DOI:
10.1039/D5DT00443H
(Paper)
Dalton Trans., 2025,
54, 6812-6821
Regioselective oxidative bromination of arenes by a metal–organic framework-confined mono-bipyridyl iron(III) catalyst†
Received
22nd February 2025
, Accepted 24th March 2025
First published on 24th March 2025
Abstract
Oxidative bromination of arenes is an effective and environmentally friendly method for synthesizing bromoarenes. We have developed a highly robust zirconium metal–organic framework (MOF)-supported mono-bipyridyl iron(III) chloride catalyst (bpy-UiO-FeCl3) for oxidative bromination of arenes using H2O2 as the oxidant and KBr as the bromine source. The bpy-UiO-FeCl3 catalyst exhibits high conversion rates for various substituted arenes, yielding significant amounts of bromoarenes with excellent regioselectivity and recyclability under mild reaction conditions. The MOF catalyst outperforms its homogeneous counterparts in terms of both activity and regioselectivity due to the stabilization of the mononuclear bipyridyl-iron(III) species within the active sites within the MOF pores. Furthermore, the confinement of these active sites within the robust, well-defined, and uniform porous framework enhances the regioselectivity of bromination through shape-selective catalysis. The mechanism of bpy-UiO-FeCl3-catalyzed oxidative bromination of arenes was thoroughly investigated by a combination of control experiments, spectroscopic analyses, and computational studies. These findings underscore the importance of MOFs in the development of heterogeneous catalysts based on Earth-abundant metals for the sustainable synthesis of haloarenes.
Introduction
Halogenation reactions have gained significant importance as organohalides are essential chemicals with significant efficacy in pharmaceutical sciences,1 materials sciences,2 imaging techniques,3 and organic synthesis.4–6 Bromoarenes, in particular, are important synthetic precursors for carbon–carbon bond formation reactions through Heck,7 Stille,8 and Suzuki9 transmetallation processes. Furthermore, bromoaromatics serve as potent antibacterial, antifungal, and antiviral agents, as well as industrial intermediates in the production of pharmaceuticals, agrochemicals, and other specialty products.10–20 Traditionally, bromination reactions are carried out using hazardous, toxic, and corrosive molecular bromine, often in combination with chlorinated solvents.21,22 This approach poses significant environmental and health risks due to molecular bromine's toxicity and corrosive nature. Alternative methods involving electrophilic bromination using N-bromosuccinimide,23,24 alkyl bromide/sodium hydride/DMSO combinations,25 bromodimethylsulfonium bromide26 and a hexamethylenetetramine bromine complex27 have been explored.
Oxidative bromination has emerged as an attractive and environmentally benign alternative, as it generates electrophilic bromine using various oxidants.28–34 This method offers a more sustainable and economically viable pathway to synthesize bromoaromatics compared to classical electrophilic substitutions. In particular, hydrogen peroxide is considered a promising oxidant for oxidative bromination, as the byproduct is only water. Most catalytic systems for oxidative bromination of arenes reported to date require acids,35–39 which, while inexpensive and readily available, pose challenges related to product separation and hazardous waste generation.40,41 Although oxidative bromination of arenes using bromide salts as halogen sources and oxidants has been explored,34,42–45 there remains a pressing need for low-cost, Earth-abundant, non-toxic catalysts that enable oxidative bromination with high yields and excellent regioselectivity under mild conditions.
Metal–organic frameworks (MOFs) have attracted considerable interest for developing robust single-site heterogeneous Earth-abundant catalysts for various applications owing to their high porosity, crystallinity, and molecular tunability, enabling post-synthetic functionalization.46–62 In particular, UiO-MOFs are unique due to the exceptional thermal and chemical stability provided by Zr6(μ3-O)4(μ3-OH)4 secondary building units (SBUs) and linear dicarboxylate bridging linkers.63–66 The post-synthetic modification of MOFs enables the functionalization of their organic linkers, facilitating the formation of single-site base-metal catalysts upon metalation. The rigid and porous MOF stabilizes coordinatively unsaturated and solution inaccessible base-metal species via active-site isolation by preventing multinuclear deactivation pathways.67–75
In addition, MOF-supported single-site catalysts combine the advantages of homogeneous catalysis, including uniform active site distribution, with the stability and recyclability of heterogeneous systems. Moreover, the confinement of active sites within the robust, well-defined and tunable porous frameworks increases the regioselectivity of the reaction via shape-selective catalysis.76–81 Herein, we report the development of a highly active, selective and recyclable MOF-supported monomeric 2,2′-bipyridyl iron(III) chloride catalyst (bpy-UiO-FeCl3) for oxidative bromination of arenes using H2O2 as the oxidant and KBr as the bromine source, affording bromoarenes with high yields and excellent regioselectivity under mild conditions (Fig. 1).
