Carbonylation aqueous biphasic

Figure 2.29. Pd/tppt.s-catalysed carbonylations in aqueous biphasic media.

The Boots Hoechst Celanese (BHC) ibuprofen process involves palladium-catalyzed carbonylation of a benzylic alcohol (IBPE). More recently, we performed this reaction in an aqueous biphasic system using Pd/tppts as the catalyst (Figure 9.6 tppts = triphenylphosphinetrisulfonate). This process has the advantage of easy removal of the catalyst, resulting in less contamination of the product. 

Carbonylation of aromatic halides is of great industrial interest and several efforts were made to produce the corresponding benzoic acids in aqueous (biphasic) reactions. The tendency of an aromatic C-X bond to react in an oxidative addition onto Pd(0) as required by the reaction mechanism (Scheme 5.4) decrease in the order X = I > Br > Cl so much that chloroarenes are notoriously unreactive in such reactions. 

The salt production can be circumvented by performing the selective Pd/ tppts-catalysed carbonylation of benzyl alcohol in an acidic aqueous biphasic system (Fig. 1.36) [106]. This methodology was also applied to the synthesis of ibuprofen (see earlier) by biphasic carbonylation of l-(4-isobutylphenyl)ethanol [107] and to the biphasic hydrocarboxylation of olefins [108]. 

To determine the mode of operation (see below) it is useful to group these homogeneous catalysts into aqueous biphasic systems (see Section 3.1.1.1) and nonaqueous biphasic systems (see Section 3.1.1.2). Gas-liquid-liquid reactions are also involved in organometallic phase transfer catalysis, e. g., in biphasic carbonylation of benzyl chloride to phenylacetic acid by the catalyst system NaCo(CO)4/Bu4NBr/NaOH [21]. Here, the biphasic system consists of an organic solvent and aqueous alkali. 

Hydroformylation and Carbonylation Reactions in Aqueous Biphasic Systems... 

All these observations were empirical, individual results of unsystematic experiments. Since water had been judged, as mentioned, to be incompatible with the metal carbonyl catalysts of the oxo process, this solvent was not a seriously considered alternative. This paper points the way to the introduction of water as a future-oriented solvent for industrial homogeneous catalysis. Applications of phase transfer catalysis will not be considered here (since they require additional, cost-increasing phase transfer agents), but the emphasis will be placed on aqueous biphasic homogeneous catalysis and its status and possibilities. 

The tenside phosphines 38 (n = 1, 2, 3) containing amino and phosphonate moieties were used as ligands to impart surfactant properties to Pd catalysts for the carbonylation (cf. Section 6.5) of benzyl chloride to phenylacetic acid under aqueous-biphase conditions [66], The recovery of the Pd/38 catalyst after the carbonylation reaction, however, was only 85-92%. 

Interestingly, the nitro group can be selectively reduced to an amino group at TO Ns of some thousands, even in the presence of halide substituents or a vinyl group [3] although recycling of the catalyst was not possible due to decompsition. The reductive carbonylation of 5-hydroxymethylfurfural under aqueous biphasic conditions yields the 5-methyl derivative instead of dicarbonylation [4],... 

Industrial significance has also been acquired by the aqueous biphasic Pd-catalyzed carbonylation of benzyl chloride to phenylacetic acid [Eq. (1)]. Once more, TPPTS is the ligand of choice [4]. 

Two-phase, or biphasic, catalysis has gained increasing attention over the past two decades. One driving force undoubtedly was the successful implementation of large-scale applications in industry. Rhodium-catalyzed aqueous biphasic propylene hydroformylation, performed by the Ruhrchemie/Rhone-Polenc process, represents the most important carbonylation reaction today, with a total outcome of more than... 

Doubtless, the hydroformylation reaction was the most investigated transition metal catalyzed carbonylation reactions in ionic liquids. This is mainly because of the industrial importance of this reaction that is in operation in various plants, which in some of them operates in aqueous biphasic regimes. The intense academic and industrial interest is mainly because of the limitations of the current aqueous-phase process to short-chain (heavier olefins in water for an effective and reasonable reaction rate to occur. 

As an alternative to the use of fluorous tag, fluorous aqueous biphasic systems have also been explored. Recently, fluorous biphasic system composed of fluorous Lewis acid ytterbium perfluorooctanesulfonate [Yb(OPf)3], fluorous solvent perfluorocarbon has been used in the synthesis of benzodiazepines from OPD and carbonyl compounds [127]. Conceptually, the fluorous catalyst with perfluoroalkylated tails can dissolve into the fluorous phase containing the product after the reaction. The study has been extended later to the use of fluorous aqueous emulsion expecting that the organic substrate will remain in the interfacial area between a fluorous phase and aqueous media. Thus another synthesis of benzodiazepines has been reported by the same group by carrying out the reaction in a fluorous aqueous emulsion system composed of perfluorooctane and potassium perfluorooctanesulfonate at room temperature (Scheme 38) [128]. Moreover, the emulsion could be recovered and recycled without significant loss of activity. 

