In the crystal structures of the diastereoisomers of
O-tosylcinchonidine [(9
R)-cinchon-9-yl 4-methylbenzenesulfonate], (I), and
O-tosylcinchonine [(9
S)-cinchon-9-yl 4-methylbenzenesulfonate], (II), both C
26H
28N
2O
3S, both molecules are in an
anti-closed conformation and, in each case, the position of the aryl ring of the tosylate system is influenced by an intramolecular C-H
O hydrogen bond. The molecular packing in (I) is influenced by weak intermolecular C-H
O and C-H
interactions. The crystal structure of (II) features C-H
interactions and van der Waals forces only. The computational investigations using RHF/6-31G**
ab initio and AM1 semi-empirical methods performed for (I) and (II) and their protonated species show that the conformational and energetic parameters of the molecules are correlated with differences in their reactivity in hydrolysis to the corresponding 9-epibases.
Supporting information
CCDC references: 687193; 687195
Compounds (I) and (II) were obtained by the method described by Kowalik et
al. (1999) and their analytical data (IR, 1H NMR and 13C NMR) are in
good agreement with those found in Brunner & Bügler (1997) for (I) and
Kowalik et al. (1999) for (II). Crystals of both compounds suitable for
X-ray diffraction analysis were grown by slow evaporation of diethyl
ether–hexane (1:1) solutions.
The assumed absolute stereochemistry of compound (I) was confirmed by
refinement of the Flack (1983) parameter. In the absence of Friedel pairs, the
absolute configuration of compound (II) was assigned from absolute
configuration of cinchonine as starting reagent in the stereoconservative
synthesis. For both compounds, all hydrogen atoms were fixed geometrically and
treated as riding on their parent C atoms with C—H distances of 0.93 Å
(aromatic), 0.96 Å (CH3), 0.97 Å (CH2) and 0.98 Å (CH) and with
Uiso(H) = 1.5Ueq(C).
For both compounds, data collection: KM4B8 (Gałdecki et al., 1996); cell refinement: KM4B8 (Gałdecki et al., 1996); data reduction: DATAPROC (Gałdecki et al., 1995); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997). Software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and WinGX (Farrugia, 1997) for (I); SHELXL97 (Sheldrick, 2008) and WinGX (Farrugia, 1999) for (II).
(I)
O-Tosyl cinchonidine
top
Crystal data top
C26H28N2O3S | Dx = 1.280 Mg m−3 |
Mr = 448.56 | Melting point = 407–408 K |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 25 reflections |
a = 9.4591 (13) Å | θ = 19.4–34.6° |
b = 10.094 (2) Å | µ = 1.48 mm−1 |
c = 24.370 (4) Å | T = 293 K |
V = 2326.9 (7) Å3 | Prism, colourless |
Z = 4 | 0.45 × 0.40 × 0.10 mm |
F(000) = 952 | |
Data collection top
Kuma KM-4 four-circle diffractometer | 1717 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.034 |
Graphite monochromator | θmax = 80.5°, θmin = 3.6° |
ω–2θ scans | h = −1→12 |
Absorption correction: multi-scan (Blessing, 1995) | k = −1→12 |
Tmin = 0.363, Tmax = 0.748 | l = −31→1 |
3726 measured reflections | 2 standard reflections every 100 reflections |
3508 independent reflections | intensity decay: 0.0% |
Refinement top
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.064 | w = 1/[σ2(Fo2) + (0.0716P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.167 | (Δ/σ)max < 0.001 |
S = 1.06 | Δρmax = 0.30 e Å−3 |
3508 reflections | Δρmin = −0.33 e Å−3 |
290 parameters | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
1 restraint | Extinction coefficient: 0.0085 (6) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), 604 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.00 (3) |
Crystal data top
C26H28N2O3S | V = 2326.9 (7) Å3 |
Mr = 448.56 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 9.4591 (13) Å | µ = 1.48 mm−1 |
b = 10.094 (2) Å | T = 293 K |
c = 24.370 (4) Å | 0.45 × 0.40 × 0.10 mm |
Data collection top
Kuma KM-4 four-circle diffractometer | 1717 reflections with I > 2σ(I) |
Absorption correction: multi-scan (Blessing, 1995) | Rint = 0.034 |
Tmin = 0.363, Tmax = 0.748 | 2 standard reflections every 100 reflections |
3726 measured reflections | intensity decay: 0.0% |
3508 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.064 | H-atom parameters constrained |
wR(F2) = 0.167 | Δρmax = 0.30 e Å−3 |
S = 1.06 | Δρmin = −0.33 e Å−3 |
3508 reflections | Absolute structure: Flack (1983), 604 Friedel pairs |
290 parameters | Absolute structure parameter: 0.00 (3) |
1 restraint | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s.
planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor
wR and goodness of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The threshold expression of F2 >
σ(F2) is used only for calculating R-factors(gt) etc.
and is not relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R- factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
S1 | 0.26610 (8) | 0.23628 (18) | 0.50781 (3) | 0.0584 (4) | |
