Reactions in neat water

Reactions in neat water can be feasible if and only if at least the major reagents are soluble in water. In the case when the efficiency of the catalytic process is sufficiently high, the process may run even if the solubility of the major reagent(s) is moderate or even quite poor. In such a case, the reagent that is poorly soluble in water shall form a separate phase serving as a feedstock for the reaction, which actually takes place in the aqueous phase. This technique is widely used, and owing to its practical importance it is described below in the paragraph on reactions in biphasic systems under phase-separation conditions. 

In general, reactions in which at least one of the reacting compounds is insoluble in water can be either homogenized by the addition of as much as possible of a suitable water-miscible cosolvent, or carried out in heterogeneous systems, using, as was noted above, (i) phase-transfer, (ii) phase-separation, or (iii) solubilization techniques. 

Aqueous catalysis brought forward an ingenious and amazingly simple solution to combine the reaction itself and the workup of the reaction mixture, commonly done by shaking it with water in a separatory funnel. The 

The simplest realization of solubilization phenomena is the well-known micellar catalysis, and the most complex is the operation of biological membranes [1, 2]. Practical application of solubilization depends on the development of systems that allow processing on the preparative scale. Simple micelles can rarely satisfy this requirement, as the solubilizing ability of such systems is quite low. High solubilizing ability is a feature of well-balanced surfactant systems, such as microemulsions and related media, establishing a perfect interpenetration of immiscible reagents. 

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A later report demonstrated similar chemistry under milder conditions. The apparently reduced effectiveness of the PTA in the previous work was noted, as was a further report where Pd/MjCOj/PTA had been demonstrated to catalyze the Heck reaction in water in excellent yield under mild conditions. This chemistry was therefore adapted to the solid phase. After tethering 4-iodobenzoic acid to TentaGel resin, the reaction with ethyl acrylate was examined and found to be successful with the conditions shown in Scheme 2. Initial attempts to run the reaction in neat water failed to convert starting material to product in much more than about 50% yield, but introduction of a DMF-water solvent mixture solved this problem. The chemistry was adapted for the coupling of a number of olefins (generally those with attached electron-withdrawing groups). In contrast to the previous report, where these reactions were shown with reversal of polarity (i.e., the reaction of solution-phase iodides and bromides with resin-bound 4-vinylbenzoic acid), no products were obtained in these reversed cases. 

Scheme 15.12 Mizoroki-Heck reaction in neat water in the presence of basic Amberlite IRA-400.

The reactions in neat water without organic cosolvent are restricted to water-soluble reagents or are run in heterogeneous phase-transfer assisted systems. In search of a general approach to process all sorts of substrates— hydrophilic and hydrophobic—in... 

Recycling of the catalyst is achieved by either sedimentation of polymer by hexane from aqueous organic solvent, or heating of reaction mixture above room temperature for the reactions in neat water. As the hydrophile-lipophile balance of the polymer varies with temperature, the increase of temperature renders the material less hydrophilic. Catalyst activity is reported not to be degraded after as much as 10 reuses. This is one of the most spectacular durability records set so far in recyclable Pd-catalyzed processes. 

Though the hydrogenation of the double bond is one of the basic catalytic reactions in Pd chemistry, httle has been published on aqueous variants of this process. Hydrogenation of o ,j8-unsaturated aldehydes in recyclable biphasic systems in the presence of TPPTS complex of palladium has been studied. - Also, a biphasic hydrogenation of nitrocompounds in the presence of PdCla and TPPTS under mild conditions has been reported. Room temperature homocoupling of aryl iodides was achieved in neat water or water-acetone mixture in the presence of Pd/C or Pd(OAc)2, and Zn dust (Scheme 87). The addition of 18-crown-6 was required for the reaction in neat water. The reactions are run under aerobic conditions. The effect of phosphine is negative. - ... 

Figure 1.26 A cross-section of products successfully prepared by the Heck-Matsuda reaction in neat water...

