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In 4-fluoroisoquinoline-5-sulfonyl chloride, C
9H
5ClFNO
2S, (I), one of the two sulfonyl O atoms lies approximately on the isoquinoline plane as a result of minimizing the steric repulsion between the chlorosulfonyl group and the neighbouring F atom. In (
S)-(−)-4-fluoro-
N-(1-hydroxypropan-2-yl)isoquinoline-5-sulfonamide, C
12H
13FN
2O
3S, (II), there are two crystallographically independent molecules (
Z′ = 2). The molecular conformations of these two molecules differ in that the amine group of one forms an intramolecular bifurcated hydrogen bond with the F and OH groups, whilst the other forms only a single intramolecular N—H
F hydrogen bond. The N—H
F hydrogen bonds correspond to weak coupling between the N(H) and
19F nuclei, observed in the
1H NMR solution-state spectra. In (
S)-(−)-4-[(4-fluoroisoquinolin-5-yl)sulfonyl]-3-methyl-1,4-diazepan-1-ium chloride, C
15H
19FN
3O
2S
+·Cl
−, (III), the isoquinoline plane is slightly deformed, suggestive of a steric effect induced by the bulky substituent on the sulfonyl group.
Supporting information
CCDC references: 906597; 906598; 906599
A pilot-scale production of (III) was achieved, where (I) and (II) were the
reaction intermediates (Gomi et al., 2011). Compound (I) was
synthesized from 4-fluoroisoquinoline. Plate-like crystals of (I) were grown
by slow diffusion of hexane vapour into a chloroform solution.
Compound (II) was prepared by the reaction of (I) with
(S)-(+)-2-aminopropan-1-ol. The specific rotation, [α]D, of (II) at
292 K is -18.36° (c = 0.54, CHCl3, where c is the
concentration in units of grams per 100 ml). 1H NMR (400 MHz, CDCl3): δ
1.06 (3H, d, J = 6.3 Hz), 1.78 (1H, t, J
= 5.1 Hz), 3.43–3.59 (3H, m), 5.34 (1H, t, J = 7.1 Hz),
7.77 (1H, t, J = 7.8 Hz), 8.23–8.28 (1H, m), 8.60 (1H,
d, J = 5.4 Hz), 8.68 (1H, dd, J = 7.8, 1.2 Hz),
9.19 (1H, s) (Gomi et al., 2011). Plate-like crystals of
(II)
were grown by slow diffusion of hexane vapour into an acetone solution.
Compound (III) was prepared from (I) and (S)-(+)-tert-butyl
3-methyl-1,4-diazepane-1-carboxylate (Gomi et al., 2012). The
specific
rotation, [α]D, of (III) at 293 K is -8.82° (c = 1.00, H2O).
Plate-like crystals of (III) were grown by slow diffusion of ethyl acetate
vapour into a methanol solution.
The coordinates of the amide H atoms in (II) were refined with the N—H
distances restrained to 0.86 (1) Å. This revealed a pyramidal configuration
around the N34 atom of molecule B with reasonable hydrogen-bond
geometry in contrast to the almost flat configuration around the N15 atom of
molecule A. All the other H atoms were positioned geometrically and
refined as riding, with C—H = 0.93 (aromatic), 0.96 (methyl), 0.97 (CH2)
or 0.98 Å (sp3 CH), O—H = 0.82 Å, and 0.90 Å (NH2), and
with Uiso(H) = 1.2Ueq(parent). Methyl-group orientations
were obtained by allowing rotation about the C—C bond.
For (II), Friedel pairs were averaged before the final refinement, since the
Flack (1983) parameter was estimated to be 0.4 (3). The absolute
structure was
assigned based on the known absolute configuration of the
(S)-2-aminopropan-1-ol group.
For (III), the absolute structure was assigned based on the known absolute
configuration of the (S)-3-methyl-1,4-diazepane group. This assignment
is tentatively supported by the value obtained for the Flack (1983)
parameter.
For all compounds, data collection: WinAFC Diffractometer Control Software (Rigaku, 1999); cell refinement: WinAFC Diffractometer Control Software (Rigaku, 1999); data reduction: CrystalStructure (Rigaku, 2010); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: CrystalStructure (Rigaku, 2010).
(I) 4-Fluoroisoquinoline-5-sulfonyl chloride
top
Crystal data top
C9H5ClFNO2S | F(000) = 496.00 |
Mr = 245.66 | Dx = 1.700 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71069 Å |
Hall symbol: -P 2yn | Cell parameters from 25 reflections |
a = 8.070 (3) Å | θ = 10.0–12.5° |
b = 15.353 (3) Å | µ = 0.61 mm−1 |
c = 7.789 (2) Å | T = 293 K |
β = 96.08 (3)° | Plate, colourless |
V = 959.6 (5) Å3 | 0.55 × 0.50 × 0.30 mm |
Z = 4 | |
Data collection top
Rigaku AFC-7R diffractometer | 1621 reflections with F2 > 2σ(F2) |
Radiation source: Rigaku rotating Mo anode | Rint = 0.040 |
Graphite plate monochromator | θmax = 27.5° |
ω/2θ scans | h = −10→3 |
Absorption correction: ψ scan (North et al., 1968) | k = 0→19 |
Tmin = 0.730, Tmax = 0.834 | l = −10→10 |
2444 measured reflections | 3 standard reflections every 150 reflections |
2202 independent reflections | intensity decay: none |
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)] = 0.059 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.164 | H-atom parameters constrained |
S = 1.05 | w = 1/[σ2(Fo2) + (0.1016P)2 + 0.2981P] where P = (Fo2 + 2Fc2)/3 |
2202 reflections | (Δ/σ)max < 0.001 |
136 parameters | Δρmax = 0.26 e Å−3 |
0 restraints | Δρmin = −0.70 e Å−3 |
Crystal data top
C9H5ClFNO2S | V = 959.6 (5) Å3 |
Mr = 245.66 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 8.070 (3) Å | µ = 0.61 mm−1 |
b = 15.353 (3) Å | T = 293 K |
c = 7.789 (2) Å | 0.55 × 0.50 × 0.30 mm |
β = 96.08 (3)° | |
Data collection top
Rigaku AFC-7R diffractometer | 1621 reflections with F2 > 2σ(F2) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.040 |
Tmin = 0.730, Tmax = 0.834 | 3 standard reflections every 150 reflections |
2444 measured reflections | intensity decay: none |
2202 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.059 | 0 restraints |
wR(F2) = 0.164 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.26 e Å−3 |
2202 reflections | Δρmin = −0.70 e Å−3 |
136 parameters | |
Special details top
Refinement. Refinement was performed using all reflections. The weighted R-factor
(wR) and goodness of fit (S) are based on F2.
