research papers
The crystal structure of the metastable form C polymorph of nifedipine [C17H18N2O6, 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate] was determined by means of direct-space techniques applied to high-resolution synchrotron powder diffraction data. The polymorph crystallizes in the space group and exhibits a molecular packing significantly different from that of the stable modification, with molecules aligned in an orthogonal configuration inside the unit cell. The molecular conformation, on the other hand, remains substantially unmodified between the two polymorphs. Additionally, in situ thermal characterization of nifedipine crystallization behaviour was performed, confirming the nucleation of another metastable polymorph (form B) prior to the complete crystallization of the stable modification. A complete structural characterization of form B was not possible owing to its very limited stability interval.
Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108768111021653/kd5048sup1.cif | |
Rietveld powder data file (CIF format) https://doi.org/10.1107/S0108768111021653/kd5048Isup2.rtv |
CCDC reference: 842187
Computing details top
4-(2-nitrophenyl)-2,6-dimethyl-3,5dicarbomethoxy-1,4-dihydropyridine top
Crystal data top
C17H18N2O6 | γ = 81.782 (1)° |
Mr = 346.34 | V = 1685.5 (9) Å3 |
Triclinic, P1 | Z = 4 |
a = 9.864 (1) Å | Synchrotron radiation, λ = 0.50000 Å |
b = 13.893 (9) Å | µ = 0.05 mm−1 |
c = 14.287 (3) Å | T = 298 K |
α = 61.227 (3)° | yellow |
β = 79.827 (2)° | cylinder, 14 × 0.7 mm |
Data collection top
Two-theta/omega SNB Diffractometer - ESRF | Scan method: step |
Specimen mounting: capillary | 2θmin = 1.5°, 2θmax = 12.0°, 2θstep = 0.002° |
Data collection mode: transmission |
Refinement top
Rp = 0.151 | 15 parameters |
Rwp = 0.172 | 0 restraints |
Rexp = 0.017 | 0 constraints |
RBragg = 0.151 | H-atom parameters not refined |
12508 data points | Background function: fourth-order polynomial |
Profile function: Pseudo Voigt |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
x | y | z | Biso*/Beq | ||
N1a | 0.8931 (3) | 1.1105 (2) | 0.2731 (4) | 1.51* | |
C1a | 1.0089 (4) | 1.0494 (2) | 0.2567 (2) | 1.51* | |
C2a | 1.0841 (3) | 1.1058 (2) | 0.1456 (3) | 1.51* | |
C3a | 1.0381 (3) | 0.9478 (3) | 0.3391 (3) | 1.51* | |
C4a | 1.1650 (3) | 0.8799 (4) | 0.3387 (3) | 1.51* | |
O1a | 1.2597 (5) | 0.9113 (5) | 0.2670 (2) | 1.51* | |
