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

Pöppler, A.-C.; Corlett, E.K.; Pearce, H.; Seymour, M.P.; Reid, M.; Montgomery, M.G.; Brown, S.P.

doi:10.1107/S2053229617000870

nmr crystallography

STRUCTURAL
CHEMISTRY

ISSN: 2053-2296

Volume 73| Part 3| March 2017| Pages 149-156

https://doi.org/10.1107/S2053229617000870

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

Ann-Christin Pöppler,^a,^b Emily K. Corlett,^a,^c Harriet Pearce,^a,^c Mark P. Seymour,^d Matthew Reid,^d,^e Mark G. Montgomery ^d and Steven P. Brown ^a ^*

^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.

Keywords: NMR crystallography; solid-state NMR; dithianon; pyrimethanil; cocrystal; hydrogen bonding; C—H⋯π interactions; fungicides.

CCDC reference: 1507863

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 ). 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 ), 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 ) 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 ) 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 ).

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 ; Elena et al., 2006 ; Harris et al., 2009 ; Bonhomme et al., 2012 ). 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 ), 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 ; Yates et al., 2007 ), 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 ; Dudenko et al., 2013 ; Stevens et al., 2014 ; Kerr et al., 2015 ; Sardo et al., 2015 ; Luedeker et al., 2016 ), 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), 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.

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

Crystal data, data collection and structure refinement details are summarized in Table 1. 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 U_iso(H) = 1.2–1.5U_eq(parent)], after which the positions were refined with riding constraints (Cooper et al., 2010 ).

Table 1
Experimental details

Crystal data
Chemical formula	C₁₄H₄N₂O₂S₂·C₁₂H₁₃N₃
M_r	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)
V (Å³)	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 )
T_min, T_max	0.596, 1.000
No. of measured, independent and observed [I > 2.0σ(I)] reflections	5143, 3160, 2667
R_int	0.035
θ_max (°)	58.9
(sin θ/λ)_max (Å⁻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
Δρ_max, Δρ_min (e Å⁻³)	0.43, −0.37
Computer programs: CrysAlis PRO (Agilent, 2014), SUPERFLIP (Palatinus & Chapuis, 2007 ), CRYSTALS (Betteridge et al., 2003 ), CAMERON (Watkin et al., 1996 ) and Mercury (Macrae et al., 2006 ).

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 ) on the ¹H channel was used for the CP contact time. During acquisition of a ¹³C FID, SPINAL64 (Fung et al., 2000 ) 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 ; Schnell et al., 1998 ) 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 ).

2.4. DFT calculations

Calculations were performed using CASTEP (Clark et al., 2005 ; Academic Release Version 8.0) and employed the PBE exchange-correlational functional (Perdew et al., 1996 ). For both geometry optimization and NMR shielding calculations, a plane-wave basis set with ultrasoft pseudopotentials (Vanderbilt, 1990 ) 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; Yates et al., 2007) 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. As shown in Fig. 1(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 ) between two DI molecules; note that the relative strengths of these interactions is investigated below (see §3.5) 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(b) and 1(c), respectively. As can be seen from the representation along the crystallographic a axis in Fig. 1(c), the packing is based on assemblies of blocks of four molecules; four molecules (PM–DI–DI–PM) are arranged in a layer (Fig. 1a), forming a block that is perpendicular to an adjacent block of four molecules, thus building up the `zigzag' arrangement.

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 presents a ¹³C CP MAS NMR 1D spectrum (Fig. 2a) of the DI–PM cocrystal, together with three stick spectra (Figs. 2b, 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. 2b, red labels) or nonprotonated C atoms (Figs. 2c and 2d, blue and green labels, respectively). The distinction between Figs. 2(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).

