Carbonylation reactions, biphasic

Much less attention has been focused on carbonylation reactions in ionic liquids. The biphasic palladium-catalyzed alkoxy carbonylation of styrene. Scheme 2, in [bmim][BF4]—cyclohexane has been reported. ... 

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. 

C-C coupling reactions include Pd-catalyzed carbonylations as well as Heck reactions. Biphasic operations are reported as being particularly efficient. Allyl and benzyl chlorides have been converted in two-phase systems to the corresponding acids with or without phase-transfer catalysts (eq. (6)) [154-157, 237]. 

It should also be noted that less-reactive chloroarenes can be carbonylated under biphasic conditions using bis(tricyclohexylphosphine)palladium dichloride as the metal catalyst. Again, the presence of a PT agent does not alfect the reaction... 

Hydroformylation and Carbonylation Reactions in Aqueous Biphasic Systems... 

As an extension to a biphasic system reported previously, de Mello and coworkers [77] described the incorporation of a silica-supported Pd catalyst into a fluidic system and investigated the gas-solid-liquid carbonylation reaction of an aryl halide (24), an amine (134) and carbon monoxide (Scheme 6.33), to afford the respective N-benzylbenzamide (135). To conduct the reaction, a solution of aryl halide and amine, in THF, was pumped through the reactor at a flow rate of 10 pi min-1, where it was mixed with CO (2 seem) in a T-mixer, prior to passing through the packed-bed reactor [1 mm i.d. x 45 cm (length)]. Maintaining the system at 75 °C,... 

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%. 

The carbonylation of chloroarenes has been described by Alper and Grushin [27] and Jenner and Bentaleb [28], While the former showed that square-planar complexes of divalent palladium, [ L2PdCl2], where L = tertiary phosphine, are active catalysts for the biphasic carbonylation of aromatic halides, including chloroarenes (when L = tricyclohexylphosphine), to the corresponding carboxylic acids, the latter demonstrated that chloroarenes can be converted into aromatic acids via catalytic reaction with aqueous methyl formate under biphasic conditions. [ PdCl2(PCy3)2] was the most efficient catalyst. The addition of [ Ru3(CO)12] and ammonium formate improved yield and selectivity of the carbonylation reaction. The mechanism should involve oxidative addition of the C—Cl bond to a zero-valent Pd species followed by CO insertion. However, the palladium catalyst may also directly activate methyl formate. Compared to other carbonylations of aryl-Hal compounds the procedure is quite convenient (no solvent, no initial pressurization) [27]. 

Apart from hydroformylations, other biphasic carbonylation reactions of organic substrates are still a relatively unexplored research area. So far, nearly all reported reactions in a two-phase system suffer similarly to their homogeneous counter-... 

In view of the vast number of homogeneous carbonylation reactions known it is easy to say that biphasic carbonylations have not yet reached their culmination point. Moreover, the actual importance of other two-phase media, e.g., fluorous biphasic systems [26] (cf. Section 7.2), will lead to further exploitation for carbonylations. 

Apart from hydroformylations, the potential advantages of two-phase catalysis for other carbonylation reactions have not been thoroughly evaluated. Only a few examples of carbonylation reactions under biphasic conditions have been described. 

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... 

This chapter will focus on biphasic carbonylation reactions that are divided by reaction types. Mainly results from 2005 and younger literature are covered. 

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. 

Similarly, Pd/tppts was used by Hoechst (Kohlpainter and Beller, 1997) as the catalyst in the synthesis of phenylacetic acid by biphasic carbonylation of benzyl chloride (Fig. 2.29). The new process replaces a classical synthesis by reaction of benzyl chloride with sodium cyanide, followed by hydrolysis of the resulting benzyl cyanide. Although the new process produces one equivalent of sodium chloride, this is substantially less salt production than in the original process. Moreover, sodium cyanide is about seven times as expensive per kg as carbon monoxide. 

We have exploited this base catalysis of the oxygen exchange process to effect oxygen lability in the less electrophilic carbonyl sites of neutral metal carbonyl species. Because [MCOOH] intermediates are readily decarboxylated in the presence of excess hydroxide ion, in order to observe oxygen exchange processes in neutral metal carbonyl complexes it was convenient to carry out these reactions in a biphasic system employing phase transfer catalysis () (16, 17. 18). Under conditions (eq. 7) the... 

Figure 5.14 Sol-gel immobilized TEMPO is an off-the-shelf alcohol oxidation catalyst. In a biphasic reaction system and in organic solvent it yields carbonyls in water it yields carboxylates.

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. 

In the carbonylation of allyl halides the highly toxic [Ni(CO)4] catalyst could be replaced by [Ni(CN)2], which yielded [Ni(CN)(CO)jr under the reaction conditions [17]. The cyanotricarbonylnickel(0) anion is a versatile catalyst of carbonylations under phase transfer conditions [18], however, hydroxycarbonylation of allyl chloride proceeds effectively without PT catalysts in a genuine biphasic system, as well. 

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. 

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 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. 

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... 

As expected, cyclohexanone hydrogenation performed in an IL has a longer reaction time than in solventless conditions. Where using iridium nanoparticles dispersed in an IL, the biphasic hydrogenation of cyclohexanone could be performed at least 15 times, without any considerable loss in catalytic activity this contrasted with the use of nanoparticles in solventless conditions, when the catalytic activity begins to decHne after the third cycle. The standard experimental conditions established for the hydrogenation of other carbonyl compounds were 75 °C, 4atm of H2 and a molar substrate Ir ratio of 250. 

A biphasic system consisting of the ionic liquid [BMIM]PF6 and water was used for the epoxidation reactions of a, 3-unsaturated carbonyl compounds with hydrogen peroxide as an oxidant at room temperature 202). This biphasic catalytic system compared favorably with the traditional phase transfer catalysts. For example, under similar conditions (15°C and a substrate/NaOH ratio of five), the [BMIM]PF6/H20 biphasic system showed a mesityl oxide conversion of 100% with 98% selectivity to oc, 3-epoxyketone, whereas the phase-transfer catalyst with tet-rabutylammonium bromide in a CH2CI2/H2O biphasic system gave a conversion of only 5% with 85% selectivity. 

A butoxylcarbonylation reaction was conducted in a liquid-liquid biphasic system under process conditions, but the removal of the product was conducted in a liquid-solid biphasic system at a lower temperature (84). lodobenzene or 4-bromoacetophenone reacted with CO at a pressure of 1-8 atm in the presence of a palladium-benzothiazole complex catalyst in the ionic liquid [TBA]Br (m.p. = 110°C) in the presence of Et3N base. The catalyst/ionic liquid system was recycled by extractive removal of the butyl ester product with diethyl ether. The solid residue, containing the catalyst, [TBA]Br, and Et3N.HBr, remained effective in subsequent carbonylation tests. After each cycle, the yields were still close to the initial value. A slight decrease in yield was attributed to a loss of catalyst during handling. 

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