Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270103024065/sx1125sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270103024065/sx1125IIsup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270103024065/sx1125III_IVsup3.hkl |
CCDC references: 235347; 235348
For the preparation of (6S)-6-isobutylpiperidine-2,4-dione, (II), tetramethylammonium triacetoxyborohydride (293 mg, 1.11 mmol) was added to a stirred solution of I (100 mg, 0.37 mmol) in a mixture of acetonitrile and 15% v/v acetic acid at room temperature. After 48 h, the mixture was quenched with water. Acetonitrile was evaporated under reduced pressure and replaced with ethyl acetate, which was extracted using water and brine. The organic layer was dried over Na2SO4, filtered and evaporated to afford a residue that was purified by flash chromatography (ethyl acetate) to give pure (II) (53 mg, 84%). Colorless single crystals of (II), suitable for X-ray analysis, were grown from a mixture of dichloromethane and diisopropyl ether (1:3) (m.p. 395–397 K). 1H NMR (300 MHz, CDCl3): δ 7.24 (bs, 1H), 3.80–3.65 (m, 1H), 3.32 (d, J = 19.8 Hz, 1H), 3.20 (d, J = 19.8 Hz), 2.68 (dd, J = 16.3, 4.2 Hz, 1H), 2.31 (dd, J = 16.3, 8.8 Hz, 1H), 1.82–1.62 (m, 1H), 1.57–1.27 (m, 2H), 0.90 (d, J = 2.1 Hz, 3H), 0.87 (d, J = 2.1 Hz, 3H); For the preparation of 4-hydroxy-6-isobutylpiperidin-2-one, (III)/(IV), sodium borohydride (67 mg, 1.77 mmol) was added to a stirred solution of (II) (100 mg, 0.59 mmol) in a mixture of dichloromethane and 10% v/v acetic acid at room temperature. After 72 h, the mixture was quenched with water. Dichloromethane was evaporated under reduced pressure and replaced with ethyl acetate, which was extracted using water and brine. The organic layer was dried over Na2SO4, filtered and evaporated to afford a residue that was purified by flash chromatography (ethyl acetate–acetic acid, 95:5), giving a 84:16 mixture (63 mg, 62%) of (III) and the corresponding (4S,6S) diastereomer, (IV). Colorless single crystals of (III/IV), suitable for X-ray analysis, were grown from a mixture of dichloromethane and diisopropyl ether (1:3); the ratio between (III) and (IV) changed to 75:25 (determined by NMR); (m.p. 418–420 K). Spectroscopic analysis of the major diastereomer, (III): 1H NMR (300 MHz, CD3OD): δ 4.03–3.93 (m, 1H), 3.49–3.40 (m, 1H), 2.61 (ddd, J = 17.2, 5.6, 2.2 Hz, 1H), 2.20–2.11 (m, 2H), 1.79–1.68 (m, 1H), 1.50–1.41 (m, 1H), 1.39–1.22 (m, 2H), 0.94 (d, J = 3.8 Hz, 3H), 0.92 (d, J = 3.8 Hz, 3H).
Because of the lack of any significant anomalous dispersion effects, the absolute configuration could not be determined from the diffraction experiment, so Friedel pairs were merged prior to refinement. All H atoms were placed at calculated positions and refined using a riding model, with C—H distances of 0.93–0.97 Å, an N—H distance of 0.88 Å and an O—H distance of 0.82 Å. The Uiso(H) parameters were fixed at 1.2Ueq(C,N) for methyl, methylene and NH groups, and 1.5Ueq(C,O) for methyl and OH groups. In the (III/IV) crystal structure, the distances between Csp3 atoms in the disordered piperidine rings were restrained to 1.50 (2) Å. The C41, O21 and C51 atoms of the 0.288 (8)-occupancy molecule of (IV) were refined isotropically.
Data collection: COLLECT (Nonius, 1998) for (II); COLLECT software (Nonius, 1998) for III_IV. Cell refinement: COLLECT for (II); COLLECT software (Nonius, 1998) for III_IV. For both compounds, data reduction: HKL Suite (Otwinoski & Minor, 1997). Program(s) used to solve structure: SIR92 (Altomare et al., 1994) for (II); SIR_92 (Altomare et al., 1994) for III_IV. For both compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997). Molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and WebLab ViewerPro 3.5 (MSI, 1999) for (II); ORTEP-3 for Windows (Farrugia, 1997), WebLab ViewerPro 3.5 (MSI, 1999) for III_IV. Software used to prepare material for publication: WinGX (Farrugia, 1999) for (II); WinGX publication routines (Farrugia, 1999) for III_IV.
C9H15NO2 | Z = 2 |
Mr = 169.22 | F(000) = 184 |
Triclinic, P1 | Dx = 1.16 Mg m−3 |
Hall symbol: P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 5.0760 (2) Å | Cell parameters from 7698 reflections |
b = 10.0760 (4) Å | θ = 2.1–26.3° |
c = 10.1210 (5) Å | µ = 0.08 mm−1 |
α = 95.691 (1)° | T = 293 K |
β = 102.529 (1)° | Prism, colorless |
γ = 103.730 (2)° | 0.2 × 0.1 × 0.1 mm |
V = 484.65 (4) Å3 |
Nonius KAPPACCD diffractometer | 1334 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.040 |
