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The crystal structures of three new solvates of olanzapine [systematic name: 2-methyl-4-(4-methylpiperazin-1-yl)-10
H-thieno[2,3-
b][1,5]benzodiazepine], namely olanzapine acetic acid monosolvate, C
17H
20N
4S·C
2H
4O
2, (I), olanzapine propan-2-ol hemisolvate monohydrate, C
17H
20N
4S·0.5C
3H
8O·H
2O, (II), and olanzapine propan-2-one hemisolvate monohydrate, C
17H
20N
4S·0.5C
3H
6O·H
2O, (III), are presented and compared with other known olanzapine forms. There is a fairly close resemblance of the molecular conformation for all studied analogues. The crystal structures are built up through olanzapine dimers, which are characterized
via C-H
interactions between the aliphatic fragment (1-methylpiperazin-4-yl) and the aromatic fragment (benzene system). All solvent (guest) molecules participate in hydrogen-bonding networks. The crystal packing is sustained
via intermolecular N
host-H
O
guest, O
guest-H
N
host, O
guest-H
O
guest and C
host-H
O
guest hydrogen bonds. It should be noted that the solvent propan-2-ol in (II) and propan-2-one in (III) show orientational disorder. The propan-2-ol molecule lies close to a twofold axis, while the propan-2-one molecule resides strictly on a twofold axis through the carbonyl C atom. In both cases, the water molecules present positional disorder of the H atoms.
Supporting information
CCDC references: 926831; 926832; 926833
Suitable diffraction-quality monocrystals of (I)–(III) were obtained by slow
evaporation of the solvents from the corresponding solution of olanzapine
[acetic acid, water–propan-2-ol (1:1 v/v) and
water–propan-2-one (1:1 v/v), respectively] at room
temperature. Olanzapine and the solvents were purchased from Sigma–Aldrich
Inc.
H atoms, except those of the disordered solvent molecules, were located in
difference Fourier maps but were treated differently in the refinements. Those
bonded to C atoms were subsequently geometrically optimized and refined as
riding atoms, with C—H = 0.93 Å for CH groups, 0.97 Å for secondary
CH2 groups and 0.96 Å for CH3 groups, and with Uiso(H) =
1.2Ueq(C) for methine and methylene H atoms or 1.5Ueq(C) for
methyl H atoms. H atoms bonded to N atoms were refined freely. One of the
water H atoms in each of (II) and (III) is disordered over two sites
(0.5:0.5). Water H atoms were restrained to have an O—H bond length of
0.82 (1) Å. The H atoms of methyl group C8 in all the olanzapine molecules,
and methyl group C19 in the acetic acid solvent molecule of (I), were
disordered over six sites, each with a site-occupancy factor of 0.5. The
propan-2-ol solvent molecule of (II) and the propan-2-one solvent molecule of
(III) both exhibit 0.5:0.5 site-occupancy disorder around a twofold axis.
[Correct diffractometer given for (III)?]
For all compounds, data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-Plus (Bruker, 2008); data reduction: SAINT-Plus (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009).
(I) 2-Methyl-4-(4-methylpiperazin-1-yl)-10
H-thieno[2,3-
b][1,5]benzodiazepine acetic acid monosolvate
top
Crystal data top
C17H20N4S·C2H4O2 | F(000) = 792 |
Mr = 372.49 | Dx = 1.305 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: -P 2ybc | Cell parameters from 9926 reflections |
a = 10.1474 (1) Å | θ = 4.4–65.9° |
b = 12.8562 (1) Å | µ = 1.69 mm−1 |
c = 14.5494 (1) Å | T = 296 K |
β = 92.92° | Plate, yellow |
V = 1895.61 (3) Å3 | 0.20 × 0.15 × 0.10 mm |
Z = 4 | |
Data collection top
Bruker SMART APEXII CCD area-detector diffractometer | 3298 independent reflections |
Radiation source: 30W microsource with MonoCap capillary | 3201 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.020 |
ω scans | θmax = 66.4°, θmin = 4.4° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −12→11 |
Tmin = 0.729, Tmax = 0.849 | k = −14→15 |
22793 measured reflections | l = −16→17 |
Refinement top
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)] = 0.033 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.094 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0508P)2 + 0.522P] where P = (Fo2 + 2Fc2)/3 |
3298 reflections | (Δ/σ)max < 0.001 |
246 parameters | Δρmax = 0.27 e Å−3 |
8 restraints | Δρmin = −0.16 e Å−3 |
Crystal data top
C17H20N4S·C2H4O2 | V = 1895.61 (3) Å3 |
Mr = 372.49 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 10.1474 (1) Å | µ = 1.69 mm−1 |
b = 12.8562 (1) Å | T = 296 K |
c = 14.5494 (1) Å | 0.20 × 0.15 × 0.10 mm |
β = 92.92° | |
Data collection top
Bruker SMART APEXII CCD area-detector diffractometer | 3298 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 3201 reflections with I > 2σ(I) |
Tmin = 0.729, Tmax = 0.849 | Rint = 0.020 |
22793 measured reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.033 | 8 restraints |
wR(F2) = 0.094 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.27 e Å−3 |
3298 reflections | Δρmin = −0.16 e Å−3 |
246 parameters | |
Special details top
Geometry. Bond distances, angles etc. have been calculated using the rounded
fractional coordinates. All su's are estimated from the variances of the
(full) variance-covariance matrix. The cell e.s.d.'s are taken into account in
the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user
for potential systematic errors. Weighted R-factors wR and all
goodnesses of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The observed criterion of F2 > σ(F2)
is used only for calculating -R-factor-obs 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 (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
S1 | 0.45237 (4) | −0.07053 (3) | 0.79115 (2) | 0.0446 (1) | |
N1 | 0.65019 (11) | 0.15984 (9) | 0.58964 (8) | 0.0402 (3) | |
N2 | 0.64466 (13) | 0.07813 (10) | 0.77878 (8) | 0.0424 (4) | |
N3 | 0.43690 (11) | 0.18777 (10) | 0.53895 (8) | 0.0427 (4) | |
N4 | 0.25039 (12) | 0.26759 (9) | 0.40282 (8) | 0.0413 (4) | |
C1 | 0.75508 (13) | 0.10578 (11) | 0.63476 (10) | 0.0378 (4) | |
C2 | 0.75906 (14) | 0.07071 (10) | 0.72642 (10) | 0.0390 (4) | |
C3 | 0.53228 (13) | 0.03049 (11) | 0.73826 (9) | 0.0374 (4) | |
C4 | 0.47610 (13) | 0.05178 (11) | 0.65303 (9) | 0.0359 (4) | |
C5 | 0.52763 (13) | 0.13579 (10) | 0.59543 (9) | 0.0359 (4) | |
C6 | 0.36849 (13) | −0.01695 (11) | 0.62963 (10) | 0.0384 (4) | |
C7 | 0.34205 (14) | −0.08577 (11) | 0.69670 (10) | 0.0419 (4) | |
C8 | 0.23938 (16) | −0.16921 (13) | 0.69635 (13) | 0.0554 (6) | |
C9 | 0.87637 (15) | 0.03289 (12) | 0.76707 (11) | 0.0475 (5) | |
C10 | 0.98955 (15) | 0.02677 (13) | 0.71845 (12) | 0.0527 (5) | |
C11 | 0.98592 (15) | 0.05653 (13) | 0.62757 (12) | 0.0509 (5) | |
C12 | 0.87048 (14) | 0.09684 (12) | 0.58710 (11) | 0.0450 (4) | |
C13 | 0.30222 (14) | 0.21050 (12) | 0.56269 (10) | 0.0409 (4) | |
C14 | 0.21039 (14) | 0.19900 (12) | 0.47803 (11) | 0.0454 (5) | |
C15 | 0.39011 (16) | 0.24938 (13) | 0.38412 (10) | 0.0476 (5) | |
C16 | 0.48019 (14) | 0.26012 (13) | 0.46909 (10) | 0.0473 (5) | |
C17 | 0.1655 (2) | 0.24862 (15) | 0.31893 (12) | 0.0624 (6) | |
O1 | 0.17092 (13) | 0.45622 (9) | 0.41745 (9) | 0.0610 (4) | |
O2 | 0.30001 (15) | 0.49414 (12) | 0.53834 (9) | 0.0764 (5) | |
C18 | 0.21494 (16) | 0.51836 (12) | 0.48081 (10) | 0.0470 (5) | |
C19 | 0.1540 (2) | 0.62456 (15) | 0.47671 (14) | 0.0681 (7) | |