O2a | 1.1645 (2) | 0.7767 (3) | 0.4185 (2) | 1.51* | |
C5a | 1.2509 (2) | 0.6963 (4) | 0.3938 (3) | 1.51* | |
C6a | 0.9355 (4) | 0.8930 (2) | 0.4397 (4) | 1.51* | |
C7a | 0.8315 (4) | 0.9783 (3) | 0.4548 (2) | 1.51* | |
C8a | 0.7427 (3) | 0.9444 (3) | 0.5567 (4) | 1.51* | |
O3a | 0.7321 (2) | 0.8532 (4) | 0.6329 (2) | 1.51* | |
O4a | 0.6681 (3) | 1.0326 (3) | 0.5604 (5) | 1.51* | |
C9a | 0.5406 (4) | 1.0101 (3) | 0.6337 (2) | 1.51* | |
C10a | 0.8131 (2) | 1.0806 (5) | 0.3713 (4) | 1.51* | |
C11a | 0.7141 (4) | 1.1711 (2) | 0.3751 (3) | 1.51* | |
C12a | 0.8600 (2) | 0.8076 (3) | 0.4326 (2) | 1.51* | |
C13a | 0.7752 (3) | 0.8459 (3) | 0.3496 (2) | 1.51* | |
C14a | 0.7053 (3) | 0.7777 (5) | 0.3335 (3) | 1.51* | |
C15a | 0.7193 (3) | 0.6634 (2) | 0.3975 (2) | 1.51* | |
C16a | 0.8036 (4) | 0.6216 (5) | 0.4777 (3) | 1.51* | |
C17a | 0.8722 (4) | 0.6922 (2) | 0.4942 (4) | 1.51* | |
N2a | 0.9558 (4) | 0.6376 (3) | 0.5845 (3) | 1.51* | |
O5a | 1.0251 (5) | 0.5538 (3) | 0.6000 (2) | 1.51* | |
O6a | 0.9512 (3) | 0.6832 (5) | 0.6403 (3) | 1.51* | |
N1b | 0.6575 (3) | 0.6033 (3) | 0.7749 (2) | 1.51* | |
C1b | 0.7201 (2) | 0.5724 (4) | 0.8655 (4) | 1.51* | |
C2b | 0.7983 (3) | 0.6618 (3) | 0.8564 (4) | 1.51* | |
C3b | 0.7069 (3) | 0.4676 (3) | 0.9480 (3) | 1.51* | |
C4b | 0.7521 (4) | 0.4275 (4) | 1.0534 (3) | 1.51* | |
O1b | 0.7428 (2) | 0.3334 (2) | 1.1231 (2) | 1.51* | |
O2b | 0.7933 (4) | 0.5042 (2) | 1.0712 (3) | 1.51* | |
C5b | 0.9022 (2) | 0.4678 (4) | 1.1397 (5) | 1.51* | |
C6b | 0.6475 (5) | 0.3798 (2) | 0.9353 (3) | 1.51* | |
C7b | 0.5585 (5) | 0.4318 (4) | 0.8433 (3) | 1.51* | |
C8b | 0.4720 (3) | 0.3620 (3) | 0.8325 (4) | 1.51* | |
O3b | 0.4358 (3) | 0.3715 (3) | 0.7516 (3) | 1.51* | |
O4b | 0.4345 (2) | 0.2754 (3) | 0.9301 (5) | 1.51* | |
C9b | 0.4670 (3) | 0.1666 (3) | 0.9388 (3) | 1.51* | |
C10b | 0.5699 (3) | 0.5388 (5) | 0.7672 (3) | 1.51* | |
C11b | 0.4901 (2) | 0.5992 (4) | 0.6727 (3) | 1.51* | |
C12b | 0.7644 (3) | 0.3048 (2) | 0.9147 (5) | 1.51* | |
C13b | 0.8685 (4) | 0.3548 (4) | 0.8268 (3) | 1.51* | |
C14b | 0.9795 (3) | 0.2971 (4) | 0.8018 (5) | 1.51* | |
C15b | 0.9986 (2) | 0.1833 (2) | 0.8664 (3) | 1.51* | |
C16b | 0.9023 (5) | 0.1309 (2) | 0.9547 (2) | 1.51* | |
C17b | 0.7886 (4) | 0.1905 (3) | 0.9780 (3) | 1.51* | |
N2b | 0.6910 (3) | 0.1245 (3) | 1.0726 (3) | 1.51* | |
O5b | 0.6974 (3) | 0.0253 (3) | 1.1127 (2) | 1.51* | |
O6b | 0.6062 (3) | 0.1764 (3) | 1.1075 (5) | 1.51* | |
H1a | 1.03324 | 1.18503 | 0.10139 | 0.00* | |
H2a | 1.08781 | 1.05721 | 0.10558 | 0.00* | |
H3a | 1.18742 | 1.11603 | 0.15072 | 0.00* | |
H4a | 1.24287 | 0.61674 | 0.46248 | 0.00* | |
H5a | 1.35528 | 0.71825 | 0.37122 | 0.00* | |
H6a | 1.21577 | 0.69476 | 0.32776 | 0.00* | |
H7a | 0.99105 | 0.85235 | 0.50778 | 0.00* | |
H8a | 0.87246 | 1.17229 | 0.20987 | 0.00* | |
H9a | 0.49020 | 1.08558 | 0.62962 | 0.00* | |
H10a | 0.56040 | 0.95418 | 0.71420 | 0.00* | |
H11a | 0.47279 | 0.97307 | 0.61079 | 0.00* | |
H12a | 0.72139 | 1.24236 | 0.29775 | 0.00* | |
H13a | 0.73482 | 1.19027 | 0.43496 | 0.00* | |
H14a | 0.61068 | 1.14489 | 0.39577 | 0.00* | |
H15a | 0.76514 | 0.92947 | 0.29855 | 0.00* | |
H16a | 0.64131 | 0.81091 | 0.27369 | 0.00* | |
H17a | 0.66735 | 0.61195 | 0.38498 | 0.00* | |
H18a | 0.81531 | 0.53766 | 0.52573 | 0.00* | |
H1b | 0.67552 | 0.67536 | 0.71235 | 0.00* | |
H2b | 0.78585 | 0.73383 | 0.78115 | 0.00* | |
H3b | 0.90387 | 0.63534 | 0.86292 | 0.00* | |
H4b | 0.75636 | 0.68103 | 0.92061 | 0.00* | |
H5b | 0.92557 | 0.53529 | 1.14860 | 0.00* | |
H6b | 0.99022 | 0.43648 | 1.10587 | 0.00* | |
H7b | 0.86557 | 0.40345 | 1.21708 | 0.00* | |
H8b | 0.58222 | 0.33231 | 1.00825 | 0.00* | |
H9b | 0.43135 | 0.10618 | 1.01863 | 0.00* | |
H10b | 0.57449 | 0.15371 | 0.91997 | 0.00* | |
H11b | 0.41394 | 0.15973 | 0.88279 | 0.00* | |
H12b | 0.51943 | 0.68214 | 0.62648 | 0.00* | |
H13b | 0.38069 | 0.59887 | 0.69939 | 0.00* | |
H14b | 0.51103 | 0.55921 | 0.62334 | 0.00* | |
H15b | 0.85856 | 0.43926 | 0.77954 | 0.00* | |
H16b | 1.04874 | 0.33741 | 0.73512 | 0.00* | |
H17b | 1.08189 | 0.13927 | 0.84851 | 0.00* | |
H18b | 0.91380 | 0.04714 | 1.00342 | 0.00* |
Geometric parameters (Å, º) top
N1a—C1a | 1.378 (5) | N1b—C1b | 1.383 (5) |
N1a—C10a | 1.380 (7) | N1b—C10b | 1.383 (7) |
N1a—H8a | 0.9294 | N1b—H1b | 0.9833 |
C1a—C2a | 1.496 (5) | C1b—C2b | 1.496 (7) |
C1a—C3a | 1.366 (5) | C1b—C3b | 1.369 (7) |
C2a—H1a | 1.0712 | C2b—H2b | 1.0724 |
C2a—H2a | 1.0684 | C2b—H3b | 1.0583 |
C2a—H3a | 1.0693 | C2b—H4b | 1.0746 |
C3a—C4a | 1.457 (6) | C3b—C4b | 1.461 (5) |
C3a—C6a | 1.524 (6) | C3b—C6b | 1.523 (6) |
C4a—O1a | 1.209 (5) | C4b—O1b | 1.207 (6) |
C4a—O2a | 1.335 (6) | C4b—O2b | 1.337 (7) |
O2a—C5a | 1.449 (7) | O2b—C5b | 1.452 (6) |
C5a—H4a | 1.0704 | C5b—H5b | 1.0667 |
C5a—H5a | 1.0652 | C5b—H6b | 1.0605 |
C5a—H6a | 1.0715 | C5b—H7b | 1.0735 |
