organic compounds
Diethyl 4-(1H-imidazol-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
aDepartment of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Republic of Korea
*Correspondence e-mail: dskoh@dongduk.ac.kr
In the title compound, C16H21N3O4, the 1,4-dihydropyridine ring adopts a flattened boat conformation, with the imidazole substituent in an axial orientation [dihedral angle between ring planes = 82.9 (6)°]. In the pairs of N—H⋯O and N—H⋯N hydrogen bonds with graph-set notation R22(14) connect the molecules into chains running along the c-axis direction.
CCDC reference: 1977288
Structure description
Hantzsch 1,4-dihydropyridines (1,4-DHPs) have shown broad biological activities which include calcium channel blocker (Schaller et al., 2018), antimycobacterial (Lentz et al., 2016), anticonvulsant (Prasanthi et al., 2014) and anti-tubercular (Khoshneviszadeh et al., 2009) activities. According to our recent report, they show anti-cancer activities in HCT116 human colon cancer cell lines (Ahn et al., 2018). We report herein the synthesis and of the title compound (Fig. 1).
In the title compound, the 1,4-dihydropyridine (C1–C5/N1) ring is twisted slightly from planarity, with a maximum deviation of 0.178 (1) Å at C3 (r.m.s. deviation = 0.113 Å). The dihedral angle formed between the plane of the 1,4-dihydropyridine (C1–C5/N1) and imidazole (C10–C12/N2–N3) rings is 82.9 (6)°. One of the carbonyl groups (C13=O3) lies on the same side as the methyl group at C16 with the other carbonyl group (C7=O1) on the opposite side. In the crystal, pairs of N—H⋯O and N—H⋯N hydrogen bonds with graph-set notation R22(14) connect the molecules into chains running along the c-axis direction (Table 1, Fig. 2).
Synthesis and crystallization
Methyl acetoacetate (20 mmol) and 1H-imidazole-2-carbaldehyde (10 mmol) were dissolved in 30 ml of ethanol to give a clear solution. To the mixture, ammonium acetate (10 mmol) was added and the reaction mixture was heated at 365 K for 5 h. After completion of the reaction (monitored by TLC), the mixture was cooled to room temperature to produce a solid product. This solid was recrystallized from ethanol solution to obtain single-crystal of the title compound in 61% yield.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1977288
https://doi.org/10.1107/S2414314620000346/bt4088sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314620000346/bt4088Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314620000346/bt4088Isup3.cml
