Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270105014745/fg1843sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270105014745/fg18433Lsup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270105014745/fg18433Nsup3.hkl |
CCDC references: 278553; 278554
Compounds 3N and 3L were supplied by Dr H. Kohn (Kohn et al., 1991). After extensive crystallization experiments, crystals of 3L were obtained by slow evaporation from a 1:1 benzene–chloroform solution at 278 K. The crystals took the form of small colorless needles, generally of low quality. Crystals of 3N were obtained by slow evaporation from a 1:1 chloroform–toluene mixture, and were of poor quality. Additional crystallization trials to produce better crystals were unsuccessful.
All H atoms for both compounds could be located in difference maps and were subsequently allowed for as riding atoms, except for atom H15 on N15 in 3L. For 3L, one overall isotropic displacement parameter was refined for methyl H atoms and another for the rest [Uiso(H) = 0.116 (7) and 0.079 (4) Å2, respectively]. For 3N, the corresponding values are 0.123 (16) and 0.099 (15) Å2. The range of C—H distances is 0.93–0.98 Å, and the amide N—H distances are 0.86 Å. The N15—H15 bond length in 3L is 0.90 (3) Å.
For both compounds, data collection: Picker Operating Manual (Picker, 1967); cell refinement: Picker Operating Manual; data reduction: DATRDN The X-ray System (Stewart, 1976); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.
C12H17N3O3 | Dx = 1.279 Mg m−3 |
Mr = 251.29 | Cu Kα radiation, λ = 1.54178 Å |
Orthorhombic, Pbcn | Cell parameters from 3 reflections |
a = 17.998 (5) Å | θ = 19–44° |
b = 7.112 (3) Å | µ = 0.77 mm−1 |
c = 20.390 (6) Å | T = 294 K |
V = 2610.0 (15) Å3 | Needle, colorless |
Z = 8 | 0.47 × 0.11 × 0.07 mm |
F(000) = 1072 |
Picker FACS-1 4-circle diffractometer | 1655 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.000 |
Ni filtered radiation monochromator | θmax = 65.0°, θmin = 4.3° |
θ/2θ scan | h = 0→21 |
Absorption correction: ψ scan (North et al., 1968) | k = 0→8 |
Tmin = 0.900, Tmax = 0.944 | l = 0→23 |
2225 measured reflections | 3 standard reflections every 100 reflections |
2225 independent reflections | intensity decay: 1.9% |
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)] = 0.062 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.146 | w = 1/[σ2(Fo2) + (0.0284P)2 + 2.7803P] where P = (Fo2 + 2Fc2)/3 |
S = 1.00 | (Δ/σ)max < 0.001 |
2225 reflections | Δρmax = 0.21 e Å−3 |
172 parameters | Δρmin = −0.16 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0045 (3) |
C12H17N3O3 | V = 2610.0 (15) Å3 |
Mr = 251.29 | Z = 8 |
Orthorhombic, Pbcn | Cu Kα radiation |
a = 17.998 (5) Å | µ = 0.77 mm−1 |
b = 7.112 (3) Å | T = 294 K |
c = 20.390 (6) Å | 0.47 × 0.11 × 0.07 mm |
Picker FACS-1 4-circle diffractometer | 1655 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.000 |
Tmin = 0.900, Tmax = 0.944 | 3 standard reflections every 100 reflections |
2225 measured reflections | intensity decay: 1.9% |
2225 independent reflections |
R[F2 > 2σ(F2)] = 0.062 | 0 restraints |
wR(F2) = 0.146 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | Δρmax = 0.21 e Å−3 |
2225 reflections | Δρmin = −0.16 e Å−3 |
172 parameters |
Experimental. PICKER FACS-1 mechanical limit does not allow for data collection above θ = 65° |
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 | ||
C1 | 0.39659 (17) | 0.2949 (5) | 0.28393 (17) | 0.0605 (9) | |
H1 | 0.4364 | 0.3697 | 0.2969 | 0.079 (4)* | |
C2 | 0.3922 (2) | 0.2338 (6) | 0.21977 (19) | 0.0764 (11) | |
H2 | 0.4292 | 0.2663 | 0.1900 | 0.079 (4)* | |
C3 | 0.3335 (2) | 0.1255 (6) | 0.20012 (19) | 0.0816 (12) | |
H3 | 0.3302 | 0.0844 | 0.1569 | 0.079 (4)* | |
C4 | 0.2797 (2) | 0.0783 (6) | 0.24416 (19) | 0.0874 (13) | |
H4 | 0.2398 | 0.0043 | 0.2309 | 0.079 (4)* | |
C5 | 0.28391 (18) | 0.1390 (5) | 0.30809 (17) | 0.0673 (10) | |
H5 | 0.2465 | 0.1069 | 0.3375 | 0.079 (4)* | |
C6 | 0.34280 (15) | 0.2466 (4) | 0.32902 (15) | 0.0495 (7) | |
C7 | 0.35048 (16) | 0.3025 (4) | 0.39990 (15) | 0.0516 (8) | |
H7A | 0.3777 | 0.4199 | 0.4030 | 0.079 (4)* | |
H7B | 0.3016 | 0.3216 | 0.4188 | 0.079 (4)* | |
N8 | 0.38966 (12) | 0.1566 (3) | 0.43638 (11) | 0.0461 (6) | |
H8 | 0.4374 | 0.1605 | 0.4374 | 0.079 (4)* | |
C9 | 0.35566 (14) | 0.0184 (4) | 0.46798 (14) | 0.0432 (7) | |
C10 | 0.40705 (14) | −0.1385 (4) | 0.49143 (14) | 0.0430 (7) | |
H10 | 0.4363 | −0.0878 | 0.5279 | 0.079 (4)* | |
N11 | 0.36400 (12) | −0.2936 (3) | 0.51716 (11) | 0.0443 (6) | |
H11 | 0.3178 | −0.3046 | 0.5070 | 0.079 (4)* | |
C12 | 0.39605 (16) | −0.4203 (4) | 0.55683 (13) | 0.0466 (7) | |
C13 | 0.34744 (17) | −0.5738 (5) | 0.58287 (16) | 0.0600 (9) | |
H13A | 0.2998 | −0.5682 | 0.5618 | 0.116 (7)* | |
H13B | 0.3413 | −0.5582 | 0.6293 | 0.116 (7)* | |
H13C | 0.3701 | −0.6935 | 0.5742 | 0.116 (7)* | |
O14 | 0.28907 (9) | 0.0156 (3) | 0.48015 (11) | 0.0597 (6) | |
N15 | 0.45887 (13) | −0.1862 (4) | 0.43943 (12) | 0.0494 (6) | |
H15 | 0.4853 (18) | −0.289 (5) | 0.4504 (16) | 0.068 (11)* | |
O16 | 0.41345 (12) | −0.2489 (3) | 0.38547 (10) | 0.0578 (6) | |
C17 | 0.4510 (2) | −0.2061 (6) | 0.32599 (18) | 0.0830 (12) | |
H17A | 0.4193 | −0.2349 | 0.2895 | 0.116 (7)* | |
H17B | 0.4956 | −0.2797 | 0.3231 | 0.116 (7)* | |
H17C | 0.4635 | −0.0749 | 0.3252 | 0.116 (7)* | |
O18 | 0.46243 (11) | −0.4082 (3) | 0.57164 (10) | 0.0600 (6) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0405 (16) | 0.069 (2) | 0.072 (2) | −0.0016 (16) | 0.0018 (15) | 0.0105 (18) |
C2 | 0.059 (2) | 0.099 (3) | 0.071 (2) | 0.005 (2) | 0.0106 (18) | 0.016 (2) |
C3 | 0.095 (3) | 0.095 (3) | 0.055 (2) | −0.007 (3) | −0.009 (2) | 0.009 (2) |
C4 | 0.093 (3) | 0.097 (3) | 0.072 (2) | −0.040 (2) | −0.019 (2) | 0.019 (2) |
