nmr crystallography\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2053-2296

Single-crystal X-ray diffraction and NMR crystallography of a 1:1 cocrystal of di­thia­non and pyrimethanil

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aDepartment of Physics, University of Warwick, Coventry CV4 7AL, United Kingdom, bDepartment of Organic Chemistry, University of Würzburg, 97074 Würzburg, Germany, cMolecular Analytical Science Centre for Doctoral Training, University of Warwick, Coventry CV4 7AL, United Kingdom, dInternational Research Centre, Syngenta, Jealott's Hill, Bracknell, Berkshire RG42 6EY, United Kingdom, and eAfton Chemical, London Road, Bracknell, Berkshire RG12 2UW, United Kingdom
*Correspondence e-mail: s.p.brown@warwick.ac.uk

Edited by D. L. Bryce, University of Ottawa, Canada (Received 30 September 2016; accepted 17 January 2017; online 6 February 2017)

A single-crystal X-ray diffraction structure of a 1:1 cocrystal of two fungicides, namely di­thia­non (DI) and pyrimethanil (PM), is reported [systematic name: 5,10-dioxo-5H,10H-naphtho­[2,3-b][1,4]dithiine-2,3-dicarbo­nitrile–4,6-dimethyl-N-phenyl­pyrimidin-2-amine (1/1), C14H4N2O2S2·C12H13N2]. Following an NMR crystallography approach, experimental solid-state magic angle spinning (MAS) NMR spectra are presented together with GIPAW (gauge-including projector augmented wave) calculations of NMR chemical shieldings. Specifically, experimental 1H and 13C chemical shifts are determined from two-dimensional 1H–13C MAS NMR correlation spectra recorded with short and longer contact times so as to probe one-bond C—H connectivities and longer-range C⋯H proximities, whereas H⋯H proximities are identified in a 1H double-quantum (DQ) MAS NMR spectrum. The performing of separate GIPAW calculations for the full periodic crystal structure and for isolated mol­ecules allows the determination of the change in chemical shift upon going from an isolated mol­ecule to the full crystal structure. For the 1H NMR chemical shifts, changes of 3.6 and 2.0 ppm correspond to inter­molecular N—H⋯O and C—H⋯O hydrogen bonding, while changes of −2.7 and −1.5 ppm are due to ring current effects associated with C—H⋯π inter­actions. Even though there is a close inter­molecular S⋯O distance of 3.10 Å, it is of note that the mol­ecule-to-crystal chemical shifts for the involved sulfur or oxygen nuclei are small.

1. Introduction

With an increasing global population, limited availability of arable land, an increase in extreme weather events and growing pest resistance to certain existing agrochemical products, innovation in the agrochemical industry is as important as ever if we are to provide enough food for everyone. With lower usage rates, ease of use and more favourable toxicology profiles being important objectives, the search for and structure-based design of potential agrochemical products needs to become more efficient (Lamberth et al., 2013[Lamberth, C., Jeanmart, S., Luksch, T. & Plant, A. (2013). Science, 341, 742-746.]). One possibility in this regard is the usage of cocrystals formed between an active ingredient and coformers or other active ingredients via reversible noncovalent inter­actions. While this is an established procedure in the development of new active pharmaceutical ingredients, where it is used to increase the solubility and bioavailability (Blagden et al., 2007[Blagden, N., de Matas, M., Gavan, P. T. & York, P. (2007). Adv. Drug Deliv. Rev. 59, 617-630.]), there is also great potential to exploit cocrystals in the optimization and development of agrochemicals. For example, a reduced solubility could increase the agrochemical's residence time on the respective plant and multicomponent entities could improve the release profile (and thus absolute usage), as well as allow the simultaneous delivery of two or more active components. However, the design of suitable cocrystalline materials and prediction of their properties and formed cocrystal structures is far from being trivial. Some design strategies based on the hierarchy of inter­molecular inter­actions (Aakeroy & Salmon, 2005[Aakeroy, C. B. & Salmon, D. J. (2005). CrystEngComm, 7, 439-448.]) or the assessment of the solubilities and saturation temperatures of the pure compounds to be included in a cocrystalline arrangement (ter Horst et al., 2009[Horst, J. H. ter, Deij, M. A. & Cains, P. W. (2009). Cryst. Growth Des. 9, 1531-1537.]) are available as a guideline. However, if multiple and different hydrogen-bonding donors and acceptors are present in the mol­ecules, a reliable prediction of the resulting structure becomes very difficult (Bhatt et al., 2009[Bhatt, P. M., Azim, Y., Thakur, T. S. & Desiraju, G. R. (2009). Cryst. Growth Des. 9, 951-957.]).

NMR crystallography, namely the combination of experimental solid-state magic angle spinning (MAS) NMR with calculation of NMR parameters, is finding important application to moderately sized organic mol­ecules (Harris, 2004[Harris, R. K. (2004). Solid State Sci. 6, 1025-1037.]; Elena et al., 2006[Elena, B., Pintacuda, G., Mifsud, N. & Emsley, L. (2006). J. Am. Chem. Soc. 128, 9555-9560.]; Harris et al., 2009[Harris, R. K., Wasylishen, R. E. & Duer, M. J. (2009). Editors. NMR Crystallography. Chichester: Wiley.]; Bonhomme et al., 2012[Bonhomme, C., Gervais, C., Babonneau, F., Coelho, C., Pourpoint, F., Azais, T., Ashbrook, S. E., Griffin, J. M., Yates, J. R., Mauri, F. & Pickard, C. J. (2012). Chem. Rev. 112, 5733-5779.]). We present here an NMR crystallography analysis of the 1:1 cocrystal of two fungicides, namely di­thia­non (DI) and pyrimethanil (PM). Specifically, following a preparation protocol in Sowa et al. (2013[Sowa, C., Saxell, H. E. & Vogel, R. (2013). EU Patent EP 2197278.]), a single-crystal X-ray diffraction structure determination is reported, with this structure (after DFT geometry optimization) providing the input for a calculation, using the GIPAW (gauge-including projector augmented wave) method (Pickard & Mauri, 2001[Pickard, C. J. & Mauri, F. (2001). Phys. Rev. B 63, 245101.]; Yates et al., 2007[Yates, J. R., Pickard, C. J. & Mauri, F. (2007). Phys. Rev. B, 76, 024401.]), of the NMR chemical shieldings. The computational analysis is complemented by the recording of 1D (one-dimensional) and 2D (two-dimensional) experimental 1H and 13C MAS NMR spectra. Building upon studies of pharmaceutical cocrystals by such an NMR crystallography investigation (Tatton et al., 2013[Tatton, A. S., Pham, T. N., Vogt, F. G., Iuga, D., Edwards, A. J. & Brown, S. P. (2013). Mol. Pharm. 10, 999-1007.]; Dudenko et al., 2013[Dudenko, D. V., Yates, J. R., Harris, K. D. M. & Brown, S. P. (2013). CrystEngComm, 15, 8797-8807.]; Stevens et al., 2014[Stevens, J. S., Byard, S. J., Seaton, C. C., Sadiq, G., Davey, R. J. & Schroeder, S. L. M. (2014). Phys. Chem. Chem. Phys. 16, 1150-1160.]; Kerr et al., 2015[Kerr, H. E., Softley, L. K., Suresh, K., Nangia, A., Hodgkinson, P. & Evans, I. R. (2015). CrystEngComm, 17, 6707-6715.]; Sardo et al., 2015[Sardo, M., Santos, S. M., Babaryk, A. A., Lopez, C., Alkorta, I., Elguero, J., Claramunt, R. M. & Mafra, L. (2015). Solid State Nucl. Magn. Reson. 65, 49-63.]; Luedeker et al., 2016[Luedeker, D., Gossmann, R., Langer, K. & Brunklaus, G. (2016). Cryst. Growth Des. 16, 3087-3100.]), we present here the application of this approach to an agrochemical cocrystal.

2. Experimental and computational details

2.1. Sample preparation

The DI–PM cocrystal was prepared according to method VII in point [0041] of Sowa et al. (2013[Sowa, C., Saxell, H. E. & Vogel, R. (2013). EU Patent EP 2197278.]), i.e. dry di­thia­non and pyrimethanil (both solids) were mixed thoroughly in a 1:1 molar ratio (0.5 g of pyrimethanil) and kept at 323 K under agitation. After a couple of hours, the powdery product had changed to a dark-olive-green colour.

[Scheme 1]

2.2. Single-crystal X-ray diffraction: structure solution and refinement

Crystal data, data collection and structure refinement details are summarized in Table 1[link]. The H atoms were all located in a difference map, but those attached to C atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry [C—H = 0.93–0.98 Å and N—H = 0.86–0.89 Å, and with Uiso(H) = 1.2–1.5Ueq(parent)], after which the positions were refined with riding constraints (Cooper et al., 2010[Cooper, R. I., Thompson, A. L. & Watkin, D. J. (2010). J. Appl. Cryst. 43, 1100-1107.]).

Table 1
Experimental details

Crystal data
Chemical formula C14H4N2O2S2·C12H13N3
Mr 495.59
Crystal system, space group Monoclinic, P21/n
Temperature (K) 100
a, b, c (Å) 7.1707 (2), 22.8006 (6), 13.8237 (4)
β (°) 97.047 (3)
V3) 2243.04 (7)
Z 4
Radiation type Cu Kα
μ (mm−1) 2.45
Crystal size (mm) 0.60 × 0.10 × 0.02
 
Data collection
Diffractometer Agilent Xcalibur Onyx Ultra
Absorption correction Multi-scan (CrysAlis PRO; Agilent, 2014[Agilent (2014). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.])
Tmin, Tmax 0.596, 1.000
No. of measured, independent and observed [I > 2.0σ(I)] reflections 5143, 3160, 2667
Rint 0.035
θmax (°) 58.9
(sin θ/λ)max−1) 0.556
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.094, 0.98
No. of reflections 3141
No. of parameters 109
No. of restraints 3
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.43, −0.37
Computer programs: CrysAlis PRO (Agilent, 2014[Agilent (2014). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, Oxfordshire, England.]), SUPERFLIP (Palatinus & Chapuis, 2007[Palatinus, L. & Chapuis, G. (2007). J. Appl. Cryst. 40, 786-790.]), CRYSTALS (Betteridge et al., 2003[Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.]), CAMERON (Watkin et al., 1996[Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, Oxford, England.]) and Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]).

2.3. Solid-state NMR

1D 1H MAS and 1D 13C cross polarization (CP) MAS experiments were performed on a Bruker Avance III spectrometer operating at 1H and 13C Larmor frequencies of 600 and 150.9 MHz, respectively, using a 1.3 mm HXY (1H MAS) or a 4 mm HX (13C CP MAS) Bruker probe. In all cases, a 1H 90° pulse duration of 2.5 µs was used. 2D 1H–13C HETCOR experiments were performed on a Bruker Avance III spectrometer, using a 4 mm HXY probe in double-resonance mode. In the HETCOR pulse sequence, the following phase cycling was employed: 1H 90° pulse (90° 270°), 13C 180° pulse (2{0°} 2{180°}), 13C CP contact pulse (4{0°} 4{180°} 4{90°} 4{270°}), receiver (0° 180° 0° 180° 180° 0° 180° 0° 90° 270° 90° 270° 270° 90° 270° 90°). For CP, a 70 to 100% ramp (Metz et al., 1994[Metz, G., Wu, X. L. & Smith, S. O. (1994). J. Magn. Reson. Ser. A, 110, 219-227.]) on the 1H channel was used for the CP contact time. During acquisition of a 13C FID, SPINAL64 (Fung et al., 2000[Fung, B. M., Khitrin, A. K. & Ermolaev, K. (2000). J. Magn. Reson. 142, 97-101.]) 1H heteronuclear decoupling was applied with a pulse duration of 5.9 µs at a nutation frequency of 100 kHz. A 2D 1H DQ experiment with BABA recoupling (Sommer et al., 1995[Sommer, W., Gottwald, J., Demco, D. E. & Spiess, H. W. (1995). J. Magn. Reson. Ser. A, 113, 131-134.]; Schnell et al., 1998[Schnell, I., Lupulescu, A., Hafner, S., Demco, D. E. & Spiess, H. W. (1998). J. Magn. Reson. 133, 61-69.]) was performed on a Bruker Avance III spectrometer operating at a 1H Larmor frequency of 700 MHz using a 1.3 mm HXY Bruker probe. A 16-step phase cycle was used to select Δp = ±2 on the DQ excitation block and Δp = −1 on the z-filter 90° pulse, where p is the coherence order. In all 2D experiments, the States–TPPI method was used to achieve sign discrimination in F1. 13C and 1H chemical shifts are referenced with respect to TMS using L-alanine at natural abundance as an external reference: 177.8 ppm for the 13C carboxyl­ate resonance and 1.1 ppm for the 1H methyl resonance. All experiments were performed at room temperature, though frictional effects due to MAS increase the actual sample temperature (Langer et al., 1999[Langer, B., Schnell, I., Spiess, H. W. & Grimmer, A. R. (1999). J. Magn. Reson. 138, 182-186.]).

2.4. DFT calculations

Calculations were performed using CASTEP (Clark et al., 2005[Clark, S. J., Segall, M. D., Pickard, C. J., Hasnip, P. J., Probert, M. J., Refson, K. & Payne, M. C. (2005). Z. Kristallogr. 220, 567-570.]; Academic Release Version 8.0) and employed the PBE exchange-correlational functional (Perdew et al., 1996[Perdew, J. P., Burke, K. & Ernzerhof, M. (1996). Phys. Rev. Lett. 77, 3865-3868.]). For both geometry optimization and NMR shielding calculations, a plane-wave basis set with ultrasoft pseudopotentials (Vanderbilt, 1990[Vanderbilt, D. (1990). Phys. Rev. B, 41, 7892.]) with a maximum plane-wave cut-off energy of 700 eV was used. A Monkhorst–Pack grid of minimum sample spacing 0.05 × 2π Å−1 was used to take integrals over the Brillouin zone. Geometry optimization was performed with the unit-cell parameters fixed, starting from the single-crystal X-ray structure. The positions of the 208 atoms in the unit cell (Z = 4, Z′ = 1) were relaxed and periodic boundary conditions were applied. The space group P21/n was preserved. All distances and angles stated in the main text of this article are for the geometry-optimized crystal structure. Note also that the geometry optimization within CASTEP causes a relabelling of the atoms – in this article, we use the CASTEP numbering; see Fig. S1 in the Supporting information for a comparison with the numbering employed in the crystallographic CIF file. The GIPAW method (Pickard & Mauri, 2001[Pickard, C. J. & Mauri, F. (2001). Phys. Rev. B 63, 245101.]; Yates et al., 2007[Yates, J. R., Pickard, C. J. & Mauri, F. (2007). Phys. Rev. B, 76, 024401.]) was utilized for the NMR chemical-shielding calculations, which were performed on the geometry-optimized structure. For the isolated mol­ecule calculations, a single mol­ecule (either DI or PM) from the fully geometry optimized structure is kept in the unit cell, whose dimensions are also increased by ∼5 Å in each direction – the NMR shieldings are then calculated without any further geometry optimization.

