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. 2026 Oct 1;15(10):e70317. doi: 10.1002/open.70317

1,2,4,5‐Tetrazine‐Boron Halide Adduct Formation Unraveled in Solution and Solid State

Jona Voss 1,✉, Andreas Mix 2, Jan‐Hendrik Lamm 2, Beate Neumann 2, Hans‐Georg Stammler 2, Norbert Sewald 1
PMCID: PMC13629465  PMID: 42820753

Abstract

1,2,4,5‐Tetrazines are electron‐deficient heterocycles with four nitrogen atom‐localized lone pairs potentially acting as Lewis bases. While it has been shown that tetrazines, as electronically amphiphilic ligands, undergo anion–π, π–π, and transition metal‐based adduct formation reactions, adducts of tetrazines with main group metal Lewis acids have not yet been structurally characterized. We report spectroscopic and single crystal X‐ray diffraction (SC‐XRD) analyses of tetrazine‐boron halide adducts in solution and in the solid state, respectively. With the aid of (diffusion‐ordered) nuclear magnetic resonance (DOSY‐)NMR spectroscopy dynamic equilibria between tetrazine‐boron halide adducts have been proven, while solid state structures show localized 1:1 tetrazine‐boron halide adducts.

Keywords: DOSY NMR, Lewis acids, Lewis bases, N ligands, X‐ray diffraction

1,2,4,5‐Tetrazines form Lewis adducts with boron halides BX3 (X = Cl, Br), a process being visually observable by a vibrant color change from pink to red. In the solid state, localized 1:1 tetrazine‐BX3 adducts are present. In contrast, 1H (DOSY‐)NMR spectroscopic titration revealed dynamic equilibria between even over‐stoichiometric tetrazine‐BX3 adducts, corroborated by comparison of volumes derived theoretically, from solution and solid state.

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1. Introduction

1,2,4,5‐Tetrazines emerge as multifaceted building blocks in modern chemistry, essentially due to their four sp2 configured nitrogen atoms present in their aromatic ring and, subsequently, their energetically low π*‐type lowest unoccupied molecular orbital (LUMO) [1], making them suitable substrates for inverse electron demand Diels–Alder reactions (IEDDA) [2], anion–π‐ [3] and π–π‐interacting [4, 5, 6] adduct formation reactions, but also prone to reduction to radical anions and dihydrotetrazines [7, 8, 9]. Contrary, tetrazines exhibit an amphiphilic electronic situation due to their four nitrogen‐centered lone pairs, being able to act as Lewis bases as demonstrated by intermolecular tetrazine N⋯H contacts in the solid state [4, 10, 11] and azaphilic additions to tetrazines [12, 13, 14], particularly the formation of tetrazine‐transition metal complexes [1, 15, 16]. Generally, tetrazines are very weak bases with the conjugate acid having a pK a < 0 [16, 17, 18], giving rise to unstable adducts. However, furnishing tetrazines with donor group containing substituents in 3‐ and 6‐position, such as 2‐pyridinyl or 2‐pyrimidinyl [15, 19] stabilizes these adducts. While the field of tetrazine‐transition metal adducts has been pioneered by Kaim and others [1, 15], tetrazine‐main group element adducts remain scarcely touched. Interestingly, there is only one report on a tetrazine‐main group element adduct that can be considered, tetrazine‐borane: In 2025, Zhu and colleagues reported on intramolecularly difluoroboronated tetrazines, possessing BF2 groups coordinated by a tetrazine nitrogen atom and an oxygen atom of a pendant 2‐oxyphenyl substituent (Scheme 1a) [20]. Additionally, Wegner and colleagues postulate the formation of a catalytically active intermolecular tetrazine‐bisborane complex, which, however, could not be characterized [21]. It has recently been shown that the reaction between a bis(pyrazolyl)tetrazine and two equivalents of bis(pentafluorophenyl)borane yields a 1:2 adduct; however, the tetrazine moiety was reduced to a 1,4‐dihydrotetrazine motif under oxidative H2 release from the borane [22]. Further, the addition of tetrazine to a dialkylgallium moiety by cooperative action of a Lewis basic phosphane moiety has been shown [23]. We herein report on the characterization of Lewis acid base adducts between 3,6‐diphenyl‐1,2,4,5‐tetrazine and boron halides in solution and solid state by combination of UV‐Vis and diffusion‐ordered nuclear magnetic resonance (DOSY‐NMR) spectroscopic and single‐crystal X‐ray diffraction (SC‐XRD) analyses.

