An unusually short inter­molecular N—H⋯N hydrogen bond in crystals of the hemi-hydro­chloride salt of 1-exo-acetamido­pyrrolizidine

Bhardwaj, M.; Ai, Q.; Parkin, S.R.; Grossman, R.B.

doi:10.1107/S2056989019016517

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 76| Part 1| January 2020| Pages 77-81

https://doi.org/10.1107/S2056989019016517

Open

access

An unusually short intermolecular N—H⋯N hydrogen bond in crystals of the hemi-hydrochloride salt of 1-exo-acetamidopyrrolizidine

Minakshi Bhardwaj,^a Qianxiang Ai,^a Sean R. Parkin ^a and Robert B. Grossman ^a ^*

^aUniversity of Kentucky, Lexington, Kentucky, 40506-0055, USA
^*Correspondence e-mail: robert.grossman@uky.edu

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 4 December 2019; accepted 7 December 2019; online 1 January 2020)

The title compound [systematic name: (1R*, 8S)-2-acetamidooctahydropyrrolizin-4-ium chloride–N-[(1R, 8S)-hexahydro-1H-pyrrolizin-2-yl)acetamide (1/1)], 2(C₉H₁₆N₂O)·HCl or C₉H₁₇N₂O⁺·Cl⁻·C₉H₁₆N₂O, arose as an unexpected product when 1-exo-acetamidopyrrolizidine (AcAP; C₉H₁₆N₂O) was dissolved in CHCl₃. Within the AcAP pyrrolizidine group, the unsubstituted five-membered ring is disordered over two orientations in a 0.897 (5):0.103 (5) ratio. Two AcAP molecules related by a crystallographic twofold axis link to H⁺ and Cl⁻ ions lying on the rotation axis, thereby forming N—H⋯N and N—H⋯Cl⋯H—N hydrogen bonds. The first of these has an unusually short N⋯N separation of 2.616 (2) Å: refinement of different models against the present data set could not distinguish between a symmetrical hydrogen bond (H atom lying on the twofold axis and equidistant from the N atoms) or static or dynamic disorder models (i.e. N—H⋯N + N⋯H—N). Computational studies suggest that the disorder model is slightly more stable, but the energy difference is very small.

Keywords: crystal structure; short N—H⋯N hydrogen bond.

CCDC reference: 1970639

1. Chemical context

In the course of our ongoing studies on the biosynthesis of loline alkaloids (Schardl et al., 2007 ; Pan et al., 2018 ), we had occasion to prepare 1-exo-acetamidopyrrolizidine (C₉H₁₆N₂O; AcAP) by reduction of the corresponding oxime (Fig. 1) (Pan et al., 2014 ). As part of our effort to prove unambiguously that the major diastereomer obtained in this reaction was indeed the exo diastereomer, we attempted to obtain crystals of AcAP that were suitable for X-ray analysis. We obtained sufficiently high-quality crystals by recrystallization from CHCl₃, but to our surprise, the analysis showed that the crystals were not AcAP, but 2AcAP·HCl, with the HCl presumably originating from amine-promoted decomposition of CHCl₃. This paper describes the structure of crystalline 2AcAP·HCl, which features an unusually short ⁺N—H⋯N interaction.

Figure 1
Synthesis of AcAP.

2. Structural commentary

The molecular structure of AcAP recrystallized from CHCl₃ is a hemi-hydrochloride, 2AcAP·HCl (Fig. 2). Within the pyrrolizidine group, the unsubstituted five-membered ring is disordered over two orientations (Fig. 3). Each five-membered ring has an envelope conformation, but since the minor component occupancy is small [i.e., 0.103 (5) versus 0.897 (5)], we restrict further comment to the major component only. The `flap' atoms, C2 and C6, for the substituted (C1–C3/N4/C8) and unsubstituted (C5–C8/N4) rings, respectively, are displaced from the mean plane of the four remaining atoms (C1/C3/N4/C8 and C7/C5/N4/C8) by 0.622(1) and 0.633(2) Å, respectively. The dihedral angle between these mean planes is 56.07 (9)°. The acetamide group is characteristically almost planar (r.m.s. deviation = 0.0181 Å), but twisted from the mean plane of C1/C8/N4/C3 by a dihedral angle of 70.56 (7)°. Aside from an unusually short N—H⋯N hydrogen bond, which will be discussed in subsequent sections, all geometrical parameters are within their expected ranges (e.g., Allen et al., 1987 ).

Figure 2
An ellipsoid plot (50% probability) showing the molecular structure of 2AcAP·HCl. Unlabeled atoms are related to their labeled counterparts by a crystallographic twofold rotation (−x + 1, y, −z + $[{1\over 2}]$ ). The unusually short N—H⋯N hydrogen bond between the pyrrolizidine N atoms is highlighted by open dashed lines. Weaker N—H⋯Cl hydrogen bonds between the acetamide NH group and the Cl⁻ anion are shown as dotted lines.

