Selective Oxidation Using In Situ-Generated Hydrogen Peroxide

Abstract

ConspectusHydrogen peroxide (H₂O₂) for industrial applications is manufactured through an indirect process that relies on the sequential reduction and reoxidation of quinone carriers. While highly effective, production is typically centralized and entails numerous energy-intensive concentration steps. Furthermore, the overhydrogenation of the quinone necessitates periodic replacement, leading to incomplete atom efficiency. These factors, in addition to the presence of propriety stabilizing agents and concerns associated with their separation from product streams, have driven interest in alternative technologies for chemical upgrading. The decoupling of oxidative transformations from commercially synthesized H₂O₂ may offer significant economic savings and a reduction in greenhouse gas emissions for several industrially relevant processes. Indeed, the production and utilization of the oxidant in situ, from the elements, would represent a positive step toward a more sustainable chemical synthesis sector, offering the potential for total atom efficiency, while avoiding the drawbacks associated with current industrial routes, which are inherently linked to commercial H₂O₂ production. Such interest is perhaps now more pertinent than ever given the rapidly improving viability of green hydrogen production.The application of in situ-generated H₂O₂ has been a long-standing goal in feedstock valorization, with perhaps the most significant interest placed on propylene epoxidation. Until very recently a viable in situ alternative to current industrial oxidative processes has been lacking, with prior approaches typically hindered by low rates of conversion or poor selectivity toward desired products, often resulting from competitive hydrogenation reactions. Based on over 20 years of research, which has led to the development of catalysts for the direct synthesis of H₂O₂ that offer high synthesis rates and >99% H₂ utilization, we have recently turned our attention to a range of oxidative transformations where H₂O₂ is generated and utilized in situ. Indeed, we have recently demonstrated that it is possible to rival state-of-the-art industrial processes through in situ H₂O₂ synthesis, establishing the potential for significant process intensification and considerable decarbonization of the chemical synthesis sector.We have further established the potential of an in situ route to both bulk and fine chemical synthesis through a chemo-catalytic/enzymatic one-pot approach, where H₂O₂ is synthesized over heterogeneous surfaces and subsequently utilized by a class of unspecific peroxygenase enzymes for C-H bond functionalization. Strikingly, through careful control of the chemo-catalyst, it is possible to ensure that competitive, nonenzymatic pathways are inhibited while also avoiding the regiospecific and selectivity concerns associated with current energy-intensive industrial processes, with further cost savings associated with the operation of the chemo-enzymatic approach at near-ambient temperatures and pressures. Beyond traditional applications of chemo-catalysis, the efficacy of in situ-generated H₂O₂ (and associated oxygen-based radical species) for the remediation of environmental pollutants has also been a major interest of our laboratory, with such technology offering considerable improvements over conventional disinfection processes.We hope that this Account, which highlights the key contributions of our laboratory to the field over recent years, demonstrates the chemistries that may be unlocked and improved upon via in situ H₂O₂ synthesis and it inspires broader interest from the scientific community.

Figure 1

Simplified reaction scheme for the ammoximation of cyclohexanone via in situ H₂O₂ synthesis. Note that a wide conditions gap exists between the H₂O₂ direct synthesis and ketone ammoximation reactions, with the former favored by subambient temperatures and acidic conditions while the latter requires elevated reaction temperatures and basic conditions.

Figure 2

Ketone ammoximation via in situ H₂O₂ synthesis. (A) Catalytic activity of a 0.66% AuPd/TiO₂ catalyst, used in conjunction with TS-1, toward the in situ ammoximation of a range of ketones. (B) Comparison of catalyst support on the activity of AuPd nanoalloys toward the in situ ammoximation of cyclohexanone. Note that with the exception of the TS-1 catalyst, all other formulations were used in conjunction with TS-1 (0.075 g). (C) Effect of the Au:Pd ratio on the catalytic activity of 0.66% PdAu/TS-1 catalysts toward the in situ ammoximation of cyclohexanone. (D) Catalytic activity of 0.66% PdX/TS-1 catalysts toward the in situ ammoximation of cyclohexanone. Note that Pd:X = 1:1 (w/w). Reaction conditions (A, B): Cyclohexanone (2 mmol), NH₄HCO₃ (4 mmol), 5% H₂/N₂ (420 psi), 25% O₂/N₂ (160 psi), catalyst (0.075 g), t-BuOH (5.9 g), H₂O (7.5 g), reaction time 3 h, reaction temperature 80 °C, stirring speed 800 rpm. Reaction conditions (C, D): Same as above, but the reaction time is 6 h.