 |
| Fig. 1 Oxidative bromination of aniline using H2O2 and KBr with bpy-UiO-FeCl3 as a shape-selective catalyst. | |
Results and discussion
Synthesis and characterization of bpy-UiO-FeCl3
Bpy-UiO-FeCl3 was synthesized through the post-synthetic metalation of the freshly prepared bpy-UiO-67 MOF containing bipyridyl-functionalized linkers (Fig. 1).71,82 The synthesis involved a solvothermal reaction between ZrCl4 and 2,2′-bipyridine-5,5′-dicarboxylic acid in the presence of CF3CO2H as a modulator in DMF at 100 °C for 4 days, affording the bpy-UiO-67 MOF with a 63% yield. The resulting pristine bpy-UiO-67 MOFs feature a three-dimensional porous UiO topology,63 constructed from Zr6O4(OH)4 nodes interconnected by 2,2′-bipyridine-5,5′-dicarboxylate (bpy) bridging linkers. By stirring a THF solution of FeCl3·6H2O with a slurry of bpy-UiO-67, we obtained bpy-UiO-FeCl3, which contains bipyridyl-ligated Fe-trichloride species within its linkers. Analysis of digested bpy-UiO-FeCl3 using Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) revealed an Fe loading of approximately 45% with respect to the bipyridyl linker, which corresponds to the formula of Zr6(μ3-O)4(μ3-OH)4(bpy)6Fe2.7Cl8.1. The Powder X-Ray Diffraction (PXRD) pattern of bpy-UiO-FeCl3 resembles that of the pristine bpy-UiO-67 MOF, indicating that the crystallinity and structure of the bpy-UiO-67 MOFs are retained during post-synthetic modification (Fig. 2a). Scanning Electron Microscopy-Energy Dispersive X-ray (SEM-EDX) analysis mapping of bpy-UiO-FeCl3 demonstrated a uniform distribution of Fe and Zr ions within the MOF particles (Fig. 2b). Bpy-UiO-FeCl3 has a Brunauer–Emmett–Teller (BET) surface area of 1235 m2 g−1 and a pore size of 0.68 nm, which are smaller than those of the pristine bpy-UiO-67 MOF. This reduction in surface area and pore size is attributed to the incorporation of the iron moiety within the MOF pores (Fig. 2c). Thermogravimetric analysis (TGA) indicates that bpy-UiO-FeCl3 is thermally stable up to 450 °C (Fig. S1, ESI†). X-ray Photoelectron Spectroscopy (XPS) analysis of bpy-UiO-FeCl3 revealed the presence of Fe 2p3/2 and 2p1/2 binding energy peaks at 711.0 eV and 724.6 eV, respectively, confirming the +3 oxidation state of the iron ion (Fig. 2e). The +4 oxidation state of Zr ions in bpy-UiO-FeCl3 was confirmed via XPS, which showed Zr4+ binding energies at 182.5 eV and 184.9 eV (Fig. S11, ESI†). In the X-ray Absorption Near Edge Structure (XANES) analysis, the pre-edge energy of Fe in bpy-UiO-FeCl3 closely matched that of FeCl3 at 7114 eV, further confirming the presence of Fe3+ species (Fig. 2f). The X-band electron paramagnetic resonance (EPR) spectrum reveals a broad signal centered at g = 2.015, indicating the presence of a high-spin Fe3+ species with low magnetic anisotropy (Fig. 2d).84,85 Analysis of the Fe K-edge Extended X-ray Absorption Fine Structure (EXAFS) of bpy-UiO-FeCl3 revealed that the Fe ion is octahedrally coordinated with two nitrogen atoms of bipyridine, three chloride ions, and one CH3CN molecule (Fig. 2g). The Fe–Nbipyridine distance is 1.9 Å, while the Fe–Cla distance is 2.39 Å, the Fe–Clb distance is 2.19 Å and the Fe–NCH3CN distance is 2.09 Å (Fig. 2h). The combined EXAFS and EPR data suggest the existence of a high-spin octahedral (bpy)FeIII(Cl)3(NCCH3) species within bpy-UiO-FeCl3.
 |
| Fig. 2 (a) PXRD patterns of the simulated UiO-67 MOF (black), pristine bpy-UiO-67 (red), bpy-UiO-FeCl3 (blue), bpy-UiO-Fe recovered after run-1 of oxidative bromination of aniline (green) and bpy-UiO-Fe recovered after run-3 of catalysis (purple). (b) SEM image of bpy-UiO-FeCl3 particles along with elemental mapping of Fe and Zr. (c) N2 sorption isotherms of bpy-UiO-67 (black/red)83 and bpy-UiO-FeCl3 (gray/magenta) measured at 77 K. (d) EPR spectrum of solid bpy-UiO-FeCl3. (e) Fe 2p XPS spectrum of bpy-UiO-FeCl3. (f) XANES spectra of metallic Fe(0) foil (gray), FeCl3 (red) and bpy-UiO-FeCl3 (blue). (g) EXAFS spectra and fits of bpy-UiO-FeCl3 in the R space from 1.0 to 3.3 Å. (h) DFT-optimized structure of the bpy-FeCl3(NCCH3) moiety within bpy-UiO-FeCl3 MOFs. The bond distances are given in Å. | |
Catalytic oxidative bromination of aniline
Bpy-UiO-FeCl3 is an active heterogeneous catalyst for the oxidative bromination of aniline, utilizing H2O2 as the oxidant and KBr as the brominating agent. To optimize the reaction conditions for maximum conversion and yield, we thoroughly investigated the impact of various reaction parameters, including the reaction temperature, reaction time, solvents, substrate-to-oxidant ratio, catalyst concentration, and nature and concentration of the brominating agent. The effect of temperature on the oxidative bromination of aniline was studied over a range of 30–60 °C using 1 mmol of aniline, 4 mg of the catalyst bpy-UiO-FeCl3 (0.4 mol% of Fe), 2 mmol of H2O2, 1.1 mmol of KBr, and 5 mL of CH3CN for a duration of 2 h (Fig. 3a). The results showed that temperature variation had only a minimal effect on the conversion of aniline; however, regioselectivity decreased at higher temperatures (entries 1–3, Table S2, ESI†). The reaction time plays a critical role in evaluating the catalytic performance of the catalyst. To investigate this, the effect of reaction time on the oxidative bromination of aniline with H2O2 was examined over a range of 30–180 min (Fig. 3b). The results showed a direct correlation between the reaction time and the yield of the 4-bromoaniline product. The highest yield of 95% was achieved after 2 h, indicating that longer reaction times enhance substrate interaction and conversion, enabling the catalyst to effectively promote the desired reaction. The study revealed that CH3CN was the most efficient solvent for the bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline using H2O2, achieving a conversion rate of 98% and a selectivity of 97% for the target product (2a) within 2 h (Fig. 3c). This enhanced performance is due to acetonitrile's beneficial solvation properties, which improve the stabilization of reaction intermediates and aid in the transfer of reactants at the catalyst's active sites.
