Abstract
The ability to achieve a series of solid-state [2 + 2] cycloaddition reactions within related hydrogen-bonded co-crystals is reported. These multicomponent molecular solids contain either trans-1,2-bis(3-pyridyl)ethylene (3,3-BPE) or trans-1,2-bis(2-pyridyl)ethylene (2,2-BPE) as the reactant, along with one of two chlorinated anilines that behave as a template, namely 2,3,5,6-tetrachloroaniline (C6H3Cl4N) or 2,4,6-trichloroaniline (C6H4Cl3N). For each of the four unique organic solids, the co-crystallization process yields a three-component hydrogen-bonded assembly with a formula of either 2(C6H3Cl4N)·(3,3-BPE), 2(C6H4Cl3N)·(3,3-BPE), 2(C6H3Cl4N)·(2,2-BPE), or 2(C6H4Cl3N)·(2,2-BPE). In all co-crystals, these anilines template up to a quantitative yield for the photoreaction since they are able to engage in both N-H···N hydrogen bonds and homogeneous face-to-face π–π stacking interactions, which position the ethylene groups within the different reactant molecules in a suitable location to photoreact. These results complete the series for the remaining symmetric bipyridine-based reactants to undergo a solid-state [2 + 2] cycloaddition reaction utilizing these chlorinated anilines. This work expands and illustrates the potential for these chlorinated anilines to serve as reliable molecular templates that crystal engineers can utilize to control the organic solid state and achieve photoreactions.
1 Introduction
The intentional design of organic solids that will undergo the light-induced [2 + 2] cycloaddition reaction continues to be an active area of research within crystal engineering (Li and MacGillivray, 2025). In most cases, the photoreaction is achieved using a template-based approach since most reactants are photostable as a single-component solid (Biradha and Santra, 2013; Gan et al., 2018; Kole and Mir, 2022). The template (i.e., co-crystal former) overcomes issues with crystal packing by taking advantage of the strength and directionality of non-covalent interactions that yield a different crystal form compared to the single-component structure (MacGillivray, 2008). In general, hydrogen and halogen bonds have been utilized to position a pair of carbon–carbon double bonds (C=C) in a suitable orientation and distance to photoreact and form a cyclobutane-based product (Schmidt, 1971).
A continued focus for this research group has been the formation of photoreactive co-crystals by exploiting homogeneous face-to-face π–π stacking interactions from various chlorinated aromatics that behave as a molecular template (Andren et al., 2024; Bosch et al., 2023; Shapiro et al., 2021). Recently, we reported the ability of a pair of chlorinated anilines, namely 2,3,5,6-tetrachloroaniline (C6H3Cl4N) and 2,4,6-trichloroaniline (C6H4Cl3N) (Scheme 1), that behave as templates to achieve a photoreaction when combined with trans-1,2-bis(4-pyridyl)ethylene (4,4-BPE) (White et al., 2025). These three-component co-crystals were photoreactive since the anilines engaged in both N-H···N hydrogen bonds and π–π stacks in a homogeneous face-to-face pattern that positioned the ethylene group on the reactant in an appropriate location to photoreact. In this original contribution, density functional theory calculations determined that the homogeneous stacking pattern is preferred over a theoretical heterogeneous pattern, which is essential to achieve a photoreactive solid since the reactant was also found in an infinite and homogeneous column, which then satisfied the requirements for a [2 + 2] cycloaddition reaction (White et al., 2025).
SCHEME 1
Structures of the hydrogen-bond donors and acceptors within the various co-crystals.
