In 6-methyl-
N-(4-nitrobenzoyl)-5,6-dihydropyridin-2(1
H)-one, C
13H
12N
2O
4, (I), the piperidone ring is in a distorted half-chair conformation. In 8-methoxy-3-methyl-
N-(4-nitrobenzoyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline-1,6-dione, C
18H
20N
2O
6, (II), the heterocyclic ring is in a slightly distorted half-boat conformation, while the other six-membered ring is in a distorted chair conformation. Compound (II) presents a strong intramolecular C—H
O hydrogen bond. In both (I) and (II), the molecules interact through C—H
O interactions.
Supporting information
CCDC references: 173381; 173382
H atoms were located on stereochemical grounds, except those of the hydroxyl
groups, and were refined riding on a carrier atom with an isotropic
displacement parameter of 1.5 (for methyl H atoms) or 1.2 (for the other H
atoms) times the value of the equivalent isotropic displacement parameter of
the attached atom.
For both compounds, data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995). Program(s) used to solve structure: SHELXS86 (Sheldrick, 1985) for (I); SIR92 (Altomare et al., 1993) for (II). For both compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ZORTEP (Zsolnai, 1995); software used to prepare material for publication: PARST95 (Nardelli, 1995), PLATON (Spek, 1998) and WinGX (Farrugia, 1999).
Crystal data top
C13H12N2O4 | Dx = 1.386 Mg m−3 |
Mr = 260.25 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 25 reflections |
a = 7.3677 (9) Å | θ = 10.0–18.4° |
b = 10.054 (1) Å | µ = 0.11 mm−1 |
c = 16.834 (2) Å | T = 293 K |
V = 1247.0 (2) Å3 | Irregular, colourless |
Z = 4 | 0.20 × 0.10 × 0.05 mm |
F(000) = 544 | |
Data collection top
Enraf-Nonius CAD4-Mach3 diffractometer | Rint = 0.018 |
Radiation source: fine-focus sealed tube | θmax = 30.0° |
Graphite monochromator | h = −1→10 |
ω/2θ scans | k = −14→0 |
2382 measured reflections | l = 0→23 |
2098 independent reflections | 3 standard reflections every 30 min |
995 reflections with F2 > 2σF2 | intensity decay: 1.1% |
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)] = 0.037 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.103 | Riding |
S = 0.98 | w = 1/[σ2(Fo2) + (0.0692P)2 + 0.029P] where P = (Fo2 + 2Fc2)/3 |
2098 reflections | (Δ/σ)max < 0.001 |
173 parameters | Δρmax = 0.17 e Å−3 |
0 restraints | Δρmin = −0.18 e Å−3 |
Crystal data top
C13H12N2O4 | V = 1247.0 (2) Å3 |
Mr = 260.25 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.3677 (9) Å | µ = 0.11 mm−1 |
b = 10.054 (1) Å | T = 293 K |
c = 16.834 (2) Å | 0.20 × 0.10 × 0.05 mm |
Data collection top
Enraf-Nonius CAD4-Mach3 diffractometer | Rint = 0.018 |
2382 measured reflections | 3 standard reflections every 30 min |
2098 independent reflections | intensity decay: 1.1% |
995 reflections with F2 > 2σF2 | |
Refinement top
R[F2 > 2σ(F2)] = 0.037 | 0 restraints |
wR(F2) = 0.103 | Riding |
S = 0.98 | Δρmax = 0.17 e Å−3 |
2098 reflections | Δρmin = −0.18 e Å−3 |
173 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 on F2 for ALL reflections. Weighted R-factors
wR and all goodnesses of fit S are based on F2,
conventional R-factors R are based on F, with F
set to zero for negative F2. The observed criterion of F2 >
σ(F2) is used only for calculating R-factor-obs etc.
and is not relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R-factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
N1 | 0.5453 (3) | 0.1671 (2) | 0.83740 (12) | 0.0460 (5) | |
N2 | 1.1771 (4) | 0.2742 (3) | 0.57630 (15) | 0.0635 (7) | |
O1 | 0.7820 (3) | 0.3077 (2) | 0.85977 (13) | 0.0663 (6) | |
O2 | 1.3167 (4) | 0.2123 (3) | 0.56791 (18) | 0.0912 (8) | |
O3 | 0.6113 (3) | −0.04085 (18) | 0.79363 (12) | 0.0692 (7) | |
O4 | 1.1468 (4) | 0.3809 (3) | 0.54371 (14) | 0.0912 (8) | |
C1 | 0.6204 (4) | 0.2863 (3) | 0.86503 (15) | 0.0479 (6) | |
C2 | 0.4942 (4) | 0.3845 (3) | 0.89955 (17) | 0.0551 (7) | |
H2 | 0.5347 | 0.4705 | 0.9096 | 0.066* | |
C3 | 0.3192 (5) | 0.3512 (4) | 0.9169 (3) | 0.0857 (12) | |
H3 | 0.2513 | 0.4009 | 0.9528 | 0.103* | |
C4 | 0.2397 (4) | 0.2321 (4) | 0.8765 (2) | 0.0710 (9) | |
H4A | 0.2030 | 0.2563 | 0.8231 | 0.085* | |
H4B | 0.1324 | 0.2034 | 0.9051 | 0.085* | |
C5 | 0.3731 (4) | 0.1191 (3) | 0.87248 (15) | 0.0537 (7) | |
H5 | 0.3229 | 0.0512 | 0.8369 | 0.064* | |
C6 | 0.4086 (5) | 0.0540 (3) | 0.95254 (17) | 0.0709 (10) | |
H6A | 0.4990 | −0.0140 | 0.9466 | 0.106* | |
H6B | 0.2983 | 0.0152 | 0.9721 | 0.106* | |
H6C | 0.4511 | 0.1198 | 0.9895 | 0.106* | |
C7 | 0.6457 (4) | 0.0776 (3) | 0.79180 (14) | 0.0481 (7) | |
C8 | 0.7840 (4) | 0.1313 (2) | 0.73602 (14) | 0.0423 (6) | |
C9 | 0.7464 (4) | 0.2396 (3) | 0.68826 (16) | 0.0503 (7) | |
H9 | 0.6346 | 0.2821 | 0.6921 | 0.060* | |
C10 | 0.8738 (4) | 0.2845 (3) | 0.63531 (15) | 0.0514 (7) | |
H10 | 0.8495 | 0.3574 | 0.6030 | 0.062* | |
C11 | 1.0369 (4) | 0.2204 (2) | 0.63066 (15) | 0.0451 (6) | |
C12 | 1.0743 (4) | 0.1105 (3) | 0.67511 (17) | 0.0544 (7) | |
H12 | 1.1849 | 0.0668 | 0.6700 | 0.065* | |
C13 | 0.9459 (4) | 0.0654 (3) | 0.72753 (17) | 0.0510 (7) | |
H13 | 0.9688 | −0.0104 | 0.7576 | 0.061* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0405 (12) | 0.0525 (12) | 0.0451 (11) | −0.0082 (10) | 0.0065 (10) | −0.0066 (10) |
N2 | 0.0636 (18) | 0.0693 (16) | 0.0576 (14) | −0.0089 (15) | 0.0088 (13) | −0.0072 (14) |
O1 | 0.0473 (12) | 0.0748 (14) | 0.0768 (14) | −0.0178 (11) | 0.0087 (11) | −0.0246 (11) |
O2 | 0.0747 (17) | 0.0897 (17) | 0.109 (2) | 0.0008 (16) | 0.0425 (15) | −0.0101 (15) |
O3 | 0.0831 (16) | 0.0493 (12) | 0.0752 (14) | −0.0163 (11) | 0.0254 (14) | −0.0079 (9) |
O4 | 0.0856 (18) | 0.0983 (18) | 0.0897 (17) | −0.0168 (17) | 0.0037 (15) | 0.0384 (16) |
C1 | 0.0485 (16) | 0.0526 (15) | 0.0428 (13) | −0.0068 (14) | 0.0031 (13) | −0.0027 (12) |
C2 | 0.0562 (18) | 0.0500 (15) | 0.0590 (17) | −0.0004 (15) | 0.0070 (15) | −0.0098 (13) |
C3 | 0.060 (2) | 0.090 (2) | 0.107 (3) | 0.010 (2) | 0.003 (2) | −0.040 (2) |
C4 | 0.0401 (17) | 0.095 (2) | 0.078 (2) | −0.0012 (18) | 0.0070 (16) | −0.0131 (19) |
C5 | 0.0395 (14) | 0.0688 (17) | 0.0529 (14) | −0.0166 (16) | 0.0051 (13) | −0.0107 (14) |
C6 | 0.071 (2) | 0.083 (2) | 0.0581 (17) | −0.020 (2) | 0.0075 (17) | −0.0029 (15) |
C7 | 0.0505 (16) | 0.0472 (14) | 0.0465 (14) | −0.0069 (14) | 0.0013 (14) | −0.0056 (12) |
C8 | 0.0448 (14) | 0.0386 (12) | 0.0434 (12) | −0.0017 (13) | 0.0026 (11) | −0.0066 (11) |
C9 | 0.0435 (16) | 0.0520 (14) | 0.0553 (15) | 0.0081 (13) | 0.0019 (13) | 0.0033 (13) |
C10 | 0.0560 (17) | 0.0521 (15) | 0.0459 (13) | 0.0042 (15) | 0.0014 (14) | 0.0076 (12) |
C11 | 0.0505 (16) | 0.0443 (13) | 0.0406 (12) | −0.0039 (13) | 0.0078 (12) | −0.0039 (11) |
C12 | 0.0472 (16) | 0.0488 (14) | 0.0671 (16) | 0.0100 (14) | 0.0079 (14) | −0.0032 (13) |
C13 | 0.0530 (18) | 0.0420 (12) | 0.0578 (15) | 0.0061 (14) | 0.0052 (14) | 0.0058 (12) |
