The title
trans prolyl amide exists as a benzene solvate, C
15H
18N
2O
3·C
6H
6, with positional disorder of the prolyl ring. The molecular structure is influenced by a close intramolecular N—H
N contact that provides structural support for the intramolecular catalysis of peptidyl–prolyl
cis–
trans isomerization.
Supporting information
CCDC reference: 214161
Crystalline samples of (I) were obtained from T. Leckta (Department of Chemistry, Johns Hopkins University). Sample quality was assessed by polarized microscopy, and a single-crystal was adhered to a glass fiber using cyanoacrylate glue for subsequent crystallographic investigation.
The proline moiety of (I) exhibits positional disorder over two sites, related by an 8.8° rotation about the C1—C8 bond. The non-H atoms of the two conformers were positioned from a difference Fourier map. Since the SOFs for these two sites refined to nearly equal occupancy, 50% occupancy factors were applied to each of the two positions. Atom HN2 was located in a difference density map, and the remaining H-atom positions were treated as riding, with C—H distances of 0.95 Å (aromatic), 0.98 Å (CH3) and 0.99 Å (CH2) Riding methyl H atoms were allowed to rotate freely during refinement using the AFIX 137 command of SHELXTL.
Data collection: XSCANS (Bruker, 1999); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97; molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: X-SEED.
(±)-5-(4-Methoxyphenylaminocarbonyl)-1-azabicyclo[3.3.0]octan-2-one benzene solvate
top
Crystal data top
C15H18N2O3·C6H6 | Z = 2 |
Mr = 352.42 | F(000) = 376 |
Triclinic, P1 | Dx = 1.238 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.7611 (14) Å | Cell parameters from 16 reflections |
b = 10.1229 (15) Å | θ = 20.2–24.0° |
c = 10.7545 (13) Å | µ = 0.08 mm−1 |
α = 88.349 (9)° | T = 298 K |
β = 87.715 (9)° | Transparent plate, colourless |
γ = 62.925 (9)° | 0.81 × 0.43 × 0.12 mm |
V = 945.4 (2) Å3 | |
Data collection top
Siemens P4 diffractometer | Rint = 0.021 |
Radiation source: fine-focus sealed tube | θmax = 27.5°, θmin = 2.3° |
Graphite monochromator | h = −11→11 |
θ/2θ\ scans | k = −12→13 |
5059 measured reflections | l = −13→13 |
4295 independent reflections | 3 standard reflections every 97 reflections |
2607 reflections with I > 2σ(I) | intensity decay: <3% |
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)] = 0.054 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.134 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0438P)2 + 0.282P] where P = (Fo2 + 2Fc2)/3 |