 |
| Fig. 3 (a) Effect of temperature on %conversion and %selectivity of 4-bromoaniline for bpy-UiO-FeCl3-catalysed oxidative bromination of aniline. Reaction conditions: aniline (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), bpy-UiO-FeCl3 (4 mg, 0.4 mol% of Fe), CH3CN (5 mL), 2 h. (b) Effect of time on %conversion and %selectivity of 4-bromoaniline for bpy-UiO-FeCl3-catalysed oxidative bromination of aniline. Reaction conditions: aniline (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), bpy-UiO-FeCl3 (4 mg, 0.4 mol% of Fe), CH3CN (5 mL), 50 °C. (c) Effect of different solvents on %conversion and %selectivity of 4-bromoaniline for bpy-UiO-FeCl3-catalysed oxidative bromination of aniline. Reaction conditions: aniline (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), bpy-UiO-FeCl3 (4 mg, 0.4 mol% of Fe), solvent (5 mL), 50 °C, 2 h. (d) Effect of H2O2 amounts on %conversion and %selectivity of 4-bromoaniline for bpy-UiO-FeCl3-catalysed oxidative bromination of aniline. Reaction conditions: aniline (1 mmol), KBr (1.1 mmol), bpy-UiO-FeCl3 (4 mg, 0.4 mol% of Fe), CH3CN (5 mL), 50 °C, 2 h. (e) Effect of brominating agents on %conversion and %selectivity of 4-bromoaniline for bpy-UiO-FeCl3-catalysed oxidative bromination of aniline. Reaction conditions: aniline (1 mmol), H2O2 (2 mmol), brominating agent (1.1 mmol), bpy-UiO-FeCl3 (4 mg, 0.4 mol% of Fe), CH3CN (5 mL), 50 °C, 2 h. (f) Effect of different Fe loadings on %conversion and %selectivity of 4-bromoaniline for bpy-UiO-FeCl3-catalysed oxidative bromination of aniline. Reaction conditions: aniline (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), CH3CN (5 mL), 50 °C, 2 h. | |
In comparison, other solvents such as CH3OH, DME and DCM resulted in lower yields of 2a. A control experiment confirmed the necessity of H2O2, as no bromo product was produced in its absence (entry 8, Table S2, ESI†). An investigation of different H2O2 concentrations, while keeping other parameters constant, revealed that maximum bromination was achieved at a 1
:
2 molar ratio (Fig. 3d). In contrast, a 1
:
3 molar ratio resulted in a decreased yield (81%) and reduced para-selectivity (82%). The effect of different brominating agents on the oxidative bromination of aniline using H2O2 as the oxidant was also investigated (Fig. 3e). Among the brominating agents tested (LiBr, NaBr, and KBr), KBr demonstrated the highest efficiency, achieving 98% conversion with excellent regioselectivity for the para-product (97%). In comparison, NaBr and LiBr showed lower activities (entries 11 and 12, Table S2, ESI†). A KBr concentration of 1.1 mmol yielded the optimal results. The catalyst loading was systematically optimized to achieve maximum efficiency. It was observed that 0.4 mol% of Fe loading in bpy-UiO-FeCl3 provided the highest conversion rate of 98%. Reducing the Fe loading in the bpy-UiO-FeCl3 catalyst from 0.4 mol% to 0.2 mol% resulted in a decline in bromoaniline yield from 95% to 73%, attributed to a reduced availability of active sites. Under the optimized conditions, the reaction achieved the highest yield of 4-bromoaniline (2a) at 95%. This was accomplished using a catalyst loading of 0.4 mol% Fe, 1 mmol of aniline, 1.1 mmol of KBr, and 2 mmol of 30% aqueous H2O2 in 5 mL of CH3CN at 50 °C for 2 hours, resulting in a turn-over number (TON) of 238 (entry 2, Table S2, ESI†).
Substrate scopes for oxidative bromination of arenes
Under the optimized conditions, the oxidative bromination of aromatic substrates, including N,N-dimethylaniline (1b), anisole (1c), phenol (1d), and toluene (1e), afforded the corresponding para-bromo products (2b–2e) with isolated yields ranging from 85% to 96% and excellent selectivity (91–98%). Benzene (1f), due to its lack of activating groups, exhibited significantly lower conversion rates and required extended reaction times to achieve measurable bromination under the same conditions. In contrast, deactivated aromatic rings such as nitrobenzene (1g) and bromobenzene (1h) produced the corresponding bromo products with yields of 15–20% after 24 h at 80 °C. 4-Substituted aromatics, such as 4-methylaniline (1i) and p-xylene (1j), were selectively converted to 2-bromo-4-methylaniline (2i) and 2-bromo-p-xylene (2j) with isolated yields of 70–71%. In contrast, 2-substituted aromatics such as o-xylene (1k), 2-iodoaniline (1l), 1,2-dimethoxybenzene (1m) and catechol (1n) were also selectively converted to the corresponding bromo products (2k–n) with isolated yields of 57–72%. Similarly, 3-substituted aromatics such as 3-methylaniline (1o) and m-xylene (1p) were selectively converted to 4-bromo-3-methylaniline (2o) and 4-bromo-m-xylene (2p), respectively, achieving yields of 66–67% under the same conditions (Scheme 1).
 |
| Scheme 1 Substrate scope of oxidative bromination of arenes with bpy-UiO-FeCl3. Conditions: 1 (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), bpy-UiO-FeCl3 (4 mg, 0.4 mol% of Fe), CH3CN (5 mL), 50 °C, 2 h. Yields refer to the isolated products. Selectivity of para-bromo products is given in parentheses. aThe reaction was performed for 10 h. bThe reaction was performed for 24 h at 80 °C. | |
Control experiments
Bpy-UiO-FeCl3 acts as a heterogeneous catalyst and can be recycled at least three times while maintaining consistent activity (Fig. 4a). The PXRD pattern of the recovered MOF material after catalysis revealed no apparent change in crystallinity and structure of the MOFs (Fig. 2a). The percentage of leached Fe and Zr into the supernatant after the first run was 0.02% and 0.6%, respectively, while after the third run, it was 0.08% and 1.5%, as analyzed by ICP-OES (Table S5, ESI†). The catalytic activity of bpy-UiO-FeCl3 is over four times greater than that of the homogeneous control, bipyridine-FeCl3. The latter was synthesized by reacting 5,5′-dimethyl-2,2′-bipyridine with FeCl3·6H2O in a 1
:
1 molar ratio in THF. The time evolution plot for bpy-UiO-FeCl3 (0.4 mol% of Fe) catalyzed oxidative bromination of aniline demonstrates a linear increase in the synthesis of 4-bromoaniline, achieving 97% selectivity until 98% conversion of aniline in 2 h (Fig. 4b). In contrast, under the same reaction conditions and with equivalent Fe loading, bipyridine-FeCl3 produced only 26% yield of 4-bromoaniline in 2 hours, with a selectivity of 68% (Fig. 4b). This enhanced activity of the bpy-UiO-FeCl3 MOF is attributed to the stability of bpy-FeCl3 species, which are isolated at the linkers, preventing decomposition.
 |
| Fig. 4 (a) Plot for the %conversion of aniline and the %yield of 4-bromoaniline at various runs in the recycling of bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline. (b) Time evaluation studies of oxidative bromination of aniline using bpy-UiO-FeCl3 and its homogeneous control [(bpy)FeCl3] under identical conditions. Conditions: aniline (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), catalyst (0.4 mol% of Fe), CH3CN (5 mL), 50 °C. (c) Comparison of the catalytic activity of bpy-UiO-FeCl3 with other iron catalysts under identical reaction conditions. Conditions: aniline (1 mmol), H2O2 (2 mmol), KBr (1.1 mmol), catalyst (0.4 mol% of Fe), CH3CN (5 mL), 50 °C, 2 h. (d) Time evaluation studies of oxidative bromination of aniline, toluene, benzene and nitrobenzene under the optimized reaction conditions. | |
In addition, the bpy-UiO-FeCl3 framework features uniform and rigid pores with a size of 0.68 nm, which allow the diffusion of aniline (0.83 × 0.67 nm) and p-bromoaniline (0.97 × 0.67 nm); however, they restrict the formation of the larger product, o-bromoaniline (0.88 × 0.79 nm), resulting in the formation of p-bromoaniline with 97% selectivity through shape-selective catalysis. While the MOF pores (0.68 nm) are indeed identical to or smaller than the reported molecular widths of aniline (0.83 × 0.67 nm) and para-bromoaniline products (0.97 × 0.67 nm), molecules are not rigid and can reorient or deform during diffusion and enter the pore by aligning its narrower axis (0.67 nm) with the pore window.76 In contrast, the homogeneous bipyridine-FeCl3 catalyst lacks this structural confinement, leading to only 68% selectivity of p-bromoaniline. To confirm that the oxidative bromination reaction occurs predominantly within the pores of the bpy-UiO-FeCl3 MOF, rather than on the external surface of the MOF, an experiment was conducted using a bulky phosphine, tricyclohexylphosphine, to block the surface iron active sites.74,76 The addition of 1.2 equivalents of tricyclohexylphosphine per iron ion in the bpy-UiO-FeCl3-catalysed oxidative bromination of aniline resulted in a slight decrease in conversion to ∼88%. However, the regioselectivity for the para-bromoaniline product remained unchanged (97%). This observation suggests that the iron active sites are mostly embedded within the MOF pores, which catalyze the oxidative bromination of arenes within the pores (entry 8, Table S3, ESI†). Several controlled experiments were conducted to identify the actual catalytic species involved in the bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline to produce 4-bromoaniline. The results showed that reactions (a) without the bpy-UiO-FeCl3 catalyst (entry 3, Table S3†) and (b) with the pristine bpy-UiO-67 MOF (entry 2, Table S3†) all yielded negligible amounts of 4-bromoaniline. The results also showed that reactions (a) with bpy-UiO-FeCl2 (entry 4, Table S2†), (d) with FeCl3·6H2O (entry 5, Table S2†) and (e) with Fe nanoparticles (entry 6, Table S2†) all yielded lower amounts of 4-bromoaniline with less selectivity (Fig. 4c). This confirms that bpy-UiO-FeCl3 is the active catalyst for the oxidative bromination of aniline. The oxidative bromination of aniline ceased upon the removal of the solid MOF catalyst, indicating that the active species is embedded in the MOF solid (section 3.4, ESI†).
Mechanism exploration of bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline
The mechanism of bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline was investigated by characterizing the catalyst after catalysis and computational studies. The PXRD pattern of the recovered bpy-UiO-Fe MOF after catalysis indicates that both the structure and crystallinity of the MOF remained intact during the reaction (Fig. 2a). Additionally, the absence of any characteristic peak for metallic iron at higher 2θ angles in the same PXRD pattern suggests that Fe(0) nanoparticles or metallic Fe particulates did not form during the bromination reaction. The XPS analysis of bpy-UiO-FeCl3 after oxidative bromination of aniline identified Fe 2p3/2 and 2p1/2 binding energy peaks at 711.8 eV and 724.6 eV, respectively, confirming the +3 oxidation state of the iron ion (Fig. S12, ESI†). Again, radical pathway tests utilizing Na2SO3 and tert-butanol (TBA) as scavengers demonstrated no impact on the reaction rate, effectively ruling out the possibility of a radical mechanism (Fig. S6, ESI†).
Based on spectroscopic data and control experiments, we propose that the reaction of H2O2 with bpy-UiO-FeCl3 initially forms an Fe(III)-hydroperoxy intermediate, [FeIII-OOH] (INT-1). Subsequently, the Br− ion from KBr attacks the oxygen atom coordinated to iron in INT-1, forming the [FeIII-OBr] intermediate (INT-2) and releasing KOH. INT-2 interacts with the aniline substrate to form INT-3, where electrophilic aromatic substitution takes place. The reactive Br+ then undergoes an electrophilic attack on the aniline substrate, resulting in the formation of the bromoaniline-bound Fe(III) intermediate (INT-4) via transition state 1 (TS-1). Finally, the desired p-bromoaniline product is released from INT-4, regenerating the initial Fe(III) catalyst, bpy-UiO-Fe, and completing the catalytic cycle (Fig. 5a).
 |
| Fig. 5 (a) Proposed catalytic cycle of bpy-UiO-FeCl3-catalyzed oxidative bromination of arenes. (b) DFT-calculated free energy profile diagram of bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline at 323.15 K. | |
Evidence for the electrophilic aromatic substitution mechanism was gathered through a time-evolution study of reactions involving arenes such as aniline, toluene, benzene, and nitrobenzene under identical conditions (Fig. 4d). The reaction rates followed the trend aniline > toluene > benzene, consistent with the activating effects of electron-donating groups. In contrast, nitrobenzene did not undergo the reaction due to the deactivating influence of its electron-withdrawing nitro group, rendering the aromatic system unreactive under these conditions.
To gain a deeper understanding of the reaction pathway, we computed the entire catalytic cycle using Density Functional Theory (DFT) at the B3LYP/def2-SVP/SMD (solvent = acetonitrile) level of theory in Gaussian 09 software (Fig. 5b). The DFT-calculated free energy diagram at 323.15 K for the bpy-UiO-FeCl3-catalyzed oxidative bromination of aniline indicates that the coordination of H2O2 with the bpy-UiO-FeCl3 MOF is endergonic by 1.9 kcal mol−1. Furthermore, nucleophilic substitution of Br− on [FeIII(OOH)] leading to the formation of [FeIII(OBr)] species (INT-2) is endergonic by 30.1 kcal mol−1. In the next step, the conversion of INT-2 to INT-3 is endergonic by 0.9 kcal mol−1. The subsequent transformation of INT-3 to INT-4 via TS-1 is exergonic by 34.4 kcal mol−1, overcoming a barrier of 3.6 kcal mol−1. Finally, the release of p-bromoaniline from INT-4 regenerates the bpy-UiO-Fe MOF, which is exergonic by 9.8 kcal mol−1. DFT calculations suggest that the nucleophilic substitution of Br− on INT-1 leading to the formation of INT-2 is the turnover limiting step requiring a free activation energy of 30.1 kcal mol−1 (Fig. 5b).
Conclusions
In summary, we have successfully synthesized a porous and highly robust zirconium-based metal–organic framework (MOF)-supported mono-bipyridyl-iron(III) chloride catalyst through active-site isolation. Bpy-UiO-FeCl3 demonstrates high selectivity and recyclability for the oxidative bromination of various substituted arenes using hydrogen peroxide (H2O2) as the oxidant and potassium bromide (KBr) as the bromine source. Mono-substituted arenes were converted to para-bromoarenes with excellent selectivities ranging from 90% to 98%. The uniform and regular porous structure of the MOF facilitates shape-selective catalysis, preventing the formation of larger ortho-bromoarene products, ensuring the exclusive formation of para-bromoarenes, unlike homogeneous catalysts that typically exhibit lower selectivity. Bpy-UiO-FeCl3 is also effective for a wide range of 1,2-, 1,3-, and 1,4-substituted arenes, converting them into the desired bromo products with moderate to good yields under mild reaction conditions. Through spectroscopic and computational studies, we investigated the mechanism and identified the turnover-limiting step in the catalytic cycle. Our findings highlight the importance of MOFs in creating sustainable, Earth-abundant metal catalysts for the direct oxidative bromination of arenes, enabling the eco-friendly synthesis of haloarenes.
