Wacker process

The Wacker process or the Hoechst-Wacker process (named after the chemical companies of the same name) originally referred to the oxidation of ethylene to acetaldehyde by oxygen in water in the presence of a tetrachloropalladate catalyst. [Translated in part from .] The same basic reaction is currently used to produce aldehydes and ketones from a number of alkenes with the Monsanto process for producing acetic acid. This chemical reaction, a German invention, was the first organometallic and organopalladium reaction applied on an industrial scale. The Wacker process is similar to hydroformylation, which is also an industrial process and also leads to aldehyde compounds. The differences are that hydroformylation promotes chain extension, and uses a rhodium-based catalyst system. The Wacker process is an example of homogeneous catalysis. The palladium complex with ethylene is reminiscent of Zeise's salt, K [PtCl₃(C₂H₄)] which is a heterogeneous catalyst.

Reaction mechanism

The modern understanding of the reaction mechanism for the Wacker process (olefin oxidation via palladium(II) chloride) is described below:

The catalytic cycle can also be described as follows::$mathrm\{\; [PdCl\_4]\; ^\{2-\}\; +\; C\_2H\_4\; +\; H\_2O\; ightarrow\; CH\_3CHO\; +\; Pd\; +\; 2HCl\; +2Cl^-\}$:$mathrm\{Pd\; +\; 2CuCl\_2\; +\; 2Cl^-\; ightarrow\; [PdCl\_4]\; ^\{2-\}\; +\; 2CuCl\}$:$mathrm\{2CuCl\; +\; 1/2O\_2\; +\; 2HCl\; ightarrow\; 2CuCl\_2\; +\; H\_2O\}$

Note that all catalysts are regenerated and only the alkene and oxygen are consumed. Without copper(II) chloride and hydrochloric acid as oxidizing agents, Pd(0) (resulting from reductive elimination of Pd(II) in the final step) would precipitate out and the reaction would come to a halt (the stoichiometric reaction without catalyst regeneration was discovered in 1894). Air, pure oxygen, or a number of other oxidizers can then oxidise the resultant CuCl back to CuCl₂, allowing the cycle to repeat.

The initial stoichiometric reaction was first reported by Phillips [F.C. Phillips, Am. Chem. J., 1894, 16, 255-277.] [F.C. Phillips, Z. Anorg. Chem., 1894, 6, 213-228.] and the Wacker reaction was first reported by Smidt et al. [J. Smidt, W. Hafner, R. Jira, J. Sedlmeier, R. Sieber, R. Rüttinger, and H. Kojer, Angew. Chem., 1959, 71, 176-182.] . [W. Hafner, R. Jira, J. Sedlmeier, and J. Smidt, Chem. Ber., 1962, 95, 1575-1581.] [J. Smidt, W. Hafner, R. Jira, R. Sieber, J. Sedlmeier, and A. Sabel, Angew. Chem., Int. Ed. Engl., 1962, 1, 80-88.]

Mechanism summary

Substantial mechanistic investigation on the olefin oxidation cycle has elucidated much of the oxidation process, though some questions remain. [Henry, Patrick M. In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley & Sons: New York, 2002; p 2119. ISBN 0471315060] Several interesting key points were found:

(1) there is no H/D exchange seen in this reaction. Reaction runs with C₂D₄ in water generate CD₃CDO, and runs with C₂H₄ in D₂O generate CH₃CHO. Thus, keto-enol tautomerization is not a possible mechanistic step.

(2) There is a negligible kinetic isotope effect with fully deuterated reactants ("k" _H/"k" _D=1.07). Hence, it is inferred that hydride transfer is not a rate-determining step.

(3) a significant competitive isotope effect with C₂H₂D₂, ("k" _H/"k" _D= ~1.9), suggests that the rate determining step should be prior to oxidized product formation.

For these reasons, modern understanding of this process has the rate-determining step occurring before a series of hydride rearrangements. However, it has been recognized that experimental conditions play a crucial role in which mechanistic pathway is taken.

The bulk of mechanistic studies on the Wacker Process debated whether nucleophilic attack occurred via an external (anti-addition) pathway or via an internal (syn-addition) pathway. Studies by Stille and coworkers [James, D.E., Stille, J.K. "J. Organomet. Chem.", 1976, "108", 401. doi|10.1021/ja00423a028] [Stille, J.K., Divakarumi, R.J., "J. Organomet. Chem.", 1979, "169", 239;] [James, D.E., Hines, L.F., Stille, J.K. "J. Am. Chem. Soc.", 1976, "98", 1806 doi|10.1021/ja00423a027] apparently suggested that the Wacker Process proceeds via anti-addition, however these studies have been refuted as they assumed that changes in reaction conditions do not influence the reaction mechanism. However, other contemporary studies in high chloride concentration conditions also concluded that nucleophilic attack was an anti-addition reaction. [Baeckvall, J.E., Akermark, B., Ljunggren, S.O., "J. Am. Chem. Soc.", 1979, "101", 2411. doi|10.1021/ja00503a029] Numerous textbooks have erroneously propagated these studies as proof that the reaction occurs via an anti-addition step when in fact the mechanism is more complicated. Subsequent stereochemical studies by Patrick M. Henry and coworkers confirmed that both pathways occur and are dependent on chloride concentrations. [Francis, J.W., Henry, P.M. "Organometallics", 1991, "10", 3498. Doi|10.1021/om00056a019] [Francis, J.W., Henry, P.M. "Organometallics", 1992, "11", 2832.doi|10.1021/om00044a024]

In summary, it was determined that syn-addition occurs under low-chloride reaction concentrations (< 1 mol/L, industrial process conditions), while anti-addition occurs under high-chloride (> 3 mol/L) reaction concentrations. However, the exact pathway and the reason for this switching of pathways is still unknown.

Another key step in the Wacker process is the migration of the hydrogen from oxygen to chlorine and formation of the C-O double bond. This step is generally regarded to proceed through a so-called β-hydride elimination with a four-membered cyclic transition state:

One in silico study ["Inaccessibility of -Hydride Elimination from -OH Functional Groups in Wacker-Type Oxidation" John A. Keith, Jonas Oxgaard, and William A. Goddard, III J. Am. Chem. Soc.; 2006; 128(10) pp 3132 - 3133; doi|10.1021/ja0533139] argues that the transition state for this reaction step is unfavorable (activation energy 36.6 kcal/mol) and proposes an alternative reductive elimination reaction mechanism in which the proton directly attaches itself to chlorine with an activation energy of 18.8 kcal/mol. The proposed reaction step gets assistance from a water molecule acting as a catalyst.

Wacker-Tsuji oxidation

The so-called Wacker-Tsuji oxidation is the laboratory scale version of the above reaction, for example the conversion of 1-decene to 2-decanone with palladium(II) chloride and copper(II) chloride in a water / dimethylformamide solvent mixture in the presence of air [Jiro Tsuji, Hideo Nagashima, and Hisao Nemoto, [http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv7p0137A General Synthetic Method for the preparation of Methyl Ketones from Terminal Olefins: 2-Decanone] , Organic Syntheses, Coll. Vol. 7, p.137 (1990); Vol. 62, p.9 (1984).]

References