# Highly Selective Aldol Condensation of Furfural and Acetone Over Defective-Engineered MIL-88B Metal–Organic Frameworks

Gustavo F Bitencourt, Sancler Vasconcelos, Luana S Andrade, Vinicius Rossa, Daniel G S Quattrociocchi, Wagner A Carvalho, Mohamad El Roz, Dalmo Mandelli, Thiago M. Lima

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Gustavo F Bitencourt, Sancler Vasconcelos, Luana S Andrade, Vinicius Rossa, Daniel G S Quattrociocchi, et al. Highly Selective Aldol Condensation of Furfural and Acetone Over Defective-Engineered MIL-88B Metal–Organic Frameworks. Applied Organometallic Chemistry, 2025, 39 (8), 10.1002/aoc.70308. [hal-05311660](https:// HAL Id: hal-05311660 )

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RESEARCH ARTICLE

OPEN ACCESS

# Highly Selective Aldol Condensation of Furfural and Acetone Over Defective-Engineered MIL-88B Metal–Organic Frameworks

Gustavo F. Bitencourt<fnref n="1" />,⁴ | Sancler Vasconcelos² | Luana S. Andrade<fnref n="1" /> | Vinicius Rossa² | Daniel G. S. Quattrociocchi³ |

Wagner A. Carvalho<fnref n="1" /> | Mohamad El Roz⁴ ID | Dalmo Mandelli<fnref n="1" /> | Thiago M. Lima² ID

**Correspondence:** Dalmo Mandelli (dalmo.mandelli@ufabc.edu.br) | Thiago M. Lima (tlima@id.uff.br)

**Received:** 18 March 2025 | **Revised:** 18 March 2025 | **Accepted:** 19 June 2025

**Funding:** This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, 10.13039/501100001807, (2021/10885-6, 2021/09775-1, 2018/01258-5, 2023/08875-8, 2024), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, 10.13039/501100004586, (E-26/210.385/2018, E-26/211.575/2019, E-26/010.000.984/2019), Conselho Nacional de Desenvolvimento Científico e Tecnológico, 10.13039/501100003593, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, 10.13039/501100002322.

**Keywords:** aldol condensation | lignocellulosic biomass | MOF | structural defects

## ABSTRACT

Furfural (FUR), a valuable platform molecule derived from lignocellulosic biomass, is a promising feedstock for producing furfural acetone (FAC) through aldol condensation reactions, offering pathways to various chemical products. However, identifying efficient and sustainable catalysts for FAC production remains challenging. Here, we introduce a novel strategy employing Fe-MIL-88B and Fe-MIL-88B-NH₂ metal-organic frameworks (MOFs) composed of nonnoble metals designed to enhance catalytic efficiency in FUR conversion. In contrast to conventional synthesis methods, our approach integrates magnetic stirring during solvothermal synthesis, promoting defect formation that improves the structural and catalytic properties of the MOFs without requiring additional reagents. Extensive characterization confirmed these structural improvements, while a statistical design of experiments guided the optimization of catalytic parameters for the FUR-acetone reaction. Thermal pretreatment emerged as a critical factor in driving high FAC selectivity. Catalytic tests showed that MOFs synthesized with stirring exhibited significantly greater selectivity than those synthesized without stirring. Furthermore, functionalization with amino groups (–NH₂) reduced FUR conversion. The optimized catalyst, Fe-MIL-88B-S, achieved a remarkable 99.4% conversion and 99.9% selectivity for FAC, demonstrating stability across three cycles. This work provides a sustainable approach to catalyzing furanic conversions using defect-engineered, nonnoble metal MOFs. It underscores the potential of simplified, scalable methods for defect induction to expand MOF applications in sustainable chemical transformations.

<footnote n="1">¹Universidade Federal do ABC – UFABC, Centro de Ciências Naturais e Humanas, Santo André, Brazil | ²Universidade Federal Fluminense - UFF, Instituto de Química, Niterói, Brazil | ³Universidade Federal de Roraima - UFRR, Centro de Ciências e Tecnologia, Departamento de Química, Boa Vista, Brazil | ⁴University of Caen, UNICAEN, ENSICAEN, CNRS, Laboratoire Catalyse et Spectrochimie, Caen, France</footnote>
Significant decarbonization efforts are required to mitigate global warming, with low-carbon fuels, feedstocks, and energy sources being vital to achieving net-zero greenhouse gas emissions by 2050 [1]. Lignocellulosic biomass from agriculture and forestry residues presents a promising renewable feedstock for producing advanced biofuels and chemicals. However, its conversion is still challenging due to its recalcitrant structure and the high oxygen content of the biomass [2]. A critical step in this process involves the catalytic upgrading of sugars from cellulose and hemicellulose into platform chemicals such as furfural (FUR) and 5-(hydroxymethyl)furfural (5-HMF). FUR is particularly valuable in the bioeconomy, and the US Department of Energy has recognized it as one of the 12 most promising biobased chemicals [3]. It serves as a key precursor for high-value functional molecules, including valerate, furfuryl alcohol, furfural acetone (FAc), 5-methyltetrahydrofuran, 2-furancarboxylic acid, and other condensation derivatives, which are widely used in fuel additives, plastics, organic solvents, pharmaceuticals, and agrochemicals [4, 5]. The global demand for FUR has been steadily increasing, with production reaching approximately 700,000 t in 2022 and a market valuation of USD 556.7 million [6]. This trend is expected to persist, with an estimated annual growth rate of 7.0% from 2024 to 2030, reinforcing its strategic role in sustainable chemical manufacturing [7]. Focusing on FUR transformation via aldol condensation, this reaction pathway is crucial in producing aviation biofuels [8, 9]. However, traditional catalysts for these reactions pose environmental challenges, underscoring the need for new, industrially viable catalysts that minimize waste, reduce system corrosion, and enhance product selectivity [10].

Aldol condensation can be catalyzed by acid ($H_2SO_4$) and bases (NaOH, KOH, and Ca ($OH_2$)). Although homogeneous bases are widely employed on an industrial scale, the use of these catalysts presents significant environmental damage and technical challenges, such as difficulties with catalyst separation [6, 7]. Additionally, these catalysts can lead to unwanted side reactions, producing organic acids that neutralize the catalyst, thereby reducing its catalytic activity [11]. This degradation affects the reaction's efficiency and raises concerns about waste generation and the need for more sustainable alternatives.

As a result, there is growing interest in developing greener, more cost-effective catalytic systems for aldol condensation that minimize these drawbacks [12].

In recent years, metal-organic frameworks (MOFs) have attracted significant attention due to their distinctive structural and chemical properties, making them highly suitable for various applications [13–15]. Among these, the MIL-88 family of MOFs, composed of metal ions such as Fe (III) linked by dicarboxylate organic ligands, stands out for its versatility. This family includes various structures with different pore sizes, morphology, and functionalization tunability, making them adaptable to diverse catalytic systems [16]. A vital feature of some MOFs is the presence of coordinatively unsaturated sites (CUS) in the metal clusters, acting as Lewis acid sites, which are also crucial for biomass upgrading reactions. These local

structures are critical in the material's adsorption, transport, and reactivity [17, 18]. However, the inherent limitations of CUS, such as restricted specificity, confined coordination space, and blockage by ligands, can reduce their catalytic performance [19].

From this point of view, defect engineering has emerged as a powerful strategy, allowing researchers to enhance the functionality of MOFs beyond the capabilities of their native forms [20]. Recent studies have begun to explore structural disorder within the crystal lattice of MOFs, correlating defects with improved catalytic performance and gas absorption properties [20, 21]. Various methods have been proposed to introduce defects into MOFs, including the use of acid modulators during synthesis to create missing-linker structures in the MOFs [22], postsynthetic treatment with inorganic acids to generate missing-linker defects [23], fast precipitation techniques [24], and mixed-linker approaches that incorporate metal-ligand-fragment coassembly strategies [25]. However, many of these methods involve multiple steps or the addition of excess reagents, which can be counterproductive when considering sustainability goals [26].

To address these concerns, we propose an alternative approach inspired by mechanochemistry, which has successfully generated defects in MOFs through techniques like ball milling or mortar grinding [27, 28]. We hypothesize that incorporating stirring into the synthesis process could achieve similar defect formation by constantly agitating the reaction system and leading to faster crystallization. This method not only can facilitate the creation of defects but also eliminates the need for additional modulators, promoting a more sustainable and efficient synthesis process.