R-factor (gt) are based on F. The threshold expression of
F2 > 2σ(F2) is used only for calculating R-factor
(gt). |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.2772 (4) | −0.0232 (2) | −0.1594 (5) | 0.0571 (8) | |
N2 | 0.3504 (4) | −0.00576 (19) | −0.2983 (4) | 0.0606 (7) | |
C3 | 0.4284 (4) | 0.0726 (3) | −0.3023 (4) | 0.0549 (7) | |
C4 | 0.4338 (4) | 0.13116 (19) | −0.1704 (4) | 0.0473 (7) | |
C5 | 0.3604 (4) | 0.16752 (17) | 0.1359 (4) | 0.0432 (6) | |
C6 | 0.2727 (4) | 0.14193 (19) | 0.2702 (4) | 0.0500 (7) | |
C7 | 0.1881 (4) | 0.0621 (2) | 0.2652 (5) | 0.0581 (8) | |
C8 | 0.1916 (4) | 0.0083 (2) | 0.1275 (5) | 0.0534 (7) | |
C9 | 0.2763 (4) | 0.03319 (17) | −0.0155 (4) | 0.0455 (6) | |
C10 | 0.3607 (3) | 0.11463 (17) | −0.0163 (4) | 0.0410 (6) | |
F11 | 0.5097 (3) | 0.20776 (13) | −0.1929 (3) | 0.0639 (6) | |
S12 | 0.47932 (10) | 0.26332 (5) | 0.17663 (9) | 0.0495 (3) | |
O13 | 0.4622 (4) | 0.29341 (16) | 0.3466 (3) | 0.0660 (7) | |
O14 | 0.6413 (3) | 0.25348 (16) | 0.1227 (4) | 0.0628 (6) | |
Cl15 | 0.35201 (12) | 0.35169 (5) | 0.01771 (11) | 0.0638 (3) | |
H1 | 0.2221 | −0.0762 | −0.1553 | 0.0685* | |
H3 | 0.4805 | 0.0868 | −0.3994 | 0.0658* | |
H6 | 0.2698 | 0.1782 | 0.3655 | 0.0600* | |
H7 | 0.1293 | 0.0459 | 0.3566 | 0.0697* | |
H8 | 0.1380 | −0.0454 | 0.1267 | 0.0640* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0610 (18) | 0.0481 (17) | 0.0599 (19) | 0.0014 (13) | −0.0039 (14) | −0.0092 (14) |
N2 | 0.0691 (17) | 0.0590 (16) | 0.0517 (15) | 0.0040 (13) | −0.0032 (13) | −0.0130 (12) |
C3 | 0.0578 (17) | 0.0630 (19) | 0.0435 (15) | 0.0060 (14) | 0.0041 (13) | −0.0051 (13) |
C4 | 0.0498 (15) | 0.0480 (15) | 0.0442 (14) | 0.0014 (12) | 0.0058 (12) | 0.0011 (12) |
C5 | 0.0487 (14) | 0.0393 (13) | 0.0421 (14) | 0.0070 (11) | 0.0075 (11) | 0.0038 (11) |
C6 | 0.0605 (17) | 0.0447 (15) | 0.0468 (15) | 0.0089 (12) | 0.0144 (13) | 0.0021 (12) |
C7 | 0.0607 (18) | 0.0538 (17) | 0.0630 (18) | 0.0023 (14) | 0.0216 (15) | 0.0121 (15) |
C8 | 0.0529 (16) | 0.0408 (14) | 0.0667 (19) | −0.0031 (12) | 0.0074 (14) | 0.0067 (13) |
C9 | 0.0436 (13) | 0.0393 (13) | 0.0525 (16) | 0.0040 (11) | −0.0002 (11) | 0.0012 (12) |
C10 | 0.0411 (13) | 0.0401 (13) | 0.0417 (13) | 0.0035 (10) | 0.0035 (11) | −0.0007 (10) |
F11 | 0.0786 (13) | 0.0614 (12) | 0.0545 (11) | −0.0165 (9) | 0.0202 (9) | −0.0002 (9) |
S12 | 0.0606 (5) | 0.0420 (4) | 0.0454 (4) | −0.0027 (3) | 0.0027 (3) | −0.0029 (3) |
O13 | 0.0945 (18) | 0.0575 (14) | 0.0453 (12) | −0.0042 (12) | 0.0038 (11) | −0.0126 (10) |
O14 | 0.0506 (12) | 0.0685 (15) | 0.0689 (15) | −0.0076 (10) | 0.0049 (11) | −0.0032 (12) |
Cl15 | 0.0857 (6) | 0.0441 (5) | 0.0614 (5) | 0.0055 (4) | 0.0069 (4) | 0.0083 (3) |
Geometric parameters (Å, º) top
C1—N2 | 1.314 (5) | C8—C9 | 1.419 (5) |
C1—C9 | 1.417 (5) | C9—C10 | 1.424 (4) |
N2—C3 | 1.359 (5) | S12—O13 | 1.423 (3) |
C3—C4 | 1.363 (5) | S12—O14 | 1.423 (3) |
C4—C10 | 1.415 (4) | S12—Cl15 | 2.0394 (12) |
C4—F11 | 1.346 (4) | C1—H1 | 0.930 |
C5—C6 | 1.381 (5) | C3—H3 | 0.930 |
C5—C10 | 1.437 (4) | C6—H6 | 0.930 |
C5—S12 | 1.766 (3) | C7—H7 | 0.930 |
C6—C7 | 1.402 (5) | C8—H8 | 0.930 |
C7—C8 | 1.356 (5) | | |
| | | |
N2—C1—C9 | 124.6 (3) | C5—C10—C9 | 116.7 (3) |
C1—N2—C3 | 116.7 (3) | C5—S12—O13 | 109.46 (15) |
N2—C3—C4 | 123.0 (3) | C5—S12—O14 | 110.93 (15) |
C3—C4—C10 | 122.6 (3) | C5—S12—Cl15 | 102.46 (10) |
C3—C4—F11 | 117.2 (3) | O13—S12—O14 | 119.46 (16) |
C10—C4—F11 | 120.3 (3) | O13—S12—Cl15 | 104.86 (12) |
C6—C5—C10 | 120.7 (3) | O14—S12—Cl15 | 108.12 (12) |
C6—C5—S12 | 114.4 (2) | N2—C1—H1 | 117.715 |
C10—C5—S12 | 124.8 (2) | C9—C1—H1 | 117.718 |
C5—C6—C7 | 121.0 (3) | N2—C3—H3 | 118.507 |
C6—C7—C8 | 120.3 (4) | C4—C3—H3 | 118.508 |
C7—C8—C9 | 120.5 (3) | C5—C6—H6 | 119.507 |
C1—C9—C8 | 120.0 (3) | C7—C6—H6 | 119.505 |
C1—C9—C10 | 119.3 (3) | C6—C7—H7 | 119.866 |
C8—C9—C10 | 120.7 (3) | C8—C7—H7 | 119.873 |
C4—C10—C5 | 129.5 (3) | C7—C8—H8 | 119.729 |
C4—C10—C9 | 113.8 (3) | C9—C8—H8 | 119.726 |
| | | |
N2—C1—C9—C8 | 179.3 (3) | C6—C5—S12—Cl15 | −109.3 (2) |
N2—C1—C9—C10 | −0.6 (5) | S12—C5—C6—C7 | −172.64 (18) |
C9—C1—N2—C3 | −0.7 (5) | C10—C5—S12—O13 | −173.8 (2) |
C1—N2—C3—C4 | 0.5 (5) | C10—C5—S12—O14 | −39.8 (3) |
N2—C3—C4—C10 | 1.1 (5) | C10—C5—S12—Cl15 | 75.3 (3) |
N2—C3—C4—F11 | −177.6 (3) | S12—C5—C10—C4 | −8.8 (4) |
C3—C4—C10—C5 | 177.5 (3) | S12—C5—C10—C9 | 171.04 (16) |
C3—C4—C10—C9 | −2.4 (4) | C5—C6—C7—C8 | 0.2 (5) |
F11—C4—C10—C5 | −3.8 (4) | C6—C7—C8—C9 | −2.0 (5) |
F11—C4—C10—C9 | 176.3 (2) | C7—C8—C9—C1 | −179.2 (3) |
C6—C5—C10—C4 | 176.1 (3) | C7—C8—C9—C10 | 0.7 (5) |
C6—C5—C10—C9 | −4.0 (4) | C1—C9—C10—C4 | 2.1 (4) |
C10—C5—C6—C7 | 2.9 (4) | C1—C9—C10—C5 | −177.8 (3) |
C6—C5—S12—O13 | 1.6 (3) | C8—C9—C10—C4 | −177.9 (3) |
C6—C5—S12—O14 | 135.5 (2) | C8—C9—C10—C5 | 2.2 (4) |
(II) (
S)-(-)-4-Fluoro-
N-(1-hydroxypropan-2-yl)isoquinoline-5-
sulfonamide
top
Crystal data top
C12H13FN2O3S | F(000) = 592.00 |
Mr = 284.31 | Dx = 1.475 Mg m−3 |
Monoclinic, P21 | Melting point = 422–424 K |
Hall symbol: P 2yb | Mo Kα radiation, λ = 0.71069 Å |
a = 18.907 (8) Å | Cell parameters from 25 reflections |
b = 7.543 (3) Å | θ = 10.4–12.4° |
c = 9.173 (4) Å | µ = 0.27 mm−1 |
β = 101.88 (3)° | T = 292 K |
V = 1280.2 (9) Å3 | Plate, colourless |
Z = 4 | 0.50 × 0.50 × 0.30 mm |
Data collection top
Rigaku AFC-7R diffractometer | 2458 reflections with F2 > 2σ(F2) |
Radiation source: Rigaku rotating Mo anode | Rint = 0.038 |
Graphite plate monochromator | θmax = 27.5°, θmin = 3° |
ω scans | h = −9→24 |
Absorption correction: numerical (NUMABS; Rigaku, 1999b) | k = −9→3 |
Tmin = 0.887, Tmax = 0.922 | l = −11→11 |
3554 measured reflections | 3 standard reflections every 150 reflections |
3163 independent reflections | intensity decay: 12% |
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)] = 0.054 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.159 | w = 1/[σ2(Fo2) + (0.0972P)2 + 0.2545P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max < 0.001 |
3163 reflections | Δρmax = 0.39 e Å−3 |
351 parameters | Δρmin = −0.32 e Å−3 |
3 restraints | Absolute structure: see text |
Primary atom site location: structure-invariant direct methods | |
Crystal data top
C12H13FN2O3S | V = 1280.2 (9) Å3 |
Mr = 284.31 | Z = 4 |
Monoclinic, P21 | Mo Kα radiation |
a = 18.907 (8) Å | µ = 0.27 mm−1 |
b = 7.543 (3) Å | T = 292 K |
c = 9.173 (4) Å | 0.50 × 0.50 × 0.30 mm |
β = 101.88 (3)° | |
Data collection top
Rigaku AFC-7R diffractometer | 2458 reflections with F2 > 2σ(F2) |
Absorption correction: numerical (NUMABS; Rigaku, 1999b) | Rint = 0.038 |
Tmin = 0.887, Tmax = 0.922 | 3 standard reflections every 150 reflections |
3554 measured reflections | intensity decay: 12% |
3163 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.054 | 3 restraints |
wR(F2) = 0.159 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.08 | Δρmax = 0.39 e Å−3 |
3163 reflections | Δρmin = −0.32 e Å−3 |
351 parameters | Absolute structure: see text |
Special details top
Refinement. Refinement was performed using all reflections. The weighted R-factor
(wR) and goodness of fit (S) are based on F2.