Geometric parameters (Å, º) top
N1—C7 | 1.395 (3) | C3—C4 | 1.497 (5) |
N1—C1 | 1.399 (3) | C4—C5 | 1.504 (4) |
N1—C5 | 1.481 (3) | C5—C6 | 1.521 (4) |
N2—O2 | 1.210 (4) | C7—C8 | 1.487 (3) |
N2—O4 | 1.226 (3) | C8—C13 | 1.372 (4) |
N2—C11 | 1.482 (4) | C8—C9 | 1.382 (4) |
O1—C1 | 1.214 (3) | C9—C10 | 1.371 (4) |
O3—C7 | 1.218 (3) | C10—C11 | 1.366 (4) |
C1—C2 | 1.475 (4) | C11—C12 | 1.363 (3) |
C2—C3 | 1.364 (5) | C12—C13 | 1.370 (4) |
| | | |
C7—N1—C1 | 121.7 (2) | C4—C5—C6 | 113.4 (3) |
C7—N1—C5 | 117.6 (2) | O3—C7—N1 | 120.4 (2) |
C1—N1—C5 | 119.0 (2) | O3—C7—C8 | 120.9 (2) |
O2—N2—O4 | 123.6 (3) | N1—C7—C8 | 118.5 (2) |
O2—N2—C11 | 118.5 (3) | C13—C8—C9 | 119.6 (3) |
O4—N2—C11 | 118.0 (3) | C13—C8—C7 | 119.1 (2) |
O1—C1—N1 | 121.0 (3) | C9—C8—C7 | 121.0 (2) |
O1—C1—C2 | 121.9 (3) | C10—C9—C8 | 120.0 (3) |
N1—C1—C2 | 117.1 (3) | C11—C10—C9 | 119.0 (2) |
C3—C2—C1 | 121.0 (3) | C12—C11—C10 | 121.9 (3) |
C2—C3—C4 | 118.0 (3) | C12—C11—N2 | 119.6 (3) |
C3—C4—C5 | 111.7 (3) | C10—C11—N2 | 118.4 (2) |
N1—C5—C4 | 109.4 (2) | C11—C12—C13 | 118.8 (3) |
N1—C5—C6 | 110.2 (3) | C12—C13—C8 | 120.5 (2) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O2i | 0.93 | 2.69 | 3.619 (4) | 174 |
C3—H3···O4ii | 0.93 | 2.78 | 3.446 (5) | 130 |
C12—H12···O1iii | 0.93 | 2.66 | 3.276 (3) | 124 |
C6—H6A···O4iii | 0.96 | 2.82 | 3.710 (5) | 154 |
C9—H9···O3iv | 0.93 | 2.55 | 3.451 (4) | 163 |
Symmetry codes: (i) −x+2, y+1/2, −z+3/2; (ii) −x+3/2, −y+1, z+1/2; (iii) −x+2, y−1/2, −z+3/2; (iv) −x+1, y+1/2, −z+3/2. |
Crystal data top
C18H20N2O6 | F(000) = 1520 |
Mr = 360.36 | Dx = 1.356 Mg m−3 |
Monoclinic, I2/a | Mo Kα radiation, λ = 0.71073 Å |
a = 10.2455 (9) Å | Cell parameters from 25 reflections |
b = 12.664 (1) Å | θ = 10.0–17.2° |
c = 27.446 (3) Å | µ = 0.10 mm−1 |
β = 97.441 (9)° | T = 293 K |
V = 3531.1 (6) Å3 | Irregular, colourless |
Z = 8 | 0.25 × 0.20 × 0.15 mm |
Data collection top
Enraf-Nonius CAD4 Mach3 diffractometer | Rint = 0.046 |
Radiation source: fine-focus sealed tube | θmax = 26.3° |
Graphite monochromator | h = −12→0 |
ω/2θ scans | k = −15→15 |
7230 measured reflections | l = −33→34 |
3574 independent reflections | 3 standard reflections every 30 min |
1846 reflections with F2 > 2σF2 | intensity decay: 1.6% |
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)] = 0.044 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.0616P)2 + 1.0264P] where P = (Fo2 + 2Fc2)/3 |
3574 reflections | (Δ/σ)max < 0.001 |
237 parameters | Δρmax = 0.20 e Å−3 |
0 restraints | Δρmin = −0.25 e Å−3 |
Crystal data top
C18H20N2O6 | V = 3531.1 (6) Å3 |
Mr = 360.36 | Z = 8 |
Monoclinic, I2/a | Mo Kα radiation |
a = 10.2455 (9) Å | µ = 0.10 mm−1 |
b = 12.664 (1) Å | T = 293 K |
c = 27.446 (3) Å | 0.25 × 0.20 × 0.15 mm |
β = 97.441 (9)° | |
Data collection top
Enraf-Nonius CAD4 Mach3 diffractometer | Rint = 0.046 |
7230 measured reflections | 3 standard reflections every 30 min |
3574 independent reflections | intensity decay: 1.6% |
1846 reflections with F2 > 2σF2 | |
Refinement top
R[F2 > 2σ(F2)] = 0.044 | 0 restraints |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.20 e Å−3 |
3574 reflections | Δρmin = −0.25 e Å−3 |
237 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 on F2 for ALL reflections. Weighted R-factors
wR and all goodnesses of fit S are based on F2,
conventional R-factors R are based on F, with F
set to zero for negative F2. The observed criterion of F2 >
σ(F2) is used only for calculating R-factor-obs etc.
