organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

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

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 10 January 2020; accepted 13 January 2020; online 17 January 2020)

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 crystal structure, 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.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Hantzsch 1,4-di­hydro­pyridines (1,4-DHPs) have shown broad biological activities which include calcium channel blocker (Schaller et al., 2018[Schaller, D., Gündüz, M. G., Zhang, F. X., Zamponi, G. W. & Wolber, G. (2018). Eur. J. Med. Chem. 155, 1-12.]), anti­mycobacterial (Lentz et al., 2016[Lentz, F., Hemmer, M., Reiling, N. & Hilgeroth, A. (2016). Bioorg. Med. Chem. Lett. 26, 5896-5898.]), anti­convulsant (Prasanthi et al., 2014[Prasanthi, G., Prasad, K. V. S. R. G. & Bharathi, K. (2014). Eur. J. Med. Chem. 73, 97-104.]) and anti-tubercular (Khoshneviszadeh et al., 2009[Khoshneviszadeh, M., Edraki, N., Javidnia, K., Alborzi, A., Pourabbas, B., Mardaneh, J. & Miri, R. (2009). Bioorg. Med. Chem. 17, 1579-1586.]) activities. According to our recent report, they show anti-cancer activities in HCT116 human colon cancer cell lines (Ahn et al., 2018[Ahn, S., Lee, Y., Park, J., Lee, J., Shin, Y., Lee, Y., Koh, D. & Lim, Y. (2018). Med. Chem. 14, 851-862.]). We report herein the synthesis and crystal structure of the title compound (Fig. 1[link]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, showing the atom-labelling scheme with displacement ellipsoids drawn at the 30% probability level.

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[link], Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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.
[Figure 2]
Figure 2
Part of the crystal structure with two inter­mol­ecular hydrogen bonds (blue and yellow dashed lines) are shown. For clarity, only those H atoms involved in hydrogen bonding are shown.

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 refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C16H21N3O4
Mr 319.36
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 223
a, b, c (Å) 8.127 (7), 8.411 (9), 12.536 (10)
α, β, γ (°) 105.36 (4), 96.52 (2), 94.77 (3)
V3) 815.1 (13)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.28 × 0.21 × 0.14
 
Data collection
Diffractometer PHOTON 100 CMOS
Absorption correction Multi-scan (SADABS; Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS, Bruker AXS Inc. Madison, Wisconsin, USA.])
Tmin, Tmax 0.974, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections 33431, 3920, 3144
Rint 0.041
(sin θ/λ)max−1) 0.667
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.142, 1.06
No. of reflections 3920
No. of parameters 212
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.32, −0.23
Computer programs: APEX2 and SAINT (Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS, Bruker AXS Inc. Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data


Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: 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).

