Gabapentin and gabapentin monohydrate

Gabapentin [1-(amino­methyl)­cyclo­hexane­acetic acid, C₉H₁₇NO₂] is a zwitterion in the solid state. Its crystal structure involves extensive hydrogen bonding between the NH₃⁺ and COO^- groups of neighboring mol­ecules. The structure of gabapentin monohydrate [1-(amino­methyl)­cyclo­hexane­acetic acid monohydrate, C₉H₁₇NO₂·H₂O] also involves such hydrogen bonding and, in addition, has a hydrogen-bonding network comprising the water mol­ecules and both the NH₃⁺ and COO^- groups.

S1. Comment

Gabapentin is a new-generation antiepileptic drug that is used as add-on therapy (Placidi et al., 2000), as well as monotherapy (Chadwick et al., 1998) in patients with partial seizures (Lima, 2000; Morton & Pellock, 2000). With the introduction of gabapentin and other promising new antiepileptic drugs, safe and effective seizure control may become a reality for an increasing number of adults with epilepsy (Mattson, 1998). The mechanism of action of gabapentin remains unclear, although it is apparently dissimilar to that of other antiepileptic agents (Gee et al., 1996). Earlier data suggest that an effect of gabapentin on the formation of γ-aminobutyric acid (gaba), a non-protein amino acid that functions as a neurotransmitter, might be involved in its mechanism of action (Loescher et al., 1991). A later study in which a [3H]gabapentin-binding protein was isolated and characterized indicates that [3H]gabapentin interacts with the α2δ subunit of a voltage-dependent Ca²⁺ channel (Gee et al., 1996).

Despite intense interest in gabapentin and its polymorphs (Pesachovich et al., 1998), its crystal structure is unknown, as is that of its monohydrate. The structures of these two compounds, (I) and (II), respectively, are presented here.

Gabapentin is a zwitterion in the solid state, as shown in Fig. 1. Metrical data for the non-H atoms are given in Table 1. These data are in good agreement with those found in the low-temperature determination of the structure of γ-aminobutyric acid (gaba; Craven & Weber, 1983; Weber et al., 1983). Gaba is also a zwitterion.

The structure of gabapentin monohydrate, (II), is shown in Fig. 2. It too is a zwitterion. Metrical data for the non-H atoms are given in Table 3 and again agree well with those in gaba as well as in anhydrous gabapentin.

In gabapentin, as in gaba, there is extensive hydrogen bonding between the NH₃⁺ and COO^- groups of neighboring molecules. These hydrogen-bonding interactions are detailed in Table 2. In the monohydrate, in addition to the direct hydrogen bonding between the NH₃⁺ and COO^- groups of neighboring molecules, the O atom (OW) of the water molecule is hydrogen bonded to both groups. The hydrogen-bonding interactions are detailed in Table 4.

In gaba, the difference [0.019 (6) Å] in carboxylate C—O bond lengths was ascribed to hydrogen bonding, with the longer bond involving an O atom that forms two N—H···O bonds and the shorter bond involving the other O atom which forms only one N—H···O bond. In gabapentin, the carboxylate C—O bonds differ by 0.020 (2) Å and again the long bond involves an O atom that forms two N—H···O bonds and the short bond involves an O atom that forms only one N—H···O bond. In the monohydrate, the C—O bond lengths differ by 0.017 (3) Å, with the long bond involving an O atom that forms two N—H···O bonds and the short bond involving an O atom that forms two OW—H···O bonds. In all three compounds, the hydrogen bonds are strong.

Related literature

For related literature, see: Chadwick et al. (1998); Craven & Weber (1983); Gee et al. (1996); Lima (2000); Loescher et al. (1991); Mattson (1998); Morton & Pellock (2000); Pesachovich et al. (1998); Placidi et al. (2000); Weber et al. (1983).

S2. Experimental

The sample of gabapentin provided by Purepac Pharmaceutical Company contained crystals suitable for diffraction studies. For the preparation of the monohydrate, 160 mg of gabapentin was dissolved in 1 ml of water and 3 ml of 2-propanol was added. The resultant solution was placed in a freezer. Four days later, crystals of gabapentin monohydrate were harvested from the precipitate, which also contained gabapentin. The two materials differ in their crystal habits and are readily distinguished from one another.