4295 reflections | (Δ/σ)max < 0.001 |
312 parameters | Δρmax = 0.15 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
Crystal data top
C15H18N2O3·C6H6 | γ = 62.925 (9)° |
Mr = 352.42 | V = 945.4 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 9.7611 (14) Å | Mo Kα radiation |
b = 10.1229 (15) Å | µ = 0.08 mm−1 |
c = 10.7545 (13) Å | T = 298 K |
α = 88.349 (9)° | 0.81 × 0.43 × 0.12 mm |
β = 87.715 (9)° | |
Data collection top
Siemens P4 diffractometer | Rint = 0.021 |
5059 measured reflections | 3 standard reflections every 97 reflections |
4295 independent reflections | intensity decay: <3% |
2607 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.054 | 0 restraints |
wR(F2) = 0.134 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | Δρmax = 0.15 e Å−3 |
4295 reflections | Δρmin = −0.21 e Å−3 |
312 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 | Occ. (<1) |
O1 | 1.0387 (4) | 0.6505 (4) | 0.5250 (3) | 0.0442 (8) | 0.50 |
O2 | 0.68175 (19) | 0.6614 (2) | 0.10604 (14) | 0.0631 (5) | |
O3 | 0.42561 (17) | 0.18987 (17) | 0.27697 (13) | 0.0479 (4) | |
N1 | 0.9619 (6) | 0.6232 (8) | 0.3350 (7) | 0.0307 (13) | 0.50 |
N2 | 0.75634 (19) | 0.51634 (18) | 0.27993 (15) | 0.0366 (4) | |
C1 | 0.8457 (2) | 0.7047 (2) | 0.24025 (17) | 0.0381 (5) | |
C2 | 0.9390 (8) | 0.7214 (8) | 0.1341 (7) | 0.0515 (19) | 0.50 |
H2A | 0.9659 | 0.8030 | 0.1477 | 0.062* | 0.50 |
H2B | 0.8849 | 0.7391 | 0.0547 | 0.062* | 0.50 |
C3 | 1.0826 (8) | 0.5683 (8) | 0.1365 (6) | 0.0576 (16) | 0.50 |
H3A | 1.0645 | 0.4942 | 0.0912 | 0.069* | 0.50 |
H3B | 1.1732 | 0.5747 | 0.0979 | 0.069* | 0.50 |
C4 | 1.108 (2) | 0.526 (2) | 0.2746 (13) | 0.047 (3) | 0.50 |
H4A | 1.1325 | 0.4205 | 0.2886 | 0.056* | 0.50 |
H4B | 1.1924 | 0.5430 | 0.3059 | 0.056* | 0.50 |
C5 | 0.9436 (5) | 0.6885 (5) | 0.4438 (4) | 0.0303 (8) | 0.50 |
C6 | 0.7845 (16) | 0.8201 (17) | 0.4491 (15) | 0.054 (3) | 0.50 |
H6A | 0.7878 | 0.9068 | 0.4865 | 0.065* | 0.50 |
H6B | 0.7116 | 0.7953 | 0.4988 | 0.065* | 0.50 |
C7 | 0.7365 (7) | 0.8527 (7) | 0.3126 (6) | 0.0472 (14) | 0.50 |
H7A | 0.7514 | 0.9376 | 0.2792 | 0.057* | 0.50 |
H7B | 0.6270 | 0.8760 | 0.3051 | 0.057* | 0.50 |
O1A | 1.1298 (5) | 0.5638 (5) | 0.4652 (4) | 0.0744 (12) | 0.50 |
N1A | 0.9047 (7) | 0.6646 (8) | 0.3599 (8) | 0.0424 (17) | 0.50 |
C2A | 0.7422 (8) | 0.8651 (7) | 0.2427 (7) | 0.0675 (18) | 0.50 |
