Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100005291/qb0202sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270100005291/qb0202Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270100005291/qb0202IIsup3.hkl |
CCDC references: 145654; 145655
The title compounds were synthesized by the coupling of N,N-diprotected L-histidinol alkoxide and corresponding halides in Williamson ether syntehesis (Kovalainen et al., 1999). Colorless crystals suitable for X-ray studies were obtained by diffusion method from propanol/ethyl acetate for (I) and 2-propanol/ethanol/hexane for (II)
In the refinements, 1744 and 1724 Friedel reflections were used for (I) and (II), respectively. The H atoms were placed at calculated positions and refined as riding using SHELXL97 (Sheldrick, 1997) defaults; N—H = 0.86, C—H = 0.93 and C—H(methyl) = 0.96 Å.
Data collection: COLLECT (Nonius, 1998) for (I); Collect (Nonius, 1998) for (II). For both compounds, cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997) and WinGX (Farrugia, 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997) and WinGX.
C13H25N3O2+·2Cl− | Dx = 1.186 Mg m−3 |
Mr = 310.26 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from all reflections |
a = 7.8270 (4) Å | θ = 3.1–27.9° |
b = 12.7936 (8) Å | µ = 0.37 mm−1 |
c = 17.3523 (12) Å | T = 173 K |
V = 1737.58 (18) Å3 | Block, colourless |
Z = 4 | 0.25 × 0.20 × 0.10 mm |
F(000) = 664 |
Nonius KappaCCD diffractometer | 4090 independent reflections |
Radiation source: fine-focus sealed tube | 2791 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.062 |
ϕ scans | θmax = 27.9°, θmin = 3.1° |
Absorption correction: empirical (using intensity measurements) (Blessing, 1995) | h = −9→10 |
Tmin = 0.913, Tmax = 0.964 | k = −12→16 |
10810 measured reflections | l = −22→20 |
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)] = 0.046 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.084 | w = 1/[σ2(Fo2) + (0.0192P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.01 | (Δ/σ)max < 0.001 |
4090 reflections | Δρmax = 0.20 e Å−3 |
173 parameters | Δρmin = −0.25 e Å−3 |
0 restraints | Absolute structure: Flack (1983) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.11 (5) |
C13H25N3O2+·2Cl− | V = 1737.58 (18) Å3 |
Mr = 310.26 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.8270 (4) Å | µ = 0.37 mm−1 |
b = 12.7936 (8) Å | T = 173 K |
c = 17.3523 (12) Å | 0.25 × 0.20 × 0.10 mm |
Nonius KappaCCD diffractometer | 4090 independent reflections |
Absorption correction: empirical (using intensity measurements) (Blessing, 1995) | 2791 reflections with I > 2σ(I) |
Tmin = 0.913, Tmax = 0.964 | Rint = 0.062 |
10810 measured reflections |
R[F2 > 2σ(F2)] = 0.046 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.084 | Δρmax = 0.20 e Å−3 |
S = 1.01 | Δρmin = −0.25 e Å−3 |
4090 reflections | Absolute structure: Flack (1983) |
173 parameters | Absolute structure parameter: −0.11 (5) |
0 restraints |
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. The structures were solved by direct methods followed by Fourier synthesis and refined by anisotropic full-matrix least-squares methods for all non-H atoms. 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 | ||
Cl1 | 0.18262 (7) | 0.31574 (5) | 0.41537 (4) | 0.03577 (16) | |
Cl2 | 0.62933 (8) | 0.14581 (5) | 0.28773 (4) | 0.04348 (18) | |
N1 | 0.7369 (2) | 0.57440 (16) | 0.24749 (12) | 0.0356 (5) | |
H1 | 0.6325 | 0.5890 | 0.2321 | 0.043* | |
C2 | 0.8767 (3) | 0.62128 (19) | 0.22229 (15) | 0.0409 (6) | |
H2 | 0.8817 | 0.6758 | 0.1852 | 0.049* | |
N3 | 1.0087 (3) | 0.57846 (17) | 0.25822 (13) | 0.0391 (5) | |
H3 | 1.1165 | 0.5957 | 0.2512 | 0.047* | |
C4 | 0.9510 (3) | 0.5030 (2) | 0.30825 (15) | 0.0362 (6) | |
H4 | 1.0193 | 0.4612 | 0.3414 | 0.043* | |
C5 | 0.7786 (3) | 0.49927 (19) | 0.30136 (13) | 0.0298 (6) | |
C6 | 0.6458 (3) | 0.43096 (19) | 0.33603 (13) | 0.0332 (6) | |
H6A | 0.6124 | 0.3767 | 0.2982 | 0.040* | |
H6B | 0.5432 | 0.4733 | 0.3478 | 0.040* | |
C7 | 0.7086 (3) | 0.37780 (17) | 0.41023 (13) | 0.0297 (5) | |
H7 | 0.8225 | 0.3453 | 0.3999 | 0.036* | |
C8 | 0.7261 (3) | 0.45179 (19) | 0.47761 (14) | 0.0340 (6) | |
H8A | 0.7782 | 0.4154 | 0.5221 | 0.041* | |
H8B | 0.7995 | 0.5118 | 0.4635 | 0.041* | |
O9 | 0.5609 (2) | 0.48645 (14) | 0.49637 (10) | 0.0426 (5) | |
C10 | 0.5574 (3) | 0.5645 (2) | 0.55545 (15) | 0.0411 (7) | |
H10A | 0.6030 | 0.6314 | 0.5353 | 0.049* | |
H10B | 0.6291 | 0.5424 | 0.5995 | 0.049* | |
C11 | 0.3753 (3) | 0.57853 (19) | 0.58105 (14) | 0.0374 (6) | |
H11 | 0.3324 | 0.5091 | 0.5991 | 0.045* | |
C12 | 0.2590 (3) | 0.6153 (2) | 0.51680 (16) | 0.0454 (7) | |
H12A | 0.2627 | 0.5643 | 0.4739 | 0.054* | |
H12B | 0.3004 | 0.6833 | 0.4970 | 0.054* | |
C13 | 0.0750 (3) | 0.6271 (2) | 0.54475 (18) | 0.0545 (8) | |
H13A | 0.0043 | 0.6558 | 0.5025 | 0.065* | |
H13B | 0.0291 | 0.5574 | 0.5584 | 0.065* | |
C14 | 0.0623 (4) | 0.6989 (2) | 0.61460 (17) | 0.0571 (8) | |
H14A | 0.0927 | 0.7712 | 0.5994 | 0.069* | |
H14B | −0.0567 | 0.6994 | 0.6339 | 0.069* | |
C15 | 0.1809 (3) | 0.6624 (2) | 0.67784 (15) | 0.0499 (7) | |
H15A | 0.1432 | 0.5931 | 0.6966 | 0.060* | |
H15B | 0.1754 | 0.7120 | 0.7216 | 0.060* | |
C16 | 0.3644 (3) | 0.6549 (2) | 0.64918 (14) | 0.0439 (6) | |
H16A | 0.4393 | 0.6304 | 0.6915 | 0.053* | |
H16B | 0.4045 | 0.7249 | 0.6328 | 0.053* | |
N17 | 0.5848 (2) | 0.29315 (15) | 0.43031 (11) | 0.0318 (5) | |
H17A | 0.4776 | 0.3205 | 0.4334 | 0.048* | |
H17B | 0.6140 | 0.2646 | 0.4765 | 0.048* | |
H17C | 0.5872 | 0.2429 | 0.3932 | 0.048* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0300 (3) | 0.0386 (4) | 0.0387 (3) | 0.0019 (2) | −0.0020 (3) | 0.0042 (3) |
Cl2 | 0.0269 (3) | 0.0462 (4) | 0.0573 (4) | 0.0040 (3) | −0.0011 (3) | −0.0137 (3) |
N1 | 0.0276 (11) | 0.0380 (13) | 0.0411 (12) | 0.0031 (9) | −0.0041 (10) | 0.0109 (11) |
C2 | 0.0387 (14) | 0.0388 (16) | 0.0453 (15) | −0.0013 (13) | 0.0023 (14) | 0.0092 (12) |
N3 | 0.0271 (10) | 0.0405 (14) | 0.0497 (14) | −0.0016 (10) | 0.0053 (10) | 0.0075 (11) |
C4 | 0.0286 (13) | 0.0379 (16) | 0.0420 (16) | −0.0002 (11) | 0.0004 (12) | 0.0100 (13) |
C5 | 0.0270 (13) | 0.0303 (14) | 0.0319 (14) | 0.0034 (10) | 0.0021 (11) | 0.0019 (11) |
C6 | 0.0267 (12) | 0.0372 (15) | 0.0357 (13) | −0.0008 (11) | −0.0040 (12) | 0.0046 (11) |
C7 | 0.0210 (11) | 0.0307 (14) | 0.0372 (13) | −0.0025 (9) | 0.0012 (11) | 0.0024 (12) |
C8 | 0.0287 (13) | 0.0372 (16) | 0.0362 (14) | −0.0012 (11) | −0.0032 (11) | 0.0030 (12) |
O9 | 0.0311 (9) | 0.0452 (12) | 0.0516 (11) | 0.0001 (8) | −0.0019 (9) | −0.0177 (9) |
C10 | 0.0450 (14) | 0.0403 (17) | 0.0380 (15) | −0.0008 (12) | −0.0032 (13) | −0.0076 (13) |
C11 | 0.0415 (13) | 0.0333 (14) | 0.0376 (14) | −0.0023 (12) | 0.0001 (14) | −0.0050 (12) |
C12 | 0.0474 (16) | 0.0424 (17) | 0.0465 (16) | −0.0013 (12) | −0.0043 (14) | −0.0092 (14) |
C13 | 0.0390 (15) | 0.056 (2) | 0.068 (2) | 0.0031 (13) | −0.0078 (14) | −0.0158 (16) |
C14 | 0.0445 (15) | 0.055 (2) | 0.072 (2) | 0.0054 (14) | 0.0055 (16) | −0.0110 (17) |
C15 | 0.0599 (17) | 0.0390 (17) | 0.0507 (16) | −0.0018 (14) | 0.0095 (15) | −0.0079 (14) |
C16 | 0.0519 (15) | 0.0394 (16) | 0.0404 (14) | 0.0014 (14) | −0.0041 (14) | −0.0051 (13) |
N17 | 0.0264 (10) | 0.0325 (12) | 0.0365 (12) | −0.0020 (8) | 0.0004 (9) | 0.0008 (9) |
N1—C2 | 1.322 (3) | C8—O9 | 1.405 (3) |
N1—C5 | 1.380 (3) | O9—C10 | 1.432 (3) |
C2—N3 | 1.325 (3) | C10—C11 | 1.504 (3) |
N3—C4 | 1.375 (3) | C11—C12 | 1.514 (3) |
C4—C5 | 1.356 (3) | C11—C16 | 1.536 (3) |
C5—C6 | 1.486 (3) | C12—C13 | 1.527 (4) |
C6—C7 | 1.537 (3) | C13—C14 | 1.524 (4) |
C7—N17 | 1.495 (3) | C14—C15 | 1.511 (4) |
C7—C8 | 1.511 (3) | C15—C16 | 1.523 (4) |
C2—N1—C5 | 110.1 (2) | O9—C8—C7 | 107.09 (19) |
N1—C2—N3 | 107.6 (2) | C8—O9—C10 | 113.79 (18) |
C2—N3—C4 | 109.4 (2) | O9—C10—C11 | 108.20 (19) |
C5—C4—N3 | 107.2 (2) | C10—C11—C12 | 112.9 (2) |
C4—C5—N1 | 105.7 (2) | C10—C11—C16 | 110.8 (2) |
C4—C5—C6 | 133.0 (2) | C12—C11—C16 | 109.6 (2) |
N1—C5—C6 | 121.23 (19) | C11—C12—C13 | 111.3 (2) |
C5—C6—C7 | 112.04 (18) | C14—C13—C12 | 112.0 (2) |
N17—C7—C8 | 109.40 (18) | C15—C14—C13 | 110.5 (2) |
N17—C7—C6 | 107.95 (17) | C14—C15—C16 | 111.2 (2) |
C8—C7—C6 | 113.6 (2) | C15—C16—C11 | 110.1 (2) |
C5—N1—C2—N3 | 0.1 (3) | C7—C8—O9—C10 | −174.99 (19) |
N1—C2—N3—C4 | −0.6 (3) | C8—O9—C10—C11 | −168.7 (2) |
C2—N3—C4—C5 | 0.9 (3) | O9—C10—C11—C12 | −61.3 (3) |
N3—C4—C5—N1 | −0.7 (3) | O9—C10—C11—C16 | 175.3 (2) |
N3—C4—C5—C6 | 175.9 (2) | C10—C11—C12—C13 | 179.2 (2) |
C2—N1—C5—C4 | 0.4 (3) | C16—C11—C12—C13 | −56.7 (3) |
C2—N1—C5—C6 | −176.8 (2) | C11—C12—C13—C14 | 55.0 (3) |
C4—C5—C6—C7 | 21.0 (4) | C12—C13—C14—C15 | −54.0 (3) |
N1—C5—C6—C7 | −162.7 (2) | C13—C14—C15—C16 | 56.1 (3) |
C5—C6—C7—N17 | −166.94 (19) | C14—C15—C16—C11 | −58.9 (3) |
C5—C6—C7—C8 | 71.6 (3) | C10—C11—C16—C15 | −176.2 (2) |
N17—C7—C8—O9 | −54.8 (2) | C12—C11—C16—C15 | 58.6 (3) |
C6—C7—C8—O9 | 65.9 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···Cl2i | 0.88 | 2.20 | 3.0703 (19) | 169 |
N3—H3···Cl2ii | 0.88 | 2.20 | 3.067 (2) | 170 |
N17—H17A···Cl1 | 0.91 | 2.33 | 3.1713 (17) | 154 |
N17—H17B···Cl1iii | 0.91 | 2.21 | 3.114 (2) | 176 |
N17—H17C···Cl2 | 0.91 | 2.24 | 3.130 (2) | 167 |
Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) −x+2, y+1/2, −z+1/2; (iii) x+1/2, −y+1/2, −z+1. |
C13H18BrN3O2+·2Cl− | Dx = 1.458 Mg m−3 |
Mr = 383.11 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from all reflections |
a = 7.5530 (2) Å | θ = 2.9–27.9° |
b = 12.9964 (6) Å | µ = 2.66 mm−1 |
c = 17.7800 (9) Å | T = 173 K |
V = 1745.32 (13) Å3 | Block, colourless |
Z = 4 | 0.50 × 0.10 × 0.10 mm |
F(000) = 776 |
Nonius KappaCCD diffractometer | 4093 independent reflections |
Radiation source: fine-focus sealed tube | 2864 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.053 |
ϕ scans | θmax = 27.9°, θmin = 2.9° |
Absorption correction: empirical (using intensity measurements) (Blessing, R. H., 1995) | h = −8→9 |
Tmin = 0.350, Tmax = 0.777 | k = −17→14 |
10776 measured reflections | l = −23→17 |
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)] = 0.047 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | w = 1/[σ2(Fo2) + (0.023P)2 + 0.7817P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
4093 reflections | Δρmax = 0.34 e Å−3 |
182 parameters | Δρmin = −0.56 e Å−3 |
0 restraints | Absolute structure: Flack (1983) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.005 (10) |
C13H18BrN3O2+·2Cl− | V = 1745.32 (13) Å3 |
Mr = 383.11 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.5530 (2) Å | µ = 2.66 mm−1 |
b = 12.9964 (6) Å | T = 173 K |
c = 17.7800 (9) Å | 0.50 × 0.10 × 0.10 mm |
Nonius KappaCCD diffractometer | 4093 independent reflections |
Absorption correction: empirical (using intensity measurements) (Blessing, R. H., 1995) | 2864 reflections with I > 2σ(I) |
Tmin = 0.350, Tmax = 0.777 | Rint = 0.053 |
10776 measured reflections |
R[F2 > 2σ(F2)] = 0.047 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | Δρmax = 0.34 e Å−3 |
S = 1.04 | Δρmin = −0.56 e Å−3 |
4093 reflections | Absolute structure: Flack (1983) |
182 parameters | Absolute structure parameter: −0.005 (10) |
0 restraints |
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. The structures were solved by direct methods followed by Fourier synthesis and refined by anisotropic full-matrix least-squares methods for all non-H atoms. 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 | ||
Br1 | 1.28661 (6) | 0.73206 (4) | 0.66550 (3) | 0.05731 (16) | |
Cl1 | 0.87010 (11) | 0.24151 (8) | 0.59579 (5) | 0.0363 (2) | |
Cl2 | 0.64992 (11) | 0.54709 (7) | 0.84584 (6) | 0.0383 (2) | |
C2 | 0.1453 (6) | 0.5031 (3) | 0.8229 (3) | 0.0467 (11) | |
H2 | 0.1422 | 0.5535 | 0.8616 | 0.056* | |
C4 | 0.0644 (5) | 0.3916 (3) | 0.7372 (3) | 0.0362 (10) | |
H4 | −0.0083 | 0.3506 | 0.7055 | 0.043* | |
C5 | 0.2441 (4) | 0.3941 (3) | 0.7381 (2) | 0.0298 (9) | |
C6 | 0.3765 (5) | 0.3333 (3) | 0.6952 (2) | 0.0321 (9) | |
H6A | 0.3767 | 0.2616 | 0.7141 | 0.038* | |
H6B | 0.4958 | 0.3625 | 0.7040 | 0.038* | |
C7 | 0.3385 (4) | 0.3326 (3) | 0.6111 (2) | 0.0275 (9) | |
H7 | 0.2131 | 0.3102 | 0.6036 | 0.033* | |
C8 | 0.3621 (5) | 0.4353 (3) | 0.5733 (2) | 0.0362 (9) | |
H8A | 0.3416 | 0.4288 | 0.5186 | 0.043* | |
H8B | 0.2766 | 0.4857 | 0.5939 | 0.043* | |
C10 | 0.5933 (6) | 0.5489 (3) | 0.5386 (3) | 0.0461 (11) | |
H10A | 0.5003 | 0.6024 | 0.5354 | 0.055* | |
H10B | 0.6142 | 0.5214 | 0.4874 | 0.055* | |
C11 | 0.7618 (5) | 0.5948 (3) | 0.5692 (2) | 0.0389 (10) | |
C12 | 0.7821 (6) | 0.6129 (3) | 0.6462 (3) | 0.0459 (11) | |