O1 | 0.13605 (17) | 0.2196 (4) | 0.54796 (7) | 0.0527 (10) | |
O2 | 0.3885 (2) | 0.1817 (5) | 0.53325 (13) | 0.0792 (11) | |
O3 | 0.2180 (3) | 0.1881 (5) | 0.45660 (9) | 0.0796 (13) | |
N1 | 0.0247 (3) | 0.2361 (5) | 0.69153 (10) | 0.0606 (12) | |
N2 | 0.1832 (4) | −0.2170 (6) | 0.64076 (15) | 0.0820 (13) | |
C2 | −0.1152 (5) | 0.2772 (8) | 0.71136 (19) | 0.0762 (17) | |
H21 | −0.1241 | 0.2549 | 0.7499 | 0.114* | |
H22 | −0.1877 | 0.2294 | 0.6914 | 0.114* | |
C3 | −0.1385 (5) | 0.4302 (8) | 0.70376 (19) | 0.0769 (17) | |
H31 | −0.1545 | 0.4705 | 0.7398 | 0.115* | |
C4 | −0.0003 (5) | 0.4837 (7) | 0.68019 (16) | 0.0751 (15) | |
H41 | −0.0086 | 0.5799 | 0.6759 | 0.113* | |
C5 | 0.1176 (7) | 0.4543 (8) | 0.7210 (3) | 0.0911 (18) | |
H51 | 0.2055 | 0.4943 | 0.7089 | 0.137* | |
H52 | 0.0941 | 0.4894 | 0.7569 | 0.137* | |
C6 | 0.1323 (5) | 0.3043 (8) | 0.72352 (19) | 0.0808 (19) | |
H61 | 0.2250 | 0.2794 | 0.7099 | 0.121* | |
H62 | 0.1258 | 0.2760 | 0.7615 | 0.121* | |
C7 | 0.0312 (5) | 0.4240 (7) | 0.62566 (18) | 0.0699 (14) | |
H71 | 0.1224 | 0.4543 | 0.6125 | 0.105* | |
H72 | −0.0405 | 0.4494 | 0.5992 | 0.105* | |
C8 | 0.0323 (3) | 0.2708 (7) | 0.63326 (13) | 0.0533 (12) | |
H81 | −0.0527 | 0.2356 | 0.6155 | 0.080* | |
C9 | 0.1605 (3) | 0.2041 (7) | 0.60660 (12) | 0.0523 (14) | |
H91 | 0.2473 | 0.2506 | 0.6172 | 0.079* | |
C10 | −0.2653 (6) | 0.4535 (10) | 0.6688 (2) | 0.129 (4) | |
H101 | −0.2555 | 0.4289 | 0.6322 | 0.193* | |
C11 | −0.3844 (8) | 0.5018 (11) | 0.6816 (3) | 0.174 (6) | |
H111 | −0.4018 | 0.5286 | 0.7175 | 0.260* | |
H112 | −0.4546 | 0.5104 | 0.6551 | 0.260* | |
C22 | 0.0722 (5) | −0.1587 (8) | 0.61875 (19) | 0.0738 (16) | |
H221 | −0.0056 | −0.2112 | 0.6103 | 0.111* | |
C23 | 0.0636 (4) | −0.0230 (7) | 0.60731 (18) | 0.0612 (12) | |
H231 | −0.0180 | 0.0114 | 0.5915 | 0.092* | |
C24 | 0.1741 (3) | 0.0594 (6) | 0.61914 (13) | 0.0486 (11) | |
C25 | 0.4215 (3) | 0.0725 (9) | 0.65689 (16) | 0.084 (2) | |
H251 | 0.4264 | 0.1635 | 0.6511 | 0.125* | |
C26 | 0.5358 (5) | 0.0075 (11) | 0.6784 (3) | 0.109 (3) | |
H261 | 0.6181 | 0.0547 | 0.6857 | 0.164* | |
C27 | 0.5314 (7) | −0.1256 (11) | 0.6895 (4) | 0.132 (4) | |
H271 | 0.6090 | −0.1668 | 0.7056 | 0.198* | |
C28 | 0.4142 (5) | −0.1977 (10) | 0.6771 (2) | 0.104 (2) | |
H281 | 0.4130 | −0.2879 | 0.6847 | 0.156* | |
C29 | 0.2941 (5) | −0.1380 (8) | 0.65287 (18) | 0.0695 (17) | |
C30 | 0.2957 (4) | 0.0033 (7) | 0.64322 (16) | 0.0600 (16) | |
C31 | 0.2856 (3) | 0.4081 (6) | 0.50317 (14) | 0.0527 (12) | |
C32 | 0.3878 (5) | 0.4734 (8) | 0.5339 (2) | 0.0669 (14) | |
H321 | 0.4496 | 0.4266 | 0.5563 | 0.100* | |
C33 | 0.3952 (5) | 0.6107 (7) | 0.5302 (3) | 0.0787 (17) | |
H331 | 0.4611 | 0.6550 | 0.5517 | 0.118* | |
C34 | 0.3108 (4) | 0.6831 (8) | 0.4966 (2) | 0.0708 (14) | |
C35 | 0.2132 (4) | 0.6138 (8) | 0.4643 (3) | 0.0728 (16) | |
H351 | 0.1567 | 0.6600 | 0.4396 | 0.109* | |
C36 | 0.1993 (4) | 0.4792 (7) | 0.4684 (2) | 0.0666 (15) | |
H361 | 0.1313 | 0.4355 | 0.4477 | 0.100* | |
C37 | 0.3242 (6) | 0.8314 (8) | 0.4920 (3) | 0.102 (2) | |
H371 | 0.2936 | 0.8718 | 0.5256 | 0.153* | |
H372 | 0.2664 | 0.8626 | 0.4623 | 0.153* | |
H373 | 0.4210 | 0.8545 | 0.4852 | 0.153* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0641 (4) | 0.0481 (11) | 0.0630 (4) | 0.0020 (6) | 0.0156 (3) | 0.0066 (8) |
O1 | 0.0558 (8) | 0.053 (3) | 0.0492 (8) | −0.0007 (17) | 0.0054 (6) | 0.005 (2) |
O2 | 0.0639 (10) | 0.069 (3) | 0.1045 (18) | 0.019 (2) | 0.0194 (12) | 0.035 (3) |
O3 | 0.1084 (17) | 0.070 (4) | 0.0607 (11) | −0.009 (3) | 0.0235 (12) | −0.013 (2) |
N1 | 0.0870 (14) | 0.044 (3) | 0.0511 (11) | 0.004 (3) | 0.0104 (10) | −0.002 (3) |
N2 | 0.109 (2) | 0.049 (3) | 0.088 (2) | 0.002 (3) | 0.0007 (18) | 0.011 (4) |
C2 | 0.094 (2) | 0.059 (5) | 0.076 (2) | −0.008 (4) | 0.0252 (19) | −0.008 (5) |
C3 | 0.107 (3) | 0.060 (5) | 0.0631 (19) | 0.014 (5) | 0.020 (2) | −0.012 (5) |
C4 | 0.108 (3) | 0.038 (4) | 0.080 (2) | 0.006 (4) | 0.012 (2) | 0.004 (4) |
C5 | 0.127 (3) | 0.052 (4) | 0.094 (3) | −0.026 (5) | −0.007 (3) | −0.012 (6) |
C6 | 0.107 (3) | 0.072 (6) | 0.0630 (18) | 0.002 (5) | −0.0194 (18) | −0.009 (5) |
C7 | 0.103 (3) | 0.037 (3) | 0.069 (2) | 0.010 (4) | 0.0171 (19) | 0.004 (4) |
C8 | 0.0693 (14) | 0.040 (4) | 0.0505 (13) | 0.004 (3) | 0.0016 (10) | 0.004 (4) |
C9 | 0.0561 (11) | 0.048 (4) | 0.0533 (14) | −0.005 (3) | −0.0005 (10) | 0.006 (3) |
C10 | 0.122 (3) | 0.172 (12) | 0.092 (3) | 0.026 (7) | 0.019 (3) | 0.006 (6) |
C11 | 0.158 (5) | 0.207 (17) | 0.156 (6) | 0.074 (9) | −0.029 (5) | 0.017 (9) |
C22 | 0.091 (2) | 0.053 (4) | 0.077 (2) | −0.020 (4) | −0.006 (2) | 0.001 (5) |
C23 | 0.0681 (16) | 0.042 (3) | 0.073 (2) | −0.010 (3) | −0.0052 (16) | 0.013 (4) |
C24 | 0.0568 (13) | 0.038 (3) | 0.0508 (14) | −0.004 (3) | 0.0008 (11) | 0.000 (3) |
C25 | 0.0600 (15) | 0.103 (7) | 0.088 (2) | −0.002 (3) | −0.0134 (15) | 0.019 (5) |
C26 | 0.071 (2) | 0.134 (10) | 0.123 (4) | 0.014 (5) | −0.025 (2) | 0.040 (7) |
C27 | 0.094 (3) | 0.142 (11) | 0.159 (6) | 0.038 (6) | −0.035 (4) | 0.058 (9) |
C28 | 0.107 (3) | 0.098 (7) | 0.106 (3) | 0.030 (5) | −0.011 (2) | 0.026 (6) |
C29 | 0.0788 (19) | 0.064 (5) | 0.0659 (19) | 0.012 (4) | 0.0079 (16) | 0.012 (4) |
C30 | 0.0635 (15) | 0.060 (5) | 0.0568 (16) | 0.003 (3) | 0.0005 (13) | 0.009 (4) |
C31 | 0.0567 (12) | 0.043 (3) | 0.0578 (14) | 0.002 (2) | 0.0101 (12) | 0.005 (3) |
C32 | 0.0731 (18) | 0.060 (4) | 0.0677 (19) | −0.007 (4) | −0.0043 (17) | 0.011 (5) |
C33 | 0.084 (2) | 0.065 (5) | 0.087 (3) | −0.008 (4) | 0.000 (2) | 0.004 (6) |
C34 | 0.0757 (17) | 0.044 (3) | 0.093 (2) | −0.004 (3) | 0.0256 (19) | 0.013 (5) |
C35 | 0.0631 (16) | 0.055 (4) | 0.101 (3) | 0.009 (3) | −0.0026 (18) | 0.019 (5) |
C36 | 0.0586 (15) | 0.057 (4) | 0.084 (2) | −0.004 (3) | −0.0053 (15) | 0.019 (5) |
C37 | 0.104 (3) | 0.051 (4) | 0.150 (5) | −0.011 (4) | 0.025 (4) | 0.011 (7) |
Geometric parameters (Å, º) top
S1—O3 | 1.414 (3) | C10—H101 | 0.9300 |
S1—O2 | 1.424 (3) | C11—H111 | 0.9300 |
S1—O1 | 1.5807 (18) | C11—H112 | 0.9300 |
S1—C31 | 1.748 (6) | C22—C23 | 1.401 (8) |
O1—C9 | 1.456 (4) | C22—H221 | 0.9300 |
N1—C6 | 1.455 (6) | C23—C24 | 1.367 (7) |
N1—C8 | 1.464 (4) | C23—H231 | 0.9300 |
N1—C2 | 1.468 (5) | C24—C30 | 1.410 (5) |
N2—C22 | 1.317 (6) | C25—C26 | 1.369 (7) |
N2—C29 | 1.351 (8) | C25—C30 | 1.420 (7) |
C2—C3 | 1.571 (10) | C25—H251 | 0.9300 |
C2—H21 | 0.9700 | C26—C27 | 1.372 (12) |
C2—H22 | 0.9700 | C26—H261 | 0.9300 |
C3—C10 | 1.490 (7) | C27—C28 | 1.360 (10) |
C3—C4 | 1.526 (6) | C27—H271 | 0.9300 |
C3—H31 | 0.9800 | C28—C29 | 1.416 (7) |
C4—C7 | 1.489 (6) | C28—H281 | 0.9300 |
C4—C5 | 1.523 (7) | C29—C30 | 1.445 (10) |
C4—H41 | 0.9800 | C31—C36 | 1.377 (6) |
C5—C6 | 1.521 (10) | C31—C32 | 1.389 (6) |
C5—H51 | 0.9700 | C32—C33 | 1.390 (9) |
C5—H52 | 0.9700 | C32—H321 | 0.9300 |
C6—H61 | 0.9700 | C33—C34 | 1.357 (7) |
C6—H62 | 0.9700 | C33—H331 | 0.9300 |
C7—C8 | 1.557 (7) | C34—C35 | 1.401 (7) |
C7—H71 | 0.9700 | C34—C37 | 1.507 (9) |
C7—H72 | 0.9700 | C35—C36 | 1.368 (9) |
C8—C9 | 1.532 (5) | C35—H351 | 0.9300 |
C8—H81 | 0.9800 | C36—H361 | 0.9300 |
C9—C24 | 1.498 (8) | C37—H371 | 0.9600 |
C9—H91 | 0.9800 | C37—H372 | 0.9600 |
C10—C11 | 1.267 (4) | C37—H373 | 0.9600 |
| | | |
O3—S1—O2 | 120.8 (3) | C8—C9—H91 | 109.9 |
O3—S1—O1 | 105.03 (14) | C11—C10—C3 | 129.5 (6) |
O2—S1—O1 | 108.80 (15) | C11—C10—H101 | 115.2 |
O3—S1—C31 | 108.5 (2) | C3—C10—H101 | 115.2 |
O2—S1—C31 | 109.0 (2) | C10—C11—H111 | 120.0 |
O1—S1—C31 | 103.2 (2) | C10—C11—H112 | 120.0 |
C9—O1—S1 | 119.67 (17) | H111—C11—H112 | 120.0 |
C6—N1—C8 | 111.8 (4) | N2—C22—C23 | 124.3 (6) |
C6—N1—C2 | 108.7 (4) | N2—C22—H221 | 117.8 |
C8—N1—C2 | 107.2 (4) | C23—C22—H221 | 117.8 |
C22—N2—C29 | 116.4 (6) | C24—C23—C22 | 120.6 (5) |
N1—C2—C3 | 111.4 (5) | C24—C23—H231 | 119.7 |
N1—C2—H21 | 109.3 | C22—C23—H231 | 119.7 |
C3—C2—H21 | 109.3 | C23—C24—C30 | 117.9 (6) |
N1—C2—H22 | 109.3 | C23—C24—C9 | 119.0 (4) |
C3—C2—H22 | 109.3 | C30—C24—C9 | 123.1 (4) |
H21—C2—H22 | 108.0 | C26—C25—C30 | 121.1 (7) |
C10—C3—C4 | 114.7 (4) | C26—C25—H251 | 119.5 |
C10—C3—C2 | 109.6 (6) | C30—C25—H251 | 119.5 |
C4—C3—C2 | 105.8 (4) | C27—C26—C25 | 121.4 (7) |
C10—C3—H31 | 108.9 | C27—C26—H261 | 119.3 |
C4—C3—H31 | 108.9 | C25—C26—H261 | 119.3 |
C2—C3—H31 | 108.9 | C28—C27—C26 | 120.3 (7) |
C7—C4—C3 | 111.3 (5) | C28—C27—H271 | 119.9 |
C7—C4—C5 | 110.9 (5) | C26—C27—H271 | 119.9 |
C3—C4—C5 | 108.2 (4) | C27—C28—C29 | 121.3 (8) |
C7—C4—H41 | 108.8 | C27—C28—H281 | 119.3 |
C3—C4—H41 | 108.8 | C29—C28—H281 | 119.3 |
C5—C4—H41 | 108.8 | N2—C29—C28 | 117.6 (7) |
C6—C5—C4 | 106.7 (6) | N2—C29—C30 | 123.7 (5) |
C6—C5—H51 | 110.4 | C28—C29—C30 | 118.7 (6) |
C4—C5—H51 | 110.4 | C24—C30—C25 | 125.7 (6) |
C6—C5—H52 | 110.4 | C24—C30—C29 | 117.1 (5) |
C4—C5—H52 | 110.4 | C25—C30—C29 | 117.1 (5) |
H51—C5—H52 | 108.6 | C36—C31—C32 | 119.7 (6) |
N1—C6—C5 | 112.6 (5) | C36—C31—S1 | 119.6 (4) |
N1—C6—H61 | 109.1 | C32—C31—S1 | 120.6 (4) |
C5—C6—H61 | 109.1 | C33—C32—C31 | 118.2 (6) |
N1—C6—H62 | 109.1 | C33—C32—H321 | 120.9 |
C5—C6—H62 | 109.1 | C31—C32—H321 | 120.9 |
H61—C6—H62 | 107.8 | C34—C33—C32 | 123.1 (6) |
C4—C7—C8 | 107.3 (4) | C34—C33—H331 | 118.4 |
C4—C7—H71 | 110.3 | C32—C33—H331 | 118.4 |
C8—C7—H71 | 110.3 | C33—C34—C35 | 117.2 (6) |
C4—C7—H72 | 110.3 | C33—C34—C37 | 122.1 (6) |
C8—C7—H72 | 110.3 | C35—C34—C37 | 120.7 (6) |
H71—C7—H72 | 108.5 | C36—C35—C34 | 121.2 (6) |
N1—C8—C9 | 110.2 (4) | C36—C35—H351 | 119.4 |
N1—C8—C7 | 110.6 (5) | C34—C35—H351 | 119.4 |
C9—C8—C7 | 113.0 (4) | C35—C36—C31 | 120.4 (6) |
N1—C8—H81 | 107.6 | C35—C36—H361 | 119.8 |
C9—C8—H81 | 107.6 | C31—C36—H361 | 119.8 |
C7—C8—H81 | 107.6 | C34—C37—H371 | 109.5 |
O1—C9—C24 | 108.6 (5) | C34—C37—H372 | 109.5 |