A microporous 1 2 polycondensate obtained by the treatment of anthracenebis (resorcinol) with La(0-i-Pr)3 was also successfully applied to this reaction in neat water at neutral pH with efficient recycling of the catalyst. ... 

A combination of copper bis(dodecylsulfate) and chiral bis(oxazoline) ligands allowed the reaction to occur in neat water in the presence of a catalytic amount of carboxylic acid with ee s up to 69% for the syn isomer.A chiral bis(oxazoline) supported on a modified poly(ethylene glycol) was also shown to be an effective copper(ll) ligand for this aldol reaction in neat water, with 31-63% ee, comparable to those obtained with nonsupported ligands in the same solvent. The solubility of the ligand in water allowed for a highly convenient catalyst recycling procedure. ... 

A modified rare earth catalyst (30) which is based on a polystyrene backbone as depicted in Scheme 4.15 can be applied even in neat water. It is attached via a hydrophobic oligomeric linker which creates a nonpolar reaction environment and acts as a surfactant for the substrates. The reaction of 4-phenyl-2-butanone with tetraallyltin in water using 1.6 mol% of the scandium catalyst (30) afforded the corresponding homoallylalcohol in a yield of 95%. Interestingly, when using other solvents (dichloromethane, acetonitrile, benzene, ethanol, DMF) the yields decreased drastically, indicating a much higher reaction rate in water [98]. 

In accordance with the suggested mechanism aryl iodides react easily (Scheme 6.2). At 80-100 °C, iodobenzene and acrylic acid gave cinnamic acid in neat water with [Pd(OAc)2] as catalyst and a mix of NaHCOs and K2CO3 as base [12]. Similar reactions were mn in water/acetonitrile 1/1 with... 

Similar to the case of Suzuki couplings (6.1.2), ally lie alkylations can also be run in neat water as solvent in the presence of surfactants. In addition to the general solubihzation effect, the amphiphiles may also have a specific influence on the reaction rate. For example, the reaction of the P-ketoester substrate on Scheme 6.22 with allyl acetate, catalyzed by [Pd(PPh3)4] was only slightly accelerated by the anionic SDS (1.5 h, 18 % yield), however, the reaction rate dramatically increased in the presence of the cationic CTAB and the neutral Triton X-100 detergents, leading to 74 % and 92% yields in 1.5 h and 5 min ( ), respectively [51]. Several other carbonucleophiles were alkylated in such emulsions with excellent yields. 

Cyclopropanation is an important synthetic method, and enantioselective catalytic reactions of olefins and diazoacetates provide access to valuable products with biological activity. In general, these reactions are conducted in anhydrous solvents and in several cases water was found to diminish the rate or selectivity (or both) of a given process. Therefore it came as a surprise, that the Cyclopropanation of styrene with (+)- or (-)-menthyl diazoacetates, catalyzed by a water-soluble Ru-complex with a chiral bis(hydroxymethyldihydrooxazolyl)pyridine (hm-pybox) ligand proceeded not only faster but with much Wgher enantioselectivity (up to 97 % e.e.) than the analogous reactions in neat THF or toluene(8-28 % e.e.) (Scheme 6.34) [72]. The fine yields and enantioselectivities may be the results of an accidental favourable match of the steric and electronic properties of hm-pybox and those of the menthyl-dizaoacetates, since the hydroxyethyl or isopropyl derivatives of the ligand proved to be inferior to the hydroxymethyl compound. Nevertheless, this is the first catalytic aqueous cyclopropanation which may open the way to other similar reactions in aqueous media. 

A recent addition to this field is the polymer-supported di(2-pyridyl)-methylamine-palladium dichloride complex covalently attached to a styrene-alt-maleic acid anhydride copolymer. Turnover numbers as high as 105 were reported and a couple of microwave-heated Suzuki-Miyaura reactions could be performed in neat water [134], 2-Pyridinealdoxime-based Pd(II)-... 