Graphite monochromator | θmax = 26.3°, θmin = 2.7° |
oscillation scans | h = −5→6 |
7698 measured reflections | k = −12→12 |
1959 independent reflections | l = −12→12 |
Refinement on F2 | 5 restraints |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.043 | w = 1/[σ2(Fo2) + (0.0747P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.118 | (Δ/σ)max < 0.001 |
S = 0.94 | Δρmax = 0.14 e Å−3 |
1959 reflections | Δρmin = −0.14 e Å−3 |
217 parameters |
C9H15NO2 | γ = 103.730 (2)° |
Mr = 169.22 | V = 484.65 (4) Å3 |
Triclinic, P1 | Z = 2 |
a = 5.0760 (2) Å | Mo Kα radiation |
b = 10.0760 (4) Å | µ = 0.08 mm−1 |
c = 10.1210 (5) Å | T = 293 K |
α = 95.691 (1)° | 0.2 × 0.1 × 0.1 mm |
β = 102.529 (1)° |
Nonius KAPPACCD diffractometer | 1334 reflections with I > 2σ(I) |
7698 measured reflections | Rint = 0.040 |
1959 independent reflections |
R[F2 > 2σ(F2)] = 0.043 | 5 restraints |
wR(F2) = 0.118 | H-atom parameters constrained |
S = 0.94 | Δρmax = 0.14 e Å−3 |
1959 reflections | Δρmin = −0.14 e Å−3 |
217 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.3820 (5) | 0.1967 (3) | 0.0122 (3) | 0.0566 (7) | |
H1 | 0.5467 | 0.2368 | 0.0631 | 0.068* | |
C2 | 0.2799 (7) | 0.0638 (4) | 0.0162 (3) | 0.0540 (8) | |
O1 | 0.4126 (4) | −0.0013 (2) | 0.0917 (2) | 0.0663 (7) | |
C3 | −0.0112 (8) | −0.0081 (4) | −0.0706 (4) | 0.0689 (10) | |
H3A | −0.0064 | −0.0963 | −0.1166 | 0.083* | |
H3B | −0.1341 | −0.0276 | −0.0096 | 0.083* | |
C4 | −0.1391 (8) | 0.0665 (4) | −0.1762 (4) | 0.0635 (9) | |
O2 | −0.3847 (6) | 0.0255 (3) | −0.2350 (3) | 0.0910 (9) | |
C5 | 0.0532 (8) | 0.1930 (4) | −0.2035 (4) | 0.0678 (10) | |
H5A | −0.057 | 0.2467 | −0.254 | 0.081* | |
H5B | 0.1692 | 0.1652 | −0.2598 | 0.081* | |
C6 | 0.2382 (6) | 0.2816 (3) | −0.0717 (4) | 0.0563 (9) | |
H6 | 0.1198 | 0.3178 | −0.0209 | 0.068* | |
C7 | 0.4524 (7) | 0.4033 (4) | −0.0983 (5) | 0.0714 (10) | |
H7A | 0.6028 | 0.4374 | −0.0158 | 0.086* | |
H7B | 0.5322 | 0.3706 | −0.1699 | 0.086* | |
C8 | 0.3369 (9) | 0.5230 (5) | −0.1406 (5) | 0.0912 (15) | |
H8 | 0.1512 | 0.4846 | −0.2034 | 0.109* | |
C9 | 0.5261 (14) | 0.6112 (6) | −0.2166 (8) | 0.135 (2) | |
H9A | 0.5432 | 0.5539 | −0.2942 | 0.202* | |
H9B | 0.708 | 0.6517 | −0.1559 | 0.202* | |
H9C | 0.4455 | 0.6833 | −0.2473 | 0.202* | |
C10 | 0.3047 (15) | 0.6091 (6) | −0.0168 (8) | 0.138 (2) | |
H10A | 0.2319 | 0.6843 | −0.0451 | 0.208* | |
H10B | 0.4838 | 0.6454 | 0.0475 | 0.208* | |
H10C | 0.178 | 0.5524 | 0.0259 | 0.208* | |
N11 | 0.9458 (5) | 0.1279 (3) | 0.2813 (3) | 0.0531 (7) | |
H11 | 0.8104 | 0.0816 | 0.2136 | 0.064* | |
O11 | 0.9300 (5) | 0.3245 (3) | 0.1947 (3) | 0.0751 (8) | |
O12 | 1.7096 (6) | 0.3177 (3) | 0.5272 (3) | 0.1004 (11) | |
C17 | 0.9541 (7) | −0.1015 (4) | 0.3292 (4) | 0.0624 (9) | |
H17A | 1.0296 | −0.1165 | 0.2505 | 0.075* | |
H17B | 0.7518 | −0.1266 | 0.2966 | 0.075* | |
C18 | 1.0328 (7) | −0.1992 (4) | 0.4273 (4) | 0.0687 (10) | |
H18 | 1.2374 | −0.1717 | 0.4597 | 0.082* | |
C19 | 0.9189 (13) | −0.1900 (6) | 0.5516 (6) | 0.1128 (17) | |
H19A | 0.9765 | −0.2534 | 0.6092 | 0.169* | |
H19B | 0.7182 | −0.2133 | 0.5238 | 0.169* | |
H19C | 0.9891 | −0.0975 | 0.6013 | 0.169* | |
C20 | 0.9504 (16) | −0.3462 (6) | 0.3500 (7) | 0.133 (2) | |
H20A | 1.0018 | −0.4073 | 0.4119 | 0.2* | |
H20B | 1.0455 | −0.3492 | 0.2779 | 0.2* | |
H20C | 0.7517 | −0.3749 | 0.3113 | 0.2* | |
C12 | 1.0402 (6) | 0.2625 (4) | 0.2810 (4) | 0.0602 (9) | |
C16 | 1.0532 (7) | 0.0515 (4) | 0.3873 (4) | 0.0516 (8) | |
H16 | 0.9768 | 0.068 | 0.4665 | 0.062* | |
C15 | 1.3716 (7) | 0.1052 (4) | 0.4313 (4) | 0.0600 (9) | |
H15A | 1.4398 | 0.0686 | 0.5133 | 0.072* | |
H15B | 1.4487 | 0.0701 | 0.3598 | 0.072* | |
C14 | 1.4771 (7) | 0.2587 (4) | 0.4596 (4) | 0.0628 (10) | |
C13 | 1.2854 (8) | 0.3397 (4) | 0.3962 (5) | 0.0863 (13) | |
H13A | 1.395 | 0.4155 | 0.3625 | 0.104* | |
H13B | 1.2146 | 0.38 | 0.4677 | 0.104* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0571 (16) | 0.0540 (19) | 0.0519 (17) | 0.0146 (14) | −0.0015 (12) | 0.0100 (13) |
C2 | 0.061 (2) | 0.054 (2) | 0.0434 (18) | 0.0160 (17) | 0.0051 (15) | 0.0105 (16) |
O1 | 0.0718 (15) | 0.0600 (16) | 0.0614 (16) | 0.0210 (12) | −0.0031 (12) | 0.0183 (13) |
C3 | 0.067 (2) | 0.066 (2) | 0.060 (2) | 0.0072 (17) | −0.0031 (17) | 0.0139 (18) |
C4 | 0.066 (2) | 0.068 (2) | 0.047 (2) | 0.0178 (19) | −0.0010 (18) | 0.0061 (17) |
O2 | 0.0667 (17) | 0.102 (2) | 0.085 (2) | 0.0124 (15) | −0.0117 (14) | 0.0195 (17) |
C5 | 0.072 (2) | 0.072 (2) | 0.054 (2) | 0.0212 (18) | −0.0006 (16) | 0.0195 (17) |