and is not relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R-factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
N1 | −0.27051 (17) | 0.27646 (13) | 0.09344 (6) | 0.0420 (4) | |
N2 | −0.1820 (3) | 0.7863 (2) | 0.09830 (14) | 0.1021 (10) | |
O1 | −0.32587 (15) | 0.35954 (13) | 0.16095 (6) | 0.0539 (4) | |
O2 | 0.1583 (2) | 0.0669 (2) | 0.22006 (10) | 0.1270 (11) | |
O3 | −0.00126 (15) | 0.30550 (13) | 0.17018 (5) | 0.0504 (4) | |
O4 | −0.38402 (19) | 0.33586 (13) | 0.02204 (6) | 0.0677 (6) | |
O1N | −0.0839 (3) | 0.80535 (19) | 0.12680 (14) | 0.1349 (11) | |
O2N | −0.2495 (4) | 0.8533 (2) | 0.07863 (16) | 0.1860 (19) | |
C1 | −0.1960 (2) | 0.20576 (18) | 0.17746 (8) | 0.0466 (6) | |
H1 | −0.2540 | 0.1868 | 0.2018 | 0.056* | |
C2 | −0.2707 (2) | 0.28589 (18) | 0.14380 (8) | 0.0427 (5) | |
C4 | −0.2356 (2) | 0.17599 (17) | 0.07002 (8) | 0.0487 (6) | |
H4 | −0.2020 | 0.1946 | 0.0393 | 0.058* | |
C5 | −0.1243 (2) | 0.12273 (18) | 0.10279 (8) | 0.0506 (6) | |
H5A | −0.1026 | 0.0565 | 0.0880 | 0.061* | |
H5B | −0.0468 | 0.1675 | 0.1056 | 0.061* | |
C6 | −0.1614 (2) | 0.10179 (19) | 0.15326 (9) | 0.0540 (6) | |
H6 | −0.2424 | 0.0598 | 0.1485 | 0.065* | |
C7 | −0.0603 (3) | 0.0368 (2) | 0.18675 (11) | 0.0764 (9) | |
H7A | −0.1070 | −0.0033 | 0.2092 | 0.092* | |
H7B | −0.0206 | −0.0136 | 0.1665 | 0.092* | |
C8 | 0.0465 (3) | 0.0958 (2) | 0.21611 (9) | 0.0661 (8) | |
C9 | 0.0034 (3) | 0.1907 (2) | 0.24198 (9) | 0.0658 (8) | |
H9A | 0.0801 | 0.2282 | 0.2577 | 0.079* | |
H9B | −0.0487 | 0.1688 | 0.2673 | 0.079* | |
C10 | −0.0780 (2) | 0.2641 (2) | 0.20581 (8) | 0.0499 (6) | |
H10 | −0.1106 | 0.3229 | 0.2240 | 0.060* | |
C11 | −0.3544 (3) | 0.1051 (2) | 0.05681 (10) | 0.0689 (8) | |
H11A | −0.3902 | 0.0856 | 0.0862 | 0.103* | |
H11B | −0.3281 | 0.0426 | 0.0408 | 0.103* | |
H11C | −0.4199 | 0.1421 | 0.0351 | 0.103* | |
C12 | 0.0886 (3) | 0.3847 (3) | 0.18940 (11) | 0.0809 (9) | |
H12A | 0.0428 | 0.4375 | 0.2057 | 0.121* | |
H12B | 0.1277 | 0.4167 | 0.1631 | 0.121* | |
H12C | 0.1562 | 0.3536 | 0.2125 | 0.121* | |
C13 | −0.3227 (2) | 0.35760 (18) | 0.06124 (8) | 0.0455 (6) | |
C14 | −0.2879 (2) | 0.46904 (17) | 0.07405 (8) | 0.0438 (5) | |
C15 | −0.1688 (2) | 0.49518 (19) | 0.10161 (9) | 0.0506 (6) | |
H15 | −0.1123 | 0.4422 | 0.1149 | 0.061* | |
C16 | −0.1346 (2) | 0.5990 (2) | 0.10913 (10) | 0.0607 (7) | |
H16 | −0.0553 | 0.6171 | 0.1277 | 0.073* | |
C17 | −0.2185 (3) | 0.67560 (19) | 0.08899 (11) | 0.0638 (7) | |
C18 | −0.3371 (3) | 0.6530 (2) | 0.06144 (10) | 0.0628 (7) | |
H18 | −0.3931 | 0.7067 | 0.0484 | 0.075* | |
C19 | −0.3703 (2) | 0.54884 (19) | 0.05383 (9) | 0.0529 (6) | |
H19 | −0.4492 | 0.5315 | 0.0348 | 0.064* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0420 (10) | 0.0375 (10) | 0.0451 (10) | 0.0015 (8) | 0.0011 (8) | −0.0004 (8) |
N2 | 0.093 (2) | 0.0453 (16) | 0.166 (3) | −0.0085 (17) | 0.010 (2) | −0.0033 (18) |
O1 | 0.0454 (10) | 0.0621 (11) | 0.0557 (10) | 0.0100 (9) | 0.0120 (8) | −0.0025 (8) |
O2 | 0.0651 (15) | 0.164 (2) | 0.142 (2) | 0.0505 (16) | −0.0278 (15) | −0.0525 (19) |
O3 | 0.0419 (9) | 0.0640 (10) | 0.0448 (8) | −0.0093 (8) | 0.0041 (7) | −0.0077 (8) |
