Biphasic reactions solvent selection

For this specific task, ionic liquids containing allcylaluminiums proved unsuitable, due to their strong isomerization activity [102]. Since, mechanistically, only the linkage of two 1-butene molecules can give rise to the formation of linear octenes, isomerization activity in the solvent inhibits the formation of the desired product. Therefore, slightly acidic chloroaluminate melts that would enable selective nickel catalysis without the addition of alkylaluminiums were developed [104]. It was found that an acidic chloroaluminate ionic liquid buffered with small amounts of weak organic bases provided a solvent that allowed a selective, biphasic reaction with [(H-COD)Ni(hfacac)]. 

Obviously, the ionic liquid s ability to dissolve the ionic catalyst complex, in combination with low solvent nucleophilicity, opens up the possibility for biphasic processing. Furthermore it was found that the biphasic reaction mode in this specific reaction resulted in improved catalytic activity and selectivity and in enhanced catalyst lifetime. 

Obviously, there are many good reasons to study ionic liquids as alternative solvents in transition metal-catalyzed reactions. Besides the engineering advantage of their nonvolatile natures, the investigation of new biphasic reactions with an ionic catalyst phase is of special interest. The possibility of adjusting solubility properties by different cation/anion combinations permits systematic optimization of the biphasic reaction (with regard, for example, to product selectivity). Attractive options to improve selectivity in multiphase reactions derive from the preferential solubility of only one reactant in the catalyst solvent or from the in situ extraction of reaction intermediates from the catalyst layer. Moreover, the application of an ionic liquid catalyst layer permits a biphasic reaction mode in many cases where this would not be possible with water or polar organic solvents (due to incompatibility with the catalyst or problems with substrate solubility, for example). 

These critical aspects of the classical fluorous biphasic catalysis led in recent works to the development of protocols for the conversions with modified catalyst systems in non-fluorinated hydrocarbons as solvents. As part of the BMBE lighthouse project, Gladyzs and coworkers appHed this concept to C - C coupHng reactions (Suzuki reaction) and other metal-catalyzed addition reactions (hydrosilylation, selective alcoholysis of alkynes), which have direct relevance for the synthesis of fine chemicals and specialties [74]. 

The reaction is catalyzed by palladium complexes either pre-formed, as [Pd(TPPMS)3] [13], or prepared in situ from (usually) [Pd(OAc)2] and various phosphines [21,23-27], TPPTS being one of the most frequently used [14]. Other precursors, e.g. [ PdCl(T -C3H5) 2] and so-caUed ligandless (phosphine-free) Pd-catalysts can also be effective. In fact, in several cases a phosphine inhibition was observed [23]. The solvent can be only slightly aqueous (5 % water in CH3CN, [14]) or neat water [26]. In the latter case a biphasic reaction mixture (e.g. with toluene) facilitates catalyst separation albeit on the expense of the reaction rate. A short selection of the reactions studied in aqueous solvents is shown on Scheme 6.9. 

Figure 5.2-2 Enhanced dimer selectivity in the oligomerization of compound A due to a biphasic reaction mode with a catalyst solvent of high preferential solubility for A.

Water is cheap, relatively abundant in many part of the world, safe, and, when pure, environmentally benign [40]. It is also true that some reactions show unusual selectivity and/or rate enhancements when run in, or more accurately, on water [41]. However, a closer examination of many reactions in water reveals that in fact one or more liquid reagents have been used in large excess, so they are in fact biphasic reactions. There is also a misguided perception that water, after use as a reaction medium, can be poured down the drain [42]. On an industrial scale, there can be a considerable cost and environmental burden associated with remediation of waste water streams contaminated with solvents and organic and metal residues-see Chapters 2 and 3. 

Biphasic reaction conditions can be achieved within a wide range of operating conditions with respect to co-solvents. The most common co-solvents are the lower alcohols the purpose is to improve substrate solubility and as a consequence to increase reaction rate. Recent work with ethanol as a co-solvent shows that this is very effective at improving reaction rates [3]. It is estimated for example that the solubility of 1-octene in a 50 50 mixture of ethanol and water is 104 times greater than in water alone [3], In a comparison of several co-solvents - ethanol, methanol, acetone, and acetonitrile - it was found that ethanol was the most effective at improving reaction rates in the two-phase hydroformylation of 1-octene [4], Generally, though, the use of co-solvents in hydroformylation reactions with Rh/TPPTS catalysts is not advisable, because of diminished reaction selectivity and the possibility of acetal formation (see below). 

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