Biphasic Transfer Hydrogenations

For the simplest form of such reactions, palladium on charcoal is the catalyst and aqueous formate the hydrogen donor. Interfacial transport of formate is facilitated by an organophilic counter ion, and for the present purpose a triethylammonium ion is mostly used [48, 49]. 

There is yet another transfer/PTC hydrogenation method for the reduction of ketones to alcohols here 2-propanol in dilute NaOH is the reductant, a QX is the phase-transfer agent, and HFe3(CO)j1 (generated in situ from Fe3(CO)12) is the metal catalyst [57]. 

Aqueous/Organic-phase Oxidations Mediated by Metal and PT Catalysts 

Aqueous hydrogen peroxide is one of the cheapest and most convenient oxidants. It can be extracted into organic media with an onium salt QX as a complex [QX H2Oz] [58], Patents describe oxidations of alkenes in the additional pres- 

The relevant literature in this subfield is too voluminous to be detailed here. Overviews are available [62], and only a few recent references to the newest publications are given below. Oxidations of the following types have been performed alcohol - ketone [63] aldehyde — acid alkene — diol or epoxide [64-67] al-kene - aldehyde, acid 1-alkyne — ketoaldehyde and acid (1 C-atom shorter) internal alkyne — a,/3-epoxyketone vic-diol — 1,2-diketone [68] or hydroxyketone [69] amine — amine oxide [70] aromatic amine — nitrosobenzene, nitrobenzene, azoxybenzene [71]. 

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A benzene imidazolium-tagged ruthenium complex immobilized in [G4GiGiIm]PF6 is a highly enantioselective IL biphasic transfer hydrogenation catalyst (isopropanol/KOH) of acetophenone as compared with conventional (untagged) complexes (Figure Along the same lines, a diimide-imidazolium salt moiety associated with... 

Table 2 Results of the transfer hydrogenation of ketones with fluorinated (salen)Ir complexes under biphasic conditions ...

Water-soluble complexes constitute an important class of rhodium catalysts as they permit hydrogenation using either molecular hydrogen or transfer hydrogenation with formic acid or propan-2-ol. The advantages of these catalysts are that they combine high reactivity and selectivity with an ability to perform the reactions in a biphasic system. This allows the product to be kept separate from the catalyst and allows for an ease of work-up and cost-effective catalyst recycling. The water-soluble Rh-TPPTS catalysts can easily be prepared in situ from the reaction of [RhCl(COD)]2 with the sulfonated phosphine (Fig. 15.4) in water [17]. 

The transfer hydrogenation methods described above are sufficient to carry out laboratory-scale studies, but it is unlikely that a direct scale-up of these processes would result in identical yields and selectivities. This is because the reaction mixtures are biphasic liquid, gas. The gas which is distilled off is acetone from the IPA system, and carbon dioxide from the TEAF system. The rate of gas disengagement is related to the superficial surface area. As the process is scaled-up, or the height of the liquid increases, the ratio of surface area to volume decreases. In order to improve de-gassing, parameters such as stirring rates, reactor design and temperature are important, and these will be discussed along with other factors found important in process scale-up. 

Pioneering studies of the use of water soluble noble metal complexes of sulfonated phosphines as catalysts in aqueous biphasic systems were performed in the early 1970s, by Joo and Beck in Hungary and Kuntz at Rhone-Poulenc in France. Joo and Beck studied catalytic hydrogenations and transfer hydrogenations using Rh or Ru complexes of tppms [24]. Kuntz, on the other hand, pre-... 

Several of the factors of Figure 3 controlling the activity and selectivity of the biphasic selective hydrogenation of ,/ -unsaturated aldehydes to allylic alcohols, for instance, 3-methyl-2-butenaldehyde to 3-methyl-2-buten-l-ol (Eq. 11) with rutheni-um-sulfonated phosphine catalysts were investigated [11], such as the effect of agitation speed and the influence of aldehyde, ligand, and metal concentrations. Under optimized reaction conditions, where gas-liquid mass transfer was not rate-determining, the kinetic equation (Eq. 12) was found to apply. A zero-order dependence with respect to the concentration of the ,/i-unsaturated aldehyde was found. 

Water-soluble Rh(I) complexes containing TPPTS catalyzed the transfer hydrogenation of itaconic, mesaconic, citraconic and tiglic acids as well as that of a-acetamidoacrylic and a-acetamidocinnamic acids from HCOOM (M = Na+, K+, NH,+) [235], The reactions were ran at 50 °C for 15-67 h, during which 48-100 % conversions were achieved. Use of the chiral tetrasulfonated cyclobutanediop, 37, led to an enantiomeric excess of up to 43 %, which is close to the value obtained in biphasic hydrogenations catalyzed by the same rhodium complex [100],... 

NADP+ in a reaction with 2-propanol accompanied by formation of acetone as coproduct. Both ketone/alcohol reactions are equilibrium processes and therefore high 3delds of (f )-2-octanol are not available in a monophasic aqueous system, or in an organic-aqueous biphasic system where the partition coefficients of 2-propanol and acetone are approximately the same. It was found, however, that in a biphasic water/[bmim][(CF3S02)2N] system acetone was preferentially dissolved by the IL phase and this pulled the catalytic transfer hydrogenation of NADP+ by 2-propanol in the aqueous phase to near completion. Consequently, almost quantitative yields of (i )-2-octanol were obtained (275). 

Events around the chemical step of reduction/oxidation were monitored by directly observing the conversion of NADPH to NADP+. The kinetics are again biphasic owing to the rapidity of the hydride transfer process that the rapid phase is associated with the chemical step is verified by the observation of a Idnelic deuterium isotope effect of 3 when the transferring hydrogen of the NADPH is replaced with deuterium. This step shows a pH dependence with a pAa of 6.5 that imphcates the Aspl25 (27 in E. coli) in the proton transfer events required to complete the reduction. 

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