Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109054249/jz3168sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109054249/jz3168Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109054249/jz3168IIsup3.hkl |
CCDC references: 765486; 765487
For related literature, see: Allen (2002); Bernstein et al. (1995); Brandstätter-Kuhnert & Aepkers (1962); Brunner et al. (2003); Demole (1937); Dideberg et al. (1975); Gelbrich & Griesser (2009); Gelbrich et al. (2007); Lewis et al. (2005); Nichol & Clegg (2005); Pyżalska et al. (1980); Wilhelm & Fischer (1976); Wunderlich (1973); Zencirci et al. (2009).
Intergrown, irregular-shaped crystals of (I) were obtained from a commercial sample of narconumal (F. Hoffmann–La Roche). Additional crystallization experiments did not produce any crystals of better quality. The data collected for (I) were integrated for two separate, non-merohedrally twinned components. The final BASF parameter for the minor component was 0.356 (3).
A commercial sample of kalypnon (Boehringer und Söhne) was found to contain small, needle-shaped crystals of (II) which were clearly distinct from the rhombic crystals of the main product. The monoclinic lattice of (II) has a special geometry where the a and c axes are approximately equal in length, giving rise to imperfect pseudo-merohedral twinning. The data integration was performed out with a larger shoe box than usual in order to include the combined contributions from both twin components, and in the structure refinement the idealized pseudo-merohedral twin matrix (0 0 - 1 0 - 1 0 - 1 0 0) was applied. The final BASF parameter for the minor twin component was 0.272 (2). The data quality may also be affected by additional, small, non-merohedral twin components that could not be modelled adequately.
All H atoms were identified in a difference map. Methyl H atoms were idealized and included as rigid groups that were allowed to rotate but not tip (C—H = 0.98 Å) and refined with 1.5Ueq(C). H atoms bonded to secondary CH2 (C—H = 0.99 Å) and aromatic C atoms (C—H = 0.95 Å) were positioned geometrically and refined with Uiso = 1.2 Ueq(C). H atoms attached to N were refined with restrained distances [N—H = 0.88 (2) Å], and their Uiso parameters were refined freely.
For both compounds, data collection: COLLECT (Hooft, 1998); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997). Data reduction: EVALCCD (Duisenberg et al., 2003) for (I); HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997) for (II). For both compounds, program(s) used to solve structure: SHELXL97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP/SHELXTL (Sheldrick, 2008) and Mercury (Bruno et al., 2002); software used to prepare material for publication: publCIF (Westrip, 2009).
C11H16N2O3 | Z = 2 |
Mr = 224.26 | F(000) = 240 |
Triclinic, P1 | Dx = 1.298 Mg m−3 |
Hall symbol: -P 1 | Melting point: 332(1) K |
a = 6.4160 (7) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 7.9559 (8) Å | Cell parameters from 2190 reflections |
c = 11.9569 (12) Å | θ = 0.4–26.4° |
α = 77.574 (7)° | µ = 0.10 mm−1 |
β = 80.837 (7)° | T = 120 K |
γ = 75.518 (6)° | Block, colourless |
V = 573.51 (10) Å3 | 0.25 × 0.2 × 0.2 mm |
KappaCCD diffractometer | 2000 independent reflections |
Radiation source: Bruker Nonius FR591 rotating anode | 1386 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0 |
Detector resolution: 9.091 pixels mm-1 | θmax = 25°, θmin = 3.3° |
ϕ and ω scans | h = −7→7 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2007) | k = −9→9 |
Tmin = 0.977, Tmax = 0.981 | l = 0→14 |
2000 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.071 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.114 | w = 1/[σ2(Fo2) + (0.0042P)2 + 0.6197P] where P = (Fo2 + 2Fc2)/3 |
S = 1.18 | (Δ/σ)max < 0.001 |
2000 reflections | Δρmax = 0.32 e Å−3 |
154 parameters | Δρmin = −0.33 e Å−3 |
1 restraint | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.027 (4) |
C11H16N2O3 | γ = 75.518 (6)° |
Mr = 224.26 | V = 573.51 (10) Å3 |
Triclinic, P1 | Z = 2 |
a = 6.4160 (7) Å | Mo Kα radiation |
b = 7.9559 (8) Å | µ = 0.10 mm−1 |
c = 11.9569 (12) Å | T = 120 K |
α = 77.574 (7)° | 0.25 × 0.2 × 0.2 mm |
β = 80.837 (7)° |
KappaCCD diffractometer | 2000 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2007) | 1386 reflections with I > 2σ(I) |
Tmin = 0.977, Tmax = 0.981 | Rint = 0 |
2000 measured reflections |
R[F2 > 2σ(F2)] = 0.071 | 1 restraint |
wR(F2) = 0.114 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.18 | Δρmax = 0.32 e Å−3 |
2000 reflections | Δρmin = −0.33 e Å−3 |
154 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.0431 (4) | 0.9439 (4) | 0.1859 (2) | 0.0178 (7) | |
O2 | 0.2302 (4) | 1.0928 (3) | 0.0345 (2) | 0.0241 (6) | |
C2 | 0.2261 (5) | 0.9609 (4) | 0.1091 (3) | 0.0180 (8) | |
N3 | 0.4043 (5) | 0.8231 (4) | 0.1193 (2) | 0.0195 (7) | |
H3 | 0.522 (4) | 0.841 (5) | 0.074 (3) | 0.041 (13)* | |
O4 | 0.5950 (4) | 0.5603 (3) | 0.2026 (2) | 0.0283 (6) | |
C4 | 0.4222 (5) | 0.6678 (4) | 0.2010 (3) | 0.0200 (8) | |
C5 | 0.2236 (5) | 0.6386 (4) | 0.2817 (3) | 0.0165 (7) | |
O6 | −0.1331 (4) | 0.7966 (3) | 0.3374 (2) | 0.0236 (6) | |
C6 | 0.0318 (5) | 0.7967 (4) | 0.2716 (3) | 0.0180 (8) | |
C7 | −0.1499 (5) | 1.0909 (4) | 0.1761 (3) | 0.0229 (8) | |
H7A | −0.279 | 1.0438 | 0.1808 | 0.034* | |
H7B | −0.1333 | 1.1708 | 0.1021 | 0.034* | |
H7C | −0.1657 | 1.1558 | 0.2391 | 0.034* | |
C8 | 0.1419 (6) | 0.4828 (4) | 0.2531 (3) | 0.0213 (8) | |
H8 | −0.0056 | 0.4842 | 0.2959 | 0.026* | |
C9 | 0.2853 (6) | 0.3000 (5) | 0.2918 (3) | 0.0321 (10) | |
H9A | 0.2257 | 0.2093 | 0.2723 | 0.048* | |
H9B | 0.2896 | 0.279 | 0.3753 | 0.048* | |
H9C | 0.4324 | 0.2949 | 0.2525 | 0.048* | |
C10 | 0.1185 (6) | 0.5130 (5) | 0.1245 (3) | 0.0274 (9) | |
H10A | 0.2621 | 0.5023 | 0.0803 | 0.041* | |
H10B | 0.0299 | 0.6315 | 0.1006 | 0.041* | |
H10C | 0.0485 | 0.4246 | 0.1101 | 0.041* | |
C11 | 0.2828 (6) | 0.6007 (5) | 0.4062 (3) | 0.0252 (9) | |
H11A | 0.1569 | 0.5737 | 0.4605 | 0.03* | |
H11B | 0.404 | 0.4955 | 0.4161 | 0.03* | |
C12 | 0.3475 (6) | 0.7548 (5) | 0.4349 (3) | 0.0244 (8) | |
H12 | 0.4767 | 0.7857 | 0.3947 | 0.029* | |
C13 | 0.2382 (6) | 0.8492 (5) | 0.5113 (3) | 0.0313 (9) | |
H13A | 0.1082 | 0.8221 | 0.5531 | 0.038* | |
H13B | 0.289 | 0.9447 | 0.5248 | 0.038* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0161 (15) | 0.0174 (15) | 0.0181 (16) | −0.0012 (12) | −0.0021 (12) | −0.0025 (12) |
O2 | 0.0266 (14) | 0.0190 (14) | 0.0223 (14) | −0.0047 (11) | 0.0016 (11) | 0.0019 (12) |
C2 | 0.0196 (19) | 0.0180 (19) | 0.0181 (19) | −0.0037 (15) | −0.0027 (15) | −0.0072 (16) |
N3 | 0.0162 (17) | 0.0202 (16) | 0.0184 (16) | −0.0030 (13) | 0.0026 (13) | −0.0003 (13) |
O4 | 0.0163 (14) | 0.0284 (15) | 0.0333 (16) | 0.0009 (12) | −0.0016 (11) | 0.0014 (12) |
C4 | 0.017 (2) | 0.0208 (19) | 0.022 (2) | −0.0028 (16) | −0.0037 (15) | −0.0047 (15) |
C5 | 0.0149 (18) | 0.0167 (18) | 0.0166 (18) | −0.0022 (14) | −0.0024 (14) | −0.0015 (14) |
O6 | 0.0191 (14) | 0.0255 (14) | 0.0227 (14) | −0.0051 (10) | 0.0022 (11) | −0.0002 (11) |
C6 | 0.0167 (19) | 0.023 (2) | 0.0170 (19) | −0.0087 (15) | −0.0009 (16) | −0.0047 (16) |
C7 | 0.020 (2) | 0.0159 (19) | 0.030 (2) | 0.0015 (15) | −0.0028 (16) | −0.0045 (16) |
C8 | 0.0185 (19) | 0.0178 (18) | 0.027 (2) | −0.0047 (15) | −0.0002 (15) | −0.0041 (15) |
C9 | 0.030 (2) | 0.024 (2) | 0.044 (2) | −0.0058 (17) | −0.0137 (19) | −0.0035 (18) |
C10 | 0.031 (2) | 0.028 (2) | 0.026 (2) | −0.0085 (17) | −0.0047 (17) | −0.0067 (17) |
C11 | 0.024 (2) | 0.026 (2) | 0.024 (2) | −0.0032 (16) | −0.0040 (16) | −0.0027 (16) |
C12 | 0.0159 (19) | 0.035 (2) | 0.022 (2) | −0.0077 (16) | −0.0044 (15) | −0.0018 (17) |
C13 | 0.036 (2) | 0.034 (2) | 0.026 (2) | −0.0091 (18) | −0.0041 (18) | −0.0083 (18) |
N1—C2 | 1.386 (4) | C8—C10 | 1.531 (5) |
N1—C6 | 1.389 (4) | C8—C9 | 1.534 (5) |
N1—C7 | 1.476 (4) | C8—H8 | 1 |
O2—C2 | 1.225 (4) | C9—H9A | 0.98 |
C2—N3 | 1.372 (4) | C9—H9B | 0.98 |
N3—C4 | 1.392 (4) | C9—H9C | 0.98 |
N3—H3 | 0.881 (19) | C10—H10A | 0.98 |
O4—C4 | 1.219 (4) | C10—H10B | 0.98 |
C4—C5 | 1.506 (5) | C10—H10C | 0.98 |
C5—C6 | 1.523 (5) | C11—C12 | 1.508 (5) |
C5—C11 | 1.543 (5) | C11—H11A | 0.99 |
C5—C8 | 1.579 (5) | C11—H11B | 0.99 |
O6—C6 | 1.214 (4) | C12—C13 | 1.311 (5) |
C7—H7A | 0.98 | C12—H12 | 0.95 |
C7—H7B | 0.98 | C13—H13A | 0.95 |
C7—H7C | 0.98 | C13—H13B | 0.95 |
C2—N1—C6 | 123.6 (3) | C9—C8—C5 | 113.4 (3) |
C2—N1—C7 | 118.1 (3) | C10—C8—H8 | 107.4 |
C6—N1—C7 | 118.3 (3) | C9—C8—H8 | 107.4 |
O2—C2—N3 | 120.8 (3) | C5—C8—H8 | 107.4 |
O2—C2—N1 | 121.8 (3) | C8—C9—H9A | 109.5 |
N3—C2—N1 | 117.4 (3) | C8—C9—H9B | 109.5 |
C2—N3—C4 | 126.5 (3) | H9A—C9—H9B | 109.5 |
C2—N3—H3 | 116 (3) | C8—C9—H9C | 109.5 |
C4—N3—H3 | 117 (3) | H9A—C9—H9C | 109.5 |
O4—C4—N3 | 119.0 (3) | H9B—C9—H9C | 109.5 |
O4—C4—C5 | 123.0 (3) | C8—C10—H10A | 109.5 |
N3—C4—C5 | 118.0 (3) | C8—C10—H10B | 109.5 |
C4—C5—C6 | 114.0 (3) | H10A—C10—H10B | 109.5 |
C4—C5—C11 | 108.0 (3) | C8—C10—H10C | 109.5 |
C6—C5—C11 | 107.4 (3) | H10A—C10—H10C | 109.5 |
C4—C5—C8 | 109.6 (3) | H10B—C10—H10C | 109.5 |
C6—C5—C8 | 105.4 (3) | C12—C11—C5 | 112.0 (3) |
C11—C5—C8 | 112.5 (3) | C12—C11—H11A | 109.2 |
O6—C6—N1 | 118.9 (3) | C5—C11—H11A | 109.2 |