H2BA | 0.6619 | 0.8948 | 0.1796 | 0.081* | 0.50 |
H2BB | 0.7994 | 0.9241 | 0.2302 | 0.081* | 0.50 |
C3A | 0.6750 (11) | 0.8791 (8) | 0.3733 (8) | 0.090 (3) | 0.50 |
H3BA | 0.5896 | 0.8517 | 0.3762 | 0.108* | 0.50 |
H3BB | 0.6350 | 0.9822 | 0.4025 | 0.108* | 0.50 |
C4A | 0.8061 (19) | 0.7728 (16) | 0.4546 (15) | 0.068 (5) | 0.50 |
H4BA | 0.8600 | 0.8233 | 0.4927 | 0.081* | 0.50 |
H4BB | 0.7691 | 0.7256 | 0.5207 | 0.081* | 0.50 |
C5A | 1.0552 (8) | 0.5875 (6) | 0.3675 (5) | 0.0525 (13) | 0.50 |
C6A | 1.120 (2) | 0.535 (2) | 0.2369 (13) | 0.062 (4) | 0.50 |
H6BA | 1.1301 | 0.4351 | 0.2216 | 0.074* | 0.50 |
H6BB | 1.2216 | 0.5337 | 0.2227 | 0.074* | 0.50 |
C7A | 0.9959 (9) | 0.6547 (9) | 0.1544 (8) | 0.057 (2) | 0.50 |
H7BA | 0.9859 | 0.6122 | 0.0755 | 0.069* | 0.50 |
H7BB | 1.0196 | 0.7385 | 0.1355 | 0.069* | 0.50 |
C8 | 0.7535 (2) | 0.6241 (2) | 0.20196 (18) | 0.0391 (5) | |
C9 | 0.6704 (2) | 0.4356 (2) | 0.27087 (16) | 0.0323 (4) | |
C10 | 0.6211 (2) | 0.4088 (2) | 0.15977 (17) | 0.0398 (5) | |
H10 | 0.6438 | 0.4464 | 0.0840 | 0.048* | |
C11 | 0.5383 (2) | 0.3270 (2) | 0.15840 (17) | 0.0391 (5) | |
H11 | 0.5036 | 0.3103 | 0.0819 | 0.047* | |
C12 | 0.5070 (2) | 0.2706 (2) | 0.26785 (18) | 0.0369 (4) | |
C13 | 0.5561 (2) | 0.2978 (2) | 0.37943 (17) | 0.0407 (5) | |
H13 | 0.5339 | 0.2599 | 0.4552 | 0.049* | |
C14 | 0.6363 (2) | 0.3790 (2) | 0.38098 (17) | 0.0367 (5) | |
H14 | 0.6691 | 0.3970 | 0.4579 | 0.044* | |
C15 | 0.3857 (3) | 0.1470 (3) | 0.1639 (2) | 0.0651 (7) | |
H15A | 0.3167 | 0.2359 | 0.1176 | 0.098* | |
H15B | 0.3338 | 0.0854 | 0.1832 | 0.098* | |
H15C | 0.4793 | 0.0903 | 0.1133 | 0.098* | |
C16 | 0.0365 (3) | 1.0360 (3) | 0.2883 (2) | 0.0625 (7) | |
H16 | −0.0479 | 1.1109 | 0.3328 | 0.075* | |
C17 | 0.0551 (3) | 1.0515 (3) | 0.1624 (2) | 0.0559 (6) | |
H17 | −0.0164 | 1.1369 | 0.1194 | 0.067* | |
C18 | 0.1777 (3) | 0.9428 (3) | 0.0988 (2) | 0.0536 (6) | |
H18 | 0.1902 | 0.9528 | 0.0115 | 0.064* | |
C19 | 0.2825 (3) | 0.8194 (3) | 0.1611 (2) | 0.0503 (6) | |
H19 | 0.3674 | 0.7447 | 0.1169 | 0.060* | |
C20 | 0.2641 (3) | 0.8046 (3) | 0.2871 (2) | 0.0542 (6) | |
H20 | 0.3369 | 0.7203 | 0.3305 | 0.065* | |
C21 | 0.1406 (3) | 0.9115 (3) | 0.3498 (2) | 0.0645 (7) | |
H21 | 0.1264 | 0.8999 | 0.4366 | 0.077* | |
HN2 | 0.802 (2) | 0.502 (2) | 0.3478 (19) | 0.047 (6)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.056 (2) | 0.0506 (19) | 0.0367 (16) | −0.0331 (17) | −0.0220 (15) | 0.0121 (14) |
