Exploring the salt–cocrystal continuum with solid-state NMR using natural-abundance samples: implications for crystal engineering

Rajput, L.; Banik, M.; Yarava, J.R.; Joseph, S.; Pandey, M.K.; Nishiyama, Y.; Desiraju, G.R.

doi:10.1107/S205225251700687X

research papers

IUCrJ

Volume 4| Part 4| July 2017| Pages 466-475

ISSN: 2052-2525

https://doi.org/10.1107/S205225251700687X

CHEMISTRY | CRYSTENG

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Exploring the salt–cocrystal continuum with solid-state NMR using natural-abundance samples: implications for crystal engineering

Lalit Rajput,^a ‡ Manas Banik,^a ‡ Jayasubba Reddy Yarava,^b § Sumy Joseph,^a Manoj Kumar Pandey,^b,^c,^d Yusuke Nishiyama ^b,^c ^* and Gautam R. Desiraju ^a ^*

^aSolid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore, 560 012, India, ^bRIKEN CLST–JEOL Collaboration Center, RIKEN, Yokohama, Kanagawa 230-0045, Japan, ^cJEOL RESONANCE Inc., Musashino, Akishima, Tokyo 196-8558, Japan, and ^dDepartment of Chemistry, Indian Institute of Technology Ropar, Rupnagar, India
^*Correspondence e-mail: yunishiy@jeol.co.jp, desiraju@sscu.iisc.ernet.in

Edited by L. R. MacGillivray, University of Iowa, USA (Received 21 February 2017; accepted 8 May 2017; online 5 June 2017)

There has been significant recent interest in differentiating multicomponent solid forms, such as salts and cocrystals, and, where appropriate, in determining the position of the proton in the X—H⋯A—Y X⁻⋯H—A⁺—Y continuum in these systems, owing to the direct relationship of this property to the clinical, regulatory and legal requirements for an active pharmaceutical ingredient (API). In the present study, solid forms of simple cocrystals/salts were investigated by high-field (700 MHz) solid-state NMR (ssNMR) using samples with naturally abundant ¹⁵N nuclei. Four model compounds in a series of prototypical salt/cocrystal/continuum systems exhibiting {PyN⋯H—O—}/{PyN⁺—H⋯O⁻} hydrogen bonds (Py is pyridine) were selected and prepared. The crystal structures were determined at both low and room temperature using X-ray diffraction. The H-atom positions were determined by measuring the ¹⁵N—¹H distances through ¹⁵N-¹H dipolar interactions using two-dimensional inversely proton-detected cross polarization with variable contact-time (invCP-VC) ¹H→¹⁵N→¹H experiments at ultrafast (ν_R ≥ 60–70 kHz) magic angle spinning (MAS) frequency. It is observed that this method is sensitive enough to determine the proton position even in a continuum where an ambiguity of terminology for the solid form often arises. This work, while carried out on simple systems, has implications in the pharmaceutical industry where the salt/cocrystal/continuum condition of APIs is considered seriously.

Keywords: salt; cocrystal; continuum; natural abundance; solid-state NMR; X-ray diffraction.

CCDC references: 1529546; 1529544; 1529545; 1529547; 1529549; 1529550; 1529542; 1529548; 1529541; 1529543

1. Introduction

Detection of the H-atom position in an X—H⋯A—Y hydrogen bond is a matter of fundamental and practical importance (Jeffrey, 1997 ; Desiraju & Steiner, 1999 ). Atomic positions derived for an H atom from an X-ray analysis approximates the centroid of the electron density. Positions derived from neutron diffraction correspond to the nuclei of the atoms. Neutron-derived H-atom positions and the corresponding hydrogen-bond metrics are more accurate but this does not necessarily mean that they are chemically the most meaningful (Aakeröy & Seddon, 1993 ; Cotton & Luck, 1989 ). An X—H⋯A—Y hydrogen bond may also be considered as an extreme of a proton-transfer reaction where the other extreme is X⁻⋯H—A⁺—Y. Situations are known in which this proton-transfer reaction is mediated by a change in temperature and where the H-atom position varies smoothly between the X and A atoms (Steiner et al., 2001 ; Parkin et al., 2004 ; Wilson & Goeta, 2004 ; Grobelny et al., 2011 ).

In the pharmaceutical industry, there is considerable interest in making multicomponent molecular crystals of drugs or active pharmaceutical ingredients (APIs) in order to achieve better physical, chemical or pharmacological properties (Almarsson & Zaworotko, 2004 ; Vishweshwar et al., 2006 ; Wouters & Quéré, 2012 ). Generally, these crystals involve the formation of a hydrogen bond between the drug molecule, which is usually basic, and another compound, referred to often as a coformer, which is usually acidic. The binary crystal therefore often contains a hydrogen bond of the type (Drug)⋯H—(Coformer) and if the two molecular species are not ionized, the substance is called a `cocrystal'. The definition of this term `cocrystal' is still contentious (Desiraju, 2003 ; Dunitz, 2003 ; Bond, 2007 ; Childs et al., 2007 ; Aakeröy & Salmon, 2005 ; Aitipamula et al., 2012 ) and is in some aspects incomplete or inadequate. In any event, if the proton-transfer reaction across the hydrogen bond is complete, the multicomponent crystal that is obtained is of the form (Drug)⁺—H⋯(Coformer)⁻ and is called a `salt', whereas the intermediate state of affairs is termed a `continuum' (Fig. 1).

Figure 1
Schematic presentation of (a) a cocrystal, (b) a salt and (c) a continuum (where the H-atom position is shared between the two heavy atoms) in a typical O···H···N interaction.

For the patent protection of new multicomponent solid forms of an API, the substance to be patented must be characterized as denoted by the specifications, i.e. whether it is a salt or cocrystal. For example, some APIs were found to exhibit the tendency to transform from one drug form to another due to external forces, such as light, heat, pressure and mechanical grinding (Ikni et al., 2014 ; Pirttimäki et al., 1993 ; Shakhtshneider & Boldyrev, 1993 ; Otsuka et al., 1994 ). Therefore, a proper study of the new solid form is of the utmost importance as it is directly related to both patient safety and clinical efficacy. If this issue remains unresolved, the exploration of pharmaceutical solids becomes restricted and the competitive advantage of drug development to launch the product is lost. There are important regulatory and legal implications as to whether or not the marketed form of a drug is the `cocrystal' or `salt' form. What is of relevance here is the so-called ΔpK_a rule, which states that a salt is obtained if the pK_a difference between the drug and the coformer is greater than 3, while if the difference is less than 1, a cocrystal is obtained (Bhogala et al., 2005 ; Cruz-Cabeza, 2012 ; Ramon et al., 2014 ; Mukherjee & Desiraju, 2014 ; US–FDA, 2016 ). The intermediate region, i.e. 1 < ΔpK_a < 3, contains cases where the H atom (proton) is unusually labile and wherein it can move between the drug and coformer species. This gives rise to the so-called `salt–cocrystal continuum', a phenomenon that has been studied using a variety of crystallographic techniques (Aakeröy et al., 2007 ; Childs et al., 2007; Schmidtmann et al., 2007 ; Hathwar et al., 2010 ; Thomas et al., 2010 ; da Silva et al., 2013 ). Drug⋯coformer systems in the intermediate ΔpK_a range are of special significance in regulatory and legal contexts. Over the last decade, crystal engineering has been used extensively to modify the physicochemical properties of APIs by making new solid forms (Desiraju, 2013 ; Duggirala et al., 2016 ).

Solid-state NMR (ssNMR) methods have always been used in conjugation with diffraction methods, or alone, to determine H-atom positions in hydrogen bonds (Berglund & Vaughan, 1980 ; Rohlfing et al., 1983 ; Jeffrey & Yeon, 1986 ; Wu et al., 1998 ; Yazawa et al., 2012 ; Miah et al., 2013 ). ssNMR has also been used to ascertain the nature of the salt–cocrystal continuum in API systems (Stevens et al., 2014 ). The use of ¹⁵N ssNMR has been documented previously (Li et al., 2006 ). These applications rely on the dependence of chemical shift tensors on H-atom positions. It is obvious that ¹H chemical shift tensors are very sensitive to H-atom positions because ¹H NMR detects the H atoms directly. In addition, ¹⁵N chemical shift tensors are also affected by H-atom positions through changes in the electron distribution, thereby making it also sensitive to H-atom positions. These dependences are further corroborated by quantum chemical calculations. There are several cases where it is very difficult to obtain X-ray-quality single crystals, and powder X-ray methods are often inadequate to accurately determine H-atom positions. In addition, H-atom positions in X-ray diffraction measurements are systematically foreshortened and are at the limit of detection in any case. In such cases, ssNMR is an excellent complementary technique for determining H-atom positions. There is always the fundamental question of whether the X-ray-derived or the neutron-derived position is the more `correct' or indeed if either of these positions is `correct' at all. There are some studies that record differences between the H-atom positions determined by diffraction- and NMR-based methods (Roberts et al., 1987 ; Lorente et al., 2001 ). These disagreements arise partly from the uncertainty in the positions of the H atoms in all X-ray-diffraction-based methods on the one hand, and the fact that the determination of H-atom positions in ssNMR is based on an indirect measurement through chemical shift tensors on the other. Neutron diffraction analysis is very difficult to carry out, compared to X-ray diffraction and ssNMR, because large crystals are needed, which are often impossible to obtain, and also because one needs to collect data over an extended time period in a remote laboratory equipped with a neutron source. Noting that all three methods, i.e. X-ray diffraction, neutron diffraction and ssNMR, may give slightly different results for H-atom positions, and that none of these measurements can, strictly speaking, be used as benchmarks for each other, we embarked on the present study.

Besides the chemical shift tensor, ssNMR is able to measure internuclear N—H distances through ¹⁵N-¹H dipolar interactions, as the magnitude of the dipolar interaction is inversely proportional to the cube of the internuclear distance. This potentially gives a straightforward solution to the `salt/cocrystal/continuum' problem, while diffraction-based methods provide internuclear distances from the atomic positions themselves. However, the ¹H—X distance measurements are not easy because of the presence of intense homonuclear ¹H-¹H dipolar interactions and a very low abundance of ¹⁵N (0.4%). While the former obscures the ¹H-X dipolar interactions, the latter gives very limited sensitivity, making the measurements practically impossible. These difficulties require isotopic dilution of ¹H with ²H and/or isotopic enrichment with ¹⁵N nuclei, thus limiting their common application. Moreover, the small ¹⁵N-¹H dipolar interaction due to the small ¹⁵N gyromagnetic ratio (about 10% of ¹H) complicates the problem further.

Recent progress in fast magic angle sample spinning (MAS) technology (Nishiyama, 2016 ) has paved a new way for determining ¹H-X dipolar interactions (Paluch et al., 2013 , 2015 ; Park et al., 2013 ; Zhang et al., 2015 ; Nishiyama et al., 2016 ). Ultrafast MAS > 60 kHz, which is exclusively achieved by a very tiny rotor with a diameter of less than 1.3 mm accompanied by a small sample volume, can overcome the above-mentioned difficulties by suppressing the ¹H-¹H dipolar interactions to facilitate ¹H—X distance measurement. In addition, ultrafast MAS allows direct observation of the NMR signal through the ¹H nucleus, which is much more sensitive than ¹⁵N because of its high gyromagnetic ratio. The use of high-field magnets, which are now commonly available to researchers, improves the sensitivity further. These combinations allow the observation of ¹H-X dipolar interactions in natural-abundance samples with a limited sample volume. The one possible limitation of ¹H observation in multicomponent systems is the poor resolution of the ¹H chemical shift obtainable in ssNMR even at the maximum attainable MAS rate. However, ¹⁵N—¹H distance measurements filter out the ¹H signals which are not connected to the ¹⁵N nuclei, allowing direct measure of ¹⁵N-¹H dipolar interactions without any overlap of ¹H resonances.

This article describes a method where high-field ssNMR is used to determine accurate ¹⁵N—¹H distances in a series of prototypical salt/cocrystal/continuum systems of the type {PyN⋯H—O—}/{PyN⁺—H⋯O⁻} at natural abundance without any isotopic dilution/enrichment. Of special significance is that we have used natural-abundance samples throughout. Furthermore, the distances obtained from ssNMR data were compared with the distances obtained from single-crystal X-ray diffraction (SCXRD) data.

2. Experimental section

2.1. General procedures

All reagents were purchased from commercial sources and were used without further purification. Fourier Transform infrared (FT–IR) spectra were recorded in ATR mode with a PerkinElmer (Frontier) spectrophotometer (4000–400 cm⁻¹). Powder X-ray diffraction (PXRD) data was recorded using a Philips X'pert Pro X-ray powder diffractometer equipped with an X'cellerator detector at room temperature with a scan range 2θ = 5–40° and a step size of 0.026°. X'PertHighScore Plus values were used to compare the experimental PXRD pattern with the calculated lines from the crystal structure. Differential scanning calorimetry (DSC) was performed on a Mettler Toledo DSC 823e module with the heating rate of 5 K min⁻¹ under a nitrogen atmosphere.

2.2. Crystallization method

Crystallization experiments were carried out under ambient conditions for the four model compounds SA1, SA2, CO1 and CNT1.

SA1: N,N-Dimethypyridin-4-amine and 3-nitrobenzoic acid were taken in a 1:1 molar ratio in a conical flask and dissolved in a minimum amount of MeOH. Good-quality crystals, suitable for diffraction, were obtained after 4–5 d.

SA2: 4-Ethylpyridine and 3,5-dinitrobenzoic acid were taken in a 1:1 molar ratio in a conical flask and dissolved in a minimum amount of MeOH. Good-quality crystals, suitable for diffraction, were obtained after 5–6 d.

CO1: 3-Ethylpyridine and 4-nitrobenzoic acid were taken in a 1:1 molar ratio in a conical flask and dissolved in a minimum amount of MeOH. Good-quality crystals, suitable for diffraction, were obtained after 6–7 d.

CNT1: 4-Methylpyridine and 2,3,4,5,6-pentachlorophenol were taken in a 1:1 molar ratio in a conical flask and dissolved in a minimum amount of MeOH. Good-quality crystals, suitable for diffraction, were obtained after 6–7d.

2.3. Single-crystal X-ray diffraction

Single-crystal X-ray diffraction (SCXRD) data were collected on a Rigaku Mercury 375/M CCD (XtaLAB mini) using graphite-monochromated Mo Kα radiation at 298 and 110 K. The data were processed using CrystalClear software (Rigaku, 2009 ). Some data sets were collected on a Bruker SMART APEX (D8 QUEST) CMOS diffractometer equipped with an Oxford cryosystems N₂ open-flow cryostat using Mo Kα radiation. Data integration and data reduction were carried out with the SAINT-Plus program (Bruker, 2006 ). Structure solution and refinement were executed using SHELXL97 (Sheldrick, 2008 ) embedded in the WinGX suite (Farrugia, 1999 ) and OLEX2 (Dolomanov et al., 2009 ). Refinement of the coordinates and anisotropic displacement parameters of non-H atoms were performed using the full-matrix least-squares method. H-atom positions were located from difference Fourier maps or calculated using the riding model. However, the H atoms of the protonated pyridine and –COOH groups were located from difference Fourier maps. PLATON (Spek, 2009 ) was used to prepare material for publication.