C6a—C7a | 1.524 (6) | C6b—C7b | 1.527 (6) |
C6a—C12a | 1.539 (5) | C6b—C12b | 1.528 (6) |
C6a—H7a | 1.0665 | C6b—H8b | 1.0764 |
C7a—C8a | 1.455 (6) | C7b—C8b | 1.456 (7) |
C7a—C10a | 1.359 (7) | C7b—C10b | 1.361 (8) |
C8a—O3a | 1.213 (6) | C8b—O3b | 1.211 (6) |
C8a—O4a | 1.355 (7) | C8b—O4b | 1.363 (8) |
O4a—C9a | 1.452 (6) | O4b—C9b | 1.448 (7) |
C9a—H9a | 1.0744 | C9b—H9b | 1.0723 |
C9a—H10a | 1.0683 | C9b—H10b | 1.0583 |
C9a—H11a | 1.0765 | C9b—H11b | 1.0775 |
C10a—C11a | 1.495 (7) | C10b—C11b | 1.498 (5) |
C11a—H12a | 1.0703 | C11b—H12b | 1.0695 |
C11a—H13a | 1.0685 | C11b—H13b | 1.0792 |
C11a—H14a | 1.0764 | C11b—H14b | 1.0686 |
C12a—C13a | 1.416 (4) | C12b—C13b | 1.422 (7) |
C12a—C17a | 1.408 (6) | C12b—C17b | 1.408 (7) |
C13a—C14a | 1.371 (7) | C13b—C14b | 1.362 (7) |
C13a—H15a | 1.0333 | C13b—H15b | 1.0345 |
C14a—C15a | 1.400 (7) | C14b—C15b | 1.400 (7) |
C14a—H16a | 1.0344 | C14b—H16b | 1.0264 |
C15a—C16a | 1.378 (5) | C15b—C16b | 1.384 (5) |
C15a—H17a | 1.0323 | C15b—H17b | 1.0233 |
C16a—C17a | 1.394 (7) | C16b—C17b | 1.387 (6) |
C16a—H18a | 1.0316 | C16b—H18b | 1.0302 |
C17a—N2a | 1.475 (6) | C17b—N2b | 1.481 (5) |
N2a—O5a | 1.204 (6) | N2b—O5b | 1.208 (6) |
N2a—O6a | 1.226 (8) | N2b—O6b | 1.223 (6) |
C1a—N1a—C10a | 123.9 (4) | C1b—N1b—C10b | 123.8 (4) |
C1a—N1a—H8a | 112 | C1b—N1b—H1b | 118 |
C10a—N1a—H8a | 124 | C10b—N1b—H1b | 118 |
N1a—C1a—C2a | 112.9 (3) | N1b—C1b—C2b | 112.7 (4) |
N1a—C1a—C3a | 118.2 (3) | N1b—C1b—C3b | 118.3 (4) |
C2a—C1a—C3a | 128.9 (3) | C2b—C1b—C3b | 128.9 (4) |
C1a—C2a—H1a | 109 | C1b—C2b—H2b | 109 |
C1a—C2a—H2a | 110 | C1b—C2b—H3b | 110 |
C1a—C2a—H3a | 109 | C1b—C2b—H4b | 109 |
H1a—C2a—H2a | 110 | H2b—C2b—H3b | 111 |
H1a—C2a—H3a | 109 | H2b—C2b—H4b | 109 |
H2a—C2a—H3a | 109 | H3b—C2b—H4b | 109 |
C1a—C3a—C4a | 124.4 (3) | C1b—C3b—C4b | 124.5 (4) |
C1a—C3a—C6a | 122.0 (3) | C1b—C3b—C6b | 121.9 (4) |
C4a—C3a—C6a | 113.6 (3) | C4b—C3b—C6b | 113.6 (3) |
C3a—C4a—O1a | 122.7 (4) | C3b—C4b—O1b | 122.6 (4) |
C3a—C4a—O2a | 115.0 (4) | C3b—C4b—O2b | 115.4 (4) |
O1a—C4a—O2a | 122.0 (4) | O1b—C4b—O2b | 121.7 (4) |
C4a—O2a—C5a | 115.2 (3) | C4b—O2b—C5b | 115.6 (4) |
O2a—C5a—H4a | 109 | O2b—C5b—H5b | 109 |
O2a—C5a—H5a | 110 | O2b—C5b—H6b | 110 |
O2a—C5a—H6a | 109 | O2b—C5b—H7b | 108 |
H4a—C5a—H5a | 111 | H5b—C5b—H6b | 111 |
H4a—C5a—H6a | 109 | H5b—C5b—H7b | 109 |
H5a—C5a—H6a | 109 | H6b—C5b—H7b | 109 |
C3a—C6a—C7a | 110.9 (3) | C3b—C6b—C7b | 111.1 (3) |