R-factor (gt) are based on F. The threshold expression of
F2 > 2σ(F2) is used only for calculating R-factor
(gt). |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.7840 (3) | 0.7844 (9) | 0.3945 (7) | 0.0591 (14) | |
N2 | 0.7384 (3) | 0.8562 (8) | 0.4656 (5) | 0.0622 (12) | |
C3 | 0.6692 (4) | 0.8725 (8) | 0.3907 (6) | 0.0578 (14) | |
C4 | 0.6459 (3) | 0.8168 (8) | 0.2484 (6) | 0.0476 (11) | |
C5 | 0.6762 (3) | 0.6646 (7) | 0.0179 (5) | 0.0437 (10) | |
C6 | 0.7299 (3) | 0.5931 (8) | −0.0423 (6) | 0.0527 (12) | |
C7 | 0.8026 (4) | 0.5858 (9) | 0.0369 (7) | 0.0627 (15) | |
C8 | 0.8199 (3) | 0.6481 (9) | 0.1773 (7) | 0.0594 (13) | |
C9 | 0.7670 (3) | 0.7223 (7) | 0.2465 (6) | 0.0481 (11) | |
C10 | 0.6928 (3) | 0.7348 (7) | 0.1668 (6) | 0.0425 (10) | |
F11 | 0.57628 (15) | 0.8427 (6) | 0.1855 (4) | 0.0638 (9) | |
S12 | 0.58687 (6) | 0.65236 (16) | −0.09721 (13) | 0.0455 (3) | |
O13 | 0.5968 (3) | 0.5723 (6) | −0.2328 (5) | 0.0623 (11) | |
O14 | 0.5419 (3) | 0.5691 (7) | −0.0106 (5) | 0.0663 (11) | |
N15 | 0.5572 (2) | 0.8509 (7) | −0.1345 (5) | 0.0484 (10) | |
C16 | 0.5773 (3) | 0.9590 (7) | −0.2524 (5) | 0.0439 | |
C17 | 0.5111 (4) | 0.9955 (12) | −0.3764 (7) | 0.0691 (17) | |
C18 | 0.6133 (3) | 1.1316 (9) | −0.1867 (7) | 0.0599 (14) | |
O19 | 0.6795 (3) | 1.1016 (9) | −0.0888 (5) | 0.0836 (16) | |
H1 | 0.8317 | 0.7730 | 0.4455 | 0.0709* | |
H3 | 0.6359 | 0.9246 | 0.4393 | 0.0693* | |
H6 | 0.7185 | 0.5475 | −0.1386 | 0.0633* | |
H7 | 0.8382 | 0.5381 | −0.0079 | 0.0752* | |
H8 | 0.8676 | 0.6419 | 0.2293 | 0.0713* | |
H15 | 0.531 (3) | 0.893 (8) | −0.077 (5) | 0.0581* | |
H16 | 0.6125 | 0.8922 | −0.2954 | 0.0526* | |
H17A | 0.4902 | 0.8850 | −0.4156 | 0.0829* | |
H17B | 0.5256 | 1.0621 | −0.4545 | 0.0829* | |
H17C | 0.4761 | 1.0621 | −0.3367 | 0.0829* | |
H18A | 0.6211 | 1.2076 | −0.2672 | 0.0719* | |
H18B | 0.5810 | 1.1930 | −0.1340 | 0.0719* | |
H19 | 0.7058 | 1.0429 | −0.1310 | 0.1003* | |
C20 | 0.6944 (3) | 0.2775 (9) | 0.2561 (6) | 0.0574 (13) | |
N21 | 0.6526 (3) | 0.3453 (9) | 0.3387 (6) | 0.0647 (13) | |
C22 | 0.6850 (3) | 0.3957 (9) | 0.4770 (7) | 0.0592 (14) | |
C23 | 0.7575 (3) | 0.3761 (8) | 0.5328 (6) | 0.0505 (12) | |
C24 | 0.8813 (3) | 0.2777 (8) | 0.4884 (6) | 0.0465 (11) | |
C25 | 0.9183 (3) | 0.2007 (8) | 0.3908 (6) | 0.0547 (13) | |
C26 | 0.8813 (3) | 0.1472 (10) | 0.2472 (6) | 0.0588 (13) | |
C27 | 0.8089 (3) | 0.1738 (8) | 0.2034 (6) | 0.0538 (12) | |
C28 | 0.7699 (3) | 0.2505 (7) | 0.3022 (6) | 0.0467 (11) | |
C29 | 0.8044 (3) | 0.3054 (7) | 0.4472 (5) | 0.0429 (10) | |
F30 | 0.78313 (18) | 0.4294 (6) | 0.6742 (4) | 0.0684 (10) | |
S31 | 0.93581 (7) | 0.33073 (19) | 0.66727 (14) | 0.0528 (4) | |
O32 | 1.0075 (2) | 0.2767 (7) | 0.6646 (5) | 0.0695 (12) | |
O33 | 0.9239 (3) | 0.5136 (7) | 0.7014 (6) | 0.0720 (12) | |
N34 | 0.9070 (3) | 0.2080 (7) | 0.7889 (5) | 0.0515 (10) | |
C35 | 0.9142 (3) | 0.0149 (8) | 0.7768 (6) | 0.0499 | |
C36 | 0.9832 (4) | −0.0566 (11) | 0.8768 (8) | 0.0726 (17) | |
C37 | 0.8483 (3) | −0.0711 (9) | 0.8195 (6) | 0.0570 (13) | |
O38 | 0.78193 (19) | 0.0050 (7) | 0.7446 (5) | 0.0641 (11) | |
H20 | 0.6729 | 0.2444 | 0.1595 | 0.0689* | |
H22 | 0.6567 | 0.4463 | 0.5378 | 0.0710* | |
H25 | 0.9679 | 0.1834 | 0.4192 | 0.0656* | |
H26 | 0.9067 | 0.0936 | 0.1824 | 0.0705* | |
H27 | 0.7852 | 0.1413 | 0.1080 | 0.0645* | |
H34 | 0.8650 (16) | 0.245 (9) | 0.796 (7) | 0.0618* | |
H35 | 0.9147 | −0.0152 | 0.6731 | 0.0599* | |
H36A | 1.0246 | −0.0075 | 0.8459 | 0.0871* | |
H36B | 0.9842 | −0.1835 | 0.8690 | 0.0871* | |
H36C | 0.9841 | −0.0237 | 0.9783 | 0.0871* | |
H37A | 0.8481 | −0.1966 | 0.7964 | 0.0683* | |
H37B | 0.8521 | −0.0594 | 0.9261 | 0.0683* | |
H38 | 0.7781 | −0.0057 | 0.6544 | 0.0769* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.053 (3) | 0.058 (4) | 0.060 (3) | −0.005 (3) | −0.003 (3) | 0.006 (3) |
N2 | 0.076 (3) | 0.055 (3) | 0.049 (3) | −0.002 (3) | −0.003 (2) | −0.003 (3) |
C3 | 0.073 (4) | 0.053 (4) | 0.048 (3) | 0.005 (3) | 0.014 (3) | −0.004 (3) |
C4 | 0.052 (3) | 0.043 (3) | 0.047 (3) | −0.001 (3) | 0.0083 (19) | 0.003 (3) |
C5 | 0.043 (3) | 0.042 (3) | 0.047 (3) | −0.001 (2) | 0.0111 (18) | 0.007 (3) |
C6 | 0.062 (3) | 0.049 (3) | 0.050 (3) | 0.006 (3) | 0.018 (3) | 0.005 (3) |
C7 | 0.058 (3) | 0.062 (4) | 0.075 (4) | 0.014 (3) | 0.030 (3) | 0.014 (4) |
C8 | 0.046 (3) | 0.056 (3) | 0.077 (4) | 0.005 (3) | 0.013 (3) | 0.011 (4) |
C9 | 0.050 (3) | 0.038 (3) | 0.054 (3) | −0.003 (2) | 0.005 (2) | 0.006 (3) |
C10 | 0.049 (3) | 0.034 (3) | 0.046 (3) | −0.0001 (19) | 0.0112 (19) | 0.0052 (19) |
F11 | 0.0520 (16) | 0.089 (3) | 0.0505 (15) | 0.0160 (19) | 0.0116 (12) | −0.0043 (19) |
S12 | 0.0494 (6) | 0.0416 (6) | 0.0451 (6) | −0.0060 (6) | 0.0090 (5) | −0.0007 (6) |
O13 | 0.076 (3) | 0.055 (3) | 0.053 (2) | 0.003 (2) | 0.0046 (19) | −0.0087 (18) |
O14 | 0.062 (3) | 0.065 (3) | 0.071 (3) | −0.021 (2) | 0.0117 (19) | 0.007 (3) |
N15 | 0.048 (2) | 0.052 (3) | 0.050 (2) | 0.006 (2) | 0.0181 (16) | 0.002 (2) |
C16 | 0.0428 | 0.0467 | 0.0425 | 0.0028 | 0.0098 | 0.0026 |
C17 | 0.057 (4) | 0.086 (5) | 0.059 (4) | 0.006 (4) | 0.001 (3) | 0.006 (4) |
C18 | 0.058 (3) | 0.056 (4) | 0.068 (4) | −0.007 (3) | 0.018 (3) | −0.004 (3) |
O19 | 0.058 (3) | 0.123 (5) | 0.068 (3) | −0.018 (3) | 0.010 (2) | −0.036 (3) |