O4 | 0.0803 (13) | 0.0574 (11) | 0.0569 (10) | 0.0114 (10) | −0.0229 (10) | −0.0050 (9) |
O1N | 0.113 (2) | 0.0641 (16) | 0.221 (3) | −0.0273 (15) | −0.001 (2) | −0.0295 (18) |
O2N | 0.178 (3) | 0.0435 (14) | 0.312 (5) | −0.0020 (18) | −0.062 (3) | 0.027 (2) |
C1 | 0.0371 (12) | 0.0592 (14) | 0.0451 (12) | 0.0010 (11) | 0.0112 (10) | 0.0118 (11) |
C2 | 0.0315 (11) | 0.0488 (13) | 0.0478 (13) | −0.0028 (10) | 0.0047 (10) | −0.0003 (11) |
C4 | 0.0579 (15) | 0.0391 (12) | 0.0482 (13) | 0.0006 (11) | 0.0038 (11) | −0.0030 (10) |
C5 | 0.0478 (14) | 0.0394 (13) | 0.0640 (15) | 0.0046 (11) | 0.0051 (11) | −0.0036 (11) |
C6 | 0.0482 (14) | 0.0502 (14) | 0.0606 (15) | −0.0039 (11) | −0.0043 (12) | 0.0100 (12) |
C7 | 0.081 (2) | 0.0606 (18) | 0.0826 (19) | 0.0099 (16) | −0.0083 (17) | 0.0153 (15) |
C8 | 0.0566 (17) | 0.083 (2) | 0.0556 (16) | 0.0176 (15) | −0.0035 (13) | 0.0084 (14) |
C9 | 0.0585 (16) | 0.094 (2) | 0.0433 (13) | 0.0141 (15) | −0.0012 (12) | 0.0037 (14) |
C10 | 0.0446 (13) | 0.0658 (16) | 0.0388 (12) | 0.0085 (12) | 0.0038 (10) | −0.0026 (11) |
C11 | 0.0735 (19) | 0.0509 (15) | 0.0757 (18) | −0.0097 (14) | −0.0151 (15) | −0.0065 (14) |
C12 | 0.0674 (19) | 0.102 (2) | 0.0717 (19) | −0.0344 (18) | 0.0024 (15) | −0.0200 (17) |
C13 | 0.0416 (13) | 0.0468 (13) | 0.0463 (13) | 0.0052 (11) | −0.0014 (11) | −0.0001 (11) |
C14 | 0.0408 (13) | 0.0439 (13) | 0.0467 (13) | 0.0024 (10) | 0.0054 (10) | 0.0034 (10) |
C15 | 0.0368 (12) | 0.0457 (13) | 0.0684 (15) | 0.0025 (11) | 0.0030 (11) | 0.0030 (12) |
C16 | 0.0416 (14) | 0.0521 (15) | 0.0877 (19) | −0.0060 (12) | 0.0058 (13) | −0.0022 (14) |
C17 | 0.0613 (18) | 0.0411 (14) | 0.0898 (19) | −0.0029 (13) | 0.0131 (15) | −0.0001 (13) |
C18 | 0.0671 (18) | 0.0445 (15) | 0.0758 (18) | 0.0102 (13) | 0.0056 (15) | 0.0091 (13) |
C19 | 0.0514 (14) | 0.0525 (15) | 0.0524 (14) | 0.0057 (12) | −0.0023 (11) | 0.0027 (12) |
Geometric parameters (Å, º) top
N1—C2 | 1.388 (3) | C4—C5 | 1.516 (3) |
N1—C13 | 1.414 (3) | C4—C11 | 1.519 (3) |
N1—C4 | 1.490 (3) | C5—C6 | 1.507 (3) |
N2—O2N | 1.180 (4) | C6—C7 | 1.533 (3) |
N2—O1N | 1.216 (4) | C7—C8 | 1.475 (4) |
N2—C17 | 1.464 (4) | C8—C9 | 1.492 (4) |
O1—C2 | 1.217 (2) | C9—C10 | 1.526 (3) |
O2—C8 | 1.194 (3) | C13—C14 | 1.486 (3) |
O3—C12 | 1.417 (3) | C14—C19 | 1.386 (3) |
O3—C10 | 1.431 (3) | C14—C15 | 1.390 (3) |
O4—C13 | 1.206 (2) | C15—C16 | 1.370 (3) |
C1—C2 | 1.512 (3) | C16—C17 | 1.364 (4) |
C1—C6 | 1.537 (3) | C17—C18 | 1.376 (4) |
C1—C10 | 1.540 (3) | C18—C19 | 1.371 (3) |
| | | |
C2—N1—C13 | 120.7 (2) | O2—C8—C7 | 122.0 (3) |
C2—N1—C4 | 122.3 (2) | O2—C8—C9 | 122.9 (3) |
C13—N1—C4 | 116.3 (2) | C7—C8—C9 | 115.1 (2) |
O2N—N2—O1N | 122.5 (3) | C8—C9—C10 | 110.5 (2) |
O2N—N2—C17 | 119.2 (3) | O3—C10—C9 | 111.4 (2) |
O1N—N2—C17 | 118.3 (3) | O3—C10—C1 | 107.2 (2) |
C12—O3—C10 | 113.2 (2) | C9—C10—C1 | 111.4 (2) |
C2—C1—C6 | 116.0 (2) | O4—C13—N1 | 120.2 (2) |
C2—C1—C10 | 106.8 (2) | O4—C13—C14 | 120.6 (2) |
C6—C1—C10 | 114.8 (2) | N1—C13—C14 | 118.8 (2) |
O1—C2—N1 | 120.8 (2) | C19—C14—C15 | 119.4 (2) |
O1—C2—C1 | 120.1 (2) | C19—C14—C13 | 118.9 (2) |
N1—C2—C1 | 119.0 (2) | C15—C14—C13 | 121.4 (2) |
N1—C4—C5 | 109.2 (2) | C16—C15—C14 | 120.0 (2) |
N1—C4—C11 | 112.2 (2) | C17—C16—C15 | 119.1 (2) |
C5—C4—C11 | 113.4 (2) | C16—C17—C18 | 122.7 (2) |
C6—C5—C4 | 111.3 (2) | C16—C17—N2 | 118.5 (3) |
C5—C6—C7 | 114.5 (2) | C18—C17—N2 | 118.8 (3) |
C5—C6—C1 | 110.3 (2) | C19—C18—C17 | 117.9 (2) |
C7—C6—C1 | 112.1 (2) | C18—C19—C14 | 121.0 (2) |
C8—C7—C6 | 116.8 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5B···O3 | 0.97 | 2.49 | 3.124 (3) | 123 |
C11—H11C···O4 | 0.96 | 2.52 | 3.078 (3) | 118 |
C15—H15···O3 | 0.93 | 2.48 | 3.379 (3) | 163 |
C4—H4···O4i | 0.98 | 2.68 | 3.576 (3) | 152 |
C7—H7B···O1Nii | 0.97 | 2.58 | 3.354 (4) | 136 |
C11—H11B···O2Nii | 0.96 | 2.69 | 3.393 (4) | 130 |
C7—H7A···O2iii | 0.97 | 2.59 | 3.399 (4) | 141 |
C9—H9B···O1iv | 0.97 | 2.51 | 3.473 (3) | 171 |
C11—H11A···O1Nv | 0.96 | 2.76 | 3.418 (5) | 126 |
C12—H12C···O2vi | 0.96 | 2.67 | 3.407 (4) | 134 |
C16—H16···O1vii | 0.93 | 2.43 | 3.337 (3) | 166 |
C19—H19···O4viii | 0.93 | 2.73 | 3.382 (3) | 128 |
Symmetry codes: (i) −x−1/2, y, −z; (ii) x, y−1, z; (iii) x−1/2, −y, z; (iv) −x−1/2, −y+1/2, −z+1/2; (v) x−1/2, −y+1, z; (vi) −x+1/2, −y+1/2, −z+1/2; (vii) x+1/2, −y+1, z; (viii) −x−1, −y+1, −z. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C13H12N2O4 | C18H20N2O6 |
Mr | 260.25 | 360.36 |
Crystal system, space group | Orthorhombic, P212121 | Monoclinic, I2/a |
Temperature (K) | 293 | 293 |
a, b, c (Å) | 7.3677 (9), 10.054 (1), 16.834 (2) | 10.2455 (9), 12.664 (1), 27.446 (3) |
α, β, γ (°) | 90, 90, 90 | 90, 97.441 (9), 90 |
V (Å3) | 1247.0 (2) | 3531.1 (6) |
Z | 4 | 8 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.11 | 0.10 |
Crystal size (mm) | 0.20 × 0.10 × 0.05 | 0.25 × 0.20 × 0.15 |
|
Data collection |
Diffractometer | Enraf-Nonius CAD-4 MACH3 diffractometer | Enraf-Nonius CAD-4 MACH3 diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed (F2 > 2σF2) reflections | 2382, 2098, 995 | 7230, 3574, 1846 |
Rint | 0.018 | 0.046 |
(sin θ/λ)max (Å−1) | 0.703 | 0.623 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.037, 0.103, 0.98 | 0.044, 0.113, 1.01 |
No. of reflections | 2098 | 3574 |
No. of parameters | 173 | 237 |
H-atom treatment | Riding | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.17, −0.18 | 0.20, −0.25 |
Selected geometric parameters (Å, º) for (I) topN1—C7 | 1.395 (3) | N2—O2 | 1.210 (4) |
N1—C1 | 1.399 (3) | N2—O4 | 1.226 (3) |
N1—C5 | 1.481 (3) | N2—C11 | 1.482 (4) |
| | | |
C7—N1—C1 | 121.7 (2) | O2—N2—O4 | 123.6 (3) |
C7—N1—C5 | 117.6 (2) | O2—N2—C11 | 118.5 (3) |
C1—N1—C5 | 119.0 (2) | O4—N2—C11 | 118.0 (3) |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O2i | 0.93 | 2.69 | 3.619 (4) | 174 |
C3—H3···O4ii | 0.93 | 2.78 | 3.446 (5) | 130 |
C12—H12···O1iii | 0.93 | 2.66 | 3.276 (3) | 124 |
C6—H6A···O4iii | 0.96 | 2.82 | 3.710 (5) | 154 |
C9—H9···O3iv | 0.93 | 2.55 | 3.451 (4) | 163 |
Symmetry codes: (i) −x+2, y+1/2, −z+3/2; (ii) −x+3/2, −y+1, z+1/2; (iii) −x+2, y−1/2, −z+3/2; (iv) −x+1, y+1/2, −z+3/2. |
Cremer & Pople's puckering parameters topRing | | | q2Å | q3Å | ϕ2° | θ2° | QÅ |
N1-C1-C2-C3-C4-C5 | | | 0.27 (2) | -0.32 (2) | 38 (5) | 139 (3) | 0.42 (2) |
Selected geometric parameters (Å, º) for (II) topN1—C2 | 1.388 (3) | N2—O2N | 1.180 (4) |