3. Results and discussion

3.1. Single-crystal X-ray diffraction structure

The single-crystal X-ray diffraction structure of the DI–PM cocrystal is schematically represented in Fig. 1[link]. As shown in Fig. 1[link](a), a chain of mol­ecules is held together by N—H⋯O and C—H⋯O hydrogen bonds (between DI and PM mol­ecules) and by putative S⋯O inter­actions (Burling & Goldstein, 1992[Burling, F. T. & Goldstein, B. M. (1992). J. Am. Chem. Soc. 114, 2313-2320.]) between two DI mol­ecules; note that the relative strengths of these inter­actions is investigated below (see §3.5[link]) using GIPAW calculations of NMR chemical shieldings. The further packing of two chains of mol­ecules as `layers' and a `zigzag' arrangement of chains are shown in Figs. 1[link](b) and 1(c), respectively. As can be seen from the representation along the crystallographic a axis in Fig. 1[link](c), the packing is based on assemblies of blocks of four mol­ecules; four mol­ecules (PM–DI–DI–PM) are arranged in a layer (Fig. 1[link]a), forming a block that is perpendicular to an adjacent block of four mol­ecules, thus building up the `zigzag' arrangement.

[Figure 1]
Figure 1
Representations of the crystal structure of the DI–PM cocrystal, showing (a) the inter­molecular inter­actions within a `chain' of mol­ecules, with displacement ellipsoids drawn at the 50% probability level, (b) the packing of two chains of mol­ecules as `layers' and (c) the `zigzag' arrangement of chains (viewed along the crystallographic a axis). In parts (b) and (c), the unit cell is shown, indicating the a, b and c unit-cell axes.

3.2. Experimental and calculated 13C chemical shifts

Fig. 2[link] presents a 13C CP MAS NMR 1D spectrum (Fig. 2[link]a) of the DI–PM cocrystal, together with three stick spectra (Figs. 2[link]b, 2c and 2d) that represent 13C chemical shifts calculated using the GIPAW method for the DI–PM crystal structure. Specifically, the calculated 13C chemical shifts are presented in three groups according to whether they correspond to direct one-bond C—H connectivities (Fig. 2[link]b, red labels) or nonprotonated C atoms (Figs. 2[link]c and 2d, blue and green labels, respectively). The distinction between Figs. 2[link](c) and 2(d) corresponds to whether cross peaks corresponding to a longer-range C⋯H proximity are observed in 1H–13C 2D correlation spectra (see §3.4[link]).

[Figure 2]
Figure 2
(a) A 1H (600 MHz)–13C CP MAS (12.5 kHz) NMR spectrum of the DI–PM cocrystal (* denote spinning sidebands), together with (b)–(d) stick spectra corresponding to calculated (GIPAW) 13C chemical shifts (see Table 2[link]). Separate stick spectra are presented according to whether correlation peaks corresponding to (b) direct C—H bonds or (c) longer-range C⋯H proximities are observed in the 1H–13C 2D spectra presented in Fig. 4[link], or (d) where no experimental correlation peaks are observed. In the CP MAS experiment, a contact time of 1.4 ms was used and 1024 transients were co-added for a recycle delay of 57 s.

3.3. One- and two-dimensional 1H MAS NMR spectra

Figs. 3[link](a) and 3(b) present 1H NMR spectra of the DI–PM cocrystal recorded at a fast MAS frequency of 60 kHz; specifically, a one-pulse one-dimensional spectrum in Fig. 3[link](a), together with vertical lines corresponding to calculated (GIPAW) 1H chemical shifts, as well as a 2D DQ spectrum in Fig. 3[link](b). In addition, Fig. 3[link](c) presents a 1H–13C 2D correlation spectrum of the DI–PM cocrystal; note that this spectrum has been rotated through 90° from its usual representation such that the direct (13C) dimension is vertical. In this way, it is possible to directly compare (see vertical dashed lines) 1H chemical shifts of peaks in the 1H–13C (Fig. 3[link]c) and 1H DQ 2D (Fig. 3[link]b) and 1H 1D (Fig. 3[link]a) spectra. Two separate spectral regions are presented in Fig. 3[link](c) corresponding to (top) the methyl resonances at a 13C chemical shift close to 25 ppm and (bottom) the aromatic CH resonances with 13C chemical shifts between 110 and 140 ppm.

[Figure 3]
Figure 3
MAS NMR spectra of the DI–PM cocrystal, showing (a) a 1H (600 MHz) MAS (60 kHz) one-pulse spectrum (16 transients were co-added for a recycle delay of 15 s), (b) a 2D 1H (700 MHz) DQ MAS (60 kHz) spectrum (the dashed diagonal line indicates the F1 = 2F2 DQ–SQ diagonal) recorded using one rotor period of BABA recoupling (32 transients were co-added for each of 200 t1 FIDs using a recycle delay of 6 s, corresponding to a total experiment time of 12 h) and (c) a 1H (500 MHz)–13C HETCOR MAS (12.5 kHz) spectrum recorded using FSLG 1H homonuclear decoupling in t1 and a short CP transfer duration of 100 µs (104 transients were co-added for each of 128 t1 FIDs using a recycle delay of 6 s, corresponding to a total experimental time of 22 h). The vertical lines in part (a) correspond to calculated (GIPAW) 1H chemical shifts. For the 1H–13C NMR spectrum in part (c), two separate spectral regions are presented corresponding to methyl and aromatic C—H groups; note that this spectrum has been rotated through 90° from its usual representation [the 13C dimension corresponds to direct (t2) acquisition]. The base contour level is at (b) 7% and (c) 20% of the maximum peak height.

The 1H–13C correlation spectrum in Fig. 3[link](c) was recorded using a short CP contact time of 100 µs to transfer magnetization from 1H to 13C, such that cross peaks correspond to one-bond C—H connectivities. The spreading of the resonances into two dimensions in Fig. 3[link](c) allows the identification of two and ten resolved cross peaks for the CH3 and aromatic CH groups, respectively. The value of such a 1H–13C correlation spectrum in resolving and assigning the experimental 1H chemical shifts is thus evident. Table 2[link] lists the calculated (GIPAW) and experimental 13C chemical shifts (sorted in order of increasing chemical shift). For directly bonded C—H connectivities, H-atom labels and calculated (GIPAW) and experimental 1H chemical shifts are presented in normal font.

