The importance of screening solid-state phases of a racemic modification of a chiral drug: thermodynamic and structural characterization of solid-state phases of etiracetam

In this contribution different solid-state forms of the racemic compound (RS)-2-(2-oxo-pyrrolidin-1yl)-butyramide are studied from a structural and thermal point of view. Three different solid-state phases were identified, including two polymorphs and one hydrate phase. Comparison is made with the structure of the (S)-enantiomer, for which only one solid-state phase is known. The basic structural motif found in both polymorphs of the racemic compound is similar, but the basic motif observed for the hydrate differs. These synthons could in principle be used in future polymorph prediction studies to screen for possible alternative forms of the enantiopure compound. Based on the structure of the hydrate, further efforts should therefore be made in order to identify a hydrate structure of the enantiopure compound. Studying the different phases of a racemic compound can therefore help to guide polymorphic screening of an enantiopure compound.

Computing details

Data collection: CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET) (compiled Jan 5 2010,16:28:46) for Etiracetam_FI. Cell refinement: CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET) (compiled Jan 5 2010,16:28:46) for Etiracetam_FI. Data reduction: CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET) (compiled Jan 5 2010,16:28:46) for Etiracetam_FI. Program(s) used to solve structure: sir92 for Etiracetam_FI. For all compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

Figures

(Etiracetam_FI)

Crystal data

C8H14N2O2	F(000) = 368
Mr = 170.21	Dx = 1.296 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3065 reflections
a = 9.5932 (3) Å	θ = 3.4–32.5°
b = 7.8325 (3) Å	µ = 0.09 mm^−1
c = 11.9547 (4) Å	T = 293 K
β = 103.830 (3)°	Bipyramid, colorless
V = 872.22 (5) Å^3	0.22 × 0.18 × 0.15 mm
Z = 4

Data collection

Xcalibur, Ruby, Gemini ultra diffractometer	2891 independent reflections
Radiation source: fine-focus sealed tube	2102 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.017
Detector resolution: 10.3712 pixels mm^-1	θmax = 32.6°, θmin = 3.4°
ω scans	h = −14→14
Absorption correction: multi-scan CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET) (compiled Jan 5 2010,16:28:46) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.	k = −9→11
Tmin = 0.980, Tmax = 0.986	l = −8→18
5882 measured reflections

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.122	H atoms treated by a mixture of independent and constrained refinement
S = 1.01	w = 1/[σ^2(Fo^2) + (0.077P)^2] where P = (Fo^2 + 2Fc^2)/3
2891 reflections	(Δ/σ)max < 0.001
118 parameters	Δρmax = 0.30 e Å^−3
0 restraints	Δρmin = −0.17 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.