H12 | 0.6882 | 0.5960 | 0.6795 | 0.055* | |
C13 | 0.9358 (5) | 0.6549 (3) | 0.6748 (3) | 0.0445 (11) | |
H13 | 0.9484 | 0.6665 | 0.7273 | 0.053* | |
C14 | 1.0709 (5) | 0.6797 (3) | 0.6258 (3) | 0.0398 (11) | |
C15 | 1.0548 (6) | 0.6643 (3) | 0.5495 (3) | 0.0435 (11) | |
H15 | 1.1476 | 0.6834 | 0.5163 | 0.052* | |
C16 | 0.8996 (6) | 0.6201 (3) | 0.5221 (3) | 0.0428 (11) | |
H16 | 0.8887 | 0.6072 | 0.4697 | 0.051* | |
N1 | 0.2900 (4) | 0.4646 (2) | 0.79212 (19) | 0.0389 (8) | |
H1 | 0.3990 | 0.4815 | 0.8044 | 0.047* | |
N3 | 0.0076 (4) | 0.4607 (3) | 0.7915 (2) | 0.0437 (10) | |
H3 | −0.1035 | 0.4738 | 0.8029 | 0.052* | |
N17 | 0.4571 (3) | 0.2545 (2) | 0.57478 (17) | 0.0286 (7) | |
H17A | 0.4347 | 0.2523 | 0.5245 | 0.043* | |
H17B | 0.4363 | 0.1915 | 0.5953 | 0.043* | |
H17C | 0.5722 | 0.2723 | 0.5825 | 0.043* | |
O9 | 0.5377 (3) | 0.4685 (2) | 0.58729 (18) | 0.0411 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.0446 (2) | 0.0638 (3) | 0.0635 (3) | −0.0103 (2) | −0.0040 (2) | −0.0043 (3) |
Cl1 | 0.0283 (4) | 0.0481 (6) | 0.0327 (5) | −0.0046 (4) | −0.0018 (4) | −0.0014 (5) |
Cl2 | 0.0287 (4) | 0.0416 (6) | 0.0444 (7) | 0.0023 (4) | 0.0029 (4) | −0.0095 (5) |
C2 | 0.051 (2) | 0.043 (3) | 0.046 (3) | 0.0032 (19) | 0.007 (2) | −0.017 (2) |
C4 | 0.028 (2) | 0.038 (2) | 0.043 (3) | 0.0013 (16) | 0.0007 (18) | −0.007 (2) |
C5 | 0.029 (2) | 0.031 (2) | 0.029 (2) | −0.0011 (14) | −0.0005 (15) | −0.0036 (19) |
C6 | 0.0248 (19) | 0.037 (2) | 0.035 (2) | 0.0032 (16) | −0.0008 (16) | −0.0047 (19) |
C7 | 0.0225 (18) | 0.027 (2) | 0.034 (2) | 0.0030 (13) | −0.0004 (15) | −0.0038 (17) |
C8 | 0.0339 (19) | 0.037 (2) | 0.038 (3) | 0.0017 (17) | −0.0049 (18) | −0.0015 (19) |
C10 | 0.051 (3) | 0.040 (3) | 0.047 (3) | −0.0110 (19) | 0.001 (2) | 0.002 (2) |
C11 | 0.046 (3) | 0.035 (2) | 0.035 (3) | −0.0025 (17) | −0.0012 (19) | 0.0039 (19) |
C12 | 0.049 (2) | 0.049 (3) | 0.040 (3) | −0.012 (2) | 0.007 (2) | 0.001 (2) |
C13 | 0.053 (3) | 0.039 (3) | 0.041 (3) | −0.0062 (19) | −0.002 (2) | 0.001 (2) |
C14 | 0.039 (2) | 0.035 (3) | 0.046 (3) | −0.0023 (17) | −0.0001 (19) | −0.001 (2) |
C15 | 0.045 (2) | 0.044 (3) | 0.042 (3) | 0.0008 (19) | 0.005 (2) | 0.003 (2) |
C16 | 0.049 (3) | 0.048 (3) | 0.031 (3) | −0.0057 (19) | 0.0024 (19) | 0.003 (2) |
N1 | 0.0307 (16) | 0.044 (2) | 0.042 (2) | −0.0033 (16) | 0.0000 (15) | −0.0122 (17) |
N3 | 0.0318 (19) | 0.050 (2) | 0.049 (3) | 0.0070 (15) | 0.0094 (16) | −0.009 (2) |
N17 | 0.0254 (13) | 0.0289 (19) | 0.0314 (18) | −0.0011 (13) | −0.0008 (12) | −0.0004 (15) |
O9 | 0.0375 (15) | 0.0347 (16) | 0.051 (2) | −0.0079 (11) | −0.0061 (13) | 0.0075 (15) |
Br1—C14 | 1.901 (4) | C8—O9 | 1.416 (4) |
C2—N3 | 1.303 (5) | C10—O9 | 1.421 (5) |
C2—N1 | 1.321 (5) | C10—C11 | 1.508 (6) |
C4—C5 | 1.358 (5) | C11—C16 | 1.376 (6) |
C4—N3 | 1.387 (5) | C11—C12 | 1.396 (6) |
C5—N1 | 1.371 (5) | C12—C13 | 1.379 (6) |
C5—C6 | 1.485 (5) | C13—C14 | 1.380 (6) |
C6—C7 | 1.523 (6) | C14—C15 | 1.376 (6) |
C7—N17 | 1.500 (4) | C15—C16 | 1.394 (6) |
C7—C8 | 1.505 (5) | ||
N3—C2—N1 | 108.8 (4) | C16—C11—C10 | 120.8 (4) |
C5—C4—N3 | 106.6 (4) | C12—C11—C10 | 120.9 (4) |
C4—C5—N1 | 106.1 (4) | C13—C12—C11 | 121.3 (4) |
C4—C5—C6 | 130.9 (4) | C12—C13—C14 | 118.8 (5) |
N1—C5—C6 | 123.0 (3) | C15—C14—C13 | 121.5 (4) |
C5—C6—C7 | 112.4 (3) | C15—C14—Br1 | 119.6 (3) |
N17—C7—C8 | 109.7 (3) | C13—C14—Br1 | 118.9 (4) |
N17—C7—C6 | 108.3 (3) | C14—C15—C16 | 118.7 (4) |
C8—C7—C6 | 114.2 (3) | C11—C16—C15 | 121.4 (4) |
O9—C8—C7 | 107.7 (3) | C2—N1—C5 | 109.6 (3) |
O9—C10—C11 | 108.7 (4) | C2—N3—C4 | 109.0 (3) |
C16—C11—C12 | 118.3 (4) | C8—O9—C10 | 113.2 (3) |
N3—C4—C5—N1 | −0.5 (5) | C12—C13—C14—Br1 | −177.3 (3) |
N3—C4—C5—C6 | 176.7 (4) | C13—C14—C15—C16 | −1.6 (7) |
C4—C5—C6—C7 | 50.0 (6) | Br1—C14—C15—C16 | 176.2 (3) |
N1—C5—C6—C7 | −133.3 (4) | C12—C11—C16—C15 | −1.1 (7) |
C5—C6—C7—N17 | −169.7 (3) | C10—C11—C16—C15 | 178.8 (4) |
C5—C6—C7—C8 | 67.8 (4) | C14—C15—C16—C11 | 1.9 (7) |
N17—C7—C8—O9 | −65.0 (4) | N3—C2—N1—C5 | 0.1 (5) |
C6—C7—C8—O9 | 56.9 (4) | C4—C5—N1—C2 | 0.2 (5) |
O9—C10—C11—C16 | 138.2 (4) | C6—C5—N1—C2 | −177.2 (4) |
O9—C10—C11—C12 | −41.9 (6) | N1—C2—N3—C4 | −0.4 (5) |
C16—C11—C12—C13 | −0.1 (7) | C5—C4—N3—C2 | 0.6 (5) |
C10—C11—C12—C13 | −180.0 (4) | C7—C8—O9—C10 | 163.6 (3) |
C11—C12—C13—C14 | 0.4 (7) | C11—C10—O9—C8 | 166.9 (3) |
C12—C13—C14—C15 | 0.5 (7) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···Cl2 | 0.88 | 2.20 | 3.075 (3) | 170 |
N3—H3···Cl2i | 0.88 | 2.23 | 3.081 (3) | 164 |
N17—H17A···Cl1ii | 0.91 | 2.20 | 3.103 (3) | 176 |
N17—H17B···Cl2iii | 0.91 | 2.25 | 3.148 (3) | 171 |
N17—H17C···Cl1 | 0.91 | 2.30 | 3.146 (3) | 155 |
Symmetry codes: (i) x−1, y, z; (ii) x−1/2, −y+1/2, −z+1; (iii) −x+1, y−1/2, −z+3/2. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C13H25N3O2+·2Cl− | C13H18BrN3O2+·2Cl− |
Mr | 310.26 | 383.11 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, P212121 |
Temperature (K) | 173 | 173 |
a, b, c (Å) | 7.8270 (4), 12.7936 (8), 17.3523 (12) | 7.5530 (2), 12.9964 (6), 17.7800 (9) |
V (Å3) | 1737.58 (18) | 1745.32 (13) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.37 | 2.66 |
Crystal size (mm) | 0.25 × 0.20 × 0.10 | 0.50 × 0.10 × 0.10 |
Data collection | ||
Diffractometer | Nonius KappaCCD diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | Empirical (using intensity measurements) (Blessing, 1995) | Empirical (using intensity measurements) (Blessing, R. H., 1995) |
Tmin, Tmax | 0.913, 0.964 | 0.350, 0.777 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 10810, 4090, 2791 | 10776, 4093, 2864 |
Rint | 0.062 | 0.053 |
(sin θ/λ)max (Å−1) | 0.658 | 0.658 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.046, 0.084, 1.01 | 0.047, 0.090, 1.04 |
No. of reflections | 4090 | 4093 |
No. of parameters | 173 | 182 |
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) | 0.20, −0.25 | 0.34, −0.56 |
Absolute structure | Flack (1983) | Flack (1983) |
Absolute structure parameter | −0.11 (5) | −0.005 (10) |
Computer programs: COLLECT (Nonius, 1998), Collect (Nonius, 1998), DENZO (Otwinowski & Minor, 1997), DENZO, SHELXS97 (Sheldrick, 1997) and WinGX (Farrugia, 1999), SHELXL97 (Sheldrick, 1997) and WinGX.
The histamine H3-receptor is located on neurones of the central and autonomic nervous system where it regulates the release of histamine and some other neurotransmitters (Arrang et al., 1983; Schlicker et al., 1994; Hill et al., 1997). Many possible therapeutic targets for H3-receptor ligands have been suggested, such as, Alzheimer's disease, narcolepsy, schizophrenia and epilepsy (Leurs et al., 1995; Stark et al., 1996).
2(S)-Amino-3-[1H-imidazol-4(5)-yl]propyl cyclohexylmethyl ether dihydrochloride, (I), and 2(S)-amino-3-(1H-imidazol-4(5)-yl)propyl 4-bromobenzyl ether dihydrochloride, (II), were synthesized by Kovalainen et al. (1999) for evaluation of the histamine H3-receptor activation mechanism. The crystal structures of (I) and (II) were determined to reveal the absolute configuration, the low-energy conformation, and to further evaluate histamine H3-receptor–ligand interactions.
Both compounds crystallize in the orthorhombic system with one cation and two chloride ions in the asymmetric unit. The imidazole ring and amino group are protonated in the both structures. For compound (I), the non-bonded intramolecular distances N3···C14 and N3···O9 are 9.772 (4) and 5.545 (3) Å, respectively, and for compound (II), the distances N3···C14, N3···O9 and N3···Br1 are 9.015 (5), 5.406 (4) and 10.525 (3) Å, respectively.