2.4. ssNMR experimental details

The N—H distances/dipolar couplings are measured by two-dimensional inversely proton-detected cross polarization with variable contact-time (invCP-VC) experiments at ultrafast MAS frequencies (60–70 kHz) (Park et al., 2013; Nishiyama et al., 2016). In CP-VC experiments, the oscillatory behaviour during CP build-up is observed by monitoring the NMR signal intensities with various contact times of CP (Paluch et al., 2013, 2015). The Fourier transformation of the NMR signal intensity with respect to the contact time gives two well-separated narrow peaks/singularities of the Pake-like dipolar powder pattern. Although the overall dipolar powder pattern is very sensitive to experimental imperfections, the separation between two singularities gives a reliable measure of the size of the N—H dipolar interactions (Paluch et al., 2015). While MAS averages out all the homonuclear (¹H-¹H) and heteronuclear (¹⁵N-¹H) dipolar interactions, the simultaneous rf irradiation during CP on ¹H and ¹⁵N hinders the averaging, in effect recoupling the ¹⁵N-¹H dipolar interactions (Hartmann & Hahn, 1962 ). This results in oscillatory magnetization transfer between ¹H and ¹⁵N during CP (Müller et al., 1974 ). Generally, this oscillatory behaviour is only observed at ultrafast MAS, since it is obscured by residual ¹H-¹H dipolar interactions at moderate MAS rates (Paluch et al., 2015). The sensitivity is maximized by the introduction of the ¹H indirect detection approach (Müller, 1979 ; Bodenhausen & Ruben, 1980 ) into the CP-VC scheme. The initial magnetization is first transferred from ¹H to ¹⁵N and then back-transferred to ¹H magnetization for detection. Since the gyromagnetic ratio of ¹H is ∼10 times larger than that of ¹⁵N, the initial magnetization of ¹H is much greater than that of ¹⁵N and, therefore, significant sensitivity enhancement can be achieved. This can be implemented in the invCP-VC scheme as shown in Fig. 2. First, ramped-amplitude cross polarization (RAMP-CP) is used for magnetization transfer from ¹H to ¹⁵N (Metz et al., 1994 ). This prepares the initial ¹⁵N magnetization which is indirectly observed at the end of the sequence. It is important to remove the unwanted residual ¹H magnetization by the homonuclear rotary resonance recoupling (HORROR) sequence on the ¹H channel (Nielsen et al., 1994 ; Ishii et al., 2001 ), since more than 99% of ¹H does not have a ¹⁵N neighbour in a natural-abundance sample. During HORROR irradiation, the ¹⁵N magnetization is stored along the z axis by a pair of ¹⁵N 90° pulses, such that time-evolution and transversal relaxation of ¹⁵N are avoided. ¹⁵N magnetization is then back-transferred to ¹H by the second constant CP with variable contact times. Finally, the ¹H signal is acquired under a weak ¹⁵N-¹H heteronuclear WALTZ decoupling irradiation (Shaka et al., 1983 ) on ¹⁵N (Wickramasinghe et al., 2015 ). The ¹H signal intensity thus obtained is modulated by the ¹⁵N-¹H dipolar interaction, which is recoupled by the second constant CP, giving dipolar oscillation. The time-domain data thus obtained are Fourier transformed into frequency-domain data in both dimensions. DC correction (subtracting the average of the final one-eighth points from the total data points) in the ¹H-¹⁵N dipolar dimension should be applied prior to the Fourier transformation to remove the intense central peak. The peak position in the direct dimension represents the ¹H chemical shift, whereas the separation of the peaks (Δ) in the indirect dimension reflects the ¹⁵N-¹H dipolar coupling, which is converted to an ¹⁵N—¹H distance (d_{1H - 15N}) using the following relationship:

$[{d_{{\rm{1H}} - {\rm{15N}}}}\left({\mathop {\rm A}\limits^ \circ } \right) = {\left({{{120.1} \over {\sqrt 2 \Delta \left({{\rm{kHz}}} \right)}}{{{\gamma _{15{\rm{N}}}}} \over {{\gamma _{1{\rm{H}}}}}}} \right)^{{1 \mathord{\left/ {\vphantom {1 3}} \right. \kern-\nulldelimiterspace} 3}}}, \eqno(1)]$

where $[{\gamma _{{\rm{1H}}\left({{\rm{15N}}} \right)}}]$ is the gyromagnetic ratio of ¹H(¹⁵N) and $[{{{\gamma _{{\rm{15N}}}}} \mathord{\left/ {\vphantom {{{\gamma _{{\rm{15N}}}}} {{\gamma _{{\rm{1H}}}}}}} \right. \kern-\nulldelimiterspace} {{\gamma _{{\rm{1H}}}}}}]$ = 0.10136. The equation with the scaling factor of $[\sqrt 2]$ in the invCP-VC experiment is derived from Eq. 2.15 in Schmidt-Rohr & Spiess (1994 ). Because of the inverse cubic relationship between the internuclear distance and the magnitude of the dipolar coupling, even for systems with small variations in a distance, the separation of dipolar splitting is significantly different. Consequently, precise N—H internuclear distances can be measured from the experiment. For example, the separations (Δ) for 1.0 and 1.1 Å N—H distances are 8.6 and 6.5 kHz, respectively. Moreover, for longer N—H distances, Δ becomes smaller (Δ = 0.3 kHz for 3 Å); therefore, only those protons with very short ¹⁵N—¹H distances show splitting in the indirect dimension and the other protons do not show any splitting.

Figure 2
The pulse sequence used to record the two-dimensional inversely proton-detected cross polarization with variable contact-time (invCP-VC) spectra.

All the data were collected on a 700 MHz (JNM-ECA700II, Jeol RESONANCE Inc.) NMR spectrometer. For each experiment, about 0.8 mg samples were packed separately into a zirconia sample rotor with an outer diameter of 1 mm. All the experimental parameters used to record the invCP-VC experiments on CO1, CNT1, SA2 and SA1 are given in Table 1. DQ Hartmann–Hahn CP matching conditions (ν_1H + ν_15N = ν_R) were used for all four samples (Laage et al., 2009 ). Optimization of the DQ CP condition was carried out using ¹⁵N₃-labelled L-histidine·HCl·H₂O or ¹³C₃,¹⁵N-labelled L-alanine by maximizing the ¹H NMR spectra observed with the sequence shown in Fig. 2 with a fixed second contact time (typically 1 ms). The experimental conditions can be further verified by observing the invCP-VC spectra of a ¹⁵N₃-labelled L-histidine sample. Two N—H protons of the imidazole ring should give splittings of 6.9 and 7.6 kHz if all the experimental conditions are properly adjusted.

Table 1
All the experimental parameters used to record the invCP-VC experiments

Compound	Spectrometer frequency (MHz)	MAS rate (kHz)	¹H 90° (µs)	¹⁵N 90° (µs)	Scans	Recycle delay (s)	Contact time (First CP)	Contact time (Second CP)	Total experiment time (days)
SA1	700	60	0.9	2.2	288	70	1.0 ms	10 µs–0.71 ms (15 increments)	3.5
SA2	700	70	0.9	2.2	736	20	1.5 ms	30 µs–1.02 ms (34 increments)	5.8
CO1	700	70	1	5	320	8	2.0 ms	0 µs–1.52 ms (151 increments)	4.5
CNT1	700	70	0.7	5	136	70	2.0 ms	0 µs–1 ms (51 increments)	5.0

3. Results and discussion

For this study, we have prepared four solid forms composed of 3-nitrobenzoic acid and N,N-dimethypyridin-4-amine (SA1) (Saha et al., 2015 ), 3,5-dinitrobenzoic acid and 4-ethylpyridine (SA2), and 4-nitrobenzoic acid and 3-ethylpyridine (CO1). We also examined the well-studied case of pentachlorophenol and 4-methylpyridine (CNT1) (Malarski et al., 1987 ; Steiner et al., 2001) (Fig. 3). All the solid forms were crystallized and characterized by DSC, FT–IR spectroscopy, PXRD, SCXRD and ssNMR. In order to confirm the solid form, i.e. the salt/cocrystal/continuum, SCXRD data were collected at room temperature and at 110 K.

Figure 3
Schematic representation of the compounds used in the present study, showing (a) SA1 (3-nitrobenzoic acid and N,N-dimethypyridin-4-amine), (b) SA2 (3,5-dinitrobenzoic acid and 4-ethylpyridine), (c) CO1 (4-nitrobenzoic acid and 3-ethylpyridine) and (d) CNT1 (pentachlorophenol and 4-methylpyridine).

The invCP-VC experiment has several advantages compared to previously reported heteronuclear distance measurement methods (Ramamoorthy et al., 1999 ; Ladizhansky & Vega, 2000 ; van Rossum et al., 2000 ). These include: (i) accurate estimation of N—H distances [due to the larger dipolar scaling factor (K_sc = 1/ $[\sqrt 2]$ )]; (ii) straightforward experimental settings; (iii) robustness towards experimental imperfections, such as rf inhomogeneity, Hartmann–Hahn mismatch, rf offset and chemical shift anisotropies; (iv) higher sensitivity due to ¹H detection; and (v) the small sample volume (typically less than 1 mg). While the ¹⁵N—¹H distance measurement in a natural-abundance amino acid using the invCP-VC method was demonstrated earlier, the level of difficulty in the measurement is higher for multicomponent systems, especially for cocrystals that are associated with longer ¹⁵N—¹H distances. In multicomponent systems, a larger number of ¹H resonances are expected than in a small amino acid. This results in the lower sensitivity and potential signal overlaps. The low sensitivity is partially overcome by the high magnetic field. An additional sensitivity improvement was achieved simply by applying a large number of transients. It typically took four to five days to collect each set of data (Table 1). The limited spectral resolution of ¹H nuclei even at an ultrafast MAS rate potentially produces ¹H resonance overlaps. Fortunately, invCP-VC experiments on the ¹⁵N—¹H system filtered out ¹H signals from atoms which are not bonded directly to ¹⁵N. Thus, the signal overlaps can easily be avoided in salt/cocrystal/continuum systems which typically include only one N—H hydrogen-bonding pair. Longer ¹⁵N—¹H distances result in smaller ¹⁵N-¹H dipolar interactions. This may introduce the effect of remote ¹⁵N-¹H dipolar interactions which are usually suppressed by the strongest ¹⁵N-¹H dipolar interactions. This effect depends on numerous factors, including the size of each dipolar interaction and the relative orientation of each N—H vector. We calculated the invCP-VC spectrum of CO1, which shows the longest N—H distances, to evaluate the effects of the second and third nearest-neighbour H atoms. It was shown that these remote N-H dipolar interactions only broaden the invCP-VC spectra and do not affect the peak positions, i.e. ¹⁵N—¹H distances (Fig. S14 in the supporting information). Therefore, we conclude that one may safely rely on dipolar splitting to obtain ¹H—¹⁵N distances, even for cocrystals.

One of the major requirements of the two-dimensional invCP-VC ¹H→¹⁵N→¹H experiment with natural-abundance samples is to have as short a ¹H spin lattice relaxation time (T₁) as possible. However, in pharmaceutical cocrystals, T₁ is generally long for N—H protons. The long T₁ relaxation time results in impractical total experimental times and limits the application of two-dimensional invCP-VC ¹H→¹⁵N→¹H experiments on actual samples. The application of a rotor-synchronized train of 180° pulses (i.e. RFDR or radio-frequency driven recoupling) during the recycle period (Ye et al., 2014 ) and/or the addition of a paramagnetic dopant (Wickramasinghe et al., 2007 ) to the system can be used to reduce T₁ values somewhat. For our purpose, we have used the RFDR-based approach in three of the samples (CO1, SA1 and SA2) to reduce the T₁ relaxation times. Besides, paramagnetic doping was avoided to preserve the sample purity. While the T₁ relaxation time for an NH proton in the case of CNT1 is also very long (70 s), the uniform ¹H T₁ relaxation hampers the application of the RFDR pulse train and data were collected without RFDR irradiation. The one-dimensional ¹H→¹⁵N→¹H-filtered spectra of all four samples under study give isolated N—H resonances (Fig. S15 in the supporting information). All other unwanted peaks are completely suppressed. In other words, this experiment provides a method for the precise assignment of N—H proton resonances in cases where the signals are overlapped with other ¹H resonances (C—H protons) and allows a more accurate and reliable measurement of N—H distances. This highlights the additional advantages of invCP-VC experiments for multicomponent systems where severe overlap of ¹H resonances is expected.

The two-dimensional invCP-VC spectra were plotted with the horizontal and vertical axes representing the ¹H chemical shift and the size of the ¹⁵N-¹H dipolar couplings, respectively (Fig. 4). The above-mentioned procedure overcomes the difficulties, including low abundance and thus sensitivity of ¹⁵N, small ¹⁵N-¹H dipolar coupling, complex multicomponent systems and long ¹H T₁ relaxation time, and clearly gives splitting in the indirect dimension. The observed separations between two singularities/¹⁵N-¹H dipolar splittings for SA1, SA2, CO1 and CNT1 were found to be 5.36, 4.37, 2.01 and 2.96 kHz, respectively, corresponding to ¹⁵N—¹H distances of 1.17, 1.25, 1.62 and 1.43 Å. From SCXRD at 298 K, the ¹⁵N—¹H distances were 1.01, 1.20, 1.54 and 0.99 Å (without normalization), and at 110 K, they were 0.99, 1.18, 1.57 and 1.17 Å for SA1, SA2, CO1 and CNT1, respectively (Table 2). Crystal data, data collection and structure refinement details are summarized in Table 3.

Table 2
¹⁵N—¹H distance (Å) measurements by SCXRD^a and ssNMR for the four investigated solid forms

Compound	SCXRD (298 K)	SCXRD (298 K) Normalized	SCXRD (110 K)	SCXRD (110 K) Normalized	ssNMR
SA1	1.01 (3)	1.01	0.99 (2)	1.01	1.17
SA2	1.20 (3)	1.01	1.18 (3)	1.01	1.25
CO1	1.54 (4)	1.65	1.57 (3)	1.64	1.62
CNT1	0.99 (9)	1.01	1.17 (6)	1.01	1.43
Note: (a) data sets were collected on a Rigaku XtaLAB mini diffractometer.

Table 3
Crystallographic parameters of compounds SA1, SA2, CO1 and CNT1

	SA1 (RT)	SA1 (LT)	SA2 (RT)	SA2 (LT)	CO1 (RT)
Chemical formula	C₁₄H₁₅N₃O₄	C₁₄H₁₅N₃O₄	C₁₄H₁₃N₃O₆	C₁₄H₁₃N₃O₆	C₁₄H₁₄N₂O₄
Mr	289.29	289.29	319.27	319.27	274.27
Crystal system	Monoclinic	Monoclinic	Monoclinic	Monoclinic	Triclinic
Space group	C2/c	C2/c	P2₁/c	P2₁/c	P $[\overline{1}]$
Temperature (K)	298	110	298	110	298
a (Å)	28.86 (2)	28.685 (2)	8.574 (9)	8.439 (6)	6.730 (2)
b (Å)	6.791 (5)	6.783 (3)	14.346 (2)	14.091 (9)	7.186 (2)
c (Å)	14.243 (1)	13.975 (7)	12.190 (1)	12.167 (8)	14.298 (3)
α (°)	90	90	90	90	88.158 (6)
β (°)	95.410 (1)	94.175 (7)	94.440 (1)	95.500 (1)	88.340 (6)
γ (°)	90	90	90	90	78.636 (5)
V (Å³)	2779 (3)	2712 (2)	1495 (3)	1440.0 (2)	677.4 (3)
Z	8	8	4	4	2
D_calcd(Mg m⁻³)	1.383	1.417	1.419	1.472	1.345
μ (mm⁻¹)	0.103	0.106	0.113	0.117	0.100
F(000)	1216	1216	664	664	288
Total reflections	12517	12292	13680	13152	5680
Unique reflections	2729	2662	2936	2815	2634
Observed reflections [I > 2σ(I)]	2388	2507	2597	2683	1543
R_int	0.059	0.060	0.080	0.097	0.040
R₁ [I > 2σ(I)]	0.0498	0.0383	0.0555	0.0400	0.0646
wR₂	0.1414	0.1119	0.1737	0.1248	0.1894
Completeness (%)	99.6	99.7	99.9	99.6	99.2
Goodness-of-fit	1.081	1.099	1.135	1.143	1.037
CCDC No.	1529544	1529546	1529547	1529545	1529550
Diffractometer	Rigaku	Rigaku	Rigaku	Rigaku	Rigaku

	CO1 (LT)	CNT1 (RT)	CNT1 (LT)	CNT1 (RT)	CNT1 (LT)
Chemical formula	C₁₄H₁₄N₂O₄	C₁₂H₈Cl₅NO	C₁₂H₈Cl₅NO	C₁₂H₈Cl₅NO	C₁₂H₈Cl₅NO
Mr	274.27	359.44	359.44	359.44	359.44
Crystal system	Triclinic	Triclinic	Triclinic	Triclinic	Triclinic
Space group	P $[\overline{1}]$	P $[\overline{1}]$	P $[\overline{1}]$	P $[\overline{1}]$	P $[\overline{1}]$
Temperature (K)	110	298	110	298	110
a (Å)	6.631 (5)	7.389 (8)	7.316 (6)	7.386 (8)	7.338 (8)
b (Å)	7.032 (6)	8.922 (8)	8.942 (8)	8.920 (1)	8.899 (9)
c (Å)	14.216 (1)	12.014 (1)	11.763 (9)	12.023 (1)	11.825 (1)
α (°)	87.967 (2)	69.82 (3)	70.15 (4)	69.770 (3)	69.945 (5)
β (°)	88.58 (3)	85.61 (4)	84.67 (4)	85.869 (3)	85.055 (5)
γ (°)	80.207 (2)	76.26 (4)	76.24 (4)	76.324 (4)	76.133 (5)
V (Å³)	652.6 (9)	722.1 (1)	703.0 (1)	722.1 (1)	704.2 (1)
Z	2	2	2	2	2
D_calcd(Mg m⁻³)	1.396	1.653	1.698	1.653	1.695
μ (mm⁻¹)	0.104	0.993	1.020	0.993	1.018
F(000)	288	360	360	360	360
Total reflections	6144	6793	6521	6870	11629
Unique reflections	2555	2815	2741	2799	2756
Observed reflections [I > 2σ(I)]	2366	2152	2421	1751	2106
R_int	0.071	0.063	0.054	0.039	0.052
R₁ [I > 2σ(I)]	0.0427	0.0505	0.0402	0.0466	0.0396
wR₂	0.1338	0.1943	0.1513	0.1288	0.1034
Completeness (%)	99.6	99.6	99.4	98.9	99.7
Goodness-of-fit	1.105	1.155	1.299	1.040	1.102
CCDC No.	1529549	1529548	1529542	1529543	1529541
Diffractometer	Rigaku	Rigaku	Rigaku	Bruker	Bruker

Figure 4
The molecular structures and the two-dimensional invCP-VC spectra (¹⁵N-¹H dipolar couplings versus ¹H chemical shift) of SA1, SA2, CO1 and CNT1.