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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.79178 (10)	0.05261 (14)	0.38805 (9)	0.0374 (2)
H1A	0.8676	−0.0203	0.4312	0.045*
H1B	0.8339	0.1408	0.3496	0.045*
C2	0.68108 (12)	−0.05037 (16)	0.30221 (10)	0.0451 (3)
H2A	0.7007	−0.0471	0.2263	0.054*
H2B	0.6803	−0.1684	0.3267	0.054*
C3	0.53957 (11)	0.03635 (15)	0.30150 (10)	0.0427 (3)
H3A	0.5140	0.1169	0.2382	0.051*
H3B	0.4632	−0.0471	0.2941	0.051*
C4	0.56468 (9)	0.12746 (11)	0.41579 (8)	0.0309 (2)
C5	0.77402 (9)	0.21574 (12)	0.56912 (8)	0.02737 (19)
H5	0.6965	0.2537	0.6038	0.033*
C6	0.87028 (9)	0.09563 (12)	0.65596 (8)	0.02850 (19)
C7	0.85501 (11)	0.37558 (13)	0.54663 (9)	0.0379 (2)
H7A	0.8966	0.4312	0.6195	0.045*
H7B	0.9330	0.3420	0.5125	0.045*
C8	0.75959 (13)	0.50108 (16)	0.46770 (12)	0.0523 (3)
H8A	0.7314	0.4539	0.3915	0.079*
H8B	0.8111	0.6057	0.4656	0.079*
H8C	0.6757	0.5234	0.4959	0.079*
N1	0.70754 (7)	0.12708 (10)	0.46327 (6)	0.02767 (18)
N2	0.82835 (10)	−0.06625 (12)	0.65596 (8)	0.0386 (2)
O1	0.47334 (7)	0.19244 (10)	0.45907 (7)	0.0419 (2)
O2	0.97979 (8)	0.14929 (10)	0.72218 (7)	0.0431 (2)
H2C	0.7450 (15)	−0.0998 (17)	0.6112 (12)	0.049 (4)*
H2D	0.8786 (17)	−0.1362 (19)	0.7068 (14)	0.061 (4)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0325 (5)	0.0451 (6)	0.0350 (5)	0.0000 (4)	0.0087 (4)	−0.0070 (4)
C2	0.0487 (6)	0.0468 (6)	0.0354 (5)	0.0014 (5)	0.0014 (5)	−0.0096 (5)
C3	0.0382 (5)	0.0436 (6)	0.0374 (5)	−0.0029 (4)	−0.0082 (4)	−0.0027 (4)
C4	0.0237 (4)	0.0283 (4)	0.0357 (5)	−0.0008 (3)	−0.0025 (3)	0.0041 (4)
C5	0.0232 (4)	0.0282 (4)	0.0277 (4)	0.0009 (3)	0.0002 (3)	−0.0033 (3)
C6	0.0246 (4)	0.0311 (4)	0.0276 (4)	0.0016 (3)	0.0018 (3)	−0.0022 (3)
C7	0.0326 (5)	0.0306 (5)	0.0439 (6)	−0.0039 (4)	−0.0037 (4)	0.0023 (4)
C8	0.0497 (6)	0.0393 (6)	0.0596 (8)	−0.0017 (5)	−0.0036 (6)	0.0136 (5)
N1	0.0207 (3)	0.0321 (4)	0.0274 (4)	−0.0007 (3)	0.0004 (3)	−0.0035 (3)
N2	0.0320 (4)	0.0325 (4)	0.0435 (5)	−0.0023 (3)	−0.0065 (4)	0.0069 (4)
O1	0.0234 (3)	0.0424 (4)	0.0568 (5)	0.0049 (3)	0.0033 (3)	−0.0007 (3)
O2	0.0362 (4)	0.0373 (4)	0.0438 (4)	−0.0029 (3)	−0.0138 (3)	−0.0012 (3)

Geometric parameters (Å, º)