H2 | 0.6601 (17) | 0.0574 (14) | 0.8346 (13) | 0.052 (5)* | |
H6 | 0.32090 | −0.01450 | 0.57330 | 0.0460* | |
H8A | 0.24510 | −0.20530 | 0.75420 | 0.0830* | 0.500 |
H8B | 0.25370 | −0.21740 | 0.64740 | 0.0830* | 0.500 |
H8C | 0.15350 | −0.13850 | 0.68720 | 0.0830* | 0.500 |
H8D | 0.18980 | −0.16880 | 0.63840 | 0.0830* | 0.500 |
H8E | 0.18110 | −0.15680 | 0.74510 | 0.0830* | 0.500 |
H8F | 0.28140 | −0.23560 | 0.70530 | 0.0830* | 0.500 |
H9 | 0.87870 | 0.01130 | 0.82810 | 0.0570* | |
H10 | 1.06780 | 0.00270 | 0.74700 | 0.058 (5)* | |
H11 | 1.06050 | 0.04960 | 0.59350 | 0.058 (5)* | |
H12 | 0.86980 | 0.11870 | 0.52610 | 0.0540* | |
H13A | 0.29720 | 0.28090 | 0.58630 | 0.0490* | |
H13B | 0.27590 | 0.16300 | 0.61020 | 0.0490* | |
H14A | 0.21100 | 0.12730 | 0.45740 | 0.0540* | |
H14B | 0.12110 | 0.21620 | 0.49360 | 0.0540* | |
H15A | 0.41670 | 0.29870 | 0.33820 | 0.0570* | |
H15B | 0.39930 | 0.18000 | 0.35900 | 0.0570* | |
H16A | 0.57030 | 0.24460 | 0.45450 | 0.0570* | |
H16B | 0.47730 | 0.33090 | 0.49210 | 0.0570* | |
H17A | 0.17510 | 0.17770 | 0.29970 | 0.0930* | |
H17B | 0.19110 | 0.29430 | 0.27080 | 0.0930* | |
H17C | 0.07510 | 0.26150 | 0.33180 | 0.0930* | |
H1 | 0.204 (2) | 0.3982 (8) | 0.4204 (17) | 0.0910* | |
H19A | 0.08920 | 0.62770 | 0.42640 | 0.1020* | 0.63 (3) |
H19B | 0.22130 | 0.67560 | 0.46790 | 0.1020* | 0.63 (3) |
H19C | 0.11250 | 0.63840 | 0.53330 | 0.1020* | 0.63 (3) |
H19D | 0.19280 | 0.66680 | 0.52530 | 0.1020* | 0.37 (3) |
H19E | 0.06070 | 0.61890 | 0.48380 | 0.1020* | 0.37 (3) |
H19F | 0.16950 | 0.65600 | 0.41840 | 0.1020* | 0.37 (3) |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0512 (2) | 0.0453 (2) | 0.0377 (2) | 0.0055 (2) | 0.0075 (2) | 0.0103 (1) |
N1 | 0.0376 (6) | 0.0391 (6) | 0.0434 (6) | −0.0003 (5) | −0.0015 (5) | 0.0065 (5) |
N2 | 0.0483 (7) | 0.0473 (7) | 0.0311 (6) | 0.0033 (5) | −0.0033 (5) | −0.0021 (5) |
N3 | 0.0350 (6) | 0.0503 (7) | 0.0429 (6) | 0.0034 (5) | 0.0038 (5) | 0.0170 (5) |
N4 | 0.0456 (7) | 0.0389 (7) | 0.0387 (6) | 0.0042 (5) | −0.0042 (5) | 0.0038 (5) |
C1 | 0.0371 (7) | 0.0328 (7) | 0.0430 (7) | −0.0014 (5) | −0.0036 (5) | −0.0022 (6) |
C2 | 0.0418 (7) | 0.0344 (7) | 0.0400 (7) | 0.0018 (5) | −0.0048 (6) | −0.0069 (5) |
C3 | 0.0422 (7) | 0.0358 (7) | 0.0345 (7) | 0.0069 (6) | 0.0042 (5) | 0.0007 (5) |
C4 | 0.0365 (7) | 0.0361 (7) | 0.0350 (7) | 0.0033 (5) | 0.0015 (5) | 0.0026 (5) |
C5 | 0.0384 (7) | 0.0353 (7) | 0.0340 (6) | 0.0017 (5) | 0.0006 (5) | 0.0013 (5) |
C6 | 0.0378 (7) | 0.0377 (7) | 0.0396 (7) | 0.0028 (5) | 0.0008 (5) | 0.0033 (6) |
C7 | 0.0413 (7) | 0.0369 (7) | 0.0479 (8) | 0.0046 (6) | 0.0078 (6) | 0.0044 (6) |
C8 | 0.0530 (9) | 0.0440 (9) | 0.0700 (11) | −0.0039 (7) | 0.0105 (8) | 0.0105 (8) |
C9 | 0.0522 (8) | 0.0461 (8) | 0.0428 (8) | 0.0077 (7) | −0.0113 (6) | −0.0054 (6) |
C10 | 0.0423 (8) | 0.0504 (9) | 0.0637 (10) | 0.0087 (7) | −0.0136 (7) | −0.0093 (7) |
C11 | 0.0366 (8) | 0.0520 (9) | 0.0638 (10) | −0.0007 (6) | 0.0007 (7) | −0.0063 (7) |
C12 | 0.0401 (7) | 0.0468 (8) | 0.0478 (8) | −0.0047 (6) | −0.0001 (6) | 0.0002 (6) |
C13 | 0.0396 (7) | 0.0420 (8) | 0.0417 (7) | 0.0053 (6) | 0.0069 (6) | 0.0084 (6) |
C14 | 0.0390 (7) | 0.0432 (8) | 0.0538 (9) | 0.0010 (6) | 0.0002 (6) | 0.0099 (6) |
C15 | 0.0537 (9) | 0.0488 (9) | 0.0409 (7) | 0.0083 (7) | 0.0085 (6) | 0.0117 (6) |
C16 | 0.0393 (7) | 0.0527 (9) | 0.0502 (8) | 0.0001 (6) | 0.0050 (6) | 0.0196 (7) |
C17 | 0.0750 (12) | 0.0569 (10) | 0.0528 (9) | 0.0024 (9) | −0.0202 (8) | −0.0045 (8) |
O1 | 0.0730 (8) | 0.0457 (6) | 0.0615 (7) | 0.0094 (6) | −0.0226 (6) | −0.0098 (6) |
O2 | 0.0933 (10) | 0.0778 (9) | 0.0550 (7) | 0.0177 (8) | −0.0264 (7) | −0.0188 (6) |
C18 | 0.0538 (9) | 0.0491 (9) | 0.0382 (8) | −0.0022 (7) | 0.0028 (6) | −0.0020 (6) |
C19 | 0.0845 (13) | 0.0472 (10) | 0.0725 (12) | 0.0051 (9) | 0.0036 (10) | −0.0066 (8) |
Geometric parameters (Å, º) top
S1—C3 | 1.7320 (14) | C6—H6 | 0.9300 |
S1—C7 | 1.7388 (15) | C8—H8B | 0.9600 |
O1—C18 | 1.283 (2) | C8—H8E | 0.9600 |
O2—C18 | 1.212 (2) | C8—H8F | 0.9600 |
O1—H1 | 0.818 (13) | C8—H8D | 0.9600 |
N1—C5 | 1.2884 (17) | C8—H8A | 0.9600 |
N1—C1 | 1.4056 (18) | C8—H8C | 0.9600 |
N2—C3 | 1.3981 (19) | C9—H9 | 0.9300 |
N2—C2 | 1.4238 (19) | C10—H10 | 0.9300 |
N3—C13 | 1.4562 (18) | C11—H11 | 0.9300 |
N3—C16 | 1.462 (2) | C12—H12 | 0.9300 |
N3—C5 | 1.3757 (18) | C13—H13B | 0.9700 |
N4—C14 | 1.478 (2) | C13—H13A | 0.9700 |
N4—C17 | 1.478 (2) | C14—H14B | 0.9700 |
N4—C15 | 1.476 (2) | C14—H14A | 0.9700 |
N2—H2 | 0.862 (19) | C15—H15B | 0.9700 |
C1—C2 | 1.406 (2) | C15—H15A | 0.9700 |
C1—C12 | 1.396 (2) | C16—H16A | 0.9700 |
C2—C9 | 1.390 (2) | C16—H16B | 0.9700 |
C3—C4 | 1.3659 (19) | C17—H17C | 0.9600 |
C4—C5 | 1.4788 (19) | C17—H17B | 0.9600 |
C4—C6 | 1.4322 (19) | C17—H17A | 0.9600 |
C6—C7 | 1.354 (2) | C18—C19 | 1.499 (2) |
C7—C8 | 1.495 (2) | C19—H19A | 0.9600 |
C9—C10 | 1.381 (2) | C19—H19B | 0.9600 |
C10—C11 | 1.375 (2) | C19—H19C | 0.9600 |
C11—C12 | 1.385 (2) | C19—H19D | 0.9600 |
C13—C14 | 1.513 (2) | C19—H19E | 0.9600 |
C15—C16 | 1.506 (2) | C19—H19F | 0.9600 |
| | | |
C3—S1—C7 | 91.75 (7) | H8C—C8—H8E | 56.00 |
C18—O1—H1 | 113.8 (16) | H8C—C8—H8F | 141.00 |
C1—N1—C5 | 124.15 (12) | H8D—C8—H8E | 109.00 |
C2—N2—C3 | 114.51 (11) | H8D—C8—H8F | 109.00 |
C5—N3—C13 | 124.29 (12) | H8E—C8—H8F | 109.00 |
C13—N3—C16 | 110.86 (11) | H8B—C8—H8D | 56.00 |
C5—N3—C16 | 120.58 (11) | C10—C9—H9 | 119.00 |
C14—N4—C17 | 110.03 (12) | C2—C9—H9 | 119.00 |
C15—N4—C17 | 110.28 (12) | C9—C10—H10 | 120.00 |
C14—N4—C15 | 110.15 (11) | C11—C10—H10 | 120.00 |
C3—N2—H2 | 111.6 (12) | C10—C11—H11 | 120.00 |
C2—N2—H2 | 111.7 (12) | C12—C11—H11 | 120.00 |
N1—C1—C2 | 125.87 (12) | C11—C12—H12 | 119.00 |
N1—C1—C12 | 116.31 (13) | C1—C12—H12 | 119.00 |
C2—C1—C12 | 117.41 (13) | N3—C13—H13B | 110.00 |
N2—C2—C1 | 120.07 (12) | C14—C13—H13A | 110.00 |
N2—C2—C9 | 119.99 (13) | C14—C13—H13B | 110.00 |
C1—C2—C9 | 119.89 (13) | H13A—C13—H13B | 108.00 |
S1—C3—C4 | 111.74 (10) | N3—C13—H13A | 110.00 |
S1—C3—N2 | 122.10 (10) | N4—C14—H14A | 109.00 |
N2—C3—C4 | 126.07 (13) | N4—C14—H14B | 109.00 |
C3—C4—C5 | 121.17 (12) | C13—C14—H14B | 109.00 |
C3—C4—C6 | 111.72 (12) | H14A—C14—H14B | 108.00 |
C5—C4—C6 | 127.10 (12) | C13—C14—H14A | 109.00 |
N3—C5—C4 | 116.62 (11) | N4—C15—H15A | 109.00 |
N1—C5—C4 | 125.64 (12) | C16—C15—H15A | 109.00 |
N1—C5—N3 | 117.60 (12) | C16—C15—H15B | 109.00 |
C4—C6—C7 | 114.11 (13) | N4—C15—H15B | 109.00 |
S1—C7—C6 | 110.65 (11) | H15A—C15—H15B | 108.00 |
S1—C7—C8 | 120.26 (11) | N3—C16—H16B | 110.00 |
C6—C7—C8 | 129.04 (14) | C15—C16—H16A | 110.00 |
C2—C9—C10 | 121.23 (15) | C15—C16—H16B | 110.00 |
C9—C10—C11 | 119.62 (15) | H16A—C16—H16B | 108.00 |
C10—C11—C12 | 119.58 (15) | N3—C16—H16A | 110.00 |
C1—C12—C11 | 122.18 (15) | N4—C17—H17A | 110.00 |
N3—C13—C14 | 109.50 (12) | N4—C17—H17B | 109.00 |
N4—C14—C13 | 111.30 (12) | H17A—C17—H17B | 109.00 |
N3—C16—C15 | 108.73 (12) | H17A—C17—H17C | 109.00 |
C7—C6—H6 | 123.00 | H17B—C17—H17C | 109.00 |
C4—C6—H6 | 123.00 | N4—C17—H17C | 109.00 |
C7—C8—H8A | 109.00 | O1—C18—C19 | 114.26 (14) |
C7—C8—H8B | 109.00 | O2—C18—C19 | 122.64 (15) |
C7—C8—H8D | 109.00 | O1—C18—O2 | 123.09 (15) |
C7—C8—H8E | 109.00 | C18—C19—H19A | 110.00 |
C7—C8—H8C | 109.00 | C18—C19—H19B | 109.00 |
H8A—C8—H8B | 109.00 | C18—C19—H19C | 109.00 |
H8A—C8—H8C | 110.00 | C18—C19—H19D | 109.00 |
H8A—C8—H8D | 141.00 | C18—C19—H19E | 109.00 |
H8A—C8—H8E | 56.00 | C18—C19—H19F | 109.00 |
H8A—C8—H8F | 56.00 | H19A—C19—H19B | 109.00 |
H8B—C8—H8C | 109.00 | H19A—C19—H19C | 109.00 |
C7—C8—H8F | 109.00 | H19B—C19—H19C | 109.00 |
H8B—C8—H8E | 141.00 | H19D—C19—H19E | 109.00 |
H8B—C8—H8F | 56.00 | H19D—C19—H19F | 109.00 |
H8C—C8—H8D | 56.00 | H19E—C19—H19F | 109.00 |
| | | |
C3—S1—C7—C6 | 0.52 (12) | C12—C1—C2—C9 | 2.5 (2) |
C3—S1—C7—C8 | 178.39 (13) | N1—C1—C12—C11 | 172.22 (14) |
C7—S1—C3—N2 | −176.25 (12) | C12—C1—C2—N2 | 179.75 (13) |
C7—S1—C3—C4 | 0.57 (11) | N1—C1—C2—C9 | −169.84 (13) |
C5—N1—C1—C12 | 144.11 (14) | N1—C1—C2—N2 | 7.4 (2) |
C1—N1—C5—N3 | −172.39 (12) | C1—C2—C9—C10 | −1.4 (2) |
C5—N1—C1—C2 | −43.5 (2) | N2—C2—C9—C10 | −178.70 (14) |
C1—N1—C5—C4 | 3.1 (2) | N2—C3—C4—C5 | −3.8 (2) |
C3—N2—C2—C9 | −127.65 (14) | S1—C3—C4—C6 | −1.47 (15) |
C2—N2—C3—C4 | −56.81 (19) | N2—C3—C4—C6 | 175.20 (13) |
C2—N2—C3—S1 | 119.54 (12) | S1—C3—C4—C5 | 179.56 (10) |
C3—N2—C2—C1 | 55.09 (17) | C6—C4—C5—N1 | −141.58 (15) |
C13—N3—C16—C15 | −60.26 (16) | C6—C4—C5—N3 | 33.9 (2) |
C16—N3—C13—C14 | 60.91 (15) | C3—C4—C5—N3 | −147.26 (13) |
C13—N3—C5—N1 | −148.91 (13) | C3—C4—C6—C7 | 1.93 (18) |
C16—N3—C5—C4 | −170.14 (12) | C5—C4—C6—C7 | −179.17 (13) |
C5—N3—C16—C15 | 141.97 (13) | C3—C4—C5—N1 | 37.2 (2) |
C5—N3—C13—C14 | −142.31 (13) | C4—C6—C7—C8 | −179.09 (14) |
C16—N3—C5—N1 | 5.75 (19) | C4—C6—C7—S1 | −1.47 (16) |
C13—N3—C5—C4 | 35.20 (19) | C2—C9—C10—C11 | −1.4 (2) |
C15—N4—C14—C13 | 53.76 (15) | C9—C10—C11—C12 | 3.0 (2) |
C14—N4—C15—C16 | −54.25 (16) | C10—C11—C12—C1 | −1.9 (2) |
C17—N4—C15—C16 | −175.88 (13) | N3—C13—C14—N4 | −57.37 (16) |
C17—N4—C14—C13 | 175.54 (13) | N4—C15—C16—N3 | 57.06 (17) |
C2—C1—C12—C11 | −0.8 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N4 | 0.82 (1) | 1.77 (1) | 2.5679 (17) | 166 (2) |
N2—H2···O2i | 0.862 (19) | 2.041 (19) | 2.8998 (18) | 174.4 (17) |
C8—H8F···N2i | 0.96 | 2.52 | 3.468 (2) | 171 |
Symmetry code: (i) −x+1, y−1/2, −z+3/2. |
(II) 2-Methyl-4-(4-methylpiperazin-1-yl)-10
H-thieno[2,3-
b][1,5]benzodiazepine propan-2-ol hemisolvate monohydrate
top
Crystal data top
C17H20N4S·0.5C3H8O·H2O | F(000) = 1544 |
Mr = 360.51 | Dx = 1.249 Mg m−3 |
Monoclinic, C2/c | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: -C 2yc | Cell parameters from 9708 reflections |
a = 24.5414 (4) Å | θ = 2.8–67.0° |
b = 12.5088 (3) Å | µ = 1.63 mm−1 |
c = 15.3096 (4) Å | T = 296 K |
β = 125.314 (1)° | Prism, yellow |
V = 3835.01 (16) Å3 | 0.40 × 0.25 × 0.20 mm |
Z = 8 | |
Data collection top
Bruker SMART APEXII CCD area-detector diffractometer | 3385 independent reflections |
Radiation source: 30W microsource with MonoCap capillary | 3341 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.021 |
ω scans | θmax = 67.0°, θmin = 4.2° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −29→29 |
Tmin = 0.63, Tmax = 0.74 | k = −14→14 |
23622 measured reflections | l = −17→18 |
Refinement top
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)] = 0.035 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.100 | w = 1/[σ2(Fo2) + (0.0574P)2 + 1.6621P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
3385 reflections | Δρmax = 0.19 e Å−3 |
264 parameters | Δρmin = −0.18 e Å−3 |
5 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc* = kFc[1+0.001Fc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.00175 (13) |
Crystal data top
C17H20N4S·0.5C3H8O·H2O | V = 3835.01 (16) Å3 |
Mr = 360.51 | Z = 8 |
Monoclinic, C2/c | Cu Kα radiation |
a = 24.5414 (4) Å | µ = 1.63 mm−1 |
b = 12.5088 (3) Å | T = 296 K |
c = 15.3096 (4) Å | 0.40 × 0.25 × 0.20 mm |
β = 125.314 (1)° | |
Data collection top
Bruker SMART APEXII CCD area-detector diffractometer | 3385 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 3341 reflections with I > 2σ(I) |
Tmin = 0.63, Tmax = 0.74 | Rint = 0.021 |
23622 measured reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.035 | 5 restraints |
wR(F2) = 0.100 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.19 e Å−3 |
3385 reflections | Δρmin = −0.18 e Å−3 |
264 parameters | |
Special details top
Geometry. Bond distances, angles etc. have been calculated using the rounded
fractional coordinates. All su's are estimated from the variances of the
(full) variance-covariance matrix. The cell e.s.d.'s are taken into account in
the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user
for potential systematic errors. Weighted R-factors wR and all
goodnesses of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The observed criterion of F2 > σ(F2)
is used only for calculating -R-factor-obs 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 (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
S1 | 0.29248 (2) | 0.15475 (3) | 0.24465 (3) | 0.0562 (2) | |
N1 | 0.16736 (5) | 0.37335 (9) | 0.31448 (9) | 0.0433 (3) | |
N2 | 0.18683 (6) | 0.29524 (10) | 0.15343 (10) | 0.0498 (4) | |
N3 | 0.27114 (5) | 0.41962 (8) | 0.46204 (9) | 0.0427 (3) | |
N4 | 0.35058 (6) | 0.54962 (9) | 0.64855 (9) | 0.0516 (4) | |
C1 | 0.12178 (6) | 0.30669 (10) | 0.22787 (10) | 0.0415 (4) | |
C2 | 0.12802 (6) | 0.27120 (11) | 0.14713 (10) | 0.0449 (4) | |
C3 | 0.24439 (6) | 0.25447 (11) | 0.24650 (11) | 0.0436 (4) | |
C4 | 0.26632 (6) | 0.28005 (10) | 0.34846 (10) | 0.0408 (4) | |
C5 | 0.23144 (6) | 0.36005 (9) | 0.37018 (10) | 0.0391 (4) | |
C6 | 0.32309 (6) | 0.21755 (10) | 0.42610 (11) | 0.0456 (4) | |
C7 | 0.34344 (7) | 0.14723 (11) | 0.38342 (13) | 0.0525 (4) | |
C8 | 0.39945 (9) | 0.06788 (15) | 0.43890 (17) | 0.0761 (6) | |
C9 | 0.07649 (7) | 0.21363 (13) | 0.06055 (12) | 0.0565 (5) | |
C10 | 0.01868 (7) | 0.19057 (14) | 0.05237 (13) | 0.0648 (5) | |
C11 | 0.01205 (7) | 0.22423 (13) | 0.13151 (13) | 0.0589 (5) | |
C12 | 0.06272 (6) | 0.28217 (11) | 0.21718 (12) | 0.0493 (4) | |
C13 | 0.33583 (6) | 0.46104 (11) | 0.49335 (11) | 0.0455 (4) | |
C14 | 0.38135 (7) | 0.47709 (11) | 0.61347 (12) | 0.0531 (4) | |
C15 | 0.28651 (8) | 0.50498 (12) | 0.61717 (12) | 0.0541 (5) | |
C16 | 0.23996 (7) | 0.48954 (11) | 0.49777 (11) | 0.0467 (4) | |
C17 | 0.39478 (10) | 0.56624 (17) | 0.76489 (13) | 0.0824 (7) | |
O1 | 0.09446 (11) | 0.4207 (2) | −0.1806 (3) | 0.0896 (10) | 0.500 |
C18 | 0.02263 (12) | 0.4235 (4) | −0.2581 (4) | 0.0852 (18) | 0.500 |
C19 | 0.0052 (4) | 0.3084 (5) | −0.2976 (7) | 0.186 (4) | 0.500 |
C20 | −0.0074 (7) | 0.4381 (11) | −0.1952 (9) | 0.252 (8) | 0.500 |
O1W | 0.17970 (6) | 0.24588 (9) | −0.03978 (10) | 0.0603 (4) | |
H2 | 0.1835 (8) | 0.2743 (13) | 0.0950 (15) | 0.056 (4)* | |
H6 | 0.34410 | 0.22470 | 0.49940 | 0.0550* | |
H8A | 0.40140 | 0.02920 | 0.38670 | 0.1140* | 0.500 |
H8B | 0.39190 | 0.01880 | 0.47910 | 0.1140* | 0.500 |
H8C | 0.44090 | 0.10480 | 0.48650 | 0.1140* | 0.500 |
H8D | 0.42140 | 0.07270 | 0.51480 | 0.1140* | 0.500 |
H8E | 0.43090 | 0.08310 | 0.42240 | 0.1140* | 0.500 |
H8F | 0.38190 | −0.00290 | 0.41500 | 0.1140* | 0.500 |
H9 | 0.08110 | 0.19030 | 0.00740 | 0.0680* | |
H10 | −0.01560 | 0.15260 | −0.00620 | 0.0780* | |
H11 | −0.02640 | 0.20800 | 0.12720 | 0.0710* | |
H12 | 0.05730 | 0.30560 | 0.26940 | 0.0590* | |
H13A | 0.32960 | 0.52860 | 0.45750 | 0.0550* | |
H13B | 0.35620 | 0.41110 | 0.47170 | 0.0550* | |
H14A | 0.39020 | 0.40870 | 0.64910 | 0.0640* | |
H14B | 0.42360 | 0.50660 | 0.63320 | 0.0640* | |
H15A | 0.26600 | 0.55270 | 0.64020 | 0.0650* | |
H15B | 0.29400 | 0.43680 | 0.65260 | 0.0650* | |
H16A | 0.19840 | 0.45810 | 0.47930 | 0.0560* | |
H16B | 0.22990 | 0.55820 | 0.46210 | 0.0560* | |
H17A | 0.37430 | 0.61550 | 0.78580 | 0.1240* | |
H17B | 0.43670 | 0.59480 | 0.78410 | 0.1240* | |
H17C | 0.40230 | 0.49920 | 0.80080 | 0.1240* | |
H1 | 0.11010 | 0.47990 | −0.17670 | 0.1080* | 0.500 |
H18 | 0.00730 | 0.47620 | −0.31520 | 0.1280* | 0.500 |
H19A | 0.03970 | 0.27900 | −0.30190 | 0.2800* | 0.500 |
H19B | −0.03650 | 0.30690 | −0.36710 | 0.2800* | 0.500 |
H19C | 0.00150 | 0.26680 | −0.24850 | 0.2800* | 0.500 |
H20A | 0.00020 | 0.51000 | −0.16860 | 0.3770* | 0.500 |
H20B | 0.01330 | 0.38900 | −0.13610 | 0.3770* | 0.500 |
H20C | −0.05450 | 0.42450 | −0.24110 | 0.3770* | 0.500 |
H2AW | 0.22061 (16) | 0.247 (5) | −0.004 (4) | 0.1270* | 0.500 |
H1W | 0.1672 (11) | 0.1840 (19) | −0.0775 (18) | 0.085 (6)* | |
H2BW | 0.156 (2) | 0.291 (4) | −0.085 (4) | 0.1270* | 0.500 |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0518 (2) | 0.0613 (3) | 0.0584 (3) | −0.0023 (2) | 0.0336 (2) | −0.0165 (2) |
N1 | 0.0373 (5) | 0.0427 (6) | 0.0443 (6) | −0.0011 (4) | 0.0204 (5) | −0.0021 (4) |
N2 | 0.0483 (6) | 0.0599 (7) | 0.0403 (6) | −0.0044 (5) | 0.0251 (5) | −0.0001 (5) |
N3 | 0.0395 (5) | 0.0395 (5) | 0.0472 (6) | −0.0054 (4) | 0.0239 (5) | −0.0100 (4) |
N4 | 0.0558 (7) | 0.0399 (6) | 0.0382 (6) | 0.0039 (5) | 0.0151 (5) | −0.0043 (4) |
C1 | 0.0359 (6) | 0.0382 (6) | 0.0409 (7) | 0.0012 (5) | 0.0167 (5) | 0.0038 (5) |
C2 | 0.0403 (7) | 0.0441 (7) | 0.0401 (7) | 0.0005 (5) | 0.0173 (6) | 0.0044 (5) |
C3 | 0.0408 (7) | 0.0446 (7) | 0.0458 (7) | −0.0068 (5) | 0.0252 (6) | −0.0057 (5) |
C4 | 0.0364 (6) | 0.0374 (6) | 0.0431 (7) | −0.0058 (5) | 0.0198 (5) | −0.0063 (5) |
C5 | 0.0400 (6) | 0.0345 (6) | 0.0407 (7) | −0.0037 (5) | 0.0221 (5) | −0.0015 (5) |
C6 | 0.0392 (7) | 0.0409 (7) | 0.0460 (7) | −0.0043 (5) | 0.0184 (6) | −0.0080 (5) |
C7 | 0.0418 (7) | 0.0462 (7) | 0.0598 (9) | −0.0022 (5) | 0.0238 (7) | −0.0098 (6) |
C8 | 0.0578 (9) | 0.0629 (10) | 0.0878 (13) | 0.0129 (8) | 0.0307 (9) | −0.0127 (9) |
C9 | 0.0477 (8) | 0.0631 (9) | 0.0417 (7) | −0.0007 (6) | 0.0160 (6) | −0.0049 (6) |
C10 | 0.0407 (8) | 0.0707 (10) | 0.0531 (9) | −0.0081 (7) | 0.0099 (7) | −0.0101 (7) |
C11 | 0.0344 (7) | 0.0662 (9) | 0.0610 (9) | −0.0041 (6) | 0.0188 (7) | 0.0007 (7) |
C12 | 0.0372 (7) | 0.0523 (8) | 0.0504 (8) | 0.0024 (5) | 0.0208 (6) | 0.0035 (6) |
C13 | 0.0397 (7) | 0.0412 (7) | 0.0502 (7) | −0.0064 (5) | 0.0229 (6) | −0.0088 (5) |
C14 | 0.0443 (7) | 0.0433 (7) | 0.0509 (8) | 0.0029 (6) | 0.0156 (6) | −0.0045 (6) |
C15 | 0.0697 (9) | 0.0425 (7) | 0.0532 (8) | 0.0050 (6) | 0.0374 (8) | −0.0019 (6) |
C16 | 0.0476 (7) | 0.0400 (7) | 0.0531 (8) | 0.0003 (5) | 0.0295 (6) | −0.0056 (6) |
C17 | 0.0872 (13) | 0.0775 (12) | 0.0414 (9) | 0.0141 (10) | 0.0135 (8) | −0.0089 (8) |
O1 | 0.0529 (13) | 0.0697 (16) | 0.106 (2) | 0.0034 (11) | 0.0227 (14) | 0.0286 (15) |
C18 | 0.053 (2) | 0.105 (4) | 0.082 (3) | −0.007 (2) | 0.030 (2) | 0.009 (3) |
C19 | 0.110 (5) | 0.209 (8) | 0.197 (9) | −0.050 (6) | 0.064 (6) | −0.132 (8) |
C20 | 0.227 (11) | 0.274 (14) | 0.269 (17) | 0.075 (13) | 0.151 (11) | −0.061 (13) |
O1W | 0.0735 (7) | 0.0471 (6) | 0.0731 (8) | −0.0033 (5) | 0.0497 (7) | −0.0040 (5) |
Geometric parameters (Å, º) top
S1—C3 | 1.7286 (16) | C6—H6 | 0.9300 |
S1—C7 | 1.7363 (17) | C8—H8E | 0.9600 |
O1—C18 | 1.449 (6) | C8—H8F | 0.9600 |
O1—H1 | 0.8200 | C8—H8B | 0.9600 |
O1W—H2AW | 0.82 (4) | C8—H8C | 0.9600 |
O1W—H1W | 0.91 (2) | C8—H8A | 0.9600 |
O1W—H2BW | 0.82 (5) | C8—H8D | 0.9600 |
N1—C5 | 1.295 (2) | C9—H9 | 0.9300 |
N1—C1 | 1.4107 (17) | C10—H10 | 0.9300 |
N2—C2 | 1.422 (2) | C11—H11 | 0.9300 |
N2—C3 | 1.400 (2) | C12—H12 | 0.9300 |
N3—C16 | 1.461 (2) | C13—H13B | 0.9700 |
N3—C13 | 1.463 (2) | C13—H13A | 0.9700 |
N3—C5 | 1.3778 (16) | C14—H14B | 0.9700 |
N4—C14 | 1.467 (2) | C14—H14A | 0.9700 |
N4—C17 | 1.469 (2) | C15—H15B | 0.9700 |
N4—C15 | 1.463 (3) | C15—H15A | 0.9700 |
N2—H2 | 0.89 (2) | C16—H16A | 0.9700 |
C1—C2 | 1.403 (2) | C16—H16B | 0.9700 |
C1—C12 | 1.396 (2) | C17—H17C | 0.9600 |
C2—C9 | 1.392 (2) | C17—H17A | 0.9600 |
C3—C4 | 1.3629 (19) | C17—H17B | 0.9600 |
C4—C6 | 1.432 (2) | C18—C19 | 1.524 (8) |
C4—C5 | 1.474 (2) | C18—C20 | 1.525 (18) |
C6—C7 | 1.352 (2) | C18—H18 | 0.9800 |
C7—C8 | 1.499 (3) | C19—H19C | 0.9600 |
C9—C10 | 1.381 (3) | C19—H19A | 0.9600 |
C10—C11 | 1.378 (3) | C19—H19B | 0.9600 |
C11—C12 | 1.381 (2) | C20—H20A | 0.9600 |
C13—C14 | 1.515 (2) | C20—H20B | 0.9600 |
C15—C16 | 1.507 (2) | C20—H20C | 0.9600 |
| | | |
C3—S1—C7 | 91.99 (8) | H8D—C8—H8F | 109.00 |
C18—O1—H1 | 110.00 | H8A—C8—H8B | 109.00 |
H2AW—O1W—H1W | 106 (5) | H8B—C8—H8C | 109.00 |
H2AW—O1W—H2BW | 123 (6) | H8B—C8—H8D | 56.00 |
H1W—O1W—H2BW | 104 (4) | H8B—C8—H8E | 141.00 |
C1—N1—C5 | 122.97 (13) | H8E—C8—H8F | 110.00 |
C2—N2—C3 | 112.31 (13) | C2—C9—H9 | 119.00 |
C5—N3—C13 | 121.29 (13) | C10—C9—H9 | 120.00 |
C5—N3—C16 | 119.45 (13) | C11—C10—H10 | 120.00 |
C13—N3—C16 | 111.69 (11) | C9—C10—H10 | 120.00 |
C14—N4—C17 | 110.85 (15) | C10—C11—H11 | 120.00 |
C15—N4—C17 | 110.62 (15) | C12—C11—H11 | 120.00 |
C14—N4—C15 | 109.07 (12) | C1—C12—H12 | 119.00 |
C2—N2—H2 | 111.7 (14) | C11—C12—H12 | 119.00 |
C3—N2—H2 | 111.6 (13) | C14—C13—H13B | 110.00 |
C2—C1—C12 | 117.53 (13) | C14—C13—H13A | 110.00 |
N1—C1—C12 | 116.47 (13) | N3—C13—H13B | 110.00 |
N1—C1—C2 | 125.75 (15) | H13A—C13—H13B | 108.00 |
N2—C2—C9 | 120.13 (14) | N3—C13—H13A | 110.00 |
N2—C2—C1 | 119.80 (12) | N4—C14—H14A | 110.00 |
C1—C2—C9 | 120.07 (16) | H14A—C14—H14B | 108.00 |
N2—C3—C4 | 125.34 (15) | C13—C14—H14A | 110.00 |
S1—C3—C4 | 111.52 (11) | N4—C14—H14B | 110.00 |
S1—C3—N2 | 122.90 (11) | C13—C14—H14B | 110.00 |
C3—C4—C5 | 121.42 (13) | N4—C15—H15B | 109.00 |
C5—C4—C6 | 126.62 (12) | C16—C15—H15A | 109.00 |
C3—C4—C6 | 111.91 (13) | N4—C15—H15A | 109.00 |
N1—C5—C4 | 125.52 (12) | H15A—C15—H15B | 108.00 |
N1—C5—N3 | 118.40 (13) | C16—C15—H15B | 109.00 |
N3—C5—C4 | 115.92 (13) | C15—C16—H16B | 110.00 |
C4—C6—C7 | 114.08 (13) | C15—C16—H16A | 110.00 |
C6—C7—C8 | 129.13 (16) | N3—C16—H16A | 110.00 |
S1—C7—C8 | 120.35 (13) | H16A—C16—H16B | 108.00 |
S1—C7—C6 | 110.49 (12) | N3—C16—H16B | 110.00 |
C2—C9—C10 | 120.99 (16) | N4—C17—H17A | 109.00 |
C9—C10—C11 | 119.59 (16) | N4—C17—H17B | 109.00 |
C10—C11—C12 | 119.75 (18) | N4—C17—H17C | 109.00 |
C1—C12—C11 | 122.06 (15) | H17A—C17—H17B | 110.00 |
N3—C13—C14 | 110.11 (13) | H17A—C17—H17C | 110.00 |
N4—C14—C13 | 110.61 (13) | H17B—C17—H17C | 109.00 |
N4—C15—C16 | 111.38 (15) | O1—C18—C20 | 106.8 (6) |
N3—C16—C15 | 109.71 (14) | C19—C18—C20 | 103.7 (7) |
C7—C6—H6 | 123.00 | O1—C18—C19 | 103.4 (5) |
C4—C6—H6 | 123.00 | C20—C18—H18 | 114.00 |
C7—C8—H8A | 109.00 | O1—C18—H18 | 114.00 |
C7—C8—H8C | 109.00 | C19—C18—H18 | 114.00 |
C7—C8—H8D | 109.00 | C18—C19—H19B | 109.00 |
C7—C8—H8B | 109.00 | H19A—C19—H19C | 109.00 |
H8A—C8—H8D | 141.00 | C18—C19—H19C | 109.00 |
H8A—C8—H8E | 56.00 | H19A—C19—H19B | 110.00 |
H8A—C8—H8C | 110.00 | C18—C19—H19A | 109.00 |
C7—C8—H8E | 109.00 | H19B—C19—H19C | 110.00 |
C7—C8—H8F | 109.00 | C18—C20—H20C | 110.00 |
H8A—C8—H8F | 56.00 | H20A—C20—H20C | 109.00 |