SCHEME 1.

SCHEME 1

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(a) Tetrazine‐borane adducts reported in the literature [20, 21] (R = alkyl, alkenyl, aryl; R′ = H, Me, OMe, Br) and adducts discussed in this work and (b) synthesis of tetrazine 3 from benzonitrile 1 and adduct formation reactions with boron halides.

2. Results and Discussion

In 2019 Wombacher and colleagues might have given the first hints to the presence of a tetrazine‐boron adduct, attempting a methyl deprotection of a (methoxymethyl)tetrazine with BBr3, during which the tetrazine’s typical reddish‐pink color changed to orange [24]. Addition of methanol after completion of the reaction re‐established the tetrazine’s parent color, hinting to the labile nature of the putatively formed adduct. Eager to elaborate on this phenomenon, we investigated the reaction between structurally simple 3,6‐diphenyl‐1,2,4,5‐tetrazine (TzPh2, 3) [25] and boron halides.

Thiol‐catalyzed condensation between benzonitrile 1 and hydrazine hydrate affords 1,4‐dihydrotetrazine (dTzPh2, 2), which was structurally characterized by SC‐XRD (see below and Supporting Information), and is readily oxidized by CuII‐catalysis with air to obtain tetrazine 3 (Scheme 1b).

Immediate color change from pink to orange was observed after addition of BCl3 and BBr3 to a solution of tetrazine 3 in CH2Cl2, being in line with Wombacher’s report [24]. UV–Vis spectroscopic analyses of the obtained solutions (Figure 1, left) revealed hypsochromic shifts of the tetrazine’s parent absorption band at 547 to 498 nm (3 • n BCl3) and to 506 nm (3 • n BBr3), respectively, matching the observed color change from pink to orange [26].

FIGURE 1.

FIGURE 1

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Left: UV–Vis spectra of TzPh2 3 and the adducts TzPh2 3 • BX3 (X = Cl, Br) in dichloromethane (the spectra were virtually similar for n = 1, 2.5); right: expanded regions of 1H NMR spectra (600 MHz, 293 K, dichloromethane‐d 2) of TzPh2 3 with different equivalents n of BCl3 and BBr3 (signal sets remain virtually isochronous with more equivalents of BX3).

1H NMR spectroscopic investigation of mixtures of tetrazine 3 and BX3 (X = F, Cl, Br, I) showed different findings: While addition of the weakest Lewis acid BF3 to tetrazine 3 caused no significant shift of the signals, mixtures with BCl3 and most notably with BBr3 caused shifts of all observable signals hinting to adduct formation. Addition of BI3 caused immediate and complete degradation of tetrazine 3. Clearly, the association process of tetrazine with BX3 correlates with the Lewis acidity of boron trihalides increasing in the order BF3 < BCl3 < BBr3 < BI3 [27, 28, 29]. Looking more closely at the 1H NMR spectra of tetrazine 3 + n BX3 (with n = 0–5.0 and X = Cl, Br; Figure 1, right) two major findings can be observed: First, spectra of tetrazine 3 + 0.5 BX3 show single signal sets for the protons of both phenyl substituents, indicative for dynamic B⋯N contacts between the adjacent N atoms. Second, for tetrazine 3 + n BBr3 from n = 0 to 1.0 the signals shift toward each other, while only showing a small shift up to n = 2.0 and remaining virtually isochronous for n = 2–5, indicating that tetrazine 3 is nearly coordinatively saturated with one equivalent of BBr3. Contrary, tetrazine 3 seems to be coordinatively saturated only with at least two equivalents of BCl3 as indicated by merging signals from n = 0 to 2.0. Upon addition of methanol to mixtures of tetrazine 3 and BCl3 or BBr3, the tetrazine’s parent pink color is retained and re‐isolation of tetrazine 3 can be confirmed by NMR analyses.

The adduct formation reactions of TzPh2 3 with BX3 (X = Cl, Br) were also monitored by 1H diffusion ordered (DOSY‐)NMR spectroscopy (Figure 2). Titration of TzPh2 3 with up to 5.0 equivalents of BX3 (X = Cl, Br) confirmed the trends observed from the 1H NMR spectra. A comparison with the solvodynamic volume of free tetrazine, V s(TzPh2 3) = 262 ± 8 Å3, shows that V s of 3 + n BBr3 strictly increases up to n = 1 with 545 ± 16 Å3 and up to n = 2 with 469 ± 14 Å3 for 3 + n BCl3. Even though only small shifts in the 1H NMR spectra of tetrazine 3 + n BBr3 were observed with n > 1 (see Figure 1, right), DOSY analyses clearly show the presence of larger aggregates with n = 2 (V s = 618 ± 19 Å3). Within the margins of error, solvodynamic volumes stagnate for both adducts with increasing n each (see also Supporting Information: Chapter 3).

FIGURE 2.

FIGURE 2

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Solvodynamic volumes V s of TzPh2 3 + n BX3 (X = Cl, Br) with different equivalents of BX3 (n = 0–5.0) obtained from 1H DOSY‐NMR spectroscopic measurements with mean errors in dichloromethane‐d 2 at 293 K (refer to Supporting Information: Chapter 3).

Notably, the largest solvodynamic volume V s,max of 3 + n BBr3 still is about 32% larger than V s,max of 3 + n BCl3 (both obtained with n = 2), even though BCl3 and BBr3 show similar van der Waals volumes V vdW of 87.2 and 92.3 Å3 (ΔV vdW = 5.1 Å3), respectively (see Supporting Information: Chapter 3). It is likely that the adduct 3 • n BBr3, is a significantly more polar species than 3 • n BCl3 [27, 28, 29] and possesses a larger solvation shell consisting of polar molecules such as BBr3 itself and dichloromethane. Even though V s,max(3 + n BCl3) is only reached with n ≥ 2, three major indications prompt that the dominant species in solution still is a 1:1 adduct, 3 • BCl3: First, since both BCl3 and BBr3 have similar V vdW, but BBr3 is the stronger Lewis acid, the fact that tetrazine 3 already shows strong adduct formation with just one equivalent of BBr3 indicates that tetrazine 3 is only coordinatively monosaturated in the presence of an excess of BCl3 (n ≥ 2). Second, 2′,5′‐di‐tert‐butyl‐p‐terphenyl (p‐Ter t Bu2) was synthesized as reference compound resembling tetrazine 3 • 2 BX3 with V vdW = 434 Å3 [compared with similar V vdW of 3 • 2 BCl3 (415 Å3) and 3 • 2 BBr3 (425 Å3)] and V s = 634 ± 19 Å3, which exceeds V s,max(3 + n BCl3) by 35% (for more information see Tables S2 and S3). Given both matching V vdW and V s, as well as the additionally observed homotopicity of the phenyl substituents from 1H NMR signals of TzPh2 3 • 2 BX3 (X = Cl, Br, Figure 1, right), the symmetrically substituted p‐Ter t Bu2 (Figure 3) is likely to be a suitable model compound for 1:2 tetrazine‐BX3 adducts.

FIGURE 3.

FIGURE 3

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Molecular structure of p‐Ter t Bu2 as determined by SC‐XRD measurement with selected bond lengths (in Å). Thermal ellipsoids depicted at 50% probability. Hydrogen atoms were omitted for clarity. The omitted bond lengths of the central phenylene unit are generated by symmetry due to inversion at the ring centroid (symmetry code: 2 − X, 1 − Y, 1 − Z).

Strikingly, V s(p‐Ter t Bu2) = 634 ± 19 Å3 matches V s(3 + 2 BBr3) = 618 ± 19 Å3, indicating that tetrazine 3 is capable of accommodating up to two equivalents of BBr3 but not of BCl3. Third, evidence for 1:1 adduct formation was given by SC‐XRD measurements of crystals obtained from concentrated ortho‐difluorobenzene solutions of tetrazine 3 with excesses of BCl3 and BBr3 (Figure 4) [30].

FIGURE 4.