Figure 3
An ellipsoid plot (50% probability) showing disorder of the non-substituted half of the pyrrolizidine ring. The refined major:minor component occupancy factors are 0.897 (5):0.103 (5).

3. Supramolecular features

The primary structural motif within crystals of 2AcAP·HCl consists of a pair of homochiral AcAP molecules hydrogen bonded to H⁺ and Cl⁻ ions about a crystallographic twofold axis of space group C2/c. Based on electron density alone, the H⁺ cation and Cl⁻ anion both appear to be located on the twofold axis. As a result of the twofold symmetry axis, the hydrogen bond N4—H4N⋯N4ⁱ [symmetry code: (i) −x + 1, y, −z + $[{1\over 2}]$ ] appears to be symmetric, and since d_N⋯N = 2.616 (2) Å (Table 1), it is exceptionally short (see Database survey section, below). Similarly, since the refined H⁺ position lies on the twofold axis and is equidistant from N4 and N4ⁱ, the refined N⋯H interatomic distance appears unusually long at 1.3080 (12) Å. The whole hydrogen-bonded ensemble makes an R₃³(12) supramolecular motif. For the short N4—H4N⋯N4ⁱ hydrogen bond, a difference-Fourier map (Fig. 4) clearly shows an elongated region of electron density centered on the twofold axis corresponding to the position of the refined H4N hydrogen atom. The true location of H4N, however, remains ambiguous based on X-ray data alone. Possibilities include strictly symmetric (i.e., on the twofold axis exactly halfway between N4 and N4ⁱ), statically disordered (i.e., 50% on each of N4 and N4ⁱ) or dynamically disordered (i.e., exchanging rapidly between N4 and N4ⁱ). Alternative strategies for H4N inclusion in the model refined equally well (see Refinement, below), so we settled on the simplest approach, following the recommendations of Fábry (2018 ). Nonetheless, the ambiguity prompted us to analyze the potential energy surface of the H4N position via computational methods for single versus double energy well character (see Computational analysis, below). In addition to the strong N—H⋯N hydrogen bond, weaker N2—H2—Cl1—H2ⁱ—N2ⁱ interactions link the twofold-related acetamide groups to the Cl⁻ anion [N⋯Cl = 3.2263 (11) Å]. The twist of the twofold-related hydrogen-bonded pyrrolizidine moieties relative to each other, as defined by the torsion angle C8—N4⋯N4ⁱ—C8ⁱ is −69.82 (16)°. The almost planar acetamide group forms a dihedral angle with its twofold-related counterpart of 20.18 (3)°. The only other intramolecular interactions are van der Waals contacts. Estimates of the relative fractions of intermolecular contacts between individual atom types derived from a Hirshfeld-surface analysis using CrystalExplorer (Turner et al., 2017 ; Tan et al., 2019 ) are complicated by the ring disorder and by the N4—H4N⋯N4ⁱ hydrogen bond. Nevertheless, all contacts appear to involve hydrogen atoms, with the overwhelming majority being H⋯H (65.3%). The Cl⁻ anion and the acetamide O atom each reside in pockets surrounded by hydrogen atoms, giving H⋯Cl/Cl⋯H (16.2%) and H⋯O/O⋯H (12.4%), with the remainder being N⋯H/H⋯N and C⋯H/H⋯C contacts.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4N⋯N4ⁱ	1.31 (1)	1.31 (1)	2.616 (2)	178 (3)
N2—H2N⋯Cl1	0.94 (2)	2.29 (2)	3.2263 (11)	176.4 (16)
Symmetry code: (i) $[-x+1, y, -z+{\script{1\over 2}}]$ .

Figure 4
A difference-Fourier map showing elongated electron density for the hydrogen atom involved in the short N—H⋯N hydrogen bond of 2AcAP·HCl.

4. Database survey

A search of the Cambridge Structure Database (version 5.40, Nov. 2018; Groom et al., 2016 ) on the bicyclic pyrrolizidine core of AcAP yielded 584 hits. Of these, 41 are protonated at the ring N atom, but only three of those bear a substituent (other than H) at the 1-position of the pyrrolizidine ring system (assuming standard IUPAC ring numbering). CSD entry BRPYLZ (Wilson & Sawicki, 1979 ) is a bromide salt of a bromine derivative, and CPYRZD (Soderberg, 1971 ) is a zwitterion, with a carboxylate group at the 1-position and a bromo substituent at the 2-position. The relative stereochemistry of BRPYLZ and CPYRZD, however, are different from AcAP. CSD entry EDOTUP (Bhardwaj et al., 2017 ) was a precursor to AcAP, and is the most closely related currently deposited structure.