With the goal of expanding this research to the remaining symmetric bipyridine-based reactants, namely trans-1,2-bis(3-pyridyl)ethylene (3,3-BPE) and trans-1,2-bis(2-pyridyl)ethylene (2,2-BPE) (Scheme 1), a series of co-crystallization and photochemical studies were performed. The combination of these reactants and the two previously studied chlorinated anilines yielded four additional co-crystals, namely 2(C6H3Cl4N)·(3,3-BPE), 2(C6H4Cl3N)·(3,3-BPE), 2(C6H3Cl4N)·(2,2-BPE), and 2(C6H4Cl3N)·(2,2-BPE). In all cases, a hydrogen-bonded three-component co-crystal was obtained, where again the chlorinated anilines engage in both N-H···N hydrogen bonds and homogeneous face-to-face π–π stacking interactions that position the ethylene group to undergo a photoreaction upon exposure to ultraviolet light. In three of the four co-crystals, a quantitative photoreaction was achieved, generating a stereoselective photoproduct, either rctt-tetrakis(3-pyridyl)cyclobutane (3,3-TPCB) (Scheme 2a) or rctt-tetrakis(2-pyridyl)cyclobutane (2,2-TPCB) (Scheme 2b). The results presented in this study illustrate that these chlorinated anilines are an emerging class of molecular templates to achieve various solid-state [2 + 2] cycloaddition reactions. Finally, taking advantage of the strong tendencies of these chlorinated anilines, along with other functionalized chlorinated benzenes, to stack in infinite and homogeneous arrays that engage in various non-covalent interactions illustrates their great potential as an unexplored co-crystal former for controlling the physical and chemical properties of organic solids.
SCHEME 2
Structure of the solid-state [2 + 2] cycloaddition reaction of (a) 3,3-BPE to produce 3,3-TPCB and (b) 2,2-BPE to produce 2,2-TPCB.
2 Experimental section
2.1 Materials
The templates 2,3,5,6-tetrachloroaniline (C6H3Cl4N) and 2,4,6-trichloroaniline (C6H4Cl3N) along with the reactant trans-1,2-bis(2-pyridyl)ethylene (2,2-BPE) were all purchased from Sigma-Aldrich Chemical (St. Louis, MO, United States) and used as received. The reactant trans-1,2-bis(3-pyridyl)ethylene (3,3-BPE) was prepared using a previously reported method (Gordillo et al., 2013; Quentin and MacGillivray, 2020a; 2020b). Reagent-grade ethanol was also purchased from Sigma-Aldrich Chemical and was used without purification. All co-crystallization studies were performed in 20 mL scintillation vials.
2.2 General methods
Photoreactions were conducted using UV-radiation from a 450 W medium-pressure mercury lamp in an ACE glass photochemistry cabinet. Each co-crystal was dried and placed between a pair of Pyrex glass plates for irradiation. Then, all of the glass-plated co-crystal samples were placed into the photoreactor and exposed to broadband ultraviolet light from the mercury vapor bulb. All of the co-crystal solids were mixed daily to expose a fresh surface to ultraviolet light. The photoreactivity of each co-crystal was determined using 1H nuclear magnetic resonance spectroscopy (1H NMR) on a Bruker Ascend Evo 400 MHz Spectrometer using DMSO-d6 as the solvent. Single-crystal X-ray diffraction data were collected on a Bruker D8 VENTURE DUO diffractometer equipped with an IµS 3.0 microfocus source operated at 75 W (50 kV, 1.5 mA) to generate Mo Kα radiation (λ = 0.71073 Å) using a PHOTON III detector. Powder X-ray diffraction data were collected at room temperature on a Bruker D8 Advance X-ray Diffractometer using Cu Kα radiation (λ = 1.54056 Å) between 5° and 40° two-theta.
2.3 Synthesis of co-crystals that contain trans-1,2-bis(3-pyridyl)ethylene
Co-crystals of 2(C6H3Cl4N)·(3,3-BPE) and 2(C6H4Cl3N)·(3,3-BPE) were both prepared by dissolving 25.0 mg of 3,3-BPE in 2.0 mL of ethanol, which was then combined with a separate 1.0 mL ethanol solution containing either 63.4 mg of C6H3Cl4N or 53.9 mg of C6H4Cl3N (1:2 molar ratio). The caps were removed from the combined solutions to allow for slow evaporation. Within 2 days, along with the loss of most solvent, crystals formed that were suitable for single-crystal and powder X-ray diffraction experiments.