X-ray crystallography is a powerful and widely accepted technique for structure determination. Since X-rays are scattered by the electrons of an atom, the results of an X-ray-based structure determination give the centroids of the electron density, which correspond to the centres of the nuclei in heavier atoms. In securing light-atom positions, and especially H-atom positions, X-ray diffraction has its limitations. The electron density of an H atom is not centred around the H-atom nucleus, but is aspherically displaced towards the covalently bonded heavier atom (X—H⋯A—Y). As a result, X-ray-determined X−H distances generally appear to be shorter than the true internuclear distance (Desiraju & Steiner, 1999; Lusi & Barbour, 2011 ). This problem can be avoided by the use of neutron diffraction (ND) analysis, in which the positional and anisotropic displacement parameters of the H atoms can be refined. But the distance (X−H) derived from ND analysis corresponds to the internuclear distance, since the scattering centres are the atomic nuclei.

In this regard, a comparison between the ND- and ssNMR-derived X−H distance would appear to be significant. In fact, there are several important reports where the NMR-derived distances of L-histidine·HCl·H₂O were compared with the ND-derived distances (Zhao et al., 2001 ; Paluch et al., 2015). We have also demonstrated that the invCP-VC method applied to L-histidine·HCl·H₂O gives as reliable an internuclear N—H distance as the ND method (Nishiyama et al., 2016). However, ND is expensive and limited by availability. It also requires a large amount of samples or a large-sized crystal, which is often difficult to grow. Therefore, alternatively, a comparison of the neutron-normalized (NN) X-ray distance, in lieu of the neutron-derived distance, with the ssNMR-derived distance can be considered reliably meaningful. It should be noted that the NN X-ray distance is an outcome of the analysis of available XRD and ND crystal structure data in the Cambridge Structural Database (Groom et al., 2016 ), where the X-ray-derived distance is extended by shifting the X−H bond vector to the average neutron-derived distance (Allen & Bruno, 2010 ). This is a widely used procedure.

The ssNMR X−H distances of CO1 (1.62 Å) and SA1 (1.17 Å) show a fair agreement with the NN X-ray distances of CO1 (1.65 Å) and SA1 (1.01 Å). The observed differences in the measured ¹⁵N—¹H distances from the two methods (XRD/ND and ssNMR) could be attributed to: (i) inaccurate proton positions due to a low scattering cross sectional area of the H atoms, (ii) different timescales of measurements (tens of µs in NMR and ps in XRD/ND) and, therefore, averaging of the libratory motions at different timescales, and (iii) dissimilar distance dependence (1/r³ in NMR and 1/r in XRD/ND) which ultimately resulted in a longer distance for NMR compared to XRD (Ishii et al., 1997 ). Since the current approach gives the internuclear distances directly, unlike diffraction-based methods, where the distances are calculated from the positions of the nuclei, ssNMR-based approaches are appropriately complementary to the other methods.

From ssNMR, the ¹⁵N—¹H distance in SA1 is 1.17 Å and is the smallest in comparison to the corresponding distances in SA2, CNT1 and CO1. This clearly suggests that SA1 is a `salt' in which complete transfer of the proton across the hydrogen bond from acid to pyridine has taken place. Similarly, the longer distance observed for CO1 (1.62 Å) clearly rules out any possibility of the transfer of the proton from the acid to pyridine, confirming that CO1 is a `cocrystal'. Interestingly, SA2, which is an adduct of a strong acid and a strong base, is a case of a continuum, despite having ΔpK_a > 3, with an ¹⁵N—¹H distance of 1.25 Å from ssNMR, half of the N—O distance (2.54 Å by SCXRD at both temperatures). CNT1 shows the importance of locating accurate proton positions in these classifications. In this example, unlike in the previously discussed continuum scenario, the distance obtained from SCXRD and ssNMR were not comparable. The SCXRD distance was completely misleading due to poor data quality. From the difference Fourier map, the residual electron density is delocalized over a region between the two heavy atoms (O and N) and the proton position had to be fixed at 0.99 Å (SCXRD at 298 K, Rigaku XtaLAB mini). Further refinements were not sustained. Alternatively, the SCXRD measurement was carried out on a Bruker SMART APEX (D8 QUEST) CMOS diffractometer. The N—H distance was 1.65 Å at room temperature, i.e. 0.18 Å longer than obtained by Steiner et al. (2001). In other words, locating the proton position in a salt–cocrystal continuum is ambiguous from SCXRD data as it is somewhat machine dependent. Neutron normalization of the X-ray distance, in this regard, is also not appropriate since neutron normalization adjusts the H-atom position to an average distance, and practically ignores the polarization effect caused by the acceptor atom in a strongly hydrogen-bonded system. In this regard, a comparative study with ND data of a system where large crystals could be obtained would appear to be the next step. None of the compounds studied here was available in the form of large crystals.

The ¹⁵N—¹H distance of CNT1 obtained by invCP-VC ssNMR is 1.43 Å at room temperature, which suggests that CNT1 behaves more like a `cocrystal' at room temperature (N⋯O = 2.54 Å by SCXRD). Previous studies on CNT1 with variable-temperature time-of-flight neutron diffraction shows that the N—H distance increases with temperature and that it is 1.306 Å at 200 K (Steiner et al., 2001). Therefore, at room temperature, the N—H distance is expected to be longer than 1.306 Å. As a result, the N—H distance at room temperature determined by ssNMR can be considered to be as reliable as neutron diffraction data. In this situation, the two-dimensional invCP-VC method turns out to be a significant tool for location of precise proton positions through dipolar coupling, especially in proton-disordered systems. In addition, the present ssNMR technique is advantageous as it can be performed on microcrystalline, or even amorphous, samples with laboratory-based NMR equipment.

4. Conclusions

We have carried out two-dimensional inversely proton-detected CP-VC ssNMR measurements at fast MAS to determine N—H distances with naturally abundant ¹⁵N nuclei in multicomponent solid forms. N—H distances vary with the length of the hydrogen bond between the two individual components of a salt, cocrystal or continuum, and these distances were measured through two well-separated singularities of the Pake-like dipolar powder pattern. The measured distances can be easily used to locate the proton positions in such systems and hence a clear distinction between salt, cocrystal and continuum may be established. The technique will be useful where the ΔpK_a rule has limitations, especially in the range 1 < ΔpK_a < 3. We believe that the method presented in this work will have an impact on the pharmaceutical industry. Further, the method can be utilized for microcrystalline samples where obtaining a single crystal is difficult. Our future studies will be directed towards the implementation of this technique in more complex systems, such as to differentiate polyamorphous solid forms.

Supporting information

CCDC references: 1529546; 1529544; 1529545; 1529547; 1529549; 1529550; 1529542; 1529548; 1529541; 1529543

Crystal structure: contains datablocks SA-1-LT, SA-1-RT, SA-2-LT, SA-2-RT, CO-1-LT, CO-1-RT, CNT-1-LT, CNT-1-RT, CNT1-LT, CNT1-RT. DOI: https://doi.org/10.1107/S205225251700687X/lq5005sup1.cif

Spectra and hydrogen-bonding details. DOI: https://doi.org/10.1107/S205225251700687X/lq5005sup2.pdf

Structure factors for CNT-1 (LT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005CNT-1-LTsup3.hkl

Structure factors for CNT-1 (RT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005CNT-1-RTsup4.hkl

Structure factors for CNT1 (LT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005CNT1-LTsup5.hkl

Structure factors for CNT1 (RT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005CNT1-RTsup6.hkl

Structure factors for CO1 (LT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005CO-1-LTsup7.hkl

Structure factors for CO1 (RT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005CO-1-RTsup8.hkl

Structure factors for SA1 (LT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005SA-1-LTsup9.hkl

Structure factors for SA1 (RT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005SA-1-RTsup10.hkl

Structure factors for SA2 (LT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005SA-2-LTsup11.hkl

Structure factors for SA2 (RT). DOI: https://doi.org/10.1107/S205225251700687X/lq5005SA-2-RTsup12.hkl

CML file for SA1. DOI: https://doi.org/10.1107/S205225251700687X/lq5005SA-1sup13.cml

CML file for SA2. DOI: https://doi.org/10.1107/S205225251700687X/lq5005SA-2sup14.cml

CML file for CO1. DOI: https://doi.org/10.1107/S205225251700687X/lq5005CO-1sup15.cml

CML file for CNT1. DOI: https://doi.org/10.1107/S205225251700687X/lq5005CNT1sup16.cml

CML file for CNT-1. DOI: https://doi.org/10.1107/S205225251700687X/lq5005CNT-1sup17.cml

Computing details top

For all compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 2008).

(SA-1-LT) top

Crystal data top

C₇H₄NO₄·C₇H₁₁N₂	D_x = 1.417 Mg m⁻³
M_r = 289.29	Melting point: 160-163 K
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 28.685 (15) Å	Cell parameters from 5097 reflections
b = 6.783 (3) Å	θ = 2.8–33.7°
c = 13.975 (7) Å	µ = 0.11 mm⁻¹
β = 94.175 (7)°	T = 110 K
V = 2712 (2) Å³	Block, colorless
Z = 8	0.22 × 0.19 × 0.18 mm
F(000) = 1216

Data collection top

Rigaku diffractometer	2662 independent reflections
Radiation source: fine-focus sealed tube	2507 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.060
profile data from ω–scans	θ_max = 26.0°, θ_min = 1.4°
Absorption correction: multi-scan SADABS	h = −35→35
T_min = 0.828, T_max = 1.000	k = −8→8
12292 measured reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.112	H atoms treated by a mixture of independent and constrained refinement
S = 1.10	w = 1/[σ²(F_o²) + (0.0601P)² + 1.1467P] where P = (F_o² + 2F_c²)/3
2662 reflections	(Δ/σ)_max < 0.001
250 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Special details top

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > 2σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.24504 (4)	−0.03795 (18)	0.10802 (9)	0.0239 (3)
C2	0.20300 (4)	0.02431 (18)	0.06753 (9)	0.0230 (3)
C3	0.19100 (4)	0.22795 (18)	0.06892 (8)	0.0190 (3)
C4	0.22451 (4)	0.35419 (18)	0.11737 (8)	0.0218 (3)
C5	0.26592 (4)	0.28117 (18)	0.15571 (8)	0.0219 (3)
C6	0.13944 (5)	0.5071 (2)	0.03136 (10)	0.0289 (3)
C7	0.11823 (5)	0.1691 (2)	−0.02857 (10)	0.0310 (3)
C8	0.09586 (5)	−0.02538 (18)	0.22057 (9)	0.0249 (3)
C9	0.05720 (5)	−0.11388 (19)	0.17238 (10)	0.0304 (3)
C10	0.02023 (5)	−0.00051 (19)	0.13326 (9)	0.0253 (3)
C11	0.02353 (4)	0.20199 (18)	0.14312 (8)	0.0201 (3)
C12	0.06164 (4)	0.29390 (17)	0.19095 (8)	0.0195 (3)
C13	0.09842 (4)	0.17884 (18)	0.23038 (8)	0.0195 (3)
C14	0.14066 (4)	0.27671 (18)	0.28240 (8)	0.0205 (3)
N1	0.27652 (4)	0.08771 (15)	0.15117 (7)	0.0223 (2)
N2	0.15095 (3)	0.29770 (15)	0.02658 (7)	0.0230 (3)
N3	−0.01513 (4)	0.32432 (16)	0.10123 (7)	0.0242 (3)
O1	0.17069 (3)	0.16988 (13)	0.32505 (7)	0.0278 (2)
O2	0.14200 (3)	0.46403 (13)	0.27718 (6)	0.0251 (2)
O3	−0.01255 (4)	0.50377 (14)	0.11108 (8)	0.0372 (3)
O4	−0.04832 (3)	0.24031 (15)	0.05862 (8)	0.0361 (3)
H1	0.2560 (5)	−0.175 (2)	0.1070 (10)	0.030 (4)*
H1N	0.3077 (7)	0.040 (3)	0.1764 (13)	0.049 (5)*
H2	0.1821 (6)	−0.069 (2)	0.0357 (12)	0.035 (4)*
H4	0.2184 (6)	0.490 (3)	0.1200 (11)	0.029 (4)*
H5	0.2882 (5)	0.368 (2)	0.1829 (10)	0.025 (4)*
H6A	0.1611 (6)	0.588 (2)	−0.0070 (12)	0.036 (4)*
H6B	0.1074 (7)	0.525 (3)	0.0043 (13)	0.042 (5)*
H6C	0.1413 (5)	0.553 (2)	0.0959 (12)	0.033 (4)*
H7A	0.1345 (6)	0.081 (2)	−0.0712 (12)	0.036 (4)*
H7B	0.0971 (7)	0.251 (3)	−0.0668 (13)	0.053 (5)*
H7C	0.1020 (7)	0.086 (3)	0.0129 (13)	0.043 (5)*
H8	0.1222 (6)	−0.107 (2)	0.2468 (11)	0.029 (4)*
H9	0.0556 (6)	−0.259 (3)	0.1654 (12)	0.045 (5)*
H10	−0.0071 (6)	−0.058 (2)	0.1005 (12)	0.036 (4)*
H12	0.0633 (5)	0.435 (2)	0.1975 (10)	0.026 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0258 (6)	0.0183 (6)	0.0277 (6)	0.0009 (5)	0.0024 (5)	0.0022 (5)
C2	0.0226 (6)	0.0193 (6)	0.0270 (6)	−0.0028 (5)	0.0003 (5)	−0.0012 (5)
C3	0.0186 (6)	0.0209 (6)	0.0178 (5)	0.0002 (4)	0.0038 (4)	0.0017 (4)
C4	0.0235 (6)	0.0175 (6)	0.0247 (6)	−0.0009 (5)	0.0034 (5)	−0.0008 (5)
C5	0.0207 (6)	0.0225 (6)	0.0223 (6)	−0.0034 (5)	0.0009 (4)	−0.0003 (5)
C6	0.0295 (7)	0.0266 (7)	0.0302 (7)	0.0091 (5)	−0.0009 (5)	0.0036 (5)
C7	0.0239 (7)	0.0376 (8)	0.0305 (7)	0.0011 (6)	−0.0037 (5)	−0.0061 (6)
C8	0.0276 (7)	0.0186 (6)	0.0279 (6)	0.0022 (5)	−0.0029 (5)	0.0016 (5)
C9	0.0354 (7)	0.0161 (6)	0.0385 (7)	−0.0011 (5)	−0.0055 (6)	−0.0009 (5)
C10	0.0259 (7)	0.0214 (6)	0.0278 (6)	−0.0054 (5)	−0.0041 (5)	−0.0015 (5)
C11	0.0190 (6)	0.0206 (6)	0.0206 (6)	0.0012 (4)	0.0008 (5)	0.0023 (4)
C12	0.0206 (6)	0.0169 (6)	0.0213 (6)	−0.0013 (4)	0.0023 (5)	0.0008 (4)
C13	0.0210 (6)	0.0192 (6)	0.0183 (6)	−0.0012 (4)	0.0017 (4)	0.0008 (4)
C14	0.0199 (6)	0.0215 (6)	0.0201 (6)	−0.0010 (4)	0.0008 (4)	0.0006 (4)
N1	0.0206 (5)	0.0227 (5)	0.0234 (5)	0.0017 (4)	0.0007 (4)	0.0031 (4)
N2	0.0203 (5)	0.0239 (6)	0.0246 (5)	0.0024 (4)	−0.0006 (4)	0.0010 (4)
N3	0.0212 (5)	0.0245 (6)	0.0266 (5)	0.0005 (4)	−0.0011 (4)	0.0000 (4)
O1	0.0245 (5)	0.0233 (5)	0.0344 (5)	0.0009 (3)	−0.0070 (4)	0.0038 (4)
O2	0.0244 (5)	0.0182 (4)	0.0317 (5)	−0.0026 (3)	−0.0050 (4)	0.0001 (3)
O3	0.0335 (5)	0.0207 (5)	0.0554 (7)	0.0044 (4)	−0.0106 (5)	0.0019 (4)
O4	0.0256 (5)	0.0361 (6)	0.0443 (6)	0.0007 (4)	−0.0136 (4)	−0.0053 (4)