N1—C13 | 1.414 (3) | N2—O1N | 1.216 (4) |
N1—C4 | 1.490 (3) | N2—C17 | 1.464 (4) |
| | | |
C2—N1—C13 | 120.7 (2) | O2N—N2—O1N | 122.5 (3) |
C2—N1—C4 | 122.3 (2) | O2N—N2—C17 | 119.2 (3) |
C13—N1—C4 | 116.3 (2) | O1N—N2—C17 | 118.3 (3) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5B···O3 | 0.97 | 2.49 | 3.124 (3) | 123 |
C11—H11C···O4 | 0.96 | 2.52 | 3.078 (3) | 118 |
C15—H15···O3 | 0.93 | 2.48 | 3.379 (3) | 163 |
C4—H4···O4i | 0.98 | 2.68 | 3.576 (3) | 152 |
C7—H7B···O1Nii | 0.97 | 2.58 | 3.354 (4) | 136 |
C11—H11B···O2Nii | 0.96 | 2.69 | 3.393 (4) | 130 |
C7—H7A···O2iii | 0.97 | 2.59 | 3.399 (4) | 141 |
C9—H9B···O1iv | 0.97 | 2.51 | 3.473 (3) | 171 |
C11—H11A···O1Nv | 0.96 | 2.76 | 3.418 (5) | 126 |
C12—H12C···O2vi | 0.96 | 2.67 | 3.407 (4) | 134 |
C16—H16···O1vii | 0.93 | 2.43 | 3.337 (3) | 166 |
C19—H19···O4viii | 0.93 | 2.73 | 3.382 (3) | 128 |
Symmetry codes: (i) −x−1/2, y, −z; (ii) x, y−1, z; (iii) x−1/2, −y, z; (iv) −x−1/2, −y+1/2, −z+1/2; (v) x−1/2, −y+1, z; (vi) −x+1/2, −y+1/2, −z+1/2; (vii) x+1/2, −y+1, z; (viii) −x−1, −y+1, −z. |
Cremer & Pople's puckering parameters topRing | | | q2Å | q3Å | ϕ2° | θ2° | QÅ |
C1-C6-C7-C8-C9-C10 | | | 0.11 (2) | 0.47 (2) | -95 (11) | 13 (3) | 0.49 (2) |
N1-C2-C1-C6-C5-C4 | | | 0.297 (3) | 0.380 (3) | -122.4 (5) | 38.2 (3) | 0.482 (3) |
Glutamate is the major excitatory neurotransmitter in the brain and can act on three major types of ligand-gated ion channels that are defined by the activity of the subtype-selective agonists NMDA (N-methyl-D-aspartate), kainate and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) (Ornstein et al., 1994). In the search for new therapeutic agents which are potent and selective antagonists of glutamate, the excitatory amino acid antagonist activities of a series of decahydroisoquinoline-3-carboxylic acids were explored. It was found that compound (III) possessses both NMDA and AMPA receptor antagonist activity (Simmons et al., 1998; O'Neill et al., 1998). \sch
A new route to the synthesis of (III) was proposed, based on an intermolecular Diels-Alder cycloaddition reaction of a 6-substituted dihydropyridone with an appropriate diene. This key reaction would need a group at position 6 (to the nitrogen) in an axial position, so that, before the cycloaddition reaction was tried a crystal structure determination of (I) was undertaken. After confirmation that the methyl group (at position 6, labelled C5 in the figure) occupied an axial position, a thermally induced Diels-Alder reaction was done using the highly reactive Danishefsky's diene, (IV). As the Diels-Alder reaction could lead to several different products and as the relative stereochemistry of this product is of great importance for the next reaction steps, the crystal structure of (II) was determined.