S3. Refinement

The positional and isotropic displacement parameters of all H atoms were refined. The refined C—H distances are in the range 0.95 (2)–1.02 (2) Å for gabapentin and 0.96 (2)–1.05 (2) Å for gabapentin monohydrate.

Computing details

For both compounds, data collection: SMART (Bruker, 2000); cell refinement: SMART; data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997a); molecular graphics: SHELXTL/PC (Sheldrick, 1997b); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The structure of gabapentin shown with 50% probability displacement ellipsoids, except for the H atoms, which are drawn as small circles.
	Fig. 2. The structure of gabapentin monohydrate shown with 50% probability displacement ellipsoids, except for the H atoms, which are drawn as small circles. The O atom of the water molecule is OW.

(I) 1-(aminomethyl)cyclohexaneacetic acid

Crystal data

C9H17NO2	F(000) = 376
Mr = 171.24	Dx = 1.257 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 5.8759 (6) Å	Cell parameters from 2674 reflections
b = 6.9198 (7) Å	θ = 6.2–28.1°
c = 22.262 (2) Å	µ = 0.09 mm^−1
β = 90.080 (2)°	T = 153 K
V = 905.18 (16) Å^3	Needle, colourless
Z = 4	0.30 × 0.09 × 0.09 mm

Data collection

Bruker SMART 1000 CCD diffractometer	1572 reflections with I > 2σ(I)
Radiation source: standard-focus sealed tube	Rint = 0.042
Graphite monochromator	θmax = 28.3°, θmin = 1.8°
ω scans	h = −7→7
7951 measured reflections	k = −8→8
2147 independent reflections	l = −29→29

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.118	All H-atom parameters refined
S = 0.98	w = 1/[σ^2(Fo^2) + (0.0752Fo^2)^2]
2147 reflections	(Δ/σ)max < 0.001
177 parameters	Δρmax = 0.39 e Å^−3
0 restraints	Δρmin = −0.21 e Å^−3