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

). 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

, 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(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(a), together with vertical lines corresponding to calculated (GIPAW) ¹H chemical shifts, as well as a 2D DQ spectrum in Fig. 3(b). In addition, Fig. 3(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. 3c) and ¹H DQ 2D (Fig. 3b) and ¹H 1D (Fig. 3a) spectra. Two separate spectral regions are presented in Fig. 3(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
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(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(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 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 cocrystal^b

Atom label		¹³C		¹H
C	H	δ_calc	δ_expt	δ_calc	δ_expt
C65	H22/H23/H24^c	15.3	23.9	1.8	1.9
C68	H26/H27/H28^c	17.2	25.7	2.0	2.0
C66	H25	111.5	112.6	3.4	4.0
C1	–	113.8	114.4^d	–	–
C14	–	114.5	114.4^d	–	–
C2	–	115.5	114.4^d	–	–
C13	–	115.9	114.4^d	–	–
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	H1^e	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	H4^e	128.6	129.8	8.5	8.2
C60	H19	129.3	130.2	7.3	7.8
C4	–	130.1	131.1^d	–	–
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	141.4^d	–	–
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	176.5^d	–	–
C8	–	179.9	178.2^d	–	–
Notes: (a) calculated isotropic chemical shifts are determined from calculated chemical shieldings according to δ_calc = σ_ref − σ_calc, where σ_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 C—H 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 H atoms. (d) Experimental chemical shifts taken from the ¹³C CP MAS spectrum (Fig. 2a) since no cross peaks are observed in the ¹H–¹³C spectra presented in Figs. 4(b) and 4(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(c), open bars denote the calculated (GIPAW) C7 and C6 ¹³C chemical shifts.

Fig. 4 compares ¹H–¹³C correlation spectra recorded with three different CP contact times of 100 µs (Fig. 4a), 500 µs (Fig. 4b) and 1 ms (Fig. 4c); Fig. 4(a) is a copy of Fig. 3(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). 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
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

) 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

(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

) 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(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 , 2012 ) 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, red crosses correspond to calculated (GIPAW) ¹³C and ¹H chemical shifts. Specifically, in Fig. 4(a), red crosses correspond to direct C—H one-bond connectivities (C—H distances under 1.2 Å), while in Figs. 4(b) and 4(c), red crosses are presented for C—H proximities between 1.2 and 2.2 Å (Fig. 4b), and between 2.2 and 3.0 Å (Fig. 4c). 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. 4a and Table 2), 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 and 3a, and Table 2), 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 ; Ashbrook & McKay, 2016 ), 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), 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 ).

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 ; Pickard et al., 2007 ; Webber, Elena et al., 2010 ), 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 ; Schmidt et al., 2006 ; Mafra et al., 2012 ). 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 ; Sebastiani, 2006 ; Uldry et al., 2008 ; Mafra et al., 2012). Consider Table 3, which presents the change in ¹H chemical shift upon going from an isolated molecule to the full crystal, Δδ_{crystal–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. 1a; the N⋯O and H⋯O distances are 2.95 and 1.96 Å, respectively, with a 162° N—H⋯O angle). Interestingly, Δδ_{crystal–molecule} = 2.0 ppm for the aromatic CH H21 atom, for which Fig. 1(a) identifies an intermolecular C—H⋯O so-called weak hydrogen-bonding (Desiraju & Steiner, 1999 ; Yates et al., 2005; Uldry et al., 2008) 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 Δδ_{crystal–molecule} exceeds 1 ppm, are H25 (−2.7 ppm) and H2 (−1.6 ppm); as shown in Fig. 5, 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 ; Mafra et al., 2012; Brown, 2012).

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

Atom	δ_exp	δ_crystal	δ_molecule	Δδ_{crystal–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
H22/23/24^b	1.9	1.8	1.9	−0.1
H25	4.0	3.4	6.1	−2.7
H26/27/28^b	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 δ_calc = σ_ref − σ_calc, where σ_ref equals 30.0 ppm; (b) for CH₃ groups, the calculated ¹H chemical shifts correspond to the average over the three H atoms.

Figure 5
Schematic representations showing C—H⋯π interactions for aromatic atoms (a) H25 and (b) H2.