To the best of our knowledge, the aldol condensation of biomass-derived FUR and acetone has not yet been conducted using MOFs such as Fe-MIL-88B or Fe-MIL-88B-NH₂, which are composed of abundant, cheap, and nonnoble metals. By introducing stirring during the synthesis process, we propose an approach to defect engineering that customizes the structural and textural properties of Fe-MIL-88B. This method is expected to optimize surface area, control particle size, and enhance the accessibility of active sites, all while avoiding additional modulators to boost catalytic activity. We also optimized the reaction parameters for the aldol condensation using the design of experiments (DOE) and statistical analysis to validate this approach. A crucial factor was the effect of pretreatment time, which made evident the importance of a proper activation procedure for the catalysis. Afterward, our findings demonstrated that MOFs synthesized with the stirring method exhibit superior catalytic activity compared to conventional nonstirring methods. In addition, catalyst functionalization with the amino group (-NH₂) reduced the productivity toward the desired product. The most effective material, Fe-MIL-88B-s, achieved a FUR conversion of 99.4% with 99.9% selectivity for FAc. This catalyst also demonstrated stability over three consecutive cycles, with less than a 20% loss in activity. Importantly, this work highlights a one-pot synthesis approach to enhance defects in MOF-based materials, offering a compelling alternative to postsynthesis processes that often require multiple steps or the addition of acid and base modulators.
## 2 | Experimental Methodology

### 2.1 | Chemicals and Materials

All reagents and chemicals were used as purchased without further purification. 2-Aminoterephthalic acid (BDC-NH₂), terephthalic acid (BDC), FUR, FeCl₃·6H₂O, and N,N-dimethylformamide (DMF) were bought from Sigma-Aldrich. Isopropyl alcohol, ethanol, acetone, and hydrogen peroxide 30% were purchased from LabSynth Ltda.

### 2.2 | Synthesis of Fe-MIL-88B and Fe-MIL-88B-NH₂

The conventional solvothermal synthesis used for this work followed the procedure of Sun et al. with modifications [29]. For the synthesis of Fe-MIL-88B, 2.9 g (10.9 mmol) of FeCl₃·6H₂O and 0.9 g (5.5 mmol) of terephthalic acid were utilized in 15 mL of DMF. The solutions were homogenized, and the reagents were mixed while maintaining magnetic stirring for 15 min. The mixture was introduced into a stainless steel autoclave with a Teflon-lined reactor. The synthesis occurred in a sand bath at 130°C for 24 h without magnetic stirring. After this time, the system was allowed to rest at room temperature for 2 h. The resulting MOF was recovered by centrifugation (3000 rpm, 10 min) and washed three times with DMF and anhydrous ethanol (100 mL). The final product was dried in an oven at 80°C overnight and then kept at 150°C for 24 h. For Fe-MIL-88B-NH₂, the same procedure was followed, but the organic ligand was changed to 2-aminoterephthalic acid. These materials were labeled as Fe-MIL-88B-ns and Fe-MIL-88B-NH₂-ns.

An alternative synthesis approach for these MOFs induced defects without additional reagents. The previous procedure was employed, but magnetic stirring was utilized throughout the 24 h. Thus, the synthesis took place in a sand bath at 130°C for 24 h with magnetic stirring at 500 rpm. These materials were labeled as Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s.

### 2.3 | Characterization of Materials

The powder X-ray diffraction (XRD) measurements were carried out using a Bruker AXS-D8 Focus with CuKα (λ=1.54056 Å) radiation source, between 2θ range of 5–50° at the scan rate of 0.02° s min⁻¹. The Fourier transform infrared spectroscopy (FT-IR) was performed on a Varian Agilent 640 spectrophotometer with direct sample insertion into the ATR. The spectrum was measured between 4000 and 500 cm⁻¹ with a resolution of 16 scans. The nitrogen, carbon, and hydrogen content were measured using the elemental analyzer FlashEA 1112 from Thermo Scientific. The samples were degassed overnight before analysis and were made in duplicates. The oxygen content was calculated by comparing all the inorganic composition (Fe) plus the C, N, H, and Cl amounts. Textural properties characterization was acquired at N₂ physisorption at 77 K using the Quantachrome Nova 2200 Surface Area and Pore Size Analyzer. Samples were activated before analysis under vacuum at 150°C for 24 h. The surface area was obtained by the Brunauer–Emmett–Teller method (BET) in the P/P₀ range=0.05–0.30 or 0.005–0.015, total pore volume was calculated at P/P₀=0.97, and nonlocal

density functional theory (NLDFT) was used to calculate the pore size distribution [30, 31]. The micrographs of the materials were obtained in a scanning electron microscope—FEI Quanta 250. In contrast, the elemental mapping by Energy-dispersive X-ray spectroscopy (EDS) was obtained in a Compact SEM JEOL/EO. The inorganic composition of each material was obtained by flame atomic absorption spectrometry (FAAS). The solid samples were digested in a microwave oven (CEM Discovery) and then filtered with 0.45-µm PVDF syringe filters. The digested samples were diluted according to the calibration curves of Fe³⁺. The digestion method involves adding, in a 10-mL microwave bottle with a lid, 400 µL of H₂SO₄ in 1500 µL of ultrapure H₂O, the sample (2–3 mg), and 100 µL of 30% H₂O₂. The samples were subjected to microwave irradiation (100–150 W) at 150°C for 5 min until a clear solution was formed [31]. The thermogravimetric analyses were obtained in a TGA (SETSYS Evolution) in air atmosphere. For these analyses, 6–8 mg of each sample was weighed in an alumina crucible. The analysis parameters were the heating rate at 5°C min⁻¹ under a flow rate of 40 mL min⁻¹ of gas until a temperature of 700°C [31]. The X-ray photoelectron spectroscopy (XPS) analysis was made using K-Alpha equipment (Thermo Scientific). All spectra were calibrated using an advantageous C1s peak centered at 284.8-eV binding energy. The spectra were obtained with an Al Kα radiation source (1486.6 eV).

### 2.4 | Catalytic Tests of Aldol Condensation of FUR and Acetone

#### 2.4.1 | Preliminary Tests

Catalytic tests were conducted in 15-mL Ace tube glass reactors containing 50 mg of catalyst, 750 µL of acetone, and 83 µL of FUR (molar ratio A:F=10:1) at 130°C and 150°C under magnetic stirring (750 rpm) for 24 h [32]. The catalyst activation was carried out at 150°C for 20 h. After the reaction, the reactor was cooled to room temperature. The solution was filtered and diluted with acetone to prepare the samples for quantification. Vials were prepared by mixing 20 µL of the filtered sample and adding it to 1500 µL of acetone (Ratio 1:75—sample:solvent). The products and remaining reactants were identified and quantified via gas chromatography coupled to mass spectrometry (GC–MS) using a Shimadzu QP2010 Plus/Autosampler AOC-20s. The column used was a SupelcoWax 8 column (30 m×0.25 mm×0.25 µm). Operating parameters included inlet temperature 230°C and oven temperature ramp from 100 to 230°C at 10°C min⁻¹. All injections in the GC–MS were automatically taken considering 1 µL of volume of the diluted samples. The results reported are based on triplicate experiments. Furfural conversion (X~FUR~) and product selectivity (S~X~) were calculated using Equations 1 and 2 based on the peak areas detected in the chromatograms (A~X~). Here, A~FUR~ represents the area of the FUR peak in each chromatogram, while A~X~ denotes the area of each detected product peak. The denominator in these calculations corresponds to the total sum of all product peak areas observed in the chromatograms [33].

$$X_{\text{FUR}}(\%) = 100\% - A_{\text{FUR}}(\%) \qquad (1)$$

$$S_{X}(\%) = \frac{A_{X}}{A_{X} + A_{Y} + A_{Z} + \dots} 100\% \qquad (2)$$
<table><caption>**TABLE 1** | Matrix of 2³ experimental design with three central points to investigate the influence of independent variables on furfural conversion (dependent variable).</caption><thead><tr><th rowspan="2">Reactions</th><th colspan="3">Theoretical values</th><th colspan="3">Real values</th></tr><tr><th>Temp. (°C) X1</th><th>Stirring (rpm) X2</th><th>Molar ratio (A:F) X3</th><th>Temp. (°C) X1</th><th>Stirring (rpm) X2</th><th>Molar ratio (A:F) X3</th></tr></thead><tbody><tr><td>1</td><td>-1</td><td>-1</td><td>-1</td><td>90</td><td>250</td><td>5:1</td></tr><tr><td>2</td><td>1</td><td>-1</td><td>-1</td><td>150</td><td>250</td><td>5:1</td></tr><tr><td>3</td><td>-1</td><td>1</td><td>-1</td><td>90</td><td>1250</td><td>5:1</td></tr><tr><td>4</td><td>1</td><td>1</td><td>-1</td><td>150</td><td>1250</td><td>5:1</td></tr><tr><td>5</td><td>-1</td><td>-1</td><td>1</td><td>90</td><td>250</td><td>15:1</td></tr><tr><td>6</td><td>1</td><td>-1</td><td>1</td><td>150</td><td>250</td><td>15:1</td></tr><tr><td>7</td><td>-1</td><td>1</td><td>1</td><td>90</td><td>1250</td><td>15:1</td></tr><tr><td>8</td><td>1</td><td>1</td><td>1</td><td>150</td><td>1250</td><td>15:1</td></tr><tr><td>9</td><td>0</td><td>0</td><td>0</td><td>120</td><td>750</td><td>10:1</td></tr><tr><td>10</td><td>0</td><td>0</td><td>0</td><td>120</td><td>750</td><td>10:1</td></tr><tr><td>11</td><td>0</td><td>0</td><td>0</td><td>120</td><td>750</td><td>10:1</td></tr></tbody></table>