O6—C6—C5 | 121.0 (3) | C12—C11—H11B | 109.2 |
N1—C6—C5 | 120.1 (3) | C5—C11—H11B | 109.2 |
N1—C7—H7A | 109.5 | H11A—C11—H11B | 107.9 |
N1—C7—H7B | 109.5 | C13—C12—C11 | 124.7 (3) |
H7A—C7—H7B | 109.5 | C13—C12—H12 | 117.7 |
N1—C7—H7C | 109.5 | C11—C12—H12 | 117.7 |
H7A—C7—H7C | 109.5 | C12—C13—H13A | 120 |
H7B—C7—H7C | 109.5 | C12—C13—H13B | 120 |
C10—C8—C9 | 110.4 (3) | H13A—C13—H13B | 120 |
C10—C8—C5 | 110.6 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3···O2i | 0.88 (2) | 1.99 (2) | 2.866 (4) | 174 (4) |
C12—H12···O6ii | 0.95 | 2.51 | 3.424 (4) | 163 |
Symmetry codes: (i) −x+1, −y+2, −z; (ii) x+1, y, z. |
C14H20N2O3 | F(000) = 568 |
Mr = 264.32 | Dx = 1.237 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 2756 reflections |
a = 10.2825 (11) Å | θ = 0.4–26.7° |
b = 13.2972 (16) Å | µ = 0.09 mm−1 |
c = 10.3959 (10) Å | T = 120 K |
β = 92.999 (7)° | Needle, colourless |
V = 1419.5 (3) Å3 | 0.1 × 0.03 × 0.02 mm |
Z = 4 |
KappaCCD diffractometer | 2440 independent reflections |
Radiation source: Bruker Nonius FR591 rotating anode | 1367 reflections with I > 2σ(I) |
10cm confocal mirrors monochromator | Rint = 0.147 |
Detector resolution: 4096x4096pixels / 62x62mm pixels mm-1 | θmax = 25°, θmin = 3.1° |
ϕ and ω scans | h = −12→12 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2007) | k = −13→15 |
Tmin = 0.991, Tmax = 1.000 | l = −11→12 |
11137 measured reflections |
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)] = 0.080 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.127 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.21 | w = 1/[σ2(Fo2) + (0.0057P)2 + 0.6664P] where P = (Fo2 + 2Fc2)/3 |
2440 reflections | (Δ/σ)max < 0.001 |
180 parameters | Δρmax = 0.33 e Å−3 |
1 restraint | Δρmin = −0.29 e Å−3 |
C14H20N2O3 | V = 1419.5 (3) Å3 |
Mr = 264.32 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 10.2825 (11) Å | µ = 0.09 mm−1 |
b = 13.2972 (16) Å | T = 120 K |
c = 10.3959 (10) Å | 0.1 × 0.03 × 0.02 mm |
β = 92.999 (7)° |
KappaCCD diffractometer | 2440 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2007) | 1367 reflections with I > 2σ(I) |
Tmin = 0.991, Tmax = 1.000 | Rint = 0.147 |
11137 measured reflections |
R[F2 > 2σ(F2)] = 0.080 | 1 restraint |
wR(F2) = 0.127 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.21 | Δρmax = 0.33 e Å−3 |
2440 reflections | Δρmin = −0.29 e Å−3 |
180 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.6312 (4) | 0.1080 (2) | 0.7806 (4) | 0.0229 (9) | |
C2 | 0.6267 (5) | 0.0031 (3) | 0.7883 (5) | 0.0274 (11) | |
O2 | 0.5460 (3) | −0.0410 (2) | 0.8480 (3) | 0.0355 (9) | |
N3 | 0.7246 (4) | −0.0472 (3) | 0.7292 (4) | 0.0310 (10) | |
H3 | 0.743 (5) | −0.1094 (18) | 0.752 (4) | 0.055 (16)* | |
O4 | 0.9001 (3) | −0.0615 (2) | 0.6108 (3) | 0.0472 (10) | |
C4 | 0.8190 (5) | −0.0071 (4) | 0.6561 (5) | 0.0327 (12) | |
C5 | 0.8148 (4) | 0.1050 (3) | 0.6316 (4) | 0.0284 (12) | |
O6 | 0.7160 (3) | 0.2525 (2) | 0.7095 (3) | 0.0356 (8) | |
C6 | 0.7185 (5) | 0.1609 (3) | 0.7114 (5) | 0.0267 (11) | |
C7 | 0.5246 (4) | 0.1651 (3) | 0.8424 (4) | 0.0306 (12) | |
H7A | 0.4971 | 0.1278 | 0.9187 | 0.037* | |
H7B | 0.5579 | 0.2316 | 0.8717 | 0.037* | |
C8 | 0.4100 (5) | 0.1793 (4) | 0.7490 (5) | 0.0357 (13) | |
H8 | 0.3583 | 0.1221 | 0.7263 | 0.043* | |
C9 | 0.3764 (5) | 0.2670 (4) | 0.6962 (5) | 0.0391 (13) | |
H9 | 0.4278 | 0.324 | 0.7204 | 0.047* | |
C10 | 0.2651 (5) | 0.2826 (4) | 0.6023 (5) | 0.0511 (15) | |
H10A | 0.1977 | 0.322 | 0.6426 | 0.077* | |
H10B | 0.2292 | 0.2172 | 0.5751 | 0.077* | |
H10C | 0.2946 | 0.3188 | 0.5271 | 0.077* | |
C11 | 0.9511 (4) | 0.1496 (4) | 0.6548 (5) | 0.0382 (13) | |
H11A | 1.0117 | 0.1136 | 0.5999 | 0.046* | |
H11B | 0.9491 | 0.2209 | 0.6274 | 0.046* | |
C12 | 1.0030 (5) | 0.1443 (4) | 0.7910 (5) | 0.0437 (14) | |
H12 | 0.9696 | 0.1897 | 0.8516 | 0.052* | |
C13 | 1.0944 (5) | 0.0786 (4) | 0.8320 (5) | 0.0498 (15) | |
H13 | 1.1266 | 0.0335 | 0.7703 | 0.06* | |
C14 | 1.1495 (6) | 0.0707 (5) | 0.9662 (5) | 0.0635 (18) | |
H14A | 1.2444 | 0.078 | 0.9672 | 0.095* | |
H14B | 1.1276 | 0.0049 | 1.0016 | 0.095* | |
H14C | 1.113 | 0.1239 | 1.0187 | 0.095* | |
C15 | 0.7702 (5) | 0.1215 (3) | 0.4879 (4) | 0.0363 (13) | |
H15A | 0.7752 | 0.1943 | 0.4687 | 0.044* | |
H15B | 0.8325 | 0.0868 | 0.4336 | 0.044* | |
C16 | 0.6338 (5) | 0.0850 (4) | 0.4487 (5) | 0.0437 (14) | |
H16A | 0.6152 | 0.0984 | 0.3569 | 0.065* | |
H16B | 0.5704 | 0.1206 | 0.4993 | 0.065* | |
H16C | 0.6278 | 0.0126 | 0.4648 | 0.065* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.028 (2) | 0.018 (2) | 0.024 (2) | −0.0022 (17) | 0.0106 (16) | −0.0004 (18) |
C2 | 0.028 (3) | 0.027 (3) | 0.027 (3) | −0.005 (2) | 0.003 (2) | −0.004 (3) |
O2 | 0.034 (2) | 0.035 (2) | 0.038 (2) | −0.0033 (16) | 0.0133 (16) | 0.0074 (17) |
N3 | 0.035 (3) | 0.018 (2) | 0.041 (3) | 0.003 (2) | 0.017 (2) | 0.003 (2) |
O4 | 0.050 (2) | 0.0272 (19) | 0.067 (3) | 0.0081 (19) | 0.0345 (19) | 0.006 (2) |
C4 | 0.038 (3) | 0.025 (3) | 0.036 (3) | 0.003 (2) | 0.007 (2) | 0.007 (3) |
C5 | 0.024 (3) | 0.027 (3) | 0.036 (3) | −0.004 (2) | 0.013 (2) | −0.003 (2) |
O6 | 0.040 (2) | 0.0183 (16) | 0.050 (2) | −0.0016 (16) | 0.0135 (15) | −0.0018 (18) |
C6 | 0.035 (3) | 0.018 (2) | 0.028 (3) | −0.003 (2) | 0.001 (2) | −0.003 (2) |
C7 | 0.024 (3) | 0.032 (3) | 0.037 (3) | 0.003 (2) | 0.018 (2) | −0.007 (2) |
C8 | 0.029 (3) | 0.035 (3) | 0.044 (3) | −0.003 (2) | 0.014 (2) | −0.005 (3) |
C9 | 0.035 (3) | 0.046 (3) | 0.037 (3) | −0.001 (3) | 0.009 (2) | −0.007 (3) |
C10 | 0.040 (3) | 0.067 (4) | 0.048 (4) | 0.005 (3) | 0.010 (3) | 0.007 (3) |
C11 | 0.033 (3) | 0.039 (3) | 0.044 (3) | 0.000 (3) | 0.016 (2) | 0.002 (3) |
C12 | 0.030 (3) | 0.039 (3) | 0.062 (4) | −0.006 (3) | 0.002 (3) | 0.009 (3) |
C13 | 0.044 (4) | 0.056 (4) | 0.050 (4) | −0.011 (3) | 0.011 (3) | 0.005 (3) |
C14 | 0.058 (4) | 0.074 (5) | 0.058 (4) | −0.019 (3) | −0.004 (3) | 0.016 (4) |
C15 | 0.049 (3) | 0.027 (3) | 0.034 (3) | 0.004 (3) | 0.012 (2) | 0.003 (3) |
C16 | 0.056 (4) | 0.038 (3) | 0.038 (3) | −0.014 (3) | 0.007 (3) | −0.002 (3) |
N1—C6 | 1.374 (5) | C10—H10A | 0.98 |
N1—C2 | 1.398 (5) | C10—H10B | 0.98 |
N1—C7 | 1.505 (5) | C10—H10C | 0.98 |
C2—O2 | 1.213 (5) | C11—C12 | 1.489 (7) |
C2—N3 | 1.379 (6) | C11—H11A | 0.99 |
N3—C4 | 1.371 (6) | C11—H11B | 0.99 |
N3—H3 | 0.881 (19) | C12—C13 | 1.336 (7) |
O4—C4 | 1.217 (5) | C12—H12 | 0.95 |
C4—C5 | 1.513 (6) | C13—C14 | 1.482 (7) |
C5—C6 | 1.518 (6) | C13—H13 | 0.95 |
C5—C11 | 1.530 (6) | C14—H14A | 0.98 |
C5—C15 | 1.555 (6) | C14—H14B | 0.98 |
O6—C6 | 1.219 (4) | C14—H14C | 0.98 |
C7—C8 | 1.499 (6) | C15—C16 | 1.519 (6) |
C7—H7A | 0.99 | C15—H15A | 0.99 |
C7—H7B | 0.99 | C15—H15B | 0.99 |
C8—C9 | 1.327 (6) | C16—H16A | 0.98 |
C8—H8 | 0.95 | C16—H16B | 0.98 |
C9—C10 | 1.480 (7) | C16—H16C | 0.98 |
C9—H9 | 0.95 | ||
C6—N1—C2 | 124.4 (4) | H10A—C10—H10B | 109.5 |
C6—N1—C7 | 118.4 (4) | C9—C10—H10C | 109.5 |
C2—N1—C7 | 116.9 (4) | H10A—C10—H10C | 109.5 |
O2—C2—N3 | 121.9 (4) | H10B—C10—H10C | 109.5 |
O2—C2—N1 | 122.5 (4) | C12—C11—C5 | 114.3 (4) |
N3—C2—N1 | 115.6 (4) | C12—C11—H11A | 108.7 |
C4—N3—C2 | 127.8 (4) | C5—C11—H11A | 108.7 |
C4—N3—H3 | 111 (3) | C12—C11—H11B | 108.7 |
C2—N3—H3 | 119 (3) | C5—C11—H11B | 108.7 |
O4—C4—N3 | 120.2 (4) | H11A—C11—H11B | 107.6 |
O4—C4—C5 | 122.3 (5) | C13—C12—C11 | 123.1 (5) |
N3—C4—C5 | 117.5 (4) | C13—C12—H12 | 118.5 |
C4—C5—C6 | 113.8 (4) | C11—C12—H12 | 118.5 |
C4—C5—C11 | 109.7 (4) | C12—C13—C14 | 125.1 (6) |
C6—C5—C11 | 110.0 (4) | C12—C13—H13 | 117.5 |
C4—C5—C15 | 107.8 (4) | C14—C13—H13 | 117.5 |
C6—C5—C15 | 106.8 (4) | C13—C14—H14A | 109.5 |
C11—C5—C15 | 108.6 (3) | C13—C14—H14B | 109.5 |
O6—C6—N1 | 120.4 (4) | H14A—C14—H14B | 109.5 |
O6—C6—C5 | 119.6 (4) | C13—C14—H14C | 109.5 |
N1—C6—C5 | 119.9 (4) | H14A—C14—H14C | 109.5 |
C8—C7—N1 | 110.6 (4) | H14B—C14—H14C | 109.5 |
C8—C7—H7A | 109.5 | C16—C15—C5 | 115.7 (4) |
N1—C7—H7A | 109.5 | C16—C15—H15A | 108.4 |
C8—C7—H7B | 109.5 | C5—C15—H15A | 108.4 |
N1—C7—H7B | 109.5 | C16—C15—H15B | 108.4 |
H7A—C7—H7B | 108.1 | C5—C15—H15B | 108.4 |
C9—C8—C7 | 123.8 (5) | H15A—C15—H15B | 107.4 |
C9—C8—H8 | 118.1 | C15—C16—H16A | 109.5 |
C7—C8—H8 | 118.1 | C15—C16—H16B | 109.5 |
C8—C9—C10 | 124.9 (5) | H16A—C16—H16B | 109.5 |
C8—C9—H9 | 117.6 | C15—C16—H16C | 109.5 |
C10—C9—H9 | 117.6 | H16A—C16—H16C | 109.5 |
C9—C10—H10A | 109.5 | H16B—C16—H16C | 109.5 |
C9—C10—H10B | 109.5 |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3···O6i | 0.88 (2) | 1.92 (2) | 2.798 (5) | 176 (5) |
C11—H11A···O4ii | 0.99 | 2.51 | 3.432 (6) | 155 |
Symmetry codes: (i) −x+3/2, y−1/2, −z+3/2; (ii) −x+2, −y, −z+1. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C11H16N2O3 | C14H20N2O3 |
Mr | 224.26 | 264.32 |
Crystal system, space group | Triclinic, P1 | Monoclinic, P21/n |
Temperature (K) | 120 | 120 |
a, b, c (Å) | 6.4160 (7), 7.9559 (8), 11.9569 (12) | 10.2825 (11), 13.2972 (16), 10.3959 (10) |
α, β, γ (°) | 77.574 (7), 80.837 (7), 75.518 (6) | 90, 92.999 (7), 90 |
V (Å3) | 573.51 (10) | 1419.5 (3) |
Z | 2 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.10 | 0.09 |
Crystal size (mm) | 0.25 × 0.2 × 0.2 | 0.1 × 0.03 × 0.02 |
Data collection | ||
Diffractometer | KappaCCD diffractometer | KappaCCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2007) | Multi-scan (SADABS; Sheldrick, 2007) |
Tmin, Tmax | 0.977, 0.981 | 0.991, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2000, 2000, 1386 | 11137, 2440, 1367 |
Rint | 0 | 0.147 |
(sin θ/λ)max (Å−1) | 0.595 | 0.595 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.071, 0.114, 1.18 | 0.080, 0.127, 1.21 |
No. of reflections | 2000 | 2440 |
No. of parameters | 154 | 180 |
No. of restraints | 1 | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.32, −0.33 | 0.33, −0.29 |
Computer programs: COLLECT (Hooft, 1998), HKL SCALEPACK (Otwinowski & Minor, 1997), EVALCCD (Duisenberg et al., 2003), HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997), SHELXL97 (Sheldrick, 2008), XP/SHELXTL (Sheldrick, 2008) and Mercury (Bruno et al., 2002), publCIF (Westrip, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3···O2i | 0.881 (19) | 1.99 (2) | 2.866 (4) | 174 (4) |
C12—H12···O6ii | 0.95 | 2.51 | 3.424 (4) | 162.5 |
Symmetry codes: (i) −x+1, −y+2, −z; (ii) x+1, y, z. |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3···O6i | 0.881 (19) | 1.92 (2) | 2.798 (5) | 176 (5) |
C11—H11A···O4ii | 0.99 | 2.51 | 3.432 (6) | 154.6 |
Symmetry codes: (i) −x+3/2, y−1/2, −z+3/2; (ii) −x+2, −y, −z+1. |
R1 | R2 | R3 | Symmetry | Reference |
Dimer | ||||
methyl | allyl | isopropyl | inversion | (I) |
methyl | ethyl | phenyl | inversion | Lewis et al., 2005 |
p-bromophenyl | allyl | allyl | inversion | Pyżalska et al. (1980) |
cyclohexyl | allyl | allyl | inversion | Dideberg et al. (1975) |
methyl | allyl | (2R)-hex-3-yn-2-yl | none | Brunner et al. (2003) |
Chain | ||||
but-2-enyl | but-2-enyl | ethyl | 21 | (II) |
2,3-dibromopropyl | ethyl | ethyl | translation (b axis) | Gelbrich & Griesser (2009) |
methyl | β-bromoallyl | isopropyl | translation (c axis) | Wilhelm & Fischer (1976) |
methyl | ethyl | ethyl | translation (a axis) | Wunderlich (1973) |
methyl | cyclohexen-1-yl | methyl | translation (b axis) | Nichol & Clegg (2005) |
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Barbituric acid derivatives are sedative, anaesthetic, anxiolytic, hypnotic and anticonvulsant agents, which have largely been replaced in pharmaceutical use by other drugs of lower abuse liability. However, barbiturates remain a very interesting class of compounds because of their well known propensity to form multiple crystalline forms (Brandstätter-Kuhnert & Aepkers, 1962) and their hydrogen-bonding capabilities. The rigid barbiturate ring determines the geometric configuration of the potential hydrogen-bond donor and acceptor sites in the molecule (NH and carbonyl groups, see Scheme). This in turn limits the geometric diversity of the hydrogen-bond patterns that can be formed. Subsequently, the observed patterns in the subset of compounds with R1 = H are all based on a small number of standard motifs (Gelbrich et al., 2007; Zencirci et al., 2009). The number of feasible motifs should be even smaller for the related N-monosubstituted derivatives (R1 = alkyl), to which the two title compounds belong, simply because they have only one hydrogen-bond donor functionality.