In the above discussion in §3.1, 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 ; Zhang et al., 2015 ). Indeed, there is a growing literature discussing S⋯O interactions (Burling & Goldstein, 1992; Iwaoka et al., 2002 ; Beno et al., 2015). 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 shows that it is interesting that Δδ_{crystal–molecule} (note that this is the negative of the difference in calculated absolute shielding, with the latter being stated in Table 4) 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 ). 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	σ_molecule	σ_crystal	σ_{crystal–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

CCDC reference: 1507863

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2053229617000870/df3006sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2053229617000870/df3006Isup3.hkl

CASTEP cif output. DOI: https://doi.org/10.1107/S2053229617000870/df3006sup2.txt

magres file. DOI: https://doi.org/10.1107/S2053229617000870/df3006sup4.txt

Additional Tables (DQ NMR data and distances as well as a comparison of experimental and calculated (GIPAW) 13C chemical shift values) and a Figure showing the difference in the numbering schemes between the crystallographic data and the output of the GIPAW (CASTEP) calculations. DOI: https://doi.org/10.1107/S2053229617000870/df3006sup5.pdf

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·C₁₂H₁₃N₃	F(000) = 1024
M_r = 495.59	D_x = 1.467 Mg m⁻³
Monoclinic, P2₁/n	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2yn	Cell parameters from 2711 reflections
a = 7.1707 (2) Å	θ = 5.0–62.6°
b = 22.8006 (6) Å	µ = 2.45 mm⁻¹
c = 13.8237 (4) Å	T = 100 K
β = 97.047 (3)°	Plate, purple
V = 2243.04 (7) Å³	0.60 × 0.10 × 0.02 mm
Z = 4

Data collection top

Agilent Xcalibur Onyx Ultra diffractometer	2667 reflections with I > 2.0σ(I)
Mirror monochromator	R_int = 0.035
ω/2θ scans	θ_max = 58.9°, θ_min = 3.2°
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	h = −5→7
T_min = 0.596, T_max = 1.000	k = −25→25
5143 measured reflections	l = −14→15
3160 independent reflections

Refinement top

Refinement on F²	Primary atom site location: other
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.045	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.094	Method, part 1, Chebychev polynomial [weight] = 1.0/[A₀T₀(x) + A₁T₁(x) ··· + A_n-1]T_n-1(x)] where A_i are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting W = [weight] [1-(deltaF/6*sigmaF)²]² A_i are: 0.138E + 04 0.207E + 04 0.111E + 04 326.
S = 0.98	(Δ/σ)_max = 0.001
3141 reflections	Δρ_max = 0.43 e Å⁻³
109 parameters	Δρ_min = −0.37 e Å⁻³
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