C6 | 0.0567 (19) | 0.054 (2) | 0.057 (2) | 0.0202 (16) | 0.0031 (15) | 0.0147 (17) |
C7 | 0.067 (2) | 0.061 (2) | 0.080 (3) | 0.0157 (17) | 0.0034 (18) | 0.0206 (19) |
C8 | 0.081 (3) | 0.062 (3) | 0.111 (4) | 0.009 (2) | −0.013 (2) | 0.031 (3) |
C9 | 0.152 (4) | 0.085 (4) | 0.149 (6) | 0.007 (3) | 0.009 (4) | 0.059 (4) |
C10 | 0.158 (5) | 0.088 (4) | 0.174 (7) | 0.057 (4) | 0.030 (4) | 0.008 (4) |
N11 | 0.0516 (15) | 0.0565 (18) | 0.0485 (17) | 0.0166 (13) | 0.0025 (12) | 0.0130 (13) |
O11 | 0.0716 (15) | 0.0624 (17) | 0.0814 (19) | 0.0137 (12) | −0.0042 (13) | 0.0268 (14) |
O12 | 0.0732 (18) | 0.091 (2) | 0.106 (3) | 0.0038 (16) | −0.0265 (15) | 0.0249 (18) |
C17 | 0.071 (2) | 0.063 (2) | 0.056 (2) | 0.0227 (17) | 0.0131 (16) | 0.0148 (17) |
C18 | 0.072 (2) | 0.061 (2) | 0.076 (3) | 0.0275 (18) | 0.0111 (19) | 0.021 (2) |
C19 | 0.159 (4) | 0.118 (4) | 0.095 (4) | 0.059 (3) | 0.058 (3) | 0.060 (3) |
C20 | 0.203 (6) | 0.074 (3) | 0.130 (5) | 0.056 (4) | 0.032 (4) | 0.022 (3) |
C12 | 0.0485 (19) | 0.059 (2) | 0.068 (2) | 0.0141 (16) | 0.0004 (17) | 0.0175 (19) |
C16 | 0.0531 (17) | 0.059 (2) | 0.0457 (19) | 0.0198 (15) | 0.0104 (14) | 0.0160 (15) |
C15 | 0.0515 (18) | 0.073 (2) | 0.058 (2) | 0.0226 (16) | 0.0087 (15) | 0.0198 (17) |
C14 | 0.050 (2) | 0.072 (3) | 0.058 (2) | 0.0071 (17) | 0.0023 (18) | 0.0170 (19) |
C13 | 0.070 (2) | 0.062 (2) | 0.101 (3) | 0.0099 (19) | −0.021 (2) | 0.010 (2) |
C3—C4 | 1.489 (5) | C10—H10B | 0.96 |
C4—O2 | 1.210 (4) | C10—H10C | 0.96 |
C13—C14 | 1.494 (5) | N11—C12 | 1.328 (5) |
C14—O12 | 1.204 (4) | N11—C16 | 1.466 (4) |
N1—C2 | 1.325 (4) | N11—H11 | 0.86 |
N1—C6 | 1.469 (4) | O11—C12 | 1.236 (4) |
N1—H1 | 0.86 | C17—C16 | 1.516 (5) |
C2—O1 | 1.246 (4) | C17—C18 | 1.524 (5) |
C2—C3 | 1.511 (5) | C17—H17A | 0.97 |
C3—H3A | 0.97 | C17—H17B | 0.97 |
C3—H3B | 0.97 | C18—C19 | 1.497 (6) |
C4—C5 | 1.500 (6) | C18—C20 | 1.521 (7) |
C5—C6 | 1.510 (5) | C18—H18 | 0.98 |
C5—H5A | 0.97 | C19—H19A | 0.96 |
C5—H5B | 0.97 | C19—H19B | 0.96 |
C6—C7 | 1.523 (5) | C19—H19C | 0.96 |
C6—H6 | 0.98 | C20—H20A | 0.96 |
C7—C8 | 1.520 (6) | C20—H20B | 0.96 |
C7—H7A | 0.97 | C20—H20C | 0.96 |
C7—H7B | 0.97 | C12—C13 | 1.498 (5) |
C8—C10 | 1.513 (8) | C16—C15 | 1.526 (5) |
C8—C9 | 1.535 (7) | C16—H16 | 0.98 |
C8—H8 | 0.98 | C15—C14 | 1.488 (5) |
C9—H9A | 0.96 | C15—H15A | 0.97 |
C9—H9B | 0.96 | C15—H15B | 0.97 |
C9—H9C | 0.96 | C13—H13A | 0.97 |
C10—H10A | 0.96 | C13—H13B | 0.97 |
C2—N1—C6 | 125.7 (3) | C12—N11—C16 | 125.5 (3) |
C2—N1—H1 | 117.2 | C12—N11—H11 | 117.3 |
C6—N1—H1 | 117.2 | C16—N11—H11 | 117.3 |
O1—C2—N1 | 122.1 (3) | C16—C17—C18 | 116.1 (3) |
O1—C2—C3 | 119.8 (3) | C16—C17—H17A | 108.3 |
N1—C2—C3 | 118.1 (3) | C18—C17—H17A | 108.3 |
C4—C3—C2 | 117.2 (3) | C16—C17—H17B | 108.3 |
C4—C3—H3A | 108 | C18—C17—H17B | 108.3 |
C2—C3—H3A | 108 | H17A—C17—H17B | 107.4 |
C4—C3—H3B | 108 | C19—C18—C20 | 112.4 (5) |
C2—C3—H3B | 108 | C19—C18—C17 | 113.5 (3) |
H3A—C3—H3B | 107.2 | C20—C18—C17 | 109.7 (4) |
O2—C4—C3 | 120.8 (4) | C19—C18—H18 | 106.9 |
O2—C4—C5 | 123.1 (3) | C20—C18—H18 | 106.9 |
C3—C4—C5 | 116.2 (3) | C17—C18—H18 | 106.9 |
C4—C5—C6 | 111.3 (3) | C18—C19—H19A | 109.5 |
C4—C5—H5A | 109.4 | C18—C19—H19B | 109.5 |
C6—C5—H5A | 109.4 | H19A—C19—H19B | 109.5 |
C4—C5—H5B | 109.4 | C18—C19—H19C | 109.5 |
C6—C5—H5B | 109.4 | H19A—C19—H19C | 109.5 |
H5A—C5—H5B | 108 | H19B—C19—H19C | 109.5 |
N1—C6—C5 | 109.6 (3) | C18—C20—H20A | 109.5 |
N1—C6—C7 | 109.9 (3) | C18—C20—H20B | 109.5 |
C5—C6—C7 | 111.8 (3) | H20A—C20—H20B | 109.5 |
N1—C6—H6 | 108.5 | C18—C20—H20C | 109.5 |
C5—C6—H6 | 108.5 | H20A—C20—H20C | 109.5 |
C7—C6—H6 | 108.5 | H20B—C20—H20C | 109.5 |
C8—C7—C6 | 114.7 (3) | O11—C12—N11 | 123.2 (3) |
C8—C7—H7A | 108.6 | O11—C12—C13 | 120.4 (4) |
C6—C7—H7A | 108.6 | N11—C12—C13 | 116.3 (3) |
C8—C7—H7B | 108.6 | N11—C16—C17 | 108.2 (3) |
C6—C7—H7B | 108.6 | N11—C16—C15 | 108.6 (3) |
H7A—C7—H7B | 107.6 | C17—C16—C15 | 112.8 (3) |
C10—C8—C7 | 110.5 (4) | N11—C16—H16 | 109 |
C10—C8—C9 | 111.4 (5) | C17—C16—H16 | 109 |
C7—C8—C9 | 110.2 (4) | C15—C16—H16 | 109 |
C10—C8—H8 | 108.2 | C14—C15—C16 | 114.2 (3) |
C7—C8—H8 | 108.2 | C14—C15—H15A | 108.7 |
C9—C8—H8 | 108.2 | C16—C15—H15A | 108.7 |
C8—C9—H9A | 109.5 | C14—C15—H15B | 108.7 |
C8—C9—H9B | 109.5 | C16—C15—H15B | 108.7 |
H9A—C9—H9B | 109.5 | H15A—C15—H15B | 107.6 |
C8—C9—H9C | 109.5 | O12—C14—C15 | 122.5 (3) |
H9A—C9—H9C | 109.5 | O12—C14—C13 | 120.1 (3) |
H9B—C9—H9C | 109.5 | C15—C14—C13 | 117.3 (3) |
C8—C10—H10A | 109.5 | C14—C13—C12 | 116.9 (3) |
C8—C10—H10B | 109.5 | C14—C13—H13A | 108.1 |
H10A—C10—H10B | 109.5 | C12—C13—H13A | 108.1 |
C8—C10—H10C | 109.5 | C14—C13—H13B | 108.1 |
H10A—C10—H10C | 109.5 | C12—C13—H13B | 108.1 |
H10B—C10—H10C | 109.5 | H13A—C13—H13B | 107.3 |
N1—C2—C3—C4 | 12.6 (5) | C2—C3—C4—O2 | −168.9 (4) |
C2—C3—C4—C5 | 11.0 (5) | O2—C4—C5—C6 | 135.9 (4) |
C3—C4—C5—C6 | −43.9 (5) | C2—N1—C6—C7 | −155.4 (3) |
C4—C5—C6—N1 | 52.7 (4) | N1—C6—C7—C8 | −160.3 (3) |
C2—N1—C6—C5 | −32.1 (5) | C5—C6—C7—C8 | 77.7 (4) |
C6—N1—C2—C3 | −1.1 (5) | C6—C7—C8—C10 | 78.3 (5) |
C4—C5—C6—C7 | 174.8 (3) | C6—C7—C8—C9 | −158.2 (4) |
N11—C12—C13—C14 | 27.0 (6) | C16—C17—C18—C19 | 60.2 (5) |
C15—C14—C13—C12 | −16.2 (6) | C16—C17—C18—C20 | −173.2 (4) |
C16—C15—C14—C13 | −21.6 (5) | C16—N11—C12—O11 | −174.5 (3) |
N11—C16—C15—C14 | 47.2 (4) | C12—N11—C16—C17 | −163.0 (3) |
C12—N11—C16—C15 | −40.1 (4) | C18—C17—C16—N11 | −177.0 (3) |
C16—N11—C12—C13 | 3.0 (5) | C18—C17—C16—C15 | 62.7 (4) |
C17—C16—C15—C14 | 167.2 (3) | C16—C15—C14—O12 | 160.5 (4) |
C6—N1—C2—O1 | −178.9 (3) | O12—C14—C13—C12 | 161.7 (4) |
O1—C2—C3—C4 | −169.5 (3) | O11—C12—C13—C14 | −155.4 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O11 | 0.86 | 2.04 | 2.899 (3) | 176 |
N11—H11···O1 | 0.86 | 2.05 | 2.878 (3) | 161 |
C9H17NO2 | F(000) = 376 |
Mr = 171.24 | Dx = 1.166 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 2173 reflections |
a = 12.9121 (6) Å | θ = 1.0–26.4° |
b = 5.3871 (3) Å | µ = 0.08 mm−1 |
c = 14.8945 (7) Å | T = 100 K |
β = 109.692 (2)° | Prism, colorless |
V = 975.45 (8) Å3 | 0.2 × 0.1 × 0.1 mm |
Z = 4 |
Nonius KAPPACCD diffractometer | 1760 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.079 |
Graphite monochromator | θmax = 26.3°, θmin = 2.6° |
oscillation scans | h = −16→16 |
18084 measured reflections | k = −6→6 |
2196 independent reflections | l = −18→17 |
Refinement on F2 | 7 restraints |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.043 | w = 1/[σ2(Fo2) + (0.0769P)2 + 0.0386P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.114 | (Δ/σ)max = 0.002 |
S = 1.01 | Δρmax = 0.16 e Å−3 |
2196 reflections | Δρmin = −0.19 e Å−3 |
236 parameters |
C9H17NO2 | V = 975.45 (8) Å3 |
Mr = 171.24 | Z = 4 |
Monoclinic, P21 | Mo Kα radiation |
a = 12.9121 (6) Å | µ = 0.08 mm−1 |
b = 5.3871 (3) Å | T = 100 K |
c = 14.8945 (7) Å | 0.2 × 0.1 × 0.1 mm |
β = 109.692 (2)° |
Nonius KAPPACCD diffractometer | 1760 reflections with I > 2σ(I) |
18084 measured reflections | Rint = 0.079 |
2196 independent reflections |
R[F2 > 2σ(F2)] = 0.043 | 7 restraints |
wR(F2) = 0.114 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.16 e Å−3 |
2196 reflections | Δρmin = −0.19 e Å−3 |
236 parameters |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
O1 | 0.67946 (11) | 0.6828 (3) | 1.04958 (10) | 0.0319 (4) | |
N1 | 0.68232 (14) | 0.7075 (4) | 0.89926 (12) | 0.0295 (5) | |
H1 | 0.7277 | 0.5802 | 0.9122 | 0.035* | |
C2 | 0.64628 (17) | 0.7824 (5) | 0.96856 (15) | 0.0291 (6) | |
O2 | 0.4449 (4) | 1.2792 (11) | 0.8307 (4) | 0.0404 (11) | 0.712 (8) |
H2 | 0.4097 | 1.2476 | 0.8675 | 0.061* | 0.712 (8) |
C3 | 0.5635 (2) | 0.9892 (5) | 0.94855 (17) | 0.0379 (6) | 0.712 (8) |
H3A | 0.5883 | 1.1094 | 1.0018 | 0.045* | 0.712 (8) |
H3B | 0.4929 | 0.9186 | 0.949 | 0.045* | 0.712 (8) |
C4 | 0.5416 (3) | 1.1311 (8) | 0.8560 (2) | 0.0315 (11) | 0.712 (8) |
H4 | 0.6053 | 1.2451 | 0.8645 | 0.038* | 0.712 (8) |
C5 | 0.5391 (3) | 0.9472 (8) | 0.7780 (2) | 0.0295 (10) | 0.712 (8) |
H5A | 0.5218 | 1.0351 | 0.7163 | 0.035* | 0.712 (8) |
H5B | 0.4811 | 0.8216 | 0.7718 | 0.035* | 0.712 (8) |
C6 | 0.6543 (2) | 0.8153 (5) | 0.80329 (16) | 0.0331 (6) | 0.712 (8) |
H6 | 0.7118 | 0.9371 | 0.8011 | 0.04* | 0.712 (8) |
C7 | 0.6439 (2) | 0.6083 (5) | 0.73134 (17) | 0.0372 (6) | |
H7A | 0.7047 | 0.4889 | 0.7586 | 0.045* | |
H7B | 0.574 | 0.5189 | 0.7218 | 0.045* | |
C8 | 0.6463 (2) | 0.6931 (6) | 0.63432 (15) | 0.0405 (7) | |
H8 | 0.5987 | 0.8437 | 0.6145 | 0.049* | |
C9 | 0.5981 (3) | 0.4876 (7) | 0.56153 (19) | 0.0618 (9) | |
H9A | 0.603 | 0.5362 | 0.4997 | 0.093* | |
H9B | 0.5208 | 0.4609 | 0.5551 | 0.093* | |
H9C | 0.6395 | 0.3338 | 0.5831 | 0.093* | |
C10 | 0.7618 (2) | 0.7602 (8) | 0.63802 (19) | 0.0609 (9) | |
H10A | 0.8096 | 0.6147 | 0.6578 | 0.091* | |
H10B | 0.7901 | 0.8949 | 0.684 | 0.091* | |
H10C | 0.7601 | 0.8143 | 0.5747 | 0.091* | |
O21 | 0.4302 (11) | 1.203 (2) | 0.8175 (9) | 0.034 (3)* | 0.288 (8) |
H21 | 0.3853 | 1.1942 | 0.8472 | 0.052* | 0.288 (8) |
C31 | 0.5635 (2) | 0.9892 (5) | 0.94855 (17) | 0.0379 (6) | 0.288 (8) |