Geometric parameters (Å, º) top

C1—N1	1.3515 (17)	C9—C10	1.3894 (19)
C1—C2	1.3613 (18)	C10—C11	1.3831 (18)
C2—C3	1.4241 (18)	C11—C12	1.3871 (17)
C3—N2	1.3397 (16)	C11—N3	1.4719 (16)
C3—C4	1.4216 (17)	C12—C13	1.3933 (17)
C4—C5	1.3606 (18)	C13—C14	1.5194 (16)
C5—N1	1.3495 (17)	C14—O1	1.2441 (15)
C6—N2	1.4610 (18)	C14—O2	1.2734 (16)
C7—N2	1.4596 (17)	N3—O4	1.2261 (14)
C8—C9	1.3910 (19)	N3—O3	1.2266 (16)
C8—C13	1.3934 (18)

N1—C1—C2	122.19 (12)	C12—C13—C8	119.01 (11)
C1—C2—C3	120.20 (11)	C12—C13—C14	119.93 (11)
N2—C3—C4	121.73 (11)	C8—C13—C14	121.06 (11)
N2—C3—C2	122.48 (11)	O1—C14—O2	125.86 (11)
C4—C3—C2	115.79 (11)	O1—C14—C13	118.36 (11)
C5—C4—C3	120.60 (12)	O2—C14—C13	115.78 (10)
N1—C5—C4	121.91 (11)	C5—N1—C1	119.26 (11)
C9—C8—C13	120.75 (11)	C3—N2—C7	121.33 (11)
C10—C9—C8	120.69 (12)	C3—N2—C6	120.83 (10)
C11—C10—C9	117.76 (11)	C7—N2—C6	117.81 (11)
C10—C11—C12	122.70 (11)	O4—N3—O3	123.64 (11)
C10—C11—N3	118.44 (11)	O4—N3—C11	117.84 (11)
C12—C11—N3	118.87 (11)	O3—N3—C11	118.51 (10)
C11—C12—C13	119.10 (11)

(SA-1-RT) top

Crystal data top

C₇H₄NO₄·C₇H₁₁N₂	D_x = 1.383 Mg m⁻³
M_r = 289.29	Melting point: 160-163 K
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 28.86 (2) Å	Cell parameters from 4323 reflections
b = 6.791 (5) Å	θ = 2.9–33.7°
c = 14.243 (10) Å	µ = 0.10 mm⁻¹
β = 95.4097 (10)°	T = 298 K
V = 2779 (3) Å³	Block, colorless
Z = 8	0.22 × 0.19 × 0.18 mm
F(000) = 1216

Data collection top

Rigaku diffractometer	2729 independent reflections
Radiation source: fine-focus sealed tube	2388 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.059
profile data from ω–scans	θ_max = 26.0°, θ_min = 1.4°
Absorption correction: multi-scan SADABS	h = −35→35
T_min = 0.835, T_max = 1.000	k = −8→8
12517 measured reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.141	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	w = 1/[σ²(F_o²) + (0.0742P)² + 0.9562P] where P = (F_o² + 2F_c²)/3
2729 reflections	(Δ/σ)_max = 0.001
246 parameters	Δρ_max = 0.21 e Å⁻³
0 restraints	Δρ_min = −0.17 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C13	0.40096 (5)	0.3197 (2)	0.27019 (10)	0.0402 (3)
O2	0.35699 (4)	0.03687 (17)	0.22487 (9)	0.0546 (3)
C12	0.43787 (5)	0.2062 (2)	0.30903 (10)	0.0405 (3)
C11	0.47601 (5)	0.2981 (2)	0.35586 (10)	0.0424 (4)
O1	0.32886 (4)	0.32828 (18)	0.17595 (10)	0.0623 (4)
C3	0.30883 (5)	0.2717 (2)	0.43211 (10)	0.0397 (3)
C14	0.35863 (5)	0.2224 (2)	0.21897 (10)	0.0440 (4)
N2	0.34892 (4)	0.2015 (2)	0.47438 (9)	0.0488 (4)
N3	0.51479 (5)	0.1768 (2)	0.39707 (10)	0.0534 (4)
C2	0.27554 (5)	0.1472 (2)	0.38306 (11)	0.0460 (4)
C4	0.29662 (6)	0.4727 (2)	0.43461 (12)	0.0490 (4)
N1	0.22393 (5)	0.4118 (2)	0.34901 (9)	0.0479 (4)
C8	0.40357 (6)	0.5229 (3)	0.28006 (13)	0.0534 (4)
C5	0.23456 (5)	0.2205 (3)	0.34415 (12)	0.0480 (4)
O3	0.51270 (5)	−0.0008 (2)	0.38680 (13)	0.0841 (5)
C1	0.25495 (6)	0.5354 (3)	0.39328 (13)	0.0520 (4)
C10	0.47894 (6)	0.4990 (3)	0.36560 (13)	0.0562 (4)
O4	0.54797 (5)	0.2601 (2)	0.43902 (12)	0.0813 (5)
C6	0.36047 (8)	−0.0062 (3)	0.47001 (17)	0.0644 (5)
C7	0.38198 (7)	0.3280 (4)	0.52967 (17)	0.0686 (6)
C9	0.44213 (7)	0.6106 (3)	0.32754 (15)	0.0660 (5)
H9	0.4432	0.7469	0.3338	0.079*
H12	0.4361 (6)	0.066 (3)	0.3009 (11)	0.048 (5)*
H5	0.2125 (7)	0.135 (3)	0.3161 (13)	0.053 (5)*
H2	0.2824 (7)	0.014 (3)	0.3785 (13)	0.060 (5)*
H4	0.3164 (8)	0.561 (3)	0.4665 (16)	0.078 (7)*
H8	0.3771 (7)	0.603 (3)	0.2548 (13)	0.059 (5)*
H1	0.2434 (7)	0.671 (3)	0.3931 (13)	0.066 (6)*
H10	0.5069 (8)	0.555 (3)	0.3951 (15)	0.073 (6)*
H6A	0.3581 (8)	−0.051 (3)	0.4071 (19)	0.088 (8)*
H6B	0.3906 (10)	−0.028 (4)	0.4964 (19)	0.096 (8)*
H1N	0.1924 (9)	0.462 (4)	0.3231 (16)	0.087 (7)*
H6C	0.3367 (9)	−0.088 (4)	0.5087 (18)	0.096 (8)*
H7A	0.4041 (11)	0.247 (5)	0.568 (2)	0.128 (10)*
H7B	0.3963 (10)	0.410 (4)	0.493 (2)	0.101 (9)*
H7C	0.3657 (9)	0.408 (4)	0.5771 (18)	0.094 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C13	0.0410 (8)	0.0394 (8)	0.0396 (7)	−0.0016 (6)	0.0012 (6)	0.0017 (6)
O2	0.0469 (6)	0.0439 (7)	0.0696 (8)	−0.0060 (5)	−0.0124 (5)	−0.0008 (5)
C12	0.0399 (8)	0.0344 (8)	0.0466 (8)	−0.0023 (6)	0.0008 (6)	0.0015 (6)
C11	0.0376 (8)	0.0430 (8)	0.0458 (8)	0.0000 (6)	0.0000 (6)	0.0019 (6)
O1	0.0501 (7)	0.0532 (7)	0.0792 (8)	0.0008 (5)	−0.0175 (6)	0.0094 (6)
C3	0.0340 (7)	0.0449 (8)	0.0404 (7)	0.0008 (6)	0.0051 (6)	0.0032 (6)
C14	0.0386 (8)	0.0461 (9)	0.0462 (8)	−0.0017 (6)	−0.0014 (6)	0.0019 (6)
N2	0.0385 (7)	0.0557 (8)	0.0510 (8)	0.0047 (6)	−0.0022 (5)	0.0027 (6)
N3	0.0409 (7)	0.0563 (9)	0.0608 (9)	0.0016 (6)	−0.0068 (6)	0.0007 (7)
C2	0.0452 (8)	0.0392 (8)	0.0532 (9)	−0.0013 (6)	0.0029 (6)	−0.0008 (7)
C4	0.0451 (8)	0.0413 (8)	0.0592 (10)	−0.0061 (7)	−0.0021 (7)	−0.0032 (7)
N1	0.0412 (7)	0.0504 (8)	0.0512 (8)	0.0028 (5)	−0.0002 (5)	0.0063 (6)
C8	0.0568 (10)	0.0385 (8)	0.0624 (10)	0.0041 (7)	−0.0083 (8)	0.0015 (7)
C5	0.0395 (8)	0.0519 (9)	0.0516 (9)	−0.0058 (7)	−0.0005 (6)	−0.0018 (7)
O3	0.0667 (9)	0.0506 (8)	0.1280 (14)	0.0103 (6)	−0.0278 (9)	0.0043 (8)
C1	0.0514 (9)	0.0395 (8)	0.0646 (10)	0.0029 (7)	0.0022 (7)	0.0037 (7)
C10	0.0532 (10)	0.0467 (9)	0.0656 (11)	−0.0113 (7)	−0.0100 (8)	−0.0040 (8)
O4	0.0533 (8)	0.0825 (10)	0.1011 (11)	0.0024 (7)	−0.0302 (7)	−0.0110 (8)
C6	0.0604 (12)	0.0620 (12)	0.0695 (13)	0.0209 (9)	0.0000 (9)	0.0100 (10)
C7	0.0453 (10)	0.0936 (17)	0.0641 (12)	−0.0012 (10)	−0.0092 (9)	−0.0131 (11)
C9	0.0738 (12)	0.0341 (9)	0.0861 (13)	−0.0041 (8)	−0.0145 (10)	−0.0032 (8)

Geometric parameters (Å, º) top

C13—C12	1.387 (2)	N2—C6	1.452 (2)
C13—C8	1.388 (2)	N2—C7	1.459 (2)
C13—C14	1.5145 (19)	N3—O3	1.216 (2)
O2—C14	1.2639 (19)	N3—O4	1.2193 (18)
C12—C11	1.381 (2)	C2—C5	1.353 (2)
C11—C10	1.373 (2)	C4—C1	1.357 (2)
C11—N3	1.4672 (19)	N1—C5	1.338 (2)
O1—C14	1.2376 (18)	N1—C1	1.340 (2)
C3—N2	1.3406 (18)	C8—C9	1.382 (3)
C3—C4	1.411 (2)	C10—C9	1.374 (3)
C3—C2	1.414 (2)

C12—C13—C8	118.68 (14)	C3—N2—C7	121.71 (16)
C12—C13—C14	120.24 (14)	C6—N2—C7	117.02 (16)
C8—C13—C14	121.08 (13)	O3—N3—O4	123.17 (15)
C11—C12—C13	119.23 (14)	O3—N3—C11	118.80 (13)
C10—C11—C12	122.45 (14)	O4—N3—C11	118.02 (15)
C10—C11—N3	118.70 (13)	C5—C2—C3	120.62 (15)
C12—C11—N3	118.85 (14)	C1—C4—C3	120.40 (15)
N2—C3—C4	122.68 (14)	C5—N1—C1	119.08 (14)
N2—C3—C2	121.77 (15)	C9—C8—C13	120.77 (15)
C4—C3—C2	115.54 (14)	N1—C5—C2	122.13 (15)
O1—C14—O2	125.70 (14)	N1—C1—C4	122.20 (16)
O1—C14—C13	118.41 (14)	C11—C10—C9	118.05 (15)
O2—C14—C13	115.89 (13)	C10—C9—C8	120.82 (16)
C3—N2—C6	121.22 (15)

(SA-2-LT) top

Crystal data top

C₇H₃N₂O₆·C₇H₁₀N	D_x = 1.473 Mg m⁻³
M_r = 319.27	Melting point: 119-122 K
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.439 (6) Å	Cell parameters from 5652 reflections
b = 14.091 (9) Å	θ = 2.4–33.8°
c = 12.167 (8) Å	µ = 0.12 mm⁻¹
β = 95.500 (11)°	T = 110 K
V = 1440.0 (17) Å³	Block, colorless
Z = 4	0.21 × 0.16 × 0.13 mm
F(000) = 664

Data collection top

Rigaku diffractometer	2815 independent reflections
Radiation source: fine-focus sealed tube	2683 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.097
profile data from ω–scans	θ_max = 26.0°, θ_min = 2.2°
Absorption correction: multi-scan SADABS	h = −10→10
T_min = 0.865, T_max = 1.000	k = −17→17
13152 measured reflections	l = −15→15

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.125	H atoms treated by a mixture of independent and constrained refinement
S = 1.14	w = 1/[σ²(F_o²) + (0.064P)² + 0.317P] where P = (F_o² + 2F_c²)/3
2815 reflections	(Δ/σ)_max < 0.001
248 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.28 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
H1N	0.456 (3)	0.2575 (19)	0.467 (2)	0.076 (7)*
H8	0.1224 (18)	0.3429 (12)	0.2389 (13)	0.022 (4)*
H10	0.038 (2)	0.1235 (12)	0.4386 (15)	0.026 (4)*
H12	0.306 (2)	0.0791 (13)	0.1781 (15)	0.034 (4)*
H1	0.527 (2)	0.1017 (13)	0.4854 (15)	0.033 (4)*
H2	0.6808 (19)	0.0090 (13)	0.3644 (14)	0.029 (4)*
H4	0.707 (2)	0.2511 (13)	0.1794 (15)	0.031 (4)*
H5	0.5597 (19)	0.3312 (12)	0.3115 (13)	0.022 (4)*
H6A	0.871 (2)	0.1059 (13)	0.1422 (15)	0.031 (4)*
H6B	0.858 (2)	0.0167 (13)	0.2149 (15)	0.030 (4)*
C14	0.30472 (14)	0.26050 (9)	0.10136 (10)	0.0192 (3)
C13	0.22438 (14)	0.21815 (9)	0.19588 (10)	0.0183 (3)
C8	0.13626 (14)	0.27749 (9)	0.25878 (10)	0.0197 (3)
C9	0.06869 (14)	0.23924 (9)	0.34798 (10)	0.0196 (3)
C10	0.08378 (15)	0.14480 (9)	0.37842 (10)	0.0200 (3)
C11	0.17268 (14)	0.08853 (9)	0.31377 (10)	0.0194 (3)
C12	0.24314 (14)	0.12263 (9)	0.22315 (10)	0.0190 (3)
N2	−0.02385 (13)	0.30238 (8)	0.41489 (9)	0.0241 (3)
N3	0.19327 (13)	−0.01231 (8)	0.34342 (9)	0.0237 (3)
O1	0.36156 (12)	0.19939 (7)	0.03716 (8)	0.0244 (2)
O2	0.31207 (12)	0.34760 (7)	0.09291 (8)	0.0266 (2)
O3	−0.04470 (13)	0.38464 (7)	0.38489 (9)	0.0358 (3)
O4	−0.07647 (13)	0.26784 (8)	0.49665 (8)	0.0354 (3)
O5	0.09484 (14)	−0.04888 (8)	0.39831 (9)	0.0366 (3)
O6	0.30787 (13)	−0.05436 (7)	0.31190 (9)	0.0324 (3)
C1	0.56982 (16)	0.12698 (10)	0.42318 (11)	0.0231 (3)
C2	0.65598 (15)	0.07589 (10)	0.35234 (11)	0.0226 (3)
C3	0.70791 (14)	0.12053 (9)	0.26002 (10)	0.0189 (3)
C4	0.67219 (15)	0.21688 (9)	0.24425 (10)	0.0207 (3)
C5	0.58611 (15)	0.26418 (9)	0.31819 (10)	0.0212 (3)
C6	0.79381 (16)	0.06533 (10)	0.17825 (11)	0.0227 (3)
C7	0.6767 (2)	0.02098 (13)	0.08992 (14)	0.0411 (4)
H7A	0.7342	−0.0138	0.0387	0.062*
H7B	0.6153	0.0701	0.0513	0.062*
H7C	0.6068	−0.0213	0.1240	0.062*
N1	0.53517 (13)	0.21897 (8)	0.40567 (9)	0.0208 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C14	0.0214 (6)	0.0198 (6)	0.0164 (6)	−0.0001 (5)	0.0019 (5)	0.0011 (4)
C13	0.0184 (6)	0.0215 (6)	0.0150 (6)	−0.0017 (4)	0.0017 (5)	−0.0008 (5)
C8	0.0207 (6)	0.0190 (6)	0.0193 (6)	0.0003 (5)	0.0015 (5)	−0.0011 (5)
C9	0.0190 (6)	0.0230 (7)	0.0172 (6)	−0.0008 (5)	0.0033 (5)	−0.0052 (5)
C10	0.0209 (6)	0.0235 (7)	0.0154 (6)	−0.0048 (5)	0.0017 (5)	−0.0013 (5)
C11	0.0217 (6)	0.0188 (6)	0.0172 (6)	−0.0029 (5)	−0.0002 (4)	0.0003 (5)
C12	0.0198 (6)	0.0210 (6)	0.0162 (6)	−0.0009 (5)	0.0014 (5)	−0.0019 (5)
N2	0.0254 (6)	0.0252 (6)	0.0224 (6)	−0.0014 (4)	0.0063 (4)	−0.0056 (4)
N3	0.0318 (6)	0.0210 (6)	0.0184 (5)	−0.0031 (5)	0.0025 (4)	0.0006 (4)
O1	0.0348 (5)	0.0202 (5)	0.0198 (5)	0.0005 (4)	0.0111 (4)	−0.0001 (3)
O2	0.0362 (5)	0.0193 (5)	0.0259 (5)	−0.0006 (4)	0.0113 (4)	0.0008 (4)
O3	0.0443 (6)	0.0246 (6)	0.0416 (6)	0.0056 (4)	0.0191 (5)	−0.0019 (4)
O4	0.0454 (6)	0.0389 (6)	0.0250 (5)	0.0021 (5)	0.0191 (5)	−0.0019 (4)
O5	0.0501 (7)	0.0284 (6)	0.0339 (6)	−0.0065 (5)	0.0172 (5)	0.0079 (4)
O6	0.0400 (6)	0.0218 (5)	0.0364 (6)	0.0054 (4)	0.0091 (5)	0.0021 (4)
C1	0.0266 (6)	0.0239 (7)	0.0194 (6)	−0.0018 (5)	0.0046 (5)	0.0031 (5)
C2	0.0258 (6)	0.0196 (7)	0.0226 (6)	−0.0005 (5)	0.0037 (5)	0.0027 (5)
C3	0.0174 (6)	0.0208 (6)	0.0184 (6)	−0.0028 (4)	0.0003 (5)	−0.0024 (4)
C4	0.0232 (6)	0.0206 (6)	0.0188 (6)	−0.0027 (5)	0.0042 (5)	0.0007 (5)
C5	0.0242 (6)	0.0185 (7)	0.0212 (6)	−0.0014 (5)	0.0041 (5)	0.0000 (5)
C6	0.0251 (6)	0.0225 (7)	0.0210 (6)	0.0013 (5)	0.0050 (5)	−0.0026 (5)
C7	0.0390 (8)	0.0437 (9)	0.0392 (9)	0.0068 (7)	−0.0039 (7)	−0.0226 (7)
N1	0.0227 (5)	0.0221 (6)	0.0179 (5)	−0.0018 (4)	0.0035 (4)	−0.0011 (4)