C5 | 0.062 (2) | 0.078 (2) | 0.062 (2) | −0.0233 (19) | −0.0049 (17) | 0.0175 (19) |
C6 | 0.0416 (15) | 0.0457 (17) | 0.0611 (18) | 0.0019 (13) | −0.0035 (14) | 0.0141 (14) |
C7 | 0.0506 (17) | 0.0406 (16) | 0.0635 (19) | 0.0035 (14) | −0.0007 (14) | 0.0070 (14) |
N8 | 0.0341 (12) | 0.0480 (14) | 0.0562 (14) | −0.0027 (11) | −0.0002 (10) | 0.0073 (12) |
C9 | 0.0325 (13) | 0.0469 (16) | 0.0501 (16) | −0.0016 (12) | −0.0047 (12) | −0.0031 (14) |
C10 | 0.0334 (13) | 0.0479 (16) | 0.0478 (16) | −0.0019 (12) | −0.0013 (12) | 0.0024 (13) |
N11 | 0.0356 (12) | 0.0490 (14) | 0.0482 (13) | −0.0012 (10) | −0.0019 (10) | 0.0066 (11) |
C12 | 0.0442 (15) | 0.0529 (17) | 0.0427 (16) | 0.0052 (14) | 0.0033 (13) | 0.0037 (14) |
C13 | 0.0604 (19) | 0.059 (2) | 0.0608 (19) | −0.0035 (16) | 0.0046 (16) | 0.0136 (17) |
O14 | 0.0333 (10) | 0.0542 (13) | 0.0915 (17) | 0.0017 (10) | 0.0047 (10) | 0.0090 (12) |
N15 | 0.0366 (13) | 0.0538 (16) | 0.0579 (15) | 0.0041 (12) | 0.0031 (12) | 0.0056 (13) |
O16 | 0.0621 (13) | 0.0578 (13) | 0.0536 (12) | −0.0020 (11) | 0.0050 (10) | −0.0008 (11) |
C17 | 0.114 (3) | 0.077 (3) | 0.058 (2) | 0.007 (2) | 0.026 (2) | 0.0061 (19) |
O18 | 0.0419 (11) | 0.0746 (15) | 0.0634 (13) | 0.0049 (11) | −0.0058 (10) | 0.0150 (12) |
C1—C6 | 1.379 (4) | C9—C10 | 1.527 (4) |
C1—C2 | 1.381 (5) | C10—N11 | 1.446 (3) |
C1—H1 | 0.93 | C10—N15 | 1.452 (3) |
C2—C3 | 1.368 (5) | C10—H10 | 0.98 |
C2—H2 | 0.93 | N11—C12 | 1.341 (3) |
C3—C4 | 1.362 (5) | N11—H11 | 0.86 |
C3—H3 | 0.93 | C12—O18 | 1.235 (3) |
C4—C5 | 1.375 (5) | C12—C13 | 1.496 (4) |
C4—H4 | 0.93 | C13—H13A | 0.96 |
C5—C6 | 1.375 (4) | C13—H13B | 0.96 |
C5—H5 | 0.93 | C13—H13C | 0.96 |
C6—C7 | 1.505 (4) | N15—O16 | 1.442 (3) |
C7—N8 | 1.458 (4) | N15—H15 | 0.90 (3) |
C7—H7A | 0.97 | O16—C17 | 1.421 (4) |
C7—H7B | 0.97 | C17—H17A | 0.96 |
N8—C9 | 1.325 (3) | C17—H17B | 0.96 |
N8—H8 | 0.86 | C17—H17C | 0.96 |
C9—O14 | 1.224 (3) | ||
C6—C1—C2 | 120.9 (3) | N8—C9—C10 | 114.5 (2) |
C6—C1—H1 | 119.5 | N11—C10—N15 | 115.5 (2) |
C2—C1—H1 | 119.5 | N11—C10—C9 | 110.3 (2) |
C3—C2—C1 | 119.9 (3) | N15—C10—C9 | 109.3 (2) |
C3—C2—H2 | 120.1 | N11—C10—H10 | 107.1 |
C1—C2—H2 | 120.1 | N15—C10—H10 | 107.1 |
C4—C3—C2 | 119.7 (4) | C9—C10—H10 | 107.1 |
C4—C3—H3 | 120.2 | C12—N11—C10 | 120.0 (2) |
C2—C3—H3 | 120.2 | C12—N11—H11 | 120.0 |
C3—C4—C5 | 120.6 (4) | C10—N11—H11 | 120.0 |
C3—C4—H4 | 119.7 | O18—C12—N11 | 121.1 (3) |
C5—C4—H4 | 119.7 | O18—C12—C13 | 122.0 (3) |
C6—C5—C4 | 120.7 (3) | N11—C12—C13 | 116.9 (3) |
C6—C5—H5 | 119.6 | C12—C13—H13A | 109.5 |
C4—C5—H5 | 119.6 | C12—C13—H13B | 109.5 |
C5—C6—C1 | 118.2 (3) | H13A—C13—H13B | 109.5 |
C5—C6—C7 | 121.0 (3) | C12—C13—H13C | 109.5 |
C1—C6—C7 | 120.7 (3) | H13A—C13—H13C | 109.5 |
N8—C7—C6 | 110.3 (2) | H13B—C13—H13C | 109.5 |
N8—C7—H7A | 109.6 | O16—N15—C10 | 105.4 (2) |
C6—C7—H7A | 109.6 | O16—N15—H15 | 104 (2) |
N8—C7—H7B | 109.6 | C10—N15—H15 | 110 (2) |
C6—C7—H7B | 109.6 | C17—O16—N15 | 108.4 (2) |
H7A—C7—H7B | 108.1 | O16—C17—H17A | 109.5 |
C9—N8—C7 | 123.5 (2) | O16—C17—H17B | 109.5 |
C9—N8—H8 | 118.2 | H17A—C17—H17B | 109.5 |
C7—N8—H8 | 118.2 | O16—C17—H17C | 109.5 |
O14—C9—N8 | 124.3 (3) | H17A—C17—H17C | 109.5 |
O14—C9—C10 | 121.2 (3) | H17B—C17—H17C | 109.5 |
C6—C1—C2—C3 | 0.7 (6) | C7—N8—C9—C10 | 168.7 (2) |
C1—C2—C3—C4 | −0.2 (6) | O14—C9—C10—N11 | 10.1 (4) |
C2—C3—C4—C5 | 0.2 (7) | N8—C9—C10—N11 | −172.2 (2) |
C3—C4—C5—C6 | −0.8 (6) | O14—C9—C10—N15 | 138.2 (3) |
C4—C5—C6—C1 | 1.3 (5) | N8—C9—C10—N15 | −44.1 (3) |
C4—C5—C6—C7 | −175.8 (3) | N15—C10—N11—C12 | 74.5 (3) |
C2—C1—C6—C5 | −1.3 (5) | C9—C10—N11—C12 | −160.9 (2) |
C2—C1—C6—C7 | 175.8 (3) | C10—N11—C12—O18 | −0.6 (4) |
C5—C6—C7—N8 | 86.9 (4) | C10—N11—C12—C13 | 178.4 (3) |
C1—C6—C7—N8 | −90.1 (3) | N11—C10—N15—O16 | 64.3 (3) |
C6—C7—N8—C9 | −92.7 (3) | C9—C10—N15—O16 | −60.8 (3) |
C7—N8—C9—O14 | −13.7 (5) | C10—N15—O16—C17 | 150.3 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···O18i | 0.86 | 2.53 | 3.212 (3) | 137 |
N11—H11···O14 | 0.86 | 2.40 | 2.687 (3) | 100 |
N11—H11···O14ii | 0.86 | 2.37 | 3.163 (3) | 153 |
N15—H15···O18iii | 0.90 (3) | 2.39 (3) | 3.221 (4) | 153 (3) |
C7—H7A···O16iv | 0.97 | 2.47 | 3.399 (4) | 161 |
C7—H7B···O14v | 0.97 | 2.48 | 3.359 (4) | 151 |
C13—H13A···O14ii | 0.96 | 2.38 | 3.290 (4) | 157 |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) −x+1/2, y−1/2, z; (iii) −x+1, −y−1, −z+1; (iv) x, y+1, z; (v) −x+1/2, y+1/2, z. |
C13H19N3O3 | Z = 2 |
Mr = 265.31 | F(000) = 284 |
Triclinic, P1 | Dx = 1.244 Mg m−3 |
a = 4.859 (2) Å | Cu Kα radiation, λ = 1.54178 Å |
b = 10.587 (3) Å | Cell parameters from 32 reflections |
c = 14.168 (4) Å | θ = 23–45° |
α = 86.84 (2)° | µ = 0.74 mm−1 |
β = 80.66 (3)° | T = 294 K |
γ = 80.28 (3)° | Needle, colorless |
V = 708.6 (4) Å3 | 0.42 × 0.09 × 0.08 mm |
Picker FACS-1 4-circle diffractometer | 737 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.085 |
Ni-filtered radiation monochromator | θmax = 45.0°, θmin = 3.2° |
θ/2θ scan | h = −4→0 |
Absorption correction: ψ scan (North et al., 1968) | k = −9→9 |
Tmin = 0.930, Tmax = 0.934 | l = −12→12 |
1338 measured reflections | 3 standard reflections every 100 reflections |
1145 independent reflections | intensity decay: 2.7% |
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)] = 0.102 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.250 | H-atom parameters constrained |
S = 1.12 | w = 1/[σ2(Fo2) + (0.0768P)2 + 2.5323P] where P = (Fo2 + 2Fc2)/3 |
1145 reflections | (Δ/σ)max < 0.001 |
174 parameters | Δρmax = 0.53 e Å−3 |
25 restraints | Δρmin = −0.30 e Å−3 |
C13H19N3O3 | γ = 80.28 (3)° |
Mr = 265.31 | V = 708.6 (4) Å3 |
Triclinic, P1 | Z = 2 |
a = 4.859 (2) Å | Cu Kα radiation |
b = 10.587 (3) Å | µ = 0.74 mm−1 |
c = 14.168 (4) Å | T = 294 K |
α = 86.84 (2)° | 0.42 × 0.09 × 0.08 mm |
β = 80.66 (3)° |
Picker FACS-1 4-circle diffractometer | 737 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.085 |
Tmin = 0.930, Tmax = 0.934 | θmax = 45.0° |
1338 measured reflections | 3 standard reflections every 100 reflections |
1145 independent reflections | intensity decay: 2.7% |
R[F2 > 2σ(F2)] = 0.102 | 25 restraints |
wR(F2) = 0.250 | H-atom parameters constrained |
S = 1.12 | Δρmax = 0.53 e Å−3 |
1145 reflections | Δρmin = −0.30 e Å−3 |
174 parameters |
Experimental. The crystal was small and of poor quality and no reflections were observable beyond theta of 45°. |
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. Refinement of 3 N indicated N15 could be split into two positions; doing so reduced R to 0.082 but resulted in non-positive definite temperature factors and poor interatomic distances for the lower occupancy position. |
x | y | z | Uiso*/Ueq | ||
O14 | 0.1023 (14) | 0.7475 (8) | 0.6884 (5) | 0.078 (3) | |
O16 | 0.4177 (18) | 0.5637 (11) | 0.8374 (7) | 0.133 (4) | |
O18 | 0.6410 (13) | 0.9777 (7) | 0.8618 (5) | 0.070 (3) | |
N8 | 0.5635 (16) | 0.7245 (8) | 0.6334 (7) | 0.065 (3) | |
H8 | 0.7308 | 0.7276 | 0.6447 | 0.099 (15)* | |
N11 | 0.2602 (15) | 0.8993 (8) | 0.8302 (6) | 0.048 (2) | |
H11 | 0.0808 | 0.9152 | 0.8298 | 0.099 (15)* | |
N15 | 0.291 (3) | 0.6784 (9) | 0.8729 (7) | 0.108 (4) | |
C1 | 0.926 (2) | 0.6332 (12) | 0.4065 (8) | 0.069 (3) | |
H1 | 0.8979 | 0.5484 | 0.4160 | 0.099 (15)* | |
C2 | 1.130 (2) | 0.6657 (14) | 0.3362 (9) | 0.088 (4) | |
H2 | 1.2367 | 0.6017 | 0.2972 | 0.099 (15)* | |
C3 | 1.182 (3) | 0.7847 (17) | 0.3213 (10) | 0.099 (5) | |
H3 | 1.3264 | 0.8019 | 0.2733 | 0.099 (15)* | |
C4 | 1.023 (3) | 0.8832 (14) | 0.3762 (11) | 0.099 (4) | |
H4 | 1.0549 | 0.9672 | 0.3648 | 0.099 (15)* | |
C5 | 0.810 (2) | 0.8522 (13) | 0.4497 (10) | 0.085 (4) | |
H5 | 0.7038 | 0.9155 | 0.4895 | 0.099 (15)* | |
C6 | 0.763 (2) | 0.7271 (12) | 0.4627 (8) | 0.059 (3) | |
C7 | 0.530 (2) | 0.6909 (13) | 0.5390 (9) | 0.081 (4) | |
H7A | 0.5310 | 0.5993 | 0.5381 | 0.099 (15)* | |
H7B | 0.3490 | 0.7343 | 0.5246 | 0.099 (15)* | |
C9 | 0.346 (2) | 0.7519 (9) | 0.7046 (8) | 0.045 (3) | |
C10 | 0.4154 (19) | 0.7731 (10) | 0.8004 (8) | 0.057 (3) | |
H10 | 0.6194 | 0.7669 | 0.7993 | 0.099 (15)* | |
C12 | 0.383 (2) | 0.9883 (10) | 0.8597 (7) | 0.051 (3) | |
C13 | 0.194 (2) | 1.1100 (10) | 0.8933 (9) | 0.077 (4) | |
H13A | 0.2483 | 1.1813 | 0.8541 | 0.123 (16)* | |
H13B | 0.0019 | 1.1031 | 0.8884 | 0.123 (16)* | |
H13C | 0.2081 | 1.1231 | 0.9587 | 0.123 (16)* | |
C17 | 0.178 (2) | 0.4949 (13) | 0.8391 (10) | 0.108 (5) | |
H17A | 0.0404 | 0.5424 | 0.8035 | 0.123 (16)* | |
H17B | 0.2516 | 0.4139 | 0.8099 | 0.123 (16)* | |
H17C | 0.0902 | 0.4806 | 0.9037 | 0.123 (16)* | |
C18 | 0.439 (3) | 0.6849 (12) | 0.9572 (9) | 0.095 (4) | |
H18A | 0.6375 | 0.6815 | 0.9342 | 0.123 (16)* | |
H18B | 0.3662 | 0.7641 | 0.9890 | 0.123 (16)* | |
H18C | 0.4123 | 0.6143 | 1.0013 | 0.123 (16)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O14 | 0.017 (4) | 0.142 (8) | 0.075 (6) | −0.011 (4) | −0.006 (4) | −0.022 (5) |
O16 | 0.076 (7) | 0.175 (11) | 0.130 (9) | 0.010 (7) | −0.004 (6) | 0.023 (8) |
O18 | 0.015 (4) | 0.080 (6) | 0.116 (7) | −0.012 (4) | −0.003 (4) | −0.020 (5) |
N8 | 0.022 (5) | 0.109 (8) | 0.063 (7) | −0.010 (5) | 0.004 (5) | −0.030 (6) |
N11 | 0.017 (4) | 0.041 (6) | 0.081 (7) | 0.001 (5) | 0.000 (4) | −0.004 (5) |
N15 | 0.211 (13) | 0.033 (6) | 0.048 (6) | 0.071 (7) | −0.015 (6) | −0.004 (5) |
C1 | 0.051 (7) | 0.081 (8) | 0.071 (8) | −0.020 (6) | 0.004 (5) | 0.000 (6) |
C2 | 0.061 (8) | 0.126 (10) | 0.073 (9) | −0.026 (8) | 0.017 (6) | −0.010 (9) |
C3 | 0.084 (10) | 0.146 (12) | 0.075 (10) | −0.055 (9) | 0.001 (7) | 0.012 (9) |
C4 | 0.094 (11) | 0.083 (9) | 0.126 (13) | −0.029 (8) | −0.037 (8) | 0.043 (8) |
C5 | 0.056 (7) | 0.077 (7) | 0.119 (11) | −0.004 (6) | −0.012 (6) | −0.006 (8) |
C6 | 0.033 (6) | 0.077 (7) | 0.068 (8) | −0.009 (5) | −0.011 (5) | −0.007 (6) |
C7 | 0.039 (7) | 0.127 (11) | 0.076 (10) | −0.021 (7) | 0.003 (5) | −0.012 (8) |
C9 | 0.037 (7) | 0.039 (7) | 0.058 (6) | −0.005 (5) | −0.005 (6) | −0.004 (5) |
C10 | 0.029 (6) | 0.074 (9) | 0.067 (7) | 0.004 (6) | −0.018 (6) | −0.013 (6) |
C12 | 0.051 (8) | 0.046 (7) | 0.054 (8) | −0.014 (6) | 0.005 (6) | 0.003 (6) |
C13 | 0.061 (7) | 0.043 (7) | 0.127 (11) | −0.004 (5) | −0.013 (7) | −0.015 (7) |
C17 | 0.052 (8) | 0.131 (13) | 0.147 (14) | −0.051 (8) | 0.008 (8) | −0.015 (10) |
C18 | 0.120 (11) | 0.077 (10) | 0.084 (9) | −0.020 (8) | −0.008 (8) | 0.016 (8) |
O14—C9 | 1.251 (11) | C4—H4 | 0.93 |
O16—N15 | 1.350 (11) | C5—C6 | 1.379 (15) |
O16—C17 | 1.472 (12) | C5—H5 | 0.93 |
O18—C12 | 1.242 (12) | C6—C7 | 1.516 (14) |
N8—C9 | 1.343 (11) | C7—H7A | 0.9701 |
N8—C7 | 1.443 (13) | C7—H7B | 0.97 |
N8—H8 | 0.86 | C9—C10 | 1.487 (14) |
N11—C12 | 1.318 (12) | C10—H10 | 0.98 |
N11—C10 | 1.467 (12) | C12—O18 | 1.242 (11) |
N11—H11 | 0.86 | C12—C13 | 1.504 (14) |
N15—C18 | 1.502 (13) | C13—H13A | 0.9601 |
N15—C10 | 1.521 (12) | C13—H13B | 0.96 |
C1—C6 | 1.367 (14) | C13—H13C | 0.96 |
C1—C2 | 1.359 (15) | C17—H17A | 0.96 |
C1—H1 | 0.9299 | C17—H17B | 0.96 |
C2—C3 | 1.325 (17) | C17—H17C | 0.96 |
C2—H2 | 0.9299 | C18—H18A | 0.96 |
C3—C4 | 1.381 (18) | C18—H18B | 0.96 |
C3—H3 | 0.9301 | C18—H18C | 0.9601 |
C4—C5 | 1.410 (17) | ||
N15—O16—C17 | 102.7 (10) | H7A—C7—H7B | 107.9 |
C9—N8—C7 | 123.4 (8) | O14—C9—N8 | 118.3 (9) |
C9—N8—H8 | 118.1 | O14—C9—C10 | 124.3 (9) |
C7—N8—H8 | 118.5 | N8—C9—C10 | 117.1 (9) |
C12—N11—C10 | 122.6 (8) | N11—C10—C9 | 106.7 (8) |
C12—N11—H11 | 118.6 | N11—C10—N15 | 104.9 (8) |
C10—N11—H11 | 118.7 | C9—C10—N15 | 109.2 (9) |
O16—N15—C18 | 101.4 (9) | N11—C10—H10 | 112.2 |
O16—N15—C10 | 103.0 (9) | C9—C10—H10 | 112.0 |
C18—N15—C10 | 103.5 (10) | N15—C10—H10 | 111.5 |
C6—C1—C2 | 118.9 (12) | O18—C12—N11 | 124.7 (9) |
C6—C1—H1 | 120.6 | O18—C12—N11 | 124.7 (9) |
C2—C1—H1 | 120.5 | O18—C12—C13 | 118.9 (11) |
C3—C2—C1 | 122.7 (14) | O18—C12—C13 | 118.9 (11) |
C3—C2—H2 | 118.8 | N11—C12—C13 | 116.4 (10) |
C1—C2—H2 | 118.5 | C12—C13—H13A | 109.8 |
C2—C3—C4 | 120.7 (14) | C12—C13—H13B | 109.1 |
C2—C3—H3 | 119.5 | H13A—C13—H13B | 109.5 |
C4—C3—H3 | 119.7 | C12—C13—H13C | 109.6 |
C3—C4—C5 | 117.8 (13) | H13A—C13—H13C | 109.5 |
C3—C4—H4 | 121.1 | H13B—C13—H13C | 109.5 |
C5—C4—H4 | 121.0 | O16—C17—H17A | 110.6 |
C6—C5—C4 | 119.5 (12) | O16—C17—H17B | 107.1 |
C6—C5—H5 | 120.2 | H17A—C17—H17B | 109.5 |
C4—C5—H5 | 120.2 | O16—C17—H17C | 110.7 |
C1—C6—C5 | 120.3 (11) | H17A—C17—H17C | 109.5 |
C1—C6—C7 | 118.7 (11) | H17B—C17—H17C | 109.5 |
C5—C6—C7 | 121.0 (11) | N15—C18—H18A | 108.4 |
N8—C7—C6 | 112.2 (9) | N15—C18—H18B | 109.4 |
N8—C7—H7A | 109.1 | H18A—C18—H18B | 109.5 |
C6—C7—H7A | 109.2 | N15—C18—H18C | 110.7 |
N8—C7—H7B | 109.2 | H18A—C18—H18C | 109.5 |
C6—C7—H7B | 109.2 | H18B—C18—H18C | 109.5 |
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···O14i | 0.86 | 2.05 | 2.901 (10) | 172 |
N11—H11···O18ii | 0.86 | 2.11 | 2.950 (9) | 165 |
C10—H10···O14i | 0.98 | 2.59 | 3.428 (11) | 144 |
C10—H10···O18 | 0.98 | 2.47 | 2.823 (12) | 101 |
C13—H13B···O18ii | 0.96 | 2.46 | 3.331 (12) | 151 |
Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z. |
Experimental details
(3L) | (3N) | |
Crystal data | ||
Chemical formula | C12H17N3O3 | C13H19N3O3 |
Mr | 251.29 | 265.31 |
Crystal system, space group | Orthorhombic, Pbcn | Triclinic, P1 |
Temperature (K) | 294 | 294 |
a, b, c (Å) | 17.998 (5), 7.112 (3), 20.390 (6) | 4.859 (2), 10.587 (3), 14.168 (4) |
α, β, γ (°) | 90, 90, 90 | 86.84 (2), 80.66 (3), 80.28 (3) |
V (Å3) | 2610.0 (15) | 708.6 (4) |
Z | 8 | 2 |
Radiation type | Cu Kα | Cu Kα |
µ (mm−1) | 0.77 | 0.74 |
Crystal size (mm) | 0.47 × 0.11 × 0.07 | 0.42 × 0.09 × 0.08 |
Data collection | ||
Diffractometer | Picker FACS-1 4-circle diffractometer | Picker FACS-1 4-circle diffractometer |
Absorption correction | ψ scan (North et al., 1968) | ψ scan (North et al., 1968) |
Tmin, Tmax | 0.900, 0.944 | 0.930, 0.934 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2225, 2225, 1655 | 1338, 1145, 737 |
Rint | 0.000 | 0.085 |
θmax (°) | 65.0 | 45.0 |
(sin θ/λ)max (Å−1) | 0.588 | 0.458 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.062, 0.146, 1.00 | 0.102, 0.250, 1.12 |
No. of reflections | 2225 | 1145 |
No. of parameters | 172 | 174 |
No. of restraints | 0 | 25 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.16 | 0.53, −0.30 |
Computer programs: Picker Operating Manual (Picker, 1967), Picker Operating Manual, DATRDN The X-ray System (Stewart, 1976), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), SHELXL97.