Table 2
Comparison of calculated (GIPAW)a and experimental 13C and 1H NMR chemical shifts (in ppm) in the DI–PM cocrystalb

Atom label 13C 1H
C H δcalc δexpt δcalc δexpt
C65 H22/H23/H24c 15.3 23.9 1.8 1.9
C68 H26/H27/H28c 17.2 25.7 2.0 2.0
C66 H25 111.5 112.6 3.4 4.0
C1 113.8 114.4d
C14 114.5 114.4d
C2 115.5 114.4d
C13 115.9 114.4d
C58 H17 120.1 119.4 9.7 9.1
C62 H21 120.2 120.3 8.4 8.0
C9 H1 126.7 125.7 7.4 7.4
C7 H1e 126.8 125.7 7.4 7.4
C61 H20 127.7 127.7 7.6 7.4
C12 H4 128.5 129.8 8.5 8.2
C6 H4e 128.6 129.8 8.5 8.2
C60 H19 129.3 130.2 7.3 7.8
C4 130.1 131.1d
C59 H18 131.5 131.2 7.7 7.7
C10 H2 132.6 133.9 5.9 6.2
C11 H3 139.2 136.8 7.6 7.7
C57 H21, H17, H29 138.5 141.5 8.4, 9.7, 10.5 8.9
C3 139.7 141.4d
C63 H29 155.5 160.1 10.5 9.1
C67 H26/H27/H28, H25 168.2 168.2 2.0, 3.4 2.8
C64 H22/H23/H24, H25 168.4 168.2 1.8, 3.4 2.8
C5 179.7 176.5d
C8 179.9 178.2d
Notes: (a) calculated isotropic chemical shifts are determined from calculated chemical shieldings according to δcalc = σrefσcalc, where σref equals 30.0 ppm for 1H and 163.2 ppm for 13C. (b) H-atom labels and calculated and experimental 1H chemical shifts are presented in normal font for direct one-bond C—H connectivities, while longer-range C⋯H proximities (corresponding to cross peaks observed in the 1H–13C spectra presented in Figs. 4[link]b and 4[link]c) are presented in italics. (c) For CH3 groups, the calculated 1H chemical shifts correspond to the average over the three H atoms. (d) Experimental chemical shifts taken from the 13C CP MAS spectrum (Fig. 2[link]a) since no cross peaks are observed in the 1H–13C spectra presented in Figs. 4[link](b) and 4[link](c). (e) Note that the C7—H1 and C6—H4 cross peaks due to longer-range C⋯H proximities cannot be distinguished from the C9—H1 and C12—H4 cross peaks due to one-bond C—H connectivities – in the stick spectrum in Fig. 2[link](c), open bars denote the calculated (GIPAW) C7 and C6 13C chemical shifts.

Fig. 4[link] compares 1H–13C correlation spectra recorded with three different CP contact times of 100 µs (Fig. 4[link]a), 500 µs (Fig. 4[link]b) and 1 ms (Fig. 4[link]c); Fig. 4[link](a) is a copy of Fig. 3[link](c), but presented in the normal orientation, i.e. with the direct (13C) dimension horizontal. It is evident that additional cross peaks are observed for longer CP contact times – these correspond to longer-range C⋯H proximities (see italics font in Table 2[link]). Notably, cross peaks are observed at 13C chemical shifts of 141.5 (atom C57), 160.1 (atom C63) and 168.2 ppm (atoms C64 and C67); these all correspond to intra­molecular proximities within the di­thia­non mol­ecule, i.e. C57 with H17 (9.1 ppm, 2.16 Å), H21 (8.0 ppm, 2.16 Å) and H29 (9.1 ppm, 2.06 Å), C63 with H29 (9.1 ppm, 2.01 Å), C64 and C67 with H25 (4.0 ppm, 2.16 and 2.17 Å) and CH3 protons (1.9 and 2.0 ppm, nearest distance 2.14 Å). Of most inter­est is the (160.1 ppm, 9.1 ppm) cross peak, which thus enables the determination of the NH 1H chemical shift.

[Figure 4]
Figure 4
1H (500 MHz)–13C HETCOR MAS (12.5 kHz) spectra of the DI–PM cocrystal recorded using FSLG 1H homonuclear decoupling (Bielecki et al., 1989[Bielecki, A., Kolbert, A. C. & Levitt, M. H. (1989). Chem. Phys. Lett. 155, 341-346.]) in t1 with a CP transfer duration of (a) 100 µs, (b) 500 µs and (c) 1 ms. The spectrum in part (a) is repeated from Fig. 3[link](c). 104 transients were co-added for each of (b) 128 or (c) 90 t1 FIDs using a recycle delay of (b) 6 or (c) 5.5 s, corresponding to a total experimental time of (b) 22 or (c) 14 h. The scaling factor in F1 was determined to be (a) and (b) 1.80 or (c) 1.73. The base contour level is at (a) 20, (b) 13 and (c) 25% of the maximum peak height. Red crosses correspond to GIPAW-calculated 1H and 13C chemical shifts (see Table 2[link]) for (a) one-bond C—H bonds and (b) and (c) C⋯H proximities between (b) 1.2 and 2.2 Å, and (c) 2.2 and 3.0 Å.

With all the 1H chemical shifts assigned, let us re-examine the 1H DQ MAS spectrum in Fig. 3[link](b). In such a spectrum, cross peaks are observed in the DQ dimension at the sum of the two single-quantum (SQ) frequencies if there is a close proximity (typically up to 3.5 Å; Brown, 2007[Brown, S. P. (2007). Prog. Nucl. Magn. Reson. Spectrosc. 50, 199-251.], 2012[Brown, S. P. (2012). Solid State Nucl. Magn. Reson. 41, 1-27.]) between the corresponding two H atoms (a full listing of H⋯H proximities under 3.5 Å for the DI–PM cocrystal is given in Table S1 of the Supporting information). Consider the two lowest-ppm aromatic CH protons H25 (4.0 ppm) and H2 (6.2 ppm) for which distinct 1H resonances are resolved in the 1H SQ dimension. For H25, the only DQ peak is at 4.0 + 2.0 = 6.0 ppm with the CH3 protons, since H25 is sandwiched between two methyl-group substituents on the PM mol­ecule. For H2, there is a DQ peak at 6.2 + 7.5 = 13.7 ppm corresponding to the intra­molecular H⋯H proximity with the neighbouring H1 (7.4 ppm, 2.50 Å) and H3 (7.7 ppm, 2.47 Å) DI aromatic CH protons, as well as a DQ peak at 6.2 + 2.0 = 8.2 ppm due to inter­molecular proximities to the PM CH3 H atoms (H23, H24, H28 and H22 at 2.90, 3.03, 3.12 and 3.12 Å, respectively). Considering the high-ppm region, DQ cross peaks for the overlapping PI NH H29 (9.1 ppm) and aromatic CH H17 (9.1 ppm) resonances are observed at 9.1 + 7.7 = 16.8 ppm for intra­molecular H29⋯H21 (2.21 Å) and H17⋯H18 (2.50 Å) proximities, as well as at 9.1 + 2.0 = 11.1 ppm for inter­molecular proximities to PM methyl-group protons (closest distances of H17⋯H26 = 2.48 Å and H29⋯H24 = 2.64 Å). For the other overlapping CH aromatic resonances, cross peaks due to intra­molecular proximities with other CH aromatic resonances, as well as inter­molecular proximities to the methyl protons, are also observed.