Author contributions
R. K. and A. K. synthesized the MOF catalyst and performed catalytic reactions. P. G. performed the DFT calculations. R. K., B. R., B. S. and M. C. characterized the MOF materials and analyzed the data. K. M. designed and supervised the entire project. K. M. and R. K. wrote the manuscript. All the authors approved the final version of the manuscript.
Data availability
The data supporting this article have been included as part of the ESI.†
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
K. M. thanks the Science and Engineering Research Board (SERB), India [CRG/2022/003553] and CSIR-HRDG [01(3040)/21/EMR-II] for financial support. R. K., P. G., B. R. and M. C. acknowledge the CSIR. A. K. acknowledges the UGC for financial support. B. S. acknowledges ANRF NPDF (PDF/2023/000250) for financial support. The authors thank Prof. B. Jayaram for providing access to his super-computing facility. We acknowledge Raja Ramanna Centre for Advanced Technology-Indore (RRCAT) for XAS measurement in the Indus-2 SRS facility. We thank Rajashri Urkude for her help in XAS measurement at RRCAT. The authors acknowledge the Central Research Facility, IIT Delhi, for XPS, NMR, BET, SEM, EPR and other instrument facilities.
References
- M. Hernandes, S. M. Cavalcanti, D. R. Moreira, W. De Azevedo Junior and A. C. Leite, Curr. Drug Targets, 2010, 11, 303–314 CAS.
- M. L. Tang and Z. Bao, Chem. Mater., 2011, 23, 446–455 CAS.
- M. J. Adam and D. S. Wilbur, Chem. Soc. Rev., 2005, 34, 153 CAS.
- D. A. Petrone, J. Ye and M. Lautens, Chem. Rev., 2016, 116, 8003–8104 CAS.
- P. A. Champagne, J. Desroches, J.-D. Hamel, M. Vandamme and J.-F. Paquin, Chem. Rev., 2015, 115, 9073–9174 CAS.
- A. Varenikov, E. Shapiro and M. Gandelman, Chem. Rev., 2021, 121, 412–484 CAS.
-
R. F. Heck, in Organic Reactions, ed. S. E. Denmark, Wiley, 1st edn, 1982, pp. 345–390 Search PubMed.
- J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508–524 Search PubMed.
- A. Suzuki, Angew. Chem., Int. Ed., 2011, 50, 6722–6737 CAS.
- D. Wischang, O. Brücher and J. Hartung, Coord. Chem. Rev., 2011, 255, 2204–2217 CAS.
- I. Saikia, A. J. Borah and P. Phukan, Chem. Rev., 2016, 116, 6837–7042 CAS.
- M. Naresh, M. Arun Kumar, M. Mahender Reddy, P. Swamy, J. Nanubolu and N. Narender, Synthesis, 2013, 45, 1497–1504 CAS.
- N. Oztaskin, S. Goksu, Y. Demir, A. Maras and İ. Gulcin, Molecules, 2022, 27, 7426 CAS.
- Y. Yoshida, T. Mino and M. Sakamoto, ACS Catal., 2021, 11, 13028–13033 CAS.
- G. W. Gribble, Acc. Chem. Res., 1998, 31, 141–152 CrossRef CAS.
-
M. J. Dagani, H. J. Barda, T. J. Benya and D. C. Sanders, in Ullmann's Encyclopedia of Industrial Chemistry, ed. Wiley-VCH, Wiley, 1st edn, 2000 Search PubMed.
- P. Ruiz-Castillo and S. L. Buchwald, Chem. Rev., 2016, 116, 12564–12649 CrossRef CAS PubMed.
- N. Longkumer, K. Richa, R. Karmaker, V. Kuotsu, A. Supong, L. Jamir, P. Bharali and U. B. Sinha, Acta Chim. Slov., 2019, 66, 276–283 CrossRef CAS PubMed.
- N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457–2483 CrossRef CAS.
- A. Jain, L. S. Duvvuri, S. Farah, N. Beyth, A. J. Domb and W. Khan, Adv. Healthcare Mater., 2014, 3, 1969–1985 CrossRef CAS PubMed.
- R. Adams and C. S. Marvel, Org. Synth., 1921, 1, 39 CrossRef.
- C. Venkatachalapathy and K. Pitchumani, Tetrahedron, 1997, 53, 2581–2584 CrossRef CAS.
- B. Das, K. Venkateswarlu, M. Krishnaiah and H. Holla, Tetrahedron Lett., 2006, 47, 8693–8697 CrossRef CAS.
- D. A. Rogers, R. G. Brown, Z. C. Brandeburg, E. Y. Ko, M. D. Hopkins, G. LeBlanc and A. A. Lamar, ACS Omega, 2018, 3, 12868–12877 CrossRef CAS PubMed.
- M. Guo, L. Varady, D. Fokas, C. Baldino and L. Yu, Tetrahedron Lett., 2006, 47, 3889–3892 CrossRef CAS.
- G. Majetich, R. Hicks and S. Reister, J. Org. Chem., 1997, 62, 4321–4326 CrossRef CAS PubMed.
- M. M. Heravi, N. Abdolhosseini and H. A. Oskooie, Tetrahedron Lett., 2005, 46, 8959–8963 CrossRef CAS.
- B. Sels, D. D. Vos, M. Buntinx, F. Pierard, A. Kirsch-De Mesmaeker and P. Jacobs, Nature, 1999, 400, 855–857 CrossRef CAS.