Data collection: APEX2 (Bruker, 2012); cell
SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: publCIF (Westrip, 2010).C16H21N3O4 | Z = 2 |
Mr = 319.36 | F(000) = 340 |
Triclinic, P1 | Dx = 1.301 Mg m−3 |
a = 8.127 (7) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 8.411 (9) Å | Cell parameters from 9982 reflections |
c = 12.536 (10) Å | θ = 2.5–28.3° |
α = 105.36 (4)° | µ = 0.10 mm−1 |
β = 96.52 (2)° | T = 223 K |
γ = 94.77 (3)° | Block, colourless |
V = 815.1 (13) Å3 | 0.28 × 0.21 × 0.14 mm |
PHOTON 100 CMOS diffractometer | 3144 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.041 |
Absorption correction: multi-scan (SADABS; Bruker, 2012) | θmax = 28.3°, θmin = 2.5° |
Tmin = 0.974, Tmax = 0.987 | h = −10→10 |
33431 measured reflections | k = −11→11 |
3920 independent reflections | l = −16→16 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.049 | H-atom parameters constrained |
wR(F2) = 0.142 | w = 1/[σ2(Fo2) + (0.0734P)2 + 0.2436P] where P = (Fo2 + 2Fc2)/3 |
S = 1.06 | (Δ/σ)max < 0.001 |
3920 reflections | Δρmax = 0.32 e Å−3 |
212 parameters | Δρmin = −0.23 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.18302 (15) | 0.47356 (14) | 0.46454 (9) | 0.0280 (3) | |
H1 | 0.1979 | 0.5159 | 0.5367 | 0.034* | |
C1 | 0.21728 (16) | 0.57673 (16) | 0.39890 (11) | 0.0251 (3) | |
C2 | 0.16729 (15) | 0.52079 (16) | 0.28644 (10) | 0.0232 (3) | |
C3 | 0.04796 (16) | 0.36033 (15) | 0.23758 (10) | 0.0229 (3) | |
H3 | 0.0781 | 0.3040 | 0.1637 | 0.028* | |
C4 | 0.06773 (16) | 0.24414 (16) | 0.31144 (11) | 0.0253 (3) | |
C5 | 0.12622 (16) | 0.30616 (17) | 0.42189 (11) | 0.0261 (3) | |
C6 | 0.3103 (2) | 0.74263 (19) | 0.46493 (12) | 0.0374 (4) | |
H6A | 0.4280 | 0.7424 | 0.4580 | 0.056* | |
H6B | 0.2959 | 0.7626 | 0.5430 | 0.056* | |
H6C | 0.2669 | 0.8296 | 0.4363 | 0.056* | |
C7 | 0.21403 (16) | 0.60658 (17) | 0.20487 (11) | 0.0258 (3) | |
O1 | 0.15784 (14) | 0.55990 (13) | 0.10544 (8) | 0.0368 (3) | |
O2 | 0.32952 (13) | 0.73897 (13) | 0.24786 (8) | 0.0333 (3) | |
C8 | 0.3728 (2) | 0.83898 (19) | 0.17506 (13) | 0.0387 (4) | |
H8A | 0.2719 | 0.8672 | 0.1369 | 0.046* | |
H8B | 0.4361 | 0.7785 | 0.1186 | 0.046* | |
C9 | 0.4771 (3) | 0.9939 (2) | 0.24842 (16) | 0.0521 (5) | |
H9A | 0.4123 | 1.0534 | 0.3030 | 0.078* | |
H9B | 0.5110 | 1.0643 | 0.2028 | 0.078* | |
H9C | 0.5754 | 0.9640 | 0.2867 | 0.078* | |
C10 | −0.13059 (16) | 0.39732 (15) | 0.21997 (10) | 0.0231 (3) | |
N2 | −0.20049 (15) | 0.42932 (16) | 0.12553 (10) | 0.0315 (3) | |