	x	y	z	U_iso*/U_eq
S1	0.57630 (11)	0.51819 (3)	0.79844 (6)	0.0223
C2	0.3685 (4)	0.48079 (13)	0.7529 (2)	0.0212
C3	0.2072 (4)	0.47646 (13)	0.7926 (2)	0.0202
S4	0.14929 (11)	0.50645 (3)	0.90297 (5)	0.0206
C5	0.3411 (4)	0.55384 (12)	0.9352 (2)	0.0177
C6	0.5006 (4)	0.55878 (12)	0.8951 (2)	0.0175
C7	0.6476 (4)	0.60247 (12)	0.9342 (2)	0.0179
O8	0.7809 (3)	0.61031 (9)	0.88850 (15)	0.0221
C9	0.6255 (4)	0.63243 (12)	1.0265 (2)	0.0167
C10	0.4604 (4)	0.62563 (12)	1.0704 (2)	0.0176
C11	0.3051 (4)	0.58862 (13)	1.0216 (2)	0.0176
O12	0.1533 (3)	0.58453 (9)	1.05284 (15)	0.0237
C13	0.4420 (4)	0.65186 (13)	1.1586 (2)	0.0214
C14	0.5889 (5)	0.68550 (14)	1.2043 (2)	0.0247
C15	0.7515 (5)	0.69313 (13)	1.1606 (2)	0.0235
C16	0.7717 (4)	0.66662 (13)	1.0719 (2)	0.0211
C17	0.0513 (5)	0.44419 (13)	0.7438 (2)	0.0227
N18	−0.0763 (4)	0.41868 (13)	0.7075 (2)	0.0334
C19	0.3871 (5)	0.45136 (14)	0.6633 (2)	0.0244
N20	0.4065 (4)	0.42677 (13)	0.5922 (2)	0.0372
N21	0.1269 (3)	0.65896 (11)	0.81861 (18)	0.0185
C22	0.1456 (4)	0.63048 (12)	0.7301 (2)	0.0193
C23	0.3046 (5)	0.63170 (13)	0.6818 (2)	0.0227
C24	0.3041 (5)	0.60183 (14)	0.5940 (2)	0.0281
C25	0.1478 (5)	0.57112 (14)	0.5532 (2)	0.0305
C26	−0.0103 (5)	0.56959 (14)	0.6017 (2)	0.0289
C27	−0.0132 (5)	0.59861 (13)	0.6889 (2)	0.0227
C28	0.2398 (4)	0.69992 (12)	0.8710 (2)	0.0172
N29	0.4071 (3)	0.71395 (10)	0.84429 (17)	0.0189
C30	0.5047 (4)	0.75525 (13)	0.8996 (2)	0.0204
C31	0.4355 (4)	0.78043 (13)	0.9782 (2)	0.0240
C32	0.2624 (5)	0.76203 (13)	1.0009 (2)	0.0233
N33	0.1612 (3)	0.72147 (11)	0.94755 (18)	0.0203
C34	0.1768 (5)	0.78633 (16)	1.0859 (3)	0.0350
C35	0.6919 (4)	0.77160 (14)	0.8698 (2)	0.0256
H131	0.3325	0.6473	1.1887	0.0272*
H141	0.5773	0.7037	1.2645	0.0304*
H151	0.8471	0.7168	1.1907	0.0275*
H161	0.8807	0.6722	1.0421	0.0261*
H231	0.4128	0.6519	0.7083	0.0274*
H241	0.4121	0.6020	0.5619	0.0339*
H251	0.1519	0.5519	0.4941	0.0370*
H261	−0.1170	0.5500	0.5748	0.0342*
H271	−0.1197	0.5972	0.7217	0.0260*
H311	0.5042	0.8085	1.0170	0.0294*
H342	0.0443	0.7782	1.0832	0.0544*
H341	0.1920	0.8277	1.0869	0.0549*
H343	0.2423	0.7710	1.1438	0.0548*
H352	0.7389	0.8070	0.9003	0.0411*
H353	0.6847	0.7771	0.8015	0.0418*
H351	0.7800	0.7420	0.8872	0.0415*
H211	0.022 (3)	0.6531 (11)	0.8421 (16)	0.0231*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0223	0.0220	0.0224	−0.0001	0.0015	−0.0055
C2	0.0274	0.0150	0.0197	0.0019	−0.0035	0.0014
C3	0.0236	0.0150	0.0203	−0.0003	−0.0043	0.0020
S4	0.0215	0.0185	0.0211	−0.0044	0.0004	−0.0018
C5	0.0202	0.0125	0.0189	0.0022	−0.0038	0.0041
C6	0.0214	0.0132	0.0169	0.0009	−0.0021	0.0022
C7	0.0197	0.0133	0.0204	0.0045	0.0009	0.0041
O8	0.0219	0.0229	0.0214	−0.0035	0.0027	−0.0011
C9	0.0188	0.0127	0.0171	0.0016	−0.0041	0.0010
C10	0.0199	0.0135	0.0184	0.0016	−0.0015	0.0037
C11	0.0187	0.0143	0.0198	0.0015	0.0023	0.0054
O12	0.0250	0.0224	0.0244	−0.0031	0.0062	0.0008
C13	0.0242	0.0199	0.0206	0.0015	0.0041	0.0008
C14	0.0338	0.0223	0.0175	−0.0007	0.0016	−0.0052
C15	0.0277	0.0184	0.0225	−0.0036	−0.0042	−0.0039
C16	0.0206	0.0174	0.0244	0.0004	−0.0003	0.0021
C17	0.0271	0.0205	0.0195	−0.0001	−0.0013	0.0002
N18	0.0413	0.0324	0.0255	−0.0073	0.0002	−0.0019
C19	0.0281	0.0203	0.0244	0.0027	0.0018	0.0001
N20	0.0423	0.0377	0.0314	0.0023	0.0037	−0.0076
N21	0.0157	0.0194	0.0204	−0.0024	0.0017	−0.0019
C22	0.0294	0.0114	0.0161	0.0038	−0.0013	0.0021
C23	0.0284	0.0181	0.0215	0.0000	0.0027	0.0018
C24	0.0429	0.0202	0.0223	0.0053	0.0090	0.0021
C25	0.0517	0.0213	0.0177	0.0021	0.0016	−0.0017
C26	0.0429	0.0167	0.0242	−0.0026	−0.0075	−0.0005
C27	0.0289	0.0183	0.0198	0.0015	−0.0020	0.0034
C28	0.0207	0.0113	0.0185	0.0042	−0.0016	0.0037
N29	0.0213	0.0152	0.0199	0.0012	0.0007	0.0033
C30	0.0215	0.0145	0.0238	0.0007	−0.0033	0.0047
C31	0.0283	0.0158	0.0267	−0.0028	−0.0013	−0.0036
C32	0.0270	0.0190	0.0235	0.0016	0.0019	−0.0027
N33	0.0224	0.0175	0.0210	0.0013	0.0029	−0.0031
C34	0.0366	0.0326	0.0373	−0.0031	0.0103	−0.0140
C35	0.0244	0.0239	0.0278	−0.0050	0.0004	0.0034