3.4. Comparison of experimental and calculated 1H and 13C chemical shifts

In the 1H–13C correlation spectra presented in Fig. 4[link], red crosses correspond to calculated (GIPAW) 13C and 1H chemical shifts. Specifically, in Fig. 4[link](a), red crosses correspond to direct C—H one-bond connectivities (C—H distances under 1.2 Å), while in Figs. 4[link](b) and 4(c), red crosses are presented for C—H proximities between 1.2 and 2.2 Å (Fig. 4[link]b), and between 2.2 and 3.0 Å (Fig. 4[link]c). We comment here on the level of agreement between experimental and calculated (GIPAW) chemical shifts. Starting with a consideration of the aromatic CH moieties (see Fig. 4[link]a and Table 2[link]), the discrepancy between experiment and calculation is within 2 ppm for the 13C chemical shifts (except for C11, where the difference is 2.4 ppm); this corresponds to the established observation that the discrepancy is within 1% of the chemical shift range (∼200 ppm for 13C chemical shifts of diamagnetic mol­ecules). For the 1H chemical shifts, while most are within the usual 0.3 ppm, some exhibit slightly larger discrepancies, notably 0.6 ppm for atoms H17 and H25.

For the two CH3 groups (see Figs. 2[link] and 3[link]a, and Table 2[link]), there is excellent agreement for the 1H chemical shifts (within 0.1 ppm), whereas the calculated 13C chemical shifts are both 8.5 ppm lower than the experimental values, although the experimental difference in 13C chemical shifts between atoms C65 and C68 of 1.8 ppm is reproduced by the calculation (difference of 1.9 ppm). The explanation for this is well known, namely, the gradient of a plot of experimental 13C chemical shifts against calculated shielding deviates slightly from −1 (Harris et al., 2007[Harris, R. K., Hodgkinson, P., Pickard, C. J., Yates, J. R. & Zorin, V. (2007). Magn. Reson. Chem. 45, S174-S186.]; Ashbrook & McKay, 2016[Ashbrook, S. E. & McKay, D. (2016). Chem. Commun. 52, 7186-7204.]), such that calculated 13C chemical shifts are too low and too high compared to experiment for low-ppm and high-ppm resonances if, as here (see Fig. 2[link]), the gradient is constrained to −1 and a single reference shielding is used. An alternative approach would be to use different reference shieldings for different regions of the spectrum (Webber, Emsley et al., 2010[Webber, A. L., Emsley, L., Claramunt, R. M. & Brown, S. P. (2010). J. Phys. Chem. A, 114, 10435-10442.]).

Returning to the 1H chemical shifts, the biggest discrepancy is for the NH proton (H29), where the calculated 1H chemical shift of 10.5 ppm is 1.4 ppm higher than the experimental value of 9.1 ppm. Such a large difference is explained by a known temperature dependence (the experimental 1H chemical shift increases upon reducing the temperature) for hydrogen-bonded protons (Brown et al., 2001[Brown, S. P., Zhu, X. X., Saalwachter, K. & Spiess, H. W. (2001). J. Am. Chem. Soc. 123, 4275-4285.]; Pickard et al., 2007[Pickard, C. J., Salager, E., Pintacuda, G., Elena, B. & Emsley, L. (2007). J. Am. Chem. Soc. 129, 8932-8933.]; Webber, Elena et al., 2010[Webber, A. L., Elena, B., Griffin, J. M., Yates, J. R., Pham, T. N., Mauri, F., Pickard, C. J., Gil, A. M., Stein, R., Lesage, A., Emsley, L. & Brown, S. P. (2010). Phys. Chem. Chem. Phys. 12, 6970-6983.]), considering that the calculation corresponds to 0 K.

3.5. Calculated mol­ecule-to-crystal changes in chemical shifts

For cases such as the DI–PM cocrystal in this article, an NMR crystallography study is able to provide new insight by means of a comparison of chemical shifts calculated for the full crystal structure with those calculated for an isolated mol­ecule (as extracted from the geometry-optimized crystal structure) (Yates et al., 2005[Yates, J. R., Pham, T. N., Pickard, C. J., Mauri, F., Amado, A. M., Gil, A. M. & Brown, S. P. (2005). J. Am. Chem. Soc. 127, 10216-10220.]; Schmidt et al., 2006[Schmidt, J., Hoffmann, A., Spiess, H. W. & Sebastiani, D. (2006). J. Phys. Chem. B, 110, 23204-23210.]; Mafra et al., 2012[Mafra, L., Santos, S. M., Siegel, R., Alves, I., Paz, F. A. A., Dudenko, D. & Spiess, H. W. (2012). J. Am. Chem. Soc. 134, 71-74.]). Specifically, a mol­ecule-to-crystal difference in chemical shift is indicative of a combination of inter­molecular inter­actions, notably hydrogen bonding and ring currents due to C—H⋯π inter­actions, whereby the latter can be separately qu­anti­fied by means of the nucleus independent chemical shift (NICS) (von Ragué Schleyer et al., 1996[Ragué Schleyer, P. von, Maerker, C., Dransfeld, A., Jiao, H. & van Eikema Hommes, N. J. R. (1996). J. Am. Chem. Soc. 118, 6317-6318.]; Sebastiani, 2006[Sebastiani, D. (2006). ChemPhysChem, 7, 164-175.]; Uldry et al., 2008[Uldry, A. C., Griffin, J. M., Yates, J. R., Perez-Torralba, M., Maria, M. D. S., Webber, A. L., Beaumont, M. L. L., Samoson, A., Claramunt, R. M., Pickard, C. J. & Brown, S. P. (2008). J. Am. Chem. Soc. 130, 945-954.]; Mafra et al., 2012[Mafra, L., Santos, S. M., Siegel, R., Alves, I., Paz, F. A. A., Dudenko, D. & Spiess, H. W. (2012). J. Am. Chem. Soc. 134, 71-74.]). Consider Table 3[link], which presents the change in 1H chemical shift upon going from an isolated mol­ecule to the full crystal, Δδcrystal–mol­ecule, for the different H atoms in the DI–PM cocrystal. The largest positive change of 3.6 ppm is observed for the NH (H29) atom that is involved in an inter­molecular N—H⋯O hydrogen bond to atom O1 (see Fig. 1[link]a; the N⋯O and H⋯O distances are 2.95 and 1.96 Å, respectively, with a 162° N—H⋯O angle). Inter­estingly, Δδcrystal–mol­ecule = 2.0 ppm for the aromatic CH H21 atom, for which Fig. 1[link](a) identifies an inter­molecular C—H⋯O so-called weak hydrogen-bonding (Desiraju & Steiner, 1999[Desiraju, G. R. & Steiner, T. (1999). In The Weak Hydrogen Bond in Structural Chemistry and Biology. Oxford University Press.]; Yates et al., 2005[Yates, J. R., Pham, T. N., Pickard, C. J., Mauri, F., Amado, A. M., Gil, A. M. & Brown, S. P. (2005). J. Am. Chem. Soc. 127, 10216-10220.]; Uldry et al., 2008[Uldry, A. C., Griffin, J. M., Yates, J. R., Perez-Torralba, M., Maria, M. D. S., Webber, A. L., Beaumont, M. L. L., Samoson, A., Claramunt, R. M., Pickard, C. J. & Brown, S. P. (2008). J. Am. Chem. Soc. 130, 945-954.]) inter­action (the C⋯O and H⋯O distances are 3.24 and 2.35 Å, respectively, with a 138° C—H⋯O angle). The other H atoms, for which the magnitude of Δδcrystal–mol­ecule exceeds 1 ppm, are H25 (−2.7 ppm) and H2 (−1.6 ppm); as shown in Fig. 5[link], these marked changes in the 1H chemical shift are a consequence of ring current effects associated with the proton pointing towards the centre of a six-membered aromatic ring of a nearby PM mol­ecule in a C—H⋯π inter­action, as has been noted previously in a number of other cases (Brouwer et al., 2008[Brouwer, D. H., Alavi, S. & Ripmeester, J. A. (2008). Phys. Chem. Chem. Phys. 10, 3857-3860.]; Mafra et al., 2012[Mafra, L., Santos, S. M., Siegel, R., Alves, I., Paz, F. A. A., Dudenko, D. & Spiess, H. W. (2012). J. Am. Chem. Soc. 134, 71-74.]; Brown, 2012[Brown, S. P. (2012). Solid State Nucl. Magn. Reson. 41, 1-27.]).