H31A | 0.5108 | 0.9588 | 0.9826 | 0.045* | 0.288 (8) |
H31B | 0.6012 | 1.149 | 0.9711 | 0.045* | 0.288 (8) |
C41 | 0.5033 (8) | 1.000 (3) | 0.8427 (6) | 0.035 (2)* | 0.288 (8) |
H41 | 0.4605 | 0.8434 | 0.8222 | 0.042* | 0.288 (8) |
C51 | 0.5854 (10) | 1.025 (2) | 0.7890 (7) | 0.035 (2)* | 0.288 (8) |
H51A | 0.5447 | 1.0455 | 0.7201 | 0.042* | 0.288 (8) |
H51B | 0.631 | 1.1755 | 0.8116 | 0.042* | 0.288 (8) |
C61 | 0.6543 (2) | 0.8153 (5) | 0.80329 (16) | 0.0331 (6) | 0.288 (8) |
H61 | 0.7258 | 0.8926 | 0.8064 | 0.04* | 0.288 (8) |
O11 | 0.81679 (11) | 0.2582 (3) | 0.94945 (9) | 0.0299 (4) | |
O12 | 1.06794 (13) | −0.2869 (4) | 1.17635 (11) | 0.0353 (4) | |
H12 | 1.1077 | −0.3 | 1.1421 | 0.053* | |
N11 | 0.83492 (14) | 0.2784 (4) | 1.10496 (12) | 0.0288 (5) | |
H11 | 0.7832 | 0.3926 | 1.0901 | 0.035* | |
C12 | 0.85924 (16) | 0.1795 (5) | 1.03320 (14) | 0.0260 (5) | |
C13 | 0.93683 (17) | −0.0382 (5) | 1.05320 (15) | 0.0293 (5) | |
H13A | 0.9836 | −0.0246 | 1.0126 | 0.035* | |
H13B | 0.8934 | −0.1929 | 1.0353 | 0.035* | |
C14 | 1.01056 (18) | −0.0561 (5) | 1.15703 (15) | 0.0304 (6) | |
H14 | 1.0651 | 0.0828 | 1.1718 | 0.037* | |
C15 | 0.94089 (19) | −0.0340 (5) | 1.21962 (15) | 0.0314 (5) | |
H15A | 0.9876 | −0.0562 | 1.2871 | 0.038* | |
H15B | 0.8844 | −0.1664 | 1.2031 | 0.038* | |
C16 | 0.88493 (17) | 0.2184 (5) | 1.20713 (14) | 0.0293 (5) | |
H16 | 0.9419 | 0.3467 | 1.2376 | 0.035* | |
C17 | 0.79473 (18) | 0.2343 (5) | 1.25201 (15) | 0.0331 (6) | |
H17A | 0.7392 | 0.1044 | 1.2232 | 0.04* | |
H17B | 0.7577 | 0.3973 | 1.2356 | 0.04* | |
C18 | 0.8344 (2) | 0.2037 (6) | 1.36104 (16) | 0.0407 (7) | |
H18 | 0.8738 | 0.0412 | 1.3769 | 0.049* | |
C19 | 0.9146 (3) | 0.4062 (7) | 1.4117 (2) | 0.0639 (9) | |
H19A | 0.8802 | 0.5689 | 1.3928 | 0.096* | |
H19B | 0.981 | 0.3946 | 1.394 | 0.096* | |
H19C | 0.9343 | 0.3857 | 1.4808 | 0.096* | |
C20 | 0.7355 (3) | 0.1922 (9) | 1.3941 (2) | 0.0708 (11) | |
H20A | 0.7603 | 0.1601 | 1.4629 | 0.106* | |
H20B | 0.6864 | 0.0585 | 1.3603 | 0.106* | |
H20C | 0.6961 | 0.3508 | 1.3805 | 0.106* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0310 (8) | 0.0337 (10) | 0.0313 (8) | 0.0044 (8) | 0.0108 (6) | 0.0069 (8) |
N1 | 0.0324 (10) | 0.0256 (11) | 0.0307 (9) | 0.0042 (10) | 0.0111 (8) | 0.0029 (9) |
C2 | 0.0244 (11) | 0.0287 (14) | 0.0341 (13) | −0.0009 (11) | 0.0098 (9) | 0.0023 (11) |
O2 | 0.037 (2) | 0.042 (3) | 0.048 (2) | 0.017 (2) | 0.0214 (18) | 0.019 (2) |
C3 | 0.0400 (13) | 0.0397 (16) | 0.0373 (13) | 0.0115 (14) | 0.0174 (10) | 0.0073 (13) |
C4 | 0.0275 (19) | 0.031 (2) | 0.0386 (19) | 0.0057 (18) | 0.0140 (14) | 0.0073 (17) |
C5 | 0.0230 (18) | 0.0264 (19) | 0.0369 (18) | −0.0010 (17) | 0.0070 (14) | 0.0055 (16) |
C6 | 0.0406 (13) | 0.0266 (13) | 0.0315 (12) | 0.0016 (12) | 0.0112 (10) | 0.0029 (11) |
C7 | 0.0395 (13) | 0.0292 (14) | 0.0374 (13) | 0.0042 (12) | 0.0056 (10) | −0.0020 (11) |
C8 | 0.0459 (13) | 0.0420 (17) | 0.0283 (11) | 0.0127 (15) | 0.0054 (10) | −0.0006 (13) |
C9 | 0.078 (2) | 0.060 (2) | 0.0373 (15) | 0.0108 (19) | 0.0059 (13) | −0.0103 (16) |
C10 | 0.0569 (16) | 0.091 (3) | 0.0349 (13) | 0.007 (2) | 0.0157 (12) | 0.0043 (18) |
C31 | 0.0400 (13) | 0.0397 (16) | 0.0373 (13) | 0.0115 (14) | 0.0174 (10) | 0.0073 (13) |
C61 | 0.0406 (13) | 0.0266 (13) | 0.0315 (12) | 0.0016 (12) | 0.0112 (10) | 0.0029 (11) |
O11 | 0.0298 (8) | 0.0322 (10) | 0.0267 (8) | 0.0029 (8) | 0.0081 (6) | 0.0025 (8) |
O12 | 0.0354 (9) | 0.0344 (10) | 0.0382 (9) | 0.0114 (9) | 0.0153 (7) | 0.0078 (9) |
N11 | 0.0281 (9) | 0.0282 (11) | 0.0287 (9) | 0.0052 (10) | 0.0078 (7) | 0.0040 (9) |
C12 | 0.0220 (10) | 0.0241 (13) | 0.0305 (12) | −0.0036 (11) | 0.0071 (8) | −0.0005 (11) |
C13 | 0.0286 (11) | 0.0290 (13) | 0.0311 (11) | 0.0010 (12) | 0.0112 (9) | −0.0006 (11) |
C14 | 0.0312 (12) | 0.0260 (13) | 0.0328 (12) | 0.0041 (12) | 0.0092 (9) | 0.0028 (11) |
C15 | 0.0331 (12) | 0.0321 (13) | 0.0283 (11) | 0.0020 (12) | 0.0095 (9) | 0.0042 (12) |
C16 | 0.0285 (11) | 0.0295 (13) | 0.0266 (10) | 0.0000 (12) | 0.0053 (8) | 0.0006 (11) |
C17 | 0.0338 (12) | 0.0346 (14) | 0.0306 (11) | 0.0058 (12) | 0.0104 (9) | 0.0020 (11) |
C18 | 0.0473 (14) | 0.0426 (16) | 0.0338 (12) | 0.0140 (15) | 0.0160 (10) | 0.0066 (13) |
C19 | 0.090 (2) | 0.055 (2) | 0.0366 (15) | 0.004 (2) | 0.0084 (14) | −0.0063 (15) |
C20 | 0.0694 (19) | 0.108 (3) | 0.0475 (16) | 0.026 (2) | 0.0354 (14) | 0.019 (2) |
O1—C2 | 1.257 (3) | C41—H41 | 1 |
N1—C2 | 1.330 (3) | C51—H51A | 0.99 |