Figure 3

Industrial viability of the in situ approach to cyclohexanone ammoximation. (A) Cyclohexanone ammoximation via in situ H₂O₂ synthesis under industrially relevant conditions. (B) Techno-economic analysis comparison of the current commercial and in situ approaches to cyclohexanone ammoximation. Reaction conditions (A): Cyclohexanone (19 wt %): NH₃ (aq) (1:1 (mol/mol)), 3.6% H₂, 6.4% O₂, 90% N₂ (580 psi, 20 mL min^–1), 0.33% Au 0.33% Pd/TS-1(acetate-O + R):Al₂O₃ (4:1) (catalyst mass = 0.42 g), t-BuOH: H₂O (9:1 (v/v), 0.005–0.10 mL min^–1), residence time 75 min at 0.01 mL min^–1 liquid flow rate and 150 min at 0.005 mL min^–1 liquid flow rate, reaction temperature 80 °C. Note 1: The catalyst was reduced (2 h, 200 °C, H₂) following an initial oxidative heat treatment (16 h, 110 °C, static air). Note 2: Reaction conditions between 0 and 1.4 h: As above with liquid flow of 0.1 mL min^–1 (purple background). Note 3: Reaction conditions between 1.4 and 12.3 h: As above with liquid flow of 0.01 mL min^–1 (green background). Note 4: Reaction conditions between 12.3 and 16 h: As above with liquid flow of 0.005 mL min^–1 (orange background). Note 5: The reader is directed to our original work for a complete techno-economic analysis.

Figure 4

Proposed reaction scheme for the oxidation of benzyl alcohol via in situ H₂O₂ synthesis.

Figure 5

Benzyl alcohol oxidation via in situ H₂O₂ synthesis. (A) Comparative performance of in situ H₂O₂ synthesis toward the oxidation of benzyl alcohol using a 1% Pd/TiO₂ catalyst. (B) Comparison of the catalytic activity of 1% Pd/TiO₂, 1% PdAu/TiO₂, and 1% PdFe/TiO₂ catalysts over sequential reactions. (C) Effect of reaction solvent on the performance of a 5% AuPd/TiO₂ catalyst. (D) Experimental (black) and simulated (red) EPR spectra of DMPO-radical adducts formed during the oxidation reaction. Reactions were conducted in the presence of DMPO and (i) 1% Pd/TiO₂ (0.083 h), (ii) 1% Pd/TiO₂ (0.5 h), (iii) 1% PdAu/TiO₂ (0.083 h), (iv) 1% PdAu/TiO₂ (0.5 h), (v) 1% PdFe/TiO₂ (0.083 h), and (vi) 1% PdFe/TiO₂ (0.5 h). Reaction conditions: Catalyst (0.01 g), benzyl alcohol (1.04 g, 9.62 mmol), solvent (7.1 g), 5% H₂/CO₂ (420 psi), 25% O₂/CO₂ (160 psi), 0.5 h, 50 °C, 1200 rpm. Note 1: In A, the concentration of commercial H₂O₂ used is comparable to that produced if all H₂ in a standard in situ reaction is converted to H₂O₂. H₂O₂ was not continually introduced into the reactor. N₂ in parentheses is indicative of a gaseous atmosphere (580 psi). For experiments carried out using H₂ or O₂ only, a gaseous mixture of 5%H₂/CO₂ (420 psi) or 25%O₂/CO₂ (160 psi) was used, with the total pressure being maintained at 580 psi using N₂. Note 2: In A–D, the solvent used was MeOH.

Figure 6

Proposed reaction pathways associated with the chemo-catalytic/enzymatic valorization of cyclohexane via in situ H₂O₂ synthesis.

