activity of the colloidal palladium catalytic system is comparable to that of the low-molecular-we ht palladium complexes, whereas the stabUity of the colloidal palladium system is much h her. The reuse of the catalyst PS-PEO-CPC was demonstrated in experiments with fresh starts as well as by thermomorphous separation of the catalyst from products (20060M154). 

A method has been developed for the continuous removal and reuse of a homogeneous rhodium hydroformylation catalyst. This is done using solvent mixtures that become miscible at reaction temperature and phase separate at lower temperatures. Such behavior is referred to as thermomorphic, and it can be used separate the expensive rhodium catalysts from the aldehydes before they are distilled. In this process, the reaction mixture phase separates into an organic phase that contains the aldehyde product and an aqueous phase that contains the rhodium catalyst. The organic phase is separated and sent to purification, and the aqueous rhodium catalyst phase is simply recycled. 

The use of thermomorphic systems has recently been studied as a way of achieving catalyst separation in homogeneous catalysis. For example, a biphasic hydroformylation catalyst system was developed to take advantage of the unusual solvent characteristics of perfluorocarbons combined with typical organic solvents (4). Fluorous/organic mixtures such as perfiuoromethylcyclohexane... 

We have demonstrated a new class of effective, recoverable thermormorphic CCT catalysts capable of producing colorless methacrylate oligomers with narrow polydispersity and low molecular weight. For controlled radical polymerization of simple alkyl methacrylates, the use of multiple polyethylene tails of moderate molecular weight (700 Da) gave the best balance of color control and catalyst activity. Porphyrin-derived thermomorphic catalysts met the criteria of easy separation from product resin and low catalyst loss per batch, but were too expensive for commercial implementation. However, the polyethylene-supported cobalt phthalocyanine complex is more economically viable due to its greater ease of synthesis. 

The idea to use solvent systems enabling homogeneous reaction conditions at elevated temperatures and liquid/liquid phase separation at lower— preferably room—temperature seems to be obvious. Nevertheless, it is only recently that thermomorphic solvent systems gain attention [30-33] for product separation or multiphase catalysis [34,35]. The main reasons for the delayed engagement is that an efficient choice of a useful solvent system is not easy to achieve. There is also a lack of experience with thermomorphic systems in general. Reactions are optimized to be carried out in solvents having certain distinct solubility and polarity characteristics. A thermomorphic solvent system of choice will have to fulfill these requirements and to show the thermomorphic effect in addition. 

Liu et al. [18] investigated the possibility of catalyst recycling in the nonaqueous hydroformylation of 1-decene by using the thermomorphic polyether phosphite 2a described earlier under phase-transfer conditions. Catalyst recovery with the procedure of phase-separable catalysis was possible with 0.92% rhodium loss in the seventh cycle. Complete olefin conversion and aldehyde yields of 98% were reached, but linear and branched aldehydes were formed in almost equal amounts. 

Fig. 3 Recycling of thermomorphic fluorous phosphine catalysts 5a,b via solid/liquid phase separations (Starting concentration of 2, 1.25 M cycle time, 8 h for 5a and 1 h for 5b)...

Fig. 7 Recycling of thermomorphic fluorous rhodium catalysts 16-Rf via solid/liquid phase separation...

Fig. 10 Additional thermomorphic fluorous catalysts that have been recovered by solid/ liquid phase separations...

The reactions were carried out at 70 °C in the so called thermomorphic solvent system (heptane/90% aqueous EtOH) which undergoes phase separation after cooling to room temperature. Alternatively, air-stable tridentate sulfur-carbon-sul-fur (SCS)-Pd(ll) catalysts (47) bound to PNIPAM or polyethyleneglycol were also prepared and used in the Heck and Suzuki reactions under thermomorphic conditions. 

An extension of these dendritic phosphine ligands for Pd-catalyzed allylic ami-nation was recently described using a thermomorphic system for separation [72]. 

Mixed systems of organic molecules and ILs that form separate phases (by thermomorphic phase separation) have been also studied by Raman spectroscopy [29]. 

Riisager, A., Fehrmann, R., Berg, R. W., van Hal, R., and Wasserscheid, R, Thermomorphic phase separation in ionic liquid-organic liquid systems-conductivity and spectroscopic characterization, Phys. Chem. Chem. Phys., 7,... 

Behr A, Johnen L, Vorholt AJ (2010) Telomerization of myrcene and catalyst separation by thermomorphic solvent systems. ChemCatChem 2 1271-1277... 

There are several different methods to separate PNIPAM-supported catalysts from the reaction mixtures. Both liquid-solid separations and liquid-liquid separations can be used. The most frequently used liquid-solid separation method takes advantage of the varying solubility of polymers in different solvents. For example, PNIP AM can be precipitated from THF into hexanes. PNI-PAM copolymers also exhibit lower critical solution temperature (LCST) behavior. Specifically, PNIPAM and its copolymers can be prepared such that these polymers are soluble in water at low temperature but precipitate when heated up. This property may be used as either a purification method or a separation tech-nique.[l 1] A thermomorphic system is a liquid-liquid biphasic system developed in our group. It uses various solvent mixtures with temperature-dependent miscibility to effect separation of catalysts from substrates and products, as shown in Figure 2. 

Keywords Soluble polymers Thermomorphic Biphasic catalysis Latent biphasic catalysis Separation... 

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. 

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