The Wacker process or the Hoechst-Wacker process (named after the chemical companies of the same name) is an industrial chemical reaction: the aerobic oxidation of ethylene to acetaldehyde in the presence of catalytic, aqueous palladium(II) chloride and copper(II) chloride.
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The Tsuji-Wacker oxidation refers to a family of reactions inspired by the Wacker process. In Tsuji-Wacker reactions, palladium(II) catalyzes transformation of α-olefins into carbonyl compounds in various solvents.
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The development of the Wacker process popularized modern organopalladium chemistry, and Tsuji-Wacker oxidations remain in use today.
History
The Wacker process was one of the first homogeneous catalysis with organopalladium chemistry applied on an industrial scale.
In an 1893 doctoral dissertation on Pennsylvanian natural gas, Francis Clifford Phillips had reported that palladium(II) chloride oxidized ethylene to acetaldehyde, but the reaction required stoichiometric quantities of palladium. It remained a niche curiosity until Wacker Chemie began developing its eponymous process in 1956.
At the time, many industrial compounds were produced via acetaldehyde from acetylene, itself from calcium carbide. The overall route exhibited poor thermodynamic efficiency and required great expense. Esso sought to market waste olefins from a new, under-construction oil refinery in Cologne close to a Wacker site. Wacker realized that ethylene would be a cheaper feedstock than acetylene, and began to investigate catalytic oxidation to ethylene oxide. However, poor patenting strategy allowed parent corporation Hoechst AG to outrace Wacker to the optimal catalysis conditions.
Wacker-Hoechst began jointly constructing pilot plants in 1958, but the relatively aggressive reaction conditions required the first large-scale use of titanium metal in the European chemical industry to protect against corrosion. Production plants started operation in 1960. Many focused on the hydroxypalladation step, which forms the C–O bond. Early reactions used conditions much milder than the industrial plants and obtained contradictory results; the modern consensus is that the step's stereochemistry is quite sensitive to chloride concentrations. found that aqueous DMF as solvent allowed for the oxidation of 1-dodecene to 2-dodecanone. Fahey noted the use of 3-methylsulfolane in place of DMF as solvent increased the yield of oxidation of 3,3-Dimethylbut-1-ene. Two years after, Tsuji applied the Clement-Selwitz conditions for selective oxidations of terminal olefins with multiple functional groups, and demonstrated its utility in synthesis of complex substrates.
Carbonylation has mainly superseded the Wacker process for modern bulk chemical synthesis, but small-scale Tsuji-Wacker reactions remain important for fine chemical and laboratory-scale syntheses.
[[File:wackonwackoff_updated.tif|center|635x635px|thumb|Catalytic cycle for the Wacker process.
Evidence
Evidence for the overall mechanism includes: Questions remain about whether the cocatalyst also helps hydroxylate the ethylene ligand.
The ethylene ligand's hydroxylation is typically a slow process. Depending on experimental conditions, it can occur either intramolecularly, from a palladium-bound hydroxido ligand, or intermolecularly. In the former case the hydroxylation is anti; in the latter, syn. Assuming small amounts of copper, experiments have shown that syn addition occurs at low chloride concentrations (< 1 mol/L, industrial process conditions) and anti addition occurs at high (> 3mol/L) concentrations. The pathway change is probably due to chloride ions saturating the catalyst. However, under strictly copper-free conditions, anti addition always occurs, and the rate no longer depends on the ethylene hydrogen isotopes.
Another key step in the Wacker process is the migration of the hydrogen from oxygen to chloride, followed by reductive elimination to form the C-O double bond. This step is generally thought to proceed through a so-called β-hydride elimination:
500px|center|Wacker hydride elimination
The cyclic four-membered transition state shown above is unlikely. In silico studies argue that the transition state for this reaction step likely involves a 7-membered ring with a (solvent) water molecule acting as a catalyst.