Geometric parameters (Å, º) top

C14—O2	1.2338 (18)	N2—O4	1.2280 (17)
C14—O1	1.2858 (17)	N3—O6	1.2266 (17)
C14—C13	1.5126 (18)	N3—O5	1.2279 (16)
C13—C12	1.392 (2)	C1—N1	1.3413 (19)
C13—C8	1.3953 (18)	C1—C2	1.382 (2)
C8—C9	1.3828 (19)	C2—C3	1.3942 (19)
C9—C10	1.384 (2)	C3—C4	1.400 (2)
C9—N2	1.4785 (17)	C3—C6	1.5029 (18)
C10—C11	1.3868 (19)	C4—C5	1.3807 (19)
C11—C12	1.3876 (19)	C5—N1	1.3458 (18)
C11—N3	1.4721 (19)	C6—C7	1.523 (2)
N2—O3	1.2228 (18)

O2—C14—O1	126.22 (12)	O3—N2—O4	124.38 (12)
O2—C14—C13	119.05 (11)	O3—N2—C9	118.33 (12)
O1—C14—C13	114.72 (12)	O4—N2—C9	117.29 (12)
C12—C13—C8	120.22 (12)	O6—N3—O5	124.19 (12)
C12—C13—C14	120.92 (11)	O6—N3—C11	117.89 (11)
C8—C13—C14	118.81 (12)	O5—N3—C11	117.92 (11)
C9—C8—C13	118.58 (12)	N1—C1—C2	121.61 (12)
C8—C9—C10	123.40 (12)	C1—C2—C3	119.48 (13)
C8—C9—N2	118.48 (12)	C2—C3—C4	117.89 (12)
C10—C9—N2	118.11 (12)	C2—C3—C6	120.57 (12)
C9—C10—C11	116.03 (12)	C4—C3—C6	121.49 (12)
C10—C11—C12	123.30 (13)	C5—C4—C3	119.91 (12)
C10—C11—N3	118.06 (11)	N1—C5—C4	120.97 (13)
C12—C11—N3	118.64 (11)	C3—C6—C7	110.98 (12)
C11—C12—C13	118.47 (12)	C1—N1—C5	120.11 (11)

(SA-2-RT) top

Crystal data top

C₇H₃N₂O₆·C₇H₁₀N	D_x = 1.419 Mg m⁻³
M_r = 319.27	Melting point: 119-122 K
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 8.574 (9) Å	Cell parameters from 5147 reflections
b = 14.346 (15) Å	θ = 1.7–33.6°
c = 12.190 (13) Å	µ = 0.11 mm⁻¹
β = 94.440 (13)°	T = 298 K
V = 1495 (3) Å³	Block, colorless
Z = 4	0.21 × 0.16 × 0.13 mm
F(000) = 664

Data collection top

Rigaku diffractometer	2936 independent reflections
Radiation source: fine-focus sealed tube	2597 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.080
profile data from ω–scans	θ_max = 26.0°, θ_min = 2.2°
Absorption correction: multi-scan SADABS	h = −10→10
T_min = 0.833, T_max = 1.000	k = −17→17
13680 measured reflections	l = −15→15

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.056	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.174	H atoms treated by a mixture of independent and constrained refinement
S = 1.14	w = 1/[σ²(F_o²) + (0.0968P)² + 0.2206P] where P = (F_o² + 2F_c²)/3
2936 reflections	(Δ/σ)_max < 0.001
248 parameters	Δρ_max = 0.26 e Å⁻³
0 restraints	Δρ_min = −0.28 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
H1N	−0.041 (4)	0.255 (2)	0.970 (3)	0.115 (10)*
H8	0.628 (2)	0.3388 (15)	0.7471 (17)	0.055 (5)*
H10	0.538 (3)	0.1206 (18)	0.940 (2)	0.076 (7)*
H12	0.802 (3)	0.0834 (17)	0.676 (2)	0.066 (6)*
H1	0.029 (3)	0.0985 (18)	0.984 (2)	0.077 (7)*
H2	0.172 (3)	0.009 (2)	0.864 (2)	0.080 (7)*
H4	0.207 (3)	0.2468 (17)	0.681 (2)	0.073 (6)*
H5	0.063 (2)	0.3231 (16)	0.8120 (18)	0.058 (5)*
H6A	0.361 (3)	0.1042 (19)	0.638 (2)	0.085 (8)*
H6B	0.356 (3)	0.0135 (19)	0.709 (2)	0.078 (7)*
N1	0.03790 (17)	0.21530 (10)	0.90713 (12)	0.0497 (4)
C1	0.0693 (2)	0.12469 (14)	0.92256 (16)	0.0562 (5)
C2	0.1527 (2)	0.07456 (13)	0.85079 (16)	0.0554 (5)
C3	0.20643 (18)	0.11811 (12)	0.75876 (14)	0.0461 (4)
C4	0.1747 (2)	0.21284 (12)	0.74503 (15)	0.0496 (4)
C5	0.0903 (2)	0.25934 (13)	0.81997 (15)	0.0518 (4)
C6	0.2904 (2)	0.06335 (15)	0.67594 (17)	0.0576 (5)
C7	0.1775 (3)	0.0194 (2)	0.5909 (3)	0.1049 (11)
H7A	0.2344	−0.0149	0.5394	0.157*
H7B	0.1165	0.0671	0.5526	0.157*
H7C	0.1092	−0.0221	0.6262	0.157*
C14	0.8082 (2)	0.26141 (12)	0.60483 (14)	0.0470 (4)
C13	0.72647 (18)	0.21817 (11)	0.69838 (13)	0.0430 (4)
C8	0.63933 (19)	0.27516 (12)	0.76338 (14)	0.0473 (4)
C9	0.57078 (19)	0.23589 (12)	0.85189 (14)	0.0474 (4)
C10	0.5843 (2)	0.14256 (13)	0.87867 (14)	0.0482 (4)
C11	0.67191 (19)	0.08839 (12)	0.81216 (13)	0.0461 (4)
C12	0.74321 (19)	0.12379 (12)	0.72273 (13)	0.0443 (4)
N2	0.4801 (2)	0.29688 (12)	0.92097 (14)	0.0619 (4)
N3	0.6909 (2)	−0.01154 (12)	0.83896 (14)	0.0617 (4)
O1	0.86720 (18)	0.20299 (9)	0.54057 (11)	0.0601 (4)
O2	0.81357 (18)	0.34689 (9)	0.59709 (12)	0.0670 (4)
O3	0.4634 (2)	0.37841 (12)	0.89479 (18)	0.0948 (6)
O4	0.4244 (2)	0.26172 (14)	1.00048 (14)	0.0880 (6)
O5	0.5973 (3)	−0.04787 (12)	0.89583 (17)	0.0982 (7)
O6	0.7998 (2)	−0.05327 (11)	0.80264 (17)	0.0895 (6)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0529 (8)	0.0514 (8)	0.0460 (8)	−0.0025 (6)	0.0103 (6)	−0.0032 (6)
C1	0.0646 (11)	0.0571 (11)	0.0485 (9)	−0.0025 (8)	0.0154 (8)	0.0070 (8)
C2	0.0633 (11)	0.0449 (9)	0.0591 (10)	0.0011 (8)	0.0125 (8)	0.0057 (8)
C3	0.0431 (8)	0.0477 (9)	0.0475 (9)	−0.0055 (6)	0.0041 (7)	−0.0042 (7)
C4	0.0550 (9)	0.0475 (9)	0.0474 (9)	−0.0062 (7)	0.0112 (7)	0.0021 (7)
C5	0.0588 (10)	0.0440 (9)	0.0537 (10)	−0.0028 (7)	0.0119 (8)	0.0002 (7)
C6	0.0590 (11)	0.0568 (10)	0.0582 (11)	0.0015 (8)	0.0128 (8)	−0.0093 (9)
C7	0.0923 (18)	0.119 (2)	0.101 (2)	0.0176 (16)	−0.0106 (15)	−0.0646 (18)
C14	0.0514 (9)	0.0462 (9)	0.0440 (8)	−0.0007 (7)	0.0074 (7)	0.0023 (7)
C13	0.0433 (8)	0.0466 (9)	0.0394 (8)	−0.0025 (6)	0.0052 (6)	−0.0014 (6)
C8	0.0478 (9)	0.0453 (9)	0.0492 (9)	−0.0004 (7)	0.0063 (7)	−0.0016 (7)
C9	0.0438 (8)	0.0543 (10)	0.0447 (8)	−0.0026 (7)	0.0080 (7)	−0.0093 (7)
C10	0.0492 (9)	0.0550 (10)	0.0410 (8)	−0.0096 (7)	0.0066 (7)	−0.0013 (7)
C11	0.0504 (9)	0.0450 (9)	0.0428 (8)	−0.0049 (7)	0.0029 (7)	0.0015 (7)
C12	0.0449 (8)	0.0460 (9)	0.0421 (8)	−0.0017 (6)	0.0051 (6)	−0.0033 (6)
N2	0.0615 (9)	0.0644 (10)	0.0618 (10)	−0.0008 (7)	0.0187 (8)	−0.0125 (8)
N3	0.0814 (11)	0.0483 (9)	0.0562 (9)	−0.0052 (8)	0.0109 (8)	0.0046 (7)
O1	0.0815 (9)	0.0487 (7)	0.0536 (7)	−0.0009 (6)	0.0275 (6)	−0.0007 (5)
O2	0.0913 (10)	0.0442 (7)	0.0695 (9)	−0.0015 (6)	0.0322 (8)	0.0038 (6)
O3	0.1151 (15)	0.0633 (10)	0.1138 (14)	0.0146 (9)	0.0584 (12)	−0.0081 (9)
O4	0.1104 (13)	0.0895 (12)	0.0709 (10)	0.0059 (10)	0.0502 (9)	−0.0063 (9)
O5	0.1370 (17)	0.0657 (10)	0.0988 (13)	−0.0121 (10)	0.0539 (12)	0.0237 (9)
O6	0.1100 (14)	0.0509 (8)	0.1118 (14)	0.0155 (8)	0.0356 (11)	0.0089 (8)

Geometric parameters (Å, º) top

N1—C1	1.338 (3)	C13—C8	1.395 (2)
N1—C5	1.343 (2)	C8—C9	1.388 (3)
C1—C2	1.375 (3)	C9—C10	1.381 (3)
C2—C3	1.393 (3)	C9—N2	1.477 (2)
C3—C4	1.393 (3)	C10—C11	1.385 (3)
C3—C6	1.506 (3)	C11—C12	1.387 (3)
C4—C5	1.380 (3)	C11—N3	1.477 (3)
C6—C7	1.502 (3)	N2—O3	1.218 (3)
C14—O2	1.231 (2)	N2—O4	1.222 (2)
C14—O1	1.278 (2)	N3—O5	1.218 (2)
C14—C13	1.517 (2)	N3—O6	1.221 (3)
C13—C12	1.391 (3)

C1—N1—C5	119.49 (16)	C9—C8—C13	118.78 (17)
N1—C1—C2	121.84 (17)	C10—C9—C8	123.00 (16)
C1—C2—C3	119.89 (18)	C10—C9—N2	118.56 (16)
C4—C3—C2	117.41 (16)	C8—C9—N2	118.44 (17)
C4—C3—C6	121.83 (16)	C9—C10—C11	116.42 (16)
C2—C3—C6	120.73 (17)	C10—C11—C12	123.13 (17)
C5—C4—C3	119.96 (16)	C10—C11—N3	118.07 (16)
N1—C5—C4	121.39 (18)	C12—C11—N3	118.79 (15)
C7—C6—C3	111.46 (19)	C11—C12—C13	118.66 (15)
O2—C14—O1	125.98 (16)	O3—N2—O4	123.99 (18)
O2—C14—C13	119.15 (15)	O3—N2—C9	118.42 (17)
O1—C14—C13	114.86 (16)	O4—N2—C9	117.58 (18)
C12—C13—C8	120.01 (16)	O5—N3—O6	123.58 (19)
C12—C13—C14	120.83 (15)	O5—N3—C11	118.37 (18)
C8—C13—C14	119.10 (16)	O6—N3—C11	118.06 (16)

(CO-1-LT) top

Crystal data top

C₇H₅NO₄·C₇H₉N	Z = 2
M_r = 274.27	F(000) = 288
Triclinic, P1	D_x = 1.396 Mg m⁻³
a = 6.631 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.032 (6) Å	Cell parameters from 2645 reflections
c = 14.216 (12) Å	θ = 2.9–33.4°
α = 87.967 (17)°	µ = 0.10 mm⁻¹
β = 88.58 (3)°	T = 110 K
γ = 80.207 (18)°	Block, colorless
V = 652.6 (9) Å³	0.21 × 0.18 × 0.14 mm