N1—C6 | 1.471 (3) | C51—H51B | 0.99 |
N1—H1 | 0.88 | O11—C12 | 1.255 (2) |
C2—C3 | 1.503 (4) | O12—C14 | 1.426 (3) |
O2—C4 | 1.422 (5) | O12—H12 | 0.84 |
O2—H2 | 0.84 | N11—C12 | 1.323 (3) |
C3—C4 | 1.517 (4) | N11—C16 | 1.475 (3) |
C3—H3A | 0.99 | N11—H11 | 0.88 |
C3—H3B | 0.99 | C12—C13 | 1.505 (3) |
C4—C5 | 1.519 (6) | C13—C14 | 1.522 (3) |
C4—H4 | 1 | C13—H13A | 0.99 |
C5—C6 | 1.575 (4) | C13—H13B | 0.99 |
C5—H5A | 0.99 | C14—C15 | 1.503 (3) |
C5—H5B | 0.99 | C14—H14 | 1 |
C6—C7 | 1.521 (3) | C15—C16 | 1.521 (4) |
C6—H6 | 1 | C15—H15A | 0.99 |
C7—C8 | 1.526 (3) | C15—H15B | 0.99 |
C7—H7A | 0.99 | C16—C17 | 1.528 (3) |
C7—H7B | 0.99 | C16—H16 | 1 |
C8—C10 | 1.517 (4) | C17—C18 | 1.538 (3) |
C8—C9 | 1.528 (4) | C17—H17A | 0.99 |
C8—H8 | 1 | C17—H17B | 0.99 |
C9—H9A | 0.98 | C18—C20 | 1.516 (4) |
C9—H9B | 0.98 | C18—C19 | 1.518 (5) |
C9—H9C | 0.98 | C18—H18 | 1 |
C10—H10A | 0.98 | C19—H19A | 0.98 |
C10—H10B | 0.98 | C19—H19B | 0.98 |
C10—H10C | 0.98 | C19—H19C | 0.98 |
O21—C41 | 1.410 (17) | C20—H20A | 0.98 |
O21—H21 | 0.84 | C20—H20B | 0.98 |
C41—C51 | 1.533 (13) | C20—H20C | 0.98 |
C2—N1—C6 | 126.8 (2) | C41—C51—H51A | 109.4 |
C2—N1—H1 | 116.6 | C41—C51—H51B | 109.4 |
C6—N1—H1 | 116.6 | H51A—C51—H51B | 108 |
O1—C2—N1 | 121.4 (2) | C14—O12—H12 | 109.5 |
O1—C2—C3 | 119.78 (19) | C12—N11—C16 | 127.2 (2) |
N1—C2—C3 | 118.86 (19) | C12—N11—H11 | 116.4 |
C2—C3—C4 | 117.1 (2) | C16—N11—H11 | 116.4 |
C2—C3—H3A | 108 | O11—C12—N11 | 121.6 (2) |
C4—C3—H3A | 108 | O11—C12—C13 | 119.90 (19) |
C2—C3—H3B | 108 | N11—C12—C13 | 118.50 (18) |
C4—C3—H3B | 108 | C12—C13—C14 | 113.42 (19) |
H3A—C3—H3B | 107.3 | C12—C13—H13A | 108.9 |
O2—C4—C3 | 113.7 (3) | C14—C13—H13A | 108.9 |
O2—C4—C5 | 111.9 (4) | C12—C13—H13B | 108.9 |
C3—C4—C5 | 108.4 (3) | C14—C13—H13B | 108.9 |
O2—C4—H4 | 107.5 | H13A—C13—H13B | 107.7 |
C3—C4—H4 | 107.5 | O12—C14—C15 | 108.8 (2) |
C5—C4—H4 | 107.5 | O12—C14—C13 | 111.4 (2) |
C4—C5—C6 | 109.7 (3) | C15—C14—C13 | 108.98 (18) |
C4—C5—H5A | 109.7 | O12—C14—H14 | 109.2 |
C6—C5—H5A | 109.7 | C15—C14—H14 | 109.2 |
C4—C5—H5B | 109.7 | C13—C14—H14 | 109.2 |
C6—C5—H5B | 109.7 | C14—C15—C16 | 110.7 (2) |
H5A—C5—H5B | 108.2 | C14—C15—H15A | 109.5 |
N1—C6—C7 | 109.3 (2) | C16—C15—H15A | 109.5 |
N1—C6—C5 | 108.3 (2) | C14—C15—H15B | 109.5 |
C7—C6—C5 | 108.1 (2) | C16—C15—H15B | 109.5 |
N1—C6—H6 | 110.4 | H15A—C15—H15B | 108.1 |
C7—C6—H6 | 110.4 | N11—C16—C15 | 110.29 (19) |
C5—C6—H6 | 110.4 | N11—C16—C17 | 107.81 (16) |
C8—C7—C6 | 115.0 (2) | C15—C16—C17 | 113.4 (2) |
C8—C7—H7A | 108.5 | N11—C16—H16 | 108.4 |
C6—C7—H7A | 108.5 | C15—C16—H16 | 108.4 |
C8—C7—H7B | 108.5 | C17—C16—H16 | 108.4 |
C6—C7—H7B | 108.5 | C16—C17—C18 | 115.09 (18) |
H7A—C7—H7B | 107.5 | C16—C17—H17A | 108.5 |
C10—C8—C7 | 111.71 (19) | C18—C17—H17A | 108.5 |
C10—C8—C9 | 111.0 (2) | C16—C17—H17B | 108.5 |
C7—C8—C9 | 108.8 (3) | C18—C17—H17B | 108.5 |
C10—C8—H8 | 108.4 | H17A—C17—H17B | 107.5 |
C7—C8—H8 | 108.4 | C20—C18—C19 | 112.1 (3) |
C9—C8—H8 | 108.4 | C20—C18—C17 | 109.3 (2) |
C8—C9—H9A | 109.5 | C19—C18—C17 | 112.1 (2) |
C8—C9—H9B | 109.5 | C20—C18—H18 | 107.7 |
H9A—C9—H9B | 109.5 | C19—C18—H18 | 107.7 |
C8—C9—H9C | 109.5 | C17—C18—H18 | 107.7 |
H9A—C9—H9C | 109.5 | C18—C19—H19A | 109.5 |
H9B—C9—H9C | 109.5 | C18—C19—H19B | 109.5 |
C8—C10—H10A | 109.5 | H19A—C19—H19B | 109.5 |
C8—C10—H10B | 109.5 | C18—C19—H19C | 109.5 |
H10A—C10—H10B | 109.5 | H19A—C19—H19C | 109.5 |
C8—C10—H10C | 109.5 | H19B—C19—H19C | 109.5 |
H10A—C10—H10C | 109.5 | C18—C20—H20A | 109.5 |
H10B—C10—H10C | 109.5 | C18—C20—H20B | 109.5 |
C41—O21—H21 | 109.5 | H20A—C20—H20B | 109.5 |
O21—C41—C51 | 108.2 (10) | C18—C20—H20C | 109.5 |
O21—C41—H41 | 108.8 | H20A—C20—H20C | 109.5 |
C51—C41—H41 | 108.8 | H20B—C20—H20C | 109.5 |
N11—C12—C13—C14 | −22.1 (3) | C61—N1—C2—C3 | 3.6 (4) |
C12—C13—C14—C15 | 49.3 (3) | C2—C31—C41—O21 | −175.2 (8) |
C13—C14—C15—C16 | −62.7 (3) | C2—N1—C61—C7 | −142.6 (2) |
C14—C15—C16—N11 | 46.8 (2) | C6—N1—C2—O1 | −176.9 (2) |
C15—C16—N11—C12 | −19.8 (3) | C6—N1—C2—C3 | 3.6 (4) |
C16—N11—C12—C13 | 7.5 (3) | O1—C2—C3—C4 | 169.7 (3) |
C12—C13—C14—O12 | 169.41 (19) | O2—C4—C5—C6 | 172.1 (3) |
C14—C15—C16—C17 | 167.86 (18) | C2—N1—C6—C7 | −142.7 (2) |
N1—C2—C3—C4 | −10.8 (4) | N1—C6—C7—C8 | −164.04 (19) |
C2—C3—C4—C5 | 40.1 (4) | C5—C6—C7—C8 | 78.3 (3) |
C3—C4—C5—C6 | −61.8 (4) | C6—C7—C8—C10 | 75.7 (3) |
C4—C5—C6—N1 | 53.9 (4) | C6—C7—C8—C9 | −161.5 (2) |
C5—C6—N1—C2 | −25.1 (4) | C16—N11—C12—O11 | −174.7 (2) |
C2—C3—C4—O2 | 165.2 (4) | O11—C12—C13—C14 | 160.0 (2) |