- B. M. Choudary, Y. Sudha and P. N. Reddy, Synlett, 1994, 450–450 CrossRef CAS.
- G. Rothenberg and J. H. Clark, Org. Process Res. Dev., 2000, 4, 270–274 CrossRef CAS.
- N. Narender, P. Srinivasu, S. J. Kulkarni and K. V. Raghavan, Synth. Commun., 2000, 30, 3669–3675 CrossRef CAS.
- B. Ganchegui and W. Leitner, Green Chem., 2007, 9, 26–29 RSC.
- A. Podgoršek, M. Zupan and J. Iskra, Angew. Chem., Int. Ed., 2009, 48, 8424–8450 CrossRef PubMed.
- D.-B. Jiang, F.-Y. Wu and H.-L. Cui, Org. Biomol. Chem., 2023, 21, 1571–1590 RSC.
- S. Mallik, K. M. Parida and S. S. Dash, J. Mol. Catal. A: Chem., 2007, 261, 172–179 CrossRef CAS.
- T. Moriuchi, Y. Fukui, T. Sakuramoto and T. Hirao, Chem. Lett., 2017, 46, 1708–1710 CrossRef CAS.
- M. R. Maurya, V. Prakash, F. Avecilla and M. Sankar, Eur. J. Inorg. Chem., 2021, 2021, 1685–1694 CrossRef CAS.
- H. H. L. B. Lima, G. R. da Silva, J. M. Pena and R. Cella, ChemistrySelect, 2017, 2, 9624–9627 CrossRef CAS.
- E. M. Gayakwad, K. P. Patel and G. S. Shankarling, New J. Chem., 2019, 43, 6001–6009 RSC.
- T. Okuhara, Chem. Rev., 2002, 102, 3641–3666 CrossRef CAS PubMed.
- K. Wilson and J. H. Clark, Pure Appl. Chem., 2000, 72, 1313–1319 CrossRef CAS.
- S. Eshwar Rao and G. Virupaiah, J. Chem. Technol. Biotechnol., 2017, 92, 2060–2074 CrossRef CAS.
- E. E. Alberto, L. M. Muller and M. R. Detty, Organometallics, 2014, 33, 5571–5581 CrossRef CAS.
- G. Zhao, E. Wang and R. Tong, ACS Sustainable Chem. Eng., 2021, 9, 6118–6125 CrossRef CAS.
- G. Pomarico, F. Sabuzi, V. Conte and P. Galloni, New J. Chem., 2019, 43, 17774–17782 RSC.
- T. Ikuno, J. Zheng, A. Vjunov, M. Sanchez-Sanchez, M. A. Ortuño, D. R. Pahls, J. L. Fulton, D. M. Camaioni, Z. Li, D. Ray, B. L. Mehdi, N. D. Browning, O. K. Farha, J. T. Hupp, C. J. Cramer, L. Gagliardi and J. A. Lercher, J. Am. Chem. Soc., 2017, 139, 10294–10301 CrossRef CAS PubMed.
- S. M. Cohen, Chem. Rev., 2012, 112, 970–1000 CrossRef CAS PubMed.
- Z. Lin, N. C. Thacker, T. Sawano, T. Drake, P. Ji, G. Lan, L. Cao, S. Liu, C. Wang and W. Lin, Chem. Sci., 2018, 9, 143–151 RSC.
- N. C. Thacker, Z. Lin, T. Zhang, J. C. Gilhula, C. W. Abney and W. Lin, J. Am. Chem. Soc., 2016, 138, 3501–3509 CrossRef CAS PubMed.
- D. Y. Osadchii, A. I. Olivos-Suarez, Á. Szécsényi, G. Li, M. A. Nasalevich, I. A. Dugulan, P. S. Crespo, E. J. M. Hensen, S. L. Veber, M. V. Fedin, G. Sankar, E. A. Pidko and J. Gascon, ACS Catal., 2018, 8, 5542–5548 CAS.
- J. N. Hall and P. Bollini, Chem. – Eur. J., 2020, 26, 16639–16643 CAS.
- Y. Yang, S. Kanchanakungwankul, S. Bhaumik, Q. Ma, S. Ahn, D. G. Truhlar and J. T. Hupp, J. Am. Chem. Soc., 2023, 145, 22019–22030 CAS.
- M. C. Simons, S. D. Prinslow, M. Babucci, A. S. Hoffman, J. Hong, J. G. Vitillo, S. R. Bare, B. C. Gates, C. C. Lu, L. Gagliardi and A. Bhan, J. Am. Chem. Soc., 2021, 143, 12165–12174 CAS.
- Y. Zhang, J. Li, X. Yang, P. Zhang, J. Pang, B. Li and H.-C. Zhou, Chem. Commun., 2019, 55, 2023–2026 CAS.
- B. Pramanik, R. Sahoo and M. C. Das, Coord. Chem. Rev., 2023, 493, 215301 CAS.
- P. Gupta, B. Rana, R. Maurya, R. Kalita, M. Chauhan and K. Manna, Chem. Sci., 2025, 16, 2785–2795 CAS.
- M. Chauhan, B. Rana, P. Gupta, R. Kalita, C. Thadhani and K. Manna, Nat. Commun., 2024, 15, 9798 CAS.
- W. Begum, M. Chauhan, R. Kalita, P. Gupta, N. Akhtar, N. Antil, R. Newar and K. Manna, ACS Catal., 2024, 14, 10427–10436 CAS.