H2 | −0.1525 | 0.4293 | 0.0669 | 0.038* | |
C11 | −0.36104 (19) | 0.4617 (2) | 0.13918 (13) | 0.0384 (4) | |
H11 | −0.4397 | 0.4889 | 0.0878 | 0.046* | |
C12 | −0.38247 (19) | 0.4467 (2) | 0.24119 (13) | 0.0373 (3) | |
H12 | −0.4814 | 0.4613 | 0.2730 | 0.045* | |
N3 | −0.23804 (14) | 0.40668 (16) | 0.29244 (9) | 0.0302 (3) | |
C13 | 0.00797 (18) | 0.06611 (17) | 0.26232 (12) | 0.0308 (3) | |
O3 | 0.02408 (19) | −0.04606 (14) | 0.30548 (11) | 0.0556 (4) | |
O4 | −0.07121 (14) | 0.03801 (12) | 0.15720 (9) | 0.0360 (3) | |
C14 | −0.1454 (2) | −0.13100 (19) | 0.10123 (14) | 0.0406 (4) | |
H14A | −0.2060 | −0.1768 | 0.1517 | 0.049* | |
H14B | −0.0586 | −0.2015 | 0.0776 | 0.049* | |
C15 | −0.2623 (2) | −0.1240 (2) | 0.00188 (14) | 0.0441 (4) | |
H15A | −0.3471 | −0.0535 | 0.0264 | 0.066* | |
H15B | −0.3149 | −0.2350 | −0.0377 | 0.066* | |
H15C | −0.2006 | −0.0790 | −0.0475 | 0.066* | |
C16 | 0.1393 (2) | 0.2112 (2) | 0.50829 (13) | 0.0372 (4) | |
H16A | 0.0529 | 0.1174 | 0.4870 | 0.056* | |
H16B | 0.1256 | 0.2835 | 0.5803 | 0.056* | |
H16C | 0.2479 | 0.1716 | 0.5132 | 0.056* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0361 (6) | 0.0299 (6) | 0.0185 (5) | 0.0004 (5) | 0.0041 (4) | 0.0086 (4) |
C1 | 0.0256 (6) | 0.0272 (6) | 0.0237 (6) | 0.0016 (5) | 0.0050 (5) | 0.0090 (5) |
C2 | 0.0240 (6) | 0.0247 (6) | 0.0222 (6) | 0.0008 (5) | 0.0045 (5) | 0.0088 (5) |
C3 | 0.0280 (6) | 0.0228 (6) | 0.0186 (6) | 0.0010 (5) | 0.0044 (5) | 0.0068 (4) |
C4 | 0.0273 (6) | 0.0246 (6) | 0.0269 (6) | 0.0043 (5) | 0.0060 (5) | 0.0111 (5) |
C5 | 0.0268 (6) | 0.0288 (7) | 0.0265 (6) | 0.0045 (5) | 0.0061 (5) | 0.0130 (5) |
C6 | 0.0467 (9) | 0.0365 (8) | 0.0239 (7) | −0.0088 (7) | 0.0006 (6) | 0.0055 (6) |
C7 | 0.0272 (6) | 0.0277 (6) | 0.0236 (6) | 0.0010 (5) | 0.0049 (5) | 0.0092 (5) |
O1 | 0.0488 (6) | 0.0388 (6) | 0.0221 (5) | −0.0082 (5) | 0.0029 (4) | 0.0124 (4) |
O2 | 0.0368 (6) | 0.0343 (5) | 0.0292 (5) | −0.0092 (4) | 0.0029 (4) | 0.0144 (4) |
C8 | 0.0481 (9) | 0.0347 (8) | 0.0352 (8) | −0.0084 (7) | 0.0090 (7) | 0.0158 (6) |
C9 | 0.0616 (12) | 0.0394 (9) | 0.0509 (10) | −0.0158 (8) | 0.0143 (9) | 0.0092 (8) |
C10 | 0.0296 (6) | 0.0211 (6) | 0.0170 (6) | −0.0020 (5) | 0.0001 (5) | 0.0055 (4) |
N2 | 0.0356 (6) | 0.0397 (7) | 0.0216 (6) | 0.0011 (5) | 0.0005 (4) | 0.0147 (5) |
C11 | 0.0332 (8) | 0.0492 (9) | 0.0336 (8) | 0.0043 (7) | −0.0072 (6) | 0.0180 (7) |
C12 | 0.0272 (7) | 0.0506 (9) | 0.0353 (8) | 0.0071 (6) | 0.0013 (6) | 0.0144 (7) |