C4—C5—C6—C7 | 172.2 (3) | O12—C14—C15—C16 | 175.55 (17) |
N1—C2—C31—C41 | 23.3 (6) | C12—N11—C16—C17 | −144.1 (2) |
C2—C31—C41—C51 | −55 (1) | N11—C16—C17—C18 | −173.9 (2) |
C31—C41—C51—C61 | 63 (1) | C15—C16—C17—C18 | 63.7 (3) |
C41—C51—C61—N1 | −35 (1) | C16—C17—C18—C20 | −173.2 (3) |
C51—C61—N1—C2 | 2.7 (7) | C16—C17—C18—C19 | 61.9 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O11 | 0.88 | 2.05 | 2.925 (3) | 172 |
N11—H11···O1 | 0.88 | 2.01 | 2.888 (3) | 172 |
O12—H12···O11i | 0.84 | 1.95 | 2.769 (2) | 164 |
O2—H2···O1ii | 0.84 | 1.98 | 2.821 (5) | 177 |
O21—H21···O1ii | 0.84 | 1.98 | 2.797 (14) | 163 |
Symmetry codes: (i) −x+2, y−1/2, −z+2; (ii) −x+1, y+1/2, −z+2. |
Experimental details
(II) | (III_IV) | |
Crystal data | ||
Chemical formula | C9H15NO2 | C9H17NO2 |
Mr | 169.22 | 171.24 |
Crystal system, space group | Triclinic, P1 | Monoclinic, P21 |
Temperature (K) | 293 | 100 |
a, b, c (Å) | 5.0760 (2), 10.0760 (4), 10.1210 (5) | 12.9121 (6), 5.3871 (3), 14.8945 (7) |
α, β, γ (°) | 95.691 (1), 102.529 (1), 103.730 (2) | 90, 109.692 (2), 90 |
V (Å3) | 484.65 (4) | 975.45 (8) |
Z | 2 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.08 | 0.08 |
Crystal size (mm) | 0.2 × 0.1 × 0.1 | 0.2 × 0.1 × 0.1 |
Data collection | ||
Diffractometer | Nonius KAPPACCD diffractometer | Nonius KAPPACCD diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7698, 1959, 1334 | 18084, 2196, 1760 |
Rint | 0.040 | 0.079 |
(sin θ/λ)max (Å−1) | 0.623 | 0.624 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.043, 0.118, 0.94 | 0.043, 0.114, 1.01 |
No. of reflections | 1959 | 2196 |
No. of parameters | 217 | 236 |
No. of restraints | 5 | 7 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.14, −0.14 | 0.16, −0.19 |
Computer programs: COLLECT (Nonius, 1998), COLLECT software (Nonius, 1998), COLLECT, HKL Suite (Otwinoski & Minor, 1997), SIR92 (Altomare et al., 1994), SIR_92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997) and WebLab ViewerPro 3.5 (MSI, 1999), ORTEP-3 for Windows (Farrugia, 1997), WebLab ViewerPro 3.5 (MSI, 1999), WinGX (Farrugia, 1999), WinGX publication routines (Farrugia, 1999).
C3—C4 | 1.489 (5) | C13—C14 | 1.494 (5) |
C4—O2 | 1.210 (4) | C14—O12 | 1.204 (4) |
N1—C2—C3—C4 | 12.6 (5) | N11—C12—C13—C14 | 27.0 (6) |
C2—C3—C4—C5 | 11.0 (5) | C15—C14—C13—C12 | −16.2 (6) |
C3—C4—C5—C6 | −43.9 (5) | C16—C15—C14—C13 | −21.6 (5) |
C4—C5—C6—N1 | 52.7 (4) | N11—C16—C15—C14 | 47.2 (4) |
C2—N1—C6—C5 | −32.1 (5) | C12—N11—C16—C15 | −40.1 (4) |
C6—N1—C2—C3 | −1.1 (5) | C16—N11—C12—C13 | 3.0 (5) |
C4—C5—C6—C7 | 174.8 (3) | C17—C16—C15—C14 | 167.2 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O11 | 0.86 | 2.04 | 2.899 (3) | 176 |
N11—H11···O1 | 0.86 | 2.05 | 2.878 (3) | 161 |
N11—C12—C13—C14 | −22.1 (3) | C5—C6—N1—C2 | −25.1 (4) |
C12—C13—C14—C15 | 49.3 (3) | C2—C3—C4—O2 | 165.2 (4) |
C13—C14—C15—C16 | −62.7 (3) | C4—C5—C6—C7 | 172.2 (3) |
C14—C15—C16—N11 | 46.8 (2) | N1—C2—C31—C41 | 23.3 (6) |
C15—C16—N11—C12 | −19.8 (3) | C2—C31—C41—C51 | −55 (1) |
C16—N11—C12—C13 | 7.5 (3) | C31—C41—C51—C61 | 63 (1) |
C12—C13—C14—O12 | 169.41 (19) | C41—C51—C61—N1 | −35 (1) |
C14—C15—C16—C17 | 167.86 (18) | C51—C61—N1—C2 | 2.7 (7) |
N1—C2—C3—C4 | −10.8 (4) | C61—N1—C2—C3 | 3.6 (4) |
C2—C3—C4—C5 | 40.1 (4) | C2—C31—C41—O21 | −175.2 (8) |
C3—C4—C5—C6 | −61.8 (4) | C2—N1—C61—C7 | −142.6 (2) |
C4—C5—C6—N1 | 53.9 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O11 | 0.88 | 2.05 | 2.925 (3) | 172 |
N11—H11···O1 | 0.88 | 2.01 | 2.888 (3) | 172 |
O12—H12···O11i | 0.84 | 1.95 | 2.769 (2) | 164 |
O2—H2···O1ii | 0.84 | 1.98 | 2.821 (5) | 177 |
O21—H21···O1ii | 0.84 | 1.98 | 2.797 (14) | 163 |
Symmetry codes: (i) −x+2, y−1/2, −z+2; (ii) −x+1, y+1/2, −z+2. |
As part of a programme to synthesize enantiopure monohydroxylated δ-lactams, we recently introduced 6-substituted-2,4-dioxopiperidine-1-carboxylates as novel chiral adducts for the asymmetric synthesis of 4-hydroxy-6-substituted-2-oxopiperidine-1-carboxylate. In this series, the pseudo-axial orientation of the side chain at the 6-position [resulting from minimization of the allylic A(1,3) strain] is believed to account for the high stereoselectivity observed in the reduction of the 4-oxo group. A variety of reductive agents and conditions have been explored. Treatment of lactam (I), bearing an isobutyl side chain at atom C6, with NaBH4 in a mixture of CH2Cl2 and 10% acetic acid affords the desired 4-hydroxy derivative in 93% yield with a 90:10 cis/trans ratio (Didierjean et al., 2003).
Surprisingly, the attempt to reduce (I) with tetramethylammonium triacetoxyborohydride in a mixture of MeCN and 15% acetic acid resulted exclusively in removal of the Boc (butyloxycarbonyl) protecting group and afforded (6S)-6-isobutyl-2,4-dioxopiperidine, (II), in 84% yield. Subsequent reduction of (II) with NaBH4 in a mixture of CH2Cl2/AcOH (9:1) gave the corresponding 4-hydroxy-6-isobutyl-2-oxopiperidine, in an 84:16 cis/trans ratio; the (4R,6S) and (4S,6S) isomers are denoted (III) and (IV), respectively The overall yield was 62% and the ratio of isomers was determined by NMR analysis of the reaction mixture. The reduction of (II) is driven by torsional effects that favour attack of the hydride reagent across the axial face of the C=O bond. A similar selectivity (85:15 cis/trans) was reported by Davis and co-workers in the reduction of the related enantiopure (R)-6-phenylpiperidine-2,4-dione (Davis et al., 2000). We present here the results of the X-ray crystallographic analyses of (II), (III) and (IV).
Compound (II) crystallizes with two independent molecules, (IIA) and (IIB), in the asymmetric unit in a triclinic cell. A view of the independent molecules with the atom numbering schemes is shown in Fig. 1. A l l bond distances and angles fall in normal limits (Allen et al., 1987) and are in agreement with the geometry of similar piperidine rings (Didierjean et al., 2003; Marin et al., 2002; Thomas et al., 1996; Bocelli & Grenier-Loustalot, 1981). The S configuration of the C atom at the 6-position of the piperidine ring was assumed from the precursor Boc-β-L-Leu-OH compound (Seebach et al., 1996). Both independent molecules, (IIA) and (IIB), reveal that the keto tautomer is favoured over the enol tautomer in the solid state. This preference is evident from the observed C3—C4 and C4—O2 bond distances in (IIA) [C13—C14 and C14—O12 in (IIB)], which are consistent with single and double bonds, respectively (Table 1). Molecules (IIA) and (IIB) show a similar conformation (Table 1). Both independent piperidine rings adopt a twisted-boat conformation, with the isobutyl group in an equatorial orientation. The C3—C4—C5—C6 and C13—C14—C15—C16 torsion angles [−43.9 (4)° and −21.6 (5)°, respectively] reveal that the conformation is more twisted in (IIA) than in (IIB).
X-ray analysis of crystals obtained from the mixture of (III) and (IV) reveals a monoclinic cell, with two independent molecules in the asymmetric unit. In one of two independent molecules, the C atoms at the 4- and 5-positions and the hydroxy group of the piperidine ring are disordered, leading to a mixture of (III) and (IV) in a 0.712 (8):0.288 (8) ratio. No detectable disorder was observed in the other independent molecule, which is the major diastereomer formed by the reduction of (II), i.e. the diastereomer (4R,6S). Thus the asymmetric unit of the crystal consists of a unit-occupancy and a 0.712 (8) occupancy (4R,6S) diastereomer (Figs. 2 and 3), and a 0.288 (8) occupancy (4S,6S) diastereomer (Fig. 4). The (4R,6S):(4S,6S) ratio in the crystals, determined by crystallographic refinement, is thus 1.712:0.288 (or 86:14), in very good agreement with NMR analysis of the reaction mixture. NMR measurements on the dissolved crystals confirmed that a mixture of the (4R,6S) and (4S,6S) isomers was present in the solid state. In the three structures, the hydroxy group at the 4-position and the isobutyl side chain at the 6-position of the piperidine ring assume an equatorial orientation (Table 3). The two structures of (III) have similar piperidine ring conformations, close to half-chair. The C atom at the 5-position is displaced 0.693 (6) Å [0.610 (3) Å] from the mean plane, defined by atoms N1, C2, C3, C4 and C6 (N11, C12, C13, C14 and C16). The six-membered ring of (IV) adopts a sofa conformation, with the C atom at the 4-position displaced 0.70 (2) Å from the mean plane defined by the five other atoms of the ring. The positions of the hydroxy O atoms in the 0.712 (8)-occupancy molecule of (III) and the 0.288 (8)-occupancy molecule of (IV) are separated by? 0.46 (1) Å. Both hydroxy groups are thus involved in the same intermolecular hydrogen bonds (Table 4).
In both structures, a typical amide–amide hydrogen-bond motif (Rychlewska & Warzatis, 2000) is observed, joining the two independent molecules via two intermolecular N—H···O=C hydrogen bonds (Figs. 5 and 6, and Tables 2 and 4). The amide H atoms, which are obviously cis to the amide carbonyl O atom, form an eight-membered ring, leading to the graph-set motif R22(8) (Bernstein et al., 1995). Both crystals show a similar molecular packing, which can be described as a regular stacking of bilayers with the isopropyl groups on the surfaces (Figs. 5 and 6). In each bilayer, the hydrogen-bonded independent dimers (Tables 2 and 4) pack together, the packing? involving mainly van der Waals interactions in the crystal of (II). In the crystal of (III)/(IV), a three-dimensional hydrogen-bond network between the dimers is observed, involving the hydroxy and carbonyl groups of the piperidine rings (Table 4 and Fig. 6). It is interesting to note that the crystals of the N-Boc-protected molecules of (II) and (III) show similar stacking of bilayers, with hydrophobic heads on the surface (Didierjean et al., 2003). Nevertheless, the molecular packing mode inside a bilayer is different. Indeed, strong OH···O=C hydrogen bonds lead to infinite chains packed in a parallel fashion, via van der Waals interactions, to form a bilayer.