Data collection top

Rigaku diffractometer	2555 independent reflections
Radiation source: fine-focus sealed tube	2366 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.071
profile data from ω–scans	θ_max = 26.0°, θ_min = 1.4°
Absorption correction: multi-scan SADABS	h = −8→8
T_min = 0.835, T_max = 1.000	k = −8→8
6144 measured reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.134	H atoms treated by a mixture of independent and constrained refinement
S = 1.11	w = 1/[σ²(F_o²) + (0.0749P)² + 0.0851P] where P = (F_o² + 2F_c²)/3
2555 reflections	(Δ/σ)_max < 0.001
237 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.33 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.26950 (18)	0.23170 (17)	0.23632 (9)	0.0198 (3)
C2	0.19022 (19)	0.21745 (17)	0.32802 (9)	0.0203 (3)
C3	−0.0210 (2)	0.27531 (19)	0.34036 (9)	0.0235 (3)
C4	−0.14047 (19)	0.34181 (19)	0.26370 (9)	0.0252 (3)
C5	−0.04746 (18)	0.35406 (18)	0.17500 (9)	0.0218 (3)
C6	0.3292 (2)	0.14700 (19)	0.40875 (9)	0.0248 (3)
C7	0.4014 (2)	0.3124 (2)	0.45763 (9)	0.0284 (3)
C12	0.56470 (18)	0.27960 (18)	0.82746 (9)	0.0197 (3)
C11	0.68389 (18)	0.27143 (17)	0.74498 (9)	0.0203 (3)
C10	0.89479 (18)	0.21779 (17)	0.75283 (8)	0.0187 (3)
C9	0.99063 (18)	0.17221 (18)	0.83820 (9)	0.0208 (3)
C8	0.86858 (18)	0.18269 (18)	0.91965 (9)	0.0202 (3)
C13	0.65621 (17)	0.23511 (16)	0.91416 (8)	0.0174 (3)
C14	0.53258 (18)	0.23554 (17)	1.00490 (8)	0.0192 (3)
N1	0.15482 (16)	0.29868 (15)	0.16176 (7)	0.0205 (3)
N2	1.02244 (16)	0.20765 (16)	0.66561 (8)	0.0237 (3)
O1	0.33936 (13)	0.31896 (13)	0.99750 (6)	0.0231 (3)
O2	0.60992 (13)	0.16336 (15)	1.07743 (6)	0.0276 (3)
O3	0.93613 (16)	0.23586 (16)	0.58977 (7)	0.0346 (3)
O4	1.20966 (14)	0.17185 (16)	0.67351 (7)	0.0362 (3)
H1	0.414 (2)	0.194 (2)	0.2198 (11)	0.025 (4)*
H1A	0.274 (4)	0.315 (3)	1.0660 (18)	0.069 (7)*
H3	−0.078 (2)	0.271 (2)	0.4033 (12)	0.028 (4)*
H4	−0.290 (3)	0.382 (3)	0.2710 (14)	0.045 (5)*
H5	−0.125 (2)	0.400 (2)	0.1210 (11)	0.019 (3)*
H6A	0.257 (3)	0.074 (2)	0.4564 (13)	0.037 (4)*
H6B	0.446 (3)	0.058 (3)	0.3831 (12)	0.035 (4)*
H7A	0.489 (3)	0.265 (3)	0.5084 (14)	0.044 (5)*
H7B	0.286 (3)	0.401 (3)	0.4846 (13)	0.036 (4)*
H7C	0.475 (3)	0.386 (3)	0.4126 (13)	0.043 (5)*
H12	0.416 (3)	0.318 (2)	0.8213 (12)	0.033 (4)*
H11	0.623 (3)	0.304 (2)	0.6842 (13)	0.032 (4)*
H9	1.135 (3)	0.131 (2)	0.8413 (12)	0.033 (4)*
H8	0.930 (2)	0.155 (2)	0.9806 (12)	0.028 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0187 (6)	0.0203 (6)	0.0201 (6)	−0.0028 (4)	0.0007 (5)	0.0003 (5)
C2	0.0231 (6)	0.0177 (6)	0.0200 (6)	−0.0032 (4)	−0.0002 (5)	0.0009 (4)
C3	0.0232 (6)	0.0248 (7)	0.0215 (6)	−0.0019 (5)	0.0056 (5)	0.0006 (5)
C4	0.0187 (6)	0.0286 (7)	0.0273 (7)	−0.0018 (5)	0.0028 (5)	0.0010 (5)
C5	0.0202 (6)	0.0241 (6)	0.0210 (6)	−0.0034 (5)	−0.0024 (5)	0.0012 (5)
C6	0.0260 (6)	0.0245 (7)	0.0217 (6)	0.0009 (5)	−0.0014 (5)	0.0034 (5)
C7	0.0294 (7)	0.0326 (7)	0.0231 (7)	−0.0057 (6)	−0.0061 (5)	0.0051 (6)
C12	0.0152 (6)	0.0215 (6)	0.0214 (6)	−0.0008 (4)	−0.0004 (5)	0.0015 (5)
C11	0.0206 (6)	0.0218 (6)	0.0178 (6)	−0.0021 (5)	−0.0023 (5)	0.0025 (5)
C10	0.0186 (6)	0.0185 (6)	0.0189 (6)	−0.0035 (4)	0.0034 (5)	0.0003 (5)
C9	0.0145 (6)	0.0217 (6)	0.0253 (6)	−0.0015 (4)	0.0001 (5)	0.0022 (5)
C8	0.0186 (6)	0.0226 (6)	0.0191 (6)	−0.0026 (5)	−0.0033 (5)	0.0031 (5)
C13	0.0159 (6)	0.0163 (6)	0.0195 (6)	−0.0014 (4)	−0.0004 (5)	0.0022 (4)
C14	0.0177 (6)	0.0208 (6)	0.0190 (6)	−0.0035 (4)	−0.0018 (5)	0.0021 (5)
N1	0.0191 (5)	0.0216 (5)	0.0208 (5)	−0.0040 (4)	0.0017 (4)	0.0000 (4)
N2	0.0227 (6)	0.0250 (6)	0.0231 (6)	−0.0038 (4)	0.0046 (4)	0.0002 (4)
O1	0.0155 (4)	0.0317 (5)	0.0197 (5)	0.0016 (3)	0.0010 (3)	0.0035 (4)
O2	0.0204 (5)	0.0417 (6)	0.0186 (5)	−0.0007 (4)	−0.0008 (4)	0.0079 (4)
O3	0.0335 (6)	0.0509 (7)	0.0186 (5)	−0.0053 (5)	0.0029 (4)	0.0014 (4)
O4	0.0192 (5)	0.0544 (7)	0.0330 (6)	−0.0020 (4)	0.0077 (4)	−0.0001 (5)

Geometric parameters (Å, º) top

C1—N1	1.3440 (18)	C11—C10	1.391 (2)
C1—C2	1.400 (2)	C10—C9	1.386 (2)
C2—C3	1.399 (2)	C10—N2	1.4807 (18)
C2—C6	1.5060 (19)	C9—C8	1.393 (2)
C3—C4	1.384 (2)	C8—C13	1.397 (2)
C4—C5	1.396 (2)	C13—C14	1.5109 (19)
C5—N1	1.3420 (19)	C14—O2	1.2184 (17)
C6—C7	1.526 (2)	C14—O1	1.3202 (17)
C12—C13	1.389 (2)	N2—O3	1.2273 (17)
C12—C11	1.3951 (19)	N2—O4	1.2311 (17)

N1—C1—C2	123.68 (12)	C10—C9—C8	117.90 (12)
C3—C2—C1	116.77 (12)	C9—C8—C13	120.38 (12)
C3—C2—C6	122.48 (12)	C12—C13—C8	120.33 (11)
C1—C2—C6	120.74 (12)	C12—C13—C14	122.11 (12)
C4—C3—C2	119.88 (12)	C8—C13—C14	117.55 (12)
C3—C4—C5	119.35 (13)	O2—C14—O1	124.54 (11)
N1—C5—C4	121.60 (12)	O2—C14—C13	121.12 (12)
C2—C6—C7	112.23 (12)	O1—C14—C13	114.33 (11)
C13—C12—C11	120.33 (12)	C5—N1—C1	118.70 (11)
C10—C11—C12	117.91 (12)	O3—N2—O4	123.75 (11)
C9—C10—C11	123.15 (11)	O3—N2—C10	118.35 (12)
C9—C10—N2	118.56 (12)	O4—N2—C10	117.90 (12)
C11—C10—N2	118.29 (12)

(CO-1-RT) top

Crystal data top

C₇H₅NO₄·C₇H₉N	Z = 2
M_r = 274.27	F(000) = 288
Triclinic, P1	D_x = 1.345 Mg m⁻³
a = 6.7302 (16) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.1859 (17) Å	Cell parameters from 4398 reflections
c = 14.298 (3) Å	θ = 3.1–27.6°
α = 88.158 (6)°	µ = 0.10 mm⁻¹
β = 88.340 (6)°	T = 298 K
γ = 78.636 (5)°	Block, colorless
V = 677.4 (3) Å³	0.21 × 0.18 × 0.14 mm

Data collection top

Rigaku diffractometer	2634 independent reflections
Radiation source: fine-focus sealed tube	1543 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.040
profile data from ω–scans	θ_max = 26.0°, θ_min = 3.1°
Absorption correction: multi-scan SADABS	h = −8→8
T_min = 0.758, T_max = 1.000	k = −8→8
5680 measured reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.065	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.189	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.1009P)²] where P = (F_o² + 2F_c²)/3
2634 reflections	(Δ/σ)_max < 0.001
225 parameters	Δρ_max = 0.20 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.2264 (4)	0.7625 (4)	0.26211 (19)	0.0535 (7)
C2	0.3039 (4)	0.7736 (4)	0.17196 (18)	0.0535 (7)
C3	0.5118 (4)	0.7161 (4)	0.1609 (2)	0.0609 (8)
C4	0.6294 (5)	0.6531 (4)	0.2368 (2)	0.0673 (8)
C5	0.5378 (4)	0.6447 (4)	0.3235 (2)	0.0596 (7)
C6	0.1675 (6)	0.8436 (5)	0.0915 (2)	0.0688 (9)
C7	0.1000 (5)	0.6857 (5)	0.0433 (2)	0.0905 (11)
H7A	0.0135	0.7372	−0.0073	0.136*
H7B	0.0268	0.6189	0.0872	0.136*
H7C	0.2163	0.5997	0.0192	0.136*
C8	0.6338 (4)	0.8179 (4)	0.58116 (19)	0.0552 (7)
C9	0.5153 (4)	0.8304 (4)	0.66133 (19)	0.0557 (7)
C10	0.6113 (4)	0.7895 (3)	0.74529 (17)	0.0501 (6)
C11	0.8184 (4)	0.7388 (4)	0.75120 (18)	0.0524 (7)
C12	0.9337 (4)	0.7283 (4)	0.67035 (18)	0.0517 (7)
C13	0.8427 (3)	0.7682 (3)	0.58431 (16)	0.0441 (6)
C14	0.9641 (4)	0.7627 (3)	0.49399 (18)	0.0508 (7)
N1	0.3398 (3)	0.6987 (3)	0.33668 (14)	0.0532 (6)
N2	0.4855 (4)	0.8009 (3)	0.83174 (18)	0.0630 (7)
O1	1.1568 (3)	0.6901 (3)	0.50124 (13)	0.0629 (6)
O2	0.8841 (3)	0.8237 (3)	0.42161 (13)	0.0797 (7)
O3	0.5720 (4)	0.7746 (4)	0.90595 (16)	0.0925 (8)
O4	0.3028 (3)	0.8370 (4)	0.82532 (16)	0.0966 (8)
H1	0.091 (4)	0.794 (3)	0.2804 (18)	0.059 (8)*
H1A	1.222 (6)	0.689 (5)	0.430 (3)	0.118 (12)*
H3	0.561 (4)	0.722 (4)	0.100 (2)	0.061 (8)*
H4	0.767 (5)	0.618 (4)	0.227 (2)	0.093 (11)*
H5	0.614 (4)	0.595 (4)	0.374 (2)	0.070 (9)*
H6A	0.238 (5)	0.916 (4)	0.050 (2)	0.083 (10)*
H6B	0.043 (6)	0.925 (5)	0.114 (3)	0.109 (12)*
H8	0.569 (5)	0.852 (4)	0.523 (2)	0.083 (9)*
H9	0.384 (4)	0.863 (4)	0.6554 (19)	0.065 (8)*
H11	0.888 (5)	0.710 (4)	0.808 (2)	0.082 (9)*
H12	1.072 (5)	0.709 (4)	0.673 (2)	0.077 (9)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0511 (16)	0.0564 (16)	0.0529 (16)	−0.0109 (13)	0.0054 (13)	−0.0058 (13)
C2	0.0622 (16)	0.0499 (15)	0.0478 (15)	−0.0099 (13)	0.0033 (12)	−0.0018 (12)
C3	0.0642 (18)	0.0679 (19)	0.0476 (17)	−0.0068 (14)	0.0097 (14)	−0.0025 (14)
C4	0.0534 (18)	0.077 (2)	0.068 (2)	−0.0051 (15)	0.0096 (15)	−0.0019 (16)
C5	0.0553 (17)	0.0681 (19)	0.0538 (17)	−0.0080 (14)	−0.0032 (14)	−0.0022 (14)
C6	0.075 (2)	0.068 (2)	0.0597 (19)	−0.0061 (18)	−0.0033 (16)	0.0050 (16)
C7	0.103 (3)	0.100 (3)	0.074 (2)	−0.033 (2)	−0.0269 (19)	0.0100 (19)
C8	0.0509 (16)	0.0636 (17)	0.0489 (16)	−0.0066 (13)	−0.0042 (12)	0.0040 (13)
C9	0.0423 (15)	0.0640 (18)	0.0595 (17)	−0.0084 (13)	−0.0006 (13)	0.0028 (14)
C10	0.0498 (15)	0.0468 (14)	0.0529 (15)	−0.0086 (12)	0.0091 (12)	−0.0049 (12)
C11	0.0535 (16)	0.0615 (16)	0.0410 (14)	−0.0079 (13)	−0.0021 (12)	−0.0024 (12)
C12	0.0417 (14)	0.0589 (16)	0.0519 (15)	−0.0037 (12)	−0.0012 (12)	−0.0004 (12)
C13	0.0440 (13)	0.0411 (13)	0.0465 (14)	−0.0065 (10)	−0.0006 (10)	−0.0011 (10)
C14	0.0553 (16)	0.0504 (15)	0.0464 (15)	−0.0103 (13)	0.0009 (12)	0.0001 (12)
N1	0.0591 (14)	0.0558 (13)	0.0455 (12)	−0.0134 (11)	0.0052 (10)	−0.0055 (10)
N2	0.0632 (16)	0.0665 (16)	0.0579 (15)	−0.0116 (12)	0.0168 (12)	−0.0048 (12)
O1	0.0472 (11)	0.0851 (14)	0.0505 (11)	0.0005 (9)	0.0053 (8)	0.0002 (10)
O2	0.0596 (13)	0.1250 (19)	0.0480 (12)	−0.0049 (12)	−0.0011 (10)	0.0155 (12)
O3	0.0951 (17)	0.132 (2)	0.0505 (13)	−0.0240 (15)	0.0121 (12)	−0.0042 (13)
O4	0.0637 (15)	0.133 (2)	0.0866 (17)	−0.0075 (14)	0.0265 (12)	−0.0055 (14)

Geometric parameters (Å, º) top

C1—N1	1.344 (3)	C9—C10	1.376 (4)
C1—C2	1.382 (4)	C10—C11	1.374 (3)
C2—C3	1.385 (4)	C10—N2	1.473 (3)
C2—C6	1.504 (4)	C11—C12	1.369 (4)
C3—C4	1.373 (4)	C12—C13	1.386 (3)
C4—C5	1.373 (4)	C13—C14	1.505 (3)
C5—N1	1.322 (3)	C14—O2	1.209 (3)
C6—C7	1.496 (4)	C14—O1	1.305 (3)
C8—C9	1.372 (4)	N2—O4	1.211 (3)
C8—C13	1.383 (3)	N2—O3	1.217 (3)

N1—C1—C2	124.0 (3)	C12—C11—C10	118.7 (2)
C1—C2—C3	116.1 (2)	C11—C12—C13	120.5 (2)
C1—C2—C6	121.1 (3)	C8—C13—C12	119.1 (2)
C3—C2—C6	122.8 (3)	C8—C13—C14	118.7 (2)
C4—C3—C2	120.4 (3)	C12—C13—C14	122.2 (2)
C3—C4—C5	119.2 (3)	O2—C14—O1	124.2 (2)
N1—C5—C4	122.1 (3)	O2—C14—C13	120.8 (2)
C7—C6—C2	112.5 (3)	O1—C14—C13	114.9 (2)
C9—C8—C13	121.4 (3)	C5—N1—C1	118.3 (2)
C8—C9—C10	117.7 (3)	O4—N2—O3	123.7 (2)
C11—C10—C9	122.6 (2)	O4—N2—C10	118.6 (2)
C11—C10—N2	119.3 (2)	O3—N2—C10	117.7 (2)
C9—C10—N2	118.2 (2)

