12920
J. Phys. Chem. B 2008, 112, 12920–12926
An Unexpected Phase Transition during the [2 + 2] Photocycloaddition Reaction of Cinnamic Acid to Truxillic Acid: Changes in Polymorphism Monitored by Solid-State NMR Ryan C. Nieuwendaal, Marko Bertmer,† and Sophia E. Hayes* Department of Chemistry and Center for Materials InnoVation, Washington UniVersity, 1 Brookings DriVe, Saint Louis, Missouri 63108 ReceiVed: July 14, 2008
We have detected a phase transition during the progress of the solid-state [2 + 2] photocycloaddition reaction of R-trans-cinnamic acid. The reaction was monitored using 13C CPMAS experiments as a function of irradiation time of the parent R-trans-cinnamic acid, which forms the product dimer, R-truxillic acid. UV light centered at 350 nm was used for photoirradiation, which is in the “tail” of the absorption band of cinnamic acid. Two different crystal polymorphs of R-truxillic acid are observed (P21/n and C2/c) at different stages of conversion of the parent crystal, assigned through 13C NMR and powder X-ray diffraction. The two polymorphs showed clear, distinguishable patterns in the 13C NMR spectra: a 2-peak versus 3-peak pattern corresponding to sites on the 4-membered sp3 hybridized ring in the photoproduct. A phase transition is observed midway through the reaction, which we have assigned to the conversion of the P21/n polymorph to the C2/c polymorph of R-truxillic acid. The packing energy of the resultant mixed crystal of cinnamic acid and truxillic acid changes during the course of the photoreaction, which allows for the C2/c polymorph of truxillic acid to appear. Both phases have been confirmed via X-ray powder diffraction. Two techniquessdifferential scanning calorimetry and solid-state CPMAS NMR using increasingly fast rotational frequenciessdemonstrate that the P21/n phase is metastable. Introduction [2 + 2] photocycloaddition reactions have been used for the purpose of solid-state synthesis and studies of topochemistry. Topochemistry, or topochemical control, refers to the principle that the solid-state packing of reactants ultimately determines the resulting products including their stereochemistry.1 Interestingly, the reaction mechanism of a simple molecular solid that undergoes the [2 + 2] photocycloaddition, R-trans-cinnamic acid, is still being researched over 100 years after its discovery. Originally, the truxillic acid photoproduct was discovered in cocaine leaves,2 and its direct synthesis was achieved in the early 1900s.3 However, the crystal structure and morphology was unsolved until 1959.4 Indeed, this photoreaction has been studied by diverse analytical methods including X-ray diffraction,5 atomic force microscopy (AFM),6 and Raman spectroscopy.7 However, the precise solid-state structure of the product(s) of this photoreaction is still not completely understood. In fact, the existence of a second crystalline polymorph of the product crystal, R-truxillic acid, has been known for almost 50 years (via powder diffraction) (ref 4), but its single crystal structure was only recently solved by Abdelmoty et al.8 This recent X-ray study strongly impacted our NMR studies, because it aided us in assigning NMR features to the newly discovered polymorph. The C2/c crystal structure provided us compelling support for the NMR assignments and has enabled us to present new data and interpretations regarding the [2 + 2] photocycloaddition reaction. Organic solid-state photoreactions that involve the photodimerization of parallel double bonds have garnered considerable * Corresponding author. Fax: (314) 935-4481. Telephone: (314) 9354624. E-mail:
[email protected]. † Present address. Universita ¨ t Leipzig, Institut fu¨r experimentelle Physik II, Linne´strasse 5, 04103 Leipzig, Germany.