Diethyl 4-(1H-imidazol-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate top
Crystal data top
C16H21N3O4Z = 2
Mr = 319.36F(000) = 340
Triclinic, P1Dx = 1.301 Mg m3
a = 8.127 (7) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.411 (9) ÅCell parameters from 9982 reflections
c = 12.536 (10) Åθ = 2.5–28.3°
α = 105.36 (4)°µ = 0.10 mm1
β = 96.52 (2)°T = 223 K
γ = 94.77 (3)°Block, colourless
V = 815.1 (13) Å30.28 × 0.21 × 0.14 mm
Data collection top
PHOTON 100 CMOS
diffractometer
3144 reflections with I > 2σ(I)
φ and ω scansRint = 0.041
Absorption correction: multi-scan
(SADABS; Bruker, 2012)
θmax = 28.3°, θmin = 2.5°
Tmin = 0.974, Tmax = 0.987h = 1010
33431 measured reflectionsk = 1111
3920 independent reflectionsl = 1616
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049H-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 reflectionsΔρmax = 0.32 e Å3
212 parametersΔρmin = 0.23 e Å3
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.18302 (15)0.47356 (14)0.46454 (9)0.0280 (3)
H10.19790.51590.53670.034*
C10.21728 (16)0.57673 (16)0.39890 (11)0.0251 (3)
C20.16729 (15)0.52079 (16)0.28644 (10)0.0232 (3)
C30.04796 (16)0.36033 (15)0.23758 (10)0.0229 (3)
H30.07810.30400.16370.028*
C40.06773 (16)0.24414 (16)0.31144 (11)0.0253 (3)
C50.12622 (16)0.30616 (17)0.42189 (11)0.0261 (3)
C60.3103 (2)0.74263 (19)0.46493 (12)0.0374 (4)
H6A0.42800.74240.45800.056*
H6B0.29590.76260.54300.056*
H6C0.26690.82960.43630.056*
C70.21403 (16)0.60658 (17)0.20487 (11)0.0258 (3)
O10.15784 (14)0.55990 (13)0.10544 (8)0.0368 (3)
O20.32952 (13)0.73897 (13)0.24786 (8)0.0333 (3)
C80.3728 (2)0.83898 (19)0.17506 (13)0.0387 (4)
H8A0.27190.86720.13690.046*
H8B0.43610.77850.11860.046*
C90.4771 (3)0.9939 (2)0.24842 (16)0.0521 (5)
H9A0.41231.05340.30300.078*
H9B0.51101.06430.20280.078*
H9C0.57540.96400.28670.078*
C100.13059 (16)0.39732 (15)0.21997 (10)0.0231 (3)
N20.20049 (15)0.42932 (16)0.12553 (10)0.0315 (3)
H20.15250.42930.06690.038*
C110.36104 (19)0.4617 (2)0.13918 (13)0.0384 (4)
H110.43970.48890.08780.046*
C120.38247 (19)0.4467 (2)0.24119 (13)0.0373 (3)
H120.48140.46130.27300.045*
N30.23804 (14)0.40668 (16)0.29244 (9)0.0302 (3)
C130.00797 (18)0.06611 (17)0.26232 (12)0.0308 (3)
O30.02408 (19)0.04606 (14)0.30548 (11)0.0556 (4)
O40.07121 (14)0.03801 (12)0.15720 (9)0.0360 (3)
C140.1454 (2)0.13100 (19)0.10123 (14)0.0406 (4)
H14A0.20600.17680.15170.049*
H14B0.05860.20150.07760.049*
C150.2623 (2)0.1240 (2)0.00188 (14)0.0441 (4)
H15A0.34710.05350.02640.066*
H15B0.31490.23500.03770.066*