O1—C9—C8 | 104.1 (3) | H371—C37—H372 | 109.5 |
C24—C9—C8 | 114.2 (4) | C34—C37—H373 | 109.5 |
O1—C9—H91 | 109.9 | H371—C37—H373 | 109.5 |
C24—C9—H91 | 109.9 | H372—C37—H373 | 109.5 |
| | | |
O3—S1—O1—C9 | 153.6 (5) | C8—C9—C24—C23 | 55.9 (5) |
O2—S1—O1—C9 | 22.9 (5) | O1—C9—C24—C30 | 120.9 (3) |
C31—S1—O1—C9 | −92.8 (5) | C8—C9—C24—C30 | −123.5 (3) |
C6—N1—C2—C3 | 61.5 (6) | C30—C25—C26—C27 | −2.5 (11) |
C8—N1—C2—C3 | −59.5 (6) | C25—C26—C27—C28 | 2.8 (14) |
N1—C2—C3—C10 | 121.6 (4) | C26—C27—C28—C29 | −0.3 (13) |
N1—C2—C3—C4 | −2.6 (6) | C22—N2—C29—C28 | 179.3 (4) |
C10—C3—C4—C7 | −58.8 (7) | C22—N2—C29—C30 | 0.3 (7) |
C2—C3—C4—C7 | 62.1 (6) | C27—C28—C29—N2 | 178.6 (6) |
C10—C3—C4—C5 | 179.1 (6) | C27—C28—C29—C30 | −2.3 (9) |
C2—C3—C4—C5 | −60.0 (6) | C23—C24—C30—C25 | 178.2 (4) |
C7—C4—C5—C6 | −57.0 (7) | C9—C24—C30—C25 | −2.4 (6) |
C3—C4—C5—C6 | 65.4 (7) | C23—C24—C30—C29 | 0.7 (6) |
C8—N1—C6—C5 | 60.9 (7) | C9—C24—C30—C29 | −179.9 (4) |
C2—N1—C6—C5 | −57.2 (6) | C26—C25—C30—C24 | −177.6 (5) |
C4—C5—C6—N1 | −5.3 (7) | C26—C25—C30—C29 | −0.2 (7) |
C3—C4—C7—C8 | −55.9 (6) | N2—C29—C30—C24 | −0.8 (7) |
C5—C4—C7—C8 | 64.6 (6) | C28—C29—C30—C24 | −179.8 (4) |
C6—N1—C8—C9 | 73.5 (6) | N2—C29—C30—C25 | −178.5 (4) |
C2—N1—C8—C9 | −167.4 (4) | C28—C29—C30—C25 | 2.5 (7) |
C6—N1—C8—C7 | −52.2 (5) | O3—S1—C31—C36 | 30.4 (3) |
C2—N1—C8—C7 | 66.8 (5) | O2—S1—C31—C36 | 163.9 (3) |
C4—C7—C8—N1 | −8.8 (5) | O1—S1—C31—C36 | −80.6 (3) |
C4—C7—C8—C9 | −132.9 (3) | O3—S1—C31—C32 | −149.1 (3) |
S1—O1—C9—C24 | −90.4 (4) | O2—S1—C31—C32 | −15.7 (4) |
S1—O1—C9—C8 | 147.6 (4) | O1—S1—C31—C32 | 99.8 (3) |
N1—C8—C9—O1 | 166.6 (5) | C36—C31—C32—C33 | 2.8 (7) |
C7—C8—C9—O1 | −69.0 (5) | S1—C31—C32—C33 | −177.6 (5) |
N1—C8—C9—C24 | 48.4 (6) | C31—C32—C33—C34 | −2.4 (9) |
C7—C8—C9—C24 | 172.8 (3) | C32—C33—C34—C35 | −0.4 (8) |
C4—C3—C10—C11 | −130.2 (10) | C32—C33—C34—C37 | −178.0 (6) |
C2—C3—C10—C11 | 111.0 (11) | C33—C34—C35—C36 | 2.9 (8) |
C29—N2—C22—C23 | 0.3 (7) | C37—C34—C35—C36 | −179.5 (6) |
N2—C22—C23—C24 | −0.4 (8) | C34—C35—C36—C31 | −2.5 (9) |
C22—C23—C24—C30 | −0.2 (7) | C32—C31—C36—C35 | −0.4 (7) |
C22—C23—C24—C9 | −179.6 (4) | S1—C31—C36—C35 | −180.0 (4) |
O1—C9—C24—C23 | −59.7 (4) | | |
Hydrogen-bond geometry (Å, º) topCgA, CgB and CgC are the centroids of the benzene, toluene and pyridine rings,
respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
C32—H321···O2 | 0.93 | 2.60 | 2.944 (9) | 103 |
C10—H101···O3i | 0.93 | 2.48 | 3.377 (7) | 163 |
C11—H111···CgAii | 0.93 | 2.98 | 3.775 (8) | 144 |
C23—H231···CgBi | 0.93 | 2.87 | 3.619 (5) | 138 |
C37—H371···CgCiii | 0.96 | 2.81 | 3.746 (7) | 165 |
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x, y+1/2, −z+3/2; (iii) x, y+1, z. |
(II)
O-Tosyl cinchonine
top
Crystal data top
C26H28N2O3S | Dx = 1.317 Mg m−3 |
Mr = 448.56 | Melting point = 447–448 K |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 25 reflections |
a = 6.8350 (13) Å | θ = 9.9–19.2° |
b = 17.7364 (16) Å | µ = 1.52 mm−1 |
c = 18.6632 (17) Å | T = 293 K |
V = 2262.5 (5) Å3 | Prism, colourless |
Z = 4 | 0.40 × 0.10 × 0.10 mm |
F(000) = 952 | |
Data collection top
Kuma KM-4 four-circle diffractometer | 1710 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.026 |
Graphite monochromator | θmax = 80.3°, θmin = 3.4° |
ω–2θ scans | h = −8→1 |
Absorption correction: ψ scan (North et al., 1968) | k = −22→1 |
Tmin = 0.571, Tmax = 0.847 | l = −1→23 |
2806 measured reflections | 2 standard reflections every 100 reflections |
2723 independent reflections | intensity decay: 0.0% |
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)] = 0.051 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.177 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.1133P)2] where P = (Fo2 + 2Fc2)/3 |
2723 reflections | (Δ/σ)max < 0.001 |
290 parameters | Δρmax = 0.45 e Å−3 |
1 restraint | Δρmin = −0.21 e Å−3 |
Crystal data top
C26H28N2O3S | V = 2262.5 (5) Å3 |
Mr = 448.56 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 6.8350 (13) Å | µ = 1.52 mm−1 |
b = 17.7364 (16) Å | T = 293 K |
c = 18.6632 (17) Å | 0.40 × 0.10 × 0.10 mm |
Data collection top
Kuma KM-4 four-circle diffractometer | 1710 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.026 |
Tmin = 0.571, Tmax = 0.847 | 2 standard reflections every 100 reflections |
2806 measured reflections | intensity decay: 0.0% |
2723 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.051 | 1 restraint |
wR(F2) = 0.177 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.45 e Å−3 |
2723 reflections | Δρmin = −0.21 e Å−3 |
290 parameters | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s.
planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor
wR and goodness of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The threshold expression of F2 >
σ(F2) is used only for calculating R-factors(gt) etc.