N3 | 0.0274 (6) | 0.0424 (7) | 0.0228 (6) | 0.0058 (5) | 0.0034 (4) | 0.0119 (5) |
C13 | 0.0350 (7) | 0.0270 (7) | 0.0325 (7) | 0.0034 (5) | 0.0064 (6) | 0.0113 (5) |
O3 | 0.0870 (10) | 0.0298 (6) | 0.0494 (7) | −0.0010 (6) | −0.0086 (7) | 0.0200 (5) |
O4 | 0.0481 (6) | 0.0242 (5) | 0.0332 (6) | −0.0033 (4) | 0.0001 (5) | 0.0083 (4) |
C14 | 0.0466 (9) | 0.0245 (7) | 0.0461 (9) | −0.0043 (6) | 0.0013 (7) | 0.0065 (6) |
C15 | 0.0401 (9) | 0.0456 (9) | 0.0402 (9) | −0.0039 (7) | 0.0046 (7) | 0.0040 (7) |
C16 | 0.0491 (9) | 0.0376 (8) | 0.0299 (7) | 0.0046 (7) | 0.0038 (6) | 0.0187 (6) |
N1—C1 | 1.3777 (19) | C9—H9B | 0.9700 |
N1—C5 | 1.385 (2) | C9—H9C | 0.9700 |
N1—H1 | 0.8700 | C10—N3 | 1.3221 (19) |
C1—C2 | 1.364 (2) | C10—N2 | 1.3558 (19) |
C1—C6 | 1.508 (2) | N2—C11 | 1.375 (2) |
C2—C7 | 1.464 (2) | N2—H2 | 0.8700 |
C2—C3 | 1.532 (2) | C11—C12 | 1.347 (2) |
C3—C10 | 1.513 (2) | C11—H11 | 0.9400 |
C3—C4 | 1.520 (2) | C12—N3 | 1.383 (2) |
C3—H3 | 0.9900 | C12—H12 | 0.9400 |
C4—C5 | 1.357 (2) | C13—O3 | 1.214 (2) |
C4—C13 | 1.476 (2) | C13—O4 | 1.350 (2) |
C5—C16 | 1.506 (2) | O4—C14 | 1.452 (2) |
C6—H6A | 0.9700 | C14—C15 | 1.496 (3) |
C6—H6B | 0.9700 | C14—H14A | 0.9800 |
C6—H6C | 0.9700 | C14—H14B | 0.9800 |
C7—O1 | 1.2239 (19) | C15—H15A | 0.9700 |
C7—O2 | 1.3434 (19) | C15—H15B | 0.9700 |
O2—C8 | 1.4473 (19) | C15—H15C | 0.9700 |
C8—C9 | 1.506 (2) | C16—H16A | 0.9700 |
C8—H8A | 0.9800 | C16—H16B | 0.9700 |
C8—H8B | 0.9800 | C16—H16C | 0.9700 |
C9—H9A | 0.9700 | ||
C1—N1—C5 | 123.55 (12) | H9A—C9—H9B | 109.5 |
C1—N1—H1 | 118.2 | C8—C9—H9C | 109.5 |
C5—N1—H1 | 118.2 | H9A—C9—H9C | 109.5 |
C2—C1—N1 | 118.86 (13) | H9B—C9—H9C | 109.5 |
C2—C1—C6 | 128.14 (12) | N3—C10—N2 | 110.72 (13) |
N1—C1—C6 | 113.00 (13) | N3—C10—C3 | 126.17 (12) |
C1—C2—C7 | 124.90 (13) | N2—C10—C3 | 123.10 (12) |
C1—C2—C3 | 120.01 (11) | C10—N2—C11 | 107.57 (12) |
C7—C2—C3 | 115.05 (12) | C10—N2—H2 | 126.2 |
C10—C3—C4 | 111.44 (10) | C11—N2—H2 | 126.2 |
C10—C3—C2 | 111.01 (12) | C12—C11—N2 | 105.92 (13) |
C4—C3—C2 | 110.65 (12) | C12—C11—H11 | 127.0 |
C10—C3—H3 | 107.9 | N2—C11—H11 | 127.0 |
C4—C3—H3 | 107.9 | C11—C12—N3 | 110.26 (14) |
C2—C3—H3 | 107.9 | C11—C12—H12 | 124.9 |
C5—C4—C13 | 121.28 (13) | N3—C12—H12 | 124.9 |
C5—C4—C3 | 120.13 (13) | C10—N3—C12 | 105.53 (13) |
C13—C4—C3 | 118.36 (13) | O3—C13—O4 | 121.56 (14) |
C4—C5—N1 | 119.54 (12) | O3—C13—C4 | 127.60 (15) |
C4—C5—C16 | 126.95 (14) | O4—C13—C4 | 110.84 (12) |
N1—C5—C16 | 113.51 (13) | C13—O4—C14 | 116.62 (12) |
C1—C6—H6A | 109.5 | O4—C14—C15 | 106.98 (14) |
C1—C6—H6B | 109.5 | O4—C14—H14A | 110.3 |
H6A—C6—H6B | 109.5 | C15—C14—H14A | 110.3 |
C1—C6—H6C | 109.5 | O4—C14—H14B | 110.3 |
H6A—C6—H6C | 109.5 | C15—C14—H14B | 110.3 |
H6B—C6—H6C | 109.5 | H14A—C14—H14B | 108.6 |
O1—C7—O2 | 122.36 (12) | C14—C15—H15A | 109.5 |
O1—C7—C2 | 123.54 (13) | C14—C15—H15B | 109.5 |
O2—C7—C2 | 114.06 (12) | H15A—C15—H15B | 109.5 |
C7—O2—C8 | 117.63 (12) | C14—C15—H15C | 109.5 |
O2—C8—C9 | 106.51 (14) | H15A—C15—H15C | 109.5 |
O2—C8—H8A | 110.4 | H15B—C15—H15C | 109.5 |
C9—C8—H8A | 110.4 | C5—C16—H16A | 109.5 |
O2—C8—H8B | 110.4 | C5—C16—H16B | 109.5 |
C9—C8—H8B | 110.4 | H16A—C16—H16B | 109.5 |
H8A—C8—H8B | 108.6 | C5—C16—H16C | 109.5 |
C8—C9—H9A | 109.5 | H16A—C16—H16C | 109.5 |
C8—C9—H9B | 109.5 | H16B—C16—H16C | 109.5 |
C5—N1—C1—C2 | 11.5 (2) | C3—C2—C7—O2 | −174.61 (11) |
C5—N1—C1—C6 | −168.01 (13) | O1—C7—O2—C8 | 7.2 (2) |
N1—C1—C2—C7 | −171.32 (12) | C2—C7—O2—C8 | −175.03 (12) |
C6—C1—C2—C7 | 8.1 (2) | C7—O2—C8—C9 | 169.35 (14) |
N1—C1—C2—C3 | 11.18 (19) | C4—C3—C10—N3 | 32.28 (17) |
C6—C1—C2—C3 | −169.38 (13) | C2—C3—C10—N3 | −91.54 (16) |
C1—C2—C3—C10 | 96.34 (14) | C4—C3—C10—N2 | −149.20 (12) |
C7—C2—C3—C10 | −81.40 (14) | C2—C3—C10—N2 | 86.98 (15) |
C1—C2—C3—C4 | −27.93 (17) | N3—C10—N2—C11 | 0.37 (16) |
C7—C2—C3—C4 | 154.33 (11) | C3—C10—N2—C11 | −178.36 (12) |
C10—C3—C4—C5 | −98.67 (15) | C10—N2—C11—C12 | −0.51 (17) |
C2—C3—C4—C5 | 25.35 (17) | N2—C11—C12—N3 | 0.48 (19) |
C10—C3—C4—C13 | 75.95 (15) | N2—C10—N3—C12 | −0.07 (16) |
C2—C3—C4—C13 | −160.02 (12) | C3—C10—N3—C12 | 178.60 (12) |
C13—C4—C5—N1 | 179.24 (12) | C11—C12—N3—C10 | −0.26 (18) |
C3—C4—C5—N1 | −6.29 (19) | C5—C4—C13—O3 | −11.3 (2) |
C13—C4—C5—C16 | −0.2 (2) | C3—C4—C13—O3 | 174.13 (16) |
C3—C4—C5—C16 | 174.29 (13) | C5—C4—C13—O4 | 169.00 (12) |
C1—N1—C5—C4 | −14.2 (2) | C3—C4—C13—O4 | −5.56 (17) |
C1—N1—C5—C16 | 165.30 (13) | O3—C13—O4—C14 | 3.9 (2) |
C1—C2—C7—O1 | −174.51 (14) | C4—C13—O4—C14 | −176.41 (12) |
C3—C2—C7—O1 | 3.1 (2) | C13—O4—C14—C15 | 165.03 (13) |
C1—C2—C7—O2 | 7.8 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···N3i | 0.87 | 2.05 | 2.913 (3) | 175 |
N2—H2···O1ii | 0.87 | 2.18 | 2.979 (3) | 152 |
Symmetry codes: (i) −x, −y+1, −z+1; (ii) −x, −y+1, −z. |
Funding information
The authors acknowledge financial support from the Basic Science Research Program (award No. NRF-2019R1F1A1058747).
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