H15C0.20060.07900.04750.066*
C160.1393 (2)0.2112 (2)0.50829 (13)0.0372 (4)
H16A0.05290.11740.48700.056*
H16B0.12560.28350.58030.056*
H16C0.24790.17160.51320.056*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0361 (6)0.0299 (6)0.0185 (5)0.0004 (5)0.0041 (4)0.0086 (4)
C10.0256 (6)0.0272 (6)0.0237 (6)0.0016 (5)0.0050 (5)0.0090 (5)
C20.0240 (6)0.0247 (6)0.0222 (6)0.0008 (5)0.0045 (5)0.0088 (5)
C30.0280 (6)0.0228 (6)0.0186 (6)0.0010 (5)0.0044 (5)0.0068 (4)
C40.0273 (6)0.0246 (6)0.0269 (6)0.0043 (5)0.0060 (5)0.0111 (5)
C50.0268 (6)0.0288 (7)0.0265 (6)0.0045 (5)0.0061 (5)0.0130 (5)
C60.0467 (9)0.0365 (8)0.0239 (7)0.0088 (7)0.0006 (6)0.0055 (6)
C70.0272 (6)0.0277 (6)0.0236 (6)0.0010 (5)0.0049 (5)0.0092 (5)
O10.0488 (6)0.0388 (6)0.0221 (5)0.0082 (5)0.0029 (4)0.0124 (4)
O20.0368 (6)0.0343 (5)0.0292 (5)0.0092 (4)0.0029 (4)0.0144 (4)
C80.0481 (9)0.0347 (8)0.0352 (8)0.0084 (7)0.0090 (7)0.0158 (6)
C90.0616 (12)0.0394 (9)0.0509 (10)0.0158 (8)0.0143 (9)0.0092 (8)
C100.0296 (6)0.0211 (6)0.0170 (6)0.0020 (5)0.0001 (5)0.0055 (4)
N20.0356 (6)0.0397 (7)0.0216 (6)0.0011 (5)0.0005 (4)0.0147 (5)
C110.0332 (8)0.0492 (9)0.0336 (8)0.0043 (7)0.0072 (6)0.0180 (7)
C120.0272 (7)0.0506 (9)0.0353 (8)0.0071 (6)0.0013 (6)0.0144 (7)
N30.0274 (6)0.0424 (7)0.0228 (6)0.0058 (5)0.0034 (4)0.0119 (5)
C130.0350 (7)0.0270 (7)0.0325 (7)0.0034 (5)0.0064 (6)0.0113 (5)
O30.0870 (10)0.0298 (6)0.0494 (7)0.0010 (6)0.0086 (7)0.0200 (5)
O40.0481 (6)0.0242 (5)0.0332 (6)0.0033 (4)0.0001 (5)0.0083 (4)
C140.0466 (9)0.0245 (7)0.0461 (9)0.0043 (6)0.0013 (7)0.0065 (6)
C150.0401 (9)0.0456 (9)0.0402 (9)0.0039 (7)0.0046 (7)0.0040 (7)
C160.0491 (9)0.0376 (8)0.0299 (7)0.0046 (7)0.0038 (6)0.0187 (6)
Geometric parameters (Å, º) top
N1—C11.3777 (19)C9—H9B0.9700
N1—C51.385 (2)C9—H9C0.9700
N1—H10.8700C10—N31.3221 (19)
C1—C21.364 (2)C10—N21.3558 (19)
C1—C61.508 (2)N2—C111.375 (2)
C2—C71.464 (2)N2—H20.8700
C2—C31.532 (2)C11—C121.347 (2)
C3—C101.513 (2)C11—H110.9400
C3—C41.520 (2)C12—N31.383 (2)
C3—H30.9900C12—H120.9400
C4—C51.357 (2)C13—O31.214 (2)
C4—C131.476 (2)C13—O41.350 (2)
C5—C161.506 (2)O4—C141.452 (2)
C6—H6A0.9700C14—C151.496 (3)
C6—H6B0.9700C14—H14A0.9800
C6—H6C0.9700C14—H14B0.9800
C7—O11.2239 (19)C15—H15A0.9700
C7—O21.3434 (19)C15—H15B0.9700
O2—C81.4473 (19)C15—H15C0.9700
C8—C91.506 (2)C16—H16A0.9700
C8—H8A0.9800C16—H16B0.9700
C8—H8B0.9800C16—H16C0.9700
C9—H9A0.9700
C1—N1—C5123.55 (12)H9A—C9—H9B109.5
C1—N1—H1118.2C8—C9—H9C109.5
C5—N1—H1118.2H9A—C9—H9C109.5
C2—C1—N1118.86 (13)H9B—C9—H9C109.5