C1—N1	1.4661 (12)	C5—C7	1.5307 (13)
C1—C2	1.5200 (15)	C5—C6	1.5354 (12)
C1—H1A	0.9700	C5—H5	0.9800
C1—H1B	0.9700	C6—O2	1.2285 (11)
C2—C3	1.5162 (16)	C6—N2	1.3302 (13)
C2—H2A	0.9700	C7—C8	1.5105 (15)
C2—H2B	0.9700	C7—H7A	0.9700
C3—C4	1.5089 (15)	C7—H7B	0.9700
C3—H3A	0.9700	C8—H8A	0.9600
C3—H3B	0.9700	C8—H8B	0.9600
C4—O1	1.2293 (12)	C8—H8C	0.9600
C4—N1	1.3523 (11)	N2—H2C	0.889 (14)
C5—N1	1.4507 (11)	N2—H2D	0.873 (16)
N1—C1—C2	103.10 (8)	N1—C5—H5	107.1
N1—C1—H1A	111.1	C7—C5—H5	107.1
C2—C1—H1A	111.1	C6—C5—H5	107.1
N1—C1—H1B	111.1	O2—C6—N2	122.56 (9)
C2—C1—H1B	111.1	O2—C6—C5	120.63 (8)
H1A—C1—H1B	109.1	N2—C6—C5	116.81 (8)
C3—C2—C1	104.25 (9)	C8—C7—C5	112.63 (8)
C3—C2—H2A	110.9	C8—C7—H7A	109.1
C1—C2—H2A	110.9	C5—C7—H7A	109.1
C3—C2—H2B	110.9	C8—C7—H7B	109.1
C1—C2—H2B	110.9	C5—C7—H7B	109.1
H2A—C2—H2B	108.9	H7A—C7—H7B	107.8
C4—C3—C2	104.95 (8)	C7—C8—H8A	109.5
C4—C3—H3A	110.8	C7—C8—H8B	109.5
C2—C3—H3A	110.8	H8A—C8—H8B	109.5
C4—C3—H3B	110.8	C7—C8—H8C	109.5
C2—C3—H3B	110.8	H8A—C8—H8C	109.5
H3A—C3—H3B	108.8	H8B—C8—H8C	109.5
O1—C4—N1	125.25 (9)	C4—N1—C5	123.72 (8)
O1—C4—C3	126.97 (8)	C4—N1—C1	113.29 (8)
N1—C4—C3	107.78 (8)	C5—N1—C1	122.26 (7)
N1—C5—C7	111.97 (8)	C6—N2—H2C	120.7 (9)
N1—C5—C6	111.37 (7)	C6—N2—H2D	118.8 (10)
C7—C5—C6	111.80 (7)	H2C—N2—H2D	120.1 (13)
N1—C1—C2—C3	25.12 (11)	O1—C4—N1—C5	−4.88 (15)
C1—C2—C3—C4	−23.26 (11)	C3—C4—N1—C5	174.59 (8)
C2—C3—C4—O1	−168.09 (10)	O1—C4—N1—C1	−175.25 (9)
C2—C3—C4—N1	12.45 (11)	C3—C4—N1—C1	4.22 (11)
N1—C5—C6—O2	146.74 (9)	C7—C5—N1—C4	−106.79 (10)
C7—C5—C6—O2	20.64 (12)	C6—C5—N1—C4	127.20 (9)
N1—C5—C6—N2	−33.81 (11)	C7—C5—N1—C1	62.74 (11)
C7—C5—C6—N2	−159.91 (9)	C6—C5—N1—C1	−63.27 (11)
N1—C5—C7—C8	58.15 (12)	C2—C1—N1—C4	−18.93 (11)
C6—C5—C7—C8	−176.08 (10)	C2—C1—N1—C5	170.54 (9)

(Etiracetam_FII)

Crystal data

C8H14N2O2	Z = 4
Mr = 170.21	F(000) = 368
Monoclinic, P21/c	Dx = 1.260 Mg m^−3
a = 9.3020 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 11.5223 (7) Å	µ = 0.09 mm^−1
c = 8.4172 (5) Å	T = 293 K
β = 95.966 (7)°	0.20 × 0.10 × 0.04 mm
V = 897.27 (11) Å^3

Data collection

Xcalibur, Ruby, Gemini ultra diffractometer	2982 independent reflections
Radiation source: fine-focus sealed tube	878 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.064
Detector resolution: 10.3712 pixels mm^-1	θmax = 32.6°, θmin = 3.5°
ω scans	h = −10→13
Absorption correction: multi-scan CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET) (compiled Jan 5 2010,16:28:46) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.	k = −10→17
Tmin = 0.982, Tmax = 0.996	l = −12→12
5986 measured reflections

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)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.146	H atoms treated by a mixture of independent and constrained refinement
S = 0.66	w = 1/[σ^2(Fo^2) + (0.0709P)^2] where P = (Fo^2 + 2Fc^2)/3
2982 reflections	(Δ/σ)max < 0.001
110 parameters	Δρmax = 0.19 e Å^−3
0 restraints	Δρmin = −0.17 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.

