Continuous-flow hydroformylation

Scheme 8.7. Continuous-flow hydroformylation of long chain olefins in the biphasic system IL/SCCO2...

Webb, P.B.and Sellin, M.F. and Kimene, T.E. and Williamson, S. and Slawin, A.M.Z. and Cole-Hamilton, D.J. (2003). Continuous Flow Hydroformylation of Alkenes in Supercritical Fluid-Ionic Liquid Biphasic System. J. Am. Chem. Soc., 125, 15577-15588. 

Figure 4.5 Diagram of a continuous-flow hydroformylation setup employing ionic liquids and supercritical C02...

Fig. 12.11. Rhodium complex used to generate an immobilized catalyst for continuous flow hydroformylation in 5CCO2.

Figure 9 Effect of CO/H2 flow rate on continuous-flow hydroformylation of 1-octene catalyzed by Rh/[PMIM][Pli2P(3-C6H4S03)] in the [0ctMIM][NTf2]-scC02 biphasic system. (Reprinted with permission from [16], 2003 American Chemical Society).

In 2007, a SILP-SCCO2 system was first applied to a continuous-flow process by Hintermair et al. [53]. They reported the continuous-flow hydroformylation of 1-octene (Figure 18.8) using a SILP catalyst where a rhodium complex was dissolved in [OMIM][NTf2] (l-octyl-3-mefhylimidazoliumbis(trifluoromethanesulfonamide)) supported on silica by adsorption. The system is shown schematically in Figure 18.8. 

The group of Cole-HamUton utiUzed these properties to construct a continuous flow hydroformylation system for the transformation of 1-hexene and 1-octene (Figure 7.19) [88a, 106,112]. 

Figure 5.4-1 Continuous flow apparatus as used for the hydroformylation of 1-octene in the...

In subsequent work the same supported catalysts were used in different reactor setups [20] (Figure 3.3). A vapour-phase reactor in which the supported catalyst was mounted on a bed was used for the hydroformylation of volatile alkenes such as cis-2-butene and trifluoropropene. The initial activities and selectivity s were similar to those of the homogeneous solutions, i.e. a TOF of 114 and 90% ee in the hydroformylation of trifluoropropene was reported. No rhodium was detected in the product phase, which means less then 0.8% of the loaded rhodium had leached. The results were, however, very sensitive to the conditions applied and, especially at longer reaction times, the catalyst decomposed. In a second approach the polymer supported complex was packed in a stainless steal column and installed in a continuous flow set-up. 

Figure 3.3. Asymmetric hydroformylation of non-volatile substrates using a stepwise injection into continuous flow reactor with scCC>2 as mobile phase...

TABLE 3.5. Results from the hydroformylation of 1-octene using silica-immobilised Rh(2) using a continuous flow reactor with SCCO2 as the mobile phasea... 

Figure 3.8. An early example of a hybrid support applied in the rhodium catalysed hydroformylation operated in a continuous flow reactor. Polystyrene containing phosphite ligands were grafted on inorganic silica, such that the catalyst will behave as a homogeneous catalyst when using a compatible solvent...

Horvath performed experiments using substrates with different solubilities in water and showed that, under optimal conditions, this solubility did not influence the activity [67]. These experiments clearly support the fact that the reaction takes place at the organic-water interphase. Furthermore, he performed a hydroformylation reaction in a continuous system and even under reaction conditions no leaching of rhodium complex was detected. Water obviously leaches if the SAPC is used in a continuous flow system, which in a practical application should be compensated for by using water-saturated organic solvents. 

The concept of continuous flow SILP hydroformylation was also tested in the biphasic, liquid-liquid hydroformylation of 1-octene using the Rh-norbos catalyst system [78], TOFs of 44 h"1 were achieved after 3-4 h with no sign of deactivation at prolonged reaction times. At steady-state conditions an n/iso ratio of 2.6 was obtained. No leaching of rhodium metal could be detected by ICP-AES analysis of product samples at least after these short reaction times. 

Hydroformylations were also carried out in IL/SCCO2 biphasic reaction systems [7]. In particular, it was demonstrated that continuous-flow systems could be operated successfully for the Rh-catalysed hydroformylation of hex-I-ene [24] and I-dodecene [25]. 

Figure 1 Flowsheet of the RCH/RP hydroformylation process 38 1 Continuous flow stirred tank reactor,424 2 Phase separator, 3 Stripping column, 4 Distillation column, 5 Heat exchanger, 6 Falling film evaporator, 7 Liquid vapor separator.

Species II and III (Reaction 3) were postulated to account for the catalytic behavior of these systems species II, for the amine-promoted hydrogenation activity, and species III, for continued hydroformylation activity in the presence of amine. In continuous flow experiments on polyDMBA catalysts, rhodium retention was reported to be good (9) with... 

Sellin MF, Webb PB, Cole-Hamilton DJ (2001) Continuous flow homogeneous catalysis hydroformylation of alkenes in supercritical fluid-ionic liquid biphasic mixtures. Chem Commun 8 781-782... 

In contrast, continuous flow reactors are already being used for hydrogenation reactions industrially (Licence el al., 2003). They are simple to construct and modify, and possess excellent mass- and heat-transfer properties. In academia, flow reactors have been used in conjunction with a variety of heterogeneous catalysts to carry out many reactions, including hydrogenations, dehydrogenations, hydroformylations, Friedel-Crafts acylations and alkylations, etherifications and oxidations (Hyde et al., 2001). 

In rhodium catalysed hydroformylation reactions, conversions achieved using a biphasic system were lower than those achieved in pure ionic liquid 40% in [Bmim][PF6]-scC02 99% in [Bmim][PF6] alone.However, the selectivity of linear to branched isomer was reversed and therefore these results were highly significant. This approach led to the development of a continuous-flow system for hydroformylation of alkenes, and under careful control the system could be used for several weeks without any visible sign of catalyst degradation. It should be noted that biocatalysts have also been used and recycled using biphasic ionic-liquid-carbon dioxide approaches. 

In a first approximation, the new methods correspond to the conventional solvent techniques of supported catalysts (cf Section 3.1.1.3), liquid biphasic catalysis (cf Section 3.1.1.1), and thermomorphic ( smart ) catalysts. One major difference relates to the number of reaction phases and the mass transfer between them. Owing to their miscibility with reaction gases, the use of an SCF will reduce the number of phases and potential mass transfer barriers in processes such as hydrogenation, carbonylations, oxidation, etc. For example, hydroformylation in a conventional liquid biphasic system is in fact a three-phase reaction (g/1/1), whereas it is a two-phase process (sc/1) if an SCF is used. The resulting elimination of mass transfer limitations can lead to increased reaction rates and selectiv-ities and can also facilitate continuous flow processes. Most importantly, however, the techniques summarized in Table 2 can provide entirely new solutions to catalyst immobilization which are not available with the established set of liquid solvents. 

Promising results have been reported by various laboratories since 1990 on catalysis in molten salts, notably for catalytic hydrogenation, hydroformylation, oxidation, alkoxycarbonylation, hydrodimerization/telomerization, oligomerization, and Trost-Tsuji coupling [113]. A continuous-flow application to the linear dimerization of 1-butene on an ionic-liquid nickel catalyst system reached activities with TON > 18000 [116]. 

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