- R. Newar, W. Begum, N. Akhtar, N. Antil, M. Chauhan, A. Kumar, P. Gupta, J. Malik, Balendra and K. Manna, Eur. J. Inorg. Chem., 2022, 2022, e202101019 CAS.
- R. Newar, R. Kalita, N. Akhtar, N. Antil, M. Chauhan and K. Manna, Catal. Sci. Technol., 2022, 12, 6795–6804 CAS.
- N. Antil, A. Kumar, N. Akhtar, R. Newar, W. Begum and K. Manna, Inorg. Chem., 2021, 60, 9029–9039 CAS.
- R. Kalita, W. Begum, P. Gupta, M. Chauhan, N. Akhtar, R. Newar and K. Manna, Eur. J. Inorg. Chem., 2023, 26, e202300215 CAS.
- J. H. Cavka, S. Jakobsen, U. Olsbye, N. Guillou, C. Lamberti, S. Bordiga and K. P. Lillerud, J. Am. Chem. Soc., 2008, 130, 13850–13851 Search PubMed.
- Y. Bai, Y. Dou, L.-H. Xie, W. Rutledge, J.-R. Li and H.-C. Zhou, Chem. Soc. Rev., 2016, 45, 2327–2367 CAS.
- A. Das, N. Anbu, M. Sk, A. Dhakshinamoorthy and S. Biswas, Eur. J. Inorg. Chem., 2020, 2020, 2830–2834 CAS.
- S. Yuan, J.-S. Qin, C. T. Lollar and H.-C. Zhou, ACS Cent. Sci., 2018, 4, 440–450 CAS.
- J. Baek, B. Rungtaweevoranit, X. Pei, M. Park, S. C. Fakra, Y.-S. Liu, R. Matheu, S. A. Alshmimri, S. Alshehri, C. A. Trickett, G. A. Somorjai and O. M. Yaghi, J. Am. Chem. Soc., 2018, 140, 18208–18216 CAS.
- J. Lee, O. K. Farha, J. Roberts, K. A. Scheidt, S. T. Nguyen and J. T. Hupp, Chem. Soc. Rev., 2009, 38, 1450 CAS.
- K. Manna, T. Zhang and W. Lin, J. Am. Chem. Soc., 2014, 136, 6566–6569 CAS.
- Y.-S. Wei, M. Zhang, R. Zou and Q. Xu, Chem. Rev., 2020, 120, 12089–12174 CAS.
- T. Zhang, K. Manna and W. Lin, J. Am. Chem. Soc., 2016, 138, 3241–3249 CrossRef CAS PubMed.
- C. Kutzscher, G. Nickerl, I. Senkovska, V. Bon and S. Kaskel, Chem. Mater., 2016, 28, 2573–2580 CrossRef CAS.
- N. Akhtar, M. Chauhan, P. Gupta, N. Antil and K. Manna, Dalton Trans., 2023, 52, 15384–15393 RSC.
- R. Kalita, M. Chauhan, P. Gupta, W. Begum and K. Manna, Angew. Chem., 2025, 64, e202413402 CrossRef CAS PubMed.
- P. Gupta, N. Akhtar, W. Begum, B. Rana, R. Kalita, M. Chauhan, C. Thadhani and K. Manna, Inorg. Chem., 2024, 63, 11907–11916 CrossRef CAS PubMed.
- X. Zhang, Z. Huang, M. Ferrandon, D. Yang, L. Robison, P. Li, T. C. Wang, M. Delferro and O. K. Farha, Nat. Catal., 2018, 1, 356–362 CrossRef CAS.
- R. Kalita, M. Chauhan, P. Gupta, W. Begum, C. Thadhani, B. Ghosh, Balendra, H. Bisht and K. Manna, Chem. Commun., 2024, 60, 6504–6507 Search PubMed.
- S. Horike, M. Dincǎ, K. Tamaki and J. R. Long, J. Am. Chem. Soc., 2008, 130, 5854–5855 CrossRef CAS PubMed.
- W. Zhang, G. Lu, C. Cui, Y. Liu, S. Li, W. Yan, C. Xing, Y. R. Chi, Y. Yang and F. Huo, Adv. Mater., 2014, 26, 4056–4060 CAS.
- I. Luz, C. Rösler, K. Epp, F. X. Llabrés I Xamena and R. A. Fischer, Eur. J. Inorg. Chem., 2015, 2015, 3904–3912 CAS.
- L. Yang, P. Cai, L. Zhang, X. Xu, A. A. Yakovenko, Q. Wang, J. Pang, S. Yuan, X. Zou, N. Huang, Z. Huang and H.-C. Zhou, J. Am. Chem. Soc., 2021, 143, 12129–12137 CrossRef CAS PubMed.
- Y. Zhao, S. Zhang, M. Wang, J. Han, H. Wang, Z. Li and X. Liu, Dalton Trans., 2018, 47, 4646–4652 CAS.
- R. Kalita, Y. Monga and K. Manna, New J. Chem., 2025, 49, 2071–2078 CAS.
- J. Krzystek, A. Ozarowski and J. Telser, Coord. Chem. Rev., 2006, 250, 2308–2324 CAS.
- R. J. Holmberg, T. Burns, S. M. Greer, L. Kobera, S. A. Stoian, I. Korobkov, S. Hill, D. L. Bryce, T. K. Woo and M. Murugesu, Chem. – Eur. J., 2016, 22, 7711–7715 CAS.
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