Table 3
Comparison of experimental 1H chemical shifts with calculateda (GIPAW) values (all in ppm) for the DI–PM cocrystal for the full crystal structure and an isolated di­thia­non or pyrimethanil mol­ecule

Atom δexp  δcrystal δmol­ecule Δδcrystal–mol­ecule
H1 7.4 7.4 7.8 −0.4
H2 6.2 5.9 7.4 −1.5
H3 7.7 7.6 7.4 0.2
H4 8.2 8.5 7.8 0.7
H17 9.1 9.7 9.2 0.5
H18 7.7 7.7 7.0 0.7
H19 7.8 7.3 6.6 0.7
H20 7.4 7.6 7.0 0.6
H21 8.0 8.4 6.4 2.0
H22/23/24b 1.9 1.8 1.9 −0.1
H25 4.0 3.4 6.1 −2.7
H26/27/28b 2.0 2.0 1.8 0.2
H29 9.1 10.5 6.9 3.6
Notes: (a) calculated isotropic chemical shieldings are determined from calculated chemical shieldings according to δcalc = σrefσcalc, where σref equals 30.0 ppm; (b) for CH3 groups, the calculated 1H chemical shifts correspond to the average over the three H atoms.
[Figure 5]
Figure 5
Schematic representations showing C—H⋯π inter­actions for aromatic atoms (a) H25 and (b) H2.

In the above discussion in §3.1[link], a close S⋯O distance, equal to 3.10 Å, between the O2 and S2 atoms of neighbouring DI mol­ecules was noted; this is less than the sum of the van der Waals radii (3.32 Å) (Beno et al., 2015[Beno, B. R., Yeung, K. S., Bartberger, M. D., Pennington, L. D. & Meanwell, N. A. (2015). J. Med. Chem. 58, 4383-4438.]; Zhang et al., 2015[Zhang, X., Gong, Z., Li, J. & Lu, T. (2015). J. Chem. Inf. Model. 55, 2138-2153.]). Indeed, there is a growing literature discussing S⋯O inter­actions (Burling & Goldstein, 1992[Burling, F. T. & Goldstein, B. M. (1992). J. Am. Chem. Soc. 114, 2313-2320.]; Iwaoka et al., 2002[Iwaoka, M., Takemoto, S. & Tomoda, S. (2002). J. Am. Chem. Soc. 124, 10613-10620.]; Beno et al., 2015[Beno, B. R., Yeung, K. S., Bartberger, M. D., Pennington, L. D. & Meanwell, N. A. (2015). J. Med. Chem. 58, 4383-4438.]). While we have not carried out 17O or 33S solid-state NMR experiments as part of this study, an NMR crystallography approach enables the effect of such a putative S⋯O inter­action on the oxygen and sulfur NMR chemical shieldings to be investigated by means of the GIPAW calculation that reports on all nuclei in the solid-state structure. An inspection of Table 4[link] shows that it is inter­esting that Δδcrystal–mol­ecule (note that this is the negative of the difference in calculated absolute shielding, with the latter being stated in Table 4[link]) is much larger for O1 (−98 ppm), which is involved in a N—H⋯O inter­molecular hydrogen bonding, as compared to that for O2 (−23 ppm). Moreover, the change for S2 (13 ppm) is less than that for S1 (25 ppm), with both changes being small, though there is limited information on the range of experimentally observed solid-state NMR 33S chemical shifts (Hansen et al., 2008[Hansen, M. R., Brorson, M., Bildsoe, H., Skibsted, J. & Jakobsen, H. J. (2008). J. Magn. Reson. 190, 316-326.]). We conclude that even though there is a close inter­molecular S⋯O distance of 3.10 Å in the DI–PM cocrystal, there is not a marked effect on the calculated NMR chemical shieldings for the O2 and S2 nuclei.

Table 4
Comparison of calculated (GIPAW) NMR chemical shieldings (in ppm) for the DI–PM cocrystal for the full crystal structure and an isolated di­thia­non or pyrimethanil mol­ecule

Atom σmol­ecule σcrystal σcrystal–mol­ecule
N1 −106.4 −88.9 17.5
N2 −107.2 −88.9 18.3
N9 98.9 91.4 −7.4
N10 −30.1 −33.0 −2.9
N11 −44.5 −42.4 2.1
O1 −363.4 −265.9 97.5
O2 −345.3 −322.2 23.1
S1 330.7 305.6 −25.1
S2 333.8 320.6 −13.2

4. Summary

In summary, we have presented here an NMR crystallography study of an agrochemical cocrystal. Specifically in combination with a GIPAW calculation of the NMR shieldings, 1H–13C 2D correlation spectra enable the resolution and assignment of the NH, aromatic CH and methyl resonances for the DI–PM cocrystal, while specific intra- and inter­molecular H⋯H proximities are identified in a 1H DQ MAS spectrum. The performing of separate GIPAW calculations for the full crystal structure and isolated DI and PM mol­ecules yields the change in the NMR chemical shift upon going from the mol­ecule to the crystal structure, thus allowing the qu­anti­tation of specific N—H⋯O, C—H⋯O and C—H⋯π inter­actions.

Supporting information


Computing details top

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996) and Mercury (Macrae et al., 2006); software used to prepare material for publication: CRYSTALS (Betteridge et al., 2003).

