2002 Progress Report: Green Oxidation Catalysts for Fine Chemical Synthesis

EPA Grant Number: R829553
Title: Green Oxidation Catalysts for Fine Chemical Synthesis
Investigators: Shapley, Patricia A.
Institution: University of Illinois at Urbana-Champaign
EPA Project Officer: Savage, Nora
Project Period: January 1, 2002 through December 31, 2004
Project Period Covered by this Report: January 1, 2002 through December 31, 2003
Project Amount: $325,000
RFA: Technology for a Sustainable Environment (2001) RFA Text |  Recipients Lists
Research Category: Sustainability , Pollution Prevention/Sustainable Development


The objective of this research project is to create highly selective and active catalysts for the oxidation of organic substrates with molecular oxygen. This will promote the environmentally responsible synthesis of fine chemicals by improving atom economy and reducing waste in one of the fastest growing areas of the chemical industry. We synthesize high-oxidation state organometallic complexes with oxo, nitrido, or sulfido ligands that also have open coordination sites for the binding of substrates. We examine reactions between the organometallic species and oxidizable organic molecules and we probe the mechanisms of these interactions.

Progress Summary:

Chiral Catalysts for Asymmetric Oxidation. For applications in the synthesis of pharmaceuticals and other fine chemicals, it is essential that an oxidation catalyst be highly selective. The Os-Cr and Ru-Cr bimetallic catalysts we have made are chemoselective, oxidizing only the hydroxy functional group, and regioselective, with a preference for the most sterically accessible hydroxy group. The next step is to introduce stereoselectivity in these catalysts. Molecular modeling studies have shown that the S enantiomer of [PPh4][Os(N)(CH2SiMe3)Ph(mu2-O)2CrO2] should be an effective catalyst for the oxidation of 3-chloro-1-phenyl-1-propanol, a precursor to fluoxetine (Prozac). We have succeeded in preparing the chiral catalyst. However, resolving it into separated enantiomers is tedious and results in a maximum of only 50 percent yield of the desired complex.

We have succeeded in the stereospecific synthesis of one diastereomer of [BF4][Os(N)(CH2SiMe3)Ph(S,S-chiraphos)]. The diastereomeric complexes Os(N)(CH2SiMe3)Ph(S,S-chiraphos)Cl result from the reaction of [PPh4][Os(N)(CH2SiMe3)PhCl2] with S,S-chiraphos. These are very different in steric bulk and one diastereomer selectively loses chloride upon reaction with AgBF4. We should be able to convert this diastereomer into a single enantiomer of the chiral chromate. This study is in progress. We also are examining complexes of readily available chiral amines such as quinine. We may be able to prepare chiral amine complexes stereoselectively by treatment of [PPh4][Os(N)(CH2SiMe3)3Ph] with the protonated amine. Because the amine ligands are more labile than phosphine ligands, we should be able to convert [BF4][Os(N)(CH2SiMe3)Ph(L*)2] into a variety of heterometallic complexes and have a more general method for the synthesis of asymmetric oxidation catalysts.

Selective Catalysts for Lipid Oxidation. Lipids from agricultural sources have the potential to be precursors for pharmaceuticals, agricultural chemicals, specialty lubricants, and biodegradable polymers. Such uses are currently restricted by the limited functionality in these oils.

In the first phase of this research, we have examined the oxidation of saturated fatty acids by transition metal complexes. We can readily prepare an iron(VI) oxide from ferric nitrate and potassium hypochlorite in concentrated aqueous potassium hydroxide. Purified K2FeO4 reacts with butanoic acid at one of the alpha C-H bonds to generate first CH3CH2CH(OH)CO2H, then CH3CH2C(O)CO2H. The keto acid loses CO2 and produces propanal. The reaction is selective. No products result from oxidation of the other C-H bonds in butanoic acid.

Picolinic acid, ferric chloride, and hydrogen peroxide (the "Gif" catalyst) can oxidize unfunctionalized hydrocarbons. We found that [N(n-Bu)4][Fe(NC5H4CO2)2Cl2] is a catalyst for the oxidation of fatty acids with hydrogen peroxide. The selectivity of the iron picolinate/ H2O2 system is the same as the stoichiometric oxidant K2FeO2.

In the next phase of the work, we are examining bimetallic iron(IV) complexes for these reactions. The catalyst will have an active site geometry similar to that of the enzyme methane monooxygenase and we expect that, like the enzyme, it will be able to use molecular oxygen as the secondary oxidant in C-H oxidation reactions. We are extending the list of substrates from simple fatty acids to the larger and more complex ones derived from agricultural products.