H8B—C8—H8F | 56.00 | H20B—C20—H20C | 110.00 |
H8C—C8—H8D | 56.00 | H20A—C20—H20B | 109.00 |
H8C—C8—H8E | 56.00 | C18—C20—H20A | 110.00 |
H8C—C8—H8F | 141.00 | C18—C20—H20B | 109.00 |
H8D—C8—H8E | 109.00 | | |
| | | |
C3—S1—C7—C6 | 0.43 (14) | C12—C1—C2—C9 | −0.1 (2) |
C3—S1—C7—C8 | 178.70 (16) | N1—C1—C12—C11 | 175.21 (13) |
C7—S1—C3—N2 | −174.88 (14) | C12—C1—C2—N2 | 179.18 (12) |
C7—S1—C3—C4 | −0.26 (13) | N1—C1—C2—C9 | −174.08 (13) |
C5—N1—C1—C12 | 141.77 (14) | N1—C1—C2—N2 | 5.2 (2) |
C1—N1—C5—N3 | −171.03 (12) | C1—C2—C9—C10 | 0.1 (2) |
C5—N1—C1—C2 | −44.2 (2) | N2—C2—C9—C10 | −179.24 (14) |
C1—N1—C5—C4 | 4.2 (2) | N2—C3—C4—C5 | −3.0 (2) |
C3—N2—C2—C9 | −121.43 (15) | S1—C3—C4—C6 | 0.02 (18) |
C2—N2—C3—C4 | −59.87 (19) | N2—C3—C4—C6 | 174.48 (15) |
C2—N2—C3—S1 | 114.00 (14) | S1—C3—C4—C5 | −177.47 (11) |
C3—N2—C2—C1 | 59.26 (17) | C6—C4—C5—N1 | −139.74 (16) |
C13—N3—C16—C15 | −56.26 (15) | C6—C4—C5—N3 | 35.6 (2) |
C16—N3—C13—C14 | 56.41 (14) | C3—C4—C5—N3 | −147.36 (14) |
C13—N3—C5—N1 | −142.72 (13) | C3—C4—C6—C7 | 0.3 (2) |
C16—N3—C5—C4 | −171.25 (12) | C5—C4—C6—C7 | 177.65 (15) |
C5—N3—C16—C15 | 153.70 (13) | C3—C4—C5—N1 | 37.4 (2) |
C5—N3—C13—C14 | −154.18 (12) | C4—C6—C7—C8 | −178.57 (18) |
C16—N3—C5—N1 | 4.39 (18) | C4—C6—C7—S1 | −0.51 (19) |
C13—N3—C5—C4 | 41.64 (16) | C2—C9—C10—C11 | −0.6 (2) |
C15—N4—C14—C13 | 58.48 (15) | C9—C10—C11—C12 | 1.1 (2) |
C14—N4—C15—C16 | −59.03 (15) | C10—C11—C12—C1 | −1.2 (2) |
C17—N4—C15—C16 | 178.80 (14) | N3—C13—C14—N4 | −57.44 (15) |
C17—N4—C14—C13 | −179.49 (15) | N4—C15—C16—N3 | 57.77 (16) |
C2—C1—C12—C11 | 0.7 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N1i | 0.82 | 2.36 | 3.162 (3) | 165 |
O1W—H2AW···O1Wii | 0.82 (4) | 2.13 (4) | 2.923 (2) | 162 (4) |
O1W—H1W···N4iii | 0.91 (2) | 1.91 (2) | 2.8145 (16) | 175 (2) |
N2—H2···O1W | 0.89 (2) | 2.04 (2) | 2.926 (2) | 172.5 (15) |
O1W—H2BW···O1 | 0.82 (5) | 2.12 (5) | 2.931 (3) | 170 (6) |
Symmetry codes: (i) x, −y+1, z−1/2; (ii) −x+1/2, −y+1/2, −z; (iii) −x+1/2, y−1/2, −z+1/2. |
(III) 2-Methyl-4-(4-methylpiperazin-1-yl)-10
H-thieno[2,3-
b][1,5]benzodiazepine propan-2-one hemisolvate monohydrate
top
Crystal data top
C17H20N4S·0.5C3H6O·H2O | F(000) = 1536 |
Mr = 359.50 | Dx = 1.258 Mg m−3 |
Monoclinic, C2/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -C 2yc | Cell parameters from 928 reflections |
a = 24.5759 (14) Å | θ = 3.4–22.0° |
b = 12.5608 (5) Å | µ = 0.19 mm−1 |
c = 15.1607 (9) Å | T = 296 K |
β = 125.790 (9)° | Needle, yellow |
V = 3796.3 (6) Å3 | 0.50 × 0.35 × 0.25 mm |
Z = 8 | |
Data collection top
Kuma KM-4 CCD area-detector diffractometer | 3339 independent reflections |
Graphite monochromator | 1727 reflections with I > 2σ(I) |
Detector resolution: 8.2356 pixels mm-1 | Rint = 0.045 |
ω scans | θmax = 25.0°, θmin = 1.9° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −29→29 |
Tmin = 0.91, Tmax = 0.96 | k = −14→14 |
21646 measured reflections | l = −18→16 |
Refinement top
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)] = 0.037 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | w = 1/[σ2(Fo2) + (0.0497P)2] where P = (Fo2 + 2Fc2)/3 |
S = 0.82 | (Δ/σ)max = 0.001 |
3339 reflections | Δρmax = 0.32 e Å−3 |
261 parameters | Δρmin = −0.23 e Å−3 |
27 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc* = kFc[1+0.001Fc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0008 (2) |
Crystal data top
C17H20N4S·0.5C3H6O·H2O | V = 3796.3 (6) Å3 |
Mr = 359.50 | Z = 8 |
Monoclinic, C2/c | Mo Kα radiation |
a = 24.5759 (14) Å | µ = 0.19 mm−1 |
b = 12.5608 (5) Å | T = 296 K |
c = 15.1607 (9) Å | 0.50 × 0.35 × 0.25 mm |
β = 125.790 (9)° | |
Data collection top
Kuma KM-4 CCD area-detector diffractometer | 3339 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 1727 reflections with I > 2σ(I) |
Tmin = 0.91, Tmax = 0.96 | Rint = 0.045 |
21646 measured reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.037 | 27 restraints |
wR(F2) = 0.090 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.82 | Δρmax = 0.32 e Å−3 |
3339 reflections | Δρmin = −0.23 e Å−3 |
261 parameters | |
Special details top
Geometry. Bond distances, angles etc. have been calculated using the rounded
fractional coordinates. All su's are estimated from the variances of the
(full) variance-covariance matrix. The cell e.s.d.'s are taken into account in
the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user
for potential systematic errors. Weighted R-factors wR and all
goodnesses of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The observed criterion of F2 > σ(F2)
is used only for calculating -R-factor-obs 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 (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
S1 | 0.79174 (3) | 0.85138 (5) | 0.74769 (5) | 0.0564 (2) | |
N1 | 0.66840 (9) | 0.62822 (12) | 0.81453 (14) | 0.0413 (6) | |
N2 | 0.68726 (9) | 0.70939 (14) | 0.65339 (16) | 0.0466 (7) | |
N3 | 0.77255 (8) | 0.58236 (12) | 0.96401 (13) | 0.0410 (6) | |
N4 | 0.85188 (9) | 0.44914 (13) | 1.14918 (13) | 0.0485 (7) | |
C1 | 0.62214 (10) | 0.69377 (15) | 0.72647 (16) | 0.0390 (8) | |
C2 | 0.62767 (11) | 0.73030 (16) | 0.64520 (17) | 0.0415 (8) | |
C3 | 0.74471 (11) | 0.74987 (15) | 0.74837 (18) | 0.0410 (8) | |
C4 | 0.76667 (10) | 0.72348 (15) | 0.85075 (17) | 0.0372 (8) | |
C5 | 0.73247 (11) | 0.64219 (15) | 0.87141 (16) | 0.0378 (8) | |
C6 | 0.82307 (11) | 0.78578 (16) | 0.92993 (18) | 0.0458 (8) | |
C7 | 0.84275 (11) | 0.85744 (17) | 0.88792 (18) | 0.0504 (8) | |
C8 | 0.89860 (12) | 0.9369 (2) | 0.9459 (2) | 0.0800 (11) | |
C9 | 0.57518 (12) | 0.78484 (18) | 0.55675 (18) | 0.0568 (9) | |
C10 | 0.51739 (12) | 0.8058 (2) | 0.5481 (2) | 0.0647 (10) | |
C11 | 0.51131 (12) | 0.77185 (18) | 0.6273 (2) | 0.0587 (9) | |
C12 | 0.56270 (11) | 0.71583 (17) | 0.71474 (18) | 0.0476 (8) | |
C13 | 0.83733 (10) | 0.54160 (16) | 0.99533 (16) | 0.0456 (8) | |
C14 | 0.88249 (11) | 0.52317 (17) | 1.11582 (17) | 0.0521 (8) | |
C15 | 0.78783 (11) | 0.49350 (17) | 1.11809 (17) | 0.0516 (9) | |
C16 | 0.74133 (10) | 0.51111 (16) | 0.99766 (16) | 0.0453 (8) | |
C17 | 0.89617 (13) | 0.4294 (2) | 1.26682 (18) | 0.0778 (11) | |
O1 | 0.5214 (7) | 0.7243 (5) | 0.2988 (9) | 0.361 (10) | 0.500 |
C18 | 0.5020 (5) | 0.6374 (4) | 0.2577 (8) | 0.186 (5) | 0.500 |
C19 | 0.5379 (5) | 0.5721 (10) | 0.2213 (11) | 0.220 (9) | 0.500 |
C20 | 0.4321 (4) | 0.5962 (7) | 0.2136 (9) | 0.153 (6) | 0.500 |
O1W | 0.68035 (12) | 0.75683 (15) | 0.45941 (18) | 0.0784 (9) | |
H2 | 0.6832 (10) | 0.7259 (14) | 0.5923 (17) | 0.045 (7)* | |
H6 | 0.84450 | 0.77760 | 1.00430 | 0.0550* | |
H8A | 0.91920 | 0.93330 | 1.02260 | 0.1200* | 0.500 |
H8B | 0.94010 | 0.90070 | 0.99670 | 0.1200* | 0.500 |
H8C | 0.93140 | 0.92120 | 0.93240 | 0.1200* | 0.500 |
H8D | 0.90180 | 0.97450 | 0.89400 | 0.1200* | 0.500 |
H8E | 0.88100 | 1.00720 | 0.91980 | 0.1200* | 0.500 |
H8F | 0.88970 | 0.98660 | 0.98420 | 0.1200* | 0.500 |
H9 | 0.57900 | 0.80770 | 0.50230 | 0.0680* | |
H10 | 0.48250 | 0.84310 | 0.48850 | 0.0780* | |
H11 | 0.47250 | 0.78650 | 0.62230 | 0.0700* | |
H12 | 0.55760 | 0.69200 | 0.76760 | 0.0570* | |
H13A | 0.85790 | 0.59240 | 0.97500 | 0.0550* | |
H13B | 0.83080 | 0.47530 | 0.95740 | 0.0550* | |
H14A | 0.92500 | 0.49450 | 1.13590 | 0.0620* | |
H14B | 0.89130 | 0.59040 | 1.15340 | 0.0620* | |
H15A | 0.79570 | 0.56060 | 1.15550 | 0.0620* | |
H15B | 0.76710 | 0.44510 | 1.14020 | 0.0620* | |
H16A | 0.73130 | 0.44360 | 0.96000 | 0.0540* | |
H16B | 0.69960 | 0.54180 | 0.97890 | 0.0540* | |
H17A | 0.90500 | 0.49540 | 1.30510 | 0.1160* | |
H17B | 0.93760 | 0.39930 | 1.28580 | 0.1160* | |
H17C | 0.87480 | 0.38080 | 1.28650 | 0.1160* | |
H19A | 0.54250 | 0.61390 | 0.17300 | 0.3300* | 0.500 |
H19B | 0.51230 | 0.50930 | 0.18430 | 0.3300* | 0.500 |
H19C | 0.58150 | 0.55210 | 0.28370 | 0.3300* | 0.500 |
H20A | 0.42690 | 0.59270 | 0.27150 | 0.2290* | 0.500 |
H20B | 0.42630 | 0.52640 | 0.18340 | 0.2290* | 0.500 |
H20C | 0.39900 | 0.64350 | 0.15800 | 0.2290* | 0.500 |
H2AW | 0.7207 (8) | 0.750 (6) | 0.489 (6) | 0.1180* | 0.500 |
H1W | 0.6670 (15) | 0.8128 (13) | 0.425 (2) | 0.1180* | |
H2BW | 0.656 (3) | 0.713 (4) | 0.412 (4) | 0.1180* | 0.500 |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0530 (4) | 0.0645 (4) | 0.0565 (4) | −0.0010 (3) | 0.0347 (4) | 0.0150 (3) |
N1 | 0.0347 (11) | 0.0482 (10) | 0.0370 (11) | 0.0027 (9) | 0.0187 (10) | 0.0052 (9) |
N2 | 0.0475 (13) | 0.0618 (12) | 0.0356 (13) | 0.0015 (10) | 0.0271 (12) | 0.0013 (10) |
N3 | 0.0354 (11) | 0.0453 (10) | 0.0430 (11) | 0.0065 (9) | 0.0233 (10) | 0.0131 (9) |
N4 | 0.0515 (12) | 0.0427 (11) | 0.0359 (12) | 0.0013 (9) | 0.0169 (10) | 0.0078 (9) |
C1 | 0.0354 (14) | 0.0413 (12) | 0.0352 (14) | −0.0033 (10) | 0.0178 (12) | −0.0030 (10) |
C2 | 0.0372 (14) | 0.0474 (13) | 0.0338 (13) | −0.0013 (11) | 0.0174 (12) | −0.0015 (10) |
C3 | 0.0404 (14) | 0.0435 (12) | 0.0440 (15) | 0.0058 (10) | 0.0275 (13) | 0.0046 (11) |
C4 | 0.0336 (13) | 0.0377 (12) | 0.0372 (14) | 0.0050 (10) | 0.0190 (12) | 0.0075 (10) |
C5 | 0.0408 (14) | 0.0385 (12) | 0.0358 (13) | 0.0035 (11) | 0.0234 (12) | 0.0019 (11) |
C6 | 0.0425 (14) | 0.0466 (13) | 0.0420 (14) | 0.0069 (11) | 0.0211 (13) | 0.0099 (11) |
C7 | 0.0420 (14) | 0.0467 (13) | 0.0541 (15) | 0.0000 (12) | 0.0234 (13) | 0.0083 (12) |
C8 | 0.0642 (19) | 0.0691 (17) | 0.085 (2) | −0.0201 (15) | 0.0314 (17) | 0.0073 (15) |
C9 | 0.0518 (16) | 0.0713 (16) | 0.0390 (15) | −0.0027 (14) | 0.0219 (14) | 0.0068 (13) |
C10 | 0.0397 (17) | 0.0845 (18) | 0.0464 (17) | 0.0090 (13) | 0.0119 (14) | 0.0162 (14) |
C11 | 0.0349 (14) | 0.0756 (17) | 0.0554 (17) | 0.0051 (13) | 0.0206 (14) | 0.0028 (14) |
C12 | 0.0375 (14) | 0.0616 (15) | 0.0410 (14) | −0.0006 (12) | 0.0214 (13) | 0.0019 (11) |
C13 | 0.0408 (14) | 0.0463 (13) | 0.0464 (15) | 0.0073 (11) | 0.0236 (12) | 0.0086 (10) |
C14 | 0.0420 (14) | 0.0479 (14) | 0.0511 (16) | 0.0015 (11) | 0.0187 (13) | 0.0035 (11) |
C15 | 0.0635 (17) | 0.0485 (13) | 0.0464 (16) | −0.0032 (13) | 0.0341 (14) | 0.0031 (12) |
C16 | 0.0472 (14) | 0.0462 (13) | 0.0466 (15) | 0.0024 (11) | 0.0297 (13) | 0.0080 (11) |
C17 | 0.080 (2) | 0.0792 (18) | 0.0415 (17) | −0.0038 (16) | 0.0172 (15) | 0.0128 (14) |
O1 | 0.432 (19) | 0.422 (13) | 0.387 (19) | −0.290 (15) | 0.328 (17) | −0.286 (12) |
C18 | 0.204 (10) | 0.266 (11) | 0.115 (7) | −0.202 (10) | 0.109 (7) | −0.106 (9) |
C19 | 0.225 (15) | 0.255 (14) | 0.282 (17) | −0.047 (12) | 0.206 (14) | −0.153 (12) |
C20 | 0.162 (9) | 0.151 (8) | 0.211 (12) | 0.089 (8) | 0.146 (10) | 0.103 (9) |
O1W | 0.1297 (19) | 0.0563 (11) | 0.0840 (18) | 0.0036 (14) | 0.0820 (18) | 0.0046 (10) |
Geometric parameters (Å, º) top
S1—C3 | 1.725 (3) | C6—H6 | 0.9300 |
S1—C7 | 1.726 (2) | C8—H8E | 0.9600 |
O1—C18 | 1.208 (10) | C8—H8C | 0.9600 |
O1W—H2BW | 0.82 (5) | C8—H8D | 0.9600 |
O1W—H2AW | 0.82 (6) | C8—H8B | 0.9600 |
O1W—H1W | 0.821 (19) | C8—H8F | 0.9600 |
N1—C5 | 1.291 (4) | C8—H8A | 0.9600 |
N1—C1 | 1.406 (3) | C9—H9 | 0.9300 |
N2—C2 | 1.420 (4) | C10—H10 | 0.9300 |
N2—C3 | 1.396 (3) | C11—H11 | 0.9300 |
N3—C13 | 1.462 (3) | C12—H12 | 0.9300 |
N3—C16 | 1.452 (3) | C13—H13B | 0.9700 |
N3—C5 | 1.374 (3) | C13—H13A | 0.9700 |
N4—C14 | 1.460 (3) | C14—H14A | 0.9700 |
N4—C15 | 1.464 (4) | C14—H14B | 0.9700 |
N4—C17 | 1.469 (3) | C15—H15A | 0.9700 |
N2—H2 | 0.90 (2) | C15—H15B | 0.9700 |
C1—C12 | 1.392 (4) | C16—H16B | 0.9700 |
C1—C2 | 1.394 (3) | C16—H16A | 0.9700 |
C2—C9 | 1.381 (3) | C17—H17B | 0.9600 |
C3—C4 | 1.353 (3) | C17—H17A | 0.9600 |
C4—C5 | 1.468 (4) | C17—H17C | 0.9600 |
C4—C6 | 1.424 (3) | C18—C19 | 1.525 (19) |
C6—C7 | 1.345 (4) | C18—C20 | 1.524 (18) |
C7—C8 | 1.497 (4) | C19—H19C | 0.9600 |
C9—C10 | 1.373 (5) | C19—H19A | 0.9600 |
C10—C11 | 1.362 (4) | C19—H19B | 0.9600 |
C11—C12 | 1.375 (3) | C20—H20A | 0.9600 |
C13—C14 | 1.500 (3) | C20—H20B | 0.9600 |
C15—C16 | 1.499 (3) | C20—H20C | 0.9600 |
| | | |
C3—S1—C7 | 91.82 (12) | H8C—C8—H8F | 141.00 |
H2AW—O1W—H1W | 110 (6) | H8D—C8—H8E | 56.00 |
H2AW—O1W—H2BW | 116 (7) | H8D—C8—H8F | 109.00 |
H1W—O1W—H2BW | 102 (4) | H8E—C8—H8F | 56.00 |
C1—N1—C5 | 123.2 (2) | H8A—C8—H8C | 110.00 |
C2—N2—C3 | 113.1 (2) | H8A—C8—H8D | 141.00 |
C13—N3—C16 | 111.64 (16) | H8A—C8—H8E | 109.00 |
C5—N3—C16 | 119.1 (2) | C2—C9—H9 | 120.00 |
C5—N3—C13 | 121.1 (2) | C10—C9—H9 | 119.00 |
C14—N4—C15 | 108.72 (17) | C9—C10—H10 | 120.00 |
C14—N4—C17 | 111.2 (2) | C11—C10—H10 | 120.00 |
C15—N4—C17 | 110.4 (2) | C12—C11—H11 | 120.00 |
C3—N2—H2 | 114.6 (16) | C10—C11—H11 | 120.00 |
C2—N2—H2 | 112.4 (17) | C11—C12—H12 | 119.00 |
N1—C1—C2 | 126.1 (3) | C1—C12—H12 | 119.00 |
C2—C1—C12 | 117.3 (2) | N3—C13—H13A | 110.00 |
N1—C1—C12 | 116.3 (2) | N3—C13—H13B | 110.00 |
N2—C2—C9 | 120.4 (2) | C14—C13—H13A | 110.00 |
N2—C2—C1 | 119.4 (2) | C14—C13—H13B | 110.00 |
C1—C2—C9 | 120.2 (3) | H13A—C13—H13B | 108.00 |
N2—C3—C4 | 125.4 (2) | N4—C14—H14B | 110.00 |
S1—C3—N2 | 122.70 (17) | H14A—C14—H14B | 108.00 |
S1—C3—C4 | 111.64 (18) | C13—C14—H14A | 109.00 |
C5—C4—C6 | 126.8 (2) | C13—C14—H14B | 109.00 |
C3—C4—C6 | 111.8 (2) | N4—C14—H14A | 109.00 |
C3—C4—C5 | 121.4 (2) | C16—C15—H15B | 109.00 |
N3—C5—C4 | 116.1 (2) | H15A—C15—H15B | 108.00 |
N1—C5—C4 | 125.38 (19) | C16—C15—H15A | 109.00 |
N1—C5—N3 | 118.3 (2) | N4—C15—H15A | 109.00 |
C4—C6—C7 | 114.3 (2) | N4—C15—H15B | 109.00 |
C6—C7—C8 | 128.9 (2) | N3—C16—H16A | 110.00 |
S1—C7—C6 | 110.51 (18) | N3—C16—H16B | 110.00 |
S1—C7—C8 | 120.57 (19) | C15—C16—H16A | 110.00 |
C2—C9—C10 | 121.0 (3) | C15—C16—H16B | 110.00 |
C9—C10—C11 | 119.8 (2) | H16A—C16—H16B | 108.00 |
C10—C11—C12 | 119.9 (3) | N4—C17—H17C | 109.00 |
C1—C12—C11 | 121.9 (2) | H17A—C17—H17C | 109.00 |
N3—C13—C14 | 109.8 (2) | H17B—C17—H17C | 110.00 |
N4—C14—C13 | 110.9 (2) | H17A—C17—H17B | 109.00 |
N4—C15—C16 | 111.0 (2) | N4—C17—H17A | 109.00 |
N3—C16—C15 | 109.6 (2) | N4—C17—H17B | 109.00 |
C4—C6—H6 | 123.00 | C19—C18—C20 | 113.6 (8) |
C7—C6—H6 | 123.00 | O1—C18—C19 | 122.4 (14) |
C7—C8—H8D | 109.00 | O1—C18—C20 | 122.5 (13) |
C7—C8—H8E | 109.00 | C18—C19—H19B | 109.00 |
C7—C8—H8F | 109.00 | H19A—C19—H19C | 109.00 |
H8A—C8—H8B | 56.00 | C18—C19—H19C | 109.00 |
C7—C8—H8A | 109.00 | H19A—C19—H19B | 109.00 |
C7—C8—H8B | 110.00 | C18—C19—H19A | 109.00 |
C7—C8—H8C | 109.00 | H19B—C19—H19C | 109.00 |
H8A—C8—H8F | 56.00 | C18—C20—H20C | 109.00 |
H8B—C8—H8C | 56.00 | H20A—C20—H20C | 109.00 |
H8B—C8—H8D | 109.00 | H20B—C20—H20C | 109.00 |
H8B—C8—H8E | 141.00 | H20A—C20—H20B | 109.00 |
H8B—C8—H8F | 109.00 | C18—C20—H20A | 109.00 |
H8C—C8—H8D | 56.00 | C18—C20—H20B | 110.00 |
H8C—C8—H8E | 109.00 | | |
| | | |
C3—S1—C7—C6 | −0.6 (2) | C12—C1—C2—C9 | −0.8 (3) |
C3—S1—C7—C8 | −179.1 (2) | N1—C1—C12—C11 | −174.8 (2) |
C7—S1—C3—N2 | 174.7 (2) | C12—C1—C2—N2 | −179.77 (18) |
C7—S1—C3—C4 | 0.8 (2) | N1—C1—C2—C9 | 173.0 (2) |
C5—N1—C1—C12 | −142.4 (2) | N1—C1—C2—N2 | −6.0 (3) |
C1—N1—C5—N3 | 171.70 (19) | C1—C2—C9—C10 | 1.2 (3) |
C5—N1—C1—C2 | 43.7 (3) | N2—C2—C9—C10 | −179.8 (2) |
C1—N1—C5—C4 | −3.0 (4) | N2—C3—C4—C5 | 3.6 (4) |
C3—N2—C2—C9 | 122.8 (2) | S1—C3—C4—C6 | −0.7 (3) |
C2—N2—C3—C4 | 59.4 (3) | N2—C3—C4—C6 | −174.5 (2) |
C2—N2—C3—S1 | −113.7 (2) | S1—C3—C4—C5 | 177.29 (19) |
C3—N2—C2—C1 | −58.3 (3) | C6—C4—C5—N1 | 139.5 (3) |
C13—N3—C16—C15 | 56.7 (2) | C6—C4—C5—N3 | −35.3 (4) |
C16—N3—C13—C14 | −56.6 (2) | C3—C4—C5—N3 | 147.1 (2) |
C13—N3—C5—N1 | 142.2 (2) | C3—C4—C6—C7 | 0.3 (3) |
C16—N3—C5—C4 | 171.43 (19) | C5—C4—C6—C7 | −177.6 (2) |
C5—N3—C16—C15 | −154.33 (19) | C3—C4—C5—N1 | −38.1 (4) |
C5—N3—C13—C14 | 155.17 (18) | C4—C6—C7—C8 | 178.7 (3) |
C16—N3—C5—N1 | −3.8 (3) | C4—C6—C7—S1 | 0.3 (3) |
C13—N3—C5—C4 | −42.6 (3) | C2—C9—C10—C11 | −0.5 (4) |
C15—N4—C14—C13 | −59.0 (2) | C9—C10—C11—C12 | −0.7 (4) |
C14—N4—C15—C16 | 59.4 (2) | C10—C11—C12—C1 | 1.2 (3) |
C17—N4—C15—C16 | −178.35 (19) | N3—C13—C14—N4 | 57.8 (2) |
C17—N4—C14—C13 | 179.2 (2) | N4—C15—C16—N3 | −58.3 (2) |
C2—C1—C12—C11 | −0.4 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H2AW···O1Wi | 0.82 (6) | 2.08 (6) | 2.887 (5) | 171 (6) |
O1W—H1W···N4ii | 0.82 (2) | 1.95 (2) | 2.765 (3) | 172 (4) |
N2—H2···O1W | 0.90 (2) | 2.01 (2) | 2.907 (3) | 176 (2) |
C20—H20C···O1Wiii | 0.96 | 2.22 | 3.180 (11) | 174 |
Symmetry codes: (i) −x+3/2, −y+3/2, −z+1; (ii) −x+3/2, y+1/2, −z+3/2; (iii) −x+1, y, −z+1/2. |
Experimental details
| (I) | (II) | (III) |
Crystal data |
Chemical formula | C17H20N4S·C2H4O2 | C17H20N4S·0.5C3H8O·H2O | C17H20N4S·0.5C3H6O·H2O |
Mr | 372.49 | 360.51 | 359.50 |
Crystal system, space group | Monoclinic, P21/c | Monoclinic, C2/c | Monoclinic, C2/c |
Temperature (K) | 296 | 296 | 296 |
a, b, c (Å) | 10.1474 (1), 12.8562 (1), 14.5494 (1) | 24.5414 (4), 12.5088 (3), 15.3096 (4) | 24.5759 (14), 12.5608 (5), 15.1607 (9) |
β (°) | 92.92 | 125.314 (1) | 125.790 (9) |
V (Å3) | 1895.61 (3) | 3835.01 (16) | 3796.3 (6) |
Z | 4 | 8 | 8 |
Radiation type | Cu Kα | Cu Kα | Mo Kα |
µ (mm−1) | 1.69 | 1.63 | 0.19 |
Crystal size (mm) | 0.20 × 0.15 × 0.10 | 0.40 × 0.25 × 0.20 | 0.50 × 0.35 × 0.25 |
|
Data collection |
Diffractometer | Bruker SMART APEXII CCD area-detector diffractometer | Bruker SMART APEXII CCD area-detector diffractometer | Kuma KM-4 CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) | Multi-scan (SADABS; Sheldrick, 2003) | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.729, 0.849 | 0.63, 0.74 | 0.91, 0.96 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 22793, 3298, 3201 | 23622, 3385, 3341 | 21646, 3339, 1727 |
Rint | 0.020 | 0.021 | 0.045 |
(sin θ/λ)max (Å−1) | 0.594 | 0.597 | 0.595 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.033, 0.094, 1.07 | 0.035, 0.100, 1.04 | 0.037, 0.090, 0.82 |
No. of reflections | 3298 | 3385 | 3339 |
No. of parameters | 246 | 264 | 261 |
No. of restraints | 8 | 5 | 27 |
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 | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.27, −0.16 | 0.19, −0.18 | 0.32, −0.23 |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N4 | 0.818 (13) | 1.766 (12) | 2.5679 (17) | 166 (2) |
N2—H2···O2i | 0.862 (19) | 2.041 (19) | 2.8998 (18) | 174.4 (17) |
Symmetry code: (i) −x+1, y−1/2, −z+3/2. |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···N1i | 0.82 | 2.36 | 3.162 (3) | 165 |
O1W—H2AW···O1Wii | 0.82 (4) | 2.13 (4) | 2.923 (2) | 162 (4) |
O1W—H1W···N4iii | 0.91 (2) | 1.91 (2) | 2.8145 (16) | 175 (2) |
N2—H2···O1W | 0.89 (2) | 2.04 (2) | 2.926 (2) | 172.5 (15) |
O1W—H2BW···O1 | 0.82 (5) | 2.12 (5) | 2.931 (3) | 170 (6) |
Symmetry codes: (i) x, −y+1, z−1/2; (ii) −x+1/2, −y+1/2, −z; (iii) −x+1/2, y−1/2, −z+1/2. |
Hydrogen-bond geometry (Å, º) for (III) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H2AW···O1Wi | 0.82 (6) | 2.08 (6) | 2.887 (5) | 171 (6) |
O1W—H1W···N4ii | 0.821 (19) | 1.950 (19) | 2.765 (3) | 172 (4) |
N2—H2···O1W | 0.90 (2) | 2.01 (2) | 2.907 (3) | 176 (2) |
C20—H20C···O1Wiii | 0.96 | 2.22 | 3.180 (11) | 174 |
Symmetry codes: (i) −x+3/2, −y+3/2, −z+1; (ii) −x+3/2, y+1/2, −z+3/2; (iii) −x+1, y, −z+1/2. |
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2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine, commonly known as olanzapine, belongs to the class of antipsychotic drugs. It is marketed as Zyprexa by Eli Lilly and Company, and is used in the treatment of various psychoses such as psychosis, schizophrenia, schizophreniform disorders, mild anxiety states and functional bowel disorders (Tollefson et al., 1997). Olanzapine, along with, for example, clozapine and ziprasidone, can be classed as atypical antipsychotic agents of a newer generation (Tandon & Jibson, 2003; Heresco-Levy et al., 2004; Dossenbach et al., 2004), which show better efficacy and reduced side effects, less dysphoria or less impaired cognition (Tandon, 2002). According to a recent literature survey (Lindsley, 2012), olanzapine is listed in the top 20 prescription drugs. Olanzapine is known to exist in various crystalline forms which have been well documented in the literature. It is worth remembering that the propensity of pharmaceutically active substances to assume several crystal forms with different molecular arrangements can be ascribed to the complexity of their chemical structures (Borka, 1991). Based on its inner [Molecular?] structure, a pharmaceutical crystalline compound may be one of a group of polymorphs or molecular adducts if its lattice consists of many components (Haleblian, 1975). The presence of solvent in the crystal lattice confers unique physicochemical properties on the solvates (solubility and dissolution rate), which can affect the bioavailability of the drug (Armas et al., 2007). Screening for diverse crystal modifications has become more and more important for reasons of patent establishment (Bernstein, 2002; Hilfiker, 2008), and it can provide valuable knowledge necessary for further development of the drug formulation (Rustichellia et al., 2000; Singh et al., 2000; van Tonder et al., 2004; Chadha et al., 2009). For example, organic solvates, which appear in pharmacy more rarely than hydrates (Sarma & Desiraju, 1999), may have favorable formulation properties (Byrn et al., 1999). In addition, obtaining a series of isostructural solvates offers a rare possibility to study the effects of a crystal structure on solid-state properties (Nanagia & Desiraju, 1999). Solvates can play different roles, such as space fillers or principal components of the crystal lattice, through interacting with the host molecules by specific intermolecular hydrogen-bond interactions. This paper presents a study of three new crystal structures of olanzapine solvates determined by single-crystal X-ray diffraction analysis, namely olanzapine acetic acid monosolvate, (I), olanzapine propan-2-ol hemisolvate monohydrate, (II), and olanzapine propan-2-one hemisolvate monohydrate, (III).