C20 | 0.052 (3) | 0.062 (4) | 0.054 (3) | −0.002 (3) | 0.002 (3) | 0.004 (3) |
N21 | 0.054 (3) | 0.074 (4) | 0.066 (3) | 0.010 (3) | 0.011 (2) | 0.010 (3) |
C22 | 0.047 (3) | 0.060 (4) | 0.074 (4) | 0.014 (3) | 0.020 (3) | 0.011 (3) |
C23 | 0.056 (3) | 0.048 (3) | 0.048 (3) | 0.006 (3) | 0.012 (2) | 0.001 (3) |
C24 | 0.048 (3) | 0.047 (3) | 0.045 (3) | −0.000 (2) | 0.0111 (19) | 0.002 (2) |
C25 | 0.053 (3) | 0.055 (4) | 0.058 (3) | 0.005 (3) | 0.019 (3) | 0.001 (3) |
C26 | 0.063 (3) | 0.063 (4) | 0.055 (3) | 0.006 (3) | 0.022 (3) | −0.007 (3) |
C27 | 0.060 (3) | 0.055 (4) | 0.046 (3) | −0.001 (3) | 0.011 (2) | −0.003 (3) |
C28 | 0.053 (3) | 0.040 (3) | 0.047 (3) | −0.002 (2) | 0.012 (2) | 0.004 (2) |
C29 | 0.047 (3) | 0.037 (3) | 0.046 (3) | 0.004 (2) | 0.0111 (18) | 0.002 (2) |
F30 | 0.073 (2) | 0.082 (3) | 0.0513 (17) | 0.0201 (19) | 0.0154 (15) | −0.0150 (17) |
S31 | 0.0486 (7) | 0.0520 (8) | 0.0557 (7) | −0.0092 (6) | 0.0057 (5) | −0.0051 (7) |
O32 | 0.055 (2) | 0.078 (3) | 0.073 (3) | −0.015 (2) | 0.0061 (18) | −0.006 (3) |
O33 | 0.082 (3) | 0.056 (3) | 0.076 (3) | −0.013 (3) | 0.009 (3) | −0.010 (3) |
N34 | 0.052 (3) | 0.055 (3) | 0.046 (2) | −0.000 (2) | 0.0075 (18) | −0.006 (2) |
C35 | 0.0547 | 0.0541 | 0.0418 | 0.0014 | 0.0120 | −0.0019 |
C36 | 0.063 (4) | 0.076 (5) | 0.074 (4) | 0.008 (4) | 0.004 (3) | 0.010 (4) |
C37 | 0.062 (3) | 0.063 (4) | 0.046 (3) | −0.006 (3) | 0.011 (3) | −0.003 (3) |
O38 | 0.052 (2) | 0.084 (3) | 0.055 (2) | −0.009 (2) | 0.0097 (16) | −0.015 (3) |
Geometric parameters (Å, º) top
C1—N2 | 1.301 (9) | S31—O32 | 1.421 (5) |
C1—C9 | 1.409 (8) | S31—O33 | 1.442 (5) |
N2—C3 | 1.352 (8) | S31—N34 | 1.627 (5) |
C3—C4 | 1.356 (7) | N34—C35 | 1.469 (8) |
C4—C10 | 1.415 (8) | C35—C36 | 1.531 (8) |
C4—F11 | 1.339 (6) | C35—C37 | 1.525 (9) |
C5—C6 | 1.364 (8) | C37—O38 | 1.422 (7) |
C5—C10 | 1.438 (7) | C1—H1 | 0.930 |
C5—S12 | 1.800 (5) | C3—H3 | 0.930 |
C6—C7 | 1.418 (8) | C6—H6 | 0.930 |
C7—C8 | 1.347 (9) | C7—H7 | 0.930 |
C8—C9 | 1.407 (9) | C8—H8 | 0.930 |
C9—C10 | 1.445 (7) | N15—H15 | 0.858 (10) |
S12—O13 | 1.429 (5) | C16—H16 | 0.980 |
S12—O14 | 1.424 (5) | C17—H17A | 0.960 |
S12—N15 | 1.611 (6) | C17—H17B | 0.960 |
N15—C16 | 1.466 (7) | C17—H17C | 0.960 |
C16—C17 | 1.532 (7) | C18—H18A | 0.970 |
C16—C18 | 1.533 (8) | C18—H18B | 0.970 |
C18—O19 | 1.401 (7) | O19—H19 | 0.820 |
C20—N21 | 1.306 (9) | C20—H20 | 0.930 |
C20—C28 | 1.418 (8) | C22—H22 | 0.930 |
N21—C22 | 1.345 (8) | C25—H25 | 0.930 |
C22—C23 | 1.369 (8) | C26—H26 | 0.930 |
C23—C29 | 1.405 (8) | C27—H27 | 0.930 |
C23—F30 | 1.348 (6) | N34—H34 | 0.858 (10) |
C24—C25 | 1.372 (9) | C35—H35 | 0.980 |
C24—C29 | 1.441 (7) | C36—H36A | 0.960 |
C24—S31 | 1.794 (5) | C36—H36B | 0.960 |
C25—C26 | 1.417 (8) | C36—H36C | 0.960 |
C26—C27 | 1.360 (8) | C37—H37A | 0.970 |
C27—C28 | 1.405 (8) | C37—H37B | 0.970 |
C28—C29 | 1.417 (7) | O38—H38 | 0.820 |
| | | |
N2—C1—C9 | 125.3 (5) | C36—C35—C37 | 109.7 (5) |
C1—N2—C3 | 117.1 (5) | C35—C37—O38 | 113.0 (5) |
N2—C3—C4 | 123.3 (6) | N2—C1—H1 | 117.343 |
C3—C4—C10 | 122.0 (5) | C9—C1—H1 | 117.335 |
C3—C4—F11 | 117.7 (5) | N2—C3—H3 | 118.344 |
C10—C4—F11 | 120.3 (4) | C4—C3—H3 | 118.341 |
C6—C5—C10 | 119.6 (4) | C5—C6—H6 | 118.928 |
C6—C5—S12 | 115.4 (4) | C7—C6—H6 | 118.914 |
C10—C5—S12 | 124.9 (4) | C6—C7—H7 | 120.136 |
C5—C6—C7 | 122.2 (5) | C8—C7—H7 | 120.134 |
C6—C7—C8 | 119.7 (6) | C7—C8—H8 | 119.495 |
C7—C8—C9 | 121.0 (5) | C9—C8—H8 | 119.500 |
C1—C9—C8 | 121.7 (5) | C16—N15—H15 | 121 (4) |
C1—C9—C10 | 118.1 (5) | S12—N15—H15 | 116 (4) |
C8—C9—C10 | 120.3 (5) | N15—C16—H16 | 108.150 |
C4—C10—C5 | 128.6 (5) | C17—C16—H16 | 108.149 |
C4—C10—C9 | 114.2 (5) | C18—C16—H16 | 108.141 |
C5—C10—C9 | 117.2 (5) | C16—C17—H17A | 109.469 |
C5—S12—O13 | 104.9 (3) | C16—C17—H17B | 109.466 |
C5—S12—O14 | 107.0 (3) | C16—C17—H17C | 109.470 |
C5—S12—N15 | 108.7 (3) | H17A—C17—H17B | 109.475 |
O13—S12—O14 | 120.0 (3) | H17A—C17—H17C | 109.477 |
O13—S12—N15 | 108.1 (3) | H17B—C17—H17C | 109.470 |
O14—S12—N15 | 107.8 (3) | C16—C18—H18A | 109.123 |
S12—N15—C16 | 122.8 (4) | C16—C18—H18B | 109.126 |
N15—C16—C17 | 110.6 (5) | O19—C18—H18A | 109.124 |
N15—C16—C18 | 110.1 (5) | O19—C18—H18B | 109.128 |
C17—C16—C18 | 111.6 (5) | H18A—C18—H18B | 107.855 |
C16—C18—O19 | 112.4 (6) | C18—O19—H19 | 109.468 |
N21—C20—C28 | 125.1 (5) | N21—C20—H20 | 117.430 |
C20—N21—C22 | 116.5 (5) | C28—C20—H20 | 117.430 |
N21—C22—C23 | 123.3 (6) | N21—C22—H22 | 118.364 |
C22—C23—C29 | 122.0 (5) | C23—C22—H22 | 118.368 |
C22—C23—F30 | 117.5 (6) | C24—C25—H25 | 119.753 |
C29—C23—F30 | 120.5 (5) | C26—C25—H25 | 119.754 |
C25—C24—C29 | 120.8 (5) | C25—C26—H26 | 119.787 |
C25—C24—S31 | 114.7 (4) | C27—C26—H26 | 119.790 |
C29—C24—S31 | 124.5 (4) | C26—C27—H27 | 119.993 |
C24—C25—C26 | 120.5 (5) | C28—C27—H27 | 120.009 |
C25—C26—C27 | 120.4 (6) | C35—N34—H34 | 116 (5) |
C26—C27—C28 | 120.0 (5) | S31—N34—H34 | 108 (5) |
C20—C28—C27 | 119.8 (5) | N34—C35—H35 | 108.814 |
C20—C28—C29 | 118.6 (5) | C36—C35—H35 | 108.813 |
C27—C28—C29 | 121.6 (5) | C37—C35—H35 | 108.818 |
C23—C29—C24 | 128.9 (5) | C35—C36—H36A | 109.478 |
C23—C29—C28 | 114.5 (5) | C35—C36—H36B | 109.471 |
C24—C29—C28 | 116.7 (5) | C35—C36—H36C | 109.475 |
C24—S31—O32 | 106.9 (3) | H36A—C36—H36B | 109.473 |
C24—S31—O33 | 109.0 (3) | H36A—C36—H36C | 109.462 |