interest, due to their potential utility in materials science. Researchers have employed the [2 + 2] photocycloaddition reaction for a number of interesting materials, including cinnamates,9,10 diarylethylenes,11 coumarins,12,13 stilbenecontaining materials,14 and ladderanes.15 A number of these species have been proposed as potential optical memory materials.16 Other applications of cinnamic acids have been envisioned in polymer science. For example, a recent study found that a polymer blend with cinnamate side chains could serve as a reversible photoinduced shape memory polymer when irradiated with light in the absorption band of the cinnamate moiety (ref 9). Furthermore, cinnamoyl derivatives have been utilized in methacrylate-based polymers as light-induced crack healing agents to repair fractures formed in the material by irradiation (ref 10). We have studied this photoreaction in the solid-state by employing solid-state NMR. This spectroscopic technique is noninvasive and element selective, and allows for characterization of both crystalline and amorphous solids alike, not limited to solids with repeating diffraction planes or surfaces. Solidstate NMR is ideal for distinguishing between crystalline polymorphs, applied by the pharmaceutical community for just that purpose.17-19 Furthermore, the quantitative nature of this form of spectroscopy allows the kinetics of these photoreactions to be followed,20,21 since the products, reactants and even intermediates in a complex mixture can be analyzed. In a previous study (ref 21), we utilized “broadband” irradiation to study these [2 + 2] cycloadditions in cinnamic acid. Herein, we report on results from irradiating cinnamic acid with a narrow band of wavelengths in the “tail” of the solid state absorption spectrum. The spectral region was selected on the basis of having a very low absorption coefficient, commonly referred to as the “tail” of the absorption band. This procedure is similar to that used by Enkelmann et al. (ref 5) in an earlier
10.1021/jp806218u CCC: $40.75 2008 American Chemical Society Published on Web 09/24/2008
Unexpected Phase Transition X-ray diffraction study, reporting on single crystal-to-single crystal photoconversions, in our effort to study the photoreaction via NMR (a helpful review22 of single crystal-to-single crystal [2 + 2] photodimerizations summarizes principles underlying these phenomena). In the samples we have studied, tail irradiation seems to reproduce what was observed previously, in the early stages of the photoreaction. However, at longer irradiation times, we observe differences in the truxillic acid solid-state structure, detailed below. Experimental Section The reactant, R-trans-cinnamic acid (Aldrich), was recrystallized from diethyl ether and sieved using mesh sieves to select out crystals in the size range from 1 mm to 2 mm. Samples of the resulting powder of crystallites (55 ( 1 mg) were spread in a thin layer, placed under a 150 W xenon arc lamp, and irradiated. Efforts were made to ensure that samples had similar thermal histories, in that they were exposed to the arc lamp in e10-h increments with cooling periods of 10 µm) between two quartz plates on a Cary UV-vis spectrometer with 1 nm resolution.
J. Phys. Chem. B, Vol. 112, No. 41, 2008 12921 Powder X-ray diffraction data were collected at room temperature on a Scintag-Seifert PAD V using Cu KR radiation (1.54059 Å) with an ORTEC HyperPure Germanium Crystal detector. The sample was prepared by pressing the powder into a thin layer onto Au foil, and SRM-640a silicon was used as a standard. The diffraction peaks of the different polymorphs were assigned by simulating the powder patterns from the known crystal structures in PowderCell.26 Phase transition temperatures were measured by differential scanning calorimetry (DSC) on a Mettler Toledo DSC822e, with a heating rate of 5 °C/min, under a nitrogen atmosphere. Measurements were analyzed using the Mettler Toledo Star SW 7.01 software. The phase transition temperature was taken as the midpoint of the inflection tangent, upon the first heating scan. Three heating and cooling cycles were conducted. An ab initio calculation was performed on the R-truxillic acid molecule in order to understand the conformations of the cyclobutane ring. A full geometry optimization was performed in Gaussian0327 at MP2 level of theory28 using a 6-31G** basis set.29,30 Both crystalline forms of R-truxillic acid (the C2/c (ref 8) and P21/n (ref 5) polymorphs) were used as starting points for the energy minimization, and they both led to the same structure. In this structure, the torsional angle of the cyclobutane ring was approximately zero (τ < 0.5°) as visualized in Mercury 1.4.31 The coordinates of the simulated R-truxillic acid molecule are available in the Supporting Information (S3). Results and Discussion Truxillic Acid Polymorphs. Two polymorphs of R-truxillic acid are known from single-crystal X-ray diffraction (XRD), the P21/n polymorph (ref 5) and the C2/c polymorph (ref 8). The P21/n R-truxillic acid polymorph appears to be a metastable structure (ref 8), which was first determined from single crystal XRD experiments of photoirradiated cinnamic acid. The P21/n structure has inversion symmetry and a flat cyclobutane ring, shown in Figure 1a, and its solid-state structure was found to be very similar to the gas phase (energy-minimized) structure determined by ab initio calculations using Gaussian03. Because of inversion symmetry of this molecule, one signal for the carboxylic carbon and two for the sp3 carbons in the cyclobutanering are observed. Notably, this pattern of NMR resonances is what is observed when R-truxillic acid is dissolved and a solution-phase 13C NMR spectrum is recorded, shown in Figure 1c. Two resonances are observed in the sp3 (cyclobutane) spectral region (35-55 ppm), and a single resonance is observed in the carboxylic acid region (170-180 ppm). The C2/c polymorph is formed when R-truxillic acid is recrystallized from solution (evaporation of a 1:1 mixture of acetic acid and ethyl acetate), and it is the most stable structure at room temperature (ref 8). This crystal structure was initially solved by Abdelmoty et al. via single crystal X-ray diffraction and has been independently confirmed in this study. In this structure, the cyclobutane ring is kinked (τ ) 13-14°), see Figure 1b, and the planes of the pendant phenyl rings are not parallel. These crystals form a structure that adopts “a disordered model in C2/c” (see Figure 2, parts a and b), which was recently identified by Abdelmoty et al. (ref 8) by single crystal X-ray diffraction. The term “disordered” refers to the coexistence of two different molecules of R-truxillic acid in the lattice that are “disordered about the 2-fold axis in C2/c” (ref 8). 13C CPMAS experiments were performed on these recrystallized C2/c polymorph crystals (data shown in Figure 2c), and the lack of molecular symmetry is reflected in the spectrum. There are three resonances in the cyclobutane region (39, 44, and 51
12922 J. Phys. Chem. B, Vol. 112, No. 41, 2008
Figure 1. (a) Three-dimensional rendering of P21/n truxillic acid. (b) Depiction of two cyclobutane moieties with the torsion angle (τ) indicated. A flat ring (τ ) 0°) is observed in the molecular conformation shown in part a. (c) Solution-phase 13C NMR spectrum of R-truxillic acid in d6-DMSO.
ppm) with integrated peak areas of 1:2:1, and there are two resonances in the carboxylic acid region (178 and 181 ppm). The spectrum is evidence that neither the cyclobutane carbons nor the carboxylic acid carbons are equivalent. Solid-state packing must contribute to distortions leading to the C2/c structures (including the kinked 4-membered ring), since the predicted energy-minimized structure has inversion symmetry. This C2/c phase is also clearly distinguishable from the P21/n polymorph by X-ray powder diffraction experiments as shown in Figure 5 (discussed below). An alternative hypothesis has been proposed for multiple resonances (4 peaks) observed for the 4-membered ring.32 The authors claimed that signal splittings could originate from asymmetric hydrogen bonds of the truxillic acid molecules. We believe that compelling evidence in our study is provided by both X-ray diffraction results and NMR spectra that demonstrate two structural conformations of the 4-membered ring, leading to a 2-peak or (given the resolution of our lower field and slower spinning experiments) 3-peak pattern. Photoirradiated Cinnamic Acid. We utilized the quantitative nature of NMR experiments to characterize the progress of the photodimerization through analysis of the 13C CPMAS spectra. NMR benefits from being quantitative (under appropriate conditions) and is not hampered by disorder or amorphous domains. These features make NMR an ideal tool for analyzing
Nieuwendaal et al.
Figure 2. (a, b) Two conformations of R-truxillic acid that make up the C2/c polymorph (τ ) 13-14°). (c) 13C CPMAS spectrum of recrystallized R-truxillic acid. Relative peak area of cyclobutane carbons is indicated in parentheses. * denotes spinning sidebands.
Figure 3. Solid-state optical absorption spectrum of a thin (∼10 µm) R-trans-cinnamic acid polycrystalline sample.
reaction kinetics in the solid state, such as these. Nevertheless, powder X-ray diffraction was used as a complementary tool to confirm the structures of the phases identified here. R-trans-Cinnamic acid powder samples were irradiated in a region of low absorptivity of the solid-state absorption spectrum, shown in Figure 3. This region, commonly referred to as the “tail” of the absorption band, was selected to ensure that light
Unexpected Phase Transition
J. Phys. Chem. B, Vol. 112, No. 41, 2008 12923
Figure 4. 13C CPMAS spectra of samples irradiated for 20-235 h as indicated on the figure. Resonances assignable to reactant and multiple product species can be identified. The emergence of the C2/c polymorph at irradiation times >50 h is demonstrated by the appearance of these peaks: carboxylic acid carbon at 181 ppm and cyclobutane carbons at 51 and 44 ppm. The phenyl resonances (125-135 ppm) have been intentionally clipped in order to magnify the cyclobutane and carboxylic acid spectral regions of interest, and the sp3 carbon region has been scaled (number indicated on the figure). * symbols indicate spinning sidebands.
Figure 5. Powder X-ray diffraction patterns: (a) P21/n cinnamic acid, (b) cinnamic acid sample irradiated for 49.4 h, (c) cinnamic acid sample irradiated for 80 h, and (d) pure C2/c truxillic acid. * symbols indicate peaks that can be attributed to the C2/c phase of truxillic acid. Only a portion of the 2θ range is shown; the full pattern is shown in the Supporting Information. ^ symbols indicate features not clearly assignable to either phase of truxillic acid.
could penetrate into the bulk of each crystallite, and not simply be absorbed on the surface. 13C CPMAS NMR experiments were then conducted as a function of (photon) irradiation time. A stack plot of the NMR spectra as a function of irradiation time is shown in Figure 4. The two regions with the most spectral detail have been expanded for clarity. The sp3 (cyclobutane) region has been scaled (in intensity) as indicated on the figure. We monitored the progress of the reaction by evaluating the 13C spectra for carbons unique to the reactant and product molecules. The cinnamic acid parent species is composed entirely of sp2-hybridized carbons, yielding no resonances at frequencies below 115 ppm. Cinnamic acid has two unique vinylic carbons at 118 and 146 ppm that disappear upon photoirradiation (ref 21); the area of these two peaks is
representative of the total content of reactant molecules. A carbonyl resonance at 172 ppm is also present for cinnamic acid, whose resonance shifts upon irradiation. The truxillic acid has a cyclobutane-like moiety composed of four sp3-carbons with resonances that appear in the range of 39-51 ppm and concomitantly grow as the reaction proceeds; the area of these signals is therefore representative of the total content of product in the sample. To derive the fraction of product formed, the peak area corresponding to the cyclobutane region of the truxillic acid was divided by the sum total of these selected resonances for both product and reactant molecules.33 Samples of cinnamic acid irradiated for less than 60 h (Figure 4, parts a and b) produced the P21/n polymorph of truxillic acid. This polymorph can be assigned because of the characteristic two-peak pattern in the cyclobutane spectral region (at 40.5 and 46.3 ppm), corresponding to two chemically inequivalent sites on the cyclobutane ring. This species also has one resonance (178.1 ppm) in the carboxylic acid region for the two magnetically equivalent carboxyl sites. Like the solution-phase data discussed earlier, the observation of two solid-state 13C resonances suggests that the packing of the molecule in this polymorph allows the truxillic acid to adopt the conformation with inversion symmetry, even in the solid state. The P21/n polymorphic structure was confirmed through X-ray powder diffraction, shown in Figure 5a-c. The powder diffraction profiles shown in Figure 5a-c could be indexed in the P21/n monoclinic crystal system at room temperature, indicating that cinnamic acid and truxillic acid can form a solid solution up through nearly 50 h of irradiation. Shifts in diffraction peaks are barely noticeable, but there are some changes in diffraction intensities of certain reflections, notably the decrease and broadening of the reflection at 9.9° with increasing irradiation time. The coexistence of the two P21/n phases is consistent with the XRD data shown. The evidence in the XRD pattern suggests that up to 50 h, only species with the space group P21/n are observed, which agrees with our solidstate NMR results. Note that there are two features marked by
12924 J. Phys. Chem. B, Vol. 112, No. 41, 2008
Figure 6. Differential scanning calorimetry experiment of a 30 h irradiated sample composed of 94% cinnamic acid and 6% truxillic acid. The plot shows a portion of the total range of temperatures scanned.
^ʼs in Figure 5b, that are not clearly distinguishable as P21/n truxillic acid versus C2/c truxillic acid. Simulations of the X-ray powder diffraction (in Supporting Information, Figure S2) suggest that these may be the shifted (031) reflection and a broadened (140) reflection of P21/n truxillic acid. The diffraction peaks become more broad, indicative of the loss of crystallinity and the possible formation of a solid solution of the two P21/n species. Notably, solid-state NMR is sensitive to both polymorphs of R-truxillic acid, even if the crystallinity of the sample decreases. Samples irradiated for 60 h and longer produce a mixture of the C2/c and P21/n polymorphs. Such a mixture is indicated by the appearance of an additional resonance in the carboxylic acid region (181.0 ppm), and a 3-peak pattern in the cyclobutane region with a 1:2:1 intensity ratio (at 39.0, 44.5, and 51.0 ppm, respectively) in the 13C CPMAS spectra. These changes between spectra can be seen in Figure 4c-f, indicating a new product or polymorph. Dissolution of the sample yields only R-truxillic acid molecules when monitored by solution-phase 13C NMR; so, it can be ruled out that a new side product has been formed. Furthermore, at longer irradiation times (80 hours, see Figure 5c) the powder X-ray diffraction data depict such changes, showing reflections at 11.0°, 11.2°, 16.6°, and 17.3°, consistent with the 002, 200, 110, and -111 reflections of the C2/c polymorph, respectively. It is worthwhile to note, we have found that some of the crystallites break during the irradiation at the point in the reaction where the C2/c polymorph appears. The existence of distinguishable polymorphic structures suggests that a phase change could be responsible for their formation. This hypothesis was tested by conducting DSC experiments on partially reacted samples that included only cinnamic acid and the P21/n polymorph photoproduct. Figure 6 is a DSC thermogram of a 30-h irradiated sample consisting of 6% P21/n truxillic acid · 94% cinnamic acid. The thermogram clearly shows a phase transition at the moderate temperature of only 33 °C, which was found to be irreversible. The phase transition at 33 °C was only observed during the first heating scan of the three heating and cooling cycles. The 13C CPMAS NMR of the material after heating showed the 3-peak pattern of the C2/c polymorph of R-truxillic acid, and we therefore attribute this phase transition to a conversion of the P21/n polymorph to the C2/c polymorph. (Consequently, reaction
Nieuwendaal et al.
Figure 7. 13C CPMAS spectra of the cyclobutane spectral region of truxillic acid (1) pure C2/c polymorph (from a recrystallized sample), (2) pure P21/n polymorph from an early stage photoreaction, and (3) mixed polymorphic species of P21/n + C2/c. Gaussian peak deconvolution(s) are shown. * indicates spinning sidebands.
temperatures and CPMAS experiments were monitored to ensure that temperatures 50 h (the point at which the sample composition is 22% truxillic acid · 78% cinnamic acid), the product truxillic acid produces a second phase, the more stable C2/c polymorph. Past this point, a solid solution of truxillic acid in cinnamic acid can no longer be maintained so that these samples are composed of 3 componentsunreacted cinnamic acid, P21/n truxillic acid, and C2/c truxillic acid-observable via solid-state NMR. Macroscopically, this is when the crystallites can first be visibly seen to
break or disintegrate. We note that in the previous work of Enkelmann et al. (ref 5), cinnamic acid crystals were able to be fully converted to P21/n truxillic acid in a single-crystalto-single-crystal fashion. We did not observe such behavior, possibly due to the larger crystal sizes (1-2 mm) in our experiments, leading to strained environments surrounding these growing photoproduct domains. Recent literature has reported on the ability of single-crystal to single-crystal conversions to be achieved in crystals