This structural study completes a model series of olanzapine, deposited in recent years in the Cambridge Structural Database (CSD, Version 5.34; Allen, 2002). Olanzapine has been reported as polymorphs (Reutzel-Edens et al., 2003; Wawrzycka-Gorczyca et al., 2004; Thakuria & Nangia, 2011a), hydrates (Reutzel-Edens et al., 2003; Wawrzycka-Gorczyca et al., 2007), hydrated solvates, such as olanzapine methanol solvate monohydrate (Capuano et al., 2003), olanzapine dimethyl sulfoxide monohydrate (Polla et al., 2005), olanzapine ethanol solvate dihydrate, olanzapine butan-2-ol solvate monohydrate (Wawrzycka-Gorczyca et al., 2007), other solvates, such as olanzapine methanol solvate (Wawrzycka-Gorczyca et al., 2004), olanzapine dichloromethane (Wawrzycka-Gorczyca et al., 2007), and salts, such as olanzapine nicotinic acid (Ravikumar et al., 2005), olanzapine maleate and olanzapine (bis)maleate (Thakuria & Nangia, 2011b), and olanzapine benzoate (Sridhar & Ravikumar, 2007). A close examination of the lattice parameters suggests that there are three sets of isostructural crystals. A precise quantitative comparison of the structural similarity of all known forms of olanzapine, including a clarification of the nature of the intermolecular interactions, will be published elsewhere.
All the solvates reported here crystallize in monoclinic crystal systems: (I) is in the primitive P21/c space group, with one olanzapine and one acetic acid molecule in the asymmetric unit. Conversely, the hemisolvates (II) and (III) crystallize in the C-centred C2/c space group with one olanzapine molecule and one water molecule each, and half a propan-2-ol molecule in (II) or half a propan-2-one molecule in (III) (Figs. 1–3). The olanzapine molecule consists of three fused rings, namely benzene, diazepine and thiophene, and also a 1-methylpiperazin-4-yl fragment.
The conformation of olanzapine is rather rigid and, as expected, no noticeable difference is observed between the new solvated crystal structures and those reported previously. The 1,5-diazepine rings adopt the expected boat conformation and can be described by three planes, a bow (C2/N2/C3), a central plane (C1/C2/C3/C4) and a stern plane (C1/N1/C4/C5). The bow angle is about 112–114° for the structures presented here, while the stern angle is in the range 3–4°. The benzene and thiophene systems are planar, which enables the thienobenzodiazepine ring skeleton to form an extended V-shaped conformation. It is worth mentioning that these conformations have also been observed in related antipsychotic agents (Petcher & Weber, 1974; Cosulich & Lovell, 1977; Ravikumar et al., 2005) and they enable drug–receptor binding interactions (Ravikumar et al., 2005). The piperazine rings of (I)–(III) favour an almost perfect chair conformation, with the methyl group assuming an equatorial orientation. In all three solvates, the piperazine and benzodiazepine rings are in an anticlinal conformation (N1—C5—N3—C13 torsion angles of about 150°) towards themselves. As expected, the geometries of the molecules do not show unusual features compared with other olanzapine structures. A superimposition (on the central 1,5-diazepine ring) of all known olanzapine forms is presented in Fig. 4 in order to reveal the subtle differences in the olanzapine conformations in all the currently known olanzapine crystal structures.
In the title structures, the olanzapine molecules are arranged in a herring-bone pattern, like the majority of known olanzapine forms. Apart from that, the olanzapine molecules, identically to the previously described structures, are associated in a head-to-tail motif in centrosymmetric (inversion-related) dimers, which are characterized only by C—H···π interactions between the aliphatic 1-methylpiperazin-4-yl fragment and the aromatic benzene/thiophene system. These dimers are linked through the solvent molecules, while in the anhydrous compound, (I), the olanzapine pairs are connected by the N—H···N hydrogen bonds. [Please confirm added text]
The incorporation of solvent molecules into the crystal structures leads to many intermolecular Oguest—H···Oguest, Oguest—H···Nhost, Nhost—H···Oguest and Chost—H···Oguest hydrogen bonds in all three solvates. The water solvent molecule in (II) and (III) is strongly bound to the structure (being both a donor and an acceptor of strong hydrogen bonds). Hydrogen-bonding interactions are presented in Tables 1–3. In solvates (II) and (III), one of the water H atoms is disordered over two orientations. In the first orientation, it is a donor related by a symmetry centre O1W—H2AW···O1Wi [symmetry codes: (i) -x + 1/2, -y + 1/2, -z in (II); (i) -x + 3/2, -y + 3/2, -z + 1 in (III)], and in the second orientation it is a propan-2-ol hydroxy-group donor (O1W—H2BW···O1) or a propan-2-one carbonyl O atom donor (O1W—H2BW···O1). In the case of (II), both hydrogen bonds have comparable bond lengths and angles within a 3σ range (Tables 2 and 3), while in (III) they cover a large range of contact distances. In the case of the acetic acid solvate, (I), the typical olanzapine dimers are hydrogen-bonded to the acetic acid molecules, indicating strong host–guest interactions, and also to other dimers via C—H···O interactions.
In (I), the olanzapine and acetic acid molecules are linked together by a strong O1—H1···N4 hydrogen bond which, combined with the N2—H2···O2i interaction [symmetry code: (i) -x + 1, y - 1/2, -z + 3/2], forms infinite zigzag chains (Fig. 5) along the crystallographic b axis, which can be described by the graph-set motif C22(13) in graph-set notation (Etter et al., 1990; Bernstein et al., 1995). In (II), two perpendicular chains exist: an 11-membered chain with a C22(11) graph-set motif, which runs along the b axis, and a C33(9) chain along the a axis, formed through O1W···H2—N2i, O1W—H1W···N4ii, O1W—H2AW···O1Wiii and O1W—H2BW···O1 hydrogen bonds [symmetry codes: (ii) -x + 1/2, y - 1/2, -z + 1/2; (iii) -x + 1/2, -y + 1/2, -z]. As a result, 13-membered rings, with an R44(13) motif, are formed along the b axis (Fig. 6). In (III), O1W—H1W···N4i and N2—H2···O1W intermolecular interactions link the host and guest molecules into parallel zigzag chains along the crystallographic b axis [symmetry codes: (i) -x + 3/2, y + 1/2, -z + 3/2 [Not the same symop as defined for (i) in (III) above - please check carefully]], which can be classified in graph-set notation as C22(11) (Fig. 7). A propan-2-one molecule takes part in two weak hydrogen-bond contacts, viz. O1···H2BW—O1W and C20—H20C···O1Wi [symmetry code: (i) -x + 1, y, -z + 1/2 [A different definition of (i) again - please check carefully]].
To conclude, the molecular structures of three new solvate phases of olanzapine are very similar to those of the other known analogues. The presence of olanzapine dimers, which is a characteristic feature of solid-state olanzapine structures, is confirmed. Nevertheless, the architectures of all the solvates are different. The solvent molecules play a crucial role as crystal lattice stabilizers and as significant building elements in the formation of hydrogen-bond networks. The three new olanzapine solvate phases presented here reveal two types of disorder: orientational disorder of the propan-2-ol and propan-2-one solvent molecules, and positional disorder of the solvent water molecules.