Solvent thermomorphic

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. 

To eliminate the need to recover the product by distillation, researchers are now looking at thermomorphic solvent mixtures. A thermomorphic system is characterized by solvent pairs that reversibly change from being biphasic to monophasic as a function of temperature. Many solvent pairs exhibit varying miscibility as a function of temperature. For example, methanol/cyclohexane and n-butanol/water are immiscible at ambient temperature, but have consolute temperatures (temperatures at which they become miscible) of 125°C and 49°C, respectively (3). 

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... 

Our approach is to use the inexpensive ligands that are already used industrially as well as conventional solvents. The goal of this project is to develop a thermomorphic approach to the rhodium-catalyzed hydroformylation of higher olefins (>Ce) that enhances conversion rates and ease of product recovery while minimizing catalyst degradation and loss. 

Thermomorphic solvent mixtures have been tested for hydroformylation of 1-octene and 1-dodecene to determine the ease of product recovery and catalyst recycling. Using both batch and continuous reactors, we demonstrated the efficacy of a biphasic, thermomorphic, system that had the following advantages ... 

Batch Experiments with Thermomorphic Systems. As a reference, we tested the hydroformylation of 1-octene in a completely homogeneous system using the same rhodium triphenylphosphine catalyst that is used for hydroformylation of lower aldehydes. This is sample R39 in Table 28.1, and gives us a baseline to compare the performance of our systems in terms of conversion and selectivity. To maintain consistency, we performed all the reactions at 100°C using the same amounts of reactants, catalysts and solvents. Under these conditions we only detected aldehyde products no alcohol or alkene isomers were formed. 

Continuous Experiments with Thermomorphic Systems. For the continuous experiments, we used the best solvent system we identified in the batch reactions, which was 50 50 1,4-dioxane/water. Heptane was the nonpolar solvent and CTAB the surfactant. We chose this system over the 50 50 ethanol/water system because it gave us better selectivity and there is no chance that unwanted acetal side products will be formed by the reaction of ethanol with the aldehyde. We initially used 1-octene as the olefin and after we worked out the process conditions for 1-octene, we tested the higher olefin 1-dodecene. 

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. 

On the other hand thermomorphic solvent systems can be used for industrial applications within existing equipment. In principal, it is also possible to use unmodified ligands and catalyst complexes for homogeneously catalyzed reactions. Therefore, the economic hurdles to use the system in industrial practice are not very high. 

Thermomorphic solvents show promise for upcoming use in chemical industry. This is also the case for polymeric thermomorphic solvents [36]. But there are also limitations and items for further investigations ... 

Often reactions only work satisfactory in special solvents. It is not very likely, that thermomorphic solvents or solvent mixtures will extend these options. 

Thermomorphic solvent systems are at a relatively yoimg stage of development. Compared to ionic liquids or supercritical CO2 there is much less experience available. Large-scale applications are unknown at present. There are a lot of options for the future but these will depend on further research in the area. 

Another approach to isolate the catalyst from the products is the application of perfluorinated catalytic systems, dissolved in fluorinated media [63], which are not non-miscible with the products and some commonly used solvents for catalysis like THE or toluene at ambient temperature. Typical fluorinated media include perfluorinated alkanes, trialkylamines and dialkylethers. These systems are able to switch their solubility properties for organic and organometallic compounds based on changes of the solvation ability of the solvent by moving to higher temperatures. This behavior is similar to the above-mentioned thermomorphic multiphasic PEG-modified systems [65-67]. 

IMS system temperature dependent or thermomorphic multi-component solvent system... 

From our cooperation partners. Profs. Gladysz and Dinjus, we received ligands with perfluorinated chains ( ponytails ), which show a thermomorphic solubility in organic solvents (P(et-Rf8)2(m-me-bz)) or maybe extracted with fluorous solvents (P(et-Rfs)3). P(et-Rf6)(z-pr)2 with only one perfluorinated... 

The application of thermomorphic solvent systems as a new recycUng concept was investigated in various C - C bond-forming reactions. Therefore methods for a systematic choice of solvent combinations were developed. In addition to common organic solvents more unusual solvents Hke cycHc carbonates, pyrroUdones, polyethylene glycols and lactones were used in the investigations. The phase behaviour of the new solvent systems was determined by cloud titrations. From these experiments information about the temperature dependency and an appropriate composition for the reactions could be obtained. The results were used in the development of an expert system for the solvent selection. 

Suitable thermomorphic solvent systems were appUed to the telomeriza-tion of butadiene with ethylene glycol or with carbon dioxide, to the isomer-izing hydroformylation of trans-4-octene and to the hydroaminomethylation of 1-octene with morpholine. Further investigations for the carboxytelomer-ization and for the synthesis of 4-nitrodiphenylamine were also carried out. In addition to common Ugands, PEG-modified ligands and fiuorous Ugands were used for the telomerization and the carboxytelomerization. 

Indeed, both phosphines were strongly thermomorphic, particularly with respect to the less polar solvent n-octane. Between 20 and 80 °C, the sol-ubiUty of 5a increased ca. 60-fold. Between 20 and 100 °C, the increase was 150-fold. More important were the low absolute concentrations at lower temperatures. Very httle 5a could be detected in n-octane at - 20 or 0 °C (0.104 and 0.308 mM). At 20 °C, milUmolar concentration levels were present (1.13 mM). The low temperature limits were similar for the more polar solvents toluene and chlorobenzene (Fig. 2). Although the solubiUties did not increase as much with temperature, note that those at 65 °C (> 6.5 mM) are sufficient for all of the catalytic reactions described below. 

Otera has reported that fluorous distannoxanes such as 23, which dissociate to give Lewis acidic species, catalyze transesterifications in or-ganic/fluorous solvent mixtures [8,9]. Although 23 was insoluble in toluene at room temperature, it dissolved at reflux and efficiently promoted the transformation in reaction D of Scheme 4, as well as others. The catalyst precipitated upon cooling, but a fluorous solvent extraction was utilized for recovery (100%). Another thermomorphic fluorous Lewis acid catalyst was developed by Mikami [11]. He found that the ytterbium tris(sulfonamide) 24 could be used for Friedel-Crafts acylations imder homogeneous conditions in CICH2CH2CI at 80 °C, and precipitated upon cooHng to -20 °C (reaction E, Scheme 4). 

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. 

Table 7 Results of the telomerization of myrcene in thermomorphic solvent systems...

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

In this context it is interesting to note the recent reports of fluorous catalysis without fluorous solvents [68]. The thermomorphic fluorous phosphines, P[(CH2)m(CF2)7CF3]3 (m=2 or 3) exhibit ca. 600-fold increase in n-octane solubility between -20 and 80 °C. They catalyze the addition of alcohols to methyl propiolate in a monophasic system at 65 °C and can be recovered by precipitation on cooling (Fig. 7.20) [68]. Similarly, perfluoroheptadecan-9-one catalyzed the epoxidation of olefins with hydrogen peroxide in e.g. ethyl acetate as solvent [69]. The catalyst could be recovered by cooling the reaction mixture, which resulted in its precipitation. 

Easy recycling of gold hydrosilation catalysts has also been achieved using a fluorous approach.Conversions varied from moderate to excellent for the reaction of dimethylphenylsilane with benzaldehyde. However, the mechanism is not clear at this stage. The catalyst could not be recycled in the absence of fluorous solvents under thermomorphic conditions and the formation of... 

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