The most striking feature of 2AcAP·HCl is the unusually short N—H⋯N hydrogen bond. A CSD search on the fragment `C-N(X)-H-N(X)-C′, where `X′ denotes `any group', gave 45 hits. Rejection of cases where apparent close N⋯N distances were due to disorder (four entries), and those in which the N-bound H atom was missing from the model (two entries), left 39 structures, of which three were duplicates. In the remaining 36 structures the N—H⋯N hydrogen bonds are intramolecular in 22 and intermolecular in 14. The closest N⋯N separations occur in the intramolecular N—H⋯N hydrogen-bonded structures, the shortest being 2.419 Å in EBOKOV (Wilkes et al., 2000 ). However, in these intramolecular cases, the N⋯N separation is largely dictated by the intramolecular geometry, which effectively forces the donor and acceptor N atoms into close proximity. Of the 14 CSD entries from the search that have intermolecular N—H⋯N hydrogen bonding, the closest N⋯N separation occurs in BECHOG (Glidewell & Holden, 1982 ), in which a bis(4-methylpyridine)hydrogen(I) cation sits on an inversion centre, giving an apparently symmetric N—H⋯N hydrogen bond with N⋯N distance of 2.610 (15) Å, and ROHTIR (Bock et al., 1997 ), for which the asymmetric unit contains two separate halves of a methylammonium-methylamine cation, [CH₃NH₂-H-NH₂CH₃]⁺, each sitting on centres of inversion, giving N⋯N distances of 2.620 and 2.641 Å. The N⋯N separation in 2AcAP·HCl is similar, at 2.616 (2) Å, although the difference is not significant, and well within the quoted precision estimate of BECHOG and the accuracy limits imposed by the spherical-atom scattering-factor approximation (see e.g., Dawson, 1964 ).

5. Computational analysis

A model consisting of the four 2AcAP·HCl units present in one unit cell was relaxed at the DFT level (see below for details), both with and without symmetry constraints on charge density. In the case where symmetry constraints were absent, a small displacement (0.06 Å) was applied to the hydrogen atom in the N—H⋯N hydrogen bond to break symmetry in the initial geometry. The relaxations led to two structures, one with constrained twofold symmetry (A), and one unconstrained (B). The volume difference between these theoretical models (calculations assumed absolute zero) was negligible (A_vol = 1918.85 Å³ versus B_vol = 1919.63 Å³). In the symmetric model, the N—H⋯N hydrogen atom (corresponding to H4 in the crystallographic model) is equidistant between the two nitrogen atoms (N—H = 1.290 Å), whereas in model B the N—H distances differ (N—H = 1.194 and 1.406 Å). This is in agreement with the computed charge-density line profile of N—H⋯N in structure B, as shown in Fig. 5. Structure B is calculated to be slightly more stable, but the energy difference (4.7 meV per unit cell) is vanishingly small (Fig. 6). The low energy barrier suggests dynamic disorder of the N—H⋯N hydrogen atom.

Figure 5
Computed charge-density line profile from nitrogen to nitrogen in the N—H⋯N hydrogen bond.

Figure 6
Computed potential-energy surface as a function of N—H⋯N hydrogen-atom displacement from the midpoint of the two nitrogen atoms.

Computational details: For this periodic system, density functional theory (DFT) calculations were carried out using the Vienna ab initio simulation Package (VASP) with Perdew–Burke–Ernzerhof (PBE) exchange-correlation functional (Kresse & Furthmüller, 1996a ,b ; Kresse et al., 1994 ; Perdew et al., 1996 ). The electron-ion interactions were described with the projector augmented-wave (PAW) method (Blöchl, 1994 ; Kresse & Joubert, 1999 ). The valence electronic wavefunctions were expanded on a plane-wave basis with a kinetic energy cutoff at 520 eV, and Gaussian smearing with a width of 0.05 eV was employed. The convergence criterion of the total energy was set to 10 ⁻⁵ eV in the self-consistent field loop. The Brillouin zone was sampled with a 1×2×2 Γ-centered grid. The experimental structures were relaxed until the Hellman–Feynman forces for each site were less than 0.005 eV Å⁻¹, and Grimme's DFT-D3 dispersion correction was applied with Becke–Johnson damping (Grimme et al., 2010 , 2011 ).

6. Synthesis and crystallization

AcAP was synthesized and purified according to the published procedure (Pan et al., 2014). Crystals of 2AcAP·HCl were obtained in the form of colorless plates by dissolving 20 mg of AcAP in 1 ml of CHCl₃ in a 10 ml round-bottom flask and allowing the solution to stand in a refrigerator for about a month.