C24—S31—N34 | 106.9 (3) | H36B—C36—H36C | 109.470 |
O32—S31—O33 | 118.0 (3) | C35—C37—H37A | 108.988 |
O32—S31—N34 | 107.7 (3) | C35—C37—H37B | 108.984 |
O33—S31—N34 | 107.9 (3) | O38—C37—H37A | 108.974 |
S31—N34—C35 | 117.6 (4) | O38—C37—H37B | 108.976 |
N34—C35—C36 | 112.6 (5) | H37A—C37—H37B | 107.775 |
N34—C35—C37 | 108.0 (5) | C37—O38—H38 | 109.470 |
| | | |
N2—C1—C9—C8 | 179.2 (6) | N21—C20—C28—C27 | 179.1 (6) |
N2—C1—C9—C10 | −1.5 (9) | N21—C20—C28—C29 | −2.1 (9) |
C9—C1—N2—C3 | −0.1 (9) | C28—C20—N21—C22 | 1.3 (10) |
C1—N2—C3—C4 | 0.6 (9) | C20—N21—C22—C23 | −1.1 (10) |
N2—C3—C4—C10 | 0.5 (9) | N21—C22—C23—C29 | 1.8 (10) |
N2—C3—C4—F11 | −179.0 (5) | N21—C22—C23—F30 | −179.0 (6) |
C3—C4—C10—C5 | 178.1 (5) | C22—C23—C29—C24 | 179.4 (5) |
C3—C4—C10—C9 | −2.0 (8) | C22—C23—C29—C28 | −2.4 (8) |
F11—C4—C10—C5 | −2.3 (8) | F30—C23—C29—C24 | 0.2 (9) |
F11—C4—C10—C9 | 177.5 (5) | F30—C23—C29—C28 | 178.4 (4) |
C6—C5—C10—C4 | 178.8 (5) | C25—C24—C29—C23 | 177.7 (5) |
C6—C5—C10—C9 | −1.0 (7) | C25—C24—C29—C28 | −0.4 (8) |
C10—C5—C6—C7 | −0.3 (8) | C29—C24—C25—C26 | 0.2 (9) |
C6—C5—S12—O13 | −2.5 (5) | C25—C24—S31—O32 | −0.2 (5) |
C6—C5—S12—O14 | 125.9 (4) | C25—C24—S31—O33 | 128.4 (5) |
C6—C5—S12—N15 | −117.9 (5) | C25—C24—S31—N34 | −115.3 (5) |
S12—C5—C6—C7 | −177.3 (4) | S31—C24—C25—C26 | 178.1 (4) |
C10—C5—S12—O13 | −179.3 (4) | C29—C24—S31—O32 | 177.6 (5) |
C10—C5—S12—O14 | −50.9 (5) | C29—C24—S31—O33 | −53.8 (5) |
C10—C5—S12—N15 | 65.3 (5) | C29—C24—S31—N34 | 62.5 (5) |
S12—C5—C10—C4 | −4.5 (8) | S31—C24—C29—C23 | 0.0 (8) |
S12—C5—C10—C9 | 175.7 (3) | S31—C24—C29—C28 | −178.1 (4) |
C5—C6—C7—C8 | 1.2 (10) | C24—C25—C26—C27 | 0.9 (10) |
C6—C7—C8—C9 | −0.7 (10) | C25—C26—C27—C28 | −1.7 (10) |
C7—C8—C9—C1 | 178.5 (6) | C26—C27—C28—C20 | −179.8 (6) |
C7—C8—C9—C10 | −0.7 (9) | C26—C27—C28—C29 | 1.4 (9) |
C1—C9—C10—C4 | 2.5 (7) | C20—C28—C29—C23 | 2.5 (7) |
C1—C9—C10—C5 | −177.7 (5) | C20—C28—C29—C24 | −179.1 (5) |
C8—C9—C10—C4 | −178.3 (5) | C27—C28—C29—C23 | −178.8 (5) |
C8—C9—C10—C5 | 1.5 (8) | C27—C28—C29—C24 | −0.4 (8) |
C5—S12—N15—C16 | 81.0 (4) | C24—S31—N34—C35 | 63.4 (4) |
O13—S12—N15—C16 | −32.3 (4) | O32—S31—N34—C35 | −51.2 (4) |
O14—S12—N15—C16 | −163.3 (3) | O33—S31—N34—C35 | −179.5 (3) |
S12—N15—C16—C17 | 114.7 (4) | S31—N34—C35—C36 | 94.8 (4) |
S12—N15—C16—C18 | −121.5 (4) | S31—N34—C35—C37 | −143.9 (3) |
N15—C16—C18—O19 | 65.4 (6) | N34—C35—C37—O38 | 49.3 (6) |
C17—C16—C18—O19 | −171.4 (5) | C36—C35—C37—O38 | 172.4 (5) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N15—H15···F11 | 0.86 (1) | 2.42 (5) | 2.884 (5) | 115 (5) |
N15—H15···O14i | 0.86 (1) | 2.18 (2) | 3.003 (6) | 161 (6) |
O19—H19···O38ii | 0.82 | 2.03 | 2.799 (6) | 155 |
N34—H34···F30 | 0.86 (1) | 2.20 (4) | 2.893 (6) | 137 (6) |
N34—H34···O38 | 0.86 (1) | 2.38 (7) | 2.777 (6) | 109 (5) |
O38—H38···N2iii | 0.82 | 2.03 | 2.761 (6) | 148 |
Symmetry codes: (i) −x+1, y+1/2, −z; (ii) x, y+1, z−1; (iii) x, y−1, z. |
(III) (
S)-(-)-4-[(4-Fluoroisoquinolin-5-yl)sulfonyl]-3-methyl-1,4-
diazepan-1-ium
chloride
top
Crystal data top
C15H19FN3O2S+·Cl− | F(000) = 752.00 |
Mr = 359.85 | Dx = 1.464 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71069 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 25 reflections |
a = 12.379 (8) Å | θ = 10.1–12.4° |
b = 19.294 (14) Å | µ = 0.38 mm−1 |
c = 6.835 (4) Å | T = 293 K |
V = 1633 (2) Å3 | Plate, colourless |
Z = 4 | 0.50 × 0.40 × 0.30 mm |
Data collection top
Rigaku AFC-7R diffractometer | 1504 reflections with F2 > 2σ(F2) |
Radiation source: Rigaku rotating anode | Rint = 0.040 |
Graphite plate monochromator | θmax = 27.5° |
ω scans | h = −6→16 |
Absorption correction: numerical (NUMABS; Rigaku, 1999) | k = 0→25 |
Tmin = 0.855, Tmax = 0.891 | l = −3→8 |
2428 measured reflections | 3 standard reflections every 150 reflections |
2215 independent reflections | intensity decay: none |
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)] = 0.059 | H-atom parameters constrained |
wR(F2) = 0.166 | w = 1/[σ2(Fo2) + (0.0996P)2 + 0.1864P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.001 |
2215 reflections | Δρmax = 0.37 e Å−3 |
209 parameters | Δρmin = −0.26 e Å−3 |
0 restraints | Absolute structure: Flack (1983), with 60 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.03 (18) |
Crystal data top
C15H19FN3O2S+·Cl− | V = 1633 (2) Å3 |
Mr = 359.85 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 12.379 (8) Å | µ = 0.38 mm−1 |
b = 19.294 (14) Å | T = 293 K |
c = 6.835 (4) Å | 0.50 × 0.40 × 0.30 mm |
Data collection top
Rigaku AFC-7R diffractometer | 1504 reflections with F2 > 2σ(F2) |
Absorption correction: numerical (NUMABS; Rigaku, 1999) | Rint = 0.040 |
Tmin = 0.855, Tmax = 0.891 | 3 standard reflections every 150 reflections |
2428 measured reflections | intensity decay: none |
2215 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.059 | H-atom parameters constrained |
wR(F2) = 0.166 | Δρmax = 0.37 e Å−3 |
S = 1.04 | Δρmin = −0.26 e Å−3 |
2215 reflections | Absolute structure: Flack (1983), with 60 Friedel pairs |
209 parameters | Absolute structure parameter: −0.03 (18) |
0 restraints | |
Special details top
Refinement. Refinement was performed using all reflections. The weighted R-factor
(wR) and goodness of fit (S) are based on F2.