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···O18i | 0.86 | 2.53 | 3.212 (3) | 137 |
N11—H11···O14 | 0.86 | 2.40 | 2.687 (3) | 100 |
N11—H11···O14ii | 0.86 | 2.37 | 3.163 (3) | 153 |
N15—H15···O18iii | 0.90 (3) | 2.39 (3) | 3.221 (4) | 153 (3) |
C7—H7A···O16iv | 0.97 | 2.47 | 3.399 (4) | 161 |
C7—H7B···O14v | 0.97 | 2.48 | 3.359 (4) | 151 |
C13—H13A···O14ii | 0.96 | 2.38 | 3.290 (4) | 157 |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) −x+1/2, y−1/2, z; (iii) −x+1, −y−1, −z+1; (iv) x, y+1, z; (v) −x+1/2, y+1/2, z. |
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···O14i | 0.86 | 2.05 | 2.901 (10) | 172 |
N11—H11···O18ii | 0.86 | 2.11 | 2.950 (9) | 165 |
C10—H10···O14i | 0.98 | 2.59 | 3.428 (11) | 144 |
C10—H10···O18 | 0.98 | 2.47 | 2.823 (12) | 101 |
C13—H13B···O18ii | 0.96 | 2.46 | 3.331 (12) | 151 |
Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z. |
The title compounds, 2-(acetylamino)-N-benzyl-2-(methoxyamino)acetamide (3L), and its N-methyl derivative (3N), are members of a series of functionalized α-heteroatom-substituted non-naturally occurring amino acids synthesized and tested for anticonvulsant activity (Kohn et al., 1991). These two were the most potent of the group, demonstrating median effective dose values required to prevent maximal electroshock seizures in mice comparable to the well known antiepileptic drug phenytoin. We determined the crystal structures of 3L and 3N in order to investigate the stereochemical basis for their anticonvulsant properties.
The structure of 3L is presented in Fig. 1. The asymmetric unit contains one molecule with atoms C7–C13 extended linearly, and with the two amide group planes (atoms C7/N8/C9/C10/O14 and C10/N11/C12/C13/O18) intersecting at an angle of 157.3 (1)°. The C9—C10—N11—C12 torsion angle is −160.9 (2)°. The sp3-hybridization of N15 is indicated by the sum of the bond angles at N15 of 319.4°. Four standard hydrogen bonds, weak non-standard C—H···O hydrogen bonds (Table 1) and van der Waals interactions are the main contributors to the crystal packing. The molecules are packed in head-to-head and tail-to-tail fashion, creating distinct hydrophilic and hydrophobic regions running perpendicular to the c axis, as shown in Fig. 2. The 3N chain conformation (Fig. 3) is a little more curved, with an angle of 126.4 (4)° between the two planar amide groups (atoms C7/N8/C9/C10/O14 and C10/N11/C12/C13/O18). The C9—C10—N11—C12 torsion angle is −128.5 (10)°. The replacement of the H atom at N15 in 3L with the methyl group in 3N results in a much weaker hydrogen-bonding scheme, with only two classical N—H···O interactions producing infinite molecular chains parallel to the a axis (see Table 2). Van der Waals forces and non-standard hydrogen bonds also contribute to the crystal packing, creating planar hydrophillic and hydrophobic areas parallel to the ab plane. The weaker hydrogen-bonding interactions are very probably responsible for abnormal displacement ellipsoids and mild disorder in the N15, O16, C17 and C18 positions, as well as high displacement parameters for some other atoms.. Despite these problems, the overall conformational structure of the molecules in the solid state is undoubtedly established.
We have compared the structures of 3L (Fig. 4) and 3N (Fig. 5) with that of phenytoin (Camerman & Camerman, 1971) a chemically different clinically used anticonvulsant, in order to correlate pharmacological properties with stereochemical features. The structures were superposed by maximizing the fit of three atoms in each, viz. O14, O16 and C6 in 3L, and O14, O16 and C5 in 3N, with the two carbonyl O atoms and atom C15 (for 3L) or C19 (for 3N) in phenytoin. Atom O16 was chosen, rather than the second carbonyl O atom in 3L and 3N, because the pharmacological evaluations had shown that a functionalized O atom located two atoms removed from the Cα atom was necessary for maximal activity in the series tested (Kohn et al., 1991). To yield better phenyl-group fits, rotations of 80° about C7—N8 and 90° about C6—C7 were performed for 3L, and a single rotation of 65° about C6—C7 was performed for 3N. The superpositions show that the O atoms in each molecule can occupy similar positions in space (small movements of the methoxy O atoms in 3L and 3N, via C10—N15 bond rotation, would make the correspondences exact), and the hydrophobic phenyl groups can also occupy similar regions. Since these are the stereochemical determinants of phenytoin anticonvulsant activity (Camerman & Camerman, 1981), the results are indicative that the similar activity of these compounds could be mediated through mechanisms similar to those of phenytoin.