7. Refinement

Crystal data, data collection, and structure refinement details are given in Table 2. Non-disordered carbon-bound H atoms were found in difference-Fourier maps, but subsequently included in the refinement using riding models, with constrained distances set to 0.98 Å (RCH₃), 0.99 Å (R₂CH₂) and 1.00 Å (R₃CH). Following the advice of Fábry (2018), the hydrogen atom involved in the short N—H⋯N hydrogen bond (H4N) was placed into difference-Fourier electron density and refined, albeit constrained to the twofold axis. An alternative model in which this H atom was allowed to ride at 50% occupancy on both N4 and N4ⁱ [symmetry code: (i) −x + 1, y, −z + $[{1\over 2}]$ ] refined equally well: the X-ray data alone being insufficient to establish a preference. The amide N—H hydrogen atom (H2N) was refined freely. U_iso(H) parameters for nitrogen-bound hydrogen atoms were refined, while for carbon-bound H atoms, U_iso(H) were set to values of either 1.2U_eq (R₃CH, R₂H₂) or 1.5U_eq (RCH₃) of the attached atom.

Table 2
Experimental details

Crystal data
Chemical formula	C₉H₁₇N₂O⁺·Cl⁻·C₉H₁₆N₂O
M_r	372.93
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	90
a, b, c (Å)	20.2125 (8), 9.6926 (4), 10.1458 (3)
β (°)	100.445 (1)
V (Å³)	1954.74 (13)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.22
Crystal size (mm)	0.40 × 0.36 × 0.04

Data collection
Diffractometer	Bruker D8 Venture dual source
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.885, 0.988
No. of measured, independent and observed [I > 2σ(I)] reflections	31903, 2235, 2096
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.096, 1.12
No. of reflections	2235
No. of parameters	144
No. of restraints	82
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.67, −0.22
Computer programs: APEX3 (Bruker, 2016 ), SHELXT (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ), XP in SHELXTL and SHELX (Sheldrick, 2008 ), CIFFIX (Parkin, 2013 ) and PLATON (Spek, 2009 ).

The refined displacement parameters for the Cl⁻ anion (e.g., Figs. 2 and 4) appear a little small compared to the rest of the structure. In addition, the largest residual difference map peaks (0.67 and 0.65 e Å⁻³) were close (0.37 and 0.47 Å respectively) to Cl1. Refinement of the anion as mixed Cl and Br gave an occupancy ratio of 0.934 (2):0.066 (2), a lower R-value (3.02%), and a flatter difference map (Δρ = 0.29/-0.19 e Å⁻³). However, the reaction included no known source of Br⁻, so the mixed anion model was not retained.

To ensure satisfactory refinement for disordered groups in the structure, a combination of constraints and restraints were employed. The constraints (SHELXL commands EXYZ and EADP) were used to fix overlapping fragments. Restraints were used to ensure the integrity of ill-defined or disordered groups (SHELXL commands SAME, SIMU, and RIGU). An alternative model using space group Cc (50:50 inversion twinned) was considered but rejected as it required hefty restraints and did not resolve the H4N atom ambiguity.

Supporting information

CCDC reference: 1970639

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989019016517/hb7870sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019016517/hb7870Isup2.hkl

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: APEX3 (Bruker, 2016); data reduction: APEX3 (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX (Sheldrick, 2008), CIFFIX (Parkin, 2013) and PLATON (Spek, 2009).

(1R*, 8S)-2-acetamidooctahydropyrrolizin-4-ium chloride–N-[(1R, 8S)hexahydro-1H-pyrrolizin-2-yl)acetamide (1/1) top

Crystal data top

C₉H₁₇N₂O⁺·Cl⁻·C₉H₁₆N₂O	F(000) = 808
M_r = 372.93	D_x = 1.267 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 20.2125 (8) Å	Cell parameters from 9978 reflections
b = 9.6926 (4) Å	θ = 2.3–27.5°
c = 10.1458 (3) Å	µ = 0.22 mm⁻¹
β = 100.445 (1)°	T = 90 K
V = 1954.74 (13) Å³	Plate, colourless
Z = 4	0.40 × 0.36 × 0.04 mm

Data collection top

Bruker D8 Venture dual source diffractometer	2235 independent reflections
Radiation source: microsource	2096 reflections with I > 2σ(I)
Detector resolution: 7.41 pixels mm^-1	R_int = 0.032
φ and ω scans	θ_max = 27.5°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −26→26
T_min = 0.885, T_max = 0.988	k = −12→12
31903 measured reflections	l = −11→13

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.096	w = 1/[σ²(F_o²) + (0.0375P)² + 2.4571P] where P = (F_o² + 2F_c²)/3
S = 1.12	(Δ/σ)_max < 0.001
2235 reflections	Δρ_max = 0.67 e Å⁻³
144 parameters	Δρ_min = −0.22 e Å⁻³
82 restraints	Extinction correction: SHELXL-2018/3 (Sheldrick 2018), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.005 (1)

Special details top

Experimental. The crystal was mounted using polyisobutene oil on the tip of a fine glass fibre, which was fastened in a copper mounting pin with electrical solder. It was placed directly into the cold gas stream of a liquid-nitrogen based cryostat (Hope, 1994; Parkin & Hope, 1998).