An additional information relates to the microviscosity of the PP solutions. Their macroscopic viscosity is very high. However, the Ps reaction rate constant measured above Rc0 is only slightly lower than what it is in water on a microscopic scale, the diffusive properties of Ps inside the net created in the PP solution by the polymeric chains are similar to those in neat water... 

Pyridine-catalyzed acylation of phenols using benzoyl chloride and benzoyl bromide was reported . Acylation of phenols using acetyl chloride or benzoyl chloride can be achieved using triflic acid as the catalyst in nonpolar solvents snch as methylene chloride. The role of pyridine in these reactions seems to be the intermittent formation of the benzoylpyrimidinium ions as the reactive species. The activated phenolic componnds snch as resorcinol, on the other hand, could be acylated in near-supercritical water (250-300 °C) without using any external Lewis acid catalysts (equation 47) . The equilibrium conversions in water, however, are to the extent of about 4%. Running the same reactions in neat acetic acid causes a tenfold increase in yield. 

In the cyclotrimerization of propynoic acid, trimellitic (l,2,4-fb,l l3((X)2H),) and trimesic acid (l,3,5-CgH3(CO2H)3) are obtained as the product of head-to-head or head-to-tail linkage, respectively. For the sake of comparison, reactions were conducted both in neat water and in neat THF. In all cases, the yield of the trimer was higher in the aqueous system, evidencing the high tolerance of the rhodium catalyst towards water. 

Telomerization of butadiene into 2,7-octadien-l-ol was also performed in neat water in the presence of carbon dioxide and certain trialkylamines in the presence of Pd(OAc)2/tppts or Pd(OAc)2/tppms, the structure of these amines having an important influence on the rate and the selectivity of the reaction... 

Beletskaya and co-workers have shown that the reaction is possible in neat water as solvent. Thus, aryl iodides have been carbonylated with various palladium salts lacking phosphine ligands as depicted in Eq. (4) [7]. Although this reaction is not a truely biphasic process the results are remarkable regarding catalyst efficiency. Thus, a maximum turnover number (TON) of 100000 was described (R = p-COOH, quantitative yield after 6 days). Quite different is the performance of a water-soluble palladium phosphine catalyst described by Kalck et al. [8]. The hy-drocarboxylation of the less activated bromobenzene with either Pd(TPPTS)3 or a mixture of Pd(OAc)2 and TPPTS proceeds only sluggishly (turnover frequency TOF < 10 h 1). In order to prevent decomposition of palladium an excess of phosphine has to be used. At least 15 equiv. of ligand is necessary to prevent formation of metallic palladium. Because of rapid oxidation of the ligand the re-use of the water phase is not possible. 

Furthermore, Bumagin and Beletskaya reported the first coupling in neat water in the presence of a small amount tributylamine (10 mol%) and potassium carbonate as base [23], Surprisingly, the catalyst system consists of water-insoluble tri-phenylphosphine with PdCl2 and Cul at room temperature, resulting in high yields with aryl iodides and phenylacetylene. The role of cuprous iodide was noted to be important to facilitate the reaction, which may be rationalized by two connected catalytic cycles (Scheme 2). 

Some examples of the formation and reactivity of solvated electrons have been cited earlier. Another paper is concerned with an investigation of dynamics of electron and cation generated in neat water over the femto-second timescale reported for both H2O and 020. A quite different reaction studied on the sub-ps... 

After 15 consecutive reaction cycles, only a slight loss in productivity was observed, which was ascribed to a partial oxidation of the phosphine ligand. The fact that these polymers were no longer soluble in neat water above a certain temperature was used as an alternative for separating this catalyst the polymers were precipitated upon heating and could be separated. However, this concept required the catalytic reaction to be performed at lower temperatures (10 °C), consequently resulting in longer reaction times [2],... 

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