2.4 Synthesis of co-crystals that contain trans-1,2-bis(2-pyridyl)ethylene
In a similar manner, co-crystals of 2(C6H3Cl4N)·(2,2-BPE) and 2(C6H4Cl3N)·(2,2-BPE) were prepared by dissolving 25.0 mg of 2,2-BPE in 2.0 mL of ethanol; then, it was combined with either a 1.0 mL ethanol solution of 63.4 mg of C6H3Cl4N or 53.9 mg of C6H4Cl3N (1:2 molar ratio). After combining the two solutions, the cap was removed to allow for slow evaporation. Again, within 2 days, crystals formed that were suitable for single-crystal and powder X-ray diffraction experiments after the loss of most of the ethanol.
3 Results and discussion
3.1 Structure and photoreactivity of 2(C6H3Cl4N)·(3,3-BPE)
The molecular components of 2(C6H3Cl4N)·(3,3-BPE) crystallize into the centrosymmetric monoclinic space group C2/c. Within the asymmetric unit is a whole molecule of C6H3Cl4N and half a molecule of 3,3-BPE where applying inversion symmetry generates the remainder of the reactant molecule. This three-component co-crystal is sustained primarily by N-H···N hydrogen bonds [N···N 2.997 (4) Å] that result in a discrete molecular solid (Figure 1). The second N-H group is found to engage in N-H···Cl contacts [N···Cl 3.619 (5) Å] with an ortho-chlorine, with respect to the amine group, on a neighboring aniline (Figure 2). The ethylene bridge within 3,3-BPE is found to be completely ordered at 290 K. The hydrogen-bond donor and acceptor are found twisted away from each other at a value of 42.60° within the three-component assembly at 290 K (Figure 1). Finally, these three-component hydrogen-bonded assemblies also interact with neighbors through various C-H···Cl contacts (Hathwar et al., 2010), namely linear [C···Cl 3.945 (4) Å] and bifurcated [C···Cl 3.679 (5) and 3.900 (5) Å], which generate an extended solid (Figure 3).
FIGURE 1
X-ray crystal structure of 2(C6H3Cl4N)·(3,3-BPE) illustrating the N-H···N hydrogen bonds along with the infinite homogeneous face-to-face π–π stacking pattern of the aromatic rings. The N-H···N hydrogen bonds are shown as yellow dashed lines.
FIGURE 2
X-ray crystal structure of 2(C6H3Cl4N)·(3,3-BPE) illustrating the N-H···N hydrogen bonds along with the N-H···Cl contacts. The N-H···N hydrogen bonds and N-H···Cl contacts are shown as yellow dashed lines.
FIGURE 3
X-ray crystal structure of 2(C6H3Cl4N)·(3,3-BPE) illustrating the N-H···N hydrogen bonds and the different types of C-H···Cl contacts. The N-H···N hydrogen bonds and C-H···Cl contacts are shown as yellow dashed lines.
As expected, molecules of C6H3Cl4N are found to engage in homogenous face-to-face π–π stacking interactions (Figure 1). These stacked anilines produce an infinite column with a centroid-to-centroid distance of 3.8601 (7) Å, which is equal to the crystallographic b-axis. Due to the π-stacking pattern and N-H···N hydrogen bonds, the reactant 3,3-BPE, along with the ethylene group, is also found in an infinite stack (Figure 1). As a result of translational symmetry, these reactive centers are parallel and within the distance limit to achieve a solid-state [2 + 2] cycloaddition reaction as defined by the topochemical postulate (Schmidt, 1971).
To determine whether 2(C6H3Cl4N)·(3,3-BPE) would undergo a photoreaction, a dried powdered sample was exposed to ultraviolet radiation in a photochemical cabinet from a mercury vapor bulb. A [2 + 2] cycloaddition reaction was observed using 1H NMR by the substantial loss of the olefinic signal at 7.44 ppm on 3,3-BPE, along with the concomitant appearance of a cyclobutane signal at 4.71 ppm, confirming the formation of the stereospecific photoproduct 3,3-TPCB (Scheme 2a) (Quentin and MacGillivray, 2020a). An overall yield of 98% for the solid-state [2 + 2] cycloaddition reaction was reached within 60 h of exposure (Supplementary Figures S1, S2).
To determine the purity of the bulk solid and compare it with the single-crystal structure for 2(C6H3Cl4N)·(3,3-BPE), a powder X-ray diffraction (PXRD) experiment was performed on the resulting solid. The diffractogram confirms that the solid material matches the reported co-crystal structure based on its calculated powder pattern from the single-crystal data (Supplementary Figure S9). This high level of purity for the bulk supports the observed near-quantitative yield for the photoreaction, since nearly all of the reactant molecules are in a suitable position to photoreact.
3.2 Structure and photoreactivity of 2(C6H4Cl3N)·(3,3-BPE)
The co-crystal 2(C6H4Cl3N)·(3,3-BPE) crystallizes into the centrosymmetric triclinic space group Pī. Similar to before, a whole molecule of C6H4Cl3N, along with half a molecule of 3,3-BPE, is found in the asymmetric unit. Applying inversion symmetry generates the remainder of the acceptor molecule and the three-component hydrogen-bonded co-crystal. This discrete molecular solid is sustained predominantly by N-H···N hydrogen bonds [N···N 3.093 (4) Å] (Figure 4). Unlike 2(C6H3Cl4N)·(3,3-BPE), the second N-H group in 2(C6H4Cl3N)·(3,3-BPE) does not form a hydrogen bond with any suitable acceptor group. Again, the ethylene group within 3,3-BPE is completely ordered at 290 K. The hydrogen-bond donor and acceptor are found twisted away from each other within the three-component assembly with a value of 49.06° at 290 K (Figure 4). Neighboring and stacked hydrogen-bonded assemblies are engaged in C-H···Cl contacts [C···Cl 3.736 (3) Å] between the ortho-chlorine, with respect to the amine, and the hydrogen atom between the nitrogen and ethylene bridge on the pyridine ring (Figure 4). A similar C-H···Cl contact pattern was also observed within the co-crystal 2(C6H4Cl3N)·(4,4-BPE) as previously reported by this research group (White et al., 2025).
FIGURE 4
X-ray crystal structure of 2(C6H4Cl3N)·(3,3-BPE) illustrating the N-H···N hydrogen bonds along with the infinite homogenous face-to-face π–π stacking pattern of the aromatic rings. The N-H···N hydrogen bonds and C-H···Cl contacts are shown as yellow dashed lines.
Essential to achieving a photoreactive co-crystal, both the hydrogen-bond donor and acceptor are once again found in a homogeneous face-to-face π-stacked pattern (Figure 4). These stacked aromatic rings lie along the crystallographic a-axis with a centroid-to-centroid distance of 3.890 (1) Å. Due to crystal symmetry, the ethylene groups, within the infinite column, are again found parallel and within a suitable distance to undergo a solid-state photoreaction. As previously stated, the combination of the homogeneous face-to-face π–π stacking pattern along with N-H···N hydrogen bonds positions the reactive centers in an appropriate location to undergo a [2 + 2] cycloaddition reaction.
To determine the photoreactivity of 2(C6H4Cl3N)·(3,3-BPE), a dried powdered sample was placed into a photoreactor and exposed to ultraviolet radiation. A [2 + 2] cycloaddition reaction was confirmed by the complete loss of the olefinic signal at 7.44 ppm on 3,3-BPE, along with the concomitant appearance of a cyclobutane signal associated with 3,3-TPCB at 4.71 ppm in the 1H NMR spectra (Scheme 2a) (Quentin and MacGillivray, 2020a). The yield for the [2 + 2] cycloaddition reaction reaches a quantitative level after only 16 h of exposure to ultraviolet light (Supplementary Figures S3, S4).
The structure of the bulk solid containing 2(C6H4Cl3N)·(3,3-BPE) was investigated using a PXRD experiment. Comparing the observed diffractogram to the theoretical powder pattern for the single-crystal structure of 2(C6H4Cl3N)·(3,3-BPE) confirms a high level of purity for the resulting solid (Supplementary Figure S11). This good agreement of the diffraction peaks supports the quantitative yield of the photoreaction due to the high purity of the bulk material.
3.3 Structure and photoreactivity of 2(C6H3Cl4N)·(2,2-BPE)
Single-crystal diffraction data revealed that the molecules in 2(C6H3Cl4N)·(2,2-BPE) crystallize in the centrosymmetric monoclinic space group P21/n. Within the asymmetric unit is a whole molecule of C6H3Cl4N along with half a molecule of 2,2-BPE where again inversion symmetry generates the remainder of the reactant molecule. The co-crystal 2(C6H3Cl4N)·(2,2-BPE) is held together primarily by N-H···N hydrogen bonds [N···N 3.076 (2) Å] that result in a discrete three-component hydrogen-bonded solid (Figures 5, 6). The second unique N-H group interacts with an adjacent donor via N-H···Cl contacts [N···Cl 3.677 (2) Å] to an ortho-chlorine with respect to the amine group (Figures 5, 6). The ethylene group within 2,2-BPE is found to be ordered at 290 K within 2(C6H3Cl4N)·(2,2-BPE). The hydrogen-bond donor and acceptor are twisted at 47.36° from coplanar within the discrete assembly at 290 K (Figure 6). Nearest hydrogen-bonded arrays interact via C-H···Cl contacts [C···Cl 3.709 (2) Å] between an ortho-chlorine to the amine group and an ortho-hydrogen to the ethylene bridge (Figures 5, 6). Finally, these assemblies also interact via Type I Cl···Cl interactions [Cl···Cl 3.490 (1) Å] between a pair of meta-chlorines to the amine group (Figure 7) (Mukherjee et al., 2014). The combination of all of these non-covalent interactions results in a three-dimensional extended structure.
FIGURE 5
X-ray crystal structure of 2(C6H3Cl4N)·(2,2-BPE) illustrating the N-H···N hydrogen bonds along with the N-H···Cl and C-H···Cl contacts. The N-H···N hydrogen bonds, N-H···Cl contacts, and C-H···Cl contacts are shown as yellow dashed lines.
FIGURE 6
X-ray crystal structure of 2(C6H3Cl4N)·(2,2-BPE) illustrating the N-H···N hydrogen bonds along with the infinite homogenous face-to-face π–π stacking pattern of the aromatic rings. The N-H···N hydrogen bonds and C-H···Cl contacts are shown as yellow dashed lines.
FIGURE 7
X-ray crystal structure of 2(C6H3Cl4N)·(2,2-BPE) illustrating the Type I Cl···Cl interactions between neighboring three-component hydrogen-bonded assemblies. The N-H···N hydrogen bonds, C-H···Cl contacts, and type I Cl···Cl interactions are shown as yellow dashed lines.
Paramount to the formation of a photoreactive co-crystal are the homogeneous face-to-face π–π stacking interactions of both the hydrogen-bond donor and acceptor within 2(C6H3Cl4N)·(2,2-BPE) (Figures 5, 6). These stacked aromatics result in a series of infinite columns of the template and reactant molecules. These aromatic rings, along with the ethylene group, are separated by a centroid-to-centroid distance of 3.8918 (4) Å, which is equivalent to the crystallographic b-axis. Within these infinite arrays, the ethylene groups are parallel and well within the distance requirement for a solid-state photoreaction due to translational symmetry between unit cells.