Diffraction data were collected with the crystal at 90K, which is standard practice in this laboratory for the majority of flash-cooled crystals.

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

Refinement. Refinement progress was checked using PLATON (Spek, 2009) and by an R-tensor (Parkin, 2000). The final model was further checked with the IUCr utility checkCIF.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
C1	0.63783 (6)	0.58377 (14)	0.26083 (13)	0.0182 (3)
H1	0.684523	0.622089	0.275591	0.022*
C2	0.60256 (7)	0.61745 (15)	0.11816 (14)	0.0229 (3)
H2A	0.632627	0.601397	0.052759	0.027*
H2B	0.561093	0.562062	0.092144	0.027*
C3	0.58652 (7)	0.76915 (15)	0.12835 (14)	0.0232 (3)
H3A	0.626574	0.826636	0.124182	0.028*
H3B	0.549608	0.797166	0.055229	0.028*
N4	0.56555 (6)	0.78256 (11)	0.26254 (11)	0.0184 (3)
H4N	0.500000	0.781 (3)	0.250000	0.056 (9)*
C5	0.5885 (2)	0.9121 (2)	0.3373 (3)	0.0249 (7)	0.897 (5)
H5A	0.554374	0.945176	0.388570	0.030*	0.897 (5)
H5B	0.597261	0.985720	0.275018	0.030*	0.897 (5)
C6	0.65299 (9)	0.87111 (17)	0.43106 (16)	0.0237 (4)	0.897 (5)
H6A	0.663640	0.935711	0.507555	0.028*	0.897 (5)
H6B	0.691530	0.867102	0.383296	0.028*	0.897 (5)
C7	0.63499 (12)	0.7276 (2)	0.4771 (2)	0.0209 (5)	0.897 (5)
H7A	0.675941	0.673734	0.512861	0.025*	0.897 (5)
H7B	0.606530	0.733983	0.546696	0.025*	0.897 (5)
C8	0.59630 (6)	0.66296 (13)	0.34850 (13)	0.0178 (3)	0.897 (5)
H8	0.559801	0.602145	0.370299	0.021*	0.897 (5)
C5'	0.595 (2)	0.9165 (19)	0.322 (2)	0.0249 (7)	0.103 (5)
H5'A	0.561158	0.991410	0.308580	0.030*	0.103 (5)
H5'B	0.634307	0.944647	0.282171	0.030*	0.103 (5)
C6'	0.6157 (9)	0.8793 (15)	0.4690 (15)	0.032 (3)	0.103 (5)
H6'A	0.576222	0.871718	0.513823	0.039*	0.103 (5)
H6'B	0.647840	0.947113	0.517395	0.039*	0.103 (5)
C7'	0.6489 (11)	0.739 (2)	0.458 (2)	0.030 (4)	0.103 (5)
H7'A	0.655595	0.689122	0.544614	0.036*	0.103 (5)
H7'B	0.692818	0.749314	0.428958	0.036*	0.103 (5)
C8'	0.59630 (6)	0.66296 (13)	0.34850 (13)	0.0178 (3)	0.103 (5)
H8'	0.563026	0.605013	0.385455	0.021*	0.103 (5)
N2	0.64091 (6)	0.43798 (12)	0.29157 (11)	0.0184 (3)
H2N	0.6002 (10)	0.390 (2)	0.2837 (19)	0.035 (5)*
C9	0.69841 (6)	0.36514 (14)	0.31606 (12)	0.0178 (3)
O1	0.75448 (5)	0.41694 (11)	0.32142 (11)	0.0260 (2)
C10	0.68897 (7)	0.21311 (14)	0.33748 (14)	0.0224 (3)
H10A	0.715908	0.185291	0.423611	0.034*
H10B	0.703494	0.160954	0.265024	0.034*
H10C	0.641361	0.194212	0.337727	0.034*
Cl1	0.500000	0.27309 (5)	0.250000	0.02141 (15)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0169 (6)	0.0170 (6)	0.0210 (6)	−0.0016 (5)	0.0044 (5)	0.0007 (5)
C2	0.0266 (7)	0.0247 (7)	0.0185 (6)	−0.0007 (5)	0.0071 (5)	0.0009 (5)
C3	0.0240 (7)	0.0244 (7)	0.0214 (7)	−0.0021 (5)	0.0041 (5)	0.0056 (5)
N4	0.0201 (5)	0.0139 (5)	0.0201 (6)	−0.0016 (4)	0.0006 (4)	0.0003 (4)
C5	0.0284 (13)	0.0147 (7)	0.0291 (10)	−0.0044 (6)	−0.0014 (9)	−0.0013 (6)
C6	0.0240 (9)	0.0220 (8)	0.0234 (8)	−0.0059 (6)	0.0001 (6)	−0.0025 (6)
C7	0.0237 (10)	0.0206 (8)	0.0174 (9)	0.0000 (7)	0.0015 (7)	−0.0004 (7)
C8	0.0189 (6)	0.0154 (6)	0.0187 (6)	0.0002 (5)	0.0020 (5)	0.0012 (5)
C5'	0.0284 (13)	0.0147 (7)	0.0291 (10)	−0.0044 (6)	−0.0014 (9)	−0.0013 (6)
C6'	0.033 (7)	0.028 (5)	0.033 (5)	−0.003 (5)	−0.001 (5)	−0.008 (4)
C7'	0.034 (8)	0.034 (6)	0.017 (7)	0.002 (6)	−0.003 (6)	−0.006 (5)
C8'	0.0189 (6)	0.0154 (6)	0.0187 (6)	0.0002 (5)	0.0020 (5)	0.0012 (5)
N2	0.0175 (5)	0.0155 (6)	0.0228 (6)	−0.0015 (4)	0.0049 (4)	−0.0005 (4)
C9	0.0200 (6)	0.0191 (6)	0.0142 (6)	−0.0007 (5)	0.0028 (5)	−0.0010 (5)
O1	0.0179 (5)	0.0247 (5)	0.0349 (6)	−0.0010 (4)	0.0029 (4)	0.0037 (4)
C10	0.0246 (7)	0.0178 (7)	0.0239 (7)	0.0004 (5)	0.0022 (5)	−0.0015 (5)
Cl1	0.0099 (2)	0.0177 (2)	0.0354 (3)	0.000	0.00096 (16)	0.000

Geometric parameters (Å, º) top

C1—N2	1.4460 (17)	C6—H6B	0.9900
C1—C2	1.5284 (19)	C7—C8	1.529 (2)
C1—C8	1.5347 (18)	C7—H7A	0.9900
C1—C8'	1.5347 (18)	C7—H7B	0.9900
C1—H1	1.0000	C8—H8	1.0000
C2—C3	1.513 (2)	C5'—C6'	1.521 (18)
C2—H2A	0.9900	C5'—H5'A	0.9900
C2—H2B	0.9900	C5'—H5'B	0.9900
C3—N4	1.5032 (18)	C6'—C7'	1.528 (17)
C3—H3A	0.9900	C6'—H6'A	0.9900
C3—H3B	0.9900	C6'—H6'B	0.9900
N4—H4N	1.3080 (12)	C7'—C8'	1.576 (16)
N4—C5	1.497 (2)	C7'—H7'A	0.9900
N4—C5'	1.507 (17)	C7'—H7'B	0.9900
N4—C8	1.5146 (16)	C8'—H8'	1.0000
N4—C8'	1.5146 (16)	N2—C9	1.3439 (17)
N4—H4N	1.3080 (12)	N2—H2N	0.94 (2)
C5—C6	1.520 (4)	C9—O1	1.2317 (16)
C5—H5A	0.9900	C9—C10	1.5066 (19)
C5—H5B	0.9900	C10—H10A	0.9800
C6—C7	1.532 (3)	C10—H10B	0.9800
C6—H6A	0.9900	C10—H10C	0.9800

N2—C1—C2	114.05 (11)	C8—C7—C6	102.97 (16)
N2—C1—C8	111.75 (11)	C8—C7—H7A	111.2
C2—C1—C8	103.41 (11)	C6—C7—H7A	111.2
N2—C1—C8'	111.75 (11)	C8—C7—H7B	111.2
C2—C1—C8'	103.41 (11)	C6—C7—H7B	111.2
N2—C1—H1	109.1	H7A—C7—H7B	109.1
C2—C1—H1	109.1	N4—C8—C7	105.73 (12)
C8—C1—H1	109.1	N4—C8—C1	105.05 (10)
C3—C2—C1	102.22 (11)	C7—C8—C1	116.80 (13)
C3—C2—H2A	111.3	N4—C8—H8	109.7
C1—C2—H2A	111.3	C7—C8—H8	109.7
C3—C2—H2B	111.3	C1—C8—H8	109.7
C1—C2—H2B	111.3	N4—C5'—C6'	101.8 (12)
H2A—C2—H2B	109.2	N4—C5'—H5'A	111.4
N4—C3—C2	104.18 (11)	C6'—C5'—H5'A	111.4
N4—C3—H3A	110.9	N4—C5'—H5'B	111.4
C2—C3—H3A	110.9	C6'—C5'—H5'B	111.4
N4—C3—H3B	110.9	H5'A—C5'—H5'B	109.3
C2—C3—H3B	110.9	C5'—C6'—C7'	100.7 (16)
H3A—C3—H3B	108.9	C5'—C6'—H6'A	111.6
H4N—N4—C5	106.1 (12)	C7'—C6'—H6'A	111.6
H4N—N4—C3	110.96 (17)	C5'—C6'—H6'B	111.6
C5—N4—C3	114.78 (16)	C7'—C6'—H6'B	111.6
H4N—N4—C5'	112 (2)	H6'A—C6'—H6'B	109.4
C3—N4—C5'	106.2 (15)	C6'—C7'—C8'	102.6 (11)
H4N—N4—C8	110.4 (12)	C6'—C7'—H7'A	111.2
C5—N4—C8	107.04 (14)	C8'—C7'—H7'A	111.2
C3—N4—C8	107.55 (10)	C6'—C7'—H7'B	111.2
H4N—N4—C8'	110.4 (12)	C8'—C7'—H7'B	111.2
C3—N4—C8'	107.55 (10)	H7'A—C7'—H7'B	109.2
C5'—N4—C8'	109.8 (9)	N4—C8'—C1	105.05 (10)
H4N—N4—H4N	0 (3)	N4—C8'—C7'	101.6 (8)
C5—N4—H4N	106.1 (12)	C1—C8'—C7'	105.9 (9)
C3—N4—H4N	110.96 (17)	N4—C8'—H8'	114.3
C5'—N4—H4N	112 (2)	C1—C8'—H8'	114.3
C8—N4—H4N	110.4 (12)	C7'—C8'—H8'	114.3
C8'—N4—H4N	110.4 (12)	C9—N2—C1	123.73 (11)
N4—C5—C6	104.5 (2)	C9—N2—H2N	118.0 (12)
N4—C5—H5A	110.9	C1—N2—H2N	117.9 (12)
C6—C5—H5A	110.9	O1—C9—N2	123.50 (13)
N4—C5—H5B	110.9	O1—C9—C10	122.14 (13)
C6—C5—H5B	110.9	N2—C9—C10	114.37 (12)
H5A—C5—H5B	108.9	C9—C10—H10A	109.5
C5—C6—C7	101.78 (16)	C9—C10—H10B	109.5
C5—C6—H6A	111.4	H10A—C10—H10B	109.5
C7—C6—H6A	111.4	C9—C10—H10C	109.5
C5—C6—H6B	111.4	H10A—C10—H10C	109.5
C7—C6—H6B	111.4	H10B—C10—H10C	109.5
H6A—C6—H6B	109.3

N2—C1—C2—C3	162.24 (11)	N2—C1—C8—C7	93.71 (16)
C8—C1—C2—C3	40.67 (13)	C2—C1—C8—C7	−143.19 (14)
C8'—C1—C2—C3	40.67 (13)	H4N—N4—C5'—C6'	97 (2)
C1—C2—C3—N4	−39.46 (13)	C3—N4—C5'—C6'	−142 (2)
C2—C3—N4—H4N	−97.5 (15)	C8'—N4—C5'—C6'	−26 (3)
C2—C3—N4—C5	142.30 (19)	N4—C5'—C6'—C7'	45 (3)
C2—C3—N4—C5'	140.9 (15)	C5'—C6'—C7'—C8'	−47 (2)
C2—C3—N4—C8	23.32 (13)	H4N—N4—C8'—C1	123.3 (9)
C2—C3—N4—C8'	23.32 (13)	C3—N4—C8'—C1	2.12 (13)
H4N—N4—C5—C6	141.3 (8)	C5'—N4—C8'—C1	−113 (2)
C3—N4—C5—C6	−95.81 (19)	H4N—N4—C8'—C7'	−126.5 (13)
C8—N4—C5—C6	23.5 (3)	C3—N4—C8'—C7'	112.3 (10)
N4—C5—C6—C7	−39.9 (3)	C5'—N4—C8'—C7'	−3 (2)
C5—C6—C7—C8	40.9 (2)	N2—C1—C8'—N4	−149.53 (11)
H4N—N4—C8—C7	−112.6 (9)	C2—C1—C8'—N4	−26.43 (13)
C5—N4—C8—C7	2.4 (2)	N2—C1—C8'—C7'	103.4 (9)
C3—N4—C8—C7	126.23 (14)	C2—C1—C8'—C7'	−133.5 (9)
H4N—N4—C8—C1	123.3 (9)	C6'—C7'—C8'—N4	30.6 (18)
C5—N4—C8—C1	−121.70 (19)	C6'—C7'—C8'—C1	140.1 (14)
C3—N4—C8—C1	2.12 (13)	C2—C1—N2—C9	113.29 (14)
C6—C7—C8—N4	−26.97 (19)	C8—C1—N2—C9	−129.88 (13)
C6—C7—C8—C1	89.41 (17)	C8'—C1—N2—C9	−129.88 (13)
N2—C1—C8—N4	−149.53 (11)	C1—N2—C9—O1	3.8 (2)
C2—C1—C8—N4	−26.43 (13)	C1—N2—C9—C10	−176.47 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4N···N4ⁱ	1.31 (1)	1.31 (1)	2.616 (2)	178 (3)
N2—H2N···Cl1	0.94 (2)	2.29 (2)	3.2263 (11)	176.4 (16)

Symmetry code: (i) −x+1, y, −z+1/2.

