1 Introduction
Due to the increasing demand for fossil resources and the growing concern over global warming， biomass resources are gradually being considered as an environmentally friendly alternative to fossil fuels
[1-2]. As a naturally renewable resource， biomass and its derived high-value platform compounds are becoming a key medium for reshaping the chemical industry. Among them， FDCA is an extremely attractive bio-based platform molecule， which has been listed as one of the top 12 most valuable bio-based platform molecules by the U.S. Department of Energy
[3-5]. Compared with traditional petroleum-based TPA， FDCA has similar dicarboxylic acid functional groups (
Fig.1)， which enable it to replace TPA for the synthesis of biodegradable polyethylene furanoate (PEF)
[6]. Compared with traditional polyethylene terephthalate (PET)， PEF exhibits significantly better gas barrier properties， higher mechanical strength， and thermal stability
[7-9]. More importantly， its unique biodegradability reduces long-term environmental pollution and dependence on traditional petrochemical products to a certain extent， thereby demonstrating significant economic and environmental advantages. In addition to the applications mentioned above， FDCA， as a versatile platform compound， can further be used to synthesize high-value downstream chemicals such as polyesters and polyamides through reactions like esterification， amination， hydrogenation， and polymerization
[10-12]， which fully demonstrates its broad application prospects in industrial fields.
In recent years， the global FDCA market has shown a trend of rapid growth. The market size reached \$620.82 million in 2024 and is projected to reach \$1228.18 million by 2032， with a compound annual growth rate of 8.90%
[13]. At the same time， the industrialization of FDCA has made key progress on a global scale. The Netherlands Avantium Company is the first to achieve an annual production capacity of 5000 tons of FDCA， marking the entry of FDCA into the large-scale industrialization phase
[14-16]. In addition， Japan， the United States and other countries are also advancing the development of different technological routes. Meanwhile， domestic companies such as GS Biomats and LEAF Biotech are also achieving significant progress in the research and industrialization of FDCA. However， although the production of FDCA shows a good development trend both domestically and internationally， its scaled-up production still faces numerous challenges and urgently requires technological breakthroughs and process optimization
[17-19]. Therefore， conducting systematic research on the industrial optimization and engineering scale-up of the FDCA synthesis route is crucial for overcoming the bottlenecks in large-scale production and enhancing the competitiveness of downstream products.
This paper systematically summarizes the various synthetic pathways of FDCA and conducts a comprehensive evaluation from multiple perspectives， including economy， process complexity， cost and current state of industrialization. The study finds that the oxidation route using HMF as the intermediate is regarded as the most promising synthetic route for industrialization due to its simple process， high product selectivity， and significant economic benefits. In addition， this paper systematically reviews the existing industrialization process and emerging technological routes for the oxidation of HMF to FDCA， and discusses their respective research progress and industrialization prospects. The thermocatalytic systems widely used in the industry currently occupy a dominant position in existing technologies due to their high process maturity and excellent reaction efficiency. Meanwhile， emerging routes such as electrocatalysis and biocatalysis， although showing potential for green and mild reactions， are still limited by insufficient catalyst stability and technological challenges of industrial scale-up， and their industrial application needs further breakthroughs. Based on LCA studies， the current production process of FDCA still has the problems of high energy consumption and large carbon emissions. Therefore， in the future， while actively expanding the downstream high-value-added applications of FDCA and improving the overall economic efficiency， it is also necessary to focus on developing new catalytic systems and promoting the integration of low-carbon energy sources such as green electricity and green hydrogen. Thereby， build a more efficient and energy-saving FDCA production process and help the entire industry chain achieve a green and low-carbon transformation.
2 Synthetic pathways and industrialization progress of FDCA
With the continuous development of the production process， the synthesis routes of FDCA are showing a trend of diversification. Currently， mainstream processes primarily utilize renewable biomass such as fructose， cellulose， pectin， and hemicellulose as feedstocks
[20-21]. Under specific catalytic conditions， these raw materials are first converted into key intermediates， which are then efficiently synthesized into FDCA. The current preparation routes of FDCA mainly include the HMF route， furoic acid route
[22]， hexaric acid route， and furfural route
[23]. These routes have their own characteristics in terms of catalyst systems， reaction conditions， and yields， reflecting the close integration of biomass conversion technology and green chemistry， and also providing several feasible solutions for the large-scale production of FDCA.
2.1 HMF route
In the reaction pathway for the oxidation of HMF to FDCA， fructose， with its five-membered ring structure similar to that of FDCA， does not need to undergo complex ring-closing or rearrangement steps during acid-catalyzed dehydration， thereby significantly simplifying the reaction process. Therefore， this structural advantage makes fructose the preferred feedstock in this system. In this pathway， fructose is first continuously dehydrated to form HMF under the influence of acid catalysis (
Fig.2a). Subsequently， HMF is gradually oxidized in the presence of a catalyst and oxygen， selectively converting the aldehyde (—CHO) and hydroxymethyl (—CH
2OH) groups in HMF to the carboxyl (—COOH) group， ultimately enabling the efficient production of FDCA. In addition， with its outstanding economic benefits and high yields achieved in large-scale production， this route has become the most industrially mature path in the current FDCA synthesis system. In this industrialization process， the Netherlands company Avantium takes the lead in large-scale industrialization production of FDCA based on Avantium’s YXY
® technology platform
[25-26]. The demonstration factory with an annual production capacity of 5000 tons of FDCA was successfully put into operation， which signifies a key advancement in its large-scale production and provides a stable supply of raw materials for the development of downstream high-value-added products. Another Netherlands company， AVA Biochem， focuses on the production of HMF using hydrothermal carbonization technology and couples it with oxidation processes to synthesize FDCA. With the stable operation of the company’s 10-ton pilot production line， a solid foundation has been established for future technology transfer and industrial-scale manufacturing. At the same time， China’s FDCA production capacity is at a critical stage of transitioning from pilot-scale to ten-thousand-ton production capacity. Among them， LEAF Biotech has successfully operated a pilot production line with a capacity of a thousand tons and is actively promoting the construction scheme for the world’s first 15000 tons per year FDCA production line. In addition， GS Biomats has not only achieved a stable supply of FDCA at the hundred-ton level but also launched the layout of a ten-thousand-ton level capacity， fully demonstrating China’s strong development momentum in this field.
2.2 Furoic acid route
The oxidation route with furoic acid as a key intermediate uses cellulose-rich biomass such as straw and corncobs as feedstock， and produces FDCA through a series of continuous reactions（
Fig.2b). Firstly， the cellulose in these feedstocks is converted to xylose through pretreatment and hydrolysis； subsequently， under acid catalysis， xylose undergoes dehydration and cyclization to form the important platform compound furfural； next， furfural is further converted into the key intermediate 2-furoic acid through selective oxidation； finally， 2-furoic acid undergoes a disproportionation reaction to generate the target product FDCA and by-product furan. This route involves a series of reactions， including hydrolysis， dehydration， and oxidation， and combines with the subsequent corresponding separation and purification steps， thereby constructing a complete process route from biomass to high-value chemicals. Compared to the furfural route， the —COOH in furoic acid can stabilize the furan ring， promoting the reaction to proceed more directly while effectively suppressing the occurrence of side reactions， thereby improving the purity and yield of FDCA. Moreover， furoic acid has a weaker poisoning effect on noble metal catalysts， which helps to extend catalyst life and enhance reaction stability. Based on the above significant advantages， research institutions represented by the Ningbo Institute of Materials Technology and Engineering of the Chinese Academy of Sciences are steadily advancing the industrialization of this technology. After successfully passing the pilot-scale testing and fully verifying the technical and economic feasibility， the research team has launched the construction of a thousand-ton level industrial production line， which is expected to achieve large-scale production this year. This marks a key step forward for the technology towards industrial application.
2.3 Hexaric acid route
Due to the rapid development of the pectin industry in our country， the process route for producing FDCA using pectin as feedstock and hexaric acid as a key intermediate is increasingly demonstrating significant economic value and great development prospects. In this reaction pathway， the transformation process mainly includes the following key steps： firstly， pectin undergoes hydrolysis in an acidic aqueous solution environment to generate D-galacturonic acid monomers. Subsequently， these monomers undergo oxidation， dehydration and further hydrogenation reaction to form the key intermediate hexaric acid（
Fig.2c). Finally， hexaric acid undergoes multiple dehydration and cyclization processes to ultimately form the target product FDCA. In summary， this route not only significantly reduces feedstock costs but also helps to reduce competition for resources with food crops， fully aligning with the strategic direction of green， low-carbon， and sustainable development. From an industrial perspective， the route shows great prospects for industrialization and considerable expected economic benefits. However， the technology is currently in the transition phase from laboratory research to pilot-scale demonstration and has not yet achieved industrial production. It is expected that in the next 5 to 10 years， with the breakthrough of core bottlenecks such as catalytic systems and processes， the technology is likely to achieve initial industrial application.
2.4 Furfural route
In the global furfural market， China has established a dominant position due to its structural advantage of accounting for 90% of global production capacity. This substantial capacity base provides a solid guarantee for the large-scale production of FDCA. Similar to the furoic acid route， in the process route of synthesizing FDCA using furfural as an intermediate， hemicellulose-rich straw and corncobs are also used as the raw material (
Fig.2d). In the furfural route， the hemicellulose in the biomass raw materials is first hydrolyzed to produce xylose in an acidic aqueous solution， which is then converted into the key furfural intermediate through dehydration and cyclization reactions； then， this furfural intermediate further undergoes an aldol condensation reaction under alkaline conditions to generate the important platform compound HMF. Eventually， the target product， FDCA， is successfully prepared through the repeated selective oxidation reaction of HMF mentioned above. This pathway， with its advantages of abundant raw material sources and low cost， has significant economic benefits and broad prospects for industrialization. Based on its profound technical accumulation and solid engineering validation， Zhejiang Sugar Energy Company has successfully built and put into operation a thousand-ton-level FDCA industrial production line. The successful commissioning and stable operation of the production line mark that the company has successfully achieved the key transition from laboratory research to large-scale industrial production based on its mature and reliable core technology. This not only lays a solid foundation for the future construction of a ten-thousand-ton-level FDCA factory， but also has great significance for promoting the high-quality development of the biomass-based industry.
Given the significant differences in the technical and economic characteristics of the four synthetic routes mentioned above， this study presents a comprehensive and systematic evaluation of these four FDCA synthetic routes. The evaluation is based on key perspectives， including raw material availability， process maturity， product selectivity， environmental impact， and economic feasibility (
Table 1). Among these routes， the furoic acid route depends on the existing mature industrial system for furfural， and produces FDCA via oxidation cyclization. Owing to its significant advantages of low raw material cost and stable supply， this route demonstrates considerable competitiveness in the market
[27]. However， its product selectivity remains only moderate. Currently， this route is still in the laboratory-scale amplification research stage， with several key challenges including a complex catalytic system， high energy consumption during production， and difficulties in the treatment of alkaline wastewater. These issues significantly limit its economic feasibility and environmental sustainability for industrial applications. The hexaric acid route produces FDCA via a two-step process involving dehydrogenation， cyclization and oxidation. Compared with other synthesis routes， this routes exhibits notable advantages in raw material availability. However， this route suffers from several drawbacks， including low selectivity， harsh process conditions， high energy consumption， and acidic wastewater generation during the reaction， which not only result in relatively high overall production cost but also impose a greater environmental burden. In addition， the overall technological maturity of this route remains relatively low， and it is currently confined to the laboratory research stage， imposing substantial constraints on its industrialization process. The furfural route mainly produces FDCA via oxidation-hydroxyaldol condensation， with moderate selectivity toward the target product. This route utilizes cheap and readily available furfural as feedstock， exhibiting a distinct cost advantage and relatively mature technology， and has now entered the pre-pilot stage. Nevertheless， this process features low feedstock utilization efficiency， high separation and purification costs， as well as the discharge of alkaline and bromide waste liquors. Such economic and environmental drawbacks greatly hinder its large-scale sustainable production
[28-30]. In contrast， the HMF route displays outstanding overall competitive advantages owing to its mild reaction conditions， high target product selectivity， and ability to realize pilot-scale production. This route features a relatively simplified technological process， high technological maturity， and excellent product yield， performing favorably in terms of both large-scale production feasibility and economic benefits. Although its current production cost remains at a medium to high level， it exhibits the best environmental friendliness. Accordingly， the HMF route is regarded as the most promising technology pathway for the industrialized preparation of FDCA.
Although the HMF oxidation route has great potential in the production of FDCA， its industrialization process still faces many challenges： first， the stability of HMF and its intermediates in the aqueous phase is poor， which easily induces side reactions and thus hinders the smooth progress of the entire reaction
[31-33]； second， the reaction process typically relies on high pressure and strong alkaline conditions. Such harsh reaction conditions not only intensify the corrosion of the reactor and increase process safety risks， but also generate a large amount of high-salinity wastewater， severely restricting the economic viability and green development of the process. Moreover， the reaction process still faces bottlenecks in key aspects such as selectivity control， product separation， and purification， which urgently need to be overcome. Therefore， the key to the large-scale application of the HMF oxidation route still lies in the coordinated promotion of the optimization of traditional catalytic systems and the development of new green catalytic systems， thus systematically breaking through the key bottleneck of harsh reaction conditions， low selectivity， and poor economic feasibility.
3 Mature industrialization system for the oxidation of HMF to produce FDCA
Currently， the catalytic technology for the oxidation of HMF to FDCA is developing rapidly， and the related research systems are continuously being optimized and improved. The field has now presented a pattern where mature industrialization routes and emerging catalytic strategies are advancing in parallel. Both systems are committed to enhancing the catalytic activity and product selectivity of the reaction process， while also strengthening the green sustainability of the overall process， thereby effectively promoting the deep integration and collaborative innovation of basic research and industrial applications in this field.
The technological system for the oxidation of HMF to prepare FDCA mainly includes thermal catalysis， electrocatalysis， and biocatalysis
[34-36]. Among them， the thermal catalysis system， with its advantages of a mature process route， excellent catalytic efficiency and good prospects for large-scale application， has become the mainstream system in current industrial production， and its pilot-scale industrialization is being continuously advanced.
Currently， the technological route for the thermal catalytic oxidation of HMF to produce FDCA has become mainstream， and its reaction typically follows two reaction pathways (
Fig.3). In this process， the —CH
2OH and —CHO functional groups in HMF undergo selective oxidation， thereby giving rise to two parallel pathways： In pathway 1， the —CH
2OH group in HMF is initially oxidized to —CHO， forming the intermediate 2,5-diformylfuran (DFF)， which is subsequently oxidized to 5-formyl-2-furancarboxylic acid (FFCA). In pathway 2， the —CHO group in HMF is first oxidized to —COOH， generating the intermediate 5-hydroxymethyl-2-furancarboxylic acid (HMFCA)， which is then further oxidized to FFCA. Finally， FFCA is oxidized to yield the final product， FDCA. Due to the bond energies of the —CHO bond and —OH bond in the —COOH being significantly higher than those of the C—H and C＝O bonds in the other groups， the above oxidation steps exhibit a significantly exothermic nature（Δ
H < 0）. Moreover， considering the entire process of the HMF+O
2 reaction to generate FDCA+H
2O， the participation of O
2 leads to an increase in the orderliness and a decrease in the disorderliness of the system， indicating that each oxidation step is thermodynamically spontaneous and feasible. By taking into account the effects of the reaction enthalpy change（Δ
H）and entropy change（Δ
S）on the Gibbs free energy（Δ
G）， it can be concluded that the overall process of the complete oxidation of the —CHO and —OH groups in HMF to —COOH has a high degree of thermodynamic spontaneity. According to calculations， under the condition of 298.15 K， the standard Δ
G change of this reaction is estimated to be in the range of -700 kJ/mol to -800 kJ/mol， further confirming the significant spontaneous tendency of this reaction in thermodynamics. In addition， in this reaction system， compared with oxidants such as hydrogen peroxide， O
2 exhibits a more significant reaction advantage in thermodynamics. With its lower Δ
G， O
2 is able to interact with other groups in the reaction system to be converted into stable products such as CO
2 and H
2O， releasing a large amount of energy and efficiently promoting the oxidation of HMF to produce FDCA， while avoiding the environmental burden brought by traditional oxidants and in line with the principle of green chemistry. However， although the exothermic properties of HMF oxidation to FDCA provide a thermodynamic driving force for the reaction， the large amount of heat released constitutes a severe challenge in large-scale production. The rapid accumulation of reaction heat can easily cause local overheating， which in turn leads to catalyst sintering and deactivation， as well as product decomposition. Therefore， it is essential to rely on an efficient heat exchange system to remove heat in time， prevent catalyst deactivation and the occurrence of side reactions， and ensure safe industrial production.
Although the conversion of HMF to FDCA is thermodynamically feasible， its industrialization is still mainly limited by kinetic factors. Due to the great potential of the HMF oxidation pathway in the industrial synthesis of FDCA， elucidating its intrinsic reaction mechanism has become the current research focus. To this end， Cao et al.
[37] developed a non-noble metal-based NiAl layered composite catalyst， NiAl-GCN， for the oxidation of HMF to FDCA and systematically analyzed the reaction process with density functional theory（DFT）calculations. The study shows that in the NiAl-GCN catalytic system， the oxidant t-butyl peroxide（
t-BuOOH）first decomposes to generate OH
- and O
2， which then participate in the subsequent oxidation reactions. When the HMF molecule adsorbs on the catalyst surface， the electrons of its —CH
2OH and —CHO functional groups are transferred to the Ni
2+ active site and the GCN nitrogen defect sites， respectively. This process significantly reduces the strength of the —OH and C＝O bonds， thereby driving their oxidation along different pathways（
Fig.4a）. Specifically， in the DFF pathway， HMF first adsorbs to the catalyst surface via the oxygen atom in its —CH
2OH group. Under the action of reactive oxygen species generated from the decomposition of
t-BuOOH， the —CH
2OH group undergoes β-H elimination and subsequent oxidation steps to form the key intermediate DFF. Subsequently， the —CHO in DFF forms a hemiacetal intermediate in the presence of OH
- and is further oxidized to a —COOH through a dehydrogenation reaction， transforming into FFCA. Finally， the remaining —CH
2OH group in FFCA is further oxidized via a similar mechanism， ultimately yielding the target product FDCA.
Unlike the reaction pathway of DFF， the HMFCA pathway begins with the preferential adsorption of the —CHO in the HMF molecule on the catalyst surface (
Fig.4a). In this pathway， the OH
- active species generated from the decomposition of
t-BuOOH first launches a nucleophilic attack on the —CHO in the side chain of the HMF molecule， and with the assistance of the H
2O molecule， promotes proton transfer to form an unstable diol intermediate. Subsequently， one of the —OH groups in the intermediate undergoes deprotonation under the influence of OH
-， and then coordinates with the Ni active center to form a metal alkoxide intermediate. Then， a β-H elimination reaction occurs at the Ni active center， promoting the transformation of the diol structure into —COOH， generating the intermediate HMFCA. Subsequently， the OH
- adsorbed on the Ni site further extracts a hydrogen atom from the —CH
2OH group of the HMFCA and oxidizes it to —CHO in the presence of O
2， forming the intermediate FFCA. The —CHO group in FFCA then undergoes a similar oxidation process， further converting to —COOH， ultimately yielding the target product FDCA.
In addition， the DFT calculations indicate that the energy barrier for the oxidation of HMF to DFF is significantly lower than that for its conversion to HMFCA（
Fig.4b）. The high activation energy barrier makes the HMFCA pathway thermodynamically difficult to proceed. Therefore， the DFF pathway exhibits certain advantages in both thermodynamics and kinetics due to its lower reaction energy barrier， and thus is identified as the main pathway for FDCA formation in this system.
In summary， relying on experiments and theoretical calculations， the reaction mechanism of HMF oxidation to generate FDCA in this thermal catalytic system has become relatively clear， thus providing a theoretical basis for the subsequent catalyst design. Based on this， the current research focus is on the development of catalysts with high activity， high stability， and excellent selectivity， thereby effectively reducing the reaction energy barrier and overcoming kinetic limitations， and achieving the reaction to proceed efficiently. In the current industrial research and development system for the thermal catalytic oxidation of HMF to produce FDCA， a variety of catalysts have been widely explored and applied. Among them， metal catalysts have attracted much attention due to their high catalytic activity and tunable structure. Especially for supported metal catalysts， the electronic structure of active sites and their coordination environment can be finely tuned through strong metal-support interactions， thereby optimizing the interfacial charge distribution and electron transfer process， thus significantly enhancing the catalytic activity and long-term stability of the catalysts. Based on the above advantages， supported metal catalysts with their highly dispersed active centers and synergistic interactions with the support can effectively promote the oxidation reaction of HMF， thereby achieving the efficient synthesis of the target product FDCA， while providing key theoretical foundations and guidance for the rational design of efficient industrial catalysts in the future. Here， systematically summarizes the key performance data of different types of supported metal catalysts in the oxidation of HMF to FDCA in recent years (
Table 2).
Studies have shown that constructing bimetallic active centers to regulate the interfacial electronic structure is an effective strategy to improve the oxidation of HMF to FDCA. Du et al.
[54] reported that a bimetallic RuCo/NC catalyst exhibits a significant electronic synergistic effect in the oxidation of HMF. It can be seen from the analysis results that， after the introduction of Ru and Co to form a bimetallic structure， the characteristic binding energies of both metals show obvious shifts， confirming the occurrence of electron transfer between the metals (
Fig.5a and
b). This change not only increases the electron density on the Ru surface and enhances the cleaving ability of the C—H bond but also induces the Co sites to be in an electron-deficient state， thereby promoting the oxidation process of HMF. This synergistic mechanism promotes the electron transfer and cycling process， ultimately achieving a FDCA yield of 91.92% at room temperature. Notably， after a simple H
2 regeneration treatment， the catalyst still maintained an FDCA yield of 89.21% over the fourth cycle， further demonstrating its great potential in practical applications. Wang et al.
[55] further revealed the synergistic mechanism of the PdAu bimetallic catalyst through reaction kinetics studies. The study shows that the activation energy required for the Pd
1Au
4/Sep catalyzed conversion of HMFCA to FFCA is only 33.5 kJ/mol， much lower than that of the monometallic Au/Sep catalyst (95 kJ/mol). Electronic structure analysis further reveals that the electron transfer from Pd to Au optimizes the electronic structure of the Pd-Au active sites， which can not only enhance the adsorption of HMF and its intermediates， but also effectively promote the cleavage of the C—H bond， thus accelerating the oxidation process of HMF. Under optimized conditions， the catalyst can achieve an FDCA formation rate as high as 2560.72 mmol/g/h， demonstrating excellent catalytic performance. Li et al.
[56] conducted an in-depth analysis of the electronic structure of Au
1.2Pd
1/sepiolite to investigate the synergistic mechanism of Au-Pd bimetallics. Compared to monometallic Au/sepiolite (-1.515 eV) and Pd/sepiolite (-1.459 eV)， Au
1.2Pd
1/sepiolite has the lowest d-band center value of -1.755 eV (
Fig.5c). This indicates that the bimetallic alloy structure in Au
1.2Pd
1/sepiolite effectively regulates the electronic band structure of the material， bringing the d-band center closer to the Fermi level. Moreover， Bader charge analysis further reveals the relationship between catalytic performance and electron transfer. The electron transfer number for Au
1.2Pd
1/sepiolite（i）is 1.75 eV， significantly higher than that of monometallic catalysts (
Fig.5d). Therefore， the Au
1.2Pd
1/sepiolite catalyst with the highest number of electron transfers exhibits extremely high activity. After 10 h of reaction， the FDCA yield reaches as high as 98.4%. Li et al.
[57] revealed the mechanism of the Co-Mn-Br ternary catalytic system in the catalytic oxidation of HMF. In this reaction process， Co
2+ is first oxidized to Co
3+ under the action of O
2， then， with the assistance of Co
3+， Mn
2+ is further oxidized to Mn
3+. Subsequently， Mn
3+ oxidizes Br
- to generate bromine radicals (Br•) with strong hydrogen abstraction ability. These Br• generated through electron transfer can effectively attack HMF molecules， inducing the formation of carbon-centered radicals， thereby initiating a radical chain reaction and promoting the efficient conversion of HMF. Under optimized conditions， the yield of FDCA can reach 86.01%. Similarly， Ban et al.
[58] also utilized the same Co/Mn/Br catalytic system and electron transfer mechanism to successfully produce FDCA through a radical chain reaction. The aforementioned studies collectively confirm that the electron transfer between Co and Mn is a key factor in promoting the generation of Br• species and driving the oxidation of HMF
[59-61]. Bashir et al.
[62] rationally designed a CoMn
2O
4-Ni/NiO
x ternary spinel composite catalyst via a synergistic regulation strategy of defect and redox， which was then employed for the selective oxidation of HMF to FDCA. In this composite catalyst system， Ni/NiO
x exhibits Lewis acid site characteristics owing to its abundant oxygen vacancy（O
V）， which significantly enhances the adsorption and activation of the —CHO group in the HMF molecule. Meanwhile， the highly efficient Mn
4+/Mn
3+ redox couples provided by CoMn
2O
4 can activate the oxidant NaClO and generate highly reactive oxygen species such as •OCl
-， thereby reducing the reaction energy barrier and accelerating the catalytic cycle. Particularly， the construction of the Mn
4+-O
V-Ni
2+ heterogeneous interface remarkably improves the interfacial electron transfer efficiency， which not only effectively lowers the reaction energy barrier but also stabilizes the key intermediates during the reaction， thus significantly suppressing side reactions.
In addition to constructing bimetallic active centers as mentioned above， enhancing the migration rate of lattice oxygen（O
L）through other metal ions doping is also an effective strategy for improving the oxidation of HMF to FDCA. Ma et al.
[66] successfully synthesized the Co@N-C-x catalyst via the molten salt method and applied it to the oxidative conversion of HMF to FDCA. The results demonstrate that an efficient electronic synergistic mechanism is established between the Co‑N
x sites and defective carbon sites in the optimized Co@N-C-0.1 catalyst. Specifically， Co‑N
x serves as the primary active center in this catalytic system， which not only effectively promotes the adsorption and activation of HMF molecules but also rapidly transfers electrons to neighboring defective sites owing to its excellent electrical conductivity. Subsequently， these defective sites efficiently activate molecular oxygen and generate reactive oxygen species by capturing the transferred electrons， thus participating in the subsequent oxidation steps of HMF. Under mild reaction conditions， this catalyst enables full conversion of HMF with an FDCA yield as high as over 99%， exhibiting excellent potential for industrial application. Liu et al.
[63] found that doping such as Ce， La， and other metal elements into MnO
x can significantly enhance its catalytic performance in the HMF oxidation reaction. Among all the doped samples (
Fig.5e and
f)， the Mn
6Ce
1O
x catalyst has the highest concentration of O
V. This indicates that the introduction of Ce constructs an asymmetric Mn-O-Ce structure in the MnO
x lattice， effectively weakening the strength of the Mn—O bond， thereby promoting the migration of O
L and accelerating the formation of O
V. This structural regulation not only increases the concentration of O
V on the catalyst surface but also enhances the adsorption and activation ability of the —CHO and —CH
2OH functional groups in HMF， ultimately achieving an FDCA yield of 97.2%. In addition， the catalyst exhibited excellent reusability， maintaining 100% HMF conversion and over 92% FDCA yield over five cycles. Zhang et al.
[64] utilized tunable Au/Pd/Pt noble metals to optimize the catalytic performance of O
V-rich TiO
2@HNTs composites and applied them to the oxidation of HMF. The study shows that there is a strong interaction between the O
L on the TiO
2 surface and metals， which promotes the directional transfer of electrons from the active sites of the metal to the support， causing the Au， Pd， and Pt atoms at the interface to be in an electron-deficient state and resulting in an upward shift of the d-band center. Compared with other catalysts， Au
0.5Pd
0.2Pt
0.3/TiO
2@HNTs not only exhibits the highest O
V concentration（
Fig.5g）， but its d-band center is also closest to the Fermi level（-1.438 eV）. This unique electronic structure benefits the adsorption of substrate molecules such as HMF and its intermediates， thereby significantly enhancing catalytic performance and achieving an FDCA yield of 93.6%. In addition， Liu et al.
[65] successfully prepare a series of MnO
2 nanorod catalysts with tunable crystal phases and defect concentrations by precisely controlling the synthesis temperature， and further applied them to the catalytic oxidation of HMF. Among them， the redshift of the Mn—O bond vibration and the decrease in the reduction peak temperature in α-MnO
2 confirm its higher O
V concentration and richer lattice defects (
Fig.5h and
i). Due to these properties， this catalyst can significantly enhance interfacial charge transfer and promote the adsorption and activation of superoxide radicals (•O
2-) in O
2 molecules， thereby achieving an FDCA yield of 96.7% under mild conditions.
In summary， relying on the lab's key progress in efficient catalyst design and reaction pathway optimization， the production of FDCA via thermocatalytic oxidation of HMF has successfully achieved a rapid transition from basic research to industrial application. In recent years， the industrialization process of this technology has accelerated significantly， gradually forming a global development pattern dominated by enterprises and covering different scale stages. As an internationally leading company in the field， Netherlands-based Avantium has successfully completed a pilot demonstration producing 40 tons of FDCA per year based on Avantium’s YXY® technology platform， and has officially launched the construction of a commercial factory with a capacity of 50000 tons， marking the formal transition of this technology to the large-scale industrialization stage. Meanwhile， Chinese enterprises have shown outstanding performance in industrialization promotion. GS Biomats， based on its thousand-ton HMF production line， is actively extension and exploitation of downstream industrial chains， and is fully promoting the ten-thousand-ton scale FDCA industrialization project. Zhejiang Sugar Energy Technology has also achieved stable production of a thousand tons of HMF and is committed to building a full industry chain system from HMF to FDCA and then to polyester materials. LEAF Biotech has built a hundred-ton scale demonstration factory through its independently developed catalytic technology， laying a solid foundation for subsequent capacity expansion. These developments collectively indicate that the technology of preparing FDCA via HMF thermal catalytic oxidation has fully entered the key transition period from demonstration operation to commercial application. Although the thermal catalytic system has the advantages of mature technology and a simple reaction mechanism in the synthesis of FDCA， its industrialization process still faces significant challenges. Specifically， issues such as insufficient catalyst stability， excessive energy consumption during the reaction process， and difficulties in the subsequent separation and purification of products are the fundamental barriers to the large-scale industrial application of this technology. In order to effectively break through these bottlenecks， it is urgent to promote in-depth cooperation between industry and research institutions， systematically optimize the design of catalysts and reaction systems， continuously improve technological development and equipment integration， and thereby significantly enhance the economic feasibility and market competitiveness of the thermal catalytic production process for FDCA.
4 Emerging catalysis systems for the oxidation of HMF to produce FDCA
In addition to the aforementioned conventional thermocatalytic systems， emerging catalytic technologies including electrocatalysis and biocatalysis have also achieved groundbreaking advances in recent years. Among these， electrocatalytic systems enable the precise and selective oxidation of HMF under mild electricity-driven conditions for the efficient synthesis of high-value chemicals including FDCA， and exhibit excellent reaction controllability and environmental friendly. Meanwhile， biocatalytic systems take advantage of the high specificity of enzymes to realize the green and highly selective conversion of HMF， effectively suppressing side reactions. The development of these emerging catalytic systems not only diversifies the conversion pathways of HMF but also provides new insights into the efficient valorization of biomass resources.
4.1 Electrochemical catalysis system
In addition to the thermocatalytic systems that have been industrialized， in recent years， emerging catalytic strategies such as electrocatalysis and biocatalysis have also achieved significant progress in the oxidation of HMF to produce FDCA， and have demonstrated certain potential for industrial application. Unlike the traditional thermal catalytic system that relies on high temperatures and external oxidants， the electrocatalytic oxidation process of HMF can directly drive the reaction through electron transfer at the electrode surface
[67-68]. This mechanism inherently avoids the generation of by-products and the addition of extra oxidant， demonstrating higher economy and environmental friendliness.
In the study of electrocatalytic oxidation of HMF to produce FDCA， the choice of reaction pathway mainly depends on the chemical environment of the reaction system and the regulation of the electronic structure of the catalyst's active sites by the external electric field. To elucidate the intrinsic mechanisms of different reaction pathways， Yao et al.
[69] systematically investigated the reaction pathways and mechanisms of HMF electrocatalytic oxidation to FDCA， and compared the energy barriers and feasibility of two different reaction pathways through DFT calculations. Based on the analysis of the reaction pathways， the oxidation of HMF to FDCA can proceed via two pathways (
Fig.6a). Under alkaline conditions， the reaction can proceed via pathway 1： firstly， the —CHO group in HMF undergoes nucleophilic addition mediated by OH
- to form a diol intermediate. Subsequently， this intermediate undergoes a dehydrogenation reaction under the catalytic action of the Ni
2+ active site， converting into HMFCA. The H
+ released in this step is transferred to the vicinity of NiOOH on the anode surface， and reduces it to Ni(OH)
2. Under the drive of the external electric field， Ni(OH)
2 can be further oxidized to regenerate NiOOH， thus forming a complete catalytic cycle that continuously drives the reaction. Then， the —CH
2OH group in HMFCA is further oxidized to —CHO， thereby forming FFCA. Ultimately， the —CHO group in FFCA follows a pathway similar to HMF conversion， undergoes nucleophilic addition and dehydrogenation in the presence of OH
-， and is further oxidized to the target product FDCA. Based on the analysis of the energy barrier distribution along the reaction pathway， the energy barrier for the FFCA to FDCA conversion step is significantly higher than that of other elementary steps， indicating that this step is the rate-determining step in the entire HMF oxidation reaction network (
Fig.6b). In addition， in pathway 2， the author suggests that the possible reaction mechanism is as follows： first， the —CH
2OH group in the HMF molecule undergoes cooperative adsorption with the Ni
2+ catalytic active sites on the anode surface， and then intermediate DFF is generated through —OH bond cleavage and β-H elimination steps. Subsequently， the —CHO group of DFF undergoes a hydration reaction to form an unstable geminal diol intermediate； then， this intermediate dehydrogenates through a β-hydrogen elimination process， further converting into the intermediate product FFCA. Finally， the remaining —CHO in FFCA repeats the aforementioned hydration-dehydrogenation process， yielding the target product FDCA. However， experimental results show that the DFF intermediate is almost undetectable in this system. To clarify the actual reaction pathway of HMF and its intermediates， the authors used DFT calculations to systematically simulate and compare the two pathways mentioned above. According to the energy distribution， the energy barrier for the oxidation of HMF to HMFCA is significantly lower than that for its conversion to DFF. This indicates that the formation of DFF requires overcoming a higher activation energy barrier and is thermodynamically unfavorable for the reaction to proceed. Meanwhile， it can be seen that the reaction energy barrier for pathway 1 is relatively low， indicating that it is more advantageous in terms of both thermodynamics and kinetics. Therefore， pathway 1 is identified as the main route for FDCA formation in this reaction system. Meanwhile， Du et al.
[54] have demonstrated that there are significant differences in the oxidation pathways of HMF under alkaline and non-alkaline conditions. The introduction of alkali can change the main pathway of HMF oxidation， promoting the preferential oxidation of —CHO， thereby generating the intermediate HMFCA； conversely， under non-alkaline conditions， the —CH
2OH group is more easily oxidized， subsequently forming the intermediate DFF.
With the in-depth study of electrocatalytic systems， new methods for the electrocatalytic oxidation of HMF to prepare FDCA are constantly emerging. In current research， to overcome the limitations of traditional single-component catalysts in terms of electronic conductivity and reaction activity， the synergistic regulation of the catalyst's electronic structure through multicomponent doping and heterojunction structure design has become a key approach to improving the efficiency of HMF oxidation. Yao et al.
[70] prepared an O
V-rich Ni(OH)
2/CeVO
4 bimetallic catalyst via a one-step hydrothermal method for electrocatalytic oxidation of HMF to produce FDCA. The combination of EPR results confirms that the introduction of V species significantly increases the concentration of O
V (
Fig.7a and
b)， effectively reducing the adsorption energy of HMF and the reaction energy barrier (
Fig.7c). Under optimized conditions， HMF can achieve complete conversion with an FDCA yield reaching as 97.8%. Chen et al.
[71] constructed the FeCo-modified β-Ni(OH)
2 wrinkled nanosheet catalyst and systematically investigated the key role of electron transfer in enhancing the electrocatalytic oxidation performance of HMF. They found that the doping of Fe and Co can effectively regulate the electronic structure of Ni， promote the formation of active sites of β-NiOOH， and significantly reduce the dehydrogenation energy barrier. Combined with DFT calculations， it is confirmed that the introduction of Fe-Co bimetal optimizes the adsorption energy of HMF on the catalyst surface and improves the d-band center position， achieving efficient electron transfer. This synergistic effect significantly enhances the reaction kinetics， thereby achieving efficient conversion of HMF to FDCA. Liu et al.
[72] synthesized hetero-structured Cu-Co bimetallic oxide electrocatalysts via electrodeposition coupled with electrochemical activation for HMF electrooxidation. Experimental results revealed that the incorporation of Cu effectively induced the formation of abundant O
V and promoted the generation of high-valent Co
3+ active sites， thereby markedly optimizing the electronic structure of the catalyst. DFT calculations further demonstrated that the adsorption energy of HMF on CuOCoOOH (-1.71 eV) was much lower than that on pure CoOOH (-0.63 eV)， which originated from the strong interaction between O
V and the —CHO groups of HMF， thus significantly strengthening the adsorption capacity toward the substrate. During HMF electro-oxidation， Cu preferentially boosted the oxidation of —CHO groups， whereas high-valent Co
3+ species mainly contributed to the oxidation of —OH groups. The synergistic effect between Cu and Co enabled efficient conversion of both alcohol and aldehyde functional groups. At a potential of 1.45 V， 100% HMF conversion was achieved， accompanied by an FDCA yield and Faradaic efficiency both as high as 98%， with a current density of 106.6 mA/cm
2. Furthermore， the catalyst demonstrated outstanding stability， retaining excellent catalytic activity after three consecutive cycles， highlighting its great promise for practical applications. Tao et al.
[73] successfully constructed a Cu(OH)
2@Co(OH)
2/CF heterojunction catalyst with a core-shell structure via a two-step impregnation method. Bader charge analysis revealed that approximately 1.22 electrons were transferred from the CoO
x(OH)
y to Cu(OH)
2， verifying a distinct electron transfer effect between the two phases. Specifically， the CoOOH active sites in situ generated from Co(OH)
2 can effectively adsorb and activate the —CH
2OH and —CHO groups in HMF molecules， thus accelerating the oxidation of HMF. Meanwhile， Cu(OH)
2 continuously extracts electrons from the Co sites， promoting the oxidation of Co
2+ to Co
3+ and the regeneration of CoOOH. Such electronic synergy effectively boosts the efficiency of the Co
2+/Co
3+ redox cycle， laying a solid foundation for the efficient and stable electro-oxidation of HMF. Under optimal conditions， HMF was almost completely converted， with FDCA selectivity exceeding 98% and a Faradaic efficiency as high as 98.7%. Meanwhile， Liu et al.
[74] constructed a P-Ni
3S
2/Ni/NF composite catalyst by doping P into Ni
3S
2， aiming to investigate the role of electron transfer in the electrocatalytic oxidation of HMF to FDCA. It shows that the synergistic effect between P and the Ni
3S
2/Ni heterojunction can significantly enhance interfacial electron transfer capability， thereby driving the catalyst to achieve efficient HMF electro-oxidation， resulting in a 99.2% HMF conversion， a 98.1% FDCA yield， and a 98.8% Faradaic efficiency.
In addition to methods such as multicomponent doping and heterojunction structure construction， regulating the adsorption properties and coordination environment of active sites is also an efficient approach. This method aims to enhance the adsorption and enrichment of substrate molecules through the precise design of the local environment of the catalyst， ultimately achieving efficient conversion of HMF to FDCA. Dai et al.
[75] developed an Al（OH）
3/Co（OH）
2 catalyst for the electrocatalytic oxidation of HMF. The catalyst promotes electron transfer via Co
3+ active sites to reduce the reaction energy barrier， while effectively enriching HMF at the interface through strong adsorption by Al
3+. This synergistic mechanism of adsorption and catalysis optimizes the interfacial reaction process， thereby significantly enhancing the overall reaction efficiency. Compared to other catalysts， this bimetallic catalyst exhibits higher surface potential， current density， and double-layer capacitance， indicating that it possesses a larger electrochemically active surface area and more abundant active sites（
Fig.7d~
f）. This synergistic mechanism can effectively reduce the reaction energy barrier， thereby significantly accelerating the entire reaction process. Under the reaction conditions of 1 M KOH electrolyte and 1.5 V potential， HMF is completely converted with a FDCA yield as high as 99.1%. In addition， Sun et al.
[76] prepared a nitrogen-doped carbon-coated Co
3O
4@NC composite catalyst， which exhibited remarkable catalytic performance in the electrooxidation of HMF to FDCA. Experiment results revealed that under alkaline potential-driven conditions， Co
3O
4@NC catalyst undergoes surface electronic reconstruction， in which part of the Co
2+ species in Co
3O
4 was oxidized to Co
3+， thereby generating CoOOH active centers. These active centers enhanced the adsorption capacity of OH
- via electron transfer， thereby efficiently driving the HMF oxidation process. Meanwhile， the remaining unreconstructed Co
3O
4 directly adsorbed HMF molecules by virtue of its abundant O
V and Co
2+ sites， promoting the enrichment of reactants on the catalyst surface. Under optimal reaction conditions， the catalyst achieve 99% HMF conversion， with FDCA and Faradaic efficiency both exceeding 95%. Notably， after four consecutive catalytic cycles， the HMF conversion still remained above 95%， and both FDCA yield and Faradaic efficiency were higher than 90%， demonstrating excellent catalytic stability.
Similarly， Dai et al.
[77] have demonstrated that electrical stimulation can induce surface reconstruction of Co(OH)
2/Ni-MOF， ultimately forming dual active sites rich in Co
3+ and Ni
3+. Among them， Co
3+ can effectively regulate the electronic structure of Ni， promoting the Ni
2+/Ni
3+ redox cycle， thereby significantly reducing the initial potential for HMF oxidation. Compared with single-component catalysts， the redox peaks of Ni
2+/Ni
3+ in Co(OH)
2/Ni-MOF are significantly enhanced， indicating the synergistic catalytic effect between Co
3+ and Ni
3+， which jointly enhance the activity of the HMF oxidation reaction (
Fig.7g~
l). In addition， the dual active sites exhibit excellent self-healing capabilities， enabling continuous regeneration under electrical stimulation (
Fig.7m，
n). This effectively compensates for the loss of active sites during the reaction process， thereby conferring the catalyst with exceptional long-term stability， allowing the FDCA yield to still reach 98.5% after 90 days. Chen et al.
[78] successfully prepared a Ni
3S
2/NF electrocatalyst with a high proportion of short Ni-S coordination bonds by regulating the water content. The strong electronic interaction between Ni and S effectively regulates the electronic structure of the catalyst， thereby enhancing charge transfer efficiency. At a potential of 1.45 V， the current density can reach as high as 1000 mA/cm
2， demonstrating great potential for industrial application.
Based on these laboratory research results， the electrocatalytic oxidation technology of HMF is also making significant progress on the path to industrialization. In the field of FDCA production via HMF electrocatalytic oxidation， foreign companies Avantium and BASF， with their strong technological and patent advantages， have not only successfully achieved pilot-scale production but are also committed to continuously optimizing the process to lead the future development of this field. In China， a joint team from Beijing University of Chemical Technology and Tsinghua University successfully developed a 20 kW electrolysis water-coupled HMF oxidation reaction system， achieving an important breakthrough in the electrocatalytic synthesis of FDCA from the laboratory to engineering scale. In addition， the system’s FDCA annual production capacity can reach 56 tons， providing crucial support for subsequent large-scale production. At the same time， this system， with its high yield and environmentally friendly advantages， has significant benefits in process system compatibility and sustainability， showing broad prospects for industrialization.
In summary， the electrocatalytic oxidation system effectively avoids the dependence on high-pressure environments and chemical oxidants， ensuring the safety and environmental friendliness of the production process from the source and demonstrating significant potential for industrial application. This process can also flexibly optimize reaction pathways by precisely controlling the potential， thereby ensuring the highly selective production of the target product. It is worth noting that the electrocatalytic system has achieved efficient synchronous coupling of anodic oxidation and cathodic reduction reactions. The system can not only selectively oxidize HMF to FDCA at the anode， but also simultaneously generate H
2 or other high-value products at the cathode (
Fig.8). Although HMF electrocatalytic oxidation for FDCA synthesis shows broad application prospects， its industrialization still faces a series of technical and engineering bottlenecks that need to be overcome， including high electrolyzer costs， electrode scaling
[80-81]， and mass transfer limitations， all of which restrict the transformation of this technology from the laboratory to industrial scale. Therefore， overcoming these bottlenecks is crucial for successfully achieving the industrialization of this system.
At present， to address the core challenges facing the industrialization of emerging electrocatalytic systems， such as high costs， insufficient stability， and difficulty in scale-up， recent studies have systematically investigated these issues from multiple perspectives and proposed a series of effective strategies. For cost control， the main approaches focus on the fine-tuning of the catalyst microstructure. On one hand， the intrinsic activity is enhanced by optimizing the electronic coupling effect between the metal and the support. On the other hand， rational design of core-shell structure is employed to significantly reduce the usage of precious metals while maintaining high catalytic activity. For stability enhancement， researchers have proposed the concept of“self-healing”catalytic materials. This mechanism relies on the redeposition of trace active components in the reaction medium to realize in-situ regeneration of active sites， or the design of a crystal phase capable of reversible transformation under redox conditions， thereby effectively prolonging the catalyst’s lifetime. In tackling the challenges associated with electrocatalytic scale-up， research attention is shifting from the optimization of individual active sites toward the synergistic regulation of multi-scale mass transfer processes. By employing advanced structured reactors， such as microchannel reactors and fluidized bed electrodes， the side reactions and local deactivation induced by mass-transfer limitations can be greatly alleviated. These multiple-perspective synergistic strategies are promoting the translation of emerging electrocatalytic systems from laboratory fundamental research toward practical industrial applications.
4.2 Biological catalysis system
Among various emerging systems for converting HMF to FDCA， in addition to the electrocatalytic system， biocatalysis has also become an important green synthetic system due to its significant advantages of mild reaction conditions， high product selectivity， and environmental friendliness
[17]. Compared with traditional catalytic systems， which generally have problems such as high consumption of organic solvents， high energy consumption， and difficulty in catalyst recovery， this biocatalytic system uses water as the main reaction medium and employs biodegradable enzyme catalysts， effectively avoiding the use of toxic and harmful reagents. In addition， leveraging its advantage of mild reaction conditions， this system not only significantly reduces energy consumption but also achieves efficient production of FDCA， thereby enabling a fully green transformation from raw materials to products. This process shows significant advantages in both green chemistry and technological economy， providing a promising direction for the green industrial production of FDCA.
In recent years， significant progress has been made in the study of converting HMF to FDCA through biocatalytic oxidation， which has greatly promoted in-depth exploration of the reaction mechanism. Nascimento et al.
[82] developed a biocatalytic system based on laccase (LacTV) and TEMPO mediator for the oxidation of HMF to produce FDCA and systematically elucidated the pathway and mechanism of this reaction. They found that in this reaction system， the oxidation of HMF to FDCA mainly occurs via Route B (
Fig.9). In this path， LacTV and TEMPO first generate a highly active oxoammonium ion intermediate through synergistic action. Subsequently， the oxygen atoms in the HMF substrate use their lone pair of electrons to launch a nucleophilic attack on the TEMPO-oxoammonium， thereby forming an unstable transition state intermediate. The intermediate further undergoes deprotonation of the α—C—H bond， thereby resulting in the formation of DFF. Then， the —CHO in DFF undergoes a hydration reaction in the aqueous environment to generate a gem-diol intermediate. The intermediate first launches a nucleophilic attack on the TEMPO-oxoammonium， and then undergoes deprotonation to form the FFCA. Finally， the —CHO on the other side of the FFCA undergoes a similar nucleophilic attack-deprotonation process and is ultimately converted into the target product FDCA. However， the formation of HMFCA is not detected in the reaction； thus， it indicates that Route B is the predominant pathway for the oxidation of HMF to FDCA in this catalytic system.
Although previous studies have confirmed that the conversion of HMF to FDCA mainly proceeds via the DFF intermediate， subsequent research further revealed that the pathway with HMFCA as the key intermediate is also an important route. Yang et al.
[83] developed an oxidation cascade system based on the synergistic action of aldehyde dehydrogenase (ALDHs) and laccase-TEMPO， which successfully achieved the efficient conversion of HMF to FDCA. In this reaction mechanism， the —CH
2OH of HMF is rapidly oxidized to —COOH by ALDHs under neutral pH conditions， and generating HMFCA. Subsequently， the —CH
2OH in HMFCA is further oxidized to —CHO under the catalysis of the laccase-TEMPO system， generating the key intermediate FFCA. Ultimately， the —CHO in FFCA is oxidized to —COOH under the catalysis of ALDHs， thereby efficiently producing the target product FDCA. In addition， the by-product 2,5-bis(hydroxymethyl)furan (BHMF) generated during the catalysis process can be re-oxidized to HMF by the laccase-TEMPO system， thereby improving the overall economy and reducing by-product accumulation.
In summary， biocatalytic systems with their clear reaction pathways and environmentally friendly processes， show broad application prospects in the field of catalytic oxidation. Therefore， designing and developing biocatalysts with high active sites to achieve efficient oxidation of HMF has become a key research direction in this field. Among the various biocatalysts capable of oxidizing HMF to FDCA， laccase stands out from the various enzymatic catalysts due to its mild reaction conditions， utilization of O
2 as a green oxidant， and excellent substrate adaptability. To further enhance the catalytic performance and stability of laccase in practical reactions， researchers are committed to constructing a laccase system with a controllable structure and high mass transfer efficiency， thereby effectively driving the conversion of HMF to FDCA. Yang et al.
[84] successfully constructed a three-dimensional porous laccase-copper hybrid nanoflower catalyst through an enzyme-metal coordination-driven self-assembly method. The structural design of this catalyst achieves high-loading encapsulation of enzymes， and its structure is shown in the figure below (
Fig.10a). The active sites of laccase on the surface of the nanoflowers can promote the generation of TEMPO
+ from TEMPO molecules， which then successively oxidize HMF and its intermediates. This method not only achieved efficient encapsulation of the enzyme but also significantly enhanced the stability of the catalytic system and the accessibility of active sites. Under optimized reaction conditions， the catalyst can achieve an FDCA yield of 93.09%. Similarly， Nascimento et al.
[82] also used the laccase/TEMPO system to catalyze the oxidation of HMF to prepare FDCA， and obtained a 51% yield of FDCA under optimized conditions. However， it is worth noting that the inherent limitation of a single-enzyme catalytic system lies in its inability to independently complete the complex multi-step oxidation process， which leads to the accumulation of a large amount of intermediate products， thereby resulting in low overall reaction efficiency and limited selectivity. To address these challenges， studies have proposed the use of the enzyme cascade reaction method to significantly improve the selectivity of FDCA
[85]. Yang et al.
[86] systematically investigated the synergistic effect of laccase
BpLac and oxidase
CglAlcOx in the catalytic oxidation of HMF to FDCA. The study found that the
CglAlcOx has relatively low oxidation capability for the FFCA， which limits the production of FDCA (
Fig.10b). However， the introduction of
BpLac can efficiently catalyze the further oxidation of FFCA， thereby significantly enhancing the production efficiency of FDCA (
Fig.10c). Driven by this synergistic catalytic mechanism， HMF in the reaction system can be efficiently converted， ultimately achieving an yield of FDCA of 97.5%.
Moreover， Zou et al.
[87] constructed a laccase/TEMPO-mediated enzyme-bacterium cascade biocatalytic system for the efficient oxidation of HMF to produce FDCA. The single laccase/TEMPO system could oxidize the —CH
2OH in HMF， thereby generating the intermediate DFF (
Fig.10d). However， due to the low hydration capacity of the —CHO group in the DFF molecule， it is difficult to be fully oxidized to FFCA and FDCA， which hinders the efficient progress of the reaction. In contrast， Pseudomonas putida KT2440 exhibits excellent oxidation ability towards the furan aldehyde group and can efficiently convert intermediates such as DFF and FFCA into FDCA. Through this cooperative cascade catalytic system， the limitations of the single-enzyme catalytic system are effectively overcome， paving a practical and feasible new path for the highly selective synthesis of FDCA. Swoboda et al.
[88] also developed a sequential dual-enzyme system composed of MorUPO and AaeUPO， which successfully achieved the efficient conversion of HMF to FDCA. Based on their complementary property， the dual-enzyme system significantly enhances catalytic efficiency， achieving an HMF conversion of 95% and an FDCA yield of 69% under optimized conditions， providing an efficient new route for the green synthesis of FDCA.
Adopting enzyme cascade reactions to optimize the conversion from HMF to FDCA has become an important research direction in this field. The fundamental breakthroughs achieved by this technology have not only significantly propelled the progress of biocatalytic processes but also sparked widespread attention to the pilot and industrial-scale production of FDCA. Driven by this， the relevant research field has attracted extensive international collaboration. BASF in the United States and Genomatica jointly developed an integrated bioprocess to achieve efficient oxidation of HMF to FDCA. Currently， this technology is at a critical stage in its transition from laboratory to pilot-scale development. At the same time， research teams represented by the Tianjin Institute of Industrial Biotechnology， the Chinese Academy of Sciences， and Tsinghua University successfully achieved efficient FDCA production by constructing a synergistic catalytic system that combines engineered microorganisms with oxidative enzymes. However， this technology remains confined to the laboratory stage， with no Chinese enterprises having initiated pilot-scale trials to date.
Overall， although the biocatalytic system for producing FDCA has shown great potential in laboratory studies， its industrialization still faces many inherent challenges. Currently， enzyme catalyst systems generally have problems such as low reaction efficiency， poor long-term stability， and poor tolerance to complex reaction systems
[89]. Not only that， this process also faces challenges such as high costs and difficulties in large-scale industrial amplification， which limit the industrial development of this technology. Therefore， optimizing existing catalytic systems and developing new high-performance biocatalysts to achieve a balance among efficiency， stability， and cost is the fundamental premise for realizing future industrial development.
In recent years， to overcome the bottlenecks limiting the industrial application of enzyme catalysts， researchers have carried out in-depth investigations from the perspectives of enzyme molecular design and reaction system construction. Among these， enzyme immobilization technology provides an effective strategy to tackle the easy inactivation of native enzymes. Immobilizing enzyme molecules onto suitable support materials via anchoring interactions is an important approach to enhancing their structural rigidity. This method not only significantly improves the tolerance of enzymes toward harsh conditions such as high temperature， extreme pH， and organic solvents， but also enhances their catalytic efficiency and stability while retaining high catalytic activity， laying a foundation for its long-term stable application. Furthermore， single-enzyme systems are generally unable to independently accomplish complex multi-step transformation processes. To address this challenge， multi-enzyme cascade catalytic systems have gradually emerged as a research focus. This system achieves efficient one-pot cascade reactions via the synergistic effect of multiple enzymes. This not only simplifies operational procedures and reduces the separation and purification of intermediates， but also markedly improves the economic efficiency and overall yield of the reaction， providing new guidance for the development of efficient and green biocatalytic processes.
5 Economic analysis and LCA of process systems
Among the various catalytic systems for the oxidation of HMF to produce FDCA， the thermal catalytic system has made significant progress in industrial processes due to its high reaction efficiency， mature processes， and low costs. However， although thermocatalytic routes dominate in existing industrial systems， their further development still struggles to overcome critical bottlenecks such as high energy consumption and high carbon emissions
[90-91]. Yang et al.
[92] employed LCA to systematic evaluation of current processes for the oxidation of HMF to FDCA. It is found that the production of each kilogram of FDCA will be accompanied by 3.9 kg of CO
2 emissions (
Fig.11). Of this total， only 0.87 kg originates from direct process emissions， while the vast majority of emissions mainly come from the upstream raw material extraction and production processes. Specifically， during the glucose production and processing stage， electricity consumption and thermal energy consumption contribute 0.78 kg and 0.37 kg of CO
2 emissions， respectively. In addition， in the HMF oxidation process， the O
2 as a reactant also results in 0.19 kg of CO
2 emissions， further increasing the carbon emission burden at this stage. Based on the above analysis， future research and industrial development in the field of thermal catalysis will focus on two core directions： firstly， developing more economical and environmentally friendly HMF synthesis and purification processes to reduce raw material costs and carbon emissions； and then， exploring new catalytic systems and process routes to alleviate dependence on harsh conditions such as high temperatures and pressures， thereby reduces energy consumption and costs in the production process， simplifies the process procedures， and enhances the stability and scalability of the process.
However， only relying on the optimization of catalysts and processes is still not sufficient to achieve the“deep green”production of FDCA throughout its entire life cycle. Current thermal catalytic oxidation processes generally rely on traditional fossil fuels as their energy sources. This mode of energy supply inevitably leads to the consumption of non-renewable resources and greenhouse gas emissions. From the perspective of a full LCA， this essentially undermines the carbon neutrality advantage that biomass feedstocks should inherently possess. Therefore， future development not only requires continuous optimization of catalytic systems and processes， but more importantly， it should focus on the development and utilization of clean energy such as renewable electricity， green hydrogen， and green oxygen. This fundamental transformation in energy is the core driver leading the entire industry towards green and sustainable development. By deeply integrating green energy systems with advanced catalytic technologies， it is possible not only to directly avoid carbon emissions in traditional power generation processes but also to drive the fundamental transition of high-carbon hydrogen production to green hydrogen production， thereby achieving systematic decarbonization of the industrial chain. This technological approach not only drives deep carbon reduction in core production processes but also extends green advantages across the entire lifecycle from biomass raw materials to final products， creating a complete sustainable closed-loop system. In summary， LCA studies have confirmed that the use of green electricity， green hydrogen， and green oxygen is critical to achieving full greening of the entire FDCA industrial chain. Therefore， future research and development must simultaneously focus on the continuous optimization of the catalytic system and the significant enhancement of process economics. This is not only crucial for the large-scale development of FDCA but also serves as a solid foundation for the development of its downstream industrial chain.
6 Value chain of FDCA and the specific applications of its downstream products
As a new bio-based platform chemical， FDCA， with its rigid furan ring and —COOH， can be converted into a variety of high-value derivatives through reactions
[93]， such as esterification， amidation， reduction， decarboxylation， polyesterification and acyl halide. These derivatives show broad application prospects in the industry， polymer， new materials， and sustainable packaging fields. In conclusion， constructing a value chain centered around FDCA based on renewable raw materials not only fully complies with the fundamental principles of green chemistry but also provides a good application prospect for developing a low-carbon and sustainable chemical system
[94-97].
Among the many downstream derivatives of FDCA， PEF， as a high-performance polymer， has attracted significant attention due to its enormous industrial application potential. Compared with traditional petroleum-based plastic PET， PEF synthesized from FDCA has superior tensile strength and gas barrier properties
[98-100]. Specifically， the O
2 barrier performance of PEF is 5~11 times that of PET， and the CO
2 barrier performance is 2~19 times that of PET. Moreover， LCA results indicate that compared to PET， the production of PEF is expected to reduce greenhouse gas emissions by 45% to 55% and decrease the consumption of non-renewable energy by 40% to 50%
[101]. Moreover， the tensile strength of PEF is approximately 25% higher than that of traditional PET. This feature enables PEF products to achieve significant lightweighting advantages while ensuring the integrity of packaging， thereby directly reducing the consumption of raw materials and aligning with sustainable development trends. In addition， PEF products not only demonstrate superior durability but also possess good biodegradability
[102-103]， making them more aligned with green development requirements. However， although the monomers centered on FDCA have shown great potential in replacing traditional petroleum-based polyester products in terms of performance， their high production costs seriously limit their economic feasibility and hinder large-scale market promotion. To address the cost challenges of FDCA， its industrialization application should anchor itself in high-end markets and focus on developing more high-value-added products， thereby driving its market application and the realization of high added value.
In recent years， with the continuous deepening of research into its downstream applications， the application fields of FDCA are no longer limited to the use of PEF materials， but are showing a diversified development trend from general-purpose materials to high-added-value fine chemicals. In the research field of high-performance polymers， more and more studies have focused on using FDCA as a key structural unit to construct various new high-performance polymers through copolymer modification and other means， such as functional polyesters， polyamides
[104-105]， and polyurethanes
[106]. The successful development of these polyester materials has not only significantly expanded the applications of FDCA in fields such as food packaging， industrial coatings， and electronic device casings
[107-108]， but also promoted the advancement of polymer materials toward greener and more sustainable directions.
It is worth noting that the application scope of FDCA is no longer confined to existing mature fields， but has shown broad application prospects in emerging cutting-edge directions such as high-performance polymers， special engineering plastics， and biomedical materials. In the field of specialty engineering materials， high-performance polyesters synthesized with FDCA as a key monomer are gradually breaking through the bottleneck of traditional petroleum-based polyesters， resolving the long-standing challenge that such materials cannot simultaneously balance strength， toughness and barrier properties. Taking poly(butylene 2,5-furandicarboxylate) (PBF) as a typical example， the Ningbo Institute of Materials Technology and Engineering， Chinese Academy of Sciences， adopted a“nanoscale confined crystallization”strategy， utilizing TiO
2-grafted BN nanosheets as a two-dimensional template to induce the oriented crystallization of PBF and construct a biomimetic“brick-mud”hybrid structure. The finally prepared composite material exhibits excellent comprehensive performance， with a tensile strength of 92 MPa， an elastic modulus of 3.1 GPa， and O
2 barrier properties approximately 5 times higher than those of traditional materials， whose overall performance is superior to that of conventional PET
[109]. Additionally， FDCA can undergo polymerization with diamines containing cyclobutyl or —C(CF
3)
2 groups， thereby yielding transparent polyamide films that possess both excellent thermal stability and good flexibility. These films exhibit high selectivity and permeability in CO/CH
4 and H
2/CH
4 separation， along with outstanding anti-plasticization properties， demonstrating significant practical application value in addressing practical issues such as energy shortages and environmental pollution.
In the field of biomedical materials， researchers have carried out molecular-level functional design of FDCA and its derivatives， endowing them with great potential in drug release and antibacterial material applications. FDCA itself acts as a strong chelating agent， capable of chelating with metal ions such as Ca2+， Cu2+， and Pb2+， which provides an important foundation for the application of related medical materials. Furthermore， amide compounds synthesized by the condensation of FDCA with aniline exhibit certain antibacterial activity， significantly expanding their potential applications in the field of antibacterial materials. In addition， PEF， with its excellent biodegradability， is gradually expanding into the high-end medical consumables sector， with applications including disposable medical product packaging and medical X-ray films. This fully demonstrates its great potential in replacing traditional petroleum-based materials and promoting the development of green medical devices. In the relevant research field， liquid crystalline polymers (LCPs) prepared using FDCA as a key monomer integrate outstanding functional performance and environmental sustainability， and have evolved into a core research direction for high-end green functional materials. In addition， the furan ring in FDCA has a unique rigid planar structure and high linear symmetry， which provides a key foundation for forming higher-order liquid crystal phase structures. Therefore， the LCPs prepared based on FDCA not only retain the high thermal stability and excellent mechanical strength of traditional LCPs but also exhibit better gas barrier properties. At present， various new structural LCPs have been successfully synthesized and demonstrate broad application prospects in emerging fields such as fiber composites， 5G electronic packaging， and high-barrier packaging materials. In addition， FDCA ester-based polymers prepared through esterification possess excellent thermal stability due to the furan ring in their structure， providing a key guarantee for their long-term use in high-temperature environments. Based on these performance advantages， FDCA ester-based polymers can be widely applied in fields such as high-performance packaging materials， specialty fibers， and engineering plastics. In addition， with their renewable and recyclable properties， these materials play a key role in reducing carbon emissions and improving material recycling efficiency， and are expected to promote the transformation of the entire plastics industry toward a green and sustainable direction.
In summary， FDCA， as a key platform compound that can replace traditional petroleum-based materials， plays an indispensable core role in the development of high-performance bio-based polymers and will further drive the relevant industries toward a green and low-carbon transformation. Promoting the large-scale commercial application of FDCA can not only significantly replace the use of petroleum-based products and reduce dependence on non-renewable resources， but also achieve effective carbon emission reduction throughout the entire life cycle， thereby providing key support for building a sustainable production system and strongly driving the related industries toward a green and low-carbon development. Moreover， accelerating the industrialization process of FDCA is not only to achieve high-value utilization of biomass resources， but also a core initiative to support the implementation of the national“dual carbon”strategic goals and drive the entire chemical industry towards green， low-carbon， and high-quality development.
7 Conclusion and outlook
This paper systematically summarizes the various synthetic pathways of FDCA and comprehensively evaluates them from the perspectives of economy， process complexity， cost and current state of industrialization. The study shows that the oxidation route using HMF as the raw material is considered to have the greatest potential for industrialization due to its simple process， high product selectivity， and significant economic benefits. This paper further systematically reviews and compares the development status of the mature industrial system and emerging system for the oxidation of HMF to produce FDCA. Among them， in terms of industrial applications， thermal catalysis has become dominant due to its mature processes， high reaction efficiency， and the ability to operate thermodynamically spontaneously. In contrast， although emerging systems such as electrocatalysis and biocatalysis show significant potential for green transformation， they still face challenges such as low catalyst stability and difficulties in scaling up. In addition， this paper employs the LCA method to systematically evaluate the environmental benefit of the current FDCA production process routes and further explores the development status and market prospects of its downstream product chain. Finally， based on the above analysis， the paper provides an outlook on the future development of FDCA production processes and the industry chain as follows.
(1) In the process of promoting the industrialization of the HMF oxidation pathway， achieving a large-scale， low-cost， and stable supply of HMF is a key prerequisite for the large-scale industrial production of FDCA. However， the high raw material cost of HMF significantly compresses the profit margin of FDCA， putting it at an economic disadvantage in market competition with traditional petroleum-based products such as TPA. Therefore， effectively reducing the production cost of HMF is a core measure to enhance the overall process economics of FDCA and improve its market competitiveness. To achieve this goal， it is first necessary to develop efficient HMF production processes， controlling costs from the source and thus getting rid of free from the dependence on high-cost raw materials. Then， it is essential to focus on optimizing the synthesis routes and subsequent purification processes of HMF， addressing key technical bottlenecks such as downstream separation and purification difficulties and product instability， and ultimately ensuring the stable and continuous production of HMF. The coordinated advancement of these two aspects is the key to enhancing the overall competitiveness of this technological route and achieving its large-scale production.
(2) Optimizing the reaction system and the process is also key to the efficient conversion of HMF to FDCA. Currently， most HMF catalytic systems rely on organic solvents or alkaline reaction environments， which lead to difficulties in FDCA separation， increased equipment corrosion， and a greater environmental burden， thereby limiting the overall process efficiency and sustainability. Therefore， in the future， by designing and developing green and sustainable reaction systems and combining them with continuous flow processes， it is expected to significantly reduce energy consumption and environmental impact while improving reaction efficiency. In addition， continuous-flow reaction technology， due to its excellent mass and heat transfer characteristics and ease of scale-up capacity， can effectively accelerate the reaction process， thereby improving the yield and selectivity of FDCA. Therefore， combining green media systems with continuous flow processes not only overcomes the inherent limitations of traditional intermittent reaction in process control and scale-up， but also achieves process intensification of the reaction. This method significantly promotes the development of the HMF oxidation process towards higher efficiency and lower energy consumption， providing key technological support for the large-scale industrial production of FDCA.
(3) At present， various derivatives derived from FDCA（such as PFF， polyesters， and polyamides）have successfully been commercialized， mainly used in high-value-added fields such as high-performance packaging， special industrial coatings， and eco-friendly plasticizers. To further accelerate the comprehensive commercialization process of FDCA， the key to future work lies in expanding the application scope of its downstream derivatives to achieve a diversified layout of product structure. Therefore， future research and development of high-value-added products under the FDCA should focus on key areas such as high-performance engineering plastics， bio-medical materials， new types of fibers， and composite materials. On this basis， it is necessary to continuously optimize material properties and improve synthesis and processing technologies to enhance the overall performance and market competitiveness of related products， thereby promoting their large-scale application and ultimately accelerating the commercialization process of the entire FDCA industry chain.
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