### 2.4.2 | Statistical Planning for Evaluation of Reaction Parameters

A factorial experimental design 2³ (two levels, three factors) was conducted with varying temperatures, stirring speed, and molar ratio of acetone:furfural (A:F) to investigate the influence of independent variables on furfural conversion (dependent variable). The tested temperature levels were 90°C–150°C, with 250–1250-rpm stirring, and molar ratio A:F = 5:1–15:1 (Table 1). Additionally, three central points were included for each factor along with these levels, totaling 11 reactions. The factorial design is intended to analyze these effects by considering all combinations of temperature (°C), stirring (rpm), and molar ratio of acetone:furfural (A:F) levels. The added central points assess the curvature of the response, helping to identify possible nonlinearities and allowing for the determination of the experimental error of the design. The experimental data were analyzed using Protimiza Experimental Design software (Protimiza Experimental Design, Campinas, Brazil—https://experimental-design.protimiza.com.br/).

### 2.4.3 | Pretreatment Effect

The catalyst pretreatment was evaluated by adjusting the activation time from 20 to 36 h at 150°C. Reactions were conducted using 50 mg of catalyst, with a molar ratio A:F of 15:1, at 150°C for 24 h under stirring at 250 rpm. To better understand the surface groups and/or chemical species evolution during the pretreatment, in situ FT-IR analysis at 150°C was performed using an ATR cell with a Nicolet iS50 spectrometer equipped with a Golden Gate heating controller. Spectra were recorded every 15 min over a 36-h period, with each spectrum comprising 128 scans at a resolution of 4 cm⁻¹ within the spectral range of 4000–650 cm⁻¹. The OMNIC software was used for data visualization and spectral processing [34]. Other pretreatment temperatures

were not considered based on standard synthesis protocols and stability considerations, as higher temperatures could alter pore structure or induce material degradation [35, 36].

### 2.4.4 | Time-Dependent Activity, Synthetic Method Comparison, and Catalyst Recyclability

The conversion and selectivity for target products were assessed by varying reaction times, ranging from 5 min to 24 h, for Fe-MIL-88B-s. After the time optimization, each MOF synthesized in this study was tested under these reaction conditions. Catalyst recyclability was evaluated: after an initial 36 h activation at 150°C, the catalyst underwent three sequential reaction cycles. Following each cycle, the catalyst was washed with 2 mL of acetone, filtered, and dried at 80°C, before reintroducing the reactants for the subsequent cycle. All catalytic reactions were conducted with 50 mg of catalyst, 750 µL of acetone, and 83 µL of FUR (molar ratio A:F = 15:1) at 150°C, stirring at 250 rpm until 24 h.

## 3 | Results and Discussion

### 3.1 | MOF Synthesis and Characterization

The approach of the synthetic routes discussed in this work is illustrated in Figure 1a, which compares the traditional solvothermal method to the defect-induced pathway. As is well known in MOF-related studies, solvothermal synthesis occurs in an oven to grow crystalline materials without external disturbances. Modulators can also be added to the synthetic solution to accelerate or slow the crystals' growth rate and introduce defects into the MOF structure [37]. However, to avoid using bases and acids, typically employed for this purpose [38], we investigated the addition of the stirring parameter as a mechanical method
<figure><img src="image_3.png" /><figcaption>**FIGURE 1** | (a) Scheme of the synthesis procedure comparing both methods used. (b) XRD (c) FT-IR spectra and (d) SEM of the synthesized materials.</figcaption></figure>

during the synthesis to produce defective MOFs and enhance their catalytic properties.

The XRD pattern (Figure 1b) of the synthesized Fe-MIL-88B-ns and Fe-MIL-88B-NH₂-ns was compared to the existing literature, confirming the achievement of a similar crystallographic pattern and validating the presence of the major crystalline peaks, which were marked with black symbols [39]. For instance, the primary diffraction peaks associated with the Fe-MIL-88B-ns crystal planes are identified at a lower angle region (5–18°) at $2\theta = 9.38°, 9.54°, 12.48°, 13.71°, 15.80°, 16.13°, and 16.53°. Meanwhile, the Fe-MIL-88B-NH₂-ns exhibited the main diffraction peaks at $2\theta = 9.06°, 10.10°, 11.12°, 13.63°, 17.01°, 17.71°, and 18.20°. When comparing the synthesis methods, it can be affirmed that stirring does not significantly affect the MIL-88B crystalline pattern and does not lead to amorphization [40]. However, Fe-MIL-88B-ns and Fe-MIL-88B-NH₂-ns show small shifts and intensity changes in the crystallographic peaks. These changes likely arise from losing organic linkers or metal nodes, which subtly alter atomic distances and symmetry within the crystal lattice. This implies that stirring induces the

formation of defects, resulting in more pronounced structural distortions in the MOFs [41].

Figure 1c displays the FT-IR spectra of the materials. The differences in the synthesis processes did not lead to significant changes in the infrared spectra, indicating that both methods yield similar superficial groups of the MOFs. Additionally, the Fe-MIL-88B and Fe-MIL-88B-NH₂ differ easily due to variations in the organic linker. For instance, the Fe-MIL-88B-NH₂ exhibits low-intensity bands at 3478 and 3365 cm⁻¹, attributed to the stretching of the N-H bond, and a high-intensity band at 1253 cm⁻¹ related to the C-N bond, characteristic of the -NH₂ group in 2-aminoterephthalic acid, while Fe-MIL-88B lacks these features. Furthermore, the remaining spectra of the MOFs display similar band patterns with minor shifts. The spectra exhibit a νC=O stretch between 1661–1651 cm⁻¹, corresponding to the carboxylate group of the ligands. Bands at 1560–1550 cm⁻¹, 1383–1373 cm⁻¹, and 1025–1000 cm⁻¹ are associated with the stretching of the carboxylate group (COO-), and a vibrational bending of coordinated COO- is observed at 825–800 cm⁻¹ [42]. The δC-H bend vibrations of the linker's aromatic ring appear
<figure><img src="image_4.png" /><figcaption>**FIGURE 2** | (a,b) Thermogravimetric curves under air atmosphere, (c) $N_2$ adsorption–desorption isotherms, and (d) pore size distribution obtained through the nonlocal density functional theory (NLDFT) of the synthesized materials.</figcaption></figure>

in the range of 760–745 cm⁻¹, and the stretching of the M–O bond (where M is Fe), related to the oxoclusters, is noted at 530–523 cm⁻¹.

According to Figure 1d, both Fe-MIL-88B-ns and Fe-MIL-88B-NH₂-ns display crystals with spindle and rodlike shapes, respectively, resembling the morphology and crystal size seen in other MIL-88B structures reported in the literature, confirming successful reproducibility [18, 29]. However, the crystals of Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s show some irregular lattices and small aggregates around each crystal, indicating the occurrence of multiple nucleations from a single point or the interpenetration of the crystalline structures [43]. This observation is consistent with the finding that, in a solvothermal synthesis with stirring, the reagents are in constant contact at high speed, lacking sufficient inertia for generating crystals with perfectly matched planes and well-defined morphology, in contrast to the agitation-free synthesis where the MOF can nucleate and grow more slowly [44]. Such results support the XRD differences seen previously. They offer a more straightforward method to induce defects without adding more reagents and postsynthetic treatments to the materials, enhancing catalyst synthesis's cost–time efficiency. Regarding morphological homogeneity, SEM analysis (Figure S1a) shows that the MOFs synthesized with stirring present more uniform crystal morphologies than those produced without agitation. The stirring process likely improves the uniformity of the synthesis environment, resulting in crystals with similar characteristics that do not cling to each other as much during growth.