To determine whether the co-crystal 2(C6H3Cl4N)·(2,2-BPE) would be photoreactive, a dried powdered sample was placed in a photochemical cabinet and exposed to ultraviolet light. As expected, a [2 + 2] cycloaddition reaction was observed via 1H NMR. This is evident by the loss of the olefinic signal at 7.71 ppm on 2,2-BPE, along with the simultaneous appearance of a cyclobutane signal at 4.91 ppm, which confirms the formation of the stereospecific photoproduct 2,2-TPCB (Scheme 2b) (Colmanet et al., 2025; Quentin and MacGillivray, 2020a). This quantitative yield of the cycloaddition reaction was reached within 40 h of exposure to UV light (Supplementary Figures S5, S6).
As before, the resulting bulk solid containing 2(C6H3Cl4N)·(2,2-BPE) was investigated by PXRD to determine its overall purity. When comparing the observed diffractogram to the theoretical pattern, based upon the single-crystal structure, it is clear that the solid is in good agreement with the co-crystal (Supplementary Figure S10). Similar to before, this high level of purity for the resulting solid supports the observed quantitative yield for the bulk since all of the reactant molecules are in an appropriate site to undergo a photoreaction.
3.4 Structure and photoreactivity of 2(C6H4Cl3N)·(2,2-BPE)
The molecular components within the co-crystal 2(C6H4Cl3N)·(2,2-BPE) crystallize in the centrosymmetric triclinic space group Pī. As in all the previous co-crystals, a whole hydrogen-bond donor, in this case C6H4Cl3N, along with a half of a hydrogen-bond acceptor, namely 2,2-BPE, are found in the asymmetric unit and applying inversion symmetry generates the remainder of the molecule and the three-component assembly. The co-crystal is sustained by N-H···N hydrogen bonds [N···N 3.057 (3) Å] that result in a discrete molecular solid (Figure 8). Similar to 2(C6H4Cl3N)·(3,3-BPE), the second N-H group within 2(C6H4Cl3N)·(2,2-BPE) does not form a hydrogen bond with any suitable acceptor. As observed in all of the previous co-crystals, the ethylene group within the reactant is found to be fully ordered at 290 K. The hydrogen-bonded components in the three-component assembly are rotated from each other by 47.83° at 290 K (Figure 8). The stacked three-component hydrogen-bonded assemblies interact via C-H···Cl contacts [C···Cl 3.682 (2) Å] between the ortho-chlorine and ortho-hydrogen to the amine group and ethylene bridge, respectively (Figure 8).
FIGURE 8
X-ray crystal structure of 2(C6H4Cl3N)·(2,2-BPE) illustrating the N-H···N hydrogen bonds along with the infinite homogenous face-to-face π–π stacking pattern of the aromatic rings. The N-H···N hydrogen bonds and C-H···Cl contacts are shown as yellow dashed lines.
Important to achieve a photoreactive co-crystal, the hydrogen-bond donor C6H4Cl3N, along with the reactant 2,2-BPE, is found to be π-stacked in a homogeneous and face-to-face pattern. These stacked aniline and 2,2-BPE molecules have a centroid-to-centroid distance of 3.8748 (4) Å, which is equal to the crystallographic a-axis. The reactive ethylene groups, within the infinite stacks, are again found to be parallel and within a distance that is suitable to undergo a [2 + 2] cycloaddition reaction.