FIGURE 4

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Molecular structures of TzPh2 3 • BCl3 (left) and TzPh2 3 • BBr3 (right) as determined by SC‐XRD measurements with selected bond lengths (in Å). Thermal ellipsoids depicted at 50% probability. Only one of the two molecules in the asymmetric unit of TzPh2 3 • BCl3 and TzPh2 3 • BBr3 is shown. Bottom: views along the Caryl–Caryl axes of the tetrazine units with indicated out of plane angles φ (in °). Residual solvent molecules (for TzPh2 3 • BBr3) and hydrogen atoms were omitted for clarity. The reported lengths match those described for the other molecules in the asymmetric units within a 3σ margin of error, respectively.

We would like to point out that for crystallization a greaseless Young tube should be used and all compounds should be handled under strict exclusion of both air and moisture to obtain crystals of suitable quality for SC‐XRD measurements. Obtained crystals of 3 • BX3 (X = Cl, Br) were transferred and selected under dry N2 at 240 K in cryogenic oil to prevent decomposition. Both 1:1 adducts, tetrazine 3 • BCl3 (I41/a) and 3 • BBr3 (I2/a) crystallize with two crystallographically independent molecules in the asymmetric unit each, all of which show coordination of the BX3 moiety to a single N atom each with N⋯B distances d NB of 1.632(2) and 1.616(5) Å for 3 • BCl3 and 3 • BBr3, respectively. The distance d NB of 3 • BCl3 is slightly longer than for 3 • BBr3, but both are significantly longer than for the structural analogs pyridine • BCl3 [d NB = 1.593(1) Å] [31] and pyridine • BBr3 [d NB = 1.594(1) Å] [32], matching with tetrazine’s lower basicity compared with pyridine [17]. Comparison with free tetrazine 3 [25] shows that the bonding situation of the aromatic tetrazine core gets significantly altered upon adduct formation: While d NN near to the BX3 moiety increases slightly (d NN(3) = 1.318(1) Å), d NN distal to the BX3 moiety decreases significantly (cf. Figure 4), and all d CN vary strongly between 1.321(5) and 1.376(5) Å (d CN(3) = 1.348(1) Å) [25], deforming the tetrazine core into a boat with out‐of‐plane angles of 16.4°–21.1(1)° and 19.1°–22.3(3)° for 3 • BCl3 and 3 • BBr3, respectively. The tetracoordinated boron atoms adopt nearly perfect tetragonal geometries with τ 4 [33] = 0.968 (τ 4′ [34] = 0.961) for 3 • BCl3 and τ 4 = 0.979 (τ 4′ = 0.968) for 3 • BBr3, respectively.

The volumes extracted from SC‐XRD measurements V XRD of 3 • BCl3 (379 ± 1 Å3) and 3 • BBr3 (405 ± 1 Å3) are similar in magnitude, as expected from similar V vdW (334 and 339 Å3, respectively) (Table 1). As mentioned above (Figure 2), the sizes differ in solution, likely due to a larger solvation shell of 3 • BBr3 (545 ± 19 Å3) as compared with 3 • BCl3 (344 ± 10 Å3). Even though 1H (DOSY‐)NMR data indicate that tetrazine 3 forms over‐stoichiometric adducts with excess of BBr3, only 3 • BBr3 crystallized from solution—attempts isolating 3 • 2 BBr3 as crystalline solid under various conditions failed, again hinting to the dynamic equilibria between different adducts in solution.

TABLE 1.

Comparison of van der Waals volumes (V vdW) [35], volumes extracted from SC‐XRD measurements (V XRD), and of solvodynamic volumes (V s) of tetrazine 3 and its adducts 3 • BCl3 and 3 • BBr3. V XRD were calculated by dividing the unit cell’s volumes by Z, after subtracting any volumes of cocrystallized solvent molecules with literature values (for more information refer to Supporting Information: Chapters 3 and 4).

V vdW, Å3 V XRD, Å3 V s, Å3
TzPh2 3 253 273 ± 1 262 ± 8
TzPh2 3 • BCl3 334 379 ± 1 344 ± 10a
TzPh2 3 • BBr3 339 405 ± 1 545 ± 16a
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a

Data taken from measurements of tetrazine 3 with 1.0 equivalent of BX3 (X = Cl, Br) added.

During several attempts to obtain crystals of 3 • n BBr3 with suitable quality for SC‐XRD measurements, also crystals of reduced dTzPh2 2 • 2 BBr3 were obtained from a solution of TzPh2 3 and BBr3 after several days (Figure 5, bottom).

FIGURE 5.

FIGURE 5

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Molecular structures of dTzPh2 2 (top) and dTzPh2 2 • 2 BBr3‐α (bottom) as determined by SC‐XRD measurements with selected bond lengths (in Å). Thermal ellipsoids depicted at 50% probability. Residual solvent molecules (for dTzPh2 2) and hydrogen atoms attached to C atoms were omitted for clarity. Lengths and angles of dTzPh2 2 • 2 BBr3‐α match those described for dTzPh2 2 • 2 BBr3‐β within a 3σ margin of error (see Figure S5).

Authentic samples of dTzPh2 2 • 2 BBr3 were also obtained from a mixture of dTzPh2 2 and excess BBr3. The presence of the reduced 1,4‐dihydrotetrazine motif can be anticipated not only because of residual electron density at terminal N atoms (matching with H atoms) and the structural analogy to free dTzPh2 2 (Figure 5, top), but also because of significantly shortened C⋯N distances (d CN = 1.336(4) Å) of the C=N‐donating group as compared with TzPh2 3 • BBr3 (d CN = 1.359(5) Å) being in line with the expected higher basicity of the dihydro‐Tz over the Tz core [7]. Consequently, the N⋯B distances of dTzPh2 2 • 2 BBr3 are significantly shorter (d NB = 1.560(5) Å) than for TzPh2 3 • BBr3 (d NB = 1.616(5) Å).

The generation of dTzPh2 2 from a mixture of TzPh2 3 and BBr3 was unexpected and it could be shown by UV–Vis and NMR spectroscopic analyses that this reduction is a slow process with only about 10% of dTzPh2 2 present after 3 days at room temperature (see Supporting Information: Chapter 6). With TzPh2 3 being stable in solution and no observed formation of dTzPh2 2 from a mixture of TzPh2 3 and BCl3, it is hypothesized that due to Lewis acid coordination of BBr3 to tetrazine 3 its susceptibility to reduction is increased enough to be reduced to dTzPh2 2. Likely, due to the high tendency of hydrolysis, 3 • BBr3 is reduced by bromide ions, originating from hydrolysis of the BBr3 unit with trace water, a similar reduction of tetrazine 3 being described upon coordination with Sc3+ [36]. While solid state structures of free dTzPh2 2 and dTzPh2 2 • 2 BBr3 (Figure 5) show the presence of only 1,4‐dihydro isomers, (DOSY‐)NMR spectroscopic investigation of dTzPh2 2 + n BBr3 indicate the presence of different isomers (see Supporting Information: Chapter 6, NMR spectrum 13).

3. Conclusion

1,2,4,5‐Tetrazines have been shown to act as Lewis bases forming adducts with boron halides BX3 of sufficient Lewis acidity (X = Cl, Br). While these adducts are of dynamic nature in solution as corroborated by 1H (DOSY‐)NMR titration, a comparison of molecular volumes derived theoretically, from solution, and from solid state indicates that tetrazine 3 forms 1:1 adducts with BCl3, 3 • BCl3, and is able to coordinate up to two equivalents of BBr3 forming 3 • 2 BBr3. With the aid of structures obtained from SC‐XRD measurements we report on the first structurally characterized tetrazine main group element adducts. These adducts were shown to be labile and highly prone to solvolysis, regenerating the parent tetrazine. For tetrazine 3 • n BBr3 the unprecedented reduction to the corresponding 1,4‐dihydrotetrazine 2 • 2 BBr3 was observed, a reaction that might be reasoned by reduction of the highly electron deficient adduct 3 • n BBr3 [36] through in situ formed bromide ions. Based on analyses of association processes of tetrazine‐boron halides in solution and their molecular structures, we demonstrate that tetrazines act as weak donors and form labile adducts with a reductive degradation pathway [36]; insights, which might pave the way toward the use of tetrazines in catalysis and the rational design of tetrazine‐complexes [15].