R-factor (gt) are based on F. The threshold expression of
F2 > 2σ(F2) is used only for calculating R-factor
(gt). |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.1643 (7) | 0.5537 (4) | 0.3337 (10) | 0.069 (2) | |
N2 | 0.0597 (6) | 0.5408 (3) | 0.3303 (10) | 0.0736 (18) | |
C3 | 0.0293 (6) | 0.4728 (4) | 0.3272 (11) | 0.0645 (18) | |
C4 | 0.1022 (5) | 0.4205 (3) | 0.3408 (10) | 0.0501 (14) | |
C5 | 0.2988 (5) | 0.3809 (3) | 0.3769 (9) | 0.0449 (13) | |
C6 | 0.4048 (5) | 0.4022 (4) | 0.3592 (11) | 0.0603 (17) | |
C7 | 0.4329 (6) | 0.4718 (4) | 0.3327 (12) | 0.069 (2) | |
C8 | 0.3553 (7) | 0.5213 (4) | 0.3312 (11) | 0.0655 (19) | |
C9 | 0.2459 (6) | 0.5025 (3) | 0.3419 (9) | 0.0536 (14) | |
C10 | 0.2149 (5) | 0.4310 (3) | 0.3553 (8) | 0.0454 (12) | |
F11 | 0.0624 (3) | 0.35544 (17) | 0.3319 (7) | 0.0656 (11) | |
S12 | 0.27795 (11) | 0.29499 (7) | 0.4661 (2) | 0.0452 (4) | |
O13 | 0.3823 (4) | 0.2727 (2) | 0.5288 (8) | 0.0640 (13) | |
O14 | 0.1923 (4) | 0.2964 (2) | 0.6066 (6) | 0.0567 (11) | |
N15 | 0.2408 (4) | 0.2492 (2) | 0.2804 (7) | 0.0434 (11) | |
C16 | 0.1384 (4) | 0.2091 (3) | 0.2832 (9) | 0.0429 (13) | |
C17 | 0.0841 (5) | 0.2097 (4) | 0.0823 (11) | 0.0662 (19) | |
C18 | 0.1522 (4) | 0.1361 (3) | 0.3631 (10) | 0.0460 (13) | |
N19 | 0.2405 (4) | 0.0946 (2) | 0.2697 (7) | 0.0471 (11) | |
C20 | 0.3524 (5) | 0.1194 (3) | 0.3210 (11) | 0.0546 (16) | |
C21 | 0.3978 (5) | 0.1720 (4) | 0.1788 (12) | 0.0622 (18) | |
C22 | 0.3231 (5) | 0.2328 (3) | 0.1331 (10) | 0.0560 (16) | |
Cl23 | 0.25917 (15) | −0.06375 (7) | 0.3220 (3) | 0.0633 (5) | |
H1 | 0.1859 | 0.5999 | 0.3305 | 0.0824* | |
H3 | −0.0436 | 0.4620 | 0.3153 | 0.0774* | |
H6 | 0.4594 | 0.3692 | 0.3650 | 0.0724* | |
H7 | 0.5049 | 0.4841 | 0.3160 | 0.0833* | |
H8 | 0.3745 | 0.5678 | 0.3232 | 0.0786* | |
H16 | 0.0895 | 0.2333 | 0.3729 | 0.0515* | |
H17A | 0.0873 | 0.2556 | 0.0285 | 0.0794* | |
H17B | 0.0100 | 0.1958 | 0.0955 | 0.0794* | |
H17C | 0.1209 | 0.1781 | −0.0032 | 0.0794* | |
H18A | 0.1665 | 0.1391 | 0.5023 | 0.0552* | |
H18B | 0.0846 | 0.1113 | 0.3466 | 0.0552* | |
H19A | 0.2323 | 0.0963 | 0.1389 | 0.0565* | |
H19B | 0.2338 | 0.0501 | 0.3068 | 0.0565* | |
H20A | 0.4005 | 0.0798 | 0.3257 | 0.0655* | |
H20B | 0.3507 | 0.1399 | 0.4506 | 0.0655* | |
H21A | 0.4150 | 0.1484 | 0.0574 | 0.0746* | |
H21B | 0.4647 | 0.1901 | 0.2320 | 0.0746* | |
H22A | 0.3674 | 0.2736 | 0.1132 | 0.0672* | |
H22B | 0.2866 | 0.2231 | 0.0104 | 0.0672* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.113 (7) | 0.049 (4) | 0.044 (4) | −0.002 (4) | 0.002 (5) | 0.009 (4) |
N2 | 0.099 (5) | 0.056 (4) | 0.066 (4) | 0.027 (4) | 0.006 (4) | 0.012 (3) |
C3 | 0.069 (5) | 0.060 (4) | 0.065 (5) | 0.013 (4) | 0.005 (4) | 0.010 (4) |
C4 | 0.053 (4) | 0.047 (3) | 0.050 (4) | 0.004 (3) | 0.002 (3) | 0.003 (3) |
C5 | 0.050 (3) | 0.039 (3) | 0.046 (3) | −0.008 (3) | −0.001 (3) | −0.001 (3) |
C6 | 0.057 (4) | 0.063 (4) | 0.062 (5) | −0.014 (3) | −0.007 (4) | 0.005 (4) |
C7 | 0.064 (4) | 0.079 (5) | 0.065 (5) | −0.037 (4) | −0.013 (4) | 0.011 (5) |
C8 | 0.094 (5) | 0.054 (4) | 0.048 (4) | −0.025 (4) | −0.005 (4) | 0.006 (4) |
C9 | 0.080 (4) | 0.043 (3) | 0.037 (3) | −0.009 (3) | −0.006 (4) | 0.007 (3) |
C10 | 0.057 (3) | 0.043 (3) | 0.036 (3) | 0.001 (3) | 0.002 (3) | 0.003 (3) |
F11 | 0.0479 (18) | 0.0507 (18) | 0.098 (3) | −0.0029 (15) | −0.006 (3) | 0.004 (3) |
S12 | 0.0489 (7) | 0.0385 (6) | 0.0482 (7) | −0.0019 (6) | −0.0058 (7) | −0.0006 (6) |
O13 | 0.062 (3) | 0.055 (3) | 0.076 (3) | −0.002 (2) | −0.021 (3) | 0.004 (3) |
O14 | 0.071 (3) | 0.048 (2) | 0.051 (3) | −0.005 (2) | 0.006 (3) | −0.003 (2) |
N15 | 0.041 (3) | 0.038 (2) | 0.051 (3) | −0.0021 (18) | 0.005 (3) | −0.004 (2) |
C16 | 0.037 (3) | 0.036 (3) | 0.055 (4) | 0.003 (3) | 0.001 (3) | −0.003 (3) |
C17 | 0.056 (4) | 0.059 (4) | 0.083 (6) | −0.000 (4) | −0.026 (4) | 0.005 (4) |
C18 | 0.036 (3) | 0.044 (3) | 0.058 (4) | −0.002 (3) | 0.000 (3) | 0.002 (3) |
N19 | 0.055 (3) | 0.0357 (19) | 0.051 (3) | −0.000 (2) | −0.001 (3) | 0.004 (2) |
C20 | 0.044 (3) | 0.046 (3) | 0.074 (5) | 0.013 (3) | 0.002 (4) | −0.004 (4) |
C21 | 0.047 (4) | 0.064 (4) | 0.075 (5) | 0.003 (3) | 0.016 (4) | −0.014 (4) |
C22 | 0.056 (4) | 0.060 (4) | 0.052 (4) | −0.009 (3) | 0.010 (3) | 0.005 (3) |
Cl23 | 0.0945 (13) | 0.0443 (7) | 0.0510 (8) | 0.0099 (8) | 0.0002 (9) | 0.0017 (7) |
Geometric parameters (Å, º) top
C1—N2 | 1.318 (12) | C20—C21 | 1.512 (10) |
C1—C9 | 1.415 (11) | C21—C22 | 1.525 (9) |
N2—C3 | 1.366 (9) | C1—H1 | 0.930 |
C3—C4 | 1.356 (9) | C3—H3 | 0.930 |
C4—C10 | 1.413 (9) | C6—H6 | 0.930 |
C4—F11 | 1.350 (7) | C7—H7 | 0.930 |
C5—C6 | 1.381 (9) | C8—H8 | 0.930 |
C5—C10 | 1.425 (8) | C16—H16 | 0.980 |
C5—S12 | 1.785 (6) | C17—H17A | 0.960 |
C6—C7 | 1.398 (10) | C17—H17B | 0.960 |
C7—C8 | 1.354 (11) | C17—H17C | 0.960 |
C8—C9 | 1.405 (11) | C18—H18A | 0.970 |
C9—C10 | 1.435 (8) | C18—H18B | 0.970 |
S12—O13 | 1.428 (5) | N19—H19A | 0.900 |
S12—O14 | 1.430 (5) | N19—H19B | 0.900 |
S12—N15 | 1.613 (5) | C20—H20A | 0.970 |
N15—C16 | 1.486 (7) | C20—H20B | 0.970 |
N15—C22 | 1.467 (8) | C21—H21A | 0.970 |
C16—C17 | 1.529 (10) | C21—H21B | 0.970 |
C16—C18 | 1.521 (8) | C22—H22A | 0.970 |
C18—N19 | 1.497 (7) | C22—H22B | 0.970 |
N19—C20 | 1.508 (7) | | |
| | | |
N2—C1—C9 | 124.7 (7) | C7—C6—H6 | 118.896 |
C1—N2—C3 | 116.9 (7) | C6—C7—H7 | 119.916 |
N2—C3—C4 | 122.0 (7) | C8—C7—H7 | 119.923 |
C3—C4—C10 | 123.8 (6) | C7—C8—H8 | 119.990 |
C3—C4—F11 | 116.5 (6) | C9—C8—H8 | 119.992 |
C10—C4—F11 | 119.7 (5) | N15—C16—H16 | 106.665 |
C6—C5—C10 | 118.8 (5) | C17—C16—H16 | 106.661 |
C6—C5—S12 | 116.3 (5) | C18—C16—H16 | 106.660 |
C10—C5—S12 | 124.0 (5) | C16—C17—H17A | 109.467 |
C5—C6—C7 | 122.2 (6) | C16—C17—H17B | 109.478 |
C6—C7—C8 | 120.2 (7) | C16—C17—H17C | 109.474 |
C7—C8—C9 | 120.0 (7) | H17A—C17—H17B | 109.475 |
C1—C9—C8 | 120.4 (6) | H17A—C17—H17C | 109.457 |
C1—C9—C10 | 118.9 (7) | H17B—C17—H17C | 109.477 |