150px|center|alt=Wacker process alternative transition state
Industrial process
thumb|right|Process flow diagram for the one-stage process
thumb|right|Process flow diagram for the two-stage process
Two routes are commercialized for the production of acetaldehyde: one-stage process and two-stage. The acetaldehyde yield is about 95% in either, and byproducts are chlorinated hydrocarbons, chlorinated acetaldehydes, and acetic acid. In general, 100 parts of ethene gives: The catalyst is an aqueous solution of PdCl<sub>2</sub> and CuCl<sub>2</sub>. The acetaldehyde is purified by extractive distillation followed by fractional distillation. Extractive distillation with water removes the lights ends having lower boiling points than acetaldehyde (chloromethane, chloroethane, and carbon dioxide) at the top, while water and higher-boiling byproducts, such as acetic acid, crotonaldehyde or chlorinated acetaldehydes, are withdrawn together with acetaldehyde at the bottom. favors nucleopalladation at the terminal carbon to minimize steric interaction between the palladium complex and substrate. Quinox (Figure 2, B) favors ketone formation when the substrate contains a directing group. When such substrate bind to Pd(Quinox)(OOtBu), this complex is coordinately saturated which prevents the binding of the directing group, and results in formation of the Markovnikov product. The efficiency of this ligand is also attributed to its electronic property, where anionic TBHP prefers to bind trans to the oxazoline and olefin coordinate trans to the quinoline.
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Anti-Markovnikov addition
The anti-Markovnikov addition selectivity to aldehyde can be achieved through exploiting inherent stereoelectronics of the substrate. Placement of directing group at homo-allylic (i.e. Figure 3, A) and allylic position (i.e. Figure 3, B) to the terminal olefin favors the anti-Markovnikov aldehyde product, which suggests that in the catalytic cycle the directing group chelates to the palladium complex such that water attacks at the anti-Markovnikov carbon to generate the more thermodynamically stable palladacycle. Anti-Markovnikov selectivity is also observed in styrenyl substrates (i.e. Figure 3, C), presumably via η<sup>4</sup>-palladium-styrene complex after water attacks anti-Markovnikov. More examples of substrate-controlled, anti-Markovnikov Tsuji-Wacker Oxidation of olefins are given in reviews by Namboothiri, Feringa,
Grubbs and co-workers paved way for anti-Markovnikov oxidation of stereoelectronically unbiased terminal olefins, through the use of palladium-nitrite system (Figure 2, D). In his system, the terminal olefin was oxidized to the aldehyde with high selectivity through a catalyst-control pathway. The mechanism is under investigation, however evidence
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Scope
Oxygen nucleophiles
The intermolecular oxidations of olefins with alcohols as nucleophile typically generate ketals, where as the palladium-catalyzed oxidations of olefins with carboxylic acids as nucleophile generates vinylic or allylic carboxylates. In case of diols, their reactions with alkenes typically generate ketals, whereas reactions of olefins bearing electron-withdrawing groups tend to form acetals.
Palladium-catalyzed intermolecular oxidations of dienes with carboxylic acids and alcohols as donors give 1,4-addition products. In the case of cyclohexadiene (Figure 4, A), Backvall found that stereochemical outcome of product was found to depend on concentration of LiCl. This reaction proceeds by first generating the Pd(OAc)(benzoquinone)(allyl) complex, through anti-nucleopalladation of diene with acetate as nucleophile. The absence of LiCl induces an inner sphere reductive elimination to afford the trans-acetate stereochemistry to give the trans-1,4-adduct. The presence of LiCl displaces acetate with chloride due to its higher binding affinity, which forces an outer sphere acetate attack anti to the palladium, and affords the cis-acetate stereochemistry to give the cis-1,4-adduct. Intramolecular oxidative cyclization: 2-(2-cyclohexenyl)phenol cyclizes to corresponding dihydro-benzofuran (Figure 4, B); 1-cyclohexadiene-acetic acid in presence of acetic acid cyclizes to corresponding lactone-acetate 1,4 adduct (Figure 4, C), with cis and trans selectivity controlled by LiCl presence.
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Nitrogen nucleophiles
The oxidative aminations of olefins are generally conducted with amides or imides; amines are thought to be protonated by the acidic medium or to bind the metal center too tightly to allow for the catalytic chemistry to occur. B)
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