Hydroformylation in water

3 HYDROFORMYLATION REACTIONS IN ALTERNATIVE MEDIA 8.3.1 Hydroformylation in Water 

As mentioned in the introduction, hydroformylation is an important industrial process used for the formation of aldehydes from alkenes. Some six million 

The limitations of hydroformylation reactions in water are the same as those of hydrogenation reactions, i.e. the poor solubility of the substrates (see Section 8.2.1). While aqueous-organic biphasic hydroformylation works well for alkenes with chain lengths up to C7, the solubility of longer chain alkenes is too low for viable processes. Although simple alkenes are poorly soluble, many functional alkenes have solubilities in water that are sufficiently high to avoid mass transfer problems, but at the same time this can impede separation. 

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Internal olefins (2-butene, 2-hexene) were also successfully hydroformylated in water with complexes prepared in situ from [PtCbCCOD)] and the tetrasulfonated diphosphines 37 at 100 °C and 80 bar syngas [148,149]. The same catalysts were suitable for the hydroformylation of 2- and 3-pentenoic acids and trans-2-pentenenitiile, too [150]. The -... 

Diarylethenes, 1,1-diarylallylalcohols and aryl vinyl ethers were succesfully hydroformylated in water/toluene or water/cyclohexane biphasic mixtures with a catalyst prepared in situ from[ RhCl(COD) 2] and TPPTS (Scheme 4.15). Yields of the desired linear aldehyde product were around 80%. This method was applied for the synthesis of the neuroleptics Fluspirilen and Penfluridol (Scheme 4.16) and for other pharmaceutically active compounds containing the 4,4-bis(p-fluorophenyl)butyl group [153]. 

Using RuCl(CO)(TPPTS)(BISBIS) the biphasic aqueous hydroformylation of higher olefins in the presence of the cationic surfactant CTAB ensures a TOF > 700 h and regioselectivity >96% for the linear aldehyde Piperazinium cationic surfactants were also successfully applied as catalysis promotion agents in the aq. biphasic hydroformylation of higher olefins. The property of surfactant and ligand can be assumed by the same molecule, e.g. di-sulfonated cetyl(diphenyl)phosphine 42. 1-Dodecene is hydroformylated in water/toluene (3 1) under mild conditions [olefin/Ru = 2500, CO/H2=1, P(CO + H2) = 15 bar, 42/Ru = 10] with TOF = 188 Another approach to... 

Fig. 7 Solubility of olefins [30, 31 a] and of the aldehydes obtained therefrom by hydroformylation in water [31 b, c].

Fig. 1 Comparison of 1-octene hydroformylation in water and aqueous methanol. The reaction time in water was 24 h the reaction time in 50% aqueous methanol was 5 h [10, 11],...

Olefins were hydroformylated in water-in-carbon dioxide microemulsions in the presence of organometallic catalysts formed in situ from Rh(CO)2acac and 3,3 ,3 -Phosphinidynetris(benzenesulfonic acid), trisodium salt (TPPTS) in the presence of synthesis gas. The microemulsions were supported by sodium salt of bis(2,2,3,3,4,4,5,5-octafluoro-1 -pentyl)-2-Sulfosuccinate (H(CF2)4CH200CCH2 CH(S03Na)COOCH2(CF2)4H (di-HCF4). The effects of the presence of salts and acid on the stability of microemulsions and activity were also investigated. 

Hydroformylation in Water/Acetone Formation of a Monocationic Dirhodium Catalyst... 

This chapter discusses some general aspects of the hydroformylation of alkenes in organic synthesis. It focuses mainly on regio- and stereoselective processes, and analyzes the influence of the substrate and the catalysts. Practical methods which provide high yields and selectivities, and short-cuts compared to classical organic routes will be described. Particular attention will be paid to recent advances that have helped to enlarge the synthetic application of this reaction. Section 6.7 deals with the hydroformylation of alkynes, and such key aspects as hydroformylation in water-gas shift conditions and silylformylation, particularly efficient catalytic systems and the application ofhydroformylation in organic synthesis. 

Cationic phosphine ligands containing guanidiniumphenyl moieties were originally developed in order to make use of their pronounced solubility in water [72, 73]. They were shown to form active catalytic systems in Pd-mediated C-C coupling reactions between aryl iodides and alkynes (Castro-Stephens-Sonogashira reaction) [72, 74] and Rh-catalyzed hydroformylation of olefins in aqueous two-phase systems [75]. 

Propanediol is a colorless liquid that boils at 210-211°C. It is soluble in water, alcohol, and ether. It is an intermediate for polyester production. It could be produced via the hydroformylation of ethylene oxide which yields 3-hydroxypropionaldehyde. Flydrogenation of the product produces 1,3-propanediol. 