The molecular structure of (I) is shown in Fig. 1. As stated, the methyl group at C5 is in an axial position, as required for the continuing of the reaction path. The piperidone ring is in a half-chair, distorted towards a half-boat, conformation, as indicated by the Cremer & Pople (1975) puckering parameters shown in Table 3. The lone pair of the piperidone nitrogen atom is involved in conjugation with the carbonyl groups. This is indicated by the slight lengthening of the C═O double bond [1.214 (3) Å] and the concomitant shortening of the two N-Csp2 single bonds [1.395 (3) and 1.399 (3) Å]. Accordingly the state of hybridization of the nitrogen is sp2 as shown by the sum (358.2°) of the angles around it, and the small deviation [-0.050 (2) Å] of the atom from the plane N1—C2—C4—C13.
The molecular diagram of (II) is seen in Fig. 2, showing that the two rings have a cis fused stereochemistry with a H1—C1—C6—H6 torsion angle of 41°. The heterocyclic ring is in a slightly distorted, towards a chair, half-boat conformation, whereas the other six-membered ring is in a distorted chair (towards a half-chair) conformation, as shown by the Cremer & Pople (1975) puckering parameters given in Table 6. The existence of a C—H···π interaction between C12—H12B and the C14 to C19 phenyl ring is noted. According to Ciunik et al. (1998), this kind of interaction should be characterized by three parameters. In the present structure these are the H12B···Cgi (Cg is the centroid of the C14—C19 ring) distance of 2.69 Å, the C12—H12B···Cgi angle of 158° and the angle between the H···Cg vector and the plane of the aromatic ring, which in this case is of 88° [symmetry code: (i) = 1/2 + x, 1 - y, z]. These values are in the expected ranges of 2.7–3.4 Å, 140–160° and 80–100°, respectively, as described by Ciunik et al. (1998). This compound also exhibits three intramolecular hydrogen bonds (Table 5); in fact C11—H11A···O4 and C15—H15···O3 are responsible for the particular arrangement of the phenyl ring. In order to study the influence of these hydrogen bonds in the molecular conformation a series of Potential Energy Surfaces (PES) calculations were performed (MOPAC7.01: Stewart, 1990 and Csern, 2000 and GAMESS98: Schmidt et al., 1993). The geometry optimization calculations, using AM1 and 6–31G*, showed that there is a change in the conformation involving the three C—H···O interactions, the H15···O3 distance changes from 2.49 to 2.58 Å, while the other two H5B···O3 and H11C···O4 shorten to 2.47 and 2.49 Å, respectively. The PES obtained after rotation of the C4—N1—C13—C14 torsion angle showed that there are two minima, one corresponding to the global minimimum (162.77°) which is close to the crystallographic conformation [144.0 (2)°] and the other one at -77.32°. This last conformation is around 7 kcal higher than the other and results in the loss of the C15—H15···O3 hydrogen bond. We can postulate that, in this case, the molecular conformation is driven more by the intramolecular interactions.
In both compounds the molecules interact through a series of C—H···O interactions as shown in Tables 2 and 5. Whether all these interactions are true hydrogen bonds is difficult to assert because, as pointed out by Cotton et al. (1997), `the field is getting muddier and muddier as the definition of a hydrogen bond is relaxed'. In any case the Tables include those with H···O distance less than the sum of the van der Waals radii (Pauling, 1960) plus 10% and having a C—H···O angle greater than 100°.