(CNT-1-LT) top

Crystal data top

C₆Cl₅O·C₆H₈N	F(000) = 360
M_r = 359.44	D_x = 1.698 Mg m⁻³
Triclinic, P1	Melting point: 75-79 K
a = 7.316 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.942 (8) Å	Cell parameters from 3305 reflections
c = 11.763 (9) Å	θ = 2.5–33.6°
α = 70.15 (4)°	µ = 1.02 mm⁻¹
β = 84.67 (4)°	T = 110 K
γ = 76.24 (4)°	Needle, colorless
V = 703.0 (10) Å³	0.25 × 0.16 × 0.14 mm
Z = 2

Data collection top

Rigaku diffractometer	2741 independent reflections
Radiation source: fine-focus sealed tube	2421 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.054
profile data from ω–scans	θ_max = 26.0°, θ_min = 1.8°
Absorption correction: multi-scan SADABS	h = −9→9
T_min = 0.707, T_max = 1.000	k = −11→11
6521 measured reflections	l = −14→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.151	H atoms treated by a mixture of independent and constrained refinement
S = 1.30	w = 1/[σ²(F_o²) + (0.0743P)² + 0.0744P] where P = (F_o² + 2F_c²)/3
2741 reflections	(Δ/σ)_max < 0.001
185 parameters	Δρ_max = 0.58 e Å⁻³
0 restraints	Δρ_min = −0.61 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.7730 (4)	0.2822 (3)	0.0500 (2)	0.0199 (6)
Cl1	1.12019 (11)	−0.05020 (10)	0.16138 (7)	0.0219 (2)
Cl5	1.08069 (11)	0.42010 (9)	0.35827 (7)	0.0222 (2)
Cl4	1.24737 (11)	0.15953 (10)	0.59805 (7)	0.0216 (2)
Cl2	1.29877 (12)	−0.31341 (10)	0.39982 (7)	0.0255 (2)
Cl3	1.35552 (11)	−0.21137 (10)	0.62035 (7)	0.0235 (2)
C2	1.1595 (4)	0.0078 (4)	0.2823 (3)	0.0178 (6)
C4	1.2640 (4)	−0.0649 (4)	0.4871 (3)	0.0171 (6)
O1	1.0406 (3)	0.2888 (3)	0.16786 (19)	0.0210 (5)
C1	1.1090 (4)	0.1753 (4)	0.2683 (3)	0.0161 (6)
C5	1.2148 (4)	0.1005 (4)	0.4770 (3)	0.0180 (6)
C10	0.5843 (4)	0.4188 (4)	−0.1243 (3)	0.0204 (7)
C3	1.2367 (4)	−0.1106 (4)	0.3886 (3)	0.0183 (6)
C8	0.4991 (4)	0.1942 (4)	0.0311 (3)	0.0227 (7)
H8	0.4188	0.1233	0.0638	0.027*
C6	1.1404 (4)	0.2168 (4)	0.3704 (3)	0.0173 (6)
C9	0.4602 (4)	0.3145 (4)	−0.0812 (3)	0.0218 (7)
C11	0.7374 (4)	0.4009 (4)	−0.0570 (3)	0.0188 (6)
C12	0.2926 (5)	0.3323 (5)	−0.1528 (4)	0.0341 (9)
H12A	0.2215	0.2530	−0.1080	0.051*
H12B	0.3340	0.3155	−0.2283	0.051*
H12C	0.2148	0.4398	−0.1680	0.051*
C7	0.6553 (5)	0.1798 (4)	0.0937 (3)	0.0222 (7)
H7	0.6804	0.0976	0.1678	0.027*
H11	0.817 (4)	0.464 (4)	−0.083 (3)	0.012 (8)*
H10	0.565 (5)	0.494 (5)	−0.197 (3)	0.024 (9)*
H1	0.897 (8)	0.291 (7)	0.101 (5)	0.083 (18)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0238 (14)	0.0206 (14)	0.0152 (13)	−0.0045 (11)	−0.0029 (11)	−0.0055 (11)
Cl1	0.0256 (4)	0.0247 (4)	0.0197 (4)	−0.0069 (3)	−0.0001 (3)	−0.0119 (3)
Cl5	0.0299 (4)	0.0170 (4)	0.0216 (4)	−0.0062 (3)	−0.0033 (3)	−0.0071 (3)
Cl4	0.0252 (4)	0.0274 (4)	0.0156 (4)	−0.0084 (3)	−0.0016 (3)	−0.0092 (3)
Cl2	0.0315 (5)	0.0172 (4)	0.0284 (5)	−0.0046 (3)	−0.0009 (3)	−0.0085 (3)
Cl3	0.0246 (4)	0.0240 (4)	0.0176 (4)	−0.0043 (3)	−0.0033 (3)	−0.0011 (3)
C2	0.0139 (14)	0.0241 (16)	0.0195 (15)	−0.0062 (12)	0.0034 (12)	−0.0120 (13)
C4	0.0156 (14)	0.0164 (15)	0.0155 (14)	−0.0040 (12)	−0.0001 (12)	−0.0004 (12)
O1	0.0240 (11)	0.0210 (11)	0.0164 (11)	−0.0070 (9)	−0.0047 (9)	−0.0017 (9)
C1	0.0139 (14)	0.0204 (16)	0.0158 (15)	−0.0076 (12)	0.0005 (11)	−0.0059 (12)
C5	0.0157 (15)	0.0264 (17)	0.0149 (14)	−0.0088 (13)	0.0019 (12)	−0.0085 (13)
C10	0.0245 (16)	0.0189 (16)	0.0143 (15)	0.0001 (13)	−0.0016 (13)	−0.0039 (13)
C3	0.0145 (14)	0.0183 (15)	0.0227 (16)	−0.0053 (12)	0.0030 (12)	−0.0070 (13)
C8	0.0203 (15)	0.0241 (17)	0.0275 (17)	−0.0100 (13)	0.0063 (13)	−0.0114 (14)
C6	0.0166 (15)	0.0185 (15)	0.0196 (15)	−0.0081 (12)	0.0022 (12)	−0.0077 (13)
C9	0.0205 (15)	0.0243 (17)	0.0248 (17)	−0.0010 (13)	−0.0019 (13)	−0.0156 (14)
C11	0.0181 (15)	0.0186 (15)	0.0214 (16)	−0.0052 (13)	0.0020 (12)	−0.0085 (13)
C12	0.0227 (17)	0.047 (2)	0.039 (2)	−0.0065 (16)	−0.0080 (16)	−0.0212 (18)
C7	0.0314 (17)	0.0183 (16)	0.0152 (15)	−0.0041 (13)	0.0009 (13)	−0.0048 (13)

Geometric parameters (Å, º) top

N1—C11	1.342 (4)	C4—C5	1.402 (5)
N1—C7	1.348 (4)	O1—C1	1.315 (4)
Cl1—C2	1.739 (3)	C1—C6	1.425 (4)
Cl5—C6	1.724 (3)	C5—C6	1.386 (5)
Cl4—C5	1.731 (3)	C10—C11	1.378 (5)
Cl2—C3	1.723 (4)	C10—C9	1.396 (5)
Cl3—C4	1.733 (3)	C8—C7	1.374 (5)
C2—C3	1.396 (5)	C8—C9	1.393 (5)
C2—C1	1.410 (5)	C9—C12	1.499 (5)
C4—C3	1.398 (4)

C11—N1—C7	119.4 (3)	C11—C10—C9	120.4 (3)
C3—C2—C1	122.7 (3)	C2—C3—C4	120.0 (3)
C3—C2—Cl1	119.8 (3)	C2—C3—Cl2	120.6 (2)
C1—C2—Cl1	117.6 (2)	C4—C3—Cl2	119.4 (2)
C3—C4—C5	119.1 (3)	C7—C8—C9	120.4 (3)
C3—C4—Cl3	120.3 (2)	C5—C6—C1	122.4 (3)
C5—C4—Cl3	120.6 (2)	C5—C6—Cl5	120.1 (2)
O1—C1—C2	123.5 (3)	C1—C6—Cl5	117.5 (2)
O1—C1—C6	120.9 (3)	C8—C9—C10	117.0 (3)
C2—C1—C6	115.6 (3)	C8—C9—C12	121.9 (3)
C6—C5—C4	120.3 (3)	C10—C9—C12	121.2 (3)
C6—C5—Cl4	119.9 (3)	N1—C11—C10	121.4 (3)
C4—C5—Cl4	119.8 (2)	N1—C7—C8	121.5 (3)

(CNT-1-RT) top

Crystal data top

C₆Cl₅O·C₆H₈N	F(000) = 360
M_r = 359.44	D_x = 1.653 Mg m⁻³
Triclinic, P1	Melting point: 75-79 K
a = 7.389 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.922 (8) Å	Cell parameters from 1777 reflections
c = 12.014 (12) Å	θ = 2.5–32.9°
α = 69.82 (3)°	µ = 0.99 mm⁻¹
β = 85.61 (4)°	T = 298 K
γ = 76.26 (4)°	Needle, colorless
V = 722.1 (12) Å³	0.25 × 0.16 × 0.14 mm
Z = 2

Data collection top

Rigaku diffractometer	2815 independent reflections
Radiation source: fine-focus sealed tube	2152 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.063
profile data from ω–scans	θ_max = 26.0°, θ_min = 1.8°
Absorption correction: multi-scan SADABS	h = −9→9
T_min = 0.723, T_max = 1.000	k = −11→11
6793 measured reflections	l = −14→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.051	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.194	H atoms treated by a mixture of independent and constrained refinement
S = 1.16	w = 1/[σ²(F_o²) + (0.1071P)²] where P = (F_o² + 2F_c²)/3
2815 reflections	(Δ/σ)_max = 0.039
192 parameters	Δρ_max = 0.52 e Å⁻³
0 restraints	Δρ_min = −0.60 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
H10	0.930 (6)	0.010 (5)	0.684 (4)	0.054 (13)*
H7	0.815 (5)	0.398 (5)	0.344 (4)	0.046 (11)*
H11	0.684 (5)	0.047 (5)	0.574 (4)	0.047 (12)*
H8	1.068 (7)	0.389 (6)	0.436 (5)	0.080 (15)*
H1N	0.643 (13)	0.179 (11)	0.411 (8)	0.19 (4)*
Cl1	0.42078 (16)	0.07870 (12)	0.14420 (10)	0.0545 (3)
Cl2	0.25422 (14)	0.33695 (14)	−0.09403 (9)	0.0533 (3)
Cl5	0.37352 (15)	0.55455 (14)	0.32908 (9)	0.0549 (3)
Cl4	0.19713 (17)	0.81558 (13)	0.09201 (12)	0.0637 (4)
Cl3	0.14316 (15)	0.70894 (14)	−0.12139 (10)	0.0588 (4)
C1	0.3905 (5)	0.3280 (5)	0.2269 (3)	0.0388 (8)
C3	0.2856 (5)	0.3987 (5)	0.0228 (3)	0.0390 (8)
C6	0.3381 (5)	0.4953 (5)	0.2113 (3)	0.0395 (8)
O1	0.4596 (4)	0.2132 (3)	0.3269 (2)	0.0498 (7)
C4	0.2345 (5)	0.5642 (5)	0.0099 (3)	0.0399 (8)
C5	0.2613 (5)	0.6128 (5)	0.1062 (3)	0.0412 (9)
C2	0.3611 (5)	0.2826 (4)	0.1290 (3)	0.0378 (8)
N1	0.7232 (5)	0.2236 (4)	0.4472 (3)	0.0483 (8)
C10	0.9108 (6)	0.0877 (5)	0.6198 (4)	0.0483 (10)
C9	1.0322 (5)	0.1896 (5)	0.5784 (4)	0.0493 (10)
C8	0.9945 (6)	0.3087 (6)	0.4680 (4)	0.0543 (11)
C7	0.8402 (6)	0.3221 (6)	0.4066 (4)	0.0535 (11)
C11	0.7595 (6)	0.1061 (5)	0.5523 (4)	0.0480 (10)
C12	1.1992 (7)	0.1723 (8)	0.6500 (6)	0.0852 (17)
H12A	1.2671	0.2537	0.6067	0.128*
H12B	1.2784	0.0651	0.6647	0.128*
H12C	1.1588	0.1870	0.7241	0.128*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0698 (7)	0.0401 (6)	0.0601 (7)	−0.0160 (5)	−0.0071 (5)	−0.0210 (5)
Cl2	0.0581 (6)	0.0679 (7)	0.0440 (6)	−0.0219 (5)	−0.0019 (4)	−0.0259 (5)
Cl5	0.0637 (7)	0.0598 (7)	0.0555 (6)	−0.0187 (5)	0.0035 (5)	−0.0346 (5)
Cl4	0.0694 (7)	0.0400 (6)	0.0838 (8)	−0.0108 (5)	−0.0024 (6)	−0.0238 (5)
Cl3	0.0552 (6)	0.0587 (7)	0.0503 (6)	−0.0127 (5)	−0.0078 (5)	−0.0014 (5)
C1	0.0359 (17)	0.044 (2)	0.043 (2)	−0.0169 (16)	0.0023 (15)	−0.0178 (17)
C3	0.0328 (17)	0.050 (2)	0.0411 (19)	−0.0198 (16)	0.0054 (15)	−0.0179 (17)
C6	0.0362 (17)	0.047 (2)	0.044 (2)	−0.0163 (16)	0.0044 (16)	−0.0232 (17)
O1	0.0622 (16)	0.0434 (15)	0.0445 (15)	−0.0212 (13)	−0.0075 (13)	−0.0080 (12)
C4	0.0325 (17)	0.043 (2)	0.041 (2)	−0.0120 (15)	0.0008 (15)	−0.0084 (16)
C5	0.0351 (17)	0.039 (2)	0.053 (2)	−0.0139 (15)	0.0072 (16)	−0.0177 (17)
C2	0.0366 (17)	0.0376 (19)	0.045 (2)	−0.0144 (15)	0.0020 (15)	−0.0169 (16)
N1	0.0536 (19)	0.050 (2)	0.0451 (18)	−0.0168 (16)	−0.0050 (15)	−0.0170 (16)
C10	0.053 (2)	0.044 (2)	0.042 (2)	−0.0029 (19)	−0.0054 (19)	−0.0113 (18)
C9	0.0400 (19)	0.056 (2)	0.058 (2)	−0.0003 (18)	−0.0058 (18)	−0.032 (2)
C8	0.051 (2)	0.058 (3)	0.064 (3)	−0.025 (2)	0.008 (2)	−0.026 (2)
C7	0.070 (3)	0.050 (2)	0.038 (2)	−0.020 (2)	0.000 (2)	−0.0072 (19)
C11	0.050 (2)	0.043 (2)	0.049 (2)	−0.0110 (19)	0.0005 (19)	−0.0131 (18)
C12	0.057 (3)	0.102 (5)	0.108 (4)	−0.011 (3)	−0.028 (3)	−0.050 (4)

Geometric parameters (Å, º) top

Cl1—C2	1.715 (4)	C6—C5	1.389 (5)
Cl2—C3	1.724 (4)	C4—C5	1.409 (5)
Cl5—C6	1.729 (4)	N1—C7	1.326 (5)
Cl4—C5	1.709 (4)	N1—C11	1.330 (5)
Cl3—C4	1.719 (4)	C10—C9	1.373 (6)
C1—O1	1.323 (4)	C10—C11	1.376 (6)
C1—C6	1.399 (5)	C9—C8	1.382 (6)
C1—C2	1.415 (5)	C9—C12	1.506 (6)
C3—C4	1.391 (6)	C8—C7	1.365 (6)
C3—C2	1.391 (5)

O1—C1—C6	124.0 (3)	C6—C5—Cl4	121.0 (3)
O1—C1—C2	119.5 (3)	C4—C5—Cl4	119.4 (3)
C6—C1—C2	116.4 (3)	C3—C2—C1	121.6 (4)
C4—C3—C2	120.7 (3)	C3—C2—Cl1	120.1 (3)
C4—C3—Cl2	119.5 (3)	C1—C2—Cl1	118.2 (3)
C2—C3—Cl2	119.8 (3)	C7—N1—C11	118.1 (4)
C5—C6—C1	122.7 (3)	C9—C10—C11	120.3 (4)
C5—C6—Cl5	119.8 (3)	C10—C9—C8	117.1 (4)
C1—C6—Cl5	117.5 (3)	C10—C9—C12	121.5 (5)
C3—C4—C5	118.9 (3)	C8—C9—C12	121.4 (5)
C3—C4—Cl3	121.1 (3)	C7—C8—C9	119.7 (4)
C5—C4—Cl3	120.0 (3)	N1—C7—C8	122.9 (4)
C6—C5—C4	119.6 (4)	N1—C11—C10	121.9 (4)