O2 | 0.0750 (12) | 0.0893 (13) | 0.0523 (9) | −0.0602 (11) | −0.0407 (9) | 0.0353 (9) |
O3 | 0.0547 (9) | 0.0656 (10) | 0.0434 (8) | −0.0442 (8) | −0.0108 (7) | 0.0019 (7) |
N1 | 0.020 (3) | 0.035 (3) | 0.040 (3) | −0.014 (3) | −0.017 (3) | 0.009 (2) |
N2 | 0.0415 (10) | 0.0458 (10) | 0.0329 (9) | −0.0283 (8) | −0.0161 (8) | 0.0094 (7) |
C1 | 0.0414 (11) | 0.0421 (11) | 0.0374 (10) | −0.0243 (10) | −0.0183 (9) | 0.0147 (8) |
C2 | 0.064 (5) | 0.075 (5) | 0.039 (3) | −0.051 (4) | −0.021 (3) | 0.016 (3) |
C3 | 0.057 (4) | 0.090 (5) | 0.040 (3) | −0.045 (4) | 0.002 (3) | −0.008 (3) |
C4 | 0.032 (5) | 0.055 (5) | 0.050 (6) | −0.017 (4) | −0.004 (4) | −0.010 (4) |
C5 | 0.032 (2) | 0.038 (2) | 0.030 (2) | −0.023 (2) | −0.0107 (18) | 0.0067 (16) |
C6 | 0.035 (3) | 0.064 (8) | 0.055 (4) | −0.013 (4) | −0.010 (3) | −0.008 (5) |
C7 | 0.050 (4) | 0.050 (3) | 0.042 (4) | −0.021 (3) | −0.015 (3) | −0.001 (3) |
O1A | 0.088 (3) | 0.100 (3) | 0.071 (3) | −0.072 (3) | −0.055 (2) | 0.049 (2) |
N1A | 0.042 (4) | 0.046 (4) | 0.049 (4) | −0.028 (3) | −0.021 (3) | 0.016 (3) |
C2A | 0.079 (4) | 0.055 (3) | 0.073 (4) | −0.034 (3) | −0.016 (4) | 0.015 (4) |
C3A | 0.126 (8) | 0.053 (4) | 0.084 (5) | −0.036 (5) | 0.008 (5) | 0.001 (4) |
C4A | 0.095 (11) | 0.076 (10) | 0.042 (4) | −0.047 (9) | 0.008 (6) | −0.012 (5) |
C5A | 0.061 (4) | 0.054 (3) | 0.062 (4) | −0.042 (3) | −0.023 (3) | 0.024 (3) |
C6A | 0.045 (4) | 0.059 (5) | 0.088 (13) | −0.030 (4) | 0.004 (7) | −0.009 (8) |
C7A | 0.056 (6) | 0.085 (7) | 0.049 (4) | −0.047 (5) | −0.012 (4) | 0.005 (4) |
C8 | 0.0388 (11) | 0.0480 (12) | 0.0369 (10) | −0.0250 (10) | −0.0141 (9) | 0.0113 (9) |
C9 | 0.0299 (10) | 0.0377 (10) | 0.0320 (9) | −0.0173 (9) | −0.0078 (8) | 0.0020 (8) |
C10 | 0.0430 (12) | 0.0539 (13) | 0.0310 (10) | −0.0292 (10) | −0.0061 (9) | 0.0024 (9) |
C11 | 0.0418 (12) | 0.0537 (12) | 0.0296 (10) | −0.0280 (10) | −0.0067 (8) | −0.0046 (9) |
C12 | 0.0343 (11) | 0.0427 (11) | 0.0392 (10) | −0.0220 (9) | −0.0042 (8) | −0.0016 (8) |
C13 | 0.0460 (12) | 0.0529 (12) | 0.0322 (10) | −0.0303 (11) | −0.0051 (9) | 0.0049 (9) |
C14 | 0.0426 (12) | 0.0461 (11) | 0.0288 (9) | −0.0260 (10) | −0.0108 (8) | 0.0014 (8) |
C15 | 0.0860 (19) | 0.0836 (18) | 0.0572 (14) | −0.0645 (17) | −0.0208 (13) | −0.0006 (13) |
C16 | 0.0557 (16) | 0.0591 (15) | 0.0671 (16) | −0.0213 (13) | 0.0075 (13) | −0.0120 (13) |
C17 | 0.0566 (15) | 0.0566 (15) | 0.0642 (15) | −0.0335 (13) | −0.0205 (12) | 0.0130 (12) |
C18 | 0.0637 (16) | 0.0771 (17) | 0.0391 (11) | −0.0485 (15) | −0.0092 (11) | 0.0053 (11) |
C19 | 0.0499 (14) | 0.0634 (15) | 0.0444 (12) | −0.0317 (12) | 0.0021 (10) | −0.0070 (11) |
C20 | 0.0581 (15) | 0.0565 (14) | 0.0459 (13) | −0.0242 (12) | −0.0081 (11) | 0.0056 (11) |
C21 | 0.0764 (19) | 0.0707 (17) | 0.0394 (12) | −0.0280 (15) | 0.0040 (12) | −0.0001 (12) |
Geometric parameters (Å, º) top
O2—C8 | 1.222 (2) | C20—H20 | 0.9500 |
O3—C12 | 1.374 (2) | C21—H21 | 0.9500 |
O3—C15 | 1.429 (2) | O1—C5 | 1.221 (4) |
N2—C8 | 1.347 (2) | N1—C5 | 1.326 (9) |
N2—C9 | 1.420 (2) | N1—C4 | 1.451 (18) |
N2—HN2 | 0.84 (2) | C2—C3 | 1.547 (9) |
C1—N1A | 1.403 (9) | C2—H2A | 0.9900 |
C1—C2A | 1.472 (7) | C2—H2B | 0.9900 |
C1—N1 | 1.482 (7) | C3—C4 | 1.532 (14) |
C1—C2 | 1.486 (8) | C3—H3A | 0.9900 |
C1—C8 | 1.537 (3) | C3—H3B | 0.9900 |
C1—C7A | 1.582 (9) | C4—H4A | 0.9900 |
C1—C7 | 1.592 (7) | C4—H4B | 0.9900 |
C9—C10 | 1.384 (2) | C5—C6 | 1.518 (14) |
C9—C14 | 1.394 (3) | C6—C7 | 1.539 (17) |
C10—C11 | 1.397 (3) | C6—H6A | 0.9900 |
C10—H10 | 0.9500 | C6—H6B | 0.9900 |
C11—C12 | 1.377 (3) | C7—H7A | 0.9900 |
C11—H11 | 0.9500 | C7—H7B | 0.9900 |
C12—C13 | 1.390 (3) | O1A—C5A | 1.256 (6) |
C13—C14 | 1.370 (3) | N1A—C5A | 1.318 (8) |
C13—H13 | 0.9500 | N1A—C4A | 1.480 (17) |
C14—H14 | 0.9500 | C2A—C3A | 1.509 (9) |
C15—H15A | 0.9800 | C2A—H2BA | 0.9900 |
C15—H15B | 0.9800 | C2A—H2BB | 0.9900 |
C15—H15C | 0.9800 | C3A—C4A | 1.530 (17) |
C16—C17 | 1.373 (3) | C3A—H3BA | 0.9900 |
C16—C21 | 1.378 (3) | C3A—H3BB | 0.9900 |
C16—H16 | 0.9500 | C4A—H4BA | 0.9900 |
C17—C18 | 1.375 (3) | C4A—H4BB | 0.9900 |
C17—H17 | 0.9500 | C5A—C6A | 1.524 (16) |
C18—C19 | 1.378 (3) | C6A—C7A | 1.553 (19) |
C18—H18 | 0.9500 | C6A—H6BA | 0.9900 |
C19—C20 | 1.372 (3) | C6A—H6BB | 0.9900 |
C19—H19 | 0.9500 | C7A—H7BA | 0.9900 |
C20—C21 | 1.368 (3) | C7A—H7BB | 0.9900 |
| | | |
C12—O3—C15 | 117.64 (16) | C1—C2—C3 | 101.0 (4) |
C8—N2—C9 | 126.88 (16) | C1—C2—H2A | 111.6 |
C8—N2—HN2 | 119.1 (15) | C3—C2—H2A | 111.6 |
C9—N2—HN2 | 113.3 (14) | C1—C2—H2B | 111.6 |
N1A—C1—C2A | 106.5 (4) | C3—C2—H2B | 111.6 |
C2A—C1—N1 | 124.5 (4) | H2A—C2—H2B | 109.4 |
N1A—C1—C2 | 121.8 (4) | C4—C3—C2 | 105.1 (9) |
C2A—C1—C2 | 92.2 (4) | C4—C3—H3A | 110.7 |
N1—C1—C2 | 103.3 (4) | C2—C3—H3A | 110.7 |
N1A—C1—C8 | 113.1 (4) | C4—C3—H3B | 110.7 |
C2A—C1—C8 | 108.6 (3) | C2—C3—H3B | 110.7 |
N1—C1—C8 | 113.8 (3) | H3A—C3—H3B | 108.8 |
C2—C1—C8 | 111.7 (3) | N1—C4—C3 | 104.0 (12) |
N1A—C1—C7A | 102.9 (4) | N1—C4—H4A | 111.0 |