An unusual enhancement of catalytic activity in a two-phase system has been reported by Fremy et al. (1998) for the hydroformylation of acrylic esters using Rh complex of TPTS as catalyst. Even though acrylic esters have reasonable solubility in water, rate enhancements in two-phase systems by a factor of 2 to 14 have been reported. It seems that water is not an inert solvent but also acts as a reactant or a co-ordinating solvent which can modify elementary steps of the catalytic cycle (Cornilis, 1997). 

For long chain olefins, the hydroformylation generally proceeds slowly and with low selectivity in two-phase systems due to their poor solubility in water. Monflier et al. recently reported a conversion of up to 100% and a regioselectivity of up to 95% for the Rh-catalyzed hydroformylation of dec-l-ene in water, free of organic solvent, in the presence of partially methylated 6-cyclodextrins (Eq. 3.42).173... 

Relatively little work has been devoted to the characterization of complexes in water and generally it has been assumed that for Rh-catalyzed hydroformylation similar species are formed in water as inorganic solvents, i.e., [RhH(L)2(CO)2] and [RhH(L)3(CO)] are the major species. Therefore, few references can be mentioned here which contain information about coordination complexes. In addition, a few, more recent, studies will be mentioned which do not report in situ coordination compounds. A HP NMR study of [RhH(TPPTS)3(CO)] has been reported. It was... 

The use of a water-soluble phosphine based catalyst is not a preferred choice for octene hydroformylation. Although separation of nonanal and its condensation products from an aqueous catalyst should be facile, forming nonanal at a commercially viable rate could be challenging. In order to react, octene needs to be in the same phase as the catalyst, and octane has very low solubility in water. 

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. 

So far only propene and butene are hydroformylated commercially using the RCH/RP process. A reason which has been postulated for this is the decreasing solubility in water with increasing number of C atoms in both the starting alkene and the reaction products (Figure 5.4) and the associated mass-transfer problems in the relatively complicated gas-liquid-liquid, three-phase reaction. 

With the RCH/RP process, it is possible to hydroformylate propene up to pentenes with satisfying space time yields. On the other hand, heavier aldehydes such as Cio (iso-decanal) or higher from the hydroformylation of nonene(s), decenes, etc. can not be separated from the oxo catalysts by conventional means such as distillation due to thermal instability at the required temperatures and thus especially needs the careful aqueous-biphasic separation technique. There are numerous attempts to overcome the problem of low reactivity of higher alkenes which is due to low miscibility of the alkenes in water [26,27b, 50a,58d]. These proposals can briefly be summarized as ... 

The group of Olivier-Bourbigou has shown, for example, that phosphite ligands can be used in the Rh-catalysed hydroformylation in ionic liquids as well as the well-known phosphine systems [51], Since phosphite ligands are usually unstable in aqueous media this adds, apart from the much better solubility of higher olefins in ionic liquids, another important advantage to biphasic hydroformylation using ionic liquids in comparison to the established biphasic reactions in water. 

General Procedure for the Hydroformylation/Fischer Indole Synthesis. Synthesis of Tryptamine Derivatives in Water. Aminoolefin (1 eq), aromatic hydrazine (1 eq), Rh(acac)(CO)2 (0.3 mol %) and TPPTS (1.5 mol %) are dissolved in H2SO4 (4wt% in H2O, 2.5 wt % olefin), filled in an autoclave and pressurized with lObar H2 and 50 bar CO. After stirring for 3 days at 100 °C ammonia (30 wt% in water) is added and the mixture is extracted with EtOAc. The solvent is evaporated to give the product which purified by column chromatography (silica, CH2C12, PrOH, NEt3) if necessary. 

The water-soluble ligands described above, together with many others, are used to conduct a wide range of catalytic reactions in water. These reactions include hydrogenation, hydroformylation, oxidation, C-C coupling and polymerization reactions [30], Many of these reactions are discussed in detail in Chapters 7-11. 

Water is a unique solvent because of its high polarity and ability to form a network of H-bonds. It is immiscible with many organic solvents and is therefore a suitable solvent for use in biphasic reactions in which catalysts are made preferentially soluble in the aqueous phase. Phase transfer catalysis allows the use of aqueous reagents with substrates that have low solubility in water. That water is abundant and totally non-toxic make it the perfect clean solvent, provided that solubility issues can be overcome, and it is in use as a solvent on an industrial scale for polymerization, hydroformylation, and a range of organic chemistry involving PTC. These applications are discussed further in Chapters 7-11. 

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