Funding

This work was supported by the Studienstiftung des Deutschen Volkes.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supplementary Material

OPEN-15-e70317-s001.pdf (1.8MB, pdf)

Acknowledgments

Jona Voss thanks the German National Scholarship Foundation (Studienstiftung des deutschen Volkes) for a scholarship. The authors thank Lorena Storck for the design of a graphical abstract.

Open Access funding enabled and organized by Projekt DEAL.

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article.

References

  • 1. Stetsiuk O., Abhervé A., and Avarvari N., “1,2,4,5‐Tetrazine Based Ligands and Complexes,” Dalton Transactions 49 (2020): 5759, 10.1039/D0DT00827C. [DOI] [PubMed] [Google Scholar]
  • 2. Mayer S. and Lang K., “Tetrazines in Inverse‐Electron‐Demand Diels–Alder Cycloadditions and Their Use in Biology,” Synthesis 49 (2017): 830. [Google Scholar]
  • 3. Savastano M., García‐Gallarín C., La López de Torre M. D., Bazzicalupi C., Bianchi A., and Melguizo M., “Anion‐π and Lone Pair‐π Interactions With s‐Tetrazine‐Based Ligands,” Coordination Chemistry Reviews 397 (2019): 112, 10.1016/j.ccr.2019.06.016. [DOI] [Google Scholar]
  • 4. Voss J., Stammler H. G., and Sewald N., “Synthesis and Crystal Structure of 2,2,2‐Trichloroethyl N‐{4‐6‐(1‐Hydroxyethyl)‐1,2,4,5‐Tetrazin‐3‐Ylbenzyl}carbamate,” Acta Crystallographica Section E Crystallographic Communications 81 (2025): 164, 10.1107/S205698902500bp-linebreak0441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Oxtoby N. S., Blake A. J., Champness N. R., and Wilson C., “The Role of 1,2,4,5‐Tetrazine Rings in π–π Stacking Interactions,” CrystEngComm 5 (2003): 82, 10.1039/b302187d. [DOI] [Google Scholar]
  • 6. Voss J. and Lamm J.‐H., “Crystal Structures of Products From the BBr3‐Promoted Demethylation of 3‐(methoxymethyl)‐6‐Phenyl‐1,2,4,5‐Tetrazine,” Acta Crystallographica Section E: Crystallographic Communications (2026), 10.1107/S2056989026009527, accepted for publication. [DOI] [Google Scholar]
  • 7. Kaim W., “Electronic Structure of 1,4‐Dihydro‐1,2,4,5‐Tetrazines and of Related 1,4‐Dihydroaromatic Compounds,” Journal of the Chemical Society, Perkin Transactions 2 10 (1985): 1633, 10.1039/bp-linebreakp29850001633. [DOI] [Google Scholar]
  • 8. Fischer H., Müller T., Umminger I., Neugebauer F. A., Chandra H., and Symons M. C. R., “Radical Cations and Anions of 1,2,4,5‐Tetrazines: An Electron Spin Resonance and Cyclic Voltammetric Study,” Journal of the Chemical Society, Perkin Transactions 2 3 (1988): 413, 10.1039/P29880000413. [DOI] [Google Scholar]
  • 9. Razavi S. A. A., Morsali A., and Piroozzadeh M., “Redox Metal‐Organic Framework for Photocatalytic Organic Transformation: The Role of Tetrazine Function in Radical‐Anion Pathway,” Inorganic Chemistry 61 (2022): 19134, 10.1021/acs.inorgchem.2c02733. [DOI] [PubMed] [Google Scholar]
  • 10. Krieger C., Fischer H., and Neugebauer F. A., “3,6‐Diamino‐1,2,4,5‐Tetrazine: An Example of Strong Intermolecular Hydrogen Bonding,” Acta Crystallographica Section C Crystal Structure Communications 43 (1987): 1320, 10.1107/S0108270187092011. [DOI] [Google Scholar]
  • 11. Klapötke T. M., Preimesser A., and Stierstorfer J., “Thermally Stable 3,6‐Disubstituted 1,2,4,5‐Tetrazines,” Zeitschrift für Naturforschung B 68 (2013): 1310, 10.5560/znb.2013-3237. [DOI] [Google Scholar]