and is not relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R- factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
S1 | 0.8889 (2) | 0.25918 (7) | 0.80103 (7) | 0.0777 (4) | |
O1 | 0.8696 (5) | 0.20194 (18) | 0.73655 (17) | 0.0735 (8) | |
O2 | 0.7971 (7) | 0.3287 (2) | 0.78190 (19) | 0.0930 (12) | |
O3 | 1.0864 (6) | 0.2573 (2) | 0.8184 (2) | 0.0897 (10) | |
N1 | 0.4898 (8) | 0.1078 (3) | 0.6303 (2) | 0.0861 (13) | |
N2 | 0.6875 (9) | 0.3525 (3) | 0.5181 (3) | 0.0917 (14) | |
C2 | 0.3164 (9) | 0.1018 (3) | 0.6749 (4) | 0.0946 (18) | |
H21 | 0.2013 | 0.1014 | 0.6445 | 0.142* | |
H22 | 0.3083 | 0.1458 | 0.7057 | 0.142* | |
C3 | 0.3170 (11) | 0.0306 (4) | 0.7215 (4) | 0.0960 (18) | |
H31 | 0.2226 | −0.0054 | 0.7015 | 0.144* | |
C4 | 0.5216 (11) | −0.0035 (3) | 0.7159 (3) | 0.0931 (17) | |
H41 | 0.5346 | −0.0461 | 0.7489 | 0.140* | |
C5 | 0.5523 (12) | −0.0296 (4) | 0.6391 (4) | 0.102 (2) | |
H51 | 0.4662 | −0.0715 | 0.6284 | 0.152* | |
H52 | 0.6865 | −0.0460 | 0.6323 | 0.152* | |
C6 | 0.5068 (12) | 0.0371 (3) | 0.5894 (3) | 0.102 (2) | |
H61 | 0.6102 | 0.0421 | 0.5541 | 0.153* | |
H62 | 0.3853 | 0.0276 | 0.5641 | 0.153* | |
C7 | 0.6720 (10) | 0.0573 (3) | 0.7339 (3) | 0.0876 (16) | |
H71 | 0.8015 | 0.0353 | 0.7377 | 0.131* | |
H72 | 0.6399 | 0.0812 | 0.7791 | 0.131* | |
C8 | 0.6667 (9) | 0.1160 (3) | 0.6724 (3) | 0.0751 (13) | |
H81 | 0.7784 | 0.1060 | 0.6409 | 0.113* | |
C9 | 0.6831 (7) | 0.1977 (3) | 0.6986 (3) | 0.0689 (11) | |
H91 | 0.5754 | 0.2092 | 0.7315 | 0.103* | |
C10 | 0.2530 (15) | 0.0515 (5) | 0.7960 (5) | 0.135 (3) | |
H101 | 0.2325 | 0.1025 | 0.8046 | 0.202* | |
C11 | 0.2234 (17) | 0.0067 (6) | 0.8490 (5) | 0.153 (4) | |
H111 | 0.2417 | −0.0449 | 0.8434 | 0.229* | |
H112 | 0.1838 | 0.0260 | 0.8930 | 0.229* | |
C22 | 0.8278 (10) | 0.3044 (3) | 0.5299 (3) | 0.0868 (16) | |
H221 | 0.9312 | 0.3028 | 0.4975 | 0.130* | |
C23 | 0.8328 (8) | 0.2542 (3) | 0.5892 (3) | 0.0796 (13) | |
H231 | 0.9389 | 0.2221 | 0.5954 | 0.119* | |
C24 | 0.6831 (8) | 0.2532 (3) | 0.6367 (2) | 0.0721 (11) | |
C25 | 0.3629 (8) | 0.3129 (3) | 0.6723 (3) | 0.0814 (13) | |
H251 | 0.3514 | 0.2816 | 0.7121 | 0.122* | |
C26 | 0.2221 (10) | 0.3647 (3) | 0.6596 (4) | 0.0915 (16) | |
H261 | 0.1177 | 0.3697 | 0.6912 | 0.137* | |
C27 | 0.2336 (11) | 0.4110 (4) | 0.5988 (4) | 0.105 (2) | |
H271 | 0.1340 | 0.4452 | 0.5892 | 0.157* | |
C28 | 0.3880 (11) | 0.4060 (4) | 0.5542 (4) | 0.1008 (18) | |
H281 | 0.3958 | 0.4380 | 0.5148 | 0.151* | |
C29 | 0.5370 (9) | 0.3533 (3) | 0.5664 (3) | 0.0781 (13) | |
C30 | 0.5265 (8) | 0.3051 (3) | 0.6270 (3) | 0.0718 (12) | |
C31 | 0.7531 (9) | 0.2174 (3) | 0.8694 (3) | 0.0764 (13) | |
C32 | 0.5641 (9) | 0.2398 (3) | 0.8835 (3) | 0.0841 (14) | |
H321 | 0.5079 | 0.2786 | 0.8571 | 0.126* | |
C33 | 0.4580 (10) | 0.2048 (4) | 0.9369 (3) | 0.0924 (17) | |
H331 | 0.3323 | 0.2216 | 0.9473 | 0.139* | |
C34 | 0.5362 (11) | 0.1448 (3) | 0.9754 (3) | 0.0885 (16) | |
C35 | 0.7259 (11) | 0.1250 (3) | 0.9617 (3) | 0.0929 (17) | |
H351 | 0.7833 | 0.0872 | 0.9892 | 0.139* | |
C36 | 0.8353 (10) | 0.1589 (3) | 0.9086 (3) | 0.0859 (15) | |
H361 | 0.9623 | 0.1429 | 0.8993 | 0.129* | |
C37 | 0.4185 (14) | 0.1059 (4) | 1.0331 (4) | 0.119 (3) | |
H371 | 0.2815 | 0.1125 | 1.0237 | 0.179* | |
H372 | 0.4502 | 0.1273 | 1.0789 | 0.179* | |
H373 | 0.4491 | 0.0530 | 1.0334 | 0.179* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.1167 (9) | 0.0630 (6) | 0.0534 (5) | −0.0080 (6) | −0.0040 (6) | 0.0017 (6) |
O1 | 0.106 (2) | 0.0629 (18) | 0.0519 (17) | −0.0018 (17) | −0.0010 (16) | −0.0027 (14) |
O2 | 0.160 (3) | 0.0551 (18) | 0.064 (2) | −0.003 (2) | −0.003 (2) | 0.0035 (16) |
O3 | 0.114 (2) | 0.088 (3) | 0.067 (2) | −0.015 (2) | 0.0014 (18) | 0.0022 (19) |
N1 | 0.133 (4) | 0.060 (2) | 0.066 (3) | −0.008 (2) | −0.016 (3) | 0.001 (2) |
N2 | 0.136 (4) | 0.078 (3) | 0.061 (3) | −0.004 (3) | 0.009 (3) | 0.008 (2) |
C2 | 0.106 (4) | 0.067 (3) | 0.111 (5) | −0.004 (3) | −0.011 (4) | −0.003 (3) |
C3 | 0.120 (5) | 0.085 (4) | 0.083 (4) | −0.014 (3) | 0.007 (3) | 0.001 (3) |
C4 | 0.146 (5) | 0.061 (3) | 0.072 (3) | −0.007 (3) | −0.008 (3) | 0.008 (3) |
C5 | 0.153 (6) | 0.067 (3) | 0.085 (4) | 0.000 (3) | −0.003 (4) | −0.012 (3) |
C6 | 0.162 (6) | 0.076 (3) | 0.067 (3) | −0.025 (4) | 0.002 (4) | −0.013 (3) |
C7 | 0.123 (4) | 0.070 (3) | 0.070 (3) | 0.000 (3) | −0.011 (3) | 0.014 (3) |
C8 | 0.114 (4) | 0.052 (2) | 0.058 (3) | −0.006 (2) | 0.003 (2) | 0.002 (2) |
C9 | 0.088 (3) | 0.062 (2) | 0.057 (2) | −0.001 (2) | 0.006 (2) | 0.001 (2) |
C10 | 0.183 (8) | 0.116 (6) | 0.106 (6) | −0.019 (6) | 0.037 (6) | −0.001 (5) |
C11 | 0.196 (9) | 0.157 (9) | 0.105 (6) | 0.030 (8) | 0.023 (7) | 0.020 (6) |
C22 | 0.127 (4) | 0.077 (3) | 0.056 (3) | −0.009 (3) | 0.012 (3) | 0.001 (3) |
C23 | 0.110 (3) | 0.070 (3) | 0.060 (3) | 0.000 (3) | 0.006 (2) | −0.001 (2) |
C24 | 0.105 (3) | 0.058 (3) | 0.053 (2) | −0.006 (2) | 0.002 (2) | −0.004 (2) |
C25 | 0.107 (4) | 0.066 (3) | 0.071 (3) | −0.002 (3) | −0.001 (3) | 0.003 (2) |
C26 | 0.115 (4) | 0.070 (3) | 0.089 (4) | 0.000 (3) | 0.001 (3) | 0.006 (3) |
C27 | 0.112 (4) | 0.090 (4) | 0.113 (5) | 0.005 (3) | −0.007 (4) | 0.032 (4) |
C28 | 0.123 (5) | 0.090 (4) | 0.089 (4) | 0.001 (4) | −0.001 (4) | 0.026 (3) |
C29 | 0.109 (4) | 0.068 (3) | 0.057 (3) | −0.006 (3) | −0.002 (2) | 0.007 (2) |