C8—C9—C10 | 120.7 (6) | C16—C18—H18A | 108.495 |
C4—C10—C5 | 129.0 (5) | C16—C18—H18B | 108.506 |
C4—C10—C9 | 113.4 (6) | N19—C18—H18A | 108.499 |
C5—C10—C9 | 117.6 (6) | N19—C18—H18B | 108.492 |
C5—S12—O13 | 104.6 (3) | H18A—C18—H18B | 107.513 |
C5—S12—O14 | 108.5 (3) | C18—N19—H19A | 108.823 |
C5—S12—N15 | 106.3 (3) | C18—N19—H19B | 108.820 |
O13—S12—O14 | 118.3 (3) | C20—N19—H19A | 108.823 |
O13—S12—N15 | 109.2 (3) | C20—N19—H19B | 108.820 |
O14—S12—N15 | 109.1 (3) | H19A—N19—H19B | 107.681 |
S12—N15—C16 | 121.2 (4) | N19—C20—H20A | 108.787 |
S12—N15—C22 | 117.5 (4) | N19—C20—H20B | 108.781 |
C16—N15—C22 | 119.2 (5) | C21—C20—H20A | 108.783 |
N15—C16—C17 | 111.1 (5) | C21—C20—H20B | 108.781 |
N15—C16—C18 | 113.1 (4) | H20A—C20—H20B | 107.668 |
C17—C16—C18 | 112.3 (5) | C20—C21—H21A | 108.521 |
C16—C18—N19 | 115.1 (5) | C20—C21—H21B | 108.527 |
C18—N19—C20 | 113.7 (5) | C22—C21—H21A | 108.528 |
N19—C20—C21 | 113.9 (6) | C22—C21—H21B | 108.520 |
C20—C21—C22 | 115.0 (6) | H21A—C21—H21B | 107.531 |
N15—C22—C21 | 116.5 (6) | N15—C22—H22A | 108.170 |
N2—C1—H1 | 117.641 | N15—C22—H22B | 108.158 |
C9—C1—H1 | 117.657 | C21—C22—H22A | 108.164 |
N2—C3—H3 | 119.007 | C21—C22—H22B | 108.162 |
C4—C3—H3 | 119.008 | H22A—C22—H22B | 107.332 |
C5—C6—H6 | 118.898 | | |
| | | |
N2—C1—C9—C8 | 175.6 (6) | C7—C8—C9—C1 | −177.8 (6) |
N2—C1—C9—C10 | −2.6 (10) | C7—C8—C9—C10 | 0.3 (10) |
C9—C1—N2—C3 | −2.6 (10) | C1—C9—C10—C4 | 5.4 (8) |
C1—N2—C3—C4 | 4.6 (11) | C1—C9—C10—C5 | −175.8 (5) |
N2—C3—C4—C10 | −1.3 (11) | C8—C9—C10—C4 | −172.7 (5) |
N2—C3—C4—F11 | −178.7 (6) | C8—C9—C10—C5 | 6.1 (8) |
C3—C4—C10—C5 | 177.7 (6) | C5—S12—N15—C16 | −124.6 (4) |
C3—C4—C10—C9 | −3.7 (9) | C5—S12—N15—C22 | 72.0 (4) |
F11—C4—C10—C5 | −5.1 (10) | O13—S12—N15—C16 | 123.1 (4) |
F11—C4—C10—C9 | 173.6 (5) | O13—S12—N15—C22 | −40.3 (4) |
C6—C5—C10—C4 | 170.5 (6) | O14—S12—N15—C16 | −7.7 (4) |
C6—C5—C10—C9 | −8.1 (8) | O14—S12—N15—C22 | −171.1 (3) |
C10—C5—C6—C7 | 4.0 (10) | S12—N15—C16—C17 | 143.5 (3) |
C6—C5—S12—O13 | 9.3 (6) | S12—N15—C16—C18 | −89.3 (5) |
C6—C5—S12—O14 | 136.5 (5) | S12—N15—C22—C21 | 81.4 (5) |
C6—C5—S12—N15 | −106.2 (5) | C16—N15—C22—C21 | −82.3 (6) |
S12—C5—C6—C7 | −165.8 (5) | C22—N15—C16—C17 | −53.4 (6) |
C10—C5—S12—O13 | −159.9 (5) | C22—N15—C16—C18 | 73.8 (6) |
C10—C5—S12—O14 | −32.7 (6) | N15—C16—C18—N19 | −51.7 (7) |
C10—C5—S12—N15 | 84.6 (5) | C17—C16—C18—N19 | 74.9 (6) |
S12—C5—C10—C4 | −20.5 (8) | C16—C18—N19—C20 | 70.4 (6) |
S12—C5—C10—C9 | 160.9 (4) | C18—N19—C20—C21 | −91.7 (6) |
C5—C6—C7—C8 | 2.6 (11) | N19—C20—C21—C22 | 50.1 (7) |
C6—C7—C8—C9 | −4.7 (11) | C20—C21—C22—N15 | 23.9 (8) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N19—H19A···Cl23i | 0.90 | 2.26 | 3.117 (6) | 160 |
N19—H19B···Cl23 | 0.90 | 2.22 | 3.085 (5) | 161 |
Symmetry code: (i) −x+1/2, −y, z−1/2. |
Experimental details
| (I) | (II) | (III) |
Crystal data |
Chemical formula | C9H5ClFNO2S | C12H13FN2O3S | C15H19FN3O2S+·Cl− |
Mr | 245.66 | 284.31 | 359.85 |
Crystal system, space group | Monoclinic, P21/n | Monoclinic, P21 | Orthorhombic, P212121 |
Temperature (K) | 293 | 292 | 293 |
a, b, c (Å) | 8.070 (3), 15.353 (3), 7.789 (2) | 18.907 (8), 7.543 (3), 9.173 (4) | 12.379 (8), 19.294 (14), 6.835 (4) |
α, β, γ (°) | 90, 96.08 (3), 90 | 90, 101.88 (3), 90 | 90, 90, 90 |
V (Å3) | 959.6 (5) | 1280.2 (9) | 1633 (2) |
Z | 4 | 4 | 4 |
Radiation type | Mo Kα | Mo Kα | Mo Kα |
µ (mm−1) | 0.61 | 0.27 | 0.38 |
Crystal size (mm) | 0.55 × 0.50 × 0.30 | 0.50 × 0.50 × 0.30 | 0.50 × 0.40 × 0.30 |
|
Data collection |
Diffractometer | Rigaku AFC-7R diffractometer | Rigaku AFC-7R diffractometer | Rigaku AFC-7R diffractometer |
Absorption correction | ψ scan (North et al., 1968) | Numerical (NUMABS; Rigaku, 1999b) | Numerical (NUMABS; Rigaku, 1999) |
Tmin, Tmax | 0.730, 0.834 | 0.887, 0.922 | 0.855, 0.891 |
No. of measured, independent and observed [F2 > 2σ(F2)] reflections | 2444, 2202, 1621 | 3554, 3163, 2458 | 2428, 2215, 1504 |
Rint | 0.040 | 0.038 | 0.040 |
(sin θ/λ)max (Å−1) | 0.649 | 0.650 | 0.650 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.059, 0.164, 1.05 | 0.054, 0.159, 1.08 | 0.059, 0.166, 1.04 |
No. of reflections | 2202 | 3163 | 2215 |
No. of parameters | 136 | 351 | 209 |
No. of restraints | 0 | 3 | 0 |
H-atom treatment | H-atom parameters constrained | H atoms treated by a mixture of independent and constrained refinement | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.26, −0.70 | 0.39, −0.32 | 0.37, −0.26 |
Absolute structure | ? | See text | Flack (1983), with 60 Friedel pairs |
Absolute structure parameter | ? | ? | −0.03 (18) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
N15—H15···F11 | 0.858 (10) | 2.42 (5) | 2.884 (5) | 115 (5) |
N15—H15···O14i | 0.858 (10) | 2.18 (2) | 3.003 (6) | 161 (6) |
O19—H19···O38ii | 0.820 | 2.03 | 2.799 (6) | 155 |
N34—H34···F30 | 0.858 (10) | 2.20 (4) | 2.893 (6) | 137 (6) |
N34—H34···O38 | 0.858 (10) | 2.38 (7) | 2.777 (6) | 109 (5) |
O38—H38···N2iii | 0.820 | 2.03 | 2.761 (6) | 148 |
Symmetry codes: (i) −x+1, y+1/2, −z; (ii) x, y+1, z−1; (iii) x, y−1, z. |
Hydrogen-bond geometry (Å, º) for (III) top
D—H···A | D—H | H···A | D···A | D—H···A |
N19—H19A···Cl23i | 0.900 | 2.26 | 3.117 (6) | 160 |
N19—H19B···Cl23 | 0.900 | 2.22 | 3.085 (5) | 161 |
Symmetry code: (i) −x+1/2, −y, z−1/2. |