Enallylpropymal, (I) [systematic name 1-methyl-5-(propan-2-yl)-5-(prop-2-en-1-yl)pyrimidine-2,4,6(1H, 3H,5H)-trione and also known as narconumal], was marketed as a potent sedative and hypnotic drug (Demole, 1937). Brandstätter-Kuhnert & Aepkers (1962) have studied its solid-state behaviour and found evidence for the existence of only one crystalline form. It has a melting point of 331–334 K, which is remarkably low in comparison to the other N-monosubstituted derivatives of barbituric acid listed in the same paper. The thermomicroscopic and DSC [differential scanning calorimetry?] data obtained for our crystals of (I) are consistent with the data reported by Brandstätter-Kuhnert & Aepkers (1962).
The asymmetric unit of (I) contains one formula unit (see Fig. 1a). The barbiturate ring is essentially planar so that the root mean square deviation of the six fitted atoms from the mean plane is just 0.02 Å. The analogous parameter is 0.05 Å for the C10—C8—C5—C11—C12 fragment, which involves adjacent sections of the isopropyl and allyl substituents. These two essentially planar molecular fragments lie almost perpendicular to one another and form an angle of 88.7 (1)°.
Two molecules of (I) are joined together by two N—H···O bonds to give a centrosymmetric dimer with a central R22(8) ring (Bernstein et al., 1995). This motif is present in many barbiturates with two NH hydrogen-bond donor groups (i.e. R1 = H, Zencirci et al., 2009). Neighbouring hydrogen-bonded dimers in the crystal structure of (I) are related to one another by translational symmetry. They assemble in such a way that the isopropyl and allyl moieties of adjacent dimers align themselves in an approximately antiparallel fashion (see Fig. 2). Furthermore, an (allyl)C—H···O6 interaction links the dimers into double-stranded chains which propagate parallel to the a axis (see Fig. 2 and Table 1).
Crystals of (II) {systematic name 1,5-di[(2E)-but-2-en-1-yl]-5-ethylpyrimidine-2,4,6(1H,3H,5H)-trione} were identified as an unexpected byproduct in a commercial sample of 5-(but-2-enyl)-5-ethylbarbituric acid, kalypnon (Boehringer und Söhne), obtained by our laboratory some 40 years ago. Kalypnon (also known as kalipnon, crotylbarbital, crotarbital, mepertan, barotal) was used for the treatment of insomnia during the 1960s.
The barbiturate ring of (II) is essentially planar with the root mean square deviation of the six fitted atoms from the mean plane being just 0.04 Å (Fig. 1b). The analogous deviation computed for the C12—C11—C5—C15—C16 set of atoms involving the ring atom C5 and adjacent fragments of the crotyl and ethyl substituents, is 0.03 Å. Similar to the structure of (I), the barbiturate ring and the C5-plane at C5 are almost perpendicular to one another and form an angle of 89.8 (2)°. The 1- and 5-substituted trans-crotyl groups lie on opposite sites [sides?] of the plane through the barbiturate ring, so that the associated anticlinal torsion angles N1—C7—C8—C9 and C5—C11—C12—C13 are of the opposite sign.
The molecules of (II) are linked to one another by one N—H···O bond (Table 2). The helical chains resulting from this interaction lie parallel to the b axis (see Fig. 3). Furthermore, chains that are adjacent to one another along the a axis are related by translational symmetry, while along the c axis there are centres of inversion between neighbouring chains. Two molecules belonging to neighbouring N—H···O-bonded chains are linked together via two (but-2-enyl)C—H···O4 contacts which are related by inversion symmetry (see Fig. 3 and Table 2). Altogether, N—H···O and C—H···O interactions result in a two-dimensional sheet of connected molecules that lies parallel to (101).
The crystal structures of eight N-monosubstituted barbituric acid derivatives with R1 = alkyl (see Scheme) are currently known [Cambridge Structural Database (CSD) version 5.30, update September 2009; Allen, 2002], in addition to those of (I) and (II) (see Table 3). A common feature of all these structures is the formation of a single N—H···O bond in which the NH donor and one carbonyl acceptor site per molecule are employed. More precisely, only the carbonyl group in the 4-position (see Scheme) is ever engaged in this interaction, whereas the carbonyl groups in the 2- and 6-positions are avoided, presumably because of their close proximity to the alkyl substitutent at N1.
Four of these previous examples concern the dimer motif of (I) (Brunner et al., 2003; Dideberg et al., 1975; Lewis et al., 2005; Pyżalska et al., 1980). The dimer is always centrosymmetric, with the exception of one structure of an enantiomerically pure chiral compound (Brunner et al., 2003). The N—H···O-bonded chain motif is found in (II), where the chains exhibit a 21 symmetry, and in another four compounds (Gelbrich & Griesser, 2009; Nichol & Clegg, 2005; Wilhelm & Fischer, 1976; Wunderlich, 1973), where they show translational symmetry only. Consequently, the lattice vectors which correspond with the translation of these latter four hydrogen-bonded chains (see Table 3) are very similar in length (between 6.61 and 6.80 Å).