C30 | 0.105 (3) | 0.061 (3) | 0.050 (2) | −0.011 (2) | −0.006 (2) | 0.001 (2) |
C31 | 0.109 (4) | 0.065 (3) | 0.055 (2) | −0.004 (2) | −0.003 (2) | −0.001 (2) |
C32 | 0.120 (4) | 0.068 (3) | 0.064 (3) | 0.000 (3) | −0.006 (3) | −0.003 (3) |
C33 | 0.121 (4) | 0.082 (4) | 0.075 (4) | 0.003 (3) | 0.014 (3) | −0.013 (3) |
C34 | 0.137 (5) | 0.072 (3) | 0.057 (3) | −0.009 (3) | 0.013 (3) | −0.006 (3) |
C35 | 0.146 (5) | 0.069 (3) | 0.063 (3) | 0.007 (3) | 0.007 (3) | 0.008 (3) |
C36 | 0.116 (4) | 0.077 (3) | 0.065 (3) | 0.007 (3) | 0.007 (3) | 0.008 (3) |
C37 | 0.182 (7) | 0.092 (4) | 0.084 (4) | −0.015 (5) | 0.044 (5) | 0.002 (4) |
Geometric parameters (Å, º) top
S1—O3 | 1.388 (4) | C10—H101 | 0.9300 |
S1—O2 | 1.429 (4) | C11—H111 | 0.9300 |
S1—O1 | 1.580 (3) | C11—H112 | 0.9300 |
S1—C31 | 1.743 (6) | C22—C23 | 1.420 (8) |
O1—C9 | 1.460 (6) | C22—H221 | 0.9300 |
N1—C8 | 1.450 (8) | C23—C24 | 1.355 (7) |
N1—C2 | 1.452 (9) | C23—H231 | 0.9300 |
N1—C6 | 1.473 (7) | C24—C30 | 1.423 (7) |
N2—C22 | 1.303 (8) | C25—C26 | 1.351 (8) |
N2—C29 | 1.368 (7) | C25—C30 | 1.409 (8) |
C2—C3 | 1.534 (9) | C25—H251 | 0.9300 |
C2—H21 | 0.9700 | C26—C27 | 1.403 (8) |
C2—H22 | 0.9700 | C26—H261 | 0.9300 |
C3—C10 | 1.504 (10) | C27—C28 | 1.347 (10) |
C3—C4 | 1.527 (10) | C27—H271 | 0.9300 |
C3—H31 | 0.9800 | C28—C29 | 1.401 (9) |
C4—C5 | 1.520 (9) | C28—H281 | 0.9300 |
C4—C7 | 1.528 (9) | C29—C30 | 1.420 (7) |
C4—H41 | 0.9800 | C31—C32 | 1.378 (9) |
C5—C6 | 1.535 (9) | C31—C36 | 1.389 (8) |
C5—H51 | 0.9700 | C32—C33 | 1.379 (8) |
C5—H52 | 0.9700 | C32—H321 | 0.9300 |
C6—H61 | 0.9700 | C33—C34 | 1.392 (9) |
C6—H62 | 0.9700 | C33—H331 | 0.9300 |
C7—C8 | 1.548 (7) | C34—C35 | 1.367 (10) |
C7—H71 | 0.9700 | C34—C37 | 1.511 (8) |
C7—H72 | 0.9700 | C35—C36 | 1.380 (8) |
C8—C9 | 1.533 (7) | C35—H351 | 0.9300 |
C8—H81 | 0.9800 | C36—H361 | 0.9300 |
C9—C24 | 1.518 (7) | C37—H371 | 0.9600 |
C9—H91 | 0.9800 | C37—H372 | 0.9600 |
C10—C11 | 1.285 (5) | C37—H373 | 0.9600 |
| | | |
O3—S1—O2 | 120.4 (3) | C8—C9—H91 | 109.9 |
O3—S1—O1 | 104.1 (2) | C11—C10—C3 | 127.3 (9) |
O2—S1—O1 | 109.1 (2) | C11—C10—H101 | 116.4 |
O3—S1—C31 | 109.7 (3) | C3—C10—H101 | 116.4 |
O2—S1—C31 | 108.4 (3) | C10—C11—H111 | 120.0 |
O1—S1—C31 | 103.8 (2) | C10—C11—H112 | 120.0 |
C9—O1—S1 | 118.4 (3) | H111—C11—H112 | 120.0 |
C8—N1—C2 | 112.2 (4) | N2—C22—C23 | 124.1 (5) |
C8—N1—C6 | 107.5 (5) | N2—C22—H221 | 118.0 |
C2—N1—C6 | 107.4 (5) | C23—C22—H221 | 118.0 |
C22—N2—C29 | 116.7 (5) | C24—C23—C22 | 120.0 (5) |
N1—C2—C3 | 112.5 (5) | C24—C23—H231 | 120.0 |
N1—C2—H21 | 109.1 | C22—C23—H231 | 120.0 |
C3—C2—H21 | 109.1 | C23—C24—C30 | 118.5 (5) |
N1—C2—H22 | 109.1 | C23—C24—C9 | 120.4 (5) |
C3—C2—H22 | 109.1 | C30—C24—C9 | 121.1 (4) |
H21—C2—H22 | 107.8 | C26—C25—C30 | 121.8 (5) |
C10—C3—C2 | 108.7 (6) | C26—C25—H251 | 119.1 |
C10—C3—C4 | 115.3 (7) | C30—C25—H251 | 119.1 |
C2—C3—C4 | 106.8 (5) | C25—C26—C27 | 120.0 (6) |
C10—C3—H31 | 108.6 | C25—C26—H261 | 120.0 |
C2—C3—H31 | 108.6 | C27—C26—H261 | 120.0 |
C4—C3—H31 | 108.6 | C28—C27—C26 | 120.4 (6) |
C5—C4—C7 | 109.2 (6) | C28—C27—H271 | 119.8 |
C5—C4—C3 | 108.1 (6) | C26—C27—H271 | 119.8 |
C7—C4—C3 | 108.8 (5) | C27—C28—C29 | 120.8 (6) |
C5—C4—H41 | 110.2 | C27—C28—H281 | 119.6 |
C7—C4—H41 | 110.2 | C29—C28—H281 | 119.6 |
C3—C4—H41 | 110.2 | N2—C29—C28 | 116.5 (5) |
C4—C5—C6 | 107.9 (5) | N2—C29—C30 | 123.9 (5) |
C4—C5—H51 | 110.1 | C28—C29—C30 | 119.6 (5) |
C6—C5—H51 | 110.1 | C25—C30—C29 | 117.3 (5) |
C4—C5—H52 | 110.1 | C25—C30—C24 | 125.8 (5) |
C6—C5—H52 | 110.1 | C29—C30—C24 | 116.9 (5) |
H51—C5—H52 | 108.4 | C32—C31—C36 | 119.6 (5) |
N1—C6—C5 | 111.0 (5) | C32—C31—S1 | 121.1 (5) |
N1—C6—H61 | 109.4 | C36—C31—S1 | 119.2 (5) |
C5—C6—H61 | 109.4 | C33—C32—C31 | 120.1 (6) |
N1—C6—H62 | 109.4 | C33—C32—H321 | 119.9 |
C5—C6—H62 | 109.4 | C31—C32—H321 | 119.9 |
H61—C6—H62 | 108.0 | C32—C33—C34 | 121.0 (6) |
C4—C7—C8 | 107.2 (5) | C32—C33—H331 | 119.5 |
C4—C7—H71 | 110.3 | C34—C33—H331 | 119.5 |
C8—C7—H71 | 110.3 | C35—C34—C33 | 117.7 (6) |
C4—C7—H72 | 110.3 | C35—C34—C37 | 121.4 (7) |
C8—C7—H72 | 110.3 | C33—C34—C37 | 120.9 (7) |
H71—C7—H72 | 108.5 | C34—C35—C36 | 122.4 (6) |
N1—C8—C9 | 109.1 (4) | C34—C35—H351 | 118.8 |
N1—C8—C7 | 110.7 (4) | C36—C35—H351 | 118.8 |
C9—C8—C7 | 113.4 (4) | C35—C36—C31 | 119.1 (6) |
N1—C8—H81 | 107.8 | C35—C36—H361 | 120.5 |
C9—C8—H81 | 107.8 | C31—C36—H361 | 120.5 |
C7—C8—H81 | 107.8 | C34—C37—H371 | 109.5 |
O1—C9—C24 | 109.6 (4) | C34—C37—H372 | 109.5 |
O1—C9—C8 | 105.5 (4) | H371—C37—H372 | 109.5 |
C24—C9—C8 | 111.8 (4) | C34—C37—H373 | 109.5 |
O1—C9—H91 | 109.9 | H371—C37—H373 | 109.5 |
C24—C9—H91 | 109.9 | H372—C37—H373 | 109.5 |
| | | |
O3—S1—O1—C9 | −171.9 (3) | C8—C9—C24—C23 | −65.7 (6) |
O2—S1—O1—C9 | −42.2 (4) | O1—C9—C24—C30 | −129.3 (5) |
C31—S1—O1—C9 | 73.3 (4) | C8—C9—C24—C30 | 114.1 (5) |
C8—N1—C2—C3 | −64.2 (6) | C30—C25—C26—C27 | 2.0 (9) |
C6—N1—C2—C3 | 53.6 (7) | C25—C26—C27—C28 | −2.4 (10) |
N1—C2—C3—C10 | 135.7 (6) | C26—C27—C28—C29 | 1.9 (11) |
N1—C2—C3—C4 | 10.8 (7) | C22—N2—C29—C28 | 178.9 (6) |
C10—C3—C4—C5 | 173.4 (6) | C22—N2—C29—C30 | −0.4 (9) |
C2—C3—C4—C5 | −65.8 (6) | C27—C28—C29—N2 | 179.9 (6) |
C10—C3—C4—C7 | −68.1 (7) | C27—C28—C29—C30 | −0.8 (10) |
C2—C3—C4—C7 | 52.7 (7) | C26—C25—C30—C29 | −0.9 (8) |
C7—C4—C5—C6 | −65.3 (8) | C26—C25—C30—C24 | 178.9 (5) |
C3—C4—C5—C6 | 53.0 (7) | N2—C29—C30—C25 | 179.6 (5) |
C8—N1—C6—C5 | 53.7 (7) | C28—C29—C30—C25 | 0.3 (8) |
C2—N1—C6—C5 | −67.2 (8) | N2—C29—C30—C24 | −0.3 (8) |
C4—C5—C6—N1 | 12.0 (9) | C28—C29—C30—C24 | −179.6 (5) |
C5—C4—C7—C8 | 49.4 (7) | C23—C24—C30—C25 | −178.2 (5) |
C3—C4—C7—C8 | −68.5 (6) | C9—C24—C30—C25 | 2.0 (8) |
C2—N1—C8—C9 | −78.3 (5) | C23—C24—C30—C29 | 1.6 (7) |
C6—N1—C8—C9 | 163.8 (4) | C9—C24—C30—C29 | −178.2 (4) |
C2—N1—C8—C7 | 47.2 (6) | O3—S1—C31—C32 | 150.2 (5) |
C6—N1—C8—C7 | −70.6 (6) | O2—S1—C31—C32 | 17.0 (5) |
C4—C7—C8—N1 | 16.6 (7) | O1—S1—C31—C32 | −99.0 (5) |
C4—C7—C8—C9 | 139.7 (5) | O3—S1—C31—C36 | −31.8 (5) |
S1—O1—C9—C24 | 90.2 (4) | O2—S1—C31—C36 | −165.0 (4) |
S1—O1—C9—C8 | −149.3 (3) | O1—S1—C31—C36 | 79.0 (5) |
N1—C8—C9—O1 | −176.7 (4) | C36—C31—C32—C33 | 0.6 (8) |
C7—C8—C9—O1 | 59.3 (6) | S1—C31—C32—C33 | 178.6 (4) |
N1—C8—C9—C24 | −57.6 (6) | C31—C32—C33—C34 | −2.4 (9) |
C7—C8—C9—C24 | 178.4 (5) | C32—C33—C34—C35 | 4.2 (9) |
C2—C3—C10—C11 | 175.4 (11) | C32—C33—C34—C37 | −179.1 (6) |
C4—C3—C10—C11 | −64.8 (14) | C33—C34—C35—C36 | −4.3 (9) |
C29—N2—C22—C23 | −0.3 (9) | C37—C34—C35—C36 | 179.0 (6) |
N2—C22—C23—C24 | 1.7 (9) | C34—C35—C36—C31 | 2.6 (10) |
C22—C23—C24—C30 | −2.2 (7) | C32—C31—C36—C35 | −0.7 (8) |
C22—C23—C24—C9 | 177.6 (5) | S1—C31—C36—C35 | −178.7 (5) |
O1—C9—C24—C23 | 50.9 (6) | | |
Hydrogen-bond geometry (Å, º) topCgD and CgE are the centroids of the pyridine and quinoline rings, respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
C32—H321···O2 | 0.93 | 2.58 | 2.936 (7) | 103 |
C22—H221···CgDi | 0.93 | 2.92 | 3.689 (7) | 141 |
C11—H111···CgEii | 0.93 | 2.92 | 3.681 (7) | 140 |
Symmetry codes: (i) x+1/2, −y+1/2, −z+1; (ii) −x+1, y−1/2, −z+3/2. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C26H28N2O3S | C26H28N2O3S |
Mr | 448.56 | 448.56 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, P212121 |
Temperature (K) | 293 | 293 |
a, b, c (Å) | 9.4591 (13), 10.094 (2), 24.370 (4) | 6.8350 (13), 17.7364 (16), 18.6632 (17) |
V (Å3) | 2326.9 (7) | 2262.5 (5) |
Z | 4 | 4 |
Radiation type | Cu Kα | Cu Kα |
µ (mm−1) | 1.48 | 1.52 |
Crystal size (mm) | 0.45 × 0.40 × 0.10 | 0.40 × 0.10 × 0.10 |
|
Data collection |
Diffractometer | Kuma KM-4 four-circle diffractometer | Kuma KM-4 four-circle diffractometer |
Absorption correction | Multi-scan (Blessing, 1995) | ψ scan (North et al., 1968) |
Tmin, Tmax | 0.363, 0.748 | 0.571, 0.847 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3726, 3508, 1717 | 2806, 2723, 1710 |
Rint | 0.034 | 0.026 |
(sin θ/λ)max (Å−1) | 0.640 | 0.639 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.064, 0.167, 1.06 | 0.051, 0.177, 1.01 |
No. of reflections | 3508 | 2723 |
No. of parameters | 290 | 290 |
No. of restraints | 1 | 1 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.30, −0.33 | 0.45, −0.21 |
Absolute structure | Flack (1983), 604 Friedel pairs | ? |
Absolute structure parameter | 0.00 (3) | ? |
Hydrogen-bond geometry (Å, º) for (I) topCgA, CgB and CgC are the centroids of the benzene, toluene and pyridine rings,
respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
C32—H321···O2 | 0.93 | 2.60 | 2.944 (9) | 103 |
C10—H101···O3i | 0.93 | 2.48 | 3.377 (7) | 163 |
C11—H111···CgAii | 0.93 | 2.98 | 3.775 (8) | 144 |
C23—H231···CgBi | 0.93 | 2.87 | 3.619 (5) | 138 |
C37—H371···CgCiii | 0.96 | 2.81 | 3.746 (7) | 165 |
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x, y+1/2, −z+3/2; (iii) x, y+1, z. |
Hydrogen-bond geometry (Å, º) for (II) topCgD and CgE are the centroids of the pyridine and quinoline rings, respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
C32—H321···O2 | 0.93 | 2.58 | 2.936 (7) | 103 |
C22—H221···CgDi | 0.93 | 2.92 | 3.689 (7) | 141 |
C11—H111···CgEii | 0.93 | 2.92 | 3.681 (7) | 140 |
Symmetry codes: (i) x+1/2, −y+1/2, −z+1; (ii) −x+1, y−1/2, −z+3/2. |
Studies on the difference in biological activity of natural Cinchona alkaloids with respect to their structural, stereochemical and physicochemical properties have attracted much attention owing to the pharmacological interest in these compounds (Verpoorte et al., 1988). Recently, Cinchona alkaloids and their derivatives have been investigated as natural organocatalysts giving asymmetric induction in organic reactions with the formation of stereogenic centres (Song, 2009). Transformation of natural alkaloids into pharmacologically inactive 9-epibases is known to be a two-step process: formation of sulfonate esters followed by hydrolysis in a weak acid medium (Hoffman & Frackenpohl, 2004). The first step runs with retention and the second one with inversion of the carbinol atom configuration. It was found that hydrolysis of O-tosyl derivatives is a good method for epimerization of C9 in quinine, quinidine and cinchonidine core, but is ineffective for cinchonine, since its tosylate converts slowly and not selectively to the corresponding 9-epibase (Braje et al., 2000). In order to link the differences in experimental reactivity in hydrolysis to 9-epibases with structural and energetic parameters, X-ray investigations and theoretical calculations were undertaken using cinchonidine and cinchonine tosylates, (I) and (II) (Scheme 1), as model compounds.
Structural analysis of the diastereoisomeric molecules (I) and (II) confirms the retention of the original, respective, R and S configuration at atom C9 in the crystals of both tosylates (Figs. 1 and 2, respectively). The geometry (bond lengths, angles and planarity) of the main Cinchona alkaloid skeleton is similar in (I) and (II) and related parent structures of cinchonidine and cinchone molecules (Oleksyn, 1982; Oleksyn et al., 1979). Strong thermal vibration of the exocyclic vinyl group results in an apparent shortening of the terminal C10—C11 bond to 1.177 (8) and 1.206 (12) Å in (I) and (II), respectively, in comparison with the expected Csp2═ Csp2 bond length in C*—CH═CH2 [1.299 (27) Å; Allen et al., 1987]. Both molecules adopt an anti-closed conformation with torsion angles ϕ1 = N1—C8—C9—O1 of 166.2 (4) and -176.6 (4)o, ϕ2 = N1—C8—C9—C24 of 48.1 (5) and -57.4 (5)o, ϕ3 = O1—C9—C24—C23 of -59.9 (4) and 50.8 (6)o, ϕ4 = C8—C9—C24—C23 of 55.9 (5) and -65.9 (6)o in (I) and (II), respectively, which is characteristic for e.g. O-mesyl quinidine (Braje et al., 2000) and in contrast to an anti-open conformation observed for parent alkaloids. The four conformers anti-closed, syn-closed, anti-open and syn-open (Caner et al., 2003) of the cinchonine-type molecule, showing the lowest energy, are presented in Fig. 3.
The orientation of the vinyl substituent in relation to the quinuclidine system is different in (I) and (II): the torsion angle C2—C3—C10—C11 describing this orientation is 105.4 (13)° in (I) and 175.0 (12)° in (II). The gauche conformation of the vinyl group in (I) may be caused by a weak intermolecular C10—H101···O3 hydrogen bond and C11—H111···π interaction (Table 1). Similarly, the trans conformation of the vinyl group in (II) may be a result of the weak C11—H111···π (quinoline) intermolecular interaction (Table 2). In both molecules the aryl ring of the tosyl group is inclined to the quinoline ring at an angle of 20.24 (10) and 11.51 (13)° in (I) and (II), respectively, and its position is stabilized by the C32—H321···O2 short intramolecular contact (Tables 1 and 2).
The hydrolysis of O-tosylated molecules proceeds with inversion of the C9 configuration as an SN2 attack of the nucleophilic water molecule from the opposite site to the tosylate leaving [a?] group in the substrate protonated at the quinuclidine nitrogen. This process is the most possible [favoured?] when the substrate molecule can change an anti-closed conformation, observed in the crystal, into a syn-open which is optimal for the SN2 attack in the aqueous weak acid medium. It can be assumed on the basis of known reactivity that the transition state may be formed more easily in the case of cinchonidine tosylate, (I), than in the case of cinchonine tosylate, (II). The theoretical calculations at the RHF SCF ab initio 6–31G** level (Bylaska et al., 2006; Kendall et al., 2000) show that the conformations of molecules (I) and (II) as observed in their crystals are not equi-energetically [favourbale?] with a difference of energy between the (I) and (II) conformations of ΔE = 1.45 kcal mol-1 (single-point energy calculations). Indeed, the geometry of the vinyl group obtained from the X-ray [data] is unreliable in molecules (I) and (II), but the same systematic error generated by an unrealistic bond length in the vinyl substituent during the energy calculation for both molecules makes the difference of energy reasonable. The energy minimization and full geometry optimization with initial geometries obtained from X-ray analysis for molecules (I) and (II) yielded a smaller difference of energy of 0.84 kcal mol-1 between the conformations of molecule (I) (ϕ1 = -179.2°, ϕ2 = 62.5°, ϕ3 = -44.3° and ϕ4 = 71.8°) and (II) (ϕ1 = 174.4°, ϕ2 = -67.0°, ϕ3 = 39.6° and ϕ4 = -77.0°) than that reported for the single-point calculation. It is clear that these energy values do not prevent molecule (II) from changing an unfavourable anti-closed conformation to a syn-open conformation as expected in the SN2 hydrolysis reaction. The calculations performed for N1-protonated molecules in the syn-open conformation after energy minimization and geometry optimization [ϕ1 = -54.0 and 48.9°, ϕ2 = 179.3 and 176.4°, ϕ3 = 146.8 and -144.6° and ϕ4 = -87.2 and 88.5° for (I) and (II), respectively] gave a difference of energy between the protonated, (II), and protonated, (I), species of 0.39 kcal mol-1 and, consistently, the larger energetic profit [gain?] of 1.84 kcal mol-1 after protonation of (I) than that for (II) with respect to free O-tosylates in an anti-closed conformation. Therefore, the different reactivity of (I) and (II) towards the appropriate 9-epibases may be related to a change of energy during protonation on the N1 atom and a change of conformation from anti-closed to syn-open in the hydrolysis process. In order to confirm this conclusion the hydrolysis process was modelled using the N1-protonated molecules (I) and (II) in `crystallographic' anti-closed conformation and an anion of salicylic acid in water environment (as an aqueous weak acid medium). The water environment was simulated by location of the alkaloid and salicylic acid ion in the centre of the box surrounded by 17 water molecules equilibrated at 300 K and 1013 h Pa (Jorgensen et al., 1983). The energy minimization and geometry optimization of the (I)-H+-salicylate-–H2O system using the semi-empirical AM1 method implemented in the HYPERCHEM package (Hypercube, 1998) give molecule (I) an anti-open conformation (ϕ1 = -63.7°, ϕ2 = 175.4°, ϕ3 = -17.1° and ϕ4 = 102.3°) closely related by the rotation around the C9—C24 bond to the syn-open conformation preferred for 9-epicynchonidine formation in the hydrolysis reaction (Figs. 3 and 4a). The parallel calculation for the (II)-H+-salicylate-–H2O system retains molecule (II) in unfavourable for the hydrolysis reaction anti-closed conformation (ϕ1 = -146.0°, ϕ2 = -28.5°, ϕ3 = 49.4° and ϕ4 = -65.4°) as shown in Fig. 4(b) . Additionally, the (I)-H+-salicylate- system in the gaseous phase with (I) in an anti-open conformation is more energetically stable than the (II)-H+-salicylate- system with (II) in an anti-closed conformation with a ΔE value of 8.062 kcal mol-1. As can be seen in Fig. 4, the steric hindrance of the aryl ring of the tosylate group and the quinoline ring can restrain the free rotation on the C24—C9 bond making the C9 atom more accessible to nucleophilic attack of water molecule in anti-open conformation of (I)-H+ in comparison with anti-closed conformation of (II)-H+. The stabilizing influence of the tosylate group on the conformation of (I)-H+ and (II)-H+ can result in their different behaviour in the hydrolysis reaction and higher hydrolytic stability in comparison to O-mesyl and O-acyl Cinchona alkaloid derivatives.
In conclusion, the X-ray analysis and theoretical calculations provided the geometric, conformational and energetic parameters of the diastereoisomeric molecules O-tosyl cinchonidine, (I), and O-tosyl cinchonine, (II), which were used to explain their different reactivity in hydrolysis to the respective 9-epibases. It appears that the different energetic profit [gain?] during protonation on the N1 atom and the different possibility to change of conformation from anti-closed in the crystal to syn-open favoured in the hydrolysis process can be correlated with the different reactivity of (I) and (II) towards 9-epibases in the SN2 hydrolysis process.