Gentle Hydrogen-Bond Catalysts Make Crystalline COFs in Hours

Covalent organic frameworks, the atomically precise porous polymers that chemists have spent nearly two decades trying to perfect, are usually born in harsh conditions. Strong acids or bases drive the reactions that stitch their building blocks together, but those conditions are finicky, slow and often punishing to delicate monomers. A team led by Donglin Jiang at the National University of Singapore now reports in Nature Synthesis a fundamentally different approach: hydrogen-bonding catalysis, in which a simple, reusable organocatalyst called benzimidazole guides the assembly of COFs gently, rapidly and on a scale that could finally bring these materials out of the laboratory.

The significance of the result lies in what it replaces. Conventional COF synthesis typically demands days of heating under aggressive acid- or base-catalysed conditions, extensive screening of solvents and temperatures, and careful matching of reaction conditions to each monomer combination. Even then, many products emerge with imperfect crystallinity or compromised porosity, the two properties that make COFs valuable for gas separation, catalysis, energy storage and proton conduction. The new strategy, by contrast, produces imide-, imine-, hydrazone- and sp2-carbon-linked COFs within hours, with high crystallinity and porosity, using a catalyst that can be recovered and used again.

Benzimidazole occupies a special position among organic molecules because it is amphiprotic: it can donate a hydrogen bond through its N-H group and accept one through its pyridine-like nitrogen. That dual character is the engine of the new method. Unlike conventional acid or base catalysis, which activates monomers by proton transfer, the benzimidazole catalysts engage monomers, intermediates and transition states simultaneously through explicit hydrogen-bonding interactions, lowering the energy barrier at every step of the polymerization rather than at just one.

The authors demonstrate the approach most thoroughly on imide-linked COFs, a class prized for its chemical robustness and its applications in batteries, sensing and carbon capture. In the prototypical TAPB-PMDA-COF, formed from a triamine and a dianhydride, the catalyst accelerates the imidization reaction while promoting its reversibility, so that the growing network can continuously repair defects and settle into the thermodynamically favoured crystalline state. Powder X-ray diffraction profiles of the resulting materials show sharp reflections and narrow full widths at half maximum, hallmarks of long-range order that typically require days of solvothermal treatment to achieve.

Control is a second virtue of the method. Because the catalyst acts through noncovalent interactions rather than stoichiometric consumption, the reaction outcome can be tuned simply by varying the catalyst-to-monomer ratio. This knob allows the team to balance reaction rate against error correction: too little catalyst leaves the system slow and kinetically trapped, while the right proportion drives rapid bond formation and rapid bond exchange in parallel, the combination that crystalline polymer growth requires. The same logic extends across linkage chemistries, as the team showed by preparing the imine-linked TPB-DMTP-COF, the hydrazone-linked COF-43 and the sp2-carbon-conjugated sp2c-COF-16 under the same catalytic regime.

Theoretical calculations by Hongde Yu and Thomas Heine at the Technical University of Dresden, performed with density functional theory, support this mechanistic picture. The computations indicate that hydrogen-bonding interactions with the catalyst stabilize the transition states of the linkage-forming reactions and lower activation barriers for both the forward and reverse directions. Reversibility is the crucial ingredient: a network that can break and remake its bonds while it forms is one that can anneal itself into crystallinity, whereas an irreversible polymerization locks in disorder.

Scalability has long been the Achilles heel of COF chemistry, because many celebrated syntheses yield only tens or hundreds of milligrams after days of reaction. The hydrogen-bonding protocol supports a 1,000-fold scale-up, and the catalyst itself can be reused, addressing both the cost and the waste streams that would otherwise accompany industrial production. The scaled materials retain the high crystallinity and porosity of their small-batch counterparts, suggesting that the catalytic mechanism is robust to the heat- and mass-transfer realities of larger reactors.

The practical payoff is illustrated by proton conduction, a property central to fuel cells and electrolyzers. COFs prepared by the new route achieve benchmark proton conductivity, consistent with the team’s earlier work showing that crystalline porous frameworks can serve as exceptional proton-conducting electrolytes when their pores are engineered with appropriate carrier chemistry. Because the hydrogen-bonding synthesis delivers frameworks with well-defined channels and high surface areas, the resulting membranes combine the structural order needed for efficient transport with the mechanical and chemical stability demanded by devices.

The strategy also draws on a distinguished lineage in organic chemistry. Explicit hydrogen-bonding organocatalysis, pioneered for enantioselective reactions by chemists such as Peter Schreiner and Eric Jacobsen, relies on small-molecule donors that activate substrates without transferring protons. Applying that philosophy to polymer crystallization is conceptually elegant: the same interactions that guide a single reaction’s transition state can, when applied throughout a growing network, guide the entire system toward order. The result is a synthesis that is simultaneously faster, milder and more general than the harsh protocols it replaces.

For a field whose promise has often outrun its practicality, the message is striking. A cheap, recyclable heterocycle, acting through nothing more exotic than hydrogen bonds, can now build some of the most sophisticated materials in chemistry in hours instead of days, at gram scale instead of milligram scale, and with the crystalline quality that applications demand. If the approach proves as general across monomer families as the initial results suggest, hydrogen-bonding catalysis may become the default route to covalent organic frameworks, and the porous architectures built from it may finally move from the pages of review articles into the membranes, electrodes and catalysts of working technology.

Subject of Research: Hydrogen-bonding organocatalysis for the rapid, scalable synthesis of crystalline covalent organic frameworks

Article Title: Synthesis of covalent organic frameworks through hydrogen-bonding catalysis

Article References: Ye, X., Tao, S., Yu, H., Heine, T., Shao, H., Mu, X., Liu, Y., Xu, H., Lin, M., & Jiang, D. (2026). Synthesis of covalent organic frameworks through hydrogen-bonding catalysis. Nature Synthesis. https://doi.org/10.1038/s44160-026-01180-8

Image Credits: AI Generated

DOI: 10.1038/s44160-026-01180-8

Keywords: covalent organic frameworks, hydrogen-bonding catalysis, benzimidazole, organocatalysis, porous materials, imide-linked COFs, crystallinity, proton conduction, polymer synthesis, Nature Synthesis, scale-up, reversible polymerization