Special details

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

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

	x	y	z	Uiso*/Ueq
O1	0.32783 (16)	0.22232 (14)	0.47786 (5)	0.0240 (3)
O2	0.03209 (16)	0.32934 (15)	0.42512 (5)	0.0275 (3)
N1	0.2248 (2)	0.83466 (18)	0.48502 (6)	0.0204 (3)
HN1	0.368 (3)	0.786 (2)	0.4921 (8)	0.026 (4)*
HN2	0.128 (3)	0.801 (3)	0.5156 (9)	0.036 (5)*
HN3	0.238 (3)	0.973 (3)	0.4858 (8)	0.039 (5)*
C1	0.2946 (2)	0.67267 (19)	0.38403 (6)	0.0191 (3)
C2	0.1690 (2)	0.6198 (2)	0.32528 (7)	0.0227 (3)
H2A	0.270 (2)	0.534 (2)	0.3024 (7)	0.020 (4)*
H2B	0.030 (3)	0.547 (2)	0.3354 (7)	0.026 (4)*
C3	0.1122 (2)	0.7931 (2)	0.28509 (7)	0.0256 (3)
H3A	0.042 (3)	0.746 (2)	0.2468 (9)	0.029 (4)*
H3B	−0.002 (3)	0.877 (2)	0.3054 (7)	0.024 (4)*
C4	0.3237 (2)	0.9141 (2)	0.27181 (7)	0.0262 (3)
H4A	0.438 (2)	0.836 (2)	0.2475 (7)	0.020 (4)*
H4B	0.285 (3)	1.031 (2)	0.2465 (8)	0.028 (4)*
C5	0.4363 (2)	0.9798 (2)	0.33004 (7)	0.0249 (3)
H5A	0.577 (2)	1.051 (2)	0.3221 (7)	0.026 (4)*
H5B	0.336 (3)	1.071 (2)	0.3521 (8)	0.026 (4)*
C6	0.4984 (2)	0.8074 (2)	0.36947 (7)	0.0210 (3)
H6A	0.569 (2)	0.851 (2)	0.4078 (7)	0.016 (4)*
H6B	0.618 (2)	0.730 (2)	0.3481 (7)	0.019 (4)*
C7	0.1240 (2)	0.7711 (2)	0.42632 (6)	0.0209 (3)
H7A	0.061 (2)	0.886 (2)	0.4076 (7)	0.019 (4)*
H7B	0.000 (3)	0.686 (2)	0.4339 (7)	0.022 (4)*
C8	0.3956 (2)	0.4900 (2)	0.41369 (6)	0.0203 (3)
H8A	0.486 (2)	0.425 (2)	0.3827 (7)	0.022 (4)*
H8B	0.506 (2)	0.525 (2)	0.4449 (7)	0.021 (4)*
C9	0.2368 (2)	0.33823 (19)	0.44058 (6)	0.0204 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0265 (5)	0.0210 (5)	0.0247 (6)	−0.0011 (4)	−0.0029 (4)	0.0049 (4)
O2	0.0213 (5)	0.0329 (6)	0.0282 (6)	−0.0049 (4)	−0.0012 (4)	0.0085 (5)
N1	0.0202 (6)	0.0207 (6)	0.0202 (6)	−0.0004 (4)	0.0020 (5)	0.0006 (5)
C1	0.0196 (6)	0.0194 (7)	0.0184 (7)	−0.0010 (5)	0.0012 (5)	0.0010 (5)
C2	0.0242 (7)	0.0224 (7)	0.0215 (8)	−0.0012 (5)	0.0001 (6)	0.0004 (6)
C3	0.0266 (7)	0.0283 (8)	0.0217 (8)	−0.0008 (6)	−0.0019 (6)	0.0037 (6)
C4	0.0305 (8)	0.0258 (8)	0.0223 (8)	−0.0003 (6)	0.0021 (6)	0.0051 (6)
C5	0.0253 (7)	0.0217 (7)	0.0277 (8)	−0.0023 (5)	0.0031 (6)	0.0026 (6)
C6	0.0212 (7)	0.0225 (7)	0.0192 (7)	−0.0016 (5)	0.0012 (6)	0.0009 (6)
C7	0.0194 (6)	0.0230 (7)	0.0202 (7)	0.0006 (5)	0.0007 (5)	0.0007 (6)
C8	0.0198 (6)	0.0209 (7)	0.0202 (7)	0.0000 (5)	0.0008 (6)	0.0009 (6)
C9	0.0237 (7)	0.0193 (7)	0.0181 (7)	0.0001 (5)	0.0029 (5)	−0.0016 (5)

Geometric parameters (Å, º)

O1—C9	1.2717 (17)	C3—H3B	0.995 (16)
O2—C9	1.2519 (17)	C4—C5	1.524 (2)
N1—C7	1.4998 (19)	C4—H4A	1.018 (16)
N1—HN1	0.918 (18)	C4—H4B	1.011 (18)
N1—HN2	0.92 (2)	C5—C6	1.525 (2)
N1—HN3	0.96 (2)	C5—H5A	0.978 (15)
C1—C7	1.5353 (19)	C5—H5B	0.994 (17)
C1—C2	1.544 (2)	C6—H6A	0.995 (16)
C1—C8	1.5446 (18)	C6—H6B	1.007 (15)
C1—C6	1.5524 (18)	C7—H7A	0.973 (16)
C2—C3	1.533 (2)	C7—H7B	0.954 (16)
C2—H2A	0.981 (16)	C8—C9	1.5277 (18)
C2—H2B	0.987 (16)	C8—H8A	0.982 (17)
C3—C4	1.528 (2)	C8—H8B	0.979 (15)
C3—H3A	0.999 (19)
C7—N1—HN1	113.8 (11)	H4A—C4—H4B	106.1 (13)
C7—N1—HN2	109.1 (12)	C4—C5—C6	111.07 (12)
HN1—N1—HN2	110.2 (16)	C4—C5—H5A	111.2 (9)
C7—N1—HN3	109.9 (11)	C6—C5—H5A	107.1 (9)
HN1—N1—HN3	106.7 (14)	C4—C5—H5B	110.5 (9)
HN2—N1—HN3	106.9 (15)	C6—C5—H5B	110.8 (10)
C7—C1—C2	108.23 (11)	H5A—C5—H5B	106.0 (13)
C7—C1—C8	110.60 (11)	C5—C6—C1	113.95 (11)
C2—C1—C8	110.56 (11)	C5—C6—H6A	110.9 (9)
C7—C1—C6	111.47 (11)	C1—C6—H6A	108.8 (9)
C2—C1—C6	109.45 (11)	C5—C6—H6B	108.2 (9)
C8—C1—C6	106.54 (10)	C1—C6—H6B	108.5 (8)
C3—C2—C1	114.37 (12)	H6A—C6—H6B	106.1 (12)
C3—C2—H2A	107.5 (9)	N1—C7—C1	114.03 (11)
C1—C2—H2A	107.2 (9)	N1—C7—H7A	106.4 (9)
C3—C2—H2B	110.7 (9)	C1—C7—H7A	110.5 (9)
C1—C2—H2B	108.9 (10)	N1—C7—H7B	109.2 (10)
H2A—C2—H2B	108.0 (13)	C1—C7—H7B	109.6 (10)
C4—C3—C2	111.42 (12)	H7A—C7—H7B	106.8 (13)
C4—C3—H3A	110.2 (10)	C9—C8—C1	119.68 (11)
C2—C3—H3A	109.5 (10)	C9—C8—H8A	107.1 (9)
C4—C3—H3B	108.3 (9)	C1—C8—H8A	106.4 (9)
C2—C3—H3B	109.8 (10)	C9—C8—H8B	107.2 (9)
H3A—C3—H3B	107.4 (13)	C1—C8—H8B	110.7 (9)
C5—C4—C3	110.54 (12)	H8A—C8—H8B	104.7 (12)
C5—C4—H4A	109.0 (9)	O2—C9—O1	123.48 (12)
C3—C4—H4A	110.4 (9)	O2—C9—C8	120.88 (12)
C5—C4—H4B	109.4 (10)	O1—C9—C8	115.62 (12)
C3—C4—H4B	111.2 (9)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—HN1···O1^i	0.918 (18)	1.910 (18)	2.7827 (16)	158.2 (15)
N1—HN2···O2^ii	0.92 (2)	1.85 (2)	2.7525 (16)	165.3 (16)
N1—HN3···O1^iii	0.96 (2)	1.81 (2)	2.7547 (16)	165.8 (16)

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

(II) 1-(aminomethyl)cyclohexaneacetic acid monohydrate

Crystal data

C9H17NO2·H2O	F(000) = 416
Mr = 189.25	Dx = 1.226 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 14.567 (3) Å	Cell parameters from 1958 reflections
b = 9.2153 (18) Å	θ = 2.6–28.2°
c = 7.6503 (15) Å	µ = 0.09 mm^−1
β = 93.375 (3)°	T = 153 K
V = 1025.2 (3) Å^3	Flat plate, colourless
Z = 4	0.35 × 0.26 × 0.03 mm

Data collection

Bruker SMART 1000 CCD diffractometer	2461 independent reflections
Radiation source: standard-focus sealed tube	1550 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.058
ω scans	θmax = 28.3°, θmin = 1.4°
Absorption correction: numerical face indexed	h = −19→18
Tmin = 0.972, Tmax = 0.998	k = −12→12
9122 measured reflections	l = −10→10

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.133	All H-atom parameters refined
S = 0.97	w = 1/[σ^2(Fo^2) + (0.07Fo^2)^2]
2461 reflections	(Δ/σ)max < 0.001
194 parameters	Δρmax = 0.42 e Å^−3
0 restraints	Δρmin = −0.22 e Å^−3

