COMSOL 6.4 - Ibuprofen Synthesis

Kinetic analysis of catalytic reactions is essential for understanding rate behavior as well as the reaction mechanism. Developing knowledge of intrinsic reaction kinetics and of rate equations is central to reaction engineering studies aimed at improving reactor design.

This example illustrates the reaction kinetics of a complex chemistry occurring in a perfectly stirred tank reactor. The homogeneous catalysis of 1-(4-isobutylphenyl) ethanol into the anti-inflammatory drug ibuprofen serves as the example chemistry. The model determines concentrations of reactants, intermediates, and products as functions of time for the network of chemical reactions.

The chemistry in this example involves homogeneous catalysis. As this terminology suggests, the catalyst and the reacting species are in the same phase. Most commonly, a liquid reaction mixture contains a soluble metalorganic complex that affects the catalysis. Organometallic catalysts can often be fine-tuned with respect to reaction activity and selectivity. Because these relatively expensive catalysts produce highly-refined reaction products, they commonly find application in fine chemicals or pharmaceutics.

The model focuses on the use of the Chemical Reaction Engineering Module for a kinetics investigation. You easily enter chemical reaction formulas from the keyboard, then the Reaction Engineering interface automatically generates rate expressions and material balances. It solves the equations, and you postprocess results directly in the COMSOL Desktop.

Model Description

Analyzing chemical kinetics involves solving the set of ordinary differential equations corresponding to individual steps in a network of reactions. This example illustrates the kinetics of ibuprofen synthesis. Figure 1 shows the reaction steps displayed in a catalytic cycle (Ref. 1).

Figure 1: Catalytic cycle of ibuprofen synthesis.

Prior to entering the cycle, the starting material, 1-(4-isobutylphenyl)ethanol, is first dehydrated to form 4-isobutylstyrene. This species subsequently undergoes the addition of HCl to produce the active substrate 1-(4-isobutylphenyl)ethyl chloride. The palladium catalyst must also go through an initial transformation, from L2PdCl2 (L=triphenylphosphine) to anionic L2PdCl, before becoming active. The activated catalyst then assists in the carbonylation and hydrolysis of 1-(4-isobutylphenyl)ethyl chloride, producing ibuprofen.

The following reactions represent the catalytic cycle:

(1)

(2)

(3)

(4)

(5)

(6)

(7)

Reaction 1 involves the dehydration of the reactant alcohol to form the corresponding alkene. Reaction 2 describes the hydrohalogenation of alkene, resulting in the active substrate 1-(4-isobutylphenyl)ethyl chloride. Reaction 3 shows the dehydrohalogenation of the active substrate, assisted by a base, B. Reaction 4 describes the transformation of the precatalytic species L2PdCl2 into the active anionic catalyst L2PdCl. In Reaction 5 the active substrate undergoes oxidative addition to the L2PdCl catalyst. Reaction 6 summarizes the carbonylation, and Reaction 7 describes the hydrolysis of the metalorganic species, leading to the formation of ibuprofen and regeneration of the catalyst.

In order to make species notation more manageable, this example uses the following labels:

Making use of these notations, the reaction rates corresponding to Reaction 1 through Reaction 7 are:

(8)

(9)

(10)

(11)

(12)

(13)

(14)

The Reaction Engineering interface automatically generates these expressions and displays them immediately when you enter the chemical reaction formulas. By default, the software assumes that the chemistry takes place isothermally in a perfectly stirred batch reactor.

Figure 2: A perfectly stirred batch reactor where the reactant alcohol is carbonylated to form ibuprofen by means of palladium catalysis.

With no inflow or outflow from the reactor, the change of species concentrations with time is a function only of the reaction rates:

(15)

The Reaction Engineering automatically generates the mass balance in Equation 15 for each of the species, i, in the reactions, j, accounting for the stoichiometry in the reaction formulas, ν, and solves these equations.

The model investigates two reaction conditions. The first simulation (Case 1) solves for the seven reactions displayed previously. In Case 2 you modify the reaction network with an additional reaction, altering the simulation results. Assume that the reactant alcohol and product ibuprofen (a carboxylic acid) react reversibly, forming an ester: