Synthesis, crystal structure and Hirshfeld surface analysis of diethyl 2,6-dimethyl-4-(thio­phen-3-yl)-1,4-di­hydro­pyridine-3,5-di­carboxyl­ate

Vu Quoc, T.; Tran Thi Thuy, D.; Phung Ngoc, T.; Vu Quoc, M.; Nguyen, H.; Duong Khanh, L.; Tu Quang, A.; Van Meervelt, L.

doi:10.1107/S2056989019015081

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ISSN: 2056-9890

Volume 75| Part 12| December 2019| Pages 1861-1865

https://doi.org/10.1107/S2056989019015081

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Synthesis, crystal structure and Hirshfeld surface analysis of diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate

Trung Vu Quoc,^a ^* Duong Tran Thi Thuy,^a,^b Thanh Phung Ngoc,^a,^c Manh Vu Quoc,^d Hien Nguyen,^a Linh Duong Khanh,^a Anh Tu Quang ^a and Luc Van Meervelt ^e ^*

^aFaculty of Chemistry, Hanoi National University of Education, 136 Xuan Thuy, Cau Giay, Hanoi, Vietnam, ^bBien Hoa Gifted High School, 86 Chu Van An Street, Phu Ly City, Ha Nam Province, Vietnam, ^cPhan Boi Chau Gifted High School, 119 Le Hong Phong Street, Vinh City, Nghe An Province, Vietnam, ^dFaculty of Foundation Science, College of Printing Industry, Phuc Dien, Bac Tu Liem, Hanoi, Vietnam, and ^eDepartment of Chemistry, KU Leuven, Biomolecular Architecture, Celestijnenlaan 200F, Leuven (Heverlee), B-3001, Belgium
^*Correspondence e-mail: trungvq@hnue.edu.vn, luc.vanmeervelt@kuleuven.be

Edited by J. Simpson, University of Otago, New Zealand (Received 6 November 2019; accepted 8 November 2019; online 15 November 2019)

In the title compound, C₁₇H₂₁NO₄S, the 1,4-dihydropyridine ring has an envelope conformation with the Csp³ atom at the flap. The thiophene ring is nearly perpendicular to the best plane through the 1,4-dihydropyridine ring, the dihedral angle being 82.19 (13)°. In the crystal, chains running along the b-axis direction are formed through N—H⋯O interactions between the 1,4-dihydropyridine N atom and one of the O atoms of the ester groups. Neighbouring chains are linked by C—H⋯O and C—H⋯π interactions. A Hirshfeld surface analysis shows that the most prominent contributuion to the surface contacts are H⋯H contacts (55.1%).

Keywords: crystal structure; hydrogen bonding; Hirshfeld analysis; 1,4-dihydropyridine.

CCDC references: 1964486; 1964486

1. Chemical context

1,4-Dihydropyridine derivatives exhibit a large range of biological activities (Stout & Meyers, 1982 ; Wei et al., 1989 ; Bossert & Vater, 1989 ; Mauzerall & Westheimer, 1955 ). They have been used as anticonvulsant, antidepressive, antianxiety, analgesic, antitumoral, vasodilator and anti-inflammatory agents (Sausins & Duburs, 1988 ; Boecker & Guenguerich, 1986 ; Godfraind et al., 1986 ). Some of them, such as amlodipine, felodipine and isradipine are drugs effective as calcium-channel blockers for the treatment of cardiovascular diseases and hypertension (Bossert et al., 1981 ; Nakayama & Kanoaka, 1996 ; Gordeev et al., 1996 ). 1,4-Dihydropyridines are also good precursors of the corresponding substituted pyridine derivatives and constitute useful reducing agents for imines in the presence of a catalytic amount of Lewis acid (Xia & Wang, 2005 ; Heravi et al., 2005 ; Bagley & Lubinu, 2006 ).

As a continuation of our research on the chemical and physical properties of novel polythiophenes (Nguyen et al., 2016 ; Vu et al., 2016 ), some new thiophene monomers have been prepared (Vu et al., 2017 , 2018 , 2019 ; Nguyen et al., 2017 ). In this study, the synthesis and crystal structure of diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate are presented together with a Hirshfeld surface analysis and non-covalent interaction plots.

2. Structural commentary

The title compound crystallizes in the monoclinic space group P2₁/c with one molecule in the asymmetric unit (Fig. 1). The 1,4-dihydropyridine ring (N6,C7–C11) has an envelope conformation with atom C9 at the flap [puckering parameters: Q = 0.300 (3) Å, θ = 73.9 (6)°, φ = 182.0 (5)°]. The best plane through the 1,4-dihydropyridine ring makes an angle of 82.19 (13)° with the plane through the thiophene ring (S1/C2–C5; r.m.s. deviation = 0.001 Å). Both methyl C atoms are closer to the best plane through the 1,4-dihydropyridine [deviations: C12 − 0.164 (3) Å, C23 − 0.162 (3) Å] than the C atoms of the two ester substituents [deviations: C13 − 0.363 (3) Å, C18 − 0.446 (2) Å]. All four of these C atoms are at the opposite sides with respect to the thiophene substituent which is in an axial position. Atoms O15, O19 and O20 are involved in intramolecular short contacts (Table 1). Both ester groups have a different conformation as illustrated by torsion angles C13—O15—C16—C17 [177.2 (3)°, +ap] and C18—O20—C21—C22 [85.3 (8)°, +sc].

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the thiophene S1/C2–C5 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6—H6⋯O14ⁱ	0.82 (4)	2.19 (4)	3.010 (3)	176 (3)
C5—H5⋯O19ⁱⁱ	0.93	2.52	3.220 (4)	133
C9—H9⋯O20	0.98	2.36	2.739 (3)	102
C12—H12B⋯O15	0.96	2.33	2.768 (3)	107
C23—H23C⋯O19	0.96	2.42	2.826 (4)	105
C17—H17C⋯Cg1ⁱⁱⁱ	0.96	2.79	3.720 (4)	162
Symmetry codes: (i) x, y-1, z; (ii) $[-x, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (iii) -x+1, -y+2, -z+1.

Figure 1
A view of the molecular structure of the title compound, with atom labels and displacement ellipsoids drawn at the 50% probability level. H atoms are shown as small circles of arbitrary radii.

3. Supramolecular features and Hirshfeld surface analysis

In the crystal, the 1,4-dihydropyridine N6 atom acts as a hydrogen-bond donor to the O14 atom of one of the ester groups, resulting in chain formation along the b-axis direction (Fig. 2, Table 1). Parallel chains are linked by C—H⋯O hydrogen bonds between the thiophene H5 atom and the carbonyl O19 atom of the second ester group (Fig. 2, Table 1). In addition, inversion dimers are formed by C—H⋯π interactions (Fig. 3, Table 1). No voids are observed in the crystal packing of the title compound.

Figure 2
Partial crystal packing of the title compound, showing the chain formation along the b axis by N—H⋯O interactions (blue dashed lines). Parallel chains are linked by C—H⋯O interactions (red dashed lines; see Table 1

for symmetry codes).

Figure 3
Partial crystal packing of the title compound, showing the inversion dimer formation through C—H⋯π interactions (grey dashed lines; Cg1 is the centroid of the S1/C2–C5 ring; see Table 1

for symmetry code).

In order to gain further insight into the packing, the Hirshfeld surface and fingerprint plots were calculated using CrystalExplorer (Turner et al., 2017 ). The Hirshfeld surface (Spackman & Jayatilaka, 2009 ) mapped over d_norm in Fig. 4 shows bright-red spots near the atoms participating in the already discussed intermolecular interactions. In addition a faint-red spot is present near atoms H9 and H23A indicating a short H9⋯H23A^iv contact distance of 2.276 Å [symmetry code: (iv) x, y + 1, z]. The associated two-dimensional fingerprint plots (McKinnon et al., 2007 ) are shown in Fig. 5 and give additional information about the intermolecular contacts. H⋯H Van der Waals contacts dominate (55.1%) and appear in the middle of the scattered points in the fingerprint plot (Fig. 5b). The contribution (16.4%) from the O⋯H/H⋯O contacts shows a pair of sharp spikes corresponding to the N—H⋯O interactions (Fig. 5c). In addition, C⋯H/H⋯C and S⋯H/H⋯S contacts contribute 15.7 and 9.6%, respectively, to the Hirshfeld surface. A further small contribution is from N⋯H/H⋯N contacts (1.5%, Fig. 5f). The percentage contributions of the other contact types are negligible.

Figure 4
Two views of the Hirshfeld surface mapped over d_norm for the title compound in the range −0.4662 to +1.2830 arbitrary units.

Figure 5
Full two-dimensional fingerprint plots for the title compound, showing (a) all interactions, and delineated into (b) H⋯H, (c) O⋯H/H⋯O, (d) C⋯H/H⋯C, (e) S⋯H/H⋯S, (f) N⋯H/H⋯N interactions. The d_i and d_e values are the closest internal and external distances (in Å) from a given point on the Hirshfeld surface.

Enrichment ratios (Table 2) were calculated according to the method described by Jelsch et al. (2014 ). A ratio E_XY greater than unