Crystal structure of 5-(dibenzo­furan-4-yl)-2′-deoxy­uridine

De­oxy­uridine substituted by dibenzo­furanyl at the carbon atom in base position C⁵ was synthesized and structurally characterized. The coupling was achieved by a Suzuki–Miyaura reaction utilizing the PTABS ligand and palladium(II) acetate.

Abstract

The mol­ecule of the title compound, C₂₁H₁₈N₂O₆, has a bent rather than a linear conformation supported by three intra­molecular C—H⋯O hydrogen bonds. The packing in the crystal lattice is largely determined by inter­actions between hydrogen atoms with oxygen atom lone pairs with one mol­ecule inter­acting with neigbouring mol­ecules via O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds. The title compound crystallizes in the chiral ortho­rhom­bic space group P2₁2₁2₁. Its absolute structure could not be determined crystallographically and was assumed with reference to that of the reactant 5-iodo-2′-de­oxy­uridine.

Chemical context  

As a result of their numerous applications, synthetically modified nucleoside analogues have attracted much attention in recent years. Many of these modified nucleosides show potential activity as drug candidates, biological probes etc (Huryn & Okabe, 1992 ▸). Modern trends in this field of research consider palladium complexes to be active catalysts for the efficient modification of nucleosides because of their greater ability to perform such catalytic processes in aqueous media (Agrofoglio et al., 2003 ▸; Kapdi et al., 2014 ▸). Base modification in purine and pyrimidine nucleosides, resulting in a new class of compounds with better fluorescence properties, enhancing their chances of being employed as biological probes for studying biological environments such as DNA damage, protein–DNA inter­actions and DNA probes is of great inter­est to chemical biologists as well as bio-organic chemists (Tanpure et al., 2013 ▸). Structural elucidation of such compounds is an important task in order to understand the mechanistic pathways. Herein we present the synthesis and the crystal structure of the title compound, 5-(dibenzo­furan-4-yl)-2′-de­oxy­uridine.

Structural commentary  

The title compound crystallizes in the ortho­rhom­bic space group P2₁2₁2₁ with four mol­ecules in the unit cell. The two aromatic π systems (pyrimidine and dibenzo­furan­yl), which are connected by a C—C bond [C7—C10 = 1.489 (6) Å] subtend a dihedral angle of 30.7 (2)° (Fig. 1 ▸). All bond lengths or angles are comparable to those in related compounds. Fifty two entries can be found in the Cambridge Crystallographic Database (ConQuest Version 1.19; Groom et al., 2016 ▸) for de­oxy­uridine with a substituent only in the C⁵ position of the base (i.e. C7 here) and neither substituents nor protecting groups anywhere else, nine of which are for compounds that had already been characterized (i.e. repeats, polymorphs, present/absent solvent). The bond lengths of the pyrimidine moiety observed for the title compound are very close to the average values found for related structures (see Table S1 in the Supporting information). As is typical for this class of compounds, the bond usually assigned to be a double bond within the six-membered ring (here C6=C7) is the shortest for the pyrimidine ring at 1.353 (6) Å and the bond between the second carbonyl carbon atom and the substituted carbon (here C7—C8) is the longest at 1.447 (6) Å. All four other ring atom-to-ring atom distances (N—C and C—C bonds) are shorter than 1.393 Å, indicating significant π-electron delocal­ization throughout the pyrimidine base. All this, however, is in accordance with the majority of previously reported structures.

Figure 1.

The mol­ecular structure of the title compound, showing the atom labelling and 50% probability displacement ellipsoids. Atom C7 is in the C⁵ position of the pyrimidine base according to nucleoside/nucleotide nomenclature, atom C6 in C⁶.

The relative orientation between sugar and base moieties in the title compound is also comparable with compounds in the database. The hydrogen-bonding inter­action (or distance) between the C⁶-H function (here C6) and the ring oxygen atom of the sugar (here O3) and/or the –CH₃–OH group (here O1) is useful for evaluation in this context. The C—H⋯O hydrogen-to-oxygen distances for the inter­action with the alcohol range from 2.29 to 5.98 Å (when the –CH₃–OH moiety is pointing directly towards the C–H or completely turned away, respectively; Moore et al., 1989 ▸; Basnak et al., 1996 ▸). The C—H⋯O hydrogen-to-oxygen distances for the inter­action with the furane ring oxygen atom (here O3) range from 2.26 to 3.43 Å (Greco & Tor, 2007 ▸; Basnak et al., 1996 ▸) with the vast majority of orientations allowing at least weak hydrogen bonding between this oxygen and the C⁶–H hydrogen atom. No systematic dependency between these two groups of distances was found, i.e. a very short or long hydrogen bond with the ring oxygen atom does neither lead to particularly short nor long distances of the hydrogen atom to the methanoyl oxygen atom.

Only five of the related archived structures bear directly attached aromatic π-systems. In all five cases, the orientation of the sugar and the pyrimidine moieties are relatively similar in which the C⁶–H moiety points to some extent towards the methanoyl oxygen atom of the sugar, forming a weak intra­molecular hydrogen bond and resulting in comparable mol­ecular bends. The dihedral angles between the two aromatic systems do vary and range from 11.9° for a ferrocene substituent (Song et al., 2006 ▸) to 37.2° for a para-biphenyl substituent (Gayakhe et al., 2016 ▸), indicating that the extent of delocalization of the π-systems depends on the actual type of aromatic substituent but is not particularly strong in any case.

Supra­molecular Features  

In the crystal, mol­ecules are linked by N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonds (Fig. 2 ▸ and Table 1 ▸). The mol­ecules form rows propagating along the a-axis direction, which are connected to adjacent rows in the c-axis direction by classical hydrogen bonds and in the b-axis direction only by weaker C—H⋯O contacts between two sugar moieties (C4—H4A⋯O3ⁱ, two-directional). In the c- and (by bifurcation) a-axis directions, both classical and non-classical hydrogen bonds are present (O2–H2O⋯O5ⁱⁱ; O1—H1O⋯O2^iv; N2—H2N⋯O1ⁱⁱⁱ; C13—H13⋯O4; C14—H14⋯O4ⁱⁱ). These interactions lead to the formation of slabs lying parallel to the ac plane.

Figure 2.

The crystal packing (Mercury; Macrae et al., 2006 ▸) viewed along the a axis showing the classical hydrogen bonds which lead to a two-dimensional network parallel to (010).

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4A⋯O3i	0.99	2.61	3.439 (6)	142
C6—H6⋯O6	0.95	2.34	2.915 (5)	119
C13—H13⋯O1	0.95	2.58	3.271 (6)	130
C21—H21⋯O5	0.95	2.33	2.876 (6)	116
C14—H14⋯O4ii	0.95	2.45	3.115 (6)	127
O2—H2O⋯O5ii	1.00 (5)	1.72 (5)	2.716 (5)	174 (5)
N2—H2N⋯O1iii	0.91 (5)	2.30 (5)	3.144 (5)	154 (5)
O1—H1O⋯O2iv	0.92 (6)	2.10 (6)	2.922 (5)	148 (6)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Synthesis and crystallization  

The title compound was synthesized according to our recently reported method (Bhilare et al., 2016 ▸). This involves the cross-coupling reaction of 5-iodo-2′-deoxyuridine and 4-(dibenzofuranyl)boronic acid in the presence of Pd(OAc)₂ and PTBS (phospha-triaza-adamantyl propane sulfonate) in water.

Synthesis of 5-(dibenzo­furan-4-yl)-2′-de­oxy­uridine: To a solution of palladium acetate (1.12 mg, 1.0 mol %) and PTABS ligand (2.93 mg, 2.0 mol %) in degassed water (1.0 ml) at ambient temperature under N₂ were added 5-iodo-2′-de­oxy­uridine (0.5 mmol) and the solution stirred for 5 min at 353 K. After that, the reaction mixture was allowed to cool to room temperature and then 4-(dibenzo­furan­yl)boronic acid (0.75 mmol) was added along with tri­ethyl­amine (0.14 ml, 1.0 mmol) and degassed water (2.0 ml). The resulting solution was then stirred at 353 K for 3 h. The reaction progress was monitored by TLC. After the completion of reaction, the solvent was removed in vacuo and the resultant residue obtained was purified using column chromatography in CH₂Cl₂:MeOH solvent system (96:4) to afford the desired product as a white solid (162 mg, 82% yield).

UV–visible absorption and fluorescence emission in methanol (10 µM) λ_abs = 286 nm λ_fl = 392,427. ¹H NMR (400 MHz, DMSO-d ₆) δ 11.62 (s, 1H), 8.41 (s, 1H), 8.12 (d, J = 7.4 Hz, 1H), 8.06 (d, J = 7.7 Hz, 1H), 7.67 (t, J = 7.8 Hz, 2H), 7.49 (t, J = 7.7 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 6.28 (t, J = 6.7 Hz, 1H), 5.29 (d, J = 3.8 Hz, 1H), 4.87 (t, J = 4.9 Hz, 1H), 4.27 (s, 1H), 3.81 (d, J = 2.9 Hz, 1H), 3.54 (s, 2H), 2.29–2.14 (m, 2H). ¹³C NMR (101 MHz, DMSO-d ₆) δ 161.7, 155.3, 152.9, 150.0, 140.1, 128.3, 127.6, 123.8, 123.6, 123.2, 122.8, 121.1, 120.3, 117.8, 111.7, 108.8, 87.6, 84.5, 70.5, 61.4, 39.9. ESI–MS (m/z) = 395 (M ⁺ + H⁺). Analysis calculated for C₂₁H₁₈N₂O₆: C, 63.96; H, 4.60; N, 7.10. Found: C, 63.85; H, 4.64; N, 6.98.

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The two protons on oxygen (O1, O2) and the one on nitro­gen (N2) were located and refined with a constraint for the atom—H distance (SHELXL instruction: SADI 0.05 O1 H1O O2 H2O N2 H2N), as otherwise the N—H distance became rather short and the O—H distances rather long. The respective orientations, i.e. the directions the hydrogen atoms are pointing to (particularly important for the alcohol functions), were refined without any restraints or constraints. The C-bound H atoms were included in calculated positions and treated as riding: C—H = 0.95–1.00 Å with U _iso(H) = 1.2U _eq(C).

Table 2. Experimental details.

Crystal data
Chemical formula	C21H18N2O6
M r	394.37
Crystal system, space group	Orthorhombic, P212121
Temperature (K)	170
a, b, c (Å)	6.2899 (13), 15.167 (3), 17.938 (4)
V (Å3)	1711.2 (6)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.11
Crystal size (mm)	0.46 × 0.09 × 0.09
Data collection
Diffractometer	Stoe IPDS2T
Absorption correction	Numerical face indexed (X-RED32 and X-SHAPE; Stoe & Cie, 2010 ▸)
T min, T max	0.388, 0.875
No. of measured, independent and observed [I > 2σ(I)] reflections	14640, 3696, 2704
R int	0.110
(sin θ/λ)max (Å−1)	0.642
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.057, 0.143, 0.96
No. of reflections	3696
No. of parameters	274
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.34, −0.37

Computer programs: X-AREA (Stoe & Cie, 2010 ▸), SHELXT2014 (Sheldrick, 2015a ▸), SHELXL2013 (Sheldrick, 2015b ▸), XP in SHELXTL and CIFTAB (Sheldrick, 2008 ▸), Mercury (Macrae et al., 2006 ▸) and PLATON (Spek, 2009 ▸).

Supplementary Material

CCDC reference: 1574284

Additional supporting information: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Crystal data

C21H18N2O6	Dx = 1.531 Mg m−3
Mr = 394.37	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 14682 reflections
a = 6.2899 (13) Å	θ = 6.5–54.3°
b = 15.167 (3) Å	µ = 0.11 mm−1
c = 17.938 (4) Å	T = 170 K
V = 1711.2 (6) Å3	Needle, colourless
Z = 4	0.46 × 0.09 × 0.09 mm
F(000) = 824

Data collection

Stoe IPDS2T diffractometer	3696 independent reflections
Radiation source: fine-focus sealed tube	2704 reflections with I > 2σ(I)
Detector resolution: 6.67 pixels mm-1	Rint = 0.110
ω scans	θmax = 27.1°, θmin = 3.4°
Absorption correction: numerical face indexed (X-Red32 and X-Shape; Stoe & Cie, 2010)	h = −7→8
Tmin = 0.388, Tmax = 0.875	k = −19→19
14640 measured reflections	l = −22→22

Refinement

Refinement on F2	3 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.057	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.143	w = 1/[σ2(Fo2) + (0.0841P)2] where P = (Fo2 + 2Fc2)/3
S = 0.96	(Δ/σ)max < 0.001
3696 reflections	Δρmax = 0.34 e Å−3
274 parameters	Δρmin = −0.37 e Å−3

Special details

Experimental. The reaction was carried out in a Schlenk tube using Schlenk techniques under a nitrogen atmosphere. All other reagents and solvents were purchased commercially and used without any further purification. A UV–visible spectrum of the title compound (10 µM) was measured in methanol using a UV–visible spectrophotometer with a cell of 1 cm path length. A fluorescence spectrum of the same solution was obtained using a fluorescence spectrophotometer at 298 K using a 1 cm path-length cell. The reaction was monitored by thin layer chromatography using TLC silica gel 60 F254 precoated plates (Merck). Visualization was accomplished by irradiation with UV light. C, H, and N analyses was carried out locally. NMR data (1H, 13C) of the synthesized compound were recorded locally on 500 MHz spectrometers. Mass spectroscopic analysis was carried out with a mass spectrometer from Varian Inc, US: 10 Prostar Binary LC with 500 MS IT PDA detectors.

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.4367 (6)	0.5659 (2)	0.66750 (19)	0.0316 (8)
O2	−0.1365 (5)	0.6212 (3)	0.62349 (19)	0.0355 (8)
O3	0.3555 (5)	0.6634 (2)	0.52801 (16)	0.0251 (7)
O4	0.0678 (6)	0.6179 (2)	0.33056 (18)	0.0342 (8)
O5	0.5541 (6)	0.4112 (2)	0.26958 (17)	0.0319 (8)
O6	0.6845 (5)	0.4177 (2)	0.54844 (17)	0.0271 (7)
N1	0.3167 (6)	0.5825 (2)	0.4169 (2)	0.0244 (8)
N2	0.3171 (7)	0.5149 (3)	0.3022 (2)	0.0278 (8)
C1	0.3630 (8)	0.6543 (3)	0.6624 (2)	0.0268 (10)
H1A	0.4869	0.6946	0.6612	0.032*
H1B	0.2787	0.6685	0.7074	0.032*
C2	0.2282 (7)	0.6702 (3)	0.5941 (2)	0.0238 (9)
H2	0.1672	0.7310	0.5970	0.029*
C3	0.0472 (7)	0.6046 (3)	0.5800 (2)	0.0256 (9)
H3	0.0978	0.5428	0.5880	0.031*
C4	0.0039 (7)	0.6206 (3)	0.4983 (3)	0.0264 (9)
H4A	−0.1046	0.6672	0.4915	0.032*
H4B	−0.0458	0.5660	0.4735	0.032*
C5	0.2197 (7)	0.6500 (3)	0.4670 (2)	0.0253 (9)
H5	0.2020	0.7067	0.4391	0.030*
C6	0.4901 (7)	0.5330 (3)	0.4377 (2)	0.0233 (9)
H6	0.5481	0.5409	0.4862	0.028*
C7	0.5806 (7)	0.4735 (3)	0.3914 (2)	0.0239 (9)
C8	0.4944 (7)	0.4627 (3)	0.3171 (3)	0.0262 (9)
C9	0.2231 (8)	0.5755 (3)	0.3485 (2)	0.0282 (10)
C10	0.7714 (7)	0.4220 (3)	0.4143 (2)	0.0250 (9)
C11	0.8132 (7)	0.4001 (3)	0.4874 (2)	0.0256 (10)
C12	0.7864 (8)	0.3833 (3)	0.6103 (2)	0.0271 (10)
C13	0.7096 (8)	0.3830 (3)	0.6814 (3)	0.0296 (10)
H13	0.5767	0.4090	0.6935	0.036*
C14	0.8351 (8)	0.3429 (3)	0.7351 (3)	0.0321 (10)
H14	0.7868	0.3412	0.7853	0.039*
C15	1.0316 (8)	0.3047 (3)	0.7172 (3)	0.0310 (10)
H15	1.1139	0.2775	0.7552	0.037*
C16	1.1061 (8)	0.3060 (3)	0.6454 (3)	0.0306 (10)
H16	1.2393	0.2802	0.6334	0.037*
C17	0.9829 (7)	0.3460 (3)	0.5904 (3)	0.0262 (9)
C18	0.9993 (7)	0.3562 (3)	0.5105 (3)	0.0250 (9)
C19	1.1478 (7)	0.3293 (3)	0.4577 (3)	0.0280 (10)
H19	1.2741	0.2993	0.4720	0.034*
C20	1.1057 (7)	0.3474 (3)	0.3848 (3)	0.0294 (10)
H20	1.2028	0.3278	0.3477	0.035*
C21	0.9242 (8)	0.3939 (3)	0.3626 (3)	0.0281 (10)
H21	0.9041	0.4067	0.3112	0.034*
H2O	−0.097 (9)	0.608 (4)	0.676 (3)	0.037 (15)*
H2N	0.266 (9)	0.506 (4)	0.255 (3)	0.034 (14)*
H1O	0.567 (10)	0.562 (5)	0.644 (4)	0.07 (2)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0278 (19)	0.0285 (17)	0.0385 (19)	0.0033 (13)	−0.0009 (14)	0.0040 (14)
O2	0.0208 (17)	0.054 (2)	0.0320 (19)	0.0045 (15)	0.0025 (13)	0.0041 (16)
O3	0.0267 (17)	0.0264 (15)	0.0223 (16)	−0.0019 (12)	0.0004 (12)	−0.0025 (12)
O4	0.0333 (19)	0.0388 (18)	0.0305 (17)	0.0095 (15)	−0.0064 (14)	−0.0014 (15)
O5	0.0370 (19)	0.0331 (17)	0.0255 (16)	0.0016 (14)	0.0004 (14)	−0.0086 (14)
O6	0.0269 (17)	0.0286 (16)	0.0259 (15)	0.0040 (13)	0.0028 (13)	0.0018 (12)
N1	0.024 (2)	0.0249 (18)	0.0243 (18)	0.0037 (15)	−0.0004 (15)	0.0000 (15)
N2	0.033 (2)	0.0299 (19)	0.0205 (19)	0.0018 (16)	−0.0034 (16)	−0.0039 (15)
C1	0.029 (2)	0.024 (2)	0.028 (2)	−0.0031 (18)	0.0007 (18)	−0.0005 (18)
C2	0.025 (2)	0.021 (2)	0.025 (2)	0.0013 (16)	0.0016 (18)	0.0007 (17)
C3	0.022 (2)	0.023 (2)	0.031 (2)	0.0002 (17)	0.0024 (17)	0.0028 (18)
C4	0.022 (2)	0.026 (2)	0.031 (2)	0.0039 (17)	−0.0022 (19)	−0.0032 (18)
C5	0.032 (2)	0.021 (2)	0.023 (2)	0.0024 (17)	−0.0011 (18)	−0.0010 (17)
C6	0.024 (2)	0.023 (2)	0.023 (2)	−0.0023 (16)	−0.0033 (16)	−0.0002 (16)
C7	0.024 (2)	0.021 (2)	0.026 (2)	−0.0018 (16)	0.0020 (17)	0.0012 (17)
C8	0.027 (2)	0.024 (2)	0.027 (2)	−0.0021 (17)	0.0014 (18)	0.0015 (17)
C9	0.032 (3)	0.030 (2)	0.023 (2)	−0.002 (2)	−0.0005 (18)	−0.0014 (18)
C10	0.026 (2)	0.020 (2)	0.029 (2)	−0.0015 (17)	0.0010 (18)	−0.0024 (18)
C11	0.027 (3)	0.020 (2)	0.029 (2)	0.0003 (17)	0.0060 (18)	−0.0031 (16)
C12	0.029 (2)	0.023 (2)	0.030 (2)	0.0016 (18)	−0.0041 (19)	0.0003 (18)
C13	0.036 (3)	0.023 (2)	0.030 (2)	0.0030 (19)	0.001 (2)	0.0011 (18)
C14	0.040 (3)	0.027 (2)	0.029 (2)	−0.004 (2)	−0.003 (2)	−0.0001 (19)
C15	0.030 (3)	0.028 (2)	0.036 (3)	0.0010 (19)	−0.009 (2)	0.0030 (19)
C16	0.030 (3)	0.022 (2)	0.040 (3)	0.0015 (17)	−0.006 (2)	−0.004 (2)
C17	0.024 (2)	0.023 (2)	0.032 (2)	−0.0019 (17)	−0.0003 (19)	−0.0024 (18)
C18	0.025 (2)	0.019 (2)	0.031 (2)	−0.0012 (17)	0.0012 (18)	0.0005 (17)
C19	0.026 (2)	0.017 (2)	0.041 (3)	0.0010 (16)	0.004 (2)	−0.0001 (18)
C20	0.027 (2)	0.029 (2)	0.033 (3)	0.0008 (18)	0.0083 (19)	−0.0053 (19)
C21	0.033 (3)	0.025 (2)	0.026 (2)	−0.0032 (18)	0.0028 (19)	−0.0045 (18)

Geometric parameters (Å, º)

O1—C1	1.423 (6)	C5—H5	1.0000
O1—H1O	0.92 (6)	C6—C7	1.353 (6)
O2—C3	1.417 (6)	C6—H6	0.9500
O2—H2O	1.00 (5)	C7—C8	1.447 (6)
O3—C5	1.403 (5)	C7—C10	1.489 (6)
O3—C2	1.435 (5)	C10—C11	1.379 (6)
O4—C9	1.213 (6)	C10—C21	1.402 (6)
O5—C8	1.216 (5)	C11—C18	1.408 (6)
O6—C12	1.384 (5)	C12—C13	1.364 (7)
O6—C11	1.387 (5)	C12—C17	1.405 (6)
N1—C9	1.366 (6)	C13—C14	1.386 (7)
N1—C6	1.375 (6)	C13—H13	0.9500
N1—C5	1.492 (5)	C14—C15	1.403 (7)
N2—C9	1.373 (6)	C14—H14	0.9500
N2—C8	1.393 (6)	C15—C16	1.370 (7)
N2—H2N	0.91 (5)	C15—H15	0.9500
C1—C2	1.508 (6)	C16—C17	1.394 (6)
C1—H1A	0.9900	C16—H16	0.9500
C1—H1B	0.9900	C17—C18	1.445 (6)
C2—C3	1.533 (6)	C18—C19	1.391 (6)
C2—H2	1.0000	C19—C20	1.364 (7)
C3—C4	1.511 (6)	C19—H19	0.9500
C3—H3	1.0000	C20—C21	1.399 (7)
C4—C5	1.535 (7)	C20—H20	0.9500
C4—H4A	0.9900	C21—H21	0.9500
C4—H4B	0.9900
C1—O1—H1O	109 (5)	C6—C7—C10	121.3 (4)
C3—O2—H2O	106 (3)	C8—C7—C10	119.8 (4)
C5—O3—C2	108.4 (3)	O5—C8—N2	118.5 (4)
C12—O6—C11	106.8 (3)	O5—C8—C7	127.0 (4)
C9—N1—C6	122.9 (4)	N2—C8—C7	114.4 (4)
C9—N1—C5	114.7 (4)	O4—C9—N1	122.9 (4)
C6—N1—C5	122.4 (4)	O4—C9—N2	122.8 (4)
C9—N2—C8	127.5 (4)	N1—C9—N2	114.2 (4)
C9—N2—H2N	121 (4)	C11—C10—C21	115.1 (4)
C8—N2—H2N	112 (4)	C11—C10—C7	122.8 (4)
O1—C1—C2	112.7 (4)	C21—C10—C7	122.0 (4)
O1—C1—H1A	109.1	C10—C11—O6	126.3 (4)
C2—C1—H1A	109.1	C10—C11—C18	123.5 (4)
O1—C1—H1B	109.1	O6—C11—C18	110.2 (4)
C2—C1—H1B	109.1	C13—C12—O6	125.9 (4)
H1A—C1—H1B	107.8	C13—C12—C17	123.2 (4)
O3—C2—C1	110.2 (4)	O6—C12—C17	110.8 (4)
O3—C2—C3	103.3 (3)	C12—C13—C14	116.8 (5)
C1—C2—C3	116.7 (4)	C12—C13—H13	121.6
O3—C2—H2	108.8	C14—C13—H13	121.6
C1—C2—H2	108.8	C13—C14—C15	121.5 (5)
C3—C2—H2	108.8	C13—C14—H14	119.2
O2—C3—C4	111.0 (4)	C15—C14—H14	119.2
O2—C3—C2	113.5 (4)	C16—C15—C14	120.8 (5)
C4—C3—C2	101.0 (4)	C16—C15—H15	119.6
O2—C3—H3	110.4	C14—C15—H15	119.6
C4—C3—H3	110.4	C15—C16—C17	118.8 (5)
C2—C3—H3	110.4	C15—C16—H16	120.6
C3—C4—C5	104.0 (4)	C17—C16—H16	120.6
C3—C4—H4A	111.0	C16—C17—C12	118.9 (4)
C5—C4—H4A	111.0	C16—C17—C18	135.2 (4)
C3—C4—H4B	111.0	C12—C17—C18	105.8 (4)
C5—C4—H4B	111.0	C19—C18—C11	119.8 (4)
H4A—C4—H4B	109.0	C19—C18—C17	133.7 (4)
O3—C5—N1	108.6 (3)	C11—C18—C17	106.4 (4)
O3—C5—C4	107.2 (3)	C20—C19—C18	117.6 (4)
N1—C5—C4	112.5 (4)	C20—C19—H19	121.2
O3—C5—H5	109.5	C18—C19—H19	121.2
N1—C5—H5	109.5	C19—C20—C21	122.2 (4)
C4—C5—H5	109.5	C19—C20—H20	118.9
C7—C6—N1	122.1 (4)	C21—C20—H20	118.9
C7—C6—H6	118.9	C20—C21—C10	121.7 (4)
N1—C6—H6	118.9	C20—C21—H21	119.2
C6—C7—C8	118.8 (4)	C10—C21—H21	119.2

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4A···O3i	0.99	2.61	3.439 (6)	142
C6—H6···O6	0.95	2.34	2.915 (5)	119
C13—H13···O1	0.95	2.58	3.271 (6)	130
C21—H21···O5	0.95	2.33	2.876 (6)	116
C13—H13···O4ii	0.95	2.65	3.194 (6)	117
C14—H14···O4ii	0.95	2.45	3.115 (6)	127
C1—H1B···O5ii	0.99	2.66	3.401 (6)	132
O2—H2O···O5ii	1.00 (5)	1.72 (5)	2.716 (5)	174 (5)
N2—H2N···O1iii	0.91 (5)	2.30 (5)	3.144 (5)	154 (5)
O1—H1O···O2iv	0.92 (6)	2.10 (6)	2.922 (5)	148 (6)

Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+1/2, −y+1, z+1/2; (iii) −x+1/2, −y+1, z−1/2; (iv) x+1, y, z.

Funding Statement

This work was funded by Alexander von Humboldt-Stiftung grant 3.4 - IP - DEU/1131213 to A. R. Kapdi and C. Schulzke. University Grants Commission grant to V. Gayakhe. FP7 Ideas: European Research Council grant 281257 to C. Schulzke.