research papers\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

Absolute structure of the chiral pyrrolidine derivative (2S)-methyl (Z)-5-(2-tert-but­­oxy-1-cyano-2-oxo­ethyl­­idene)pyrrolidine-2-carboxyl­ate, a com­pound with low resonant scattering

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aKey Laboratory of Materials for Energy Conversion and Storage, Institute of Molecular Science, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China, and bInstitute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
*Correspondence e-mail: ullrich.englert@ac.rwth-aachen.de

Edited by D. S. Yufit, University of Durham, England (Received 24 July 2019; accepted 4 September 2019; online 4 October 2019)

The enanti­opure monopyrrolidine derivative (2S)-methyl (Z)-5-(2-tert-but­oxy-1-cyano-2-oxo­ethyl­idene)pyrrolidine-2-carboxyl­ate, C13H18N2O4, (1), represents a potential ligand and an attractive inter­mediate for the synthesis of chiral metal com­plexes. At the mol­ecular level, the com­pound features an intra­molecular N—H⋯O hydrogen bond; neighbouring mol­ecules inter­act via N—H⋯N contacts to form chains along [100]. Due to its elemental com­position, resonant scattering of the target com­pound is entirely insignificant for diffraction experiments with Mo Kα and small even for Cu Kα radiation. A preliminary study with the harder radiation type confirmed the chiral space group and the suitability of the single crystal chosen; as expected, the results concerning the absolute structure remained com­pletely inconclusive. A second data collection with the longer wavelength gave satisfactory quality indicators for the correct handedness of the mol­ecule, albeit with high standard uncertainties. The absolute configuration has been assessed independently: CD spectra for both enanti­omers of the target mol­ecule were calculated and the spectrum for the S-configured stereoisomer was in agreement with the experiment. The Cotton effect of (1) may be ascribed to ππ* transitions from HOMO to LUMO and from HOMO to LUMO+1. As both independent techniques agree with respect to the handedness of the target mol­ecule, the absolute structure may be assigned with a high degree of confidence.

1. Introduction

Pyrrolidine derivatives have found applications as potential ligands, as organic inter­mediates and in medicinal chemistry. They can inhibit the activity of over-expressed protein tyrosine phosphatases (PTPs) of cancer cells and may be employed as anti­cancer drugs (IC50 value is 3.65 ± 0.08 µM) (Chen et al., 2017[Chen, Q.-B., Xin, X.-L. & Asia, H. A. (2017). Phys. Chem. Lett. 19, 168-171.]). By forming imine or enamine inter­mediates with aldehydes and ketones, chiral monopyrrolidine derivatives have been widely used in asymmetric catalysis, and alkyl­ation and acyl­ation reactions of aldehydes and ketones have been achieved (Jensen et al., 2012[Jensen, K. J., Dickmeiss, G., Jiang, H., Albrecht, L. & Jørgensen, K. A. (2012). Acc. Chem. Res. 45, 248-264.]). We report here the absolute configuration of the chiral pyrrolidine derivative (2S)-methyl (Z)-5-(2-tert-but­oxy-1-cyano-2-oxo­ethyl­idene)pyrrolidine-2-carboxyl­ate, (1) (Scheme 1). The com­pound has been synthesized and spectroscopically characterized by Pfaltz and co-workers (Pfaltz et al., 1977[Pfaltz, A., Bühler, N., Neier, R., Hirai, K. & Eschenmoser, A. (1977). Helv. Chim. Acta, 60, 2653-2672.]; Fritschi et al., 1988[Fritschi, H., Leutenegger, U., Siegmann, K., Pfaltz, A., Keller, W. & Kratky, C. (1988). Helv. Chim. Acta, 71, 1541-1552.]; Pfaltz, 1993[Pfaltz, A. (1993). Acc. Chem. Res. 26, 339-345.]); retention of the configuration at C1 may be assumed. No studies in medicinal chemistry have been conducted on (1), but a closely related com­pound was investigated, i.e. methyl 5-[1-cyano-2-oxo-2-(2,3,4-tri­meth­oxy­phen­yl)ethyl­idene]pro­lin­ate was screened by the National Cancer Institution, USA, against 60 human tumour cell lines and showed moderate cell-growth inhibition at 10 µM concentration for renal cancer and leukemia

[Scheme 1]
(Ghinet et al., 2012[Ghinet, A., Van Hijfte, N., Gautret, P., Rigo, B., Oulyadi, H. & Rousseau, J. (2012). Tetrahedron, 68, 1109-1116.]). To the best of our knowledge, the structure of (1) has never been investigated and its absolute configuration has not been confirmed. Our assignment relies on a combination of diffraction experiments, experimental circular dichroism (CD) spectroscopy and theoretical calculations of these spectra. We will show that diffraction results, albeit with only a modest contribution of resonant scattering, and CD spectroscopy agree in their assignment of the absolute structure, whereas a diffraction experiment without relevant anomalous dispersion remains inconclusive.

2. Experimental

2.1. Synthesis and crystallization

All reagents were commercially available and were used without further purification. The powder diffraction experiment was recorded at the Institute of Inorganic Chemistry, RWTH Aachen University, using a Stoe imaging-plate detector (IP–PSD). The diffractogram was recorded on a flat sample at ambient temperature in transmission mode using Cu Kα1 radiation. The title com­pound was synthesized following the procedure of Pfaltz (Pfaltz et al., 1977[Pfaltz, A., Bühler, N., Neier, R., Hirai, K. & Eschenmoser, A. (1977). Helv. Chim. Acta, 60, 2653-2672.]; Fritschi et al., 1988[Fritschi, H., Leutenegger, U., Siegmann, K., Pfaltz, A., Keller, W. & Kratky, C. (1988). Helv. Chim. Acta, 71, 1541-1552.]; Pfaltz, 1993[Pfaltz, A. (1993). Acc. Chem. Res. 26, 339-345.]). The reaction combines S-configured pyroglutamic acid methyl ester and tert-butyl 2-cyano­acetate; retention of the configuration at the chiral centre (*) was expected [see Scheme 1 for a summary of the synthesis for (1) according to Pfaltz et al. (1977[Pfaltz, A., Bühler, N., Neier, R., Hirai, K. & Eschenmoser, A. (1977). Helv. Chim. Acta, 60, 2653-2672.])] and is confirmed by the results reported in this work.

Crystals were grown by slow partial evaporation of a methanol solvent at ambient temperature over a period of one week. CHN microanalysis was carried out at the Institute of Organic Chemistry, RWTH Aachen University, using a HERAEUS CHNO-Rapid. Analysis calculated (%) for C13H18N2O4: C 58.74, H 6.81, N 10.52; found: C 58.62, H 6.53, N 10.72. The powder X-ray diffraction (PXRD) pattern (see Fig. 1[link]) confirms that (1) is obtained as an essentially phase-pure product; the shift of the calculated lines of two larger angles can be attributed to the different data-collection tem­peratures for the single-crystal and powder analyses. The IR spectrum shows an absorption associated with the triple bond in the nitrile group at ν(C≡N) = 2205 cm−1, in good agreement with the reported frequency of 2207 cm−1, and the 1H NMR spectrum matches that available in the literature (Fritschi et al., 1988[Fritschi, H., Leutenegger, U., Siegmann, K., Pfaltz, A., Keller, W. & Kratky, C. (1988). Helv. Chim. Acta, 71, 1541-1552.]).

[Figure 1]
Figure 1
Powder X-ray diffraction pattern of (1).

2.2. Refinement

Crystal data, data collection parameters and refinement results for both single-crystal X-ray diffraction experiments with Mo Kα (1mo) and Cu Kα (1cu) radiation are summarized in Table 1[link]. H atoms attached to C atoms were introduced in calculated positions and treated as riding, with Uiso(H) = 1.5Ueq(C) for CH3 groups and 1.2Ueq(C) otherwise. For the H atom attached to an N atom, the positional coordinates and an isotropic displacement parameter were refined freely. For the diffraction experiment (1mo), resonant scattering is insignificant; no information can de deduced from the refined enanti­opol parameter and its very high standard uncertainty. For a better com­parison with the results of (1cu) on the same single crystal, the same absolute structure model was chosen in both cases.

Table 1
Experimental details

For both determinations: C13H18N2O4, Mr = 266.29, orthorhombic, P212121, Z = 4. Experiments were carried out at 100 K using a D8 goniometer with an APEX CCD area detector. Absorption was corrected for by multi-scan methods (SADABS; Bruker, 2008[Bruker (2008). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]). H atoms were treated by a mixture of independent and constrained refinement.

  (1mo) (1cu)
Crystal data
a, b, c (Å) 7.347 (4), 10.197 (6), 18.477 (10) 7.3731 (3), 10.1909 (4), 18.4972 (7)
V3) 1384.1 (13) 1389.85 (9)
Radiation type Mo Kα Cu Kα
μ (mm−1) 0.10 0.79
Crystal size (mm) 0.35 × 0.29 × 0.28 0.35 × 0.29 × 0.28
 
Data collection
Tmin, Tmax 0.473, 0.745 0.579, 0.753
No. of measured, independent and observed [I > 2σ(I)] reflections 10626, 2290, 2051 17945, 2408, 2266
Rint 0.091 0.083
(sin θ/λ)max−1) 0.583 0.597
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.051, 0.124, 1.08 0.032, 0.077, 1.10
No. of reflections 2290 2408
No. of parameters 180 181
Δρmax, Δρmin (e Å−3) 0.21, −0.18 0.17, −0.15
Absolute structure Flack x determined using 710 quotients [(I+) − (I)]/[(I+) + (I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) Flack x determined using 879 quotients [(I+) − (I)]/[(I+) + (I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 1.1 (10) −0.04 (12)
Computer programs: SMART (Bruker, 2001[Bruker (2001). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT-Plus (Bruker, 2009[Bruker (2009). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS2013 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2017 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

2.3. CD spectroscopy

The experimental electronic circular dichroism (CD) spectrum of (1) was recorded in methanol on a Chirascan circular dichroism chiroptical spectrometer at the Institutes of Biomedical Sciences of Shanxi University; it shows a positive Cotton effect at 278.40 nm and a negative Cotton effect at 245.60 nm.

3. Results and discussion

3.1. Mol­ecular structure

The chiral com­pound (1) was obtained as an essentially monophasic crystalline product. In view of its elemental com­position, the determination of the absolute structure was expected to be challenging. With respect to resonant scattering, we calculated values of 6 and 33 for Friedif (Flack & Shmeuli, 2007[Flack, H. D. & Shmueli, U. (2007). Acta Cryst. A63, 257-265.]) for diffraction experiments with Mo and Cu Kα radiation, respectively. Even the higher second value is dangerously low if the diffraction experiments are hampered by additional com­plications, such as disorder or twinning. An initial data collection with our standard set-up (1mo) was performed to ensure sufficient quality for the selected crystal and to confirm the chiral space group: even for high enan­tio­meric excesses, a small amount of racemic solid might precipitate (Böhme & Fels, 2013[Böhme, U. & Fels, S. (2013). Acta Cryst. C69, 44-46.]).

The second data set collected with Cu Kα radiation resulted in slightly smaller standard uncertainties; all numerical values reported below therefore refer to (1cu) (see §3.3[link]). As expected, the enanti­opure com­pound (1) crystallized in a chiral space group. The asymmetric unit consists of a single mol­ecule in the space group P212121; Fig. 2[link] shows a displacement ellipsoid plot.

[Figure 2]
Figure 2
The asymmetric unit of (1) based on data set (1cu), with displacement ellipsoids enclosing 50% of electron density.

Atoms N1, N2, O3, O4, C3, C4 and C7–C10 define an almost planar core of the mol­ecule shown in Fig. 3[link]. The maximum deviation from that least-squares plane is 0.045 (2) Å for atom C3. Within the core plane, the pyrrolidine N—H group acts as a hydrogen-bond donor towards carbonyl atom O3; the hydrogen-bond geometry is summarized in Table 2[link].

Table 2
Hydrogen-bond geometry (Å, °) for (1cu)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1N⋯O3 0.81 (3) 2.13 (2) 2.714 (2) 129 (2)
N1—H1N⋯N2i 0.81 (3) 2.33 (2) 2.924 (2) 131 (2)
C11—H11B⋯O2ii 0.98 2.60 3.565 (3) 169
Symmetry codes: (i) x-1, y, z; (ii) [-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].
[Figure 3]
Figure 3
The planar core of (1).

The pyrrolidine ring is nonplanar and its C2 atom is significantly displaced from the above-defined plane by 0.364 (2) Å.

In contrast to the carboxyl­ate group (C9/O3/O4), the C5/O1/O2 group is not coplanar with the core of the mol­ecule but subtends an angle of 86.1 (2)° with the least-squares plane defined by atoms N1, N2, O3, O4, C3, C4 and C7–C10 (Fig. 2[link]). Table 3[link] contains selected torsion angles.

Table 3
Selected torsion angles (°) for (1cu)[link]

C4—N1—C1—C5 109.61 (19) N1—C1—C5—O2 −26.3 (2)
C4—N1—C1—C2 −12.9 (2) C2—C1—C5—O2 90.1 (2)
C1—N1—C4—C7 −179.84 (18) C3—C4—C7—C8 −2.4 (3)
C1—N1—C4—C3 −0.6 (2) N1—C4—C7—C9 −2.1 (3)
C2—C3—C4—N1 14.0 (2) C10—O4—C9—O3 −2.1 (3)
C6—O2—C5—O1 −2.2 (3) C4—C7—C9—O3 −1.4 (3)
C6—O2—C5—C1 179.93 (16) C8—C7—C9—O4 0.4 (3)
N1—C1—C5—O1 155.73 (19) C9—O4—C10—C13 61.8 (2)

The overall conformation of the mol­ecule suggests its use as a ditopic ligand, similar to substituted acetyl­acetones (Kremer & Englert, 2018[Kremer, M. & Englert, U. (2018). Z. Kristallogr. 233, 437-452.]). The potential coordination sites have been indicated in Fig. 3[link].

3.2. Inter­molecular contacts

The H atom of the pyrrolidine N—H group represents the only potential donor for classical hydrogen bonds. In addition to the intra­molecular N—H⋯O contact described above, it is involved in an inter­molecular N—H⋯N hydrogen bond to the nitrile group of a neighbouring mol­ecule. The resulting chain runs along [100] (Fig. 4[link]). The closest contacts perpendicular to this chain are due to nonclassical C—H⋯O inter­actions. Numerical values and symmetry operators for the short contacts have been com­piled in Table 2[link].

[Figure 4]
Figure 4
Intra- and inter­molecular hydrogen bonds in the crystal of (1). H atoms not involved in hydrogen bonds have been omitted for clarity.

3.3. Absolute structure

3.3.1. Resonant scattering

Our first intensity data collection, i.e. the (1mo) data, had provided a consistent structure model without disorder and confirmed the quality of the chosen sample. As expected, however, the commonly applied methods for assigning the absolute structure gave inconclusive results for (1mo) with its negligible resonant scattering. The Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.], 2003[Flack, H. D. (2003). Helv. Chim. Acta, 86, 905-921.]), Parsons (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) and Hooft (Hooft et al., 2010[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2010). J. Appl. Cryst. 43, 665-668.]) parameters refined to values of ca 1, with standard uncertainties equally large; no conclusions could be drawn from these numbers. Therefore, a second diffraction experiment with Cu Kα radiation, i.e. the (1cu) data, was performed on the same single crystal. Fractional coordinates and derived geometry parameters agreed with the results of (1mo) within error, but resonant scattering was more pronounced and led to information about the absolute structure, i.e. the Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]) parameter refined to −0.04 (12); very similar values and standard uncertainties were obtained for Parsons' quotient method [−0.01 (13), Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]] and Hooft's Bayesian procedure [0.01 (10), Hooft et al., 2010[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2010). J. Appl. Cryst. 43, 665-668.]].

3.3.2. CD spectra

An independent assessment of the absolute structure of (1) relies on a com­parison of the experimentally observed and theoretically calculated electronic circular dichroism (ECD) spectra; they are shown in Fig. 5[link].

[Figure 5]
Figure 5
Experimental (left) and calculated CD spectra for (1) in methanol. The spectrum in the centre corresponds to the (correct) S enanti­omer and that on the right to the alternative R enanti­omer.

The calculations were based initially on the mol­ecular geometry obtained from (1cu). Ground-state geometry optimization and subsequent frequency calculations were performed via the density functional theory (DFT) method as implemented in GAUSSIAN09 (Frisch et al., 2009[Frisch, M. J., et al. (2009). GAUSSIAN09. Gaussian, Inc., Wallingford, CT, USA. https://www.gaussian.com.]) using the B3LYP hybrid functional (Becke, 1993[Becke, A. D. (1993). J. Chem. Phys. 98, 5648-5652.]) and the 6-311++G(2d,p) basis set. The excitation energies, oscillator and rotational strengths of the excited singlet states for the optimized geometry were calculated according to the time-dependent DFT (TDDFT) method with the same functional and basis set. The effects of the solvent (methanol) were included using the polarizable continuum model (PCM) (Tomasi et al., 2005[Tomasi, J., Mennucci, B. & Cammi, R. (2005). Chem. Rev. 105, 2999-3093.]) in the integral equation formalism (IEF). With the PCM, a ground-state energy of −916.95 a.u. for (1) was obtained.

3.3.3. DFT energy levels and Kohn–Sham orbitals

The DFT energy levels show a HOMU–LUMO gap of 5.25 eV. A detailed analysis of the Kohn–Sham orbitals has been graphically summarized in Fig. 6[link]. The two lowest unoccupied orbitals are dominated by a π* region in the planar core and in the carboxyl­ate group of the methyl ester (C5/O1/O2). The absolute value of the energy difference between these LUMO and LUMO+1 orbitals is 0.72 eV. Both of them may well act as electron-acceptor orbitals when electrons from the HOMO and HOMO-1 orbitals are excited. The HOMO is dominated by the π region of the planar core of (1). The HOMO-1 essentially corresponds to a combination of σ + nN + nO orbitals; the energy difference of the HOMO and HOMO-1 amounts to 1.28 eV.

[Figure 6]
Figure 6
Selected Kohn–Sham orbitals for (1).
3.3.4. Rotational strengths and transition assignments

The contribution of different transition probabilities to the chiroptical properties of (1) were analyzed. The calculated excitation energies and oscillator and rotational strengths (in velocity form), as well as the transition assignments, have been com­piled in Table 4[link]. Results for the three excitations of the lowest energy conformer are given; they cover the spectral range 180 < λ < 350 nm.

Table 4
Excitation wavelengths (λ, nm), oscillator (f) and rotational (R, DBM) strengths and transition assignments from occupied (Occ) to virtual (Virt) orbitals

λ f R Occ–Virt Assignments
262 0.2670 0.4600 HOMO→LUMO π(coplanar)→π*(coplanar) (77%)
      HOMO→LUMO+1 π(coplanar)→π*(COO in COOCH3) (19%)
250 0.1642 −0.6047 HOMO→LUMO+1 π(coplanar)→π*(COO in COOCH3) (77%)
      HOMO→LUMO π(coplanar)→π*(coplanar) (20%)
239 0.0028 −0.0173 HOMO-1→LUMO σ+nN+nOπ*(coplanar) (89%)

Using the excitation energies and rotational strengths calculated by TDDFT, theoretical CD spectra for both stereoisomers of (1) were generated as the sum of Gaussians, centred at the calculated wavelengths λcalc with integral intensities proportional to the rotational strengths R of the corresponding transitions. The half bandwidths Γ at the Δmax/e of Gaussians were assumed as Γ = kλcalc3/2 (Brown et al., 1971[Brown, A., Kemp, C. M. & Mason, S. F. (1971). J. Chem. Soc. A, pp. 751-755.]) with k = 0.00385 to best reproduce the experiment. The experimental spectrum and calculated spectra for both enanti­omers have been com­piled in Fig. 5[link]. Ideally, experimental CD spectra of opposite enanti­omers are mirror images of each other (Flack & Bernardinelli, 2003[Flack, H. D. & Bernardinelli, G. (2003). Cryst. Eng. 6, 213-223.]).

It is obvious that the CD curve calculated for S-configured (1) is in excellent agreement with the observed curve, with only a small blue shift in the calculated maximum. The agreement confirms that our spectroscopic inter­pretation of the DFT results is correct.

The observed CD curve consists of two absorption bands, i.e. a positive band around 278 nm arising from the first ππ* transition in which electrons are transferred from the HOMO to the LUMO (77%) and from the HOMO to the LUMO+1 (19%), and a negative band around 243 nm, which can also be ascribed to the second ππ* transition and a minor contribution of a σπ* transition. The main contribution to this significant negative ππ* transition, however, is associated with the transition from HOMO to LUMO+1 (77%) and from HOMO to LUMO (20%). The σπ* transition can be assigned to electronic excitation from HOMO-1 to LUMO. Thus, the optical properties of chiral com­pound (1) are mainly dominated by a combination of ππ* transitions from HOMO to LUMO and HOMO to LUMO+1.

4. Conclusion and outlook

The absolute structure of (1) could reliably be assigned as S, despite the limited contribution of resonant scattering; a low-temperature diffraction experiment with Cu Kα radiation resulted in consistent values for the commonly applied enanti­opol parameters. Their final standard uncertainties are still rather high, but our assignment is in agreement with the expected retention at the stereocentre of the starting material and could be further corroborated by the match between experimentally observed and theoretically calculated CD spectra. The associated Cotton effect was well reproduced by our TDDFT calculations, thus confirming that our methodology was suitable. We hope to use enanti­opure (1) in future experiments as a ditopic ligand with the additional possibility to transfer central chirality from the ligand to its coordination com­plexes (Wang et al., 2015[Wang, A., Merkens, C. & Englert, U. (2015). CrystEngComm, 17, 4293-4300.]).

Supporting information


Computing details top

For both structures, data collection: SMART (Bruker, 2001); cell refinement: SMART (Bruker, 2001); data reduction: SAINT-Plus (Bruker, 2009); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2017 (Sheldrick, 2015); software used to prepare material for publication: SHELXL2017 (Sheldrick, 2015) and PLATON (Spek, 2009).

(2S)-Methyl (Z)-5-(2-tert-butoxy-1-cyano-2-oxoethylidene)pyrrolidine-2-carboxylate (1mo) top
Crystal data top
C13H18N2O4Dx = 1.278 Mg m3
Mr = 266.29Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 1389 reflections
a = 7.347 (4) Åθ = 2.3–20.4°
b = 10.197 (6) ŵ = 0.10 mm1
c = 18.477 (10) ÅT = 100 K
V = 1384.1 (13) Å3Block, colourless
Z = 40.35 × 0.29 × 0.28 mm
F(000) = 568
Data collection top
D8 goniometer with APEX CCD area detector
diffractometer
2290 independent reflections
Radiation source: Incoatec microsource2051 reflections with I > 2σ(I)
Multilayer optics monochromatorRint = 0.091
ω scansθmax = 24.5°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 88
Tmin = 0.473, Tmax = 0.745k = 1111
10626 measured reflectionsl = 2121
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.051 w = 1/[σ2(Fo2) + (0.0228P)2 + 0.6063P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.124(Δ/σ)max < 0.001
S = 1.08Δρmax = 0.21 e Å3
2290 reflectionsΔρmin = 0.18 e Å3
180 parametersAbsolute structure: Flack x determined using 710 quotients [(I+)-(I)-]/[(I+)+(I)-] (Parsons et al., 2013)
0 restraintsAbsolute structure parameter: 1.1 (10)
Primary atom site location: structure-invariant direct methods
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.4701 (4)0.3508 (3)0.57875 (17)0.0391 (9)
O20.6551 (4)0.4427 (3)0.66052 (15)0.0254 (7)
O30.7806 (4)0.8818 (3)0.62664 (16)0.0255 (7)
O41.0663 (4)0.9541 (2)0.64917 (14)0.0209 (7)
N10.7498 (4)0.6385 (3)0.56925 (18)0.0209 (8)
H1N0.678 (6)0.706 (4)0.587 (2)0.022 (11)*
N21.3786 (5)0.7260 (3)0.5969 (2)0.0288 (9)
C10.6749 (6)0.5183 (3)0.5387 (2)0.0222 (9)
H10.5822800.5419440.5012890.027*
C20.8415 (6)0.4571 (4)0.5008 (2)0.0261 (10)
H2A0.8430250.3606840.5072550.031*
H2B0.8404890.4770850.4483240.031*
C31.0056 (6)0.5202 (4)0.5376 (2)0.0225 (9)
H3A1.0559950.4622370.5756570.027*
H3B1.1024710.5405540.5021260.027*
C40.9278 (5)0.6441 (4)0.5701 (2)0.0188 (9)
C50.5863 (6)0.4285 (4)0.5946 (2)0.0250 (10)
C60.5754 (7)0.3593 (5)0.7167 (2)0.0337 (11)
H6A0.4475610.3833090.7238790.051*
H6B0.6423250.3713830.7621090.051*
H6C0.5831670.2672160.7017440.051*
C71.0311 (5)0.7484 (4)0.5966 (2)0.0191 (9)
C81.2223 (6)0.7373 (4)0.5960 (2)0.0213 (9)
C90.9428 (6)0.8655 (4)0.6249 (2)0.0195 (9)
C101.0040 (6)1.0830 (3)0.6775 (2)0.0244 (10)
C111.1794 (7)1.1500 (4)0.6988 (3)0.0343 (11)
H11A1.2602781.1549120.6567480.051*
H11B1.2388271.0997480.7373860.051*
H11C1.1528721.2387650.7162180.051*
C120.9109 (7)1.1592 (4)0.6177 (2)0.0321 (11)
H12A0.9856001.1558850.5738230.048*
H12B0.8955261.2507170.6328170.048*
H12C0.7914251.1204750.6078690.048*
C130.8851 (7)1.0623 (4)0.7430 (2)0.0339 (11)
H13A0.8614221.1468550.7663970.051*
H13B0.9471191.0038970.7771910.051*
H13C0.7695921.0226280.7280740.051*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.043 (2)0.0376 (18)0.0362 (19)0.0213 (16)0.0071 (16)0.0021 (15)
O20.0312 (16)0.0225 (13)0.0224 (15)0.0040 (13)0.0023 (13)0.0021 (12)
O30.0196 (15)0.0217 (14)0.0351 (17)0.0004 (12)0.0010 (13)0.0057 (13)
O40.0229 (14)0.0140 (13)0.0259 (16)0.0008 (11)0.0018 (12)0.0007 (12)
N10.0199 (19)0.0180 (17)0.0247 (19)0.0009 (15)0.0011 (14)0.0002 (15)
N20.026 (2)0.030 (2)0.030 (2)0.0012 (15)0.0002 (16)0.0005 (16)
C10.027 (2)0.0156 (18)0.024 (2)0.0012 (16)0.0083 (18)0.0005 (16)
C20.035 (2)0.019 (2)0.023 (2)0.001 (2)0.0034 (19)0.0032 (17)
C30.027 (2)0.0164 (19)0.024 (2)0.0032 (17)0.0009 (18)0.0004 (17)
C40.025 (2)0.017 (2)0.015 (2)0.0015 (17)0.0002 (17)0.0040 (16)
C50.027 (2)0.020 (2)0.027 (3)0.0005 (18)0.0028 (19)0.0000 (18)
C60.039 (3)0.032 (2)0.030 (3)0.004 (2)0.005 (2)0.008 (2)
C70.022 (2)0.0164 (18)0.019 (2)0.0017 (17)0.0016 (17)0.0003 (16)
C80.030 (2)0.0147 (19)0.020 (2)0.0002 (17)0.0030 (18)0.0011 (16)
C90.023 (2)0.0178 (19)0.017 (2)0.0015 (17)0.0005 (17)0.0023 (17)
C100.034 (2)0.0133 (18)0.026 (2)0.0014 (17)0.000 (2)0.0048 (16)
C110.043 (3)0.022 (2)0.038 (3)0.006 (2)0.004 (2)0.006 (2)
C120.047 (3)0.020 (2)0.030 (3)0.009 (2)0.000 (2)0.0000 (19)
C130.049 (3)0.027 (2)0.025 (2)0.004 (2)0.009 (2)0.005 (2)
Geometric parameters (Å, º) top
O1—C51.201 (5)C4—C71.395 (5)
O2—C51.327 (5)C6—H6A0.9800
O2—C61.464 (5)C6—H6B0.9800
O3—C91.204 (5)C6—H6C0.9800
O4—C91.357 (5)C7—C81.409 (6)
O4—C101.487 (5)C7—C91.456 (5)
N1—C41.309 (5)C10—C131.507 (6)
N1—C11.457 (5)C10—C111.511 (6)
N1—H1N0.93 (4)C10—C121.514 (6)
N2—C81.154 (5)C11—H11A0.9800
C1—C51.525 (6)C11—H11B0.9800
C1—C21.543 (6)C11—H11C0.9800
C1—H11.0000C12—H12A0.9800
C2—C31.527 (6)C12—H12B0.9800
C2—H2A0.9900C12—H12C0.9800
C2—H2B0.9900C13—H13A0.9800
C3—C41.510 (5)C13—H13B0.9800
C3—H3A0.9900C13—H13C0.9800
C3—H3B0.9900
C5—O2—C6115.8 (3)H6A—C6—H6C109.5
C9—O4—C10119.9 (3)H6B—C6—H6C109.5
C4—N1—C1114.7 (4)C4—C7—C8118.6 (4)
C4—N1—H1N122 (3)C4—C7—C9120.6 (3)
C1—N1—H1N123 (3)C8—C7—C9120.8 (4)
N1—C1—C5113.9 (3)N2—C8—C7178.3 (5)
N1—C1—C2102.5 (3)O3—C9—O4124.1 (4)
C5—C1—C2113.8 (3)O3—C9—C7124.3 (4)
N1—C1—H1108.8O4—C9—C7111.5 (3)
C5—C1—H1108.8O4—C10—C13109.7 (3)
C2—C1—H1108.8O4—C10—C11103.2 (3)
C3—C2—C1104.6 (3)C13—C10—C11110.4 (4)
C3—C2—H2A110.8O4—C10—C12109.6 (3)
C1—C2—H2A110.8C13—C10—C12113.3 (4)
C3—C2—H2B110.8C11—C10—C12110.1 (4)
C1—C2—H2B110.8C10—C11—H11A109.5
H2A—C2—H2B108.9C10—C11—H11B109.5
C4—C3—C2103.4 (3)H11A—C11—H11B109.5
C4—C3—H3A111.1C10—C11—H11C109.5
C2—C3—H3A111.1H11A—C11—H11C109.5
C4—C3—H3B111.1H11B—C11—H11C109.5
C2—C3—H3B111.1C10—C12—H12A109.5
H3A—C3—H3B109.1C10—C12—H12B109.5
N1—C4—C7125.5 (4)H12A—C12—H12B109.5
N1—C4—C3109.7 (4)C10—C12—H12C109.5
C7—C4—C3124.8 (3)H12A—C12—H12C109.5
O1—C5—O2124.5 (4)H12B—C12—H12C109.5
O1—C5—C1122.3 (4)C10—C13—H13A109.5
O2—C5—C1113.2 (3)C10—C13—H13B109.5
O2—C6—H6A109.5H13A—C13—H13B109.5
O2—C6—H6B109.5C10—C13—H13C109.5
H6A—C6—H6B109.5H13A—C13—H13C109.5
O2—C6—H6C109.5H13B—C13—H13C109.5
(1cu) top
Crystal data top
C13H18N2O4Dx = 1.273 Mg m3
Mr = 266.29Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P212121Cell parameters from 6101 reflections
a = 7.3731 (3) Åθ = 7.4–66.3°
b = 10.1909 (4) ŵ = 0.79 mm1
c = 18.4972 (7) ÅT = 100 K
V = 1389.85 (9) Å3Block, colourless
Z = 40.35 × 0.29 × 0.28 mm
F(000) = 568
Data collection top
D8 goniometer with APEX CCD area detector
diffractometer
2408 independent reflections
Radiation source: microsource2266 reflections with I > 2σ(I)
Multilayer optics monochromatorRint = 0.083
ω scansθmax = 67.0°, θmin = 4.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 68
Tmin = 0.579, Tmax = 0.753k = 1112
17945 measured reflectionsl = 2122
Refinement top
Refinement on F2H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full w = 1/[σ2(Fo2) + (0.0379P)2 + 0.044P]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.032(Δ/σ)max < 0.001
wR(F2) = 0.077Δρmax = 0.17 e Å3
S = 1.10Δρmin = 0.15 e Å3
2408 reflectionsExtinction correction: SHELXL2017 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
181 parametersExtinction coefficient: 0.0076 (11)
0 restraintsAbsolute structure: Flack x determined using 879 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: otherAbsolute structure parameter: 0.04 (12)
Hydrogen site location: difference Fourier map
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.4715 (2)0.35039 (16)0.57878 (9)0.0376 (4)
O20.65579 (19)0.44278 (13)0.66057 (7)0.0237 (3)
O30.78055 (18)0.88187 (13)0.62654 (8)0.0237 (3)
O41.06691 (18)0.95433 (13)0.64909 (7)0.0202 (3)
N10.7503 (2)0.63780 (17)0.56914 (9)0.0187 (4)
H1N0.692 (3)0.697 (2)0.5869 (12)0.018 (6)*
N21.3791 (2)0.72560 (18)0.59679 (10)0.0267 (4)
C10.6751 (3)0.51862 (18)0.53858 (11)0.0203 (4)
H10.5828170.5423740.5011790.024*
C20.8411 (3)0.4564 (2)0.50098 (11)0.0234 (5)
H2A0.8423500.3601430.5080200.028*
H2B0.8400370.4754750.4484980.028*
C31.0061 (3)0.52038 (19)0.53757 (11)0.0213 (5)
H3A1.0566340.4627570.5756530.026*
H3B1.1022390.5402750.5018630.026*
C40.9292 (3)0.64441 (19)0.56957 (10)0.0174 (4)
C50.5877 (3)0.4288 (2)0.59448 (12)0.0231 (5)
C60.5765 (3)0.3592 (2)0.71600 (12)0.0313 (5)
H6A0.4506240.3857320.7246330.047*
H6B0.6461580.3678590.7608750.047*
H6C0.5794130.2676230.6998200.047*
C71.0309 (3)0.74868 (19)0.59624 (10)0.0177 (4)
C81.2227 (3)0.73732 (18)0.59618 (10)0.0189 (4)
C90.9449 (3)0.86551 (18)0.62494 (10)0.0184 (4)
C101.0050 (3)1.08275 (18)0.67754 (11)0.0223 (5)
C111.1811 (3)1.1505 (2)0.69862 (13)0.0316 (5)
H11A1.2593691.1583320.6560030.047*
H11B1.2431471.0986500.7357670.047*
H11C1.1543411.2381160.7176510.047*
C120.9115 (3)1.1594 (2)0.61785 (12)0.0285 (5)
H12A0.9876901.1588640.5744260.043*
H12B0.8923011.2500880.6337010.043*
H12C0.7942851.1187120.6068710.043*
C130.8863 (3)1.0623 (2)0.74316 (12)0.0317 (5)
H13A0.8603541.1471940.7657350.047*
H13B0.9492751.0056420.7778590.047*
H13C0.7723201.0206170.7284420.047*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0368 (9)0.0376 (9)0.0386 (9)0.0201 (8)0.0091 (7)0.0024 (7)
O20.0232 (7)0.0229 (7)0.0250 (7)0.0035 (6)0.0033 (6)0.0027 (6)
O30.0129 (7)0.0230 (7)0.0353 (8)0.0011 (6)0.0011 (6)0.0047 (6)
O40.0180 (7)0.0152 (6)0.0275 (7)0.0006 (6)0.0014 (5)0.0026 (6)
N10.0145 (8)0.0154 (8)0.0262 (9)0.0022 (7)0.0009 (6)0.0020 (7)
N20.0182 (10)0.0293 (10)0.0328 (10)0.0002 (7)0.0007 (7)0.0005 (8)
C10.0182 (10)0.0169 (9)0.0257 (10)0.0003 (8)0.0065 (8)0.0009 (7)
C20.0265 (11)0.0190 (10)0.0248 (10)0.0002 (9)0.0017 (8)0.0024 (8)
C30.0196 (10)0.0191 (10)0.0253 (10)0.0038 (8)0.0003 (8)0.0015 (8)
C40.0168 (9)0.0170 (10)0.0184 (9)0.0017 (8)0.0002 (7)0.0034 (8)
C50.0182 (10)0.0202 (10)0.0310 (12)0.0001 (9)0.0045 (8)0.0021 (8)
C60.0332 (12)0.0291 (11)0.0315 (12)0.0038 (10)0.0041 (10)0.0046 (9)
C70.0140 (9)0.0175 (9)0.0216 (10)0.0015 (8)0.0008 (8)0.0013 (8)
C80.0193 (10)0.0162 (9)0.0212 (10)0.0011 (8)0.0013 (8)0.0013 (7)
C90.0199 (10)0.0163 (9)0.0189 (9)0.0026 (8)0.0019 (8)0.0028 (8)
C100.0254 (11)0.0152 (9)0.0262 (11)0.0005 (8)0.0007 (9)0.0029 (7)
C110.0337 (12)0.0220 (10)0.0391 (12)0.0057 (10)0.0048 (10)0.0058 (9)
C120.0367 (12)0.0213 (10)0.0276 (11)0.0054 (10)0.0001 (9)0.0018 (9)
C130.0423 (13)0.0272 (11)0.0254 (11)0.0010 (11)0.0044 (10)0.0048 (9)
Geometric parameters (Å, º) top
O1—C51.207 (3)C4—C71.391 (3)
O2—C51.329 (3)C6—H6A0.9800
O2—C61.456 (3)C6—H6B0.9800
O3—C91.223 (2)C6—H6C0.9800
O4—C91.352 (2)C7—C81.419 (3)
O4—C101.483 (2)C7—C91.450 (3)
N1—C41.321 (3)C10—C131.511 (3)
N1—C11.450 (3)C10—C121.518 (3)
N1—H1N0.81 (3)C10—C111.522 (3)
N2—C81.159 (3)C11—H11A0.9800
C1—C51.524 (3)C11—H11B0.9800
C1—C21.544 (3)C11—H11C0.9800
C1—H11.0000C12—H12A0.9800
C2—C31.537 (3)C12—H12B0.9800
C2—H2A0.9900C12—H12C0.9800
C2—H2B0.9900C13—H13A0.9800
C3—C41.506 (3)C13—H13B0.9800
C3—H3A0.9900C13—H13C0.9800
C3—H3B0.9900
C5—O2—C6115.70 (16)H6A—C6—H6C109.5
C9—O4—C10120.21 (15)H6B—C6—H6C109.5
C4—N1—C1115.28 (18)C4—C7—C8118.35 (18)
C4—N1—H1N119.4 (16)C4—C7—C9121.41 (17)
C1—N1—H1N125.2 (16)C8—C7—C9120.23 (18)
N1—C1—C5113.59 (17)N2—C8—C7178.6 (2)
N1—C1—C2102.49 (15)O3—C9—O4124.03 (17)
C5—C1—C2113.24 (15)O3—C9—C7123.66 (17)
N1—C1—H1109.1O4—C9—C7112.31 (16)
C5—C1—H1109.1O4—C10—C13109.97 (16)
C2—C1—H1109.1O4—C10—C12109.63 (16)
C3—C2—C1104.78 (15)C13—C10—C12113.13 (18)
C3—C2—H2A110.8O4—C10—C11103.20 (16)
C1—C2—H2A110.8C13—C10—C11110.56 (18)
C3—C2—H2B110.8C12—C10—C11109.90 (18)
C1—C2—H2B110.8C10—C11—H11A109.5
H2A—C2—H2B108.9C10—C11—H11B109.5
C4—C3—C2103.35 (15)H11A—C11—H11B109.5
C4—C3—H3A111.1C10—C11—H11C109.5
C2—C3—H3A111.1H11A—C11—H11C109.5
C4—C3—H3B111.1H11B—C11—H11C109.5
C2—C3—H3B111.1C10—C12—H12A109.5
H3A—C3—H3B109.1C10—C12—H12B109.5
N1—C4—C7125.43 (18)H12A—C12—H12B109.5
N1—C4—C3109.30 (17)C10—C12—H12C109.5
C7—C4—C3125.26 (17)H12A—C12—H12C109.5
O1—C5—O2124.1 (2)H12B—C12—H12C109.5
O1—C5—C1122.31 (19)C10—C13—H13A109.5
O2—C5—C1113.59 (16)C10—C13—H13B109.5
O2—C6—H6A109.5H13A—C13—H13B109.5
O2—C6—H6B109.5C10—C13—H13C109.5
H6A—C6—H6B109.5H13A—C13—H13C109.5
O2—C6—H6C109.5H13B—C13—H13C109.5
C4—N1—C1—C5109.61 (19)N1—C1—C5—O226.3 (2)
C4—N1—C1—C212.9 (2)C2—C1—C5—O290.1 (2)
N1—C1—C2—C320.43 (19)C3—C4—C7—C82.4 (3)
C1—N1—C4—C7179.84 (18)N1—C4—C7—C92.1 (3)
C1—N1—C4—C30.6 (2)C10—O4—C9—O32.1 (3)
C2—C3—C4—N114.0 (2)C4—C7—C9—O31.4 (3)
C6—O2—C5—O12.2 (3)C8—C7—C9—O40.4 (3)
C6—O2—C5—C1179.93 (16)C9—O4—C10—C1361.8 (2)
N1—C1—C5—O1155.73 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O30.81 (3)2.13 (2)2.714 (2)129 (2)
N1—H1N···N2i0.81 (3)2.33 (2)2.924 (2)131 (2)
C11—H11B···O2ii0.982.603.565 (3)169
Symmetry codes: (i) x1, y, z; (ii) x+2, y+1/2, z+3/2.
Excitation wavelengths (λ), oscillator (f) and rotational (R) strengths and transition assignments. top
λ(nm)fR(DBM)Occ–VirtAssignments
2620.26700.4600HOMOLUMOπcoplanarπ*coplanar (77%)
HOMOLUMO+1πcoplanarπ*COO in COOCH3(19%)
2500.1642-0.6047HOMOLUMO+1πcoplanarπ*COO in COOCH3(77%)
HOMOLUMOπcoplanarπ*coplanar (20.00%)
2390.0028-0.0173HOMO-1LUMOσ+nN+nOπ*coplanar (89%)
 

Acknowledgements

The authors acknowledge support from the One Hundred-Talent Program of Shanxi Province and thank Irmgard Kalf for help with the synthesis of (1). Funding was provided by the China Scholarship Council (scholarship to AW).

References

First citationBecke, A. D. (1993). J. Chem. Phys. 98, 5648–5652.  CrossRef CAS Web of Science Google Scholar
First citationBöhme, U. & Fels, S. (2013). Acta Cryst. C69, 44–46.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationBrown, A., Kemp, C. M. & Mason, S. F. (1971). J. Chem. Soc. A, pp. 751–755.  CrossRef Web of Science Google Scholar
First citationBruker (2001). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBruker (2008). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBruker (2009). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationChen, Q.-B., Xin, X.-L. & Asia, H. A. (2017). Phys. Chem. Lett. 19, 168–171.  CAS Google Scholar
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationFlack, H. D. (2003). Helv. Chim. Acta, 86, 905–921.  Web of Science CrossRef CAS Google Scholar
First citationFlack, H. D. & Bernardinelli, G. (2003). Cryst. Eng. 6, 213–223.  Web of Science CrossRef CAS Google Scholar
First citationFlack, H. D. & Shmueli, U. (2007). Acta Cryst. A63, 257–265.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationFrisch, M. J., et al. (2009). GAUSSIAN09. Gaussian, Inc., Wallingford, CT, USA. https://www.gaussian.comGoogle Scholar
First citationFritschi, H., Leutenegger, U., Siegmann, K., Pfaltz, A., Keller, W. & Kratky, C. (1988). Helv. Chim. Acta, 71, 1541–1552.  CSD CrossRef CAS Web of Science Google Scholar
First citationGhinet, A., Van Hijfte, N., Gautret, P., Rigo, B., Oulyadi, H. & Rousseau, J. (2012). Tetrahedron, 68, 1109–1116.  Web of Science CrossRef CAS Google Scholar
First citationHooft, R. W. W., Straver, L. H. & Spek, A. L. (2010). J. Appl. Cryst. 43, 665–668.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationJensen, K. J., Dickmeiss, G., Jiang, H., Albrecht, L. & Jørgensen, K. A. (2012). Acc. Chem. Res. 45, 248–264.  Web of Science CrossRef CAS PubMed Google Scholar
First citationKremer, M. & Englert, U. (2018). Z. Kristallogr. 233, 437–452.  Web of Science CrossRef CAS Google Scholar
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationPfaltz, A. (1993). Acc. Chem. Res. 26, 339–345.  CrossRef CAS Web of Science Google Scholar
First citationPfaltz, A., Bühler, N., Neier, R., Hirai, K. & Eschenmoser, A. (1977). Helv. Chim. Acta, 60, 2653–2672.  CrossRef CAS Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationTomasi, J., Mennucci, B. & Cammi, R. (2005). Chem. Rev. 105, 2999–3093.  Web of Science CrossRef PubMed CAS Google Scholar
First citationWang, A., Merkens, C. & Englert, U. (2015). CrystEngComm, 17, 4293–4300.  Web of Science CSD CrossRef CAS Google Scholar

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