Special details

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

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

	x	y	z	Uiso*/Ueq
O1	0.83595 (10)	0.39302 (13)	1.10528 (16)	0.0257 (3)
O2	0.89054 (10)	0.61784 (14)	1.08593 (16)	0.0295 (4)
OW	0.96959 (10)	0.84570 (16)	0.91842 (19)	0.0283 (4)
HWA	0.9419 (15)	0.766 (3)	0.953 (3)	0.042 (7)*
HWB	0.938 (2)	0.863 (3)	0.814 (4)	0.077 (10)*
N1	0.84714 (12)	0.39236 (18)	0.4660 (2)	0.0203 (4)
HN1	0.8344 (14)	0.294 (2)	0.499 (3)	0.033 (6)*
HN2	0.9057 (15)	0.411 (2)	0.508 (3)	0.028 (6)*
HN3	0.8494 (15)	0.394 (2)	0.333 (3)	0.038 (6)*
C1	0.76548 (13)	0.49637 (19)	0.7233 (2)	0.0189 (4)
C2	0.70261 (13)	0.3682 (2)	0.7676 (2)	0.0222 (4)
H2A	0.7299 (12)	0.279 (2)	0.729 (2)	0.019 (5)*
H2B	0.6992 (13)	0.362 (2)	0.899 (3)	0.025 (5)*
C3	0.60350 (15)	0.3842 (2)	0.6939 (3)	0.0319 (5)
H3A	0.5693 (14)	0.300 (2)	0.735 (3)	0.035 (6)*
H3B	0.6032 (15)	0.377 (2)	0.557 (3)	0.034 (6)*
C4	0.56156 (15)	0.5276 (3)	0.7484 (3)	0.0358 (5)
H4A	0.5583 (15)	0.529 (2)	0.883 (3)	0.039 (6)*
H4B	0.4967 (17)	0.539 (2)	0.705 (3)	0.038 (6)*
C5	0.62091 (15)	0.6548 (2)	0.6957 (3)	0.0315 (5)
H5A	0.6187 (13)	0.666 (2)	0.562 (3)	0.033 (6)*
H5B	0.5957 (13)	0.749 (2)	0.735 (3)	0.029 (5)*
C6	0.71894 (14)	0.6400 (2)	0.7735 (3)	0.0237 (4)
H6A	0.7161 (13)	0.644 (2)	0.905 (3)	0.027 (5)*
H6B	0.7582 (13)	0.723 (2)	0.742 (3)	0.026 (5)*
C7	0.78050 (13)	0.5022 (2)	0.5256 (2)	0.0207 (4)
H7A	0.7209 (13)	0.4862 (19)	0.458 (3)	0.022 (5)*
H7B	0.8059 (12)	0.603 (2)	0.496 (2)	0.014 (4)*
C8	0.86156 (13)	0.4847 (2)	0.8203 (2)	0.0193 (4)
H8A	0.8909 (13)	0.392 (2)	0.802 (2)	0.017 (5)*
H8B	0.9023 (13)	0.560 (2)	0.780 (3)	0.023 (5)*
C9	0.86289 (13)	0.50075 (19)	1.0188 (2)	0.0203 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0441 (9)	0.0240 (7)	0.0091 (6)	−0.0046 (6)	0.0023 (5)	0.0012 (5)
O2	0.0503 (9)	0.0253 (8)	0.0127 (7)	−0.0079 (6)	−0.0009 (6)	−0.0027 (5)
OW	0.0340 (8)	0.0310 (8)	0.0191 (8)	−0.0069 (6)	−0.0044 (6)	0.0039 (6)
N1	0.0273 (9)	0.0230 (9)	0.0104 (8)	−0.0003 (7)	0.0006 (6)	−0.0001 (6)
C1	0.0254 (9)	0.0224 (9)	0.0089 (8)	0.0000 (7)	0.0013 (7)	0.0009 (7)
C2	0.0269 (11)	0.0255 (11)	0.0141 (9)	−0.0007 (8)	0.0014 (8)	0.0014 (7)
C3	0.0306 (11)	0.0365 (12)	0.0284 (12)	−0.0063 (9)	−0.0005 (9)	0.0044 (9)
C4	0.0256 (12)	0.0480 (14)	0.0339 (13)	0.0045 (10)	0.0031 (10)	0.0057 (10)
C5	0.0370 (13)	0.0340 (12)	0.0236 (11)	0.0112 (10)	0.0034 (9)	0.0023 (9)
C6	0.0307 (11)	0.0252 (11)	0.0154 (10)	0.0015 (8)	0.0041 (8)	−0.0010 (8)
C7	0.0273 (10)	0.0246 (10)	0.0102 (9)	0.0040 (8)	0.0010 (7)	0.0013 (7)
C8	0.0266 (10)	0.0231 (10)	0.0083 (8)	−0.0013 (8)	0.0012 (7)	0.0001 (7)
C9	0.0257 (10)	0.0234 (10)	0.0117 (9)	0.0006 (8)	0.0014 (7)	0.0000 (7)

Geometric parameters (Å, º)