C2—C1—C6128.14 (12)N3—C10—N2110.72 (13)
N1—C1—C6113.00 (13)N3—C10—C3126.17 (12)
C1—C2—C7124.90 (13)N2—C10—C3123.10 (12)
C1—C2—C3120.01 (11)C10—N2—C11107.57 (12)
C7—C2—C3115.05 (12)C10—N2—H2126.2
C10—C3—C4111.44 (10)C11—N2—H2126.2
C10—C3—C2111.01 (12)C12—C11—N2105.92 (13)
C4—C3—C2110.65 (12)C12—C11—H11127.0
C10—C3—H3107.9N2—C11—H11127.0
C4—C3—H3107.9C11—C12—N3110.26 (14)
C2—C3—H3107.9C11—C12—H12124.9
C5—C4—C13121.28 (13)N3—C12—H12124.9
C5—C4—C3120.13 (13)C10—N3—C12105.53 (13)
C13—C4—C3118.36 (13)O3—C13—O4121.56 (14)
C4—C5—N1119.54 (12)O3—C13—C4127.60 (15)
C4—C5—C16126.95 (14)O4—C13—C4110.84 (12)
N1—C5—C16113.51 (13)C13—O4—C14116.62 (12)
C1—C6—H6A109.5O4—C14—C15106.98 (14)
C1—C6—H6B109.5O4—C14—H14A110.3
H6A—C6—H6B109.5C15—C14—H14A110.3
C1—C6—H6C109.5O4—C14—H14B110.3
H6A—C6—H6C109.5C15—C14—H14B110.3
H6B—C6—H6C109.5H14A—C14—H14B108.6
O1—C7—O2122.36 (12)C14—C15—H15A109.5
O1—C7—C2123.54 (13)C14—C15—H15B109.5
O2—C7—C2114.06 (12)H15A—C15—H15B109.5
C7—O2—C8117.63 (12)C14—C15—H15C109.5
O2—C8—C9106.51 (14)H15A—C15—H15C109.5
O2—C8—H8A110.4H15B—C15—H15C109.5
C9—C8—H8A110.4C5—C16—H16A109.5
O2—C8—H8B110.4C5—C16—H16B109.5
C9—C8—H8B110.4H16A—C16—H16B109.5
H8A—C8—H8B108.6C5—C16—H16C109.5
C8—C9—H9A109.5H16A—C16—H16C109.5
C8—C9—H9B109.5H16B—C16—H16C109.5
C5—N1—C1—C211.5 (2)C3—C2—C7—O2174.61 (11)
C5—N1—C1—C6168.01 (13)O1—C7—O2—C87.2 (2)
N1—C1—C2—C7171.32 (12)C2—C7—O2—C8175.03 (12)
C6—C1—C2—C78.1 (2)C7—O2—C8—C9169.35 (14)
N1—C1—C2—C311.18 (19)C4—C3—C10—N332.28 (17)
C6—C1—C2—C3169.38 (13)C2—C3—C10—N391.54 (16)
C1—C2—C3—C1096.34 (14)C4—C3—C10—N2149.20 (12)
C7—C2—C3—C1081.40 (14)C2—C3—C10—N286.98 (15)
C1—C2—C3—C427.93 (17)N3—C10—N2—C110.37 (16)
C7—C2—C3—C4154.33 (11)C3—C10—N2—C11178.36 (12)
C10—C3—C4—C598.67 (15)C10—N2—C11—C120.51 (17)
C2—C3—C4—C525.35 (17)N2—C11—C12—N30.48 (19)
C10—C3—C4—C1375.95 (15)N2—C10—N3—C120.07 (16)
C2—C3—C4—C13160.02 (12)C3—C10—N3—C12178.60 (12)
C13—C4—C5—N1179.24 (12)C11—C12—N3—C100.26 (18)
C3—C4—C5—N16.29 (19)C5—C4—C13—O311.3 (2)
C13—C4—C5—C160.2 (2)C3—C4—C13—O3174.13 (16)
C3—C4—C5—C16174.29 (13)C5—C4—C13—O4169.00 (12)
C1—N1—C5—C414.2 (2)C3—C4—C13—O45.56 (17)
C1—N1—C5—C16165.30 (13)O3—C13—O4—C143.9 (2)
C1—C2—C7—O1174.51 (14)C4—C13—O4—C14176.41 (12)
C3—C2—C7—O13.1 (2)C13—O4—C14—C15165.03 (13)
C1—C2—C7—O27.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···N3i0.872.052.913 (3)175
N2—H2···O1ii0.872.182.979 (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).

References

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