C3a—C6a—C12a | 110.2 (3) | C3b—C6b—C12b | 109.9 (3) |
C3a—C6a—H7a | 108 | C3b—C6b—H8b | 108 |
C7a—C6a—C12a | 110.1 (3) | C7b—C6b—C12b | 109.9 (3) |
C7a—C6a—H7a | 108 | C7b—C6b—H8b | 108 |
C12a—C6a—H7a | 109 | C12b—C6b—H8b | 110 |
C6a—C7a—C8a | 118.5 (3) | C6b—C7b—C8b | 118.7 (4) |
C6a—C7a—C10a | 120.5 (4) | C6b—C7b—C10b | 120.4 (4) |
C8a—C7a—C10a | 120.7 (4) | C8b—C7b—C10b | 120.6 (4) |
C7a—C8a—O3a | 128.9 (4) | C7b—C8b—O3b | 128.7 (4) |
C7a—C8a—O4a | 110.5 (4) | C7b—C8b—O4b | 110.8 (4) |
O3a—C8a—O4a | 120.6 (4) | O3b—C8b—O4b | 120.5 (4) |
C8a—O4a—C9a | 116.3 (4) | C8b—O4b—C9b | 116.5 (4) |
O4a—C9a—H9a | 110 | O4b—C9b—H9b | 109 |
O4a—C9a—H10a | 111 | O4b—C9b—H10b | 110 |
O4a—C9a—H11a | 109 | O4b—C9b—H11b | 109 |
H9a—C9a—H10a | 110 | H9b—C9b—H10b | 111 |
H9a—C9a—H11a | 109 | H9b—C9b—H11b | 108 |
H10a—C9a—H11a | 108 | H10b—C9b—H11b | 109 |
N1a—C10a—C7a | 120.5 (4) | N1b—C10b—C7b | 120.4 (4) |
N1a—C10a—C11a | 113.7 (4) | N1b—C10b—C11b | 113.7 (4) |
C7a—C10a—C11a | 125.8 (4) | C7b—C10b—C11b | 125.8 (4) |
C10a—C11a—H12a | 110 | C10b—C11b—H12b | 110 |
C10a—C11a—H13a | 111 | C10b—C11b—H13b | 110 |
C10a—C11a—H14a | 109 | C10b—C11b—H14b | 110 |
H12a—C11a—H13a | 110 | H12b—C11b—H13b | 110 |
H12a—C11a—H14a | 109 | H12b—C11b—H14b | 109 |
H13a—C11a—H14a | 108 | H13b—C11b—H14b | 108 |
C6a—C12a—C13a | 117.9 (3) | C6b—C12b—C13b | 117.8 (4) |
C6a—C12a—C17a | 127.9 (3) | C6b—C12b—C17b | 127.5 (4) |
C13a—C12a—C17a | 114.0 (3) | C13b—C12b—C17b | 114.5 (4) |
C12a—C13a—C14a | 123.3 (3) | C12b—C13b—C14b | 123.3 (4) |
C12a—C13a—H15a | 119 | C12b—C13b—H15b | 118 |
C14a—C13a—H15a | 118 | C14b—C13b—H15b | 119 |
C13a—C14a—C15a | 120.7 (4) | C13b—C14b—C15b | 120.1 (4) |
C13a—C14a—H16a | 120 | C13b—C14b—H16b | 120 |
C15a—C14a—H16a | 120 | C15b—C14b—H16b | 120 |
C14a—C15a—C16a | 118.3 (4) | C14b—C15b—C16b | 118.9 (3) |
C14a—C15a—H17a | 121 | C14b—C15b—H17b | 121 |
C16a—C15a—H17a | 121 | C16b—C15b—H17b | 120 |
C15a—C16a—C17a | 120.3 (4) | C15b—C16b—C17b | 120.3 (3) |
C15a—C16a—H18a | 120 | C15b—C16b—H18b | 120 |
C17a—C16a—H18a | 120 | C17b—C16b—H18b | 119 |
C12a—C17a—C16a | 123.3 (4) | C12b—C17b—C16b | 122.8 (4) |
C12a—C17a—N2a | 121.6 (4) | C12b—C17b—N2b | 122.1 (4) |
C16a—C17a—N2a | 115.1 (4) | C16b—C17b—N2b | 115.1 (3) |
C17a—N2a—O5a | 120.7 (4) | C17b—N2b—O5b | 121.2 (4) |
C17a—N2a—O6a | 116.2 (4) | C17b—N2b—O6b | 116.0 (4) |
O5a—N2a—O6a | 123.1 (4) | O5b—N2b—O6b | 122.8 (4) |