C2A—C1—C7A | 115.9 (4) | C3—C4—H4A | 111.0 |
N1—C1—C7A | 81.3 (4) | N1—C4—H4B | 111.0 |
C8—C1—C7A | 109.9 (3) | C3—C4—H4B | 111.0 |
N1A—C1—C7 | 80.2 (4) | H4A—C4—H4B | 109.0 |
N1—C1—C7 | 101.3 (4) | O1—C5—N1 | 126.0 (5) |
C2—C1—C7 | 116.0 (4) | O1—C5—C6 | 126.0 (7) |
C8—C1—C7 | 110.3 (3) | N1—C5—C6 | 108.0 (7) |
C7A—C1—C7 | 134.4 (4) | C5—C6—C7 | 104.9 (10) |
O2—C8—N2 | 124.28 (18) | C5—C6—H6A | 110.8 |
O2—C8—C1 | 119.36 (17) | C7—C6—H6A | 110.8 |
N2—C8—C1 | 116.35 (15) | C5—C6—H6B | 110.8 |
C10—C9—C14 | 118.84 (17) | C7—C6—H6B | 110.8 |
C10—C9—N2 | 123.82 (17) | H6A—C6—H6B | 108.8 |
C14—C9—N2 | 117.33 (16) | C6—C7—C1 | 105.0 (7) |
C9—C10—C11 | 120.42 (18) | C6—C7—H7A | 110.7 |
C9—C10—H10 | 119.8 | C1—C7—H7A | 110.7 |
C11—C10—H10 | 119.8 | C6—C7—H7B | 110.7 |
C12—C11—C10 | 120.04 (17) | C1—C7—H7B | 110.7 |
C12—C11—H11 | 120.0 | H7A—C7—H7B | 108.8 |
C10—C11—H11 | 120.0 | C5A—N1A—C1 | 117.0 (6) |
O3—C12—C11 | 124.71 (17) | C5A—N1A—C4A | 123.4 (9) |
O3—C12—C13 | 115.77 (17) | C1—N1A—C4A | 112.1 (8) |
C11—C12—C13 | 119.50 (17) | C1—C2A—C3A | 100.0 (5) |
C14—C13—C12 | 120.50 (18) | C1—C2A—H2BA | 111.8 |
C14—C13—H13 | 119.7 | C3A—C2A—H2BA | 111.8 |
C12—C13—H13 | 119.7 | C1—C2A—H2BB | 111.8 |
C13—C14—C9 | 120.69 (17) | C3A—C2A—H2BB | 111.8 |
C13—C14—H14 | 119.7 | H2BA—C2A—H2BB | 109.5 |
C9—C14—H14 | 119.7 | C2A—C3A—C4A | 106.4 (9) |
O3—C15—H15A | 109.5 | C2A—C3A—H3BA | 110.5 |
O3—C15—H15B | 109.5 | C4A—C3A—H3BA | 110.5 |
H15A—C15—H15B | 109.5 | C2A—C3A—H3BB | 110.5 |
O3—C15—H15C | 109.5 | C4A—C3A—H3BB | 110.5 |
H15A—C15—H15C | 109.5 | H3BA—C3A—H3BB | 108.6 |
H15B—C15—H15C | 109.5 | N1A—C4A—C3A | 100.1 (10) |
C17—C16—C21 | 119.7 (2) | N1A—C4A—H4BA | 111.8 |
C17—C16—H16 | 120.1 | C3A—C4A—H4BA | 111.8 |
C21—C16—H16 | 120.1 | N1A—C4A—H4BB | 111.8 |
C16—C17—C18 | 119.7 (2) | C3A—C4A—H4BB | 111.8 |
C16—C17—H17 | 120.1 | H4BA—C4A—H4BB | 109.5 |
C18—C17—H17 | 120.1 | O1A—C5A—N1A | 125.6 (7) |
C17—C18—C19 | 120.3 (2) | O1A—C5A—C6A | 127.0 (10) |
C17—C18—H18 | 119.9 | N1A—C5A—C6A | 107.4 (9) |
C19—C18—H18 | 119.9 | C5A—C6A—C7A | 101.9 (13) |
C20—C19—C18 | 119.9 (2) | C5A—C6A—H6BA | 111.4 |
C20—C19—H19 | 120.1 | C7A—C6A—H6BA | 111.4 |
C18—C19—H19 | 120.1 | C5A—C6A—H6BB | 111.4 |
C21—C20—C19 | 119.8 (2) | C7A—C6A—H6BB | 111.4 |
C21—C20—H20 | 120.1 | H6BA—C6A—H6BB | 109.3 |
C19—C20—H20 | 120.1 | C6A—C7A—C1 | 102.0 (8) |
C20—C21—C16 | 120.6 (2) | C6A—C7A—H7BA | 111.4 |
C20—C21—H21 | 119.7 | C1—C7A—H7BA | 111.4 |