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Fasudil hydrochloride, (IV), is a synthetic protein kinase inhibitor which is known to have a potent vasodilatory effect on the vertebral arteries (Morikawa et al., 1992). Crystal structure analyses of complexes of protein kinase A with fasudil or related compounds have been undertaken to investigate the nature of these ligands in the binding pocket (Engh et al., 1996; Breitenlechner et al., 2003). Various derivatives of fasudil have been explored, and it was found that (S)-(-)-4-[(4-fluoroisoquinolin-5-yl)sulfonyl]-3-methyl-1,4-diazepan-1-ium chloride, (III), has a much more potent and selective Rho-kinase inhibitory activity than (IV), i.e. the incorporation of an F atom at the 4-position of the isoquinoline system and the chiral attachment of a methyl group at the 2-position of the 1,4-diazepane ring dramatically improve the pharmacological action. As an illustration, the half-maximum inhibitory concentration (IC50) of (III) and fasudil are 0.03 and 0.50 µM, respectively (Gomi et al., 2011). A practical synthesis of (III) may be achieved by starting from 4-fluoroisoquinoline and passing through the intermediates 4-fluoroisoquinoline-5-sulfonyl chloride, (I), and (S)-(-)-4-fluoro-N-(1-hydroxypropan-2-yl)isoquinoline-5-sulfonamide, (II) (Gomi et al., 2011), despite (I) being less reactive than its nonfluorinated analogue.
The 1H NMR spectra of (II) suggested a coupling between N(H) and 19F through an intramolecular N—H···F hydrogen bond (Manjunatha Reddy et al., 2010). In the present study, the structures of (I), (II) and (III) have been determined in order to investigate the intramolecular interactions between the sulfonyl and F atoms at the vicinal positions. Although there is no entry for such an SO2···F combination in a naphthalene-like compound in the Cambridge Structural Database (CSD, Version 5.33 of November 2011; Allen, 2002), the structures of four naphthalene-1-sulfonates (e.g. Vennila et al., 2008) and seven naphthalene-1-sulfonamides (e.g. Navarrete-Vázquez et al., 2010) are available. These all show similar conformations of the S(═O)2O or S(═O)2N group with the naphthalene ring, namely that the C6—C5—S═O torsion angles range from -7 to 7°. This suggests that there is an intramolecular repulsion between the H atom at the vicinal 4-position and the sulfonyl O atoms. An exception is N-(2-aminoethyl)-N-methylisoquinoline-5-sulfonamide hydrochloride (Vasdev et al., 2008). There, the C6—C5—S═O torsion angle is ca -86° with a short C4—H···O(═S) nonbonded distance of 2.28 Å. Replacing the H atom at the 4-position with an F atom should mean that such short contacts are not allowed.
The orientations of the S(═O)2Cl group in (I) and the S(═O)2N groups in (II) and (III) relative to the isoquinoline ring are similar to each other, as expected (Figs. 1–3). The C6—C5—S12—O13 torsion angle in (I) is 1.6 (3)°, the corresponding angles for the two crystallographically independent molecules in (II) are -2.5 (5) and -0.2 (5)°, and that in (III) is 9.3 (6)°. In (I), the F11···S12, F11···O14 and F11···Cl15 distances are 3.037 (3), 2.667 (4) and 3.104 (3) Å, respectively, which are shorter by 0.1 to ~0.3 Å than the sum of their van der Waals radii (Bondi, 1964). The molecular packing pattern of (I) is a typical herringbone (Fig. 4), and there is an intermolecular short contact, the N2···Cl15(-x+1/2, y-1/2, -z1/2) distance being 3.129 (3) Å.
In the 1H NMR spectrum of (II), the multiplicity of the amide proton is triplet (δ 5.34), but doublet (δ 5.40) for the non-fluorinated analogue, suggesting spin–spin coupling between the amide N—H group and the active 19F nuclei (JN—H···F = 7.1 Hz). Similar through-space nuclear spin–spin couplings due to intramolecular N—H···F hydrogen bonds have been observed for 2-fluoro-N-(pyridyl)benzamides, the N···F distances being 2.722 (5)–2.753 (6) Å (Mocilac et al., 2012). The 2-fluorophenylsulfonamides do not show such intramolecular spin–spin coupling (Samarakoon et al., 2010), and this agrees with the fact that the conformations of these molecules are not suitable for the formation of intramolecular N—H···X hydrogen bonds (X = Cl: Fernandes et al., 2011; Shakuntala et al., 2011; X = I: Arshad et al., 2011). Somewhat weaker intramolecular N—H···F hydrogen bonds are observed in (II), with N···F distances of 2.884 (5) and 2.893 (6) Å and N—H···F angles of 115 (5) and 137 (6)° (Fig. 2 and Table 1).
In the following discussion, the two independent molecules of (II) are labelled A and B (for the molecules containing atoms S12 and S31, respectively). The amide N15—H15 group has another hydrogen-bond acceptor, O14(-x+1, y+1/2, -z), and this hydrogen bond links molecule A and its equivalents to form a chain around the twofold screw axis parallel to b passing through (1/2, 0, 0) (Fig. 5 and Table 1). Molecules A and B are connected by an O38—H38···N2(x, y-1, z) hydrogen bond, and these pairs are further connected by another hydrogen bond, O19—H19···O38(x, y+1, z-1), to form a zigzag molecular chain along the c axis. The N34—H34 group in molecule B forms an intramolecular bifurcated hydrogen bond, which is achieved by a pyramidal configuration around atom N34.
In (III), the isoquinoline ring is a little skewed, the C8—C9—C10—C5 torsion angle being 6.1 (8)°. Atoms F11 and S12 are displaced below and above the average plane of the isoquinoline ring by -0.233 (8) and 0.556 (7) Å, respectively, and the resulting F···S distance is 3.053 (5) Å. This may be due to the strain introduced by the bulky group attached to the sulfonyl group. A similar twist in the naphthalene ring was observed in 1,8-bis(methylsulfanyl)naphthalene, which has a nonbonded S···S distance of 2.918 (2)–2.934 (2) Å. There, the S atoms are displaced from the naphthalene ring by 0.306 (2) and -0.291 (2) Å (Glass et al., 1989). On the other hand, the twist of the naphthalene ring in 1-bromo-8-(ethysulfanyl)naphthalene is very slight, with the shifts of the S and Br atoms from the naphthalene plane both less than 0.12 Å and with S···Br distances of 3.050 (2)–3.056 (2) Å. This relative planarity is achieved mainly by the imbalance of the Br—C—C bond angles, viz. 124.1 (4)–124.5 (4)° inside and 112.3 (5)–112.8 (5)° outside (Fuller et al., 2007). In the packing structure of (III), the 1,4-diazepan-1-ium group acts as a hydrogen-bond donor to the chloride anions (Fig. 6 and Table 2). A (Cl···H—N—H···)n chain is formed around the twofold screw axis parallel to c, passing through (1/4, 0, 0).