Usually, iodides and bromides are used for the carbonylation, and chlorides are inert. I lowever, oxidative addition of aryl chlorides can be facilitated by use of bidcntatc phosphine, which forms a six-membered chelate structure and increa.scs (he electron density of Pd. For example, benzoate is prepared by the carbonylation of chlorobenzene using bis(diisopropylphosphino)propane (dippp) (456) as a ligand at 150 [308]. The use of tricyclohexylphosphine for the carbonylation of neat aryl chlorides in aqueous KOH under biphasic conditions is also recommended[309,310]. 

In order to keep the mild conditions, hydroxycarbonylation has been performed in biphasic media, maintaining the catalyst in the aqueous phase thanks to water-soluble mono- or diphosphine ligands. In the presence of the sodium salt of trisulfonated triphenylphosphine (TPPTS), palladium was shown to carbonylate efficiently acrylic ester [19], propene and light alkenes [20,21] in acidic media. For heavy alkenes the reduced activity due to the mass transfer problems between the aqueous and organic phases can be overcome by introducing an inverse phase transfer agent, and particularly dimeihyl-/-i-cyclodextrin [22,23]. Moreover, a dicationic palladium center coordinated by the bidentate diphosphine ligand 2,7-bis(sulfonato)xantphos (Fig. 2) catalyzes, in the presence of tolylsulfonic acid for stability reasons, the hydroxycarbonylation of ethylene, propene and styrene and provides a ca. 0.34 0.66 molar ratio for the two linear and branched acids [24],... 

Benzyl halides are easily carbonylated to phenylacetic acid derivatives which are valuable intermediates for Pharmaceuticals, cosmetics and fragrances [2,3], Several papers report the aqueous/organic biphasic realization of this reaction [1,19-22] (Scheme 5.3). The main characteristics of these processes are summarized in Table 5.1. 

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory dmgs (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by hydroxycarbonylation [51,53] (several more listed in [52]). The carbonylation of styrene itself serves as a useful test reaction in order to learn the properties of new catalytic systems, such as activity, selectivity to acids, regioselectivity (1/b ratio) and enantioselectivity (e.e.) in the branched product. In aqueous or in aqueous/organic biphasic systems complexes of palladium were studied exclusively, and the results are summarized in Table 5.2. 

Higher olefins have negligible solubility in water therefore their hydrocarboxylation in aqueous/organic biphasic systems needs co-solvents or phase transfer agents. With the aid of various PT catalysts 1-octene and 1-dodecene were successfully carbonylated to the corresponding carboxylic acids with good yields (< 85 %) and up to 87 % selectivity towards the formation of the linear add with a [Co2(CO)g] catalyst precursor under forcing conditions (150 °C, 200 bar CO) [57],... 

In water-heptane biphasic systems, allylic alcohols underwent rearrangement to the corresponding carbonyl compounds with a catalyst prepared in situ from RhCU.aq and TPPTS. The reactions proceeded very fast (TOP up to 2500 h ) and in most cases provided the carbonyl products quantitatively. The industrially interesting geraniol was isomerized mostly to citronelM, albeit octatrienes and tricyclene were also produced. With an increase of the pH of the aqueous phase the yield of isomerization decreased somewhat (from 48 % to 40 %), however the selectivity towards the... 

Concentrated aqueous salt solutions were used for dehydration of carbohydrates catalyzed by RuCh + Ag2S04 ( RUSO4 ) [47]. Such solvents may also help in constracting aqueous-organic biphasic media with good phase separation properties. Selective dehydroxylation of polyols and sugars was achieved in aqueous solutions with the use of anionic rathenium carbonyls, as well [48]. 

One method is to run the reaction in an aqueous buffer/organic solvent biphasic system. This makes it possible to work at high substrate and product concentrations and at the pH-optimum of the enzyme. In addition, in water-immiscible solvents the non-enzymahc addition of HCN to the carbonyl group is non-existent or extremely slow. Possible disadvantages are enzyme deactivation at the interface and the presence of organic solvent dissolved in the aqueous phase [15, 17, 18]. 

Carbonylation of Alcohols - Pd(tppts)3 catalyses the carbonylation of benzylic alcohols to the corresponding phenylacetic acids, in the presence of a Bronsted acid cocatalyst such as H2S04 or p-CH3C6H4S03H in biphasic aqueous/organic media (no organic solvent).305,451 For example, benzyl alcohol was converted to phenylacetic acid (Equation 6) and l-(4-isobutylphenyl)ethanol (IBPE) to ibuprofen (Figure 9). 

A chapter written in 1996 covers hydroformylation catalyzed by organometallic complexes in detail,219 whereas a review written 5 years later gives a summary of the advances on hydroformylation with respect to synthetic applications.220 A selection of papers in a special journal issue has been devoted to carbonylation reactions.221 A major area of the research has been the development of fluorous biphasic catalysis and the design of new catalysts for aqueous/organic biphasic catalysis to achieve high activity and regioselectivity of linear or branched aldehyde formation. 

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