C16—C21—H21 | 119.7 | C6A—C7A—H7BB | 111.4 |
C5—N1—C4 | 126.0 (9) | C1—C7A—H7BB | 111.4 |
C5—N1—C1 | 116.9 (5) | H7BA—C7A—H7BB | 109.2 |
C4—N1—C1 | 110.1 (8) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N2—HN2···N1 | 0.84 (2) | 2.39 (2) | 2.767 (8) | 108 (2) |
N2—HN2···N1A | 0.84 (2) | 2.30 (2) | 2.690 (9) | 109 (2) |
N2—HN2···O1i | 0.84 (2) | 2.13 (2) | 2.883 (2) | 148 (2) |
N2—HN2···O1Ai | 0.84 (2) | 2.13 (2) | 2.950 (4) | 162 (2) |
Symmetry code: (i) −x+2, −y+1, −z+1. |
Experimental details
Crystal data |
Chemical formula | C15H18N2O3·C6H6 |
Mr | 352.42 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 298 |
a, b, c (Å) | 9.7611 (14), 10.1229 (15), 10.7545 (13) |
α, β, γ (°) | 88.349 (9), 87.715 (9), 62.925 (9) |
V (Å3) | 945.4 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.81 × 0.43 × 0.12 |
|
Data collection |
Diffractometer | Siemens P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5059, 4295, 2607 |
Rint | 0.021 |
(sin θ/λ)max (Å−1) | 0.650 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.054, 0.134, 1.02 |
No. of reflections | 4295 |
No. of parameters | 312 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.15, −0.21 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N2—HN2···N1 | 0.84 (2) | 2.39 (2) | 2.767 (8) | 108 (2) |
N2—HN2···N1A | 0.84 (2) | 2.30 (2) | 2.690 (9) | 109 (2) |
N2—HN2···O1i | 0.84 (2) | 2.13 (2) | 2.883 (2) | 148 (2) |
N2—HN2···O1Ai | 0.84 (2) | 2.13 (2) | 2.950 (4) | 162 (2) |
Symmetry code: (i) −x+2, −y+1, −z+1. |
The amide group is a fundamental structural feature that plays an important role in the construction of molecular conformations and associations. Through a resonance-assisted process, the local geometry of the amide moiety rarely deviates from planarity, even when influenced by sterically encumbered environments (Patai, 1992; Zabicky, 1970). This conformational preference is most clearly seen from a search of the Cambrdige Structural Database (CSD, Version 5.24; Allen, 2002) for acyclic secondary amide structures, which yielded 2633 entries with 5567 C—CO—NH—C fragments. Of these entries, more than 95% adopt a planar geometry, with torsion angles of 180 (10)° (4935 fragments) or 0(10)° (102 fragments). Because of this conformational boundary and the tendency of amides to form robust hydrogen-bond interactions (Bernstein et al., 1994), the amide group offers a powerful tool for decoding the structural preferences of molecular recognition.