  • 12. Schnell S. D., Schilling M., Sklyaruk J., Linden A., Luber S., and Gademann K., “Nucleophilic Attack on Nitrogen in Tetrazines by Silyl‐Enol Ethers,” Organic Letters 23 (2021): 2426, 10.1021/acs.orglett.0c04113. [DOI] [PubMed] [Google Scholar]
  • 13. Faragó J., Novák Z., Schlosser G., Csámpai A., and Kotschy A., “The Azaphilic Addition of Organometallic Reagents on Tetrazines: Scope and Limitations,” Tetrahedron 60 (2004): 1991, 10.1016/j.tet.2004.01.013. [DOI] [Google Scholar]
  • 14. Lorincz K., Kotschy A., Tammiku‐Taul J., Sikk L., and Burk P., “Computational Study on the Reactivity of Tetrazines Toward Organometallic Reagents,” Journal of Organic Chemistry 75 (2010): 6196, 10.1021/jo101119n. [DOI] [PubMed] [Google Scholar]
  • 15. Kaim W., “The Coordination Chemistry of 1,2,4,5‐Tetrazines,” Coordination Chemistry Reviews 230 (2002): 127, 10.1016/S0010-8545(02)00044-9. [DOI] [Google Scholar]
  • 16. Kaim W. and Kohlmann S., “Four Bridging Bis Chelate Ligands With Very Low Lying π* Orbitals. MO Perturbation Calculations, Electrochemistry, and Spectroscopy of Mononuclear and Binuclear group 6 metal Tetracarbonyl Complexes,” Inorganic Chemistry 26 (1987): 68, 10.1021/ic00248a016. [DOI] [Google Scholar]
  • 17. Spanget‐Larsen J., “A Structure–Reactivity Relationship for the Basicity of Aza‐Arenes,” Journal of the Chemical Society, Perkin Transactions 2 3 (1985): 417, 10.1039/P29850000417. [DOI] [Google Scholar]
  • 18. Trifonov R. E., Zubarev V. Y., Malin A. A., and Ostrovskii V. A., “Basicity of 3,6‐Diphenyl‐1,2,4,5‐Tetrazine,” Chemistry of Heterocyclic Compounds 34 (1998): 111, 10.1007/BF02290622. [DOI] [Google Scholar]
  • 19. Schwach M., Hausen H.‐D., and Kaim W., “The First Crystal Structure of a Metal‐Stabilized Tetrazine Anion Radical: Formation of a Dicopper Complex Through Self‐Assembly in a Comproportionation Reaction,” Inorganic Chemistry 38 (1999): 2242, 10.1021/ic9814625. [DOI] [Google Scholar]
  • 20. Zhu X., Zhang J., Geng H., et al., “Difluoroboronated Tetrazine Probes for Rapid Bioorthogonal Fluorescence Activation, No‐Wash STED Imaging, and Triggered Drug Release,” Science Advances 11 (2025): eadw1098, 10.1126/sciadv.adw1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Hong L., Ahles S., Heindl A. H., et al., “An Air‐Stable Bisboron Complex: A Practical Bidentate Lewis Acid Catalyst,” Beilstein Journal of Organic Chemistry 14 (2018): 618, 10.3762/bjoc.14.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Liu H., Ju S., Tang B., et al., “Nitrogen‐Rich B(C6F5)2‐Derived Polycyclic Molecules,” Chemical Communications 62 (2026): 14577, 10.1039/D6CC03470E. [DOI] [PubMed] [Google Scholar]
  • 23. Buth J., Neumann B., Lamm J.‐H., Stammler G., Vishnevskiy Y. V., and Mitzel N. W., “Atom‐Economic ring‐Contraction of Pyridazine and Phthalazine Induced by an Oxygen‐Bridged Ga/P FLP,” Dalton Transactions 32 (2026): 11862, 10.1039/d6dt01410k. [DOI] [PubMed] [Google Scholar]
  • 24. Baalmann M., Ziegler M. J., Werther P., Wilhelm J., and Wombacher R., “Enzymatic and Site‐Specific Ligation of Minimal‐Size Tetrazines and Triazines to Proteins for Bioconjugation and Live‐Cell Imaging,” Bioconjugate Chemistry 30 (2019): 1405, 10.1021/acs.bioconjchem.9b00157. [DOI] [PubMed] [Google Scholar]