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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.8260 (2)	−0.03766 (18)	0.4563 (2)	0.0281 (5)
C2	0.7499 (3)	0.0084 (2)	0.5927 (2)	0.0393 (6)
C3	0.6682 (3)	0.1139 (2)	0.5251 (3)	0.0488 (7)
H3A	0.5693	0.1123	0.5518	0.059*
H3B	0.7139	0.1844	0.5683	0.059*
C4	0.6716 (3)	0.10935 (19)	0.3462 (3)	0.0415 (6)
H4A	0.5784	0.0860	0.2933	0.050*
H4B	0.6974	0.1843	0.3050	0.050*
C5	0.8281 (2)	−0.00310 (17)	0.1662 (2)	0.0280 (5)
H5	0.9057	−0.0607	0.1825	0.034*
C6	0.8920 (2)	0.10431 (17)	0.0933 (3)	0.0310 (5)
C7	0.7084 (3)	−0.0570 (2)	0.0539 (3)	0.0465 (7)
H7A	0.6317	−0.0004	0.0317	0.056*
H7B	0.7461	−0.0753	−0.0463	0.056*
C8	0.6452 (3)	−0.1665 (2)	0.1194 (4)	0.0685 (9)
H8A	0.7207	−0.2225	0.1435	0.103*
H8B	0.5733	−0.1980	0.0411	0.103*
H8C	0.6017	−0.1481	0.2148	0.103*
N1	0.78199 (18)	0.02277 (13)	0.32354 (19)	0.0270 (4)
N2	0.9744 (2)	0.17279 (16)	0.1912 (2)	0.0407 (5)
H2C	1.0155	0.2324	0.1543	0.049*
H2D	0.9867	0.1576	0.2918	0.049*
O1	0.91207 (17)	−0.11918 (12)	0.46377 (17)	0.0403 (4)
O2	0.87115 (19)	0.12224 (13)	−0.05084 (18)	0.0492 (5)
H2A	0.8183	0.0177	0.7019	0.080*
H2B	0.6713	−0.0616	0.6245	0.080*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0335 (13)	0.0252 (11)	0.0260 (12)	−0.0049 (11)	0.0052 (9)	−0.0005 (10)
C2	0.0506 (16)	0.0422 (13)	0.0274 (12)	0.0054 (12)	0.0145 (11)	−0.0011 (11)
C3	0.0604 (18)	0.0421 (14)	0.0476 (16)	0.0078 (13)	0.0227 (13)	−0.0057 (13)
C4	0.0447 (16)	0.0394 (13)	0.0425 (15)	0.0141 (12)	0.0149 (12)	0.0056 (12)
C5	0.0345 (12)	0.0266 (11)	0.0237 (11)	0.0015 (10)	0.0071 (9)	0.0009 (9)
C6	0.0354 (14)	0.0320 (12)	0.0269 (12)	0.0063 (11)	0.0106 (10)	−0.0011 (10)
C7	0.0512 (17)	0.0529 (15)	0.0352 (13)	−0.0122 (13)	0.0034 (12)	−0.0026 (12)
C8	0.077 (2)	0.0574 (17)	0.0707 (19)	−0.0297 (17)	0.0068 (17)	−0.0072 (16)
N1	0.0336 (10)	0.0255 (9)	0.0233 (9)	0.0056 (8)	0.0092 (8)	0.0009 (8)
N2	0.0546 (14)	0.0391 (11)	0.0284 (10)	−0.0146 (10)	0.0040 (10)	0.0061 (9)
O1	0.0523 (11)	0.0323 (8)	0.0364 (10)	0.0147 (8)	0.0044 (8)	0.0037 (7)
O2	0.0775 (14)	0.0488 (10)	0.0227 (9)	−0.0099 (9)	0.0112 (8)	0.0071 (8)

Geometric parameters (Å, º)