In contrast, syntheses without stirring lead to more pronounced agglomeration, producing crystals of varying sizes, as indicated by the particle size distribution (Figure S1b). This highlights the role of stirring as a modulator in the synthesis process, leading to a more homogeneous material. Notably, the synthesis with stirring achieved higher yields of 49.6% and 46.0% for Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s, compared to 41.9% and 39.5% for Fe-MIL-88B-ns and Fe-MIL-88B-NH₂-ns. However, SEM-EDS analysis (Figure S2) confirms that the distribution of organic and metal components remains consistent across the particles, regardless of stirring conditions.

In terms of the thermogravimetric analysis under air atmosphere (Figure 2a,b), three weight loss regions can be noted: the volatilization of humidity and trapped solvent molecules up to 225°C (Region I), the detachment of the coordinated and residual organic linkers between 225°C and 420°C (Region II), and the collapse of the framework beyond 425°C due to complete linker decomposition and transformation of Fe-MOF into iron oxides (Region III) [45]. All materials are considered stable until 225°C (Region I), showing up between 10%–20% of weight loss. However, both defective MIL-88B variants exhibit lower thermal stability than those MIL-88B produced via the conventional method, as indicated by the higher mass loss in Region II. For example, the Fe-MIL-88B-ns and Fe-MIL-88B-s have an organic linker mass loss equivalent to 53.8% and 58.0%, respectively, exposing that the stirred MOF has an additional 4.2% weight loss equivalent to the presence of terephthalic acid in the structure. The same happens for the Fe-MIL-88B-NH₂-s, which has an additional 5.4% weight loss equivalent to the
2-aminoterephthalic acid. These results indicate that the stirring parameter promoted the formation of defects and favored more uncoordinated organic linkers in the MOF structure. Besides, the decomposition curve with an irregular decay pattern in **Region II** is another indicative of the presence of defects due to nonperfect coordination with the organic linker to the metallic cluster, having a different stability behavior [27, 46]. This can be clearly seen by comparing the stirred MOFs against the conventional nonstirred MOFs. In **Region III**, all materials presented a metal oxide residue between 26% and 36%, being consistent with the literature [47].

MOFs are typically reported to have a high surface area obtained from N₂ adsorption-desorption experiments [45]; however, this is not the case for the MIL-88B family. Simulations suggest that the 3D structure of the Fe-MIL-88B at its maximum expansion (open form) should display a high surface area of 3040 m² g⁻¹ [48]. However, the structural flexibility due to temperature sensitivity and residual adsorbent solvent within the framework can diminish the affinity for N₂ adsorption. As a result, after the analysis degassing step, the framework structure changes (closed form), reducing pore accessibility, which leads to a measured low specific surface area, as reported in existing literature [49–51]. These phenomena reinforce the results presented in Table 2, which shows surface areas below 300 m²/g for all MOFs. It is crucial to emphasize that both stirred MOFs exhibited higher surface area and pore volume than the conventional variants, suggesting that defect sites may have formed in the structure of both Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s.

N₂ adsorption-desorption isotherms and pore size distribution (Figure 2c,d) were used to investigate the textural properties of

various MIL-88B samples. The N₂ isotherms for all samples displayed a Type IV pattern defined by IUPAC [52]. Regarding the pore distribution, both Fe-MIL-88B samples showed a similar profile, predominantly consisting of smaller pores (<3 nm). Meanwhile, Fe-MIL-88B-NH₂ demonstrated a more diverse distribution, with pores ranging from 4 to 20 nm and those below 3 nm. This finding indicates that, despite differing synthesis methodologies, the material structure remains consistent, with the organic ligand significantly impacting the pore size distribution profile. Notably, the stirred samples exhibited a broader range of pore sizes than the nonstirred samples, suggesting that agitation may facilitate the formation of diverse cages within the framework structure.

The composition of the synthesized MIL-88B is shown in Table 3, and the results are obtained through FAAS, elemental analysis (CNH), and XPS. By comparing each synthesis method, it can be noted that stirring resulted in MOFs with lower Fe content. For example, 19.0% (ns)×14.7% (s) and 14.5% (ns)×13.2% (s) for Fe-MIL-88B and Fe-MIL-88B-NH₂, respectively. This phenomenon likely occurs due to a more irregular nucleation process, leading to structural defects such as lower iron clusters [50]. It is possible to observe 4%–5% of Cl in all MOFs, which originates from the metal precursor used and was not completely removed during the washing step in the synthesis. Regarding the organic composition, the stirred samples exhibited a slightly higher percentage of C, N, and O than the nonstirred ones. The increase in O content may indicate the presence of more free-carboxylate groups or dangling linkers in the stirred MOFs, supporting the defective strategy [46]. Additionally, Fe-MIL-88B-NH₂ demonstrates a higher N% (~8%) content because of the -NH₂ group in the organic linker, while Fe-MIL-88B has a lower N% content (~3%) due to trapped solvent molecules (DMF) within the pores.

The XPS was used to investigate the defects between synthesis methods, and the results collected are as follows. The XPS survey (Figure S3a) revealed that all materials displayed similar peaks for Fe, O, N, and C, indicating successful synthesis and coordination of the MOF. It is important to note that a small Cl₂p peak was present in each material due to the Cl⁻ in the metal precursor that was not completely removed during washing procedures. A small peak related to the N1s in the Fe-MIL-88B, indicating the presence of trapped DMF in the pores, was also noted and corroborated the N content in the elemental analysis. Regarding the high-resolution spectra, it can be seen in Figure S3b,c that all materials obtained similar deconvolution patterns for C1s, in which the peaks near

<table><caption>TABLE 2 | Textural analysis of the MIL-88B synthesized materials.</caption><thead><tr><th rowspan="2">Parameter</th><th colspan="4">Sample</th></tr><tr><th>Fe-MIL-88B-ns</th><th>Fe-MIL-88B-s</th><th>Fe-MIL-88B-NH<sub>2</sub>-ns</th><th>Fe-MIL-88B-NH<sub>2</sub>-s</th></tr></thead><tbody><tr><td>S<sub>BET</sub> (m<sup>2</sup>g<sup>-1</sup>)</td><td>16.1</td><td>272.7</td><td>8.5</td><td>15.9</td></tr><tr><td>P<sub>v</sub> (cm<sup>3</sup>g<sup>-1</sup>)</td><td>0.014</td><td>0.246</td><td>0.011</td><td>0.054</td></tr></tbody></table>

Abbreviations: P_v, Pore volume; S_BET, Surface area obtained by BET.

<table><caption>TABLE 3 | Composition analysis of the MIL-88B synthesized materials.</caption><thead><tr><th rowspan="2">Technique</th><th rowspan="2">Element</th><th colspan="4">Percentage (%)</th></tr><tr><th>Fe-MIL-88B-ns</th><th>Fe-MIL-88B-s</th><th>Fe-MIL-88B-NH<sub>2</sub>-ns</th><th>Fe-MIL-88B-NH<sub>2</sub>-s</th></tr></thead><tbody><tr><td>CNH</td><td>C</td><td>38.9</td><td>40.0</td><td>40.4</td><td>42.1</td></tr><tr><td>CNH</td><td>H</td><td>3.5</td><td>3.7</td><td>3.5</td><td>3.7</td></tr><tr><td>CNH</td><td>N</td><td>3.2</td><td>3.3</td><td>7.5</td><td>8.0</td></tr><tr><td>FAAS</td><td>Fe</td><td>19.0</td><td>14.7</td><td>14.5</td><td>13.2</td></tr><tr><td>XPS</td><td>Cl</td><td>4.8</td><td>5.2</td><td>4.9</td><td>4.1</td></tr><tr><td>XPS/By diff.*</td><td>O</td><td>26.9/30.4</td><td>28.2/33.1</td><td>24.0/27.7</td><td>24.9/29.5</td></tr></tbody></table>

*By difference: O = 100%—(C% + H% + N% + Fe% + Cl%).
<figure><img src="image_5.png" /><figcaption>FIGURE 3 | (a,b) High-resolution XPS spectra of oxygen (O) and (c,d) iron (Fe) of the MIL-88B materials.</figcaption></figure>

284.8, 286.4, and 288.6 eV were attributed to the C-C, carboxylate (O=C-O), and C=O of the organic linker [53]. In Figure S3d, the N1s spectra can be deconvoluted into peaks related to the -NH₂ group and the C=N-C bonds at 399.0 eV and 400.3–400.7 eV due to the presence of the amino group in the 2-aminoterephthalic acid used as a linker [54].

Additionally, the O1s and Fe2p provided valuable insights into the synthesis methods and the presence of structural defects in the materials. In **Figure 3a,b**, the O1s spectra can be deconvoluted into three distinct peaks, which are attributed to oxygen atoms in the metal–oxygen–metal clusters (Fe-O-Fe), in the coordinated carboxylate group (Fe-O-C), and in the coordinated-free-carboxylate group (COOH) [55]. These peaks appear at energies of 529.7–529.9, 531.5–531.6, and 533.2–533.1 eV, respectively. Meanwhile, **Figure 3c,d** display the Fe2p spectra, which can be deconvoluted into 10 components assigned to the two satellite peaks, as well as the Fe 2p1/2 and Fe 2p3/2 peaks [56]. The deconvolution of these peaks illustrates the presence of Fe (III) and Fe (II) species and their binding energies, which are detailed in Table S1. The area under each component can be used to calculate the relative content of each contribution, providing insights into changes in the bonding environment among the materials. For example, all carboxylate groups should be fully bonded to metal nodes in a defect-free MOF. Therefore, the detection of uncoordinated carboxylate groups suggests a lack of metal nodes at specific positions, indicating the presence of structural defects. The proportion of these uncoordinated carboxylate groups can be a reliable measure of the defect density related to missing metal nodes in the MOF [55]. Missing oxygen atoms or linkers can leave iron less coordinated, causing some Fe (III) to reduce to Fe (II). An increase in Fe (II) suggests that

metal sites might be undercoordinated, indicating structural defects such as vacant metal nodes [57]. Therefore, tracking this ratio helps identify and understand defects in the material. **Table S2** illustrates the deconvolution contributions for the O1s and Fe2p spectra based on the various synthesis methods employed. In comparing the stirred synthesis with the conventional method, there is a significant increase in the free-carboxylate contribution, alongside a decrease in both the coordinated carboxylate group and the Fe-O-Fe contributions for both Fe-MIL-88B and Fe-MIL-88B-NH₂. This observation is consistent with the defect formation phenomenon caused by agitation during synthesis, further corroborated by the elemental analysis (Table 3), which shows a higher oxygen content in the stirred MOFs. The Fe distribution analysis also indicates a shift in the oxidation states, with the proportion of Fe (III) decreasing. At the same time, Fe (II) increases when the materials are synthesized under stirring conditions, suggesting the formation of undercoordinated Fe active sites or metal vacancies [58]. For instance, the Fe (III) content in Fe-MIL-88B drops from 74.9% to 69.8%, while Fe (II) rises from 25.1% to 30.2%. Additionally, a similar trend is observed for Fe-MIL-88B-NH₂.

## 3.2 | Catalytic Tests of Aldol Condensation of FUR and Acetone

### 3.2.1 | Preliminary Tests

The reaction route for the aldol condensation of FUR with acetone is presented in Scheme 1. The reaction mechanism for aldol condensation can depend on the catalyst nature, whether it is acidic, basic, or bifunctional; however, it mainly
<figure><img src="image_6.png" /><figcaption>**SCHEME 1** | Aldol condensation of FUR with acetone to produce biofuel precursors. **(Pathway I)** Reaction direction of biofuel precursors. **(Pathway II)** Competitive reaction by Cannizzaro mechanism. **(Pathway III)** Side reaction of condensation of acetone. The colored molecules were the main FUR-derived products obtained in this study.</figcaption></figure>

involves three reaction steps. In the first step, deprotonation occurs from the α-H ketones, forming enolate species. Then, the enolate reacts with the adjacent carbonyl carbon from FUR by a nucleophilic addition, and as a product, an aldol adduct is formed (a C-C bond formation). Then, the O atom from the formed adduct abstracts a proton back-transferred from the catalyst surface [59]. After that, a hydrated FUR-acetone intermediate (FAc-OH) is formed and subsequently undergoes dehydration to yield FAc, signed in the scheme as **Pathway I** [60]. However, alternative reactions may also occur with these reactants, leading to other value-added by-products. The competing route, the Cannizzaro reaction (**Pathway II**), can lead to the formation of furoic acid, which promptly undergoes an esterification reaction with an isopropanol molecule, thus forming the compound isopropyl furan-2-carboxylate (IPFC) [61]. The isopropanol molecule might be formed through an Oppenauer oxidation reaction of acetone in the presence of a Lewis acid site [62]. Additionally, acetone may undergo self-condensation (**Pathway III**) to form 4-hydroxy-4-methylpentan-2-one (DAA) and then suffer a dehydration reaction to 4-methylpent-3-en-2-one (DAE). In this context, it is found in the literature that catalysts with a significant Lewis nature (as metallic clusters in MOFs) can efficiently catalyze the aldol condensation reaction of FUR to FAc with high selectivity [11, 63, 64].

This study's novelty is based on the structure-induced defects in the Fe-MIL-88B and Fe-MIL-88B-NH₂ caused by the stirring parameter during their synthesis. Under common reaction conditions, an initial screening of the FUR conversion to the desired product FAc was performed. Afterward, an optimization study will be performed, and the results will be compared with those of the nonstirred materials.

Then, preliminary tests were conducted, and the results are summarized in Table 4. For the reaction performed at 130°C, both Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s exhibited low FUR conversion (approximately 15%). The functionalized MOF demonstrated an increase of about 5% in selectivity toward FAc. Interestingly, at 150°C, catalytic data indicated a significant enhancement in FUR conversion (up to 55%) and FAc selectivity (increasing by 15%–20%). The nonfunctionalized MOF exhibited a slightly higher selectivity (~9%) for the desired product at this temperature. This observation suggests that the FAc formation

<table><caption>**TABLE 4** | Screening of the catalytic activity of the defective MOFs with different temperatures.</caption><thead><tr><th>Sample</th><th>Temp. (°C)</th><th>Conv. (%)</th><th>S<sub>FAc</sub> (%)</th><th>S<sub>IPFC</sub> (%)</th><th>S<sub>FAc-OH</sub> (%)</th></tr></thead><tbody><tr><td>Fe-MIL-88B-s</td><td>130</td><td>16.8</td><td>23.5</td><td>75.1</td><td>1.3</td></tr><tr><td>Fe-MIL-88B-NH<sub>2</sub>-s</td><td>130</td><td>15.2</td><td>28.1</td><td>67.2</td><td>4.7</td></tr><tr><td>Fe-MIL-88B-s</td><td>150</td><td>70.6</td><td>43.5</td><td>56.5</td><td>—</td></tr><tr><td>Fe-MIL-88B-NH<sub>2</sub>-s</td><td>150</td><td>70.4</td><td>34.8</td><td>56.3</td><td>8.9</td></tr></tbody></table>

(Scheme 1—**pathway II**) is highly influenced by temperature and competes with IPFC production (Scheme 1—**pathway II**). However, IPFC emerged as the primary product in all instances, with selectivity nearing or exceeding 55%. This suggests the presence of competitive reactions, mainly via the Cannizzaro mechanism, which adversely affected selectivity toward FAc. The catalytic mechanism of the reaction can be assigned to the acidic properties of the Fe-MIL-88B materials. The Fe³⁺ ions within the metal clusters contribute significant Lewis acidity, facilitating interactions with electron-rich species and promoting catalytic activity [65].

Additionally, the carboxyl groups of the organic linkers provide Brønsted acid sites, enhancing the material's overall acidity. In the amino-functionalized MOFs, both Lewis and Brønsted acid sites are present alongside basic sites, which collectively influence the selectivity of the aldol condensation pathways. As other studies have shown, introducing -NH₂ groups reduces the overall acidity and creates a distinct reaction environment for selective FUR conversion [66, 67].

While varying the temperature alone achieved a notable increase in conversion, further analysis of reaction parameters through statistical methods can enhance FAc selectivity and FUR conversion.
Note: Reaction conditions: 50 mg of catalyst, molar ratio A:F = 10:1, 750 rpm, 130°C-150°C, and 24 h.

### 3.2.2 | Statistical Planning for Evaluation of Reaction Parameters

A DOE was conducted to determine the optimal conditions for the aldol condensation of FUR and acetone. The study of the influence of temperature, stirring, and molar ratio A:F (independent variables) on the conversion of FUR (dependent variable) was performed using a factorial experimental design of 2³ with three central points, which was explicitly structured to simultaneously evaluate the effects of the independent variables and their interactions on the dependent variable (FUR conversion). Thus, FUR conversion was evaluated using Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s as catalysts, and the results are summarized in Table 5. The optimal conditions for both MOFs were identified at 150°C, 250 rpm, and a molar ratio A:F of 15:1 (Entry 6), yielding high FUR conversions of 97.7% for Fe-MIL-88B-s and 95.7% for Fe-MIL-88B-NH₂-s. These findings indicate that both catalysts demonstrate significant activity in FUR conversion under optimized conditions, achieving comparable levels of efficiency.

Based on Table 5, which presents the tested levels and obtained responses for FUR conversion, a statistical analysis was conducted to assess the effects of the temperature, stirring speed, and molar ratio A:F. The analysis results are summarized in Tables S3-S5, regression coefficients of these independent variables, including their interactions, for both MOF catalysts. For Fe-MIL-88B-s, the significant variables influencing FUR conversion ($p \le 0.05$) were temperature (X1) and the molar ratio A:F (X3), with a positive regression coefficient of 16.74 and 6.54, respectively. This suggests that increasing the temperature from 90°C to 150°C and the molar ratio A:F from 5:1 to 15:1 enhances FUR conversion [68]. In contrast, stirring speed (X2) was not statistically significant to FUR conversion. Meanwhile, for Fe-MIL-88B-NH₂-s, X1, X2, and X3 were significant, with

regression coefficients of 8.44, -3.96, and 17.04, respectively. This indicates that raising the temperature and increasing the molar ratio A:F from 5:1 to 15:1 substantially improves FUR conversion, as more acetone molecules can react with FUR [69]. On the other hand, an increase in the stirring speed reduces the FUR conversion, possibly due to diffusional problems in the FUR molecules achieving the active sites due to excessive agitation [70]. Besides, the independent variables, when interacting with others, showed a significant effect on FUR conversion (dependent variable) only in the interaction between temperature (X1) and molar ratio A:F (X3), with this interaction being significant and positive (X1:X3). This demonstrates that the combination of the higher temperature (150°C) and a higher molar ratio (1:15) contributes to an increase of 4.99 times the FUR conversion. As illustrated in the Pareto chart (Figure 4), temperature (X1) and molar ratio A:F (X3) are the significant variables for Fe-MIL-88B. In contrast, for Fe-MIL-88B-NH₂, temperature (X1), stirring speed (X2), molar ratios A:F (X3), and the interaction between X1:X3 are shown to enhance the FUR conversion significantly.

The FUR conversion models for both MOFs were validated through analysis of variance (ANOVA), as detailed in Tables S4-S6, and by employing F-distribution with two F-tests (Equations S1-S2). The validation criteria required that (I) the calculated F1 value exceeded the tabulated F1 value ($F1_{TAB(6,4)} = 6.16$ at a 95% confidence level) and the p-value was significant ($\le 0.05$), confirming a significant difference between experiments conducted under varied conditions; and (II) the calculated F2 value was smaller than the tabulated F2 value ($F2_{TAB(2,2)} = 19.00$ at a 95% confidence level), with a nonsignificant p-value ($> 0.05$), indicating consistency among the three central points tested under identical conditions. Consequently, the equations for the models describing the response of FUR conversion could be generated, as shown in Figure 5 and Equations S3-S4. These graphs compare experimental data with model-predicted FUR conversion results for each catalyst, revealing a close alignment of data points with the proposed linear models and indicating substantial model accuracy.

<table><caption>TABLE 5 | Results for the 2³ factorial experimental design by adding three central points for the stirred MOFs.</caption><thead><tr><th rowspan="2">Reaction</th><th rowspan="2">Temp. (°C)</th><th rowspan="2">Stirring (rpm)</th><th rowspan="2">Molar ratio A:F</th><th colspan="2">Conversion (%)</th></tr><tr><th>Fe-MIL-88B-s</th><th>Fe-MIL-88B-NH<sub>2</sub>-s</th></tr></thead><tbody><tr><td>1</td><td>90</td><td>250</td><td>5:1</td><td>44.4</td><td>38.5</td></tr><tr><td>2</td><td>150</td><td>250</td><td>5:1</td><td>93.9</td><td>51.1</td></tr><tr><td>3</td><td>90</td><td>1250</td><td>5:1</td><td>46.7</td><td>40.0</td></tr><tr><td>4</td><td>150</td><td>1250</td><td>5:1</td><td>62.6</td><td>41.2</td></tr><tr><td>5</td><td>90</td><td>250</td><td>15:1</td><td>55.8</td><td>69.5</td></tr><tr><td>6</td><td>150</td><td>250</td><td>15:1</td><td>97.7</td><td>95.7</td></tr><tr><td>7</td><td>90</td><td>1250</td><td>15:1</td><td>59.9</td><td>57.2</td></tr><tr><td>8</td><td>150</td><td>1250</td><td>15:1</td><td>86.5</td><td>84.7</td></tr><tr><td>9</td><td>120</td><td>750</td><td>10:1</td><td>77.5</td><td>64.7</td></tr><tr><td>10</td><td>120</td><td>750</td><td>10:1</td><td>76.8</td><td>59.8</td></tr><tr><td>11</td><td>120</td><td>750</td><td>10:1</td><td>73.2</td><td>62.1</td></tr></tbody></table>
<figure><img src="image_7.png" /><figcaption>**FIGURE 4** | Pareto diagram of the magnitudes of the standard effects for furfural conversion (a) for Fe-MIL-88B-s and (b) for Fe-MIL-88B-NH₂-s. X1: temperature (°C); X2: stirring (rpm) and X3: molar ratio A:F. The star symbol highlights the significant variables of the process.</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>**FIGURE 5** | Graph of the experimentally obtained results versus the results obtained by the proposed model for the furfural conversion (%), using (a) Fe-MIL-88B-s and (b) Fe-MIL-88B-NH₂-s as catalysts. Experimental results are represented by the points (●), and the results obtained from the linear statistical model are represented by the line (—). The closer the points are to the line, the closer the experimental results are to the results obtained through the model. Y1 = furfural conversion, X1 = temperature (°C); X2 = stirring (rpm); and X3 = molar ratio A:F.</figcaption></figure>

Response surface plots (Figure 6) were generated using the model equations to illustrate the effects of the studied variables on FUR conversion. In these plots, the green-shaded regions indicate conditions where higher temperatures and molar ratios A:F correspond with lower stirring speed, resulting in an increased FUR conversion. These results suggest that the optimal conditions for maximizing conversion were achieved at 150°C, 250 rpm, and a molar ratio A:F of 15:1, as highlighted in Table 5. These conditions were subsequently applied in further catalytic assays.

### 3.2.3 | Pretreatment Effect

Following the optimization of aldol condensation parameters, Fe-MIL-88B-s achieved a high FUR conversion of 97.7% but with limited selectivity toward FAc (44.6%). To further enhance catalytic performance, we investigated the pretreatment time of these catalysts based on recent studies suggesting that the material activation protocol and adsorbed water critically influence catalytic activity [71]. We extended the pretreatment duration for Fe-MIL-88B-s from 20 to 36 h at 150°C. As shown in Figure 7a, this adjustment led to a slight increase in FUR conversion from 97.7% to 99.4%, but more importantly, it significantly enhanced selectivity toward FAc production, rising from 44.6% to 99.9%. The study by Oleg Kikhtyanin et al. demonstrated that the competition between the Cannizzaro reaction and aldol condensation is strongly influenced by the water content in FUR mixtures, affecting both

furfuryl alcohol selectivity and FUR conversion [62]. Our findings suggest that pretreatment is crucial in directing the reaction pathway. The excess of adsorbed or coordinated water at the Fe-MIL-88B active sites could create an environment that favors undesired side reactions. By optimizing pretreatment conditions, it is possible to minimize water interference, shifting the reaction toward FAc formation and enhancing selectivity.

Figure 7b illustrates the evolution of specific infrared bands analyzed in the in situ ATR-FT-IR, indicating changes on the catalyst surface throughout the 36-h pretreatment period. Notably, the intensity of bands at 2924 cm⁻¹ (C-H stretching from adsorbed DMF or ethanol) and 812 cm⁻¹ (coordinated carboxylate groups) decreases over time, suggesting gradual desorption. Concurrently, the uncoordinated carboxylate bands at 1583 and 1018 cm⁻¹ increase, further confirming the desorption of attached molecules. Additionally, a prominent C-H bending band at 752 cm⁻¹, associated with the benzene ring of the organic linker, emerges over time, indicating increased availability of linker groups serving as potential active sites. It is important to note that this in situ analysis was conducted with approximately 1–2 mg of catalyst directly heated. Thus, diffusion dynamics may differ from the larger catalyst mass (~750 mg) used in standard activation procedures. Figure 7c,d summarize the infrared spectral evolution of the analyzed bands during pretreatment at 150°C, supporting our findings on the activation time effect.
<figure><img src="image_9.png" /><figcaption>**FIGURE 6** | Response surfaces for FUR conversion for the different parameters using Fe-MIL-88B and Fe-MIL-88B-NH₂-s catalysts. (a) Molar ratio A:F vs. temperature, (b) Stirring vs. temperature, and (c) Molar ratio A:F vs. stirring.</figcaption></figure>

Figure 7e illustrates the Fe-MIL-88B trimeric cluster under various conditions, highlighting the impact of pretreatment on its structure. In the theoretical model, the MOF has three coordinated H₂O molecules [72]. However, water does not fully occupy this coordination in the as-synthesized state or in the partial activation scenario. During the washing process, which involves sequential immersion in DMF and ethanol, the MOF may retain the used solvent molecules or residual counterions from the metal precursor (e.g., Cl⁻). A drying and activation step is required to standardize the coordination environment and expose active sites. This process gradually removes loosely bound solvent molecules within the pores and coordinated molecules, forming uncoordinated metal sites (UMS)—active centers that can enhance catalytic performance [41]. However, careful control of activation conditions is essential, as high temperatures or rapid solvent removal can lead to structural collapse by disrupting residual guest molecules and coordinated species [31]. Additionally, in defect-rich structures, such as those with missing clusters, the uncoordinated linker moieties introduce further active sites through free-carboxylate groups (COO⁻). These structural modifications correlate with the significant increase in FAc selectivity from 44.6% to 99.9% in the Fe-MIL-88B-s, likely attributed to an extended pretreatment period. Thus, after

the complete activation of the material, improved desorption of residual and coordinated molecules was achieved, enhancing the availability of UMS and pore accessibility. Consequently, this optimized pretreatment effectively suppresses secondary reactions, such as the Cannizzaro mechanism, while promoting FAc formation [19]. Besides, these findings align with similar studies, like Vermoortele et al., who noted the significance of pretreatment conditions in the cross-aldol condensation catalyzed by UiO-66-NH₂ [73]. Likewise, recent research by Goculdas et al. showed that high-temperature activation of HSA-UiO-66-NH₂-HCl at 200°C for 12h led to dehydration of zirconium clusters, which diminished catalytic performance [74]. Following this, the subsequent catalytic experiments were conducted using 150°C for 36h as a pretreatment.

### 3.2.4 | Time-Dependent Activity, Synthetic Method Comparison, Catalyst Recyclability, and Catalytic Efficiency Based on Literature

The reaction time evaluation aimed to optimize energy usage, maximize substrate conversion, and reduce by-product formation. Determining the time required for complete conversion
<figure><img src="image_10.png" /><figcaption>**FIGURE 7** | (a) Comparison of the catalytic activity of Fe-MIL-88B-s with different pretreatment duration. (b) Normalized quantification of evo- luted surface species during pretreatment at 150°C—36 h in the in situ ATR-FT-IR. (c,d) Evolution of spectra for Fe-MIL-88B-s bands obtained in ATR-FT-IR throughout pretreatment experiment at 150°C—36 h. (e) Representation of the Fe₃-µ₃-oxo cluster of Fe-MIL-88B in different conditions.</figcaption></figure>

allows for shorter reaction periods, minimizing humin for- mation and enhancing catalyst durability [66]. The results presented in Figure 8a show a continuous increase in conver- sion over time, achieving 99.0% after 8 h and reaching 99.4% after 24 h. Selectivity for FAc becomes evident after just 3 h,

reaching 87.1% at 8 h and stabilizing at 99.9% by 24 h. This pla- teau suggests that extending the reaction beyond 24 h offers no significant benefits in selectivity or conversion. Consequently, 24 h was selected as the optimal reaction time under these conditions.
<figure><img src="image_11.png" /><figcaption>**FIGURE 8** | (a) Evaluation of FUR conversion and FAc selectivity over different reaction times. (b) Comparison of furfural and acetone aldol condensation with all the MIL-88B materials synthesized in this work. (c) Reusability data for Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s in furfural and acetone aldol condensation. Reaction conditions: 50-mg catalyst, 150°C, 250 rpm, and molar ratio A:F of 15:1. (e) Comparison of furfural and acetone aldol condensation with different acid and acid-base catalysts in the literature.</figcaption></figure>

Afterward, we compared the activity between the defective-
engineered and the conventional MOFs (Figure 8b). Regarding
the synthetic method, it can be seen that the FUR conversion is
just slightly affected (~5%) for both MOFs, but the main point
is the difference in product selectivity. Fe-MIL-88B-s and Fe-
MIL-88B-NH₂-s demonstrated increases in FAc selectivity
of 27% and 15%, respectively, compared to their nonstirred
ones. This improvement is likely due to the higher density of
defects in the stirred MOFs, which provides more accessible
active sites [19], favoring the formation of biofuel precursors
over secondary products. The selectivity reduction of 11% ob-
served in Fe-MIL-88B-NH₂-s compared to Fe-MIL-88B-s, de-
spite the presence of an amino-functionalized ligand, suggests

a minimal effect of ligand functionalization on the activity and
selectivity. This aligns with findings from Goculdas et al., who
demonstrated that introducing amino groups (-NH₂) into MOFs
does not necessarily enhance catalytic performance. Their in-
vestigation of UiO-66, UiO-66-NH₂, and UiO-66-(NH₂)₂ in
aldol condensation reactions revealed that, despite significant
variations in surface area (1286, 1538, and 803 m² g⁻¹, respec-
tively), the catalytic trends remained largely consistent in order
to decrease FUR conversion. UiO-66-NH₂ exhibited only a
minor (< 5%) decrease in FUR conversion compared to UiO-
66, while its selectivity toward FAc decreased by 15%. Notably,
UiO-66-(NH₂)₂, which contains two amino groups per ligand
and fewer structural defects, exhibited a 20% reduction in FUR
conversion and marked suppression of long-chain oxygenate
formation [74]. Thus, the authors claimed that the amino-
functionalization may have a higher influence on the diffusion
properties of the catalyst, directly impacting the selectivity
and activity of the reaction. Similarly to our work, the pres-
ence of -NH₂ groups in Fe-MIL-88B-NH₂ does not enhance the
FUR conversion. Thus, beyond acidity-basicity effects, amino
functionalization may also hinder the diffusion of reactants
through the pores. This reinforces the notion that the role of
ligand-based acidity or basicity in selectivity modulation is less
pronounced than expected, while steric and diffusional effects
may play a more relevant role. Furthermore, although the di-
rect quantification of acid groups was not feasible in this study,
incorporating an amino group theoretically lowers the overall
acidity. However, the slight reduction in selectivity implies that
the metal center is more pivotal in driving the reaction than
ligand functionalization active sites [75]. A similar trend was
reported in the literature comparing the MOFs Cu-BTC and
Fe-BTC in the same reaction, where FUR conversions were
2.7% and 26.2%, respectively, despite both materials containing
2.3 and 2.5 mmol/g of Lewis acid sites [64].

A control experiment conducted under identical conditions but
without a catalyst yielded a FUR conversion of 12.5%, yet no
FAc formation was observed. Instead, this blank test produced
only IPFC and DEA, highlighting the critical role of the MOFs.

Catalyst stability is critical for maintaining efficiency and lon-
gevity in industrial catalytic processes, especially given furfu-
ral's tendency to undergo unwanted polymerization, forming
humins that deactivate catalysts [76]. Figure 8c displays FUR
conversion and FAc selectivity for Fe-MIL-88B-s and Fe-
MIL-88B-NH₂-s across three reaction cycles. Fe-MIL-88B-s
demonstrated stable FUR conversion (~92%) over the cycles
but experienced a slight decline in FAc selectivity (~16%). In
contrast, Fe-MIL-88B-NH₂-s showed more pronounced deac-
tivation, with progressive losses in both conversion and selec-
tivity, ending at X<sub>FUR</sub> = 56.8% and S<sub>FAc</sub> = 63.8%. These findings
indicate that the amino-functionalized MOF may have a higher
affinity for humin formation, making it less amenable to reacti-
vation under the recycling protocol applied in this study. To fully
restore the catalytic performance of Fe-MIL-88B-NH₂-s, addi-
tional acetone washing and a secondary activation step would
be suitable to achieve complete regeneration.

When evaluating the catalytic performance of Fe-MIL-88B
compared to other materials reported in the literature, our
study highlights its exceptional selectivity and activity, rein-
forcing the potential of MOFs in aldol condensation reactions.
While zeolite-based catalysts have been widely explored for
the aldol condensation of FUR and acetone, investigations in-
volving MOFs remain relatively scarce. Figure 8e and TableS7
present a comparative analysis of our materials alongside other

<figure><img src="image_12.png" /><figcaption>**FIGURE 9** | Proposed mechanism for aldol condensation reaction between furfural and acetone in Fe-MIL-88B materials. The color scheme of MOF is iron, orange; oxygen, red; carbon, gray. Source: Adapted from Malkar, R. et al. (2019) and Aljammal, N. et al. (2024).</figcaption></figure>
MOFs, homogeneous catalysts (metal salts), and zeolites. The results confirm the high potential of MOFs for this reaction and demonstrate how fine-tuning their structural properties can significantly influence catalytic performance. Notably, Fe-MIL-88B-s and Fe-MIL-88B-NH₂-s exhibit superior selectivity and stability compared to all MOF-based catalysts previously reported. For instance, UiO-66, one of the most widely studied MOFs [77], achieves high FUR conversion but suffers from low FAc selectivity and poor recyclability, losing catalytic activity over successive cycles. In contrast, Fe-MIL-88B-s maintain their performance across multiple reaction cycles, underscoring their structural stability. Compared to zeolites, renowned for their strong acidity and stability, our materials demonstrate superior catalytic performance. The graph shows that most zeolites, besides having a good selectivity, range from 30% to 80% of FUR conversion. Additionally, experiments with homogeneous metal precursors, such as iron (III) nitrate and copper (II) nitrate, result in low FUR conversion and selectivity toward FAc, highlighting the crucial role of the framework in catalytic activity [64]. These findings underscore the advantages of defect-engineered Fe-MIL-88B catalysts for aldol condensation, presenting them as a promising alternative to conventional acid catalysts. Combining high selectivity, tunable properties, and enhanced stability, these MOFs offer exciting prospects for biomass valorization and related transformations, with significant potential for further optimization through structural modulation.

### 3.2.5 | Insights Into Reaction Mechanism

The aldol condensation is known to be catalyzed by acidic, basic, or acid-base catalysts [60]. In the case of MOFs, the Fe₃-µ₃-oxoclusters in Fe-MIL-88B are well known for their Lewis acid sites [78], which play a crucial role in catalyzing aldol condensation reactions. Figure 9 presents a proposed mechanism, based on previous studies with other MOFs [79, 80], for the acid-catalyzed aldol condensation of FUR and acetone over Fe-MIL-88B. In **Step I**, the acid sites serve as active centers, interacting with the carbonyl oxygen atoms of both acetone and FUR. **Step II** involves the tautomerization of acetone to its enol form, which subsequently reacts with the electrophilic carbonyl carbon of FUR. This leads to the formation of the β-hydroxy intermediate (FAc-OH) in **Step III**, which has been identified as a reaction subproduct. In **Steps IV and V**, FAc-OH undergoes dehydration, forming the final product (FAc) with the release of a water molecule, while the catalyst is regenerated.

While the general reaction mechanism applies to Fe-MIL-88B synthesized via both conventional and stirred methods, its catalytic performance is significantly influenced by defect engineering. Structural modifications, such as missing linkers and metal clusters, introduce additional active sites that enhance the availability of reactive centers and improve reactant diffusion within the framework, which can potentially increase both the activity

<figure><img src="image_13.png" /><figcaption>**FIGURE 10** | Proposed mechanism for the aldol condensation reaction between furfural and acetone in defective MIL-88B materials. The structure highlights the potential defective sites that enhance catalytic activity. For clarity, the coordination sites of the MOF are represented by spheres (A), indicating the acid sites in the trimeric Fe cluster within the MOFs, with only one UMS displaying reacted molecules. The color scheme for the MOF is as follows: iron, orange; oxygen, red; carbon, gray.</figcaption></figure>
and selectivity of the reaction [19, 81]. Based on these considerations, we propose additional mechanistic pathways (Routes A, B, and C) enabled by defect engineering, as illustrated in Figure 10.

In the case of missing linker defects (Figure 10—**Routes A and B**), the absence of organic ligands in the Fe₃-µ₃-oxoclusters is compensated by coordinated H₂O or -OH groups positioned near the UMS [82, 83]. These species actively participate in the reaction by facilitating the tautomerization of acetone.

**Route A and B:** In **Steps Ia** and **Ib**, coordinated hydroxyl groups and water act as the active centers that facilitate the tautomerization of acetone, respectively. In **Steps IIa** and **IIb**, both routes form FAc-OH, similar to the general mechanism and then regenerate the reacted -OH and H₂O. In **Steps IIIa** and **IIIb**, the FAc-OH is desorbed as an intermediate product or goes under dehydration to be transformed into FAc.

For missing cluster defects (Figure 10—**Route C**), the additional active site is the defective organic ligand that is not coordinated to the Fe₃-µ₃-oxoclusters containing free COO⁻ groups. These groups can act as catalytic sites to facilitate enolate formation [81].

**Route C:** In **Step Ic**, the FUR and acetone carbonyl groups interact with the acidic sites. In **Step Iic**, the defect-free COO⁻ group abstracts a proton from acetone, forming the enolate. In **Steps IIic** and **IVc**, the enolate reacts with the carbonyl group of FUR to form FAc-OH and then regenerates the defective free COO⁻ group. Subsequently, the mechanism follows the standard pathway to produce FAc.

These alternative mechanistic pathways provide insights into how defective sites in MOFs contribute to enhanced FAc selectivity. However, further in situ or operando spectroscopic studies are necessary to confirm these mechanisms experimentally. It is also important to note that while some variations may arise in Fe-MIL-88B-NH₂, previous DFT studies on UiO-66 and UiO-66-NH₂ suggest that the fundamental catalytic sites remain similar [84].

## 4 | Conclusions

Our study establishes a sustainable method for defect engineering in Fe-MIL-88B-based MOFs by incorporating magnetic stirring during solvothermal synthesis. This innovation leads to substantial improvements in catalytic performance for the aldol condensation of FUR and acetone. Unlike traditional approaches that often require acid/base modulators or complex postsynthesis treatments, this method successfully introduces structural modifications—such as increased surface area, controlled particle size, and enhanced active site accessibility—simply through the controlled addition of stirring. Characterization techniques, including XPS, confirm these modifications, revealing a higher density of free-carboxylate groups and notable changes in the Fe (II)/Fe (III) ratio, indicative of defect formation. Catalytic testing under scores the advantages of this engineered structure, with Fe-MIL-88B-s demonstrating superior conversion (99.4%) and selectivity (99.9%) toward FAc, outperforming MOFs synthesized without stirring and other MOFs and zeolites reported in the literature.

Furthermore, this catalyst exhibits remarkable stability, retaining over 92.6% of its initial activity after three cycles. Mechanistic insights about the reaction and the defective enhanced catalytic activity are also proposed. Furthermore, this work represents the first application of MIL-88B MOFs in the aldol condensation of FUR and acetone, establishing a foundation for further exploration of defect-engineered, nonnoble metal MOFs in renewable chemical production. These findings confirm a simpler approach to MOF optimization for biomass compound transformations and emphasize the potential of defect-engineered MOFs in promoting efficient and sustainable catalysis.

## Author Contributions

**Gustavo Felix Bitencourt:** conceptualization, data curation, formal analysis, investigation, methodology, resources, validation, and writing (original draft, review and editing). **Sancler Vasconcelos:** conceptualization, data curation, formal analysis, investigation, methodology, resources, validation, and writing (original draft, review and editing). **Luana dos Santos Andrade:** data curation, formal analysis, investigation, methodology, resources, and writing. **Vinicius Rossa:** data curation, formal analysis, investigation, methodology, resources, validation, and writing. **Daniel Garcez Quattrociocchi:** investigation and methodology. **Wagner Alves Carvalho:** resources, supervision, and funding acquisition. **Mohamad El Roz:** resources, project administration, funding acquisition, and supervision. **Dalmo Mandelli:** resources, funding acquisition, and supervision. **Thiago de Melo Lima:** resources, supervision, writing (review and editing), and funding acquisition.

## Acknowledgments

The authors would like to thank the resources provided by the Universidade Federal do ABC (UFABC), Universidade Fluminense Federal (UFF), and École nationale supérieure d'ingénieurs de Caen (ENSICAEN). We appreciate the services of multiuser central facilities (CEM-UFABC) for the experimental support. We also thank LNNano/ CNPEM (Proposal 20242469) for the XPS analyses. The Article Processing Charge for the publication of this research was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) (ROR identifier: 00x0ma614).

## Conflicts of Interest

The authors declare no conflicts of interest.

## Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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## Supporting Information

Additional supporting information can be found online in the Supporting Information section.