"Toolbox" Approach to Heterometallic Oxidation Catalysts. Complexes containing two or more different transition metals may have improved selectivity over monometallic complexes in catalytic reactions if the metals act cooperatively. However, only a few of the known heterometallic complexes react differently than homometallic or monometallic complexes in catalytic reactions. We have developed two general synthetic methods for the formation of mixed metal complexes that will be used to generate a family of potential lipid oxidation catalysts of the formula {M(N)R2}2(mu-S)2M"Lx. Initially, we treated ruthenium(VI) or osmium(VI) halides with (trimethylsilyl)thiolato complexes of a second metal (see Figure 1).

Figure 1. Ruthenium(VI) or Osmium(VI) Treated With (Trimethylsilyl)thiolato Complexes of a Second Metal

In some cases, the (trimethylsilyl)thiolato complexes of a second metal are unstable. We recently have demonstrated that [BF4][Os(N)(CH2SiMe3)2(py)(SSiMe3)] is able to react with metal halides to form sulfido-bridged, mixed-metal complexes. We have full characterization or partial characterization of six new complexes (see Figure 2). Studies characterizing their reactivity are in progress.

Figure 2. ORTEP Diagram of (dppe)Ni(mu3-S)2{Ru(N)Me2}2

One new complex contains both ruthenium(VI) and nickel(II). The reaction between Ni(dppe)(SSiMe3)2 and two equivalents of [N(n-Bu)4][Ru(N)Cl2Me2] produces ClSiMe3 and the heterometallic complex (dppe)Ni(mu3-S)2{Ru(N)Me2}2 in greater than 71 percent yield. The molecular structure of this complex shows the three metals and the two nitrido ligands in a plane with the bridging sulfur atoms above and below that plane. There is an interaction between one of the ruthenium centers and the nickel. The structure differs from that of the closely related complex (dppe)Pt(mu3-S)2{Ru(N)Me2}2, which has equivalent Pt-Ru distances and no strong metal-metal interactions. Perhaps because of the stabilization in the metal-metal interaction, (dppe)Ni(mu3-S)2{Ru(N)Me2}2 is less reactive than either (dppe)Pt(mu3-S)2{Ru(N)Me2}2 or (dppe)Pd(mu3-S)2{Ru(N)Me2}2.

Supported Analogs of Homogenous Oxidation Catalysts. Heterogeneous catalysts are generally less selective than homogeneous catalysts, but they are significantly easier to separate from the reaction medium. One part of this project involves the covalent attachment of our selective homogeneous catalysts to alumina or silica, forming catalysts that are both selective and easy to separate from the reaction medium. We have pursued two routes to new catalysts.

First, we have prepared new osmium(VI) and iron(III) complexes, in which the metal center is one vertex of a silsesquioxane cube. The high-spin iron(III) silsesquioxane complexes [N(n-Bu)4][(cyclo-C5H9)7Si7O12FeCl] and [N(n-Bu)4][(cyclo-C5H9)7Si7O12Fe(OSiMe3)] result from the reaction of (cyclo-C5H9)7Si7O9(OH)3 with either [N(n-Bu)4][FeCl4] or [N(n-Bu)4][Fe(OSiMe3)4]. Substitution of the terminal chloride or trimethyl)silanolate ligands with tert-butoxide produces [N(n-Bu)4][(cyclo-C5H9)7Si7O12Fe(OCMe3)]. Similar substitution reactions with the methyl ester of N-acetylcysteine produce [N(n-Bu)4][(cyclo-C5H9)7Si7O12Fe{SCH2CH(NHCOCH3)CO2Me}]. A dimeric complex, [(cyclo-C5H9)7Si7O12Fe(Net3)]2, forms in the reaction of (cyclo-C5H9)7Si7O9(OH)3 with NEt3 and FeCl3. The reaction between (cyclo-C5H9)7Si7O9(OH)2(OSiMe3) and [Ph4P][Os(N)Cl4] forms [PPh4][(cyclo-C5H9)7Si7O11(OSiMe3)Os(N)Cl2], a square-pyramidal Os(VI) complex with a bidentate siloxy ligand. Condensation of these cubes could produce a modified silica containing catalytically active metal centers.

Second, we prepared an osmium alkyl complex containing triethoxysilyl groups. The complex [N(n-Bu)4][Os(N){CH2Si(OEt)3}2Cl2] results from the reaction between [N(n-Bu)4][Os(N)Cl4] and two equivalents of ClMgCH2Si(OEt)3 in diethyl ether. This soluble orange crystalline complex is very similar to [N(n-Bu)4][Os(N)(CH2SiMe3)2Cl2], except that it is highly reactive with glass and silica surfaces. Upon reaction with these materials, it loses ethanol and forms a supported osmium complex. We do not yet have this supported material fully characterized. The orange material reacts with aqueous potassium chromate to yield a purple material with a spectroscopic and UV-visible pattern similar to [N(n-Bu)4][Os(N)(CH2SiMe3)2(mu-O)2CrO2.