Acknowledgements

Supercomputing resources on the Lipscomb High-Performance Computing Cluster were provided by the University of Kentucky Information Technology Department and Center for Computational Sciences (CCS).

Funding information

Funding for this research was provided by: The National Science Foundation (MRI-CHE1625732 to SRP), and by the University of Kentucky. QA acknowledges the NSF under Award DMR-1627428.

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc., Perkin Trans. 2, pp. S1–S19. Google Scholar
Bhardwaj, M., Parkin, S. & Grossman, R. B. (2017). Private communication (refcode EDOTUP). CCDC, Cambridge, England. Google Scholar
Blöchl, P. E. (1994). Phys. Rev. B, 50, 17953–17979. CrossRef Web of Science Google Scholar
Bock, H., Vaupel, T. & Schödel, H. (1997). J. Prakt. Chem. 339, 26–37. CSD CrossRef CAS Web of Science Google Scholar
Bruker (2016). APEX3. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dawson, B. (1964). Acta Cryst. 17, 990–996. CrossRef IUCr Journals Web of Science Google Scholar
Fábry, J. (2018). Acta Cryst. E74, 1344–1357. Web of Science CSD CrossRef IUCr Journals Google Scholar
Glidewell, C. & Holden, H. D. (1982). Acta Cryst. B38, 667–669. CSD CrossRef CAS IUCr Journals Google Scholar
Grimme, S., Antony, J., Ehrlich, S. & Krieg, H. (2010). J. Chem. Phys. 132, 154104. Web of Science CrossRef PubMed Google Scholar
Grimme, S., Ehrlich, S. & Goerigk, L. (2011). J. Comput. Chem. 32, 1456–1465. Web of Science CrossRef CAS PubMed Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Kresse, G. & Furthmüller, J. (1996a). Comput. Mater. Sci. 6, 15–50. CrossRef CAS Web of Science Google Scholar
Kresse, G. & Furthmüller, J. (1996b). Phys. Rev. B, 54, 11169–11186. CrossRef CAS Web of Science Google Scholar
Kresse, G., Furthmüller, J. & Hafner, J. (1994). Phys. Rev. B, 50, 13181–13185. CrossRef CAS Google Scholar
Kresse, G. & Joubert, D. (1999). Phys. Rev. B, 59, 1758–1775. Web of Science CrossRef CAS Google Scholar
Pan, J., Bhardwaj, M., Faulkner, J. R., Nagabhyru, P., Charlton, N. D., Higashi, R. M., Miller, A.-F., Young, C. A., Grossman, R. B. & Schardl, C. L. (2014). Phytochemistry, 98, 60–68. CrossRef CAS PubMed Google Scholar
Pan, J., Bhardwaj, M., Zhang, B., Chang, W.-C., Schardl, C. L., Krebs, C., Grossman, R. B. & Bollinger, J. M. (2018). Biochemistry, 57, 2074–2083. CrossRef CAS PubMed Google Scholar
Parkin, S. (2013). CIFFIX. https://xray.uky.edu/Resources/scripts/ciffix Google Scholar
Perdew, J. P., Burke, K. & Ernzerhof, M. (1996). Phys. Rev. Lett. 77, 3865–3868. CrossRef PubMed CAS Web of Science Google Scholar
Schardl, C. L., Grossman, R. B., Nagabhyru, P., Faulkner, J. R. & Mallik, U. P. (2007). Phytochemistry, 68, 980–996. CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Soderberg, E. (1971). Acta Chem. Scand., 25, 615–624. CAS Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tan, S. L., Jotani, M. M. & Tiekink, E. R. T. (2019). Acta Cryst. E75, 308–318. Web of Science CrossRef IUCr Journals Google Scholar
Turner, M. J., Mckinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer 17. The University of Western Australia. Google Scholar
Wilkes, E. N., Hambley, T. W., Lawrance, G. A. & Maeder, M. (2000). Aust. J. Chem. 53, 517–521. CSD CrossRef CAS Google Scholar
Wilson, S. R. & Sawicki, R. A. (1979). J. Org. Chem. 44, 287–291. CSD CrossRef CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.