(CNT1-LT) top

Crystal data top

C₆HCl₅O·C₆H₇N	F(000) = 360
M_r = 359.44	D_x = 1.695 Mg m⁻³
Triclinic, P1	Melting point: 75-79 K
a = 7.3382 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.8986 (9) Å	Cell parameters from 5272 reflections
c = 11.8245 (11) Å	θ = 3.2–27.5°
α = 69.945 (5)°	µ = 1.02 mm⁻¹
β = 85.055 (5)°	T = 110 K
γ = 76.133 (5)°	Needle, colorless
V = 704.17 (12) Å³	0.27 × 0.15 × 0.13 mm
Z = 2

Data collection top

Bruker P4 diffractometer	2756 independent reflections
Radiation source: fine-focus sealed tube	2106 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.052
ω scans	θ_max = 26.0°, θ_min = 3.4°
Absorption correction: empirical SADABS	h = −9→9
T_min = 0.833, T_max = 0.876	k = −10→10
11629 measured reflections	l = −14→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.103	H atoms treated by a mixture of independent and constrained refinement
S = 1.10	w = 1/[σ²(F_o²) + (0.0398P)² + 0.5163P] where P = (F_o² + 2F_c²)/3
2756 reflections	(Δ/σ)_max < 0.001
193 parameters	Δρ_max = 0.37 e Å⁻³
0 restraints	Δρ_min = −0.28 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.3903 (4)	0.8268 (4)	0.2293 (2)	0.0234 (7)
C2	0.3609 (4)	0.7824 (4)	0.1299 (3)	0.0246 (7)
C3	0.2860 (4)	0.8999 (4)	0.0232 (3)	0.0243 (7)
C4	0.2353 (4)	1.0648 (4)	0.0118 (3)	0.0257 (7)
C5	0.2618 (4)	1.1117 (4)	0.1086 (3)	0.0245 (7)
C6	0.3396 (4)	0.9937 (4)	0.2146 (3)	0.0241 (7)
C7	0.8416 (5)	0.8215 (4)	0.4054 (3)	0.0334 (8)
C8	0.9971 (5)	0.8081 (4)	0.4679 (3)	0.0338 (8)
C9	1.0356 (4)	0.6888 (4)	0.5791 (3)	0.0311 (7)
C10	0.9136 (4)	0.5841 (4)	0.6220 (3)	0.0298 (7)
C11	0.7611 (4)	0.6017 (4)	0.5552 (3)	0.0279 (7)
C12	1.2035 (5)	0.6704 (5)	0.6512 (4)	0.0537 (11)
H12A	1.2649	0.7588	0.6116	0.081*
H12B	1.2892	0.5676	0.6580	0.081*
H12C	1.1635	0.6731	0.7301	0.081*
N1	0.7245 (4)	0.7202 (3)	0.4481 (2)	0.0292 (6)
O1	0.4590 (3)	0.7125 (2)	0.32955 (18)	0.0306 (5)
Cl1	0.42125 (12)	0.57844 (9)	0.14310 (7)	0.0342 (2)
Cl2	0.25397 (11)	0.83833 (10)	−0.09585 (7)	0.0331 (2)
Cl3	0.14334 (11)	1.21033 (10)	−0.12073 (7)	0.0357 (2)
Cl4	0.19843 (12)	1.31485 (10)	0.09655 (8)	0.0394 (2)
Cl5	0.37690 (11)	1.05247 (10)	0.33437 (7)	0.0338 (2)
H1	0.581 (7)	0.720 (5)	0.378 (4)	0.090 (15)*
H7	0.807 (4)	0.904 (4)	0.332 (3)	0.019 (7)*
H8	1.078 (5)	0.874 (4)	0.434 (3)	0.035 (9)*
H10	0.929 (4)	0.499 (4)	0.695 (3)	0.032 (9)*
H11	0.677 (4)	0.528 (4)	0.579 (3)	0.028 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0207 (15)	0.0276 (16)	0.0253 (16)	−0.0111 (13)	0.0003 (12)	−0.0092 (13)
C2	0.0215 (16)	0.0248 (16)	0.0307 (16)	−0.0110 (13)	0.0030 (13)	−0.0102 (13)
C3	0.0199 (16)	0.0339 (17)	0.0246 (15)	−0.0139 (13)	0.0020 (12)	−0.0119 (13)
C4	0.0201 (15)	0.0280 (17)	0.0257 (16)	−0.0071 (13)	0.0031 (12)	−0.0046 (13)
C5	0.0223 (15)	0.0233 (15)	0.0313 (16)	−0.0093 (13)	0.0035 (13)	−0.0113 (13)
C6	0.0220 (16)	0.0298 (17)	0.0265 (16)	−0.0114 (13)	0.0035 (13)	−0.0138 (13)
C7	0.044 (2)	0.0301 (18)	0.0246 (17)	−0.0097 (16)	0.0017 (15)	−0.0073 (14)
C8	0.0338 (19)	0.036 (2)	0.041 (2)	−0.0173 (16)	0.0114 (16)	−0.0212 (16)
C9	0.0253 (17)	0.0348 (18)	0.0399 (19)	−0.0027 (14)	−0.0003 (14)	−0.0237 (15)
C10	0.0339 (19)	0.0272 (17)	0.0246 (16)	−0.0003 (14)	−0.0023 (14)	−0.0080 (14)
C11	0.0301 (18)	0.0264 (17)	0.0301 (17)	−0.0098 (14)	0.0049 (14)	−0.0118 (13)
C12	0.035 (2)	0.070 (3)	0.065 (3)	−0.0093 (19)	−0.0152 (19)	−0.033 (2)
N1	0.0302 (15)	0.0318 (15)	0.0266 (14)	−0.0079 (12)	−0.0003 (11)	−0.0103 (11)
O1	0.0380 (13)	0.0278 (12)	0.0275 (11)	−0.0134 (10)	−0.0080 (10)	−0.0050 (9)
Cl1	0.0448 (5)	0.0253 (4)	0.0362 (4)	−0.0102 (4)	−0.0048 (4)	−0.0122 (3)
Cl2	0.0371 (5)	0.0415 (5)	0.0266 (4)	−0.0135 (4)	−0.0016 (3)	−0.0155 (3)
Cl3	0.0348 (5)	0.0354 (5)	0.0302 (4)	−0.0070 (4)	−0.0047 (3)	−0.0018 (3)
Cl4	0.0467 (5)	0.0246 (4)	0.0485 (5)	−0.0071 (4)	−0.0019 (4)	−0.0144 (4)
Cl5	0.0395 (5)	0.0375 (5)	0.0331 (4)	−0.0119 (4)	0.0011 (3)	−0.0207 (3)

Geometric parameters (Å, º) top

C1—O1	1.313 (3)	C5—Cl4	1.713 (3)
C1—C6	1.394 (4)	C6—Cl5	1.731 (3)
C1—C2	1.409 (4)	C7—N1	1.338 (4)
C2—C3	1.388 (4)	C7—C8	1.372 (5)
C2—Cl1	1.717 (3)	C8—C9	1.378 (5)
C3—C4	1.386 (4)	C9—C10	1.387 (5)
C3—Cl2	1.727 (3)	C9—C12	1.503 (4)
C4—C5	1.388 (4)	C10—C11	1.373 (4)
C4—Cl3	1.720 (3)	C11—N1	1.339 (4)
C5—C6	1.391 (4)

O1—C1—C6	123.7 (3)	C4—C5—Cl4	119.7 (2)
O1—C1—C2	119.8 (3)	C6—C5—Cl4	120.4 (2)
C6—C1—C2	116.5 (3)	C5—C6—C1	122.5 (3)
C3—C2—C1	121.3 (3)	C5—C6—Cl5	119.9 (2)
C3—C2—Cl1	120.3 (2)	C1—C6—Cl5	117.7 (2)
C1—C2—Cl1	118.4 (2)	N1—C7—C8	122.1 (3)
C4—C3—C2	120.8 (3)	C7—C8—C9	120.1 (3)
C4—C3—Cl2	119.9 (2)	C8—C9—C10	117.2 (3)
C2—C3—Cl2	119.2 (2)	C8—C9—C12	121.9 (3)
C3—C4—C5	119.1 (3)	C10—C9—C12	120.9 (3)
C3—C4—Cl3	120.8 (2)	C11—C10—C9	120.4 (3)
C5—C4—Cl3	120.2 (2)	N1—C11—C10	121.5 (3)
C4—C5—C6	119.8 (3)	C7—N1—C11	118.8 (3)

(CNT1-RT) top

Crystal data top

C₆HCl₅O·C₆H₇N	F(000) = 360
M_r = 359.44	D_x = 1.653 Mg m⁻³
Triclinic, P1	Melting point: 75-79 K
a = 7.3857 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.9202 (10) Å	Cell parameters from 2874 reflections
c = 12.0227 (12) Å	θ = 3.3–24.8°
α = 69.770 (3)°	µ = 0.99 mm⁻¹
β = 85.869 (3)°	T = 298 K
γ = 76.324 (4)°	Needle, colorless
V = 722.10 (13) Å³	0.27 × 0.15 × 0.13 mm
Z = 2

Data collection top

Bruker P4 diffractometer	2799 independent reflections
Radiation source: fine-focus sealed tube	1751 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.039
ω scans	θ_max = 26.0°, θ_min = 3.3°
Absorption correction: empirical SADABS	h = −9→9
T_min = 0.836, T_max = 0.879	k = −11→11
6870 measured reflections	l = −14→14

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.129	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.0638P)²] where P = (F_o² + 2F_c²)/3
2799 reflections	(Δ/σ)_max = 0.001
193 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.1105 (4)	0.6719 (4)	0.7737 (3)	0.0408 (8)
C2	0.1617 (4)	0.5046 (4)	0.7895 (3)	0.0404 (8)
C3	0.2384 (4)	0.3884 (4)	0.8946 (3)	0.0433 (8)
C4	0.2641 (4)	0.4355 (4)	0.9899 (3)	0.0426 (8)
C5	0.2141 (4)	0.6015 (4)	0.9773 (3)	0.0406 (8)
C6	0.1394 (4)	0.7166 (4)	0.8713 (3)	0.0392 (8)
C7	0.6615 (6)	0.6777 (5)	0.5939 (3)	0.0561 (10)
C8	0.5069 (5)	0.6915 (5)	0.5312 (4)	0.0572 (10)
C9	0.4682 (5)	0.8100 (4)	0.4224 (3)	0.0519 (9)
C10	0.5902 (5)	0.9115 (5)	0.3811 (3)	0.0506 (9)
C11	0.7408 (5)	0.8926 (4)	0.4485 (3)	0.0506 (9)
C12	0.3014 (6)	0.8296 (6)	0.3485 (4)	0.0919 (15)
H12A	0.2092	0.7805	0.3989	0.138*
H12B	0.3396	0.7767	0.2906	0.138*
H12C	0.2495	0.9441	0.3089	0.138*
N1	0.7780 (4)	0.7767 (3)	0.5533 (2)	0.0507 (7)
O1	0.0424 (4)	0.7855 (3)	0.6742 (2)	0.0537 (6)
Cl1	0.12723 (13)	0.44496 (12)	0.67202 (8)	0.0598 (3)
Cl2	0.30288 (14)	0.18438 (11)	0.90896 (9)	0.0686 (3)
Cl3	0.35693 (13)	0.29155 (12)	1.12172 (8)	0.0633 (3)
Cl4	0.24580 (12)	0.66298 (12)	1.09406 (7)	0.0579 (3)
Cl5	0.07913 (13)	0.92079 (10)	0.85595 (8)	0.0585 (3)
H1	−0.059 (7)	0.780 (6)	0.639 (4)	0.124 (19)*
H7	0.695 (4)	0.597 (4)	0.668 (3)	0.057 (10)*
H8	0.433 (5)	0.617 (4)	0.568 (3)	0.073 (12)*
H10	0.567 (4)	0.994 (4)	0.313 (3)	0.045 (10)*
H11	0.824 (4)	0.957 (4)	0.424 (2)	0.041 (9)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0369 (18)	0.046 (2)	0.043 (2)	−0.0172 (15)	0.0022 (16)	−0.0147 (18)
C2	0.0381 (17)	0.0447 (19)	0.049 (2)	−0.0168 (15)	0.0065 (16)	−0.0248 (17)
C3	0.0348 (17)	0.0373 (18)	0.061 (2)	−0.0137 (14)	0.0064 (16)	−0.0181 (17)
C4	0.0334 (17)	0.046 (2)	0.0466 (19)	−0.0130 (15)	0.0030 (15)	−0.0113 (16)
C5	0.0337 (17)	0.053 (2)	0.0432 (19)	−0.0214 (16)	0.0056 (15)	−0.0197 (17)
C6	0.0340 (17)	0.0413 (18)	0.050 (2)	−0.0173 (14)	0.0080 (15)	−0.0201 (16)
C7	0.069 (3)	0.052 (2)	0.046 (2)	−0.017 (2)	−0.001 (2)	−0.013 (2)
C8	0.055 (2)	0.057 (2)	0.067 (3)	−0.025 (2)	0.012 (2)	−0.025 (2)
C9	0.048 (2)	0.053 (2)	0.063 (2)	−0.0023 (18)	−0.0047 (19)	−0.034 (2)
C10	0.056 (2)	0.046 (2)	0.043 (2)	−0.0017 (19)	−0.0043 (19)	−0.0133 (19)
C11	0.051 (2)	0.048 (2)	0.057 (2)	−0.0171 (19)	0.006 (2)	−0.0191 (19)
C12	0.063 (3)	0.107 (4)	0.115 (4)	−0.011 (2)	−0.030 (3)	−0.050 (3)
N1	0.0576 (19)	0.0523 (18)	0.0461 (17)	−0.0187 (15)	−0.0022 (15)	−0.0167 (16)
O1	0.0664 (17)	0.0485 (15)	0.0479 (15)	−0.0234 (13)	−0.0104 (13)	−0.0095 (12)
Cl1	0.0687 (6)	0.0658 (6)	0.0613 (6)	−0.0206 (5)	0.0060 (5)	−0.0394 (5)
Cl2	0.0736 (7)	0.0423 (5)	0.0915 (8)	−0.0109 (5)	−0.0021 (6)	−0.0256 (5)
Cl3	0.0578 (6)	0.0639 (6)	0.0557 (6)	−0.0133 (5)	−0.0059 (5)	−0.0037 (5)
Cl4	0.0612 (6)	0.0757 (7)	0.0487 (5)	−0.0237 (5)	−0.0005 (4)	−0.0304 (5)
Cl5	0.0725 (6)	0.0434 (5)	0.0672 (6)	−0.0168 (4)	−0.0069 (5)	−0.0243 (4)

Geometric parameters (Å, º) top

C1—O1	1.312 (4)	C5—Cl4	1.722 (3)
C1—C2	1.398 (4)	C6—Cl5	1.716 (3)
C1—C6	1.407 (4)	C7—N1	1.327 (4)
C2—C3	1.382 (4)	C7—C8	1.371 (5)
C2—Cl1	1.726 (3)	C8—C9	1.366 (5)
C3—C4	1.389 (4)	C9—C10	1.374 (5)
C3—Cl2	1.719 (3)	C9—C12	1.512 (5)
C4—C5	1.395 (4)	C10—C11	1.367 (5)
C4—Cl3	1.722 (3)	C11—N1	1.322 (4)
C5—C6	1.383 (4)

O1—C1—C2	123.7 (3)	C6—C5—Cl4	120.0 (2)
O1—C1—C6	119.8 (3)	C4—C5—Cl4	119.9 (2)
C2—C1—C6	116.5 (3)	C5—C6—C1	121.9 (3)
C3—C2—C1	122.2 (3)	C5—C6—Cl5	119.9 (2)
C3—C2—Cl1	120.0 (2)	C1—C6—Cl5	118.1 (2)
C1—C2—Cl1	117.7 (2)	N1—C7—C8	122.5 (4)
C2—C3—C4	120.2 (3)	C9—C8—C7	120.2 (4)
C2—C3—Cl2	120.6 (3)	C8—C9—C10	116.8 (3)
C4—C3—Cl2	119.2 (3)	C8—C9—C12	122.5 (4)
C3—C4—C5	119.0 (3)	C10—C9—C12	120.7 (4)
C3—C4—Cl3	120.6 (3)	C11—C10—C9	120.2 (3)
C5—C4—Cl3	120.4 (3)	N1—C11—C10	122.6 (4)
C6—C5—C4	120.1 (3)	C11—N1—C7	117.8 (3)

Footnotes

‡These authors contributed equally to this work.

§Present address: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland

Acknowledgements

LR and SJ thank the DST for a Young Scientist Fellowship. MB thanks the UGC for a Dr D. S. Kothari fellowship. GRD thanks the DST for a J. C. Bose Fellowship.

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Volume 4| Part 4| July 2017| Pages 466-475

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