We intend to compare the catalytic activity of supported materials with the soluble ones in oxidation reactions.

Original Project Timeline for Year 1. We planned to synthesize approximately 10 new, heterometallic catalysts of types {M(N)R2}2(mu3-S)2M"Lx and [N(n-Bu)4][M(N)RR'}(mu2-O)M'O2] in Year 1 of the project and survey their reactions with alcohols, alkenes, fatty acids, isoflavones, and phytosteroids.

During Year 1 of the project, we have prepared six new heterometallic complexes of formula {M(N)R2}2(mu3-S)2M"Lx and a new iron(III) oxidation catalyst. We have examined oxidation reactions of alcohols and alkenes with molecular oxygen catalyzed by the heterometallic complexes. We examined alcohol and fatty acid oxidation with hydrogen peroxide catalyzed by [N(n-Bu)4][Fe(NC6H4CO2)2Cl2]. We have also made progress in the preparation of asymmetric oxidation catalysts and prepared precursors to supported oxidation catalysts.

Students Affiliated With the Grant. Four graduate students and two undergraduate students currently are engaged in research on green oxidation catalysts for fine chemical synthesis. Douglas Pool is the most senior student. He will complete his Ph.D. thesis this semester on chiral osmium complexes and asymmetric oxidation catalysts. Jesse Kuiper, a third-year graduate student, is investigating heterometallic complexes containing ruthenium(VI) and other transition metals and is comparing the reactivities of these complexes in oxidation reactions. Johnny Giles, a first-year graduate student, is working on a project that is complementary to Jesse Kuiper's. He is studying heterometallic complexes containing osmium(VI) and other transition metals that catalyze the oxidation of complex molecules with air. Adeline Fournier, another first-year graduate student, is preparing iron-oxo catalysts for hydrocarbon and fatty acid oxidation with molecular oxygen. Smruti Amin, a senior undergraduate, is finishing a project involving the use of K2FeO4 in the stoichiometric oxidation of fatty acids. Amanda Thomas, another senior undergraduate, is using Fe(III) picolinate complexes for the oxidation of hydrocarbons and fatty acid.

Future Activities:

After analysis of the results from Year 1 of the project, we will prepare modified catalysts to tune the reactivity for individual substrates. We will optimze conditions for reactions and begin the use of supercritical carbon dioxide as a reaction solvent.

We will continue reactivity studies and begin to use water-soluble catalysts for aqueous phase oxidations of carbohydrates. We also will prepare (trialkoxysilyl)methyl-substituted catalysts and attach these to metal oxide supports for heterogeneous oxidation reactions.

During Year 3 of the project, we will continue our studies on the oxidation of alcohols, alkenes, fatty acids, isoflavones, and phytosteroids. After analysis of the results, we will use molecular modeling techniques to help us prepare modified catalysts and tune the reactivity for individual substrates. We also will prepare water-soluble catalysts and examine selective oxidation reactions in water, as well as in supercritical carbon dioxide.

Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other project views: All 16 publications 7 publications in selected types All 4 journal articles
Type Citation Project Document Sources
Journal Article Shapley PA, Bigham WS, Hay MT. New Fe(III) and Os(VI) silsesquioxanes. Inorganica Chimica Acta 2003;345:255-260. R829553 (2002)
R829553 (Final)
  • Abstract: ScienceDirect-Abstract
  • Supplemental Keywords:

    volatile organic compound, VOC, pollution prevention, green chemistry, renewable, waste reduction, oxidation, environmental chemistry., RFA, Scientific Discipline, Sustainable Industry/Business, Chemical Engineering, Environmental Chemistry, cleaner production/pollution prevention, Sustainable Environment, Technology for Sustainable Environment, Chemistry and Materials Science, New/Innovative technologies, supercritical carbon dioxide (SCCO2) technology, renewable feedstocks, oxidation, waste reduction, oxidation reactions, fine chemicals, "toolbox" of catalyst, catalysts, supercritical carbon dioxide, catalytic transformations, agricultural industry, chemcial synthesis, carbon dioxide, solvent substitute, solvent replacements, pollution prevention, Volatile Organic Compounds (VOCs), chemical transformation, environmentally-friendly chemical synthesis, green chemistry, pharmaceutical industry, renewable resource, solvents, chemical synthesis

    Progress and Final Reports:

    Original Abstract
    2004 Progress Report
    Final Report