Geometric parameters (Å, º) top

S1—C2	1.764 (3)	N21—H211	0.864 (17)
S1—C6	1.764 (3)	C22—C23	1.391 (4)
C2—C3	1.343 (4)	C22—C27	1.410 (4)
C2—C19	1.429 (4)	C23—C24	1.390 (4)
C3—S4	1.767 (3)	C23—H231	0.938
C3—C17	1.436 (4)	C24—C25	1.382 (5)
S4—C5	1.763 (3)	C24—H241	0.939
C5—C6	1.336 (4)	C25—C26	1.387 (5)
C5—C11	1.483 (4)	C25—H251	0.930
C6—C7	1.502 (4)	C26—C27	1.378 (4)
C7—O8	1.223 (4)	C26—H261	0.923
C7—C9	1.473 (4)	C27—H271	0.936
C9—C10	1.404 (4)	C28—N29	1.336 (4)
C9—C16	1.393 (4)	C28—N33	1.350 (4)
C10—C11	1.491 (4)	N29—C30	1.353 (4)
C10—C13	1.379 (4)	C30—C31	1.375 (4)
C11—O12	1.222 (4)	C30—C35	1.499 (4)
C13—C14	1.390 (4)	C31—C32	1.382 (5)
C13—H131	0.938	C31—H311	0.935
C14—C15	1.388 (5)	C32—N33	1.339 (4)
C14—H141	0.944	C32—C34	1.498 (4)
C15—C16	1.390 (4)	C34—H342	0.964
C15—H151	0.931	C34—H341	0.950
C16—H161	0.936	C34—H343	0.944
C17—N18	1.146 (4)	C35—H352	0.952
C19—N20	1.155 (4)	C35—H353	0.949
N21—C22	1.406 (4)	C35—H351	0.935
N21—C28	1.382 (4)