Figure 7

Chemo/enzymatic C–H bond oxidation, via in situ H₂O₂synthesis. (A) Comparison of the chemo-catalytic/enzymatic system (where H₂O₂ is synthesized over a 5% AuPd/TiO₂ catalyst) with the coenzymatic approach using glucose oxidase (GOx, 0.2 UmL_RM^–1) and 200 mM glucose under an oxidative atmosphere (air, 6 psi). (B) Product selectivity as a function of catalyst formulation when used in conjunction with PaDa-I. (C) Chemo-catalytic and (D) enzymatic overoxidation of cyclohexanol. Reaction conditions: Catalyst (0.001 g), substrate (10 mM), PaDa-I (15 U mL_RM^–1), phosphate buffer (100 mM, 10 mL, pH 6.0), using a gas mixture of 80% H₂/air H₂ (23 psi) and air (6 psi), X h, 20 °C, 250 rpm. Note 1: In B–D, the catalyst formulation is 1% PdX/TiO₂ (Pd:X = 1:1 (w/w)).

Figure 8

Sources of enzyme deactivation in the chemo-enzymatic approach to cyclohexane oxidation. (A) Effect of key reaction parameters and (B) homogeneous metal species on enzyme deactivation, as determined by ABTS assay. ABTS assay reaction conditions for (A) and (B): 100 μL of the reaction solution was added to 900 μL of ABTS solution (100 mM sodium citrate–phosphate buffer, pH 4.4 with 0.3 mM ABTS and 2 mM H₂O₂), and substrate conversion was followed by measuring the absorption at 418 nm (ε 418 = 36 000 M^–1 cm^–1) at 30 °C. Note for A: In the case of the blank experiment, the UPO was stirred under ambient conditions and the pressure of the buffer only. In the case of the cyclohexanol experiment, the concentration of cyclohexanol was equivalent to that present at 30% conversion of cyclohexane. The blank cyclohexane oxidation reaction conditions for (B): Metal salt ((5.1–9.4) × 10^–9 M), cyclohexane (10 mM), PaDa (15 U mLRM^–1), and phosphate buffer (100 mM, 10 mL, pH 6.0), using a gas mixture of 80% H₂ (23 psi) in air (6 psi), 2 h, 250 rpm.

Figure 9

Bioremediation via in situ H₂O₂ synthesis. (A) Proposed reaction scheme for the in situ remediation of E. coli. K12 JM109 by reactive oxygen species generated over AuPd surfaces, summarizing our observations of catalytic performance and O-centered radical speciation. (B) Comparison of microbicidal activity using aqueous NaOCl, preformed H₂O₂, and in situ-synthesized H₂O₂. Reaction conditions: Catalyst (0.12 g), 2% H₂, 20% O₂, 78% N₂, (145 psi, 42 mL min^–1), reaction solution (H₂O and E. coli K12 JM109 (2 × 10⁸ c.f.u. mL^–1) 0.2 mL min^–1 liquid flow), 0.5 h, 2 °C.

Figure 10

Oxidative degradation of phenol via in situ H₂O₂ synthesis. Comparison of catalytic activity using Pd-based catalysts (A) 1% Pd/TiO₂, (B) 0.25% Pd-0.27% Fe/TiO₂, and (C) 0.5% Pd/3% Fe-ZSM-5. (D) Performance of the 0.5% Pd/3% Fe-ZSM-5 catalyst over sequential reactions. Reaction conditions: Catalyst (0.01 g), phenol (1000 ppm, 8.5 g), 5% H₂/CO₂ (420 psi), 25% O₂/CO₂ (160 psi), 2 h, 30 °C, 2 h.

Figure 11

(A) Efficacy of the 0.5% Pd/3% Fe-ZSM-5 catalyst toward the oxidative degradation of phenol via in situ H₂O₂ synthesis as a function of the catalyst:phenol ratio. (B) Comparative performance of in situ H₂O₂ synthesis toward phenol degradation over a 0.5% Pd/0.5% Fe-ZSM-5 catalyst (0.0 1 g). Reaction conditions: Catalyst (X g), phenol (1000 ppm, 8.5 g), 5% H₂/CO₂ (420 psi), 25% O₂/CO₂ (160 psi), 2 h, 30 °C, 2 h. Note: In B, the concentration of commercial H₂O₂ used is comparable to that produced if all H₂ in a standard in situ reaction is converted to H₂O₂. H₂O₂ was not continually introduced into the reactor. N₂ in parentheses is indicative of the gaseous atmosphere (580 psi). For experiments carried out using H₂ or O₂ only, a gaseous mixture of 5% H₂/CO₂ (420 psi) or 25% O₂/CO₂ (160 psi) was used, with the balance consisting of N₂.