Biphasic water/acetonitrile

The Wacker reaction was chosen as a representative reaction since in this case the conversion of an alkene to a ketone or an aldehyde can be achieved in one step, which is of industrial relevance. The reaction was carried out in a biphasic water/ acetonitrile system at 50-60 °C in an oxygen atmosphere, using the copper/ polyaniline nanocomposite, as well as a bare copper nanocluster. In the system, copper is present in the zero-valent state supported by polyaniline. Although 2-decanone is the only product formed, the yield obtained is still relatively low. It has to be mentioned in this context that the reaction carried out in the presence of bare copper nanoclusters showed no evidence for the presence of 2-decanone, indicating that those copper nanoclusters alone do not bring about the oxidation of 1-decene. 

DKR of thioesters (Scheme 21.2) with a chiral center at the a-carbon has been achieved in a water/acetonitrile biphasic system by racemization with mild organic bases, such as trioctylamine, coupled to enantioselective hydrolysis of the thioester with subtilisin Carlsberg.28 Such an approach can be applied to a wide variety of thioesters but not oxoesters, which have less acidic a-protons. 

Using FeS04 (1.67 x 10 M) in conjunction with equimolar amounts of methyl-pyrazine-5-carboxylic acid N-oxide and trifluoroacetic acid, in a water-acetonitrile-benzene (5 5 1 v/v/v) biphasic system, with benzene-H202-FeS04 = 620 60 1, a benzene conversion of 8.6% is achieved (35 °C 4h). Hydrogen peroxide conversion is almost complete (95%) and selectivities to phenol are 97% (based on benzene) and 88% (based on H2O2) [13]. These values are definitely higher than those described in the literature for the classical Fenton system [14], whereas iron complexes with pyridine-2-carboxylic acid derivatives are reported to be completely ineffective in the oxidation of benzene under the well-knovm Gif reaction conditions [15]. 

Cheese mostly contains the carotenoids bixin and norbixin. To extract these pigments, cheese is crushed in a solution of water/tetrahydrofuran (1 1 v/v) and centrifuged. The supernatant is biphasic The aqueous phase contains norbixin, and the organic phase contains mainly bixin. Norbixin and bixin can be separated by HPLC using a linear gradient starting with 100% of water/acetone (3 2 v/v) to 100% of water/acetonitrile (1 4 v/v) in 15 minutes (Tricard et al., 1998). 

Section 3.2). Catalytic application of the iodine(V) species in the oxidation of alcohols has been reviewed by Uyanik and Ishihara [10, 75]. The first examples of a catalytic application of an iodine(V) species (i.e., IBX) in the oxidation of alcohols using Oxone as a stoichiometric oxidant were independently reported by the groups of Vinod [4] in 2005 and Giannis [5] in 2006. Vinod s group employed 20-40 mol% of 2-iodobenzoic acid in a water-acetonitrile biphasic solvent system, in which primary and secondary alcohols were oxidized to carboxylic acids and ketones, respectively (Scheme 4.44) [4]. 

A biphasic solvent system composed of tert-butyl methyl ether, -butanol, acetonitrile, and water (2 2 1 5) acidified with triflnoroacetic acid has been applied to fractionate anthocyanins. The npper (organic) phase acts as the stationary phase and the lower (aqneons) as the mobile phase. HSCCC has been applied to obtain several anthocyanin fractions from wine, red cabbage, black cnrrants, chokeber-ries, " bilberries (Vaccinium myrtillus) acylated anthocyanins, and also isolate individnal anthocyanins from wine. ... 

Monflier et al. (1997) have suggested Pd catalysed hydrocarboxylation of higher alpha olefins in which chemically modified P-cyclodextrin (especially dimethyl P-cyclodextrin) is u.sed in water in preference to a co-solvent like methanol, acetone, acetic acid, acetonitrile, etc. Here, quantitative recycling of the aqueous phase is possible due to easy phase separation without emulsions. A similar strategy has been adopted by Monflier et al. (1998) for biphasic hydrogenations for water-in.soluble aldehydes like undecenal using a water-soluble Ru/triphenylphosphine trisulphonate complex with a. suitably modified p-cyclodextrin. 