  • 25. Ranjbar‐Karimi R., CCDC 1580478: Experimental Crystal Structure Determination (Cambridge Crystallographic Data Centre, 2017). [Google Scholar]
  • 26. Wilkovitsch M., Kuba W., Keppel P., et al., “Transforming Aryl‐Tetrazines Into Bioorthogonal Scissors for Systematic Cleavage of Trans‐Cyclooctenes,” Angewandte Chemie International Edition 64 (2025): e202411707, 10.1002/anie.v64.5. [DOI] [PubMed] [Google Scholar]
  • 27. Grant D. J., Dixon D. A., Camaioni D., Potter R. G., and Christe K. O., “Lewis Acidities and Hydride, Fluoride, and X‐Affinities of the BH(3‐n)Xn Compounds for (X = F, Cl, Br, I, NH2, OH, and SH) From Coupled Cluster Theory,” Inorganic Chemistry 48 (2009): 8811, 10.1021/ic901092x. [DOI] [PubMed] [Google Scholar]
  • 28. Ranasinghe S., Li Y., Andrews M. E., Akram M. O., Thornton R. A., and Martin C. D., “Müller Versus Gutmann‐Beckett for Assessing the Lewis Acidity of Boranes,” Chemical Communications 61 (2025): 10182, 10.1039/D5CC02299A. [DOI] [PubMed] [Google Scholar]
  • 29. Thayyil A. and Parambil P. C., “Lewis Acidity Trend of Boron and Aluminium Trihalides: If Not π Back‐Bonding, What Else?,” ChemPhysChem 24 (2023): e202200761, 10.1002/cphc.bp-linebreakv24.5. [DOI] [PubMed] [Google Scholar]
  • 30.Details of the X‐ray Investigations are Given in the Tables S4–S6 in the Supporting Information. CCDC 2579984–2579989 Contain the Supplementary Crystallographic Data for this Paper. This Data can be Obtained Free of Charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/conts/retrieving.html.
  • 31. Töpel K., Hensen K., and Trömel M., “Bortrichlorid–Pyridin,” Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry 37 (1981): 969, 10.1107/S0567740881004792. [DOI] [Google Scholar]
  • 32. Iijima K., Oonishi I., and Shibata S., “The Crystal and Molecular Structure of Pyridine‐Boron Tribromide,” Chemistry Letters 12 (1983): 251, 10.1246/cl.1983.251. [DOI] [Google Scholar]
  • 33. Yang L., Powell D. R., and Houser R. P., “Structural Variation in Copper(I) Complexes With Pyridylmethylamide Ligands: Structural Analysis With a New Four‐Coordinate Geometry Index, tau4,” Dalton Transactions 9 (2007): 955, 10.1039/B617136B. [DOI] [PubMed] [Google Scholar]
  • 34. Rosiak D., Okuniewski A., and Chojnacki J., “Novel Complexes Possessing Hg–(Cl, Br, I)⋯O C Halogen Bonding and Unusual Hg2S2(Br/I)4 Kernel. The Usefulness of τ4′ Structural Parameter,” Polyhedron 146 (2018): 35, 10.1016/j.poly.2018.02.016. [DOI] [Google Scholar]
  • 35. Zhao Y. H., Abraham M. H., and Zissimos A. M., “Fast Calculation of Van der Waals Volume as a Sum of Atomic and Bond Contributions and Its Application to Drug Compounds,” Journal of Organic Chemistry 68 (2003): 7368, 10.1021/jo034808o. [DOI] [PubMed] [Google Scholar]
  • 36. Fukuzumi S., Yuasa J., and Suenobu T., “Scandium Ion‐Promoted Reduction of Heterocyclic N=N Double Bond. Hydride Transfer Vs Electron Transfer,” Journal of the American Chemical Society 124 (2002): 12566, 10.1021/ja026592y. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material

OPEN-15-e70317-s001.pdf (1.8MB, pdf)

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article.

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