C2—S1—C6	101.45 (14)	N21—C22—C27	115.5 (3)
S1—C2—C3	128.4 (2)	C23—C22—C27	119.0 (3)
S1—C2—C19	111.8 (2)	C22—C23—C24	119.6 (3)
C3—C2—C19	119.7 (3)	C22—C23—H231	120.6
C2—C3—S4	129.0 (2)	C24—C23—H231	119.7
C2—C3—C17	120.4 (3)	C23—C24—C25	121.3 (3)
S4—C3—C17	110.6 (2)	C23—C24—H241	119.7
C3—S4—C5	101.35 (14)	C25—C24—H241	118.9
S4—C5—C6	128.9 (2)	C24—C25—C26	119.0 (3)
S4—C5—C11	108.9 (2)	C24—C25—H251	119.1
C6—C5—C11	122.2 (3)	C26—C25—H251	121.9
S1—C6—C5	129.0 (2)	C25—C26—C27	120.8 (3)
S1—C6—C7	110.7 (2)	C25—C26—H261	120.2
C5—C6—C7	120.3 (3)	C27—C26—H261	118.9
C6—C7—O8	118.0 (3)	C22—C27—C26	120.2 (3)
C6—C7—C9	118.3 (3)	C22—C27—H271	119.3
O8—C7—C9	123.6 (3)	C26—C27—H271	120.5
C7—C9—C10	120.6 (3)	N21—C28—N29	120.3 (3)
C7—C9—C16	119.7 (3)	N21—C28—N33	112.5 (3)
C10—C9—C16	119.7 (3)	N29—C28—N33	127.2 (3)
C9—C10—C11	119.3 (3)	C28—N29—C30	115.5 (3)
C9—C10—C13	120.7 (3)	N29—C30—C31	121.7 (3)
C11—C10—C13	119.9 (3)	N29—C30—C35	115.9 (3)
C10—C11—C5	118.2 (3)	C31—C30—C35	122.4 (3)
C10—C11—O12	122.1 (3)	C30—C31—C32	118.3 (3)
C5—C11—O12	119.6 (3)	C30—C31—H311	121.5
C10—C13—C14	119.5 (3)	C32—C31—H311	120.2
C10—C13—H131	121.3	C31—C32—N33	121.7 (3)
C14—C13—H131	119.3	C31—C32—C34	122.1 (3)
C13—C14—C15	120.1 (3)	N33—C32—C34	116.2 (3)
C13—C14—H141	120.0	C28—N33—C32	115.6 (3)
C15—C14—H141	119.9	C32—C34—H342	113.2
C14—C15—C16	120.9 (3)	C32—C34—H341	108.8
C14—C15—H151	119.4	H342—C34—H341	107.6
C16—C15—H151	119.7	C32—C34—H343	108.7
C9—C16—C15	119.1 (3)	H342—C34—H343	110.3
C9—C16—H161	120.1	H341—C34—H343	108.1
C15—C16—H161	120.8	C30—C35—H352	111.7
C3—C17—N18	177.7 (3)	C30—C35—H353	111.4
C2—C19—N20	178.1 (3)	H352—C35—H353	107.6
C22—N21—C28	131.0 (3)	C30—C35—H351	110.5
C22—N21—H211	115.8 (12)	H352—C35—H351	107.8
C28—N21—H211	112.8 (12)	H353—C35—H351	107.7
N21—C22—C23	125.5 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C23—H231···N29	0.94	2.36	2.950 (4)	121 (1)
C27—H271···O8ⁱ	0.94	2.51	3.296 (4)	141 (1)
N21—H211···O8ⁱ	0.86	2.15	2.985 (4)	162 (2)

Symmetry code: (i) x−1, y, z.

Comparison of calculated (GIPAW)^a and experimental ¹³C and ¹H NMR chemical shifts (in ppm) in the DI–PM cocrystal^b top

Atom label	¹³C	¹H
C	H	δ_calc	δ_expt	δ_calc	δ_expt
C65	H22/H23/H24^c	15.3	23.9	1.8	1.9
C68	H26/H27/H28^c	17.2	25.7	2.0	2.0
C66	H25	111.5	112.6	3.4	4.0
C1	-	113.8	114.4^d	-	-
C14	-	114.5	114.4^d	-	-
C2	-	115.5	114.4^d	-	-
C13	-	115.9	114.4^d	-	-
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	H1^e	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	H4^e	128.6	129.8	8.5	8.2
C60	H19	129.3	130.2	7.3	7.8
C4	-	130.1	131.1^d	-	-
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	141.4^d	-	-
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	176.5^d	-	-
C8	-	179.9	178.2^d	-	-

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

Atom	δ_exp	δ_crystal	δ_molecule	Δδ_{crystal-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
H22/23/24^b	1.9	1.8	1.9	?0.1
H25	4.0	3.4	6.1	?2.7
H26/27/28^b	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 ?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

Atom	σ_molecule	σ_crystal	σ_{crystal-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	?97.6
O2	?345.3	?322.2	?23.1
S1	330.7	305.6	25.1
S2	333.8	320.6	13.2

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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