C1—O1	1.232 (2)	C5—C7	1.516 (3)
C1—N1	1.344 (2)	C5—C6	1.529 (3)
C1—C2	1.506 (3)	C5—H5	0.9800
C2—C3	1.513 (3)	C6—O2	1.226 (2)
C2—H2A	1.0679	C6—N2	1.326 (3)
C2—H2B	1.1392	C7—C8	1.520 (3)
C3—C4	1.510 (3)	C7—H7A	0.9700
C3—H3A	0.9700	C7—H7B	0.9700
C3—H3B	0.9700	C8—H8A	0.9600
C4—N1	1.459 (2)	C8—H8B	0.9600
C4—H4A	0.9700	C8—H8C	0.9600
C4—H4B	0.9700	N2—H2C	0.8600
C5—N1	1.464 (2)	N2—H2D	0.8600
O1—C1—N1	125.28 (19)	N1—C5—H5	107.0
O1—C1—C2	125.78 (19)	C7—C5—H5	107.0
N1—C1—C2	108.93 (18)	C6—C5—H5	107.0
C1—C2—C3	104.75 (17)	O2—C6—N2	122.5 (2)
C1—C2—H2A	114.0	O2—C6—C5	120.4 (2)
C3—C2—H2A	118.3	N2—C6—C5	117.11 (19)
C1—C2—H2B	107.1	C8—C7—C5	113.6 (2)
C3—C2—H2B	110.4	C8—C7—H7A	108.8
H2A—C2—H2B	102.0	C5—C7—H7A	108.8
C4—C3—C2	106.55 (17)	C8—C7—H7B	108.8
C4—C3—H3A	110.4	C5—C7—H7B	108.8
C2—C3—H3A	110.4	H7A—C7—H7B	107.7
C4—C3—H3B	110.4	C7—C8—H8A	109.5
C2—C3—H3B	110.4	C7—C8—H8B	109.5
H3A—C3—H3B	108.6	H8A—C8—H8B	109.5
N1—C4—C3	104.02 (18)	C7—C8—H8C	109.5
N1—C4—H4A	111.0	H8A—C8—H8C	109.5
C3—C4—H4A	111.0	H8B—C8—H8C	109.5
N1—C4—H4B	111.0	C1—N1—C5	123.66 (17)
C3—C4—H4B	111.0	C1—N1—C4	113.77 (17)
H4A—C4—H4B	109.0	C5—N1—C4	122.27 (17)
N1—C5—C7	112.48 (18)	C6—N2—H2C	120.0
N1—C5—C6	111.16 (16)	C6—N2—H2D	120.0
C7—C5—C6	111.84 (17)	H2C—N2—H2D	120.0
O1—C1—C2—C3	175.1 (2)	O1—C1—N1—C5	2.0 (3)
N1—C1—C2—C3	−6.5 (2)	C2—C1—N1—C5	−176.48 (17)
C1—C2—C3—C4	12.7 (2)	O1—C1—N1—C4	175.8 (2)
C2—C3—C4—N1	−14.0 (2)	C2—C1—N1—C4	−2.7 (2)
N1—C5—C6—O2	−143.52 (19)	C7—C5—N1—C1	107.8 (2)
C7—C5—C6—O2	−16.9 (3)	C6—C5—N1—C1	−125.9 (2)
N1—C5—C6—N2	39.2 (3)	C7—C5—N1—C4	−65.5 (2)
C7—C5—C6—N2	165.81 (19)	C6—C5—N1—C4	60.8 (3)
N1—C5—C7—C8	−56.1 (3)	C3—C4—N1—C1	10.6 (2)
C6—C5—C7—C8	178.0 (2)	C3—C4—N1—C5	−175.46 (18)

(Etiracetam_Hydrate)

Crystal data

C8H14N2O2·H2O	Z = 2
Mr = 188.23	F(000) = 204
Triclinic, P1	Dx = 1.252 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.2006 (5) Å	Cell parameters from 2333 reflections
b = 7.9639 (5) Å	θ = 3.4–32.6°
c = 9.5468 (6) Å	µ = 0.10 mm^−1
α = 85.293 (5)°	T = 293 K
β = 76.031 (6)°	Prism, colourless
γ = 70.023 (6)°	0.20 × 0.18 × 0.14 mm
V = 499.30 (6) Å^3

Data collection

Xcalibur, Ruby, Gemini ultra diffractometer	3290 independent reflections
Radiation source: fine-focus sealed tube	2015 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.023
Detector resolution: 10.3712 pixels mm^-1	θmax = 32.7°, θmin = 3.4°
ω scans	h = −10→10
Absorption correction: multi-scan CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.55 (release 05-01-2010 CrysAlis171 .NET) (compiled Jan 5 2010,16:28:46) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.	k = −10→12
Tmin = 0.981, Tmax = 0.987	l = −13→13
5863 measured reflections

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)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.134	H atoms treated by a mixture of independent and constrained refinement
S = 0.94	w = 1/[σ^2(Fo^2) + (0.0762P)^2] where P = (Fo^2 + 2Fc^2)/3
3290 reflections	(Δ/σ)max < 0.001
135 parameters	Δρmax = 0.24 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.

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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.64229 (18)	0.12134 (16)	0.59858 (13)	0.0423 (3)
C2	0.7691 (2)	−0.06906 (18)	0.61925 (17)	0.0581 (4)
H2A	0.9090	−0.0918	0.5675	0.070*
H2B	0.7170	−0.1513	0.5849	0.070*
C3	0.7538 (2)	−0.08979 (18)	0.78088 (17)	0.0565 (4)
H3A	0.8850	−0.1570	0.8010	0.068*
H3B	0.6581	−0.1506	0.8247	0.068*
C4	0.68020 (19)	0.10033 (17)	0.83719 (14)	0.0450 (3)
H4A	0.5826	0.1134	0.9290	0.054*
H4B	0.7926	0.1345	0.8488	0.054*
C5	0.48294 (15)	0.39969 (14)	0.73852 (11)	0.0329 (2)
H5	0.4541	0.4428	0.6443	0.039*
C6	0.27817 (15)	0.44750 (15)	0.84804 (12)	0.0343 (2)
C7	0.61868 (17)	0.49527 (16)	0.77067 (14)	0.0431 (3)
H7A	0.6497	0.4566	0.8639	0.052*
H7B	0.5464	0.6229	0.7759	0.052*
C8	0.8161 (2)	0.4582 (2)	0.65597 (17)	0.0574 (4)
H8A	0.8912	0.3326	0.6537	0.086*
H8B	0.8954	0.5233	0.6786	0.086*
H8C	0.7861	0.4954	0.5634	0.086*
N1	0.58525 (13)	0.20777 (12)	0.72503 (9)	0.0328 (2)
N2	0.19197 (16)	0.32228 (15)	0.88046 (13)	0.0457 (3)
O1	0.59756 (19)	0.19044 (14)	0.48629 (10)	0.0669 (3)
O2	0.19811 (12)	0.59925 (11)	0.90024 (10)	0.0470 (2)
O3	0.24206 (17)	−0.04415 (15)	0.79030 (14)	0.0612 (3)
H2C	0.074 (3)	0.350 (2)	0.9484 (18)	0.062 (4)*
H2D	0.244 (2)	0.217 (2)	0.8393 (17)	0.056 (4)*
H3C	0.219 (3)	−0.141 (3)	0.835 (2)	0.101 (7)*
H3D	0.287 (3)	−0.087 (3)	0.703 (2)	0.080 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0467 (6)	0.0387 (6)	0.0358 (6)	−0.0147 (5)	0.0039 (5)	−0.0065 (5)
C2	0.0600 (8)	0.0349 (7)	0.0634 (9)	−0.0104 (6)	0.0104 (7)	−0.0088 (6)
C3	0.0514 (8)	0.0395 (7)	0.0757 (10)	−0.0096 (6)	−0.0190 (7)	0.0056 (7)
C4	0.0459 (7)	0.0435 (7)	0.0429 (7)	−0.0115 (5)	−0.0122 (5)	0.0070 (5)
C5	0.0322 (5)	0.0309 (5)	0.0291 (5)	−0.0063 (4)	−0.0004 (4)	−0.0023 (4)
C6	0.0300 (5)	0.0360 (6)	0.0321 (5)	−0.0069 (4)	−0.0036 (4)	−0.0017 (4)
C7	0.0363 (6)	0.0374 (6)	0.0515 (7)	−0.0130 (5)	0.0018 (5)	−0.0091 (5)
C8	0.0393 (7)	0.0526 (8)	0.0722 (10)	−0.0180 (6)	0.0071 (6)	−0.0026 (7)
N1	0.0323 (4)	0.0297 (5)	0.0311 (5)	−0.0067 (3)	−0.0025 (4)	−0.0015 (4)
N2	0.0349 (5)	0.0408 (6)	0.0546 (7)	−0.0134 (4)	0.0067 (5)	−0.0105 (5)
O1	0.1057 (9)	0.0562 (6)	0.0325 (5)	−0.0205 (6)	−0.0116 (5)	−0.0066 (4)
O2	0.0395 (4)	0.0366 (5)	0.0529 (5)	−0.0074 (3)	0.0070 (4)	−0.0087 (4)
O3	0.0726 (7)	0.0530 (6)	0.0564 (7)	−0.0241 (5)	−0.0016 (5)	−0.0163 (5)

Geometric parameters (Å, º)

C1—O1	1.2265 (17)	C5—C6	1.5329 (14)
C1—N1	1.3430 (15)	C5—H5	0.9800
C1—C2	1.5046 (19)	C6—O2	1.2351 (13)
C2—C3	1.520 (2)	C6—N2	1.3248 (16)
C2—H2A	0.9700	C7—C8	1.5238 (16)
C2—H2B	0.9700	C7—H7A	0.9700
C3—C4	1.5199 (18)	C7—H7B	0.9700
C3—H3A	0.9700	C8—H8A	0.9600
C3—H3B	0.9700	C8—H8B	0.9600
C4—N1	1.4661 (15)	C8—H8C	0.9600
C4—H4A	0.9700	N2—H2C	0.906 (17)
C4—H4B	0.9700	N2—H2D	0.877 (17)
C5—N1	1.4535 (13)	O3—H3C	0.90 (3)
C5—C7	1.5234 (16)	O3—H3D	0.87 (2)
O1—C1—N1	124.36 (12)	C7—C5—H5	106.8
O1—C1—C2	127.01 (12)	C6—C5—H5	106.8
N1—C1—C2	108.63 (11)	O2—C6—N2	122.57 (10)
C1—C2—C3	105.22 (11)	O2—C6—C5	119.90 (10)
C1—C2—H2A	110.7	N2—C6—C5	117.51 (10)
C3—C2—H2A	110.7	C5—C7—C8	112.04 (10)
C1—C2—H2B	110.7	C5—C7—H7A	109.2
C3—C2—H2B	110.7	C8—C7—H7A	109.2
H2A—C2—H2B	108.8	C5—C7—H7B	109.2
C2—C3—C4	104.63 (11)	C8—C7—H7B	109.2
C2—C3—H3A	110.8	H7A—C7—H7B	107.9
C4—C3—H3A	110.8	C7—C8—H8A	109.5
C2—C3—H3B	110.8	C7—C8—H8B	109.5
C4—C3—H3B	110.8	H8A—C8—H8B	109.5
H3A—C3—H3B	108.9	C7—C8—H8C	109.5
N1—C4—C3	103.67 (10)	H8A—C8—H8C	109.5
N1—C4—H4A	111.0	H8B—C8—H8C	109.5
C3—C4—H4A	111.0	C1—N1—C5	122.66 (10)
N1—C4—H4B	111.0	C1—N1—C4	113.10 (10)
C3—C4—H4B	111.0	C5—N1—C4	122.51 (9)
H4A—C4—H4B	109.0	C6—N2—H2C	117.1 (10)
N1—C5—C7	111.85 (9)	C6—N2—H2D	123.1 (9)
N1—C5—C6	112.16 (9)	H2C—N2—H2D	119.8 (14)
C7—C5—C6	111.99 (9)	H3C—O3—H3D	97.8 (18)
N1—C5—H5	106.8
O1—C1—C2—C3	−172.82 (13)	O1—C1—N1—C5	−7.39 (19)
N1—C1—C2—C3	7.85 (15)	C2—C1—N1—C5	171.96 (10)
C1—C2—C3—C4	−18.25 (15)	O1—C1—N1—C4	−172.75 (12)
C2—C3—C4—N1	21.53 (13)	C2—C1—N1—C4	6.60 (14)
N1—C5—C6—O2	160.91 (10)	C7—C5—N1—C1	−110.21 (12)
C7—C5—C6—O2	34.20 (15)	C6—C5—N1—C1	122.99 (11)
N1—C5—C6—N2	−20.47 (14)	C7—C5—N1—C4	53.78 (13)
C7—C5—C6—N2	−147.19 (11)	C6—C5—N1—C4	−73.01 (12)
N1—C5—C7—C8	57.15 (13)	C3—C4—N1—C1	−18.14 (13)
C6—C5—C7—C8	−175.96 (10)	C3—C4—N1—C5	176.48 (9)