O1—C9	1.268 (2)	C3—H3A	0.98 (2)
O2—C9	1.251 (2)	C3—H3B	1.05 (2)
OW—HWA	0.88 (3)	C4—C5	1.525 (3)
OW—HWB	0.91 (3)	C4—H4A	1.03 (2)
N1—C7	1.493 (2)	C4—H4B	0.99 (2)
N1—HN1	0.96 (2)	C5—C6	1.521 (3)
N1—HN2	0.91 (2)	C5—H5A	1.03 (2)
N1—HN3	1.02 (2)	C5—H5B	0.99 (2)
C1—C7	1.542 (2)	C6—H6A	1.01 (2)
C1—C2	1.544 (2)	C6—H6B	0.99 (2)
C1—C6	1.546 (2)	C7—H7A	0.99 (2)
C1—C8	1.549 (3)	C7—H7B	1.033 (18)
C2—C3	1.526 (3)	C8—C9	1.525 (2)
C2—H2A	0.965 (19)	C8—H8A	0.969 (19)
C2—H2B	1.01 (2)	C8—H8B	0.98 (2)
C3—C4	1.524 (3)
HWA—OW—HWB	101 (2)	C5—C4—H4B	111.8 (12)
C7—N1—HN1	114.8 (12)	H4A—C4—H4B	103.4 (18)
C7—N1—HN2	112.2 (13)	C6—C5—C4	111.17 (17)
HN1—N1—HN2	106.3 (17)	C6—C5—H5A	111.9 (11)
C7—N1—HN3	110.9 (12)	C4—C5—H5A	110.6 (11)
HN1—N1—HN3	106.9 (17)	C6—C5—H5B	108.5 (12)
HN2—N1—HN3	105.2 (18)	C4—C5—H5B	111.5 (11)
C7—C1—C2	111.23 (15)	H5A—C5—H5B	102.9 (15)
C7—C1—C6	107.67 (15)	C5—C6—C1	113.28 (16)
C2—C1—C6	109.01 (15)	C5—C6—H6A	107.1 (11)
C7—C1—C8	107.22 (15)	C1—C6—H6A	108.8 (11)
C2—C1—C8	111.88 (15)	C5—C6—H6B	112.1 (11)
C6—C1—C8	109.73 (15)	C1—C6—H6B	109.2 (11)
C3—C2—C1	113.95 (16)	H6A—C6—H6B	106.0 (15)
C3—C2—H2A	111.5 (11)	N1—C7—C1	114.11 (15)
C1—C2—H2A	108.9 (11)	N1—C7—H7A	107.7 (11)
C3—C2—H2B	105.8 (11)	C1—C7—H7A	109.4 (11)
C1—C2—H2B	108.9 (11)	N1—C7—H7B	107.3 (10)
H2A—C2—H2B	107.5 (15)	C1—C7—H7B	108.6 (10)
C4—C3—C2	111.62 (18)	H7A—C7—H7B	109.6 (14)
C4—C3—H3A	112.2 (12)	C9—C8—C1	115.38 (15)
C2—C3—H3A	107.0 (12)	C9—C8—H8A	104.6 (11)
C4—C3—H3B	110.6 (11)	C1—C8—H8A	112.6 (11)
C2—C3—H3B	108.1 (12)	C9—C8—H8B	105.7 (12)
H3A—C3—H3B	107.1 (16)	C1—C8—H8B	110.4 (11)
C3—C4—C5	110.60 (18)	H8A—C8—H8B	107.6 (16)
C3—C4—H4A	109.1 (12)	O2—C9—O1	124.28 (17)
C5—C4—H4A	108.2 (13)	O2—C9—C8	118.50 (16)
C3—C4—H4B	113.3 (13)	O1—C9—C8	117.22 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
OW—HWA···O2	0.88 (3)	1.89 (3)	2.748 (2)	165 (2)
OW—HWB···O2^i	0.91 (3)	1.85 (3)	2.7503 (19)	170 (3)
N1—HN1···O1^ii	0.96 (2)	1.91 (2)	2.846 (2)	165.1 (18)
N1—HN2···OW^iii	0.91 (2)	1.97 (2)	2.796 (2)	151.0 (18)
N1—HN3···O1^iv	1.02 (2)	1.74 (2)	2.755 (2)	171.7 (19)

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