By far the most commonly used - though not the most environmentally friendly -solvent is CCl (or more usually water-CCl ). In a classic paper Sharpless et al. showed that oxidation reactions of RuO (and other some Ru-based oxidants) were accelerated by addition of a little acetonitrile to the conventional water-CCl biphasic mixture. It was suggested that the CH3CN might function as a mild donor stabilising a lower oxidation state carboxylato Ru species which could be involved in the catalytic process [260]. A comparative study of CCl, acetone, ethyl acetate, cyclohexane and acetone for cleavage of alkenes and alkynes by RuClg/aq. IO(OH)3/solvent showed that cyclohexane was the most effective [216]. Other solvents sometimes... 

IL viscosity is extremely sensitive to additives [5]. Mixtures of IL and compatible solvents and water may produce biphasic liquid systems usable in CCC. The short-chain alcohol-[C4CiIm][PFg]-water and acetonitrile-[C4CiIm][PFJ-water ternary phase diagrams have been studied [7]. Alcohols were found to have a tendency to dissolve preferentially in the aqueous upper phase producing an IL lower phase of limited volume and high viscosity [7]. Acetonitrile partitions well between the upper aqueous phase and the lower IL phase, greatly reducing the viscosity of the IL-rich lower phase. 

Depending of the results of MS, step 2 can be performed either by RP-HPLC or by SEC. For RP-HPLC, the same column as in step 1 can be used, but the fractions are eluted using linear biphasic gradients of acetonitrile in acidified water at a same flow rate and at the same temperature (an increase in the temperature would result in a better resolution). The gradient is chosen according to the following strategy from 2% to ([C]-2)% acetonitrile in 10 min and from ([C]-2)% to ([C]+15)% acetonitrile at an increase concentration of 0.2-03%, where [C] corresponds to the exact concentration of acetonitrile for the elution of the compound of interest (see Note 11). SEC is preferred when MS measurements reveal the presence of molecules with molecular masses rather distant (e.g., >10 kDa and 2 1 kDa). 

The hydrophobicity of TS-1 could also explain why the oxidation of hydrocarbons in aqueous H2C>2 is faster without added organic solvent (triphase catalysis) than in organic solution (biphase catalysis) e.g. benzene hydroxylation under triphase conditions was up to 20 times faster than in acetonitrile or acetone (biphase conditions).1741 Indeed, benzene competes more favourably with water than with organic solvents for adsorption within the micropores of hydrophobic TS-1, as furthermore confirmed through adsorption experiments.1471... 

RUO2 (5 mol) was added to the product from Step 4 (2.93 mmol) in a biphase solution of 180 ml water, 60 ml acetonitrile and 120 ml CCI4 containing NaI04 (116 mmol) and the mixture stirred vigorously 5 days. The volatile solvents were removed, the mixture extracted 3 times with 150 ml EtOAc, dried, and the product isolated in 96% yield. H-and F-NMR and elemental analysis data supplied. 

TS-1 catalyzes the hydroxylation of alkanes with dilute solutions of hydrogen peroxide in water, in a biphasic system of alkane and aqueous H2O2, or in aqueous-organic solution. The rate of reaction decreases in the solvent order butanol > butanol/water > methanol = acetonitrile = water [24, 25]. The temperature is generally lower than 55 °C in methanol, close to 100°C in water and of intermediate values in other solvents. Hydroxylation occurs at secondary and tertiary C—H bonds, while primary ones are completely inert (Equations 18.3 and 18.4). 

In view of the purification and waste disposal problems with the chromium oxidations catalytic methods with ruthenium catalysts are more attractive. Ruthenium(Vlll) oxide is a strong oxidant that will also oxidize alkenes, alkynes, sulfides, and in some cases benzyl ethers. The method is compatible with glycosidic linkages, esters and acetals, and is usually carried out in a biphasic solvent system consisting of water and a chlorinated solvent. Acetonitrile or a phase-transfer catalyst has been shown to further promote the oxidation [29,30]. Normally, a periodate or a hypochlorite salt serve as the stoichiometric oxidant generating rutheni-um(VIII) oxide from either ruthenium(IV) oxide or ruthenium(III) chloride [30]. 