Non-bonded contacts involving the amide fragment of peptidyl-prolyl residues are known to play a significant role in biological systems such as protein folding and catalysis (Fischer, 1994; Schmid et al. 1993). Although the cis–trans isomerization of amide C—N bonds is significant in these processes, the intimate details of this isomerization remain relatively vague. From theoretical results, Fischer et al. (1993, 1994) proposed an intramolecular catalytic pathway for isomerization, which involves protonation of the prolyl amidic N atom followed by free rotation about the C—N bond. The existence of intramolecular N—H···N interactions was later supported by kinetic and spectroscopic evidence of a model system composed of a family of proline compounds (Cox & Lectka, 1998, 2000); proline, (I), was one of several compounds employed in the study. Data gleaned from this investigation not only revealed an important N—H···N contact but also suggested this intramolecular interaction as a point of entry to cis–trans isomerization and a key source of catalytic behaviour. The crystal structure of proline, (I), provides additional evidence for intramolecular prolyl N—H···N interaction.
The molecular conformation of (I), as observed in the crystal structure, is shown in Fig. 1. The amide group exists as the trans isomer [C9—N2—C8—C1 = 174.2 (2)° and C9—N2—C8—O2 = −4.9 (4)°], with the prolyl fragment disordered equally over two positions (Fig. 2). This positional disorder of the prolyl ring is related by an 8.8° rotation about the C1—C8 bond. As anticipated, the amidic HN2 atom is directed towards the prolyl group and forms roughly equidistant intramolecular contacts with the disorderd prolyl N atoms. Inspection of the structural parameters of this N2—HN2···N1 interaction in Table 1 provides evidence for the existence of an intramolecular hydrogen bond. These data parallel previously reported results of the 4-bromo derivative [CSD refcode RINGAW; N···N = 2.790 (6) Å, H···N = 2.35 (5) Å and N—H.·N = 120 (4)°; Cox et al., 1997], thus supplying additional support for the N—H···N contact as a viable electrostic interaction rather than a conformational artifact.
Inspection of the crystal structure reveals pairs of molecules linked by N—H···O hydrogen bonds to form centrosymmetric motifs (Fig. 3 and Table 1). These molecular assemblies, described by N1 [S(5)R22(14)] and N2 [R42(8)] graph sets (Bernstein et al., 1995), result from association of the amidic H atom with a proline O atom of a neighbouring molecule. This intermolecular N2—HN2···O1 interaction occurs in both proline conformers and displays reasonable hydrogen-bond geometry. The amidic HN2 atom is involved in both intra- and intermolecular hydrogen bonding and forms a nearly planar three-centre motif, as evidenced from the summation of angles around HN2 for the N2—HN2···N1,O1 [344 (2)°] and N2—HN2···N1A,O1A [359 (2)°] bifurcated contacts.