5,10-Dioxo-5H,10H-naphtho[2,3-b][1,4]dithiine-2,3-dicarbonitrile–4,6-dimethyl-N-phenylpyrimidin-2-amine (1/1) top
Crystal data top
C14H4N2O2S2·C12H13N3F(000) = 1024
Mr = 495.59Dx = 1.467 Mg m3
Monoclinic, P21/nCu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2ynCell parameters from 2711 reflections
a = 7.1707 (2) Åθ = 5.0–62.6°
b = 22.8006 (6) ŵ = 2.45 mm1
c = 13.8237 (4) ÅT = 100 K
β = 97.047 (3)°Plate, purple
V = 2243.04 (7) Å30.60 × 0.10 × 0.02 mm
Z = 4
Data collection top
Agilent Xcalibur Onyx Ultra
diffractometer
2667 reflections with I > 2.0σ(I)
Mirror monochromatorRint = 0.035
ω/2θ scansθmax = 58.9°, θmin = 3.2°
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2014)
h = 57
Tmin = 0.596, Tmax = 1.000k = 2525
5143 measured reflectionsl = 1415
3160 independent reflections
Refinement top
Refinement on F2Primary atom site location: other
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.094 Method, part 1, Chebychev polynomial [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)]
where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting W = [weight] * [1-(deltaF/6*sigmaF)2]2 Ai are: 0.138E + 04 0.207E + 04 0.111E + 04 326.
S = 0.98(Δ/σ)max = 0.001
3141 reflectionsΔρmax = 0.43 e Å3
109 parametersΔρmin = 0.37 e Å3
3 restraints
Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.57630 (11)0.51819 (3)0.79844 (6)0.0223
C20.3685 (4)0.48079 (13)0.7529 (2)0.0212
C30.2072 (4)0.47646 (13)0.7926 (2)0.0202
S40.14929 (11)0.50645 (3)0.90297 (5)0.0206
C50.3411 (4)0.55384 (12)0.9352 (2)0.0177
C60.5006 (4)0.55878 (12)0.8951 (2)0.0175
C70.6476 (4)0.60247 (12)0.9342 (2)0.0179
O80.7809 (3)0.61031 (9)0.88850 (15)0.0221
C90.6255 (4)0.63243 (12)1.0265 (2)0.0167
C100.4604 (4)0.62563 (12)1.0704 (2)0.0176
C110.3051 (4)0.58862 (13)1.0216 (2)0.0176
O120.1533 (3)0.58453 (9)1.05284 (15)0.0237
C130.4420 (4)0.65186 (13)1.1586 (2)0.0214
C140.5889 (5)0.68550 (14)1.2043 (2)0.0247
C150.7515 (5)0.69313 (13)1.1606 (2)0.0235
C160.7717 (4)0.66662 (13)1.0719 (2)0.0211
C170.0513 (5)0.44419 (13)0.7438 (2)0.0227
N180.0763 (4)0.41868 (13)0.7075 (2)0.0334
C190.3871 (5)0.45136 (14)0.6633 (2)0.0244
N200.4065 (4)0.42677 (13)0.5922 (2)0.0372
N210.1269 (3)0.65896 (11)0.81861 (18)0.0185
C220.1456 (4)0.63048 (12)0.7301 (2)0.0193
C230.3046 (5)0.63170 (13)0.6818 (2)0.0227
C240.3041 (5)0.60183 (14)0.5940 (2)0.0281
C250.1478 (5)0.57112 (14)0.5532 (2)0.0305
C260.0103 (5)0.56959 (14)0.6017 (2)0.0289
C270.0132 (5)0.59861 (13)0.6889 (2)0.0227
C280.2398 (4)0.69992 (12)0.8710 (2)0.0172
N290.4071 (3)0.71395 (10)0.84429 (17)0.0189
C300.5047 (4)0.75525 (13)0.8996 (2)0.0204
C310.4355 (4)0.78043 (13)0.9782 (2)0.0240
C320.2624 (5)0.76203 (13)1.0009 (2)0.0233
N330.1612 (3)0.72147 (11)0.94755 (18)0.0203
C340.1768 (5)0.78633 (16)1.0859 (3)0.0350
C350.6919 (4)0.77160 (14)0.8698 (2)0.0256
H1310.33250.64731.18870.0272*
H1410.57730.70371.26450.0304*
H1510.84710.71681.19070.0275*
H1610.88070.67221.04210.0261*
H2310.41280.65190.70830.0274*
H2410.41210.60200.56190.0339*
H2510.15190.55190.49410.0370*
H2610.11700.55000.57480.0342*
H2710.11970.59720.72170.0260*
H3110.50420.80851.01700.0294*
H3420.04430.77821.08320.0544*
H3410.19200.82771.08690.0549*
H3430.24230.77101.14380.0548*
H3520.73890.80700.90030.0411*
H3530.68470.77710.80150.0418*
H3510.78000.74200.88720.0415*
H2110.022 (3)0.6531 (11)0.8421 (16)0.0231*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.02230.02200.02240.00010.00150.0055
C20.02740.01500.01970.00190.00350.0014
C30.02360.01500.02030.00030.00430.0020
S40.02150.01850.02110.00440.00040.0018
C50.02020.01250.01890.00220.00380.0041
C60.02140.01320.01690.00090.00210.0022
C70.01970.01330.02040.00450.00090.0041
O80.02190.02290.02140.00350.00270.0011
C90.01880.01270.01710.00160.00410.0010
C100.01990.01350.01840.00160.00150.0037
C110.01870.01430.01980.00150.00230.0054
O120.02500.02240.02440.00310.00620.0008
C130.02420.01990.02060.00150.00410.0008
C140.03380.02230.01750.00070.00160.0052
C150.02770.01840.02250.00360.00420.0039
C160.02060.01740.02440.00040.00030.0021
C170.02710.02050.01950.00010.00130.0002
N180.04130.03240.02550.00730.00020.0019
C190.02810.02030.02440.00270.00180.0001
N200.04230.03770.03140.00230.00370.0076
N210.01570.01940.02040.00240.00170.0019
C220.02940.01140.01610.00380.00130.0021
C230.02840.01810.02150.00000.00270.0018
C240.04290.02020.02230.00530.00900.0021
C250.05170.02130.01770.00210.00160.0017
C260.04290.01670.02420.00260.00750.0005
C270.02890.01830.01980.00150.00200.0034
C280.02070.01130.01850.00420.00160.0037
N290.02130.01520.01990.00120.00070.0033
C300.02150.01450.02380.00070.00330.0047
C310.02830.01580.02670.00280.00130.0036
C320.02700.01900.02350.00160.00190.0027
N330.02240.01750.02100.00130.00290.0031
C340.03660.03260.03730.00310.01030.0140
C350.02440.02390.02780.00500.00040.0034
Geometric parameters (Å, º) top
S1—C21.764 (3)N21—H2110.864 (17)
S1—C61.764 (3)C22—C231.391 (4)
C2—C31.343 (4)C22—C271.410 (4)
C2—C191.429 (4)C23—C241.390 (4)
C3—S41.767 (3)C23—H2310.938
C3—C171.436 (4)C24—C251.382 (5)
S4—C51.763 (3)C24—H2410.939
C5—C61.336 (4)C25—C261.387 (5)
C5—C111.483 (4)C25—H2510.930
C6—C71.502 (4)C26—C271.378 (4)
C7—O81.223 (4)C26—H2610.923
C7—C91.473 (4)C27—H2710.936
C9—C101.404 (4)C28—N291.336 (4)
C9—C161.393 (4)C28—N331.350 (4)
C10—C111.491 (4)N29—C301.353 (4)
C10—C131.379 (4)C30—C311.375 (4)
C11—O121.222 (4)C30—C351.499 (4)
C13—C141.390 (4)C31—C321.382 (5)
C13—H1310.938C31—H3110.935
C14—C151.388 (5)C32—N331.339 (4)
C14—H1410.944C32—C341.498 (4)
C15—C161.390 (4)C34—H3420.964
C15—H1510.931C34—H3410.950
C16—H1610.936C34—H3430.944
C17—N181.146 (4)C35—H3520.952
C19—N201.155 (4)C35—H3530.949
N21—C221.406 (4)C35—H3510.935
N21—C281.382 (4)
C2—S1—C6101.45 (14)N21—C22—C27115.5 (3)
S1—C2—C3128.4 (2)C23—C22—C27119.0 (3)