Besides ruthenium tetroxide, other ruthenium salts, such as ruthenium trichloride hydrate, may be used for oxidation of carbon-carbon double bonds. Addition of acetonitrile as a cosolvent to the carbon tetrachloride-water biphase system markedly improves the effectiveness and reliability of ruthenium-catalyzed oxidations. For example, RuCl3 H20 in conjunction with NaI04 in acetonitrile-CCl4-H20 oxidizes (Ej-S-decene to pentanoic acid in 88% yield. Ruthenium salts may also be employed for oxidations of primary alcohols to carboxylic acids, secondary alcohols to ketones, and 1,2-diols to carboxylic acids under mild conditions at room temperature, as exemplified below. However, in the absence of such readily oxidized functional groups, even aromatic rings are oxidized. 

The solvent properties of alcohols with short carbon chains are similar to those of water and such alcohols could be used as the nonaqueous catalyst phase when the products are apolar in nature. The first commercial biphasic process, the Shell Higher Olefin Process (SHOP) developed by Keim et al. [4], is nonaqueous and uses butanediol as the catalyst phase and a nickel catalyst modified with a diol-soluble phosphine, R2PCH2COOH. While ethylene is highly soluble in butanediol, the higher olefins phase-separate from the catalyst phase (cf. Section 2.3.1.3). The dimerization of butadiene to 1,3,7-octatriene was studied using triphenylphosphine-modified palladium catalyst in acetonitrile/hexafluoro-2-phe-nyl-2-propanol solvent mixtures [5]. The reaction of butadiene with phthalic acid to give octyl phthalate can be catalyzed by a nonaqueous catalyst formed in-situ from Pd(acac)2 (acac, acetylacetonate) and P(0CeH40CH3)3 in dimethyl sulfoxide (DMSO). In both systems the products are extracted from the catalyst phase by isooctane, which is separated from the final products by distillation [5]. 

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). 

It has been reported that use of a suitable co-solvent increases the concentration of the olefin in water (catalyst) while retaining the biphasic nature of the system. It has been shown that using co-solvents like ethanol, acetonitrile, methanol, ethylene glycol, and acetone, the rate can be enhanced by several times [27, 28], However, in some cases, a lower selectivity is obtained due to interaction of the co-solvent with products (e.g., formation of acetals by the reaction of ethanol and aldehyde). The hydroformylation of 1-octene with dinuclear [Rh2(/t-SR)2(CO)2(TPPTS)2] and HRh(CO)(TPPTS)3 complex catalysts has been investigated by Monteil etal. [27], which showed that ethanol was the best co-solvent. Purwanto and Delmas [28] have reported the kinetics of hydroformylation of 1-octene using [Rh(cod)Cl]2-TPPTS catalyst in the presence of ethanol as a co-solvent in the temperature range 333-353 K. First-order dependence was observed for the effect of the concentration of catalyst and of 1-octene. The effect of partial pressure of hydrogen indicates a fractional order (0.6-0.7) and substrate inhibition was observed with partial pressure of carbon monoxide. A rate eqution was proposed (Eq. 2). 

Palladium-catalyzed nucleophilic substitution of allylic substrates (Tsuji-Trost coupling) is a most important methodology in organic synthesis and therefore it is no wonder that such reactions have been developed also in aqueous systems. Carbo- and heteronucleophiles have been found to react with allylic acetates or carbonates in aqueous acetonitrile or DMSO, in water or in biphasic mixtures of the latter with butyronitrile or benzonitrile, affording the products of substitution in excellent yields (Scheme 6.19) [7-11,14,45,46], Generally, K2C03 or amines are used as additives, however in some cases the hindered strong base diazabicycloundecene (DBU) proved superior to other bases. 

Alkylation reaction 45 pi of acetonitrile, 15 pi of triethylammonium bicarbonate solution (pH 8,5) and 14 pi of methyhodide were added. The reaction was incubated at 40°C for 25 min. Afterwards 20 pi double distilled water were added. Upon cooling a biphasic system was obtained. The upper layer contained the products while the lower layer contained some of the reagents, for example detergents that were added to stabilise the enzymes used in this procedure. 20 pi of the upper layer were sampled and diluted in 45 pi of 40% acetonitrile. This solution was directly used to transfer the samples onto the matrix. 

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