The photoreactivity of 2(C6H4Cl3N)·(2,2-BPE) was investigated by taking a dried powdered sample and placing it into a photochemical cabinet to be exposed to ultraviolet light. As in previous co-crystals, a [2 + 2] cycloaddition reaction was observed by the complete loss of the olefinic signal at 7.71 ppm on 2,2-BPE, along with the concomitant appearance of a cylcobutane signal at 4.91 ppm in the 1H NMR spectra, which confirms the formation of the stereoselective photoproduct 2,2-TPCB at (Scheme 2b) (Colmanet et al., 2025; Quentin and MacGillivray, 2020a). A quantitative yield for the [2 + 2] cycloaddition reaction was reached after 60 h of exposure (Supplementary Figures S7, S8). As observed in all the co-crystals in this contribution, the combination of the homogeneous face-to-face π–π stacking pattern, along with the N-H···N hydrogen bonds, places the ethylene groups in an appropriate position to undergo a solid-state photoreaction.
The bulk solid that contained 2(C6H4Cl3N)·(2,2-BPE) was also investigated using a PXRD experiment. The observed diffractogram of the sample matches the theoretical powder pattern for the single-crystal structure of 2(C6H4Cl3N)·(2,2-BPE), which confirms a high level of purity for the bulk material (Supplementary Figure S12). This level of agreement between the observed and theoretical powder diffractograms supports the quantitative yield for the photoreaction.
4 Conclusion
In this contribution, we report the expanded application of C6H3Cl4N and C6H4Cl3N as molecular templates to achieve solid-state [2 + 2] cycloaddition reactions with the remaining two symmetric bipyridine-based reactants. In all cases, these chlorinated anilines position the ethylene group within the reactant molecule in a suitable location to photoreact due to the combination of N-H···N hydrogen bond and homogeneous face-to-face π–π stacking forces. Currently, we are investigating the catalytic ability of these templates to achieve a high-yielding photoreaction using a substoichiometric amount of the template (Colmanet et al., 2025; Holdaway et al., 2024).
Statements
Data availability statement
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
Author contributions
GW: Writing – review and editing, Data curation, Investigation. DU: Data curation, Investigation, Writing – review and editing, Formal analysis. RG: Conceptualization, Supervision, Formal analysis, Investigation, Funding acquisition, Writing – original draft, Writing – review and editing.
Funding
The authors declare that financial support was received for the research and/or publication of this article. Webster University is gratefully acknowledged for financial support in the form of various Faculty Research Grants.
Acknowledgments
Professor Leonard MacGillivray and his research group at the University of Iowa are acknowledged for the donation of the reactant 3,3-BPE used in this contribution.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The authors declare that no Generative AI was used in the creation of this manuscript.
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fchem.2025.1698626/full#supplementary-material
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Shapiro N. M. Bosch E. Unruh D. K. Krueger H. R. Groeneman R. H. (2021). Iodoperchlorobenzene acts as a dual halogen-bond donor to template a [2 + 2] cycloaddition reaction within an organic co-crystal. CrystEngComm23, 8265–8268. 10.1039/d1ce01194d
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White G. K. Unruh D. K. Krueger H. R. Groeneman R. H. (2025). Chlorinated anilines as molecular templates to achieve [2 + 2] cycloaddition reactions within organic cocrystals. ACS Omega10, 21922–21928. 10.1021/acsomega.5c01991
Summary
Keywords
co-crystal, organic solid state, [2 + 2] cycloaddition reaction, hydrogen bonding, co-crystal former
Citation
White GK, Unruh DK and Groeneman RH (2025) Expanding the application of chlorinated anilines as molecular templates to achieve a series of solid-state [2 + 2] cycloaddition reactions. Front. Chem. 13:1698626. doi: 10.3389/fchem.2025.1698626
Received
03 September 2025
Revised
30 September 2025
Accepted
28 October 2025
Published
04 December 2025
Volume
13 - 2025
Edited by
Adam A. L. Michalchuk, University of Birmingham, United Kingdom
Reviewed by
Kenneth Maly, Wilfrid Laurier University, Canada
Erick Cuevas-Yañez, Universidad Autónoma del Estado de México, Mexico
Updates
Copyright
© 2025 White, Unruh and Groeneman.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ryan H. Groeneman, ryangroeneman19@webster.edu
Disclaimer
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