S1—C2—C19111.8 (2)C22—C23—C24119.6 (3)
C3—C2—C19119.7 (3)C22—C23—H231120.6
C2—C3—S4129.0 (2)C24—C23—H231119.7
C2—C3—C17120.4 (3)C23—C24—C25121.3 (3)
S4—C3—C17110.6 (2)C23—C24—H241119.7
C3—S4—C5101.35 (14)C25—C24—H241118.9
S4—C5—C6128.9 (2)C24—C25—C26119.0 (3)
S4—C5—C11108.9 (2)C24—C25—H251119.1
C6—C5—C11122.2 (3)C26—C25—H251121.9
S1—C6—C5129.0 (2)C25—C26—C27120.8 (3)
S1—C6—C7110.7 (2)C25—C26—H261120.2
C5—C6—C7120.3 (3)C27—C26—H261118.9
C6—C7—O8118.0 (3)C22—C27—C26120.2 (3)
C6—C7—C9118.3 (3)C22—C27—H271119.3
O8—C7—C9123.6 (3)C26—C27—H271120.5
C7—C9—C10120.6 (3)N21—C28—N29120.3 (3)
C7—C9—C16119.7 (3)N21—C28—N33112.5 (3)
C10—C9—C16119.7 (3)N29—C28—N33127.2 (3)
C9—C10—C11119.3 (3)C28—N29—C30115.5 (3)
C9—C10—C13120.7 (3)N29—C30—C31121.7 (3)
C11—C10—C13119.9 (3)N29—C30—C35115.9 (3)
C10—C11—C5118.2 (3)C31—C30—C35122.4 (3)
C10—C11—O12122.1 (3)C30—C31—C32118.3 (3)
C5—C11—O12119.6 (3)C30—C31—H311121.5
C10—C13—C14119.5 (3)C32—C31—H311120.2
C10—C13—H131121.3C31—C32—N33121.7 (3)
C14—C13—H131119.3C31—C32—C34122.1 (3)
C13—C14—C15120.1 (3)N33—C32—C34116.2 (3)
C13—C14—H141120.0C28—N33—C32115.6 (3)
C15—C14—H141119.9C32—C34—H342113.2
C14—C15—C16120.9 (3)C32—C34—H341108.8
C14—C15—H151119.4H342—C34—H341107.6
C16—C15—H151119.7C32—C34—H343108.7
C9—C16—C15119.1 (3)H342—C34—H343110.3
C9—C16—H161120.1H341—C34—H343108.1
C15—C16—H161120.8C30—C35—H352111.7
C3—C17—N18177.7 (3)C30—C35—H353111.4
C2—C19—N20178.1 (3)H352—C35—H353107.6
C22—N21—C28131.0 (3)C30—C35—H351110.5
C22—N21—H211115.8 (12)H352—C35—H351107.8
C28—N21—H211112.8 (12)H353—C35—H351107.7
N21—C22—C23125.5 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C23—H231···N290.942.362.950 (4)121 (1)
C27—H271···O8i0.942.513.296 (4)141 (1)
N21—H211···O8i0.862.152.985 (4)162 (2)
Symmetry code: (i) x1, y, z.
Comparison of calculated (GIPAW)a and experimental 13C and 1H NMR chemical shifts (in ppm) in the DI–PM cocrystalb top
Atom label13C1H
CHδcalcδexptδcalcδexpt
C65H22/H23/H24c15.323.91.81.9
C68H26/H27/H28c17.225.72.02.0
C66H25111.5112.63.44.0
C1-113.8114.4d--
C14-114.5114.4d--
C2-115.5114.4d--
C13-115.9114.4d--
C58H17120.1119.49.79.1
C62H21120.2120.38.48.0
C9H1126.7125.77.47.4
C7H1e126.8125.77.47.4
C61H20127.7127.77.67.4
C12H4128.5129.88.58.2
C6H4e128.6129.88.58.2
C60H19129.3130.27.37.8
C4-130.1131.1d--
C59H18131.5131.27.77.7
C10H2132.6133.95.96.2
C11H3139.2136.87.67.7
C57H21, H17, H29138.5141.58.4, 9.7, 10.58.9
C3-139.7141.4d--
C63H29155.5160.110.59.1
C67H26/H27/H28, H25168.2168.22.0, 3.42.8
C64H22/H23/H24, H25168.4168.21.8, 3.42.8
C5-179.7176.5d--
C8-179.9178.2d--
Notes: (a) Calculated isotropic chemical shieldings are determined from calculated chemical shieldings according to ?calc = ?ref ? ?calc, where ?ref equals 30.0 ppm for 1H and 163.2 ppm for 13C. b H atom labels and calculated and experimental 1H chemical shifts are presented in normal font for direct one-bond CH connectivities, while longer-range C···H proximities (corresponding to cross peaks observed in the 1H-13C spectra presented in Figs. 4b and 4c) are presented in italics. c For CH3 groups, the calculated 1H chemical shifts correspond to the average over the three hydrogen atoms. d Experimental chemical shifts taken from 13C CP MAS spectrum (Fig. 2a) since no cross peaks are observed in the 1H-13C spectra presented in Figs. 4b and 4c. e Note that the C7-H1 and C6-H4 cross peaks due to longer-range C···H proximities cannot be distinguished from C9-H1 and C12-H4 cross peaks due to one-bond CH connectivities ? in the stick spectrum in Fig. 2b, open bars denote the calculated (GIPAW) C7 and C6 13C chemical shifts.
Table 2 Comparison of experimental 1H chemical shifts with calculateda (GIPAW) values (all in ppm) for the DI–PM cocrystal for the full crystal structure and an isolated dithianon or pyrimethanil molecule top
AtomδexpδcrystalδmoleculeΔδcrystal-molecule
H17.47.47.8?0.4
H26.25.97.4?1.5
H37.77.67.40.2
H48.28.57.80.7
H179.19.79.20.5
H187.77.77.00.7
H197.87.36.60.7
H207.47.67.00.6
H218.08.46.42.0
H22/23/24b1.91.81.9?0.1
H254.03.46.1?2.7
H26/27/28b2.02.01.80.2
H299.110.56.93.6
Notes: (a) calculated isotropic chemical shieldings are determined from calculated chemical shieldings according to ?calc = ?ref ? ?calc, where ?ref equals 30.0 ppm; (b) For CH3 groups, the calculated 1H chemical shifts correspond to the average over the three hydrogen atoms.
Table 3 Comparison of calculated (GIPAW) NMR chemical shieldings (in ppm) for the DI–PM cocrystal for the full crystal structure and an isolated dithianon or pyrimethanil molecule top
Atomσmoleculeσcrystalσcrystal-molecule
N1?106.4?88.917.5
N2?107.2?88.918.3
N998.991.4?7.4
N10?30.1?33.0?2.9
N11?44.5?42.42.1
O1?363.4?265.9?97.6
O2?345.3?322.2?23.1
S1330.7305.625.1
S2333.8320.613.2
 

Acknowledgements

ACP was supported by a Feodor Lynen Research Fellowship of the Alexander von Humboldt Foundation and a Newton Inter­national Fellowship of the Royal Society. EC and HP acknowledge funding from the Mol­ecular Analytical Sciences Centre for Doctoral Training (EPSRC grant EP/L015307/1). We thank Peter Howe (Syngenta) for helpful discussions. Computational facilities were provided by the MidPlus Regional Centre of Excellence for Computational Science, Engineering and Mathematics, under EPSRC grant EP/K000128/1, and the University of Warwick Scientific Computing Research Technology Platform. The 700 MHz NMR spectrometer was partially funded from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 639907 (for Dr J. R. Lewandowski, Department of Chemistry, University of Warwick). The experimental and calculated data for this study are provided as a supporting data set from WRAP, the Warwick Research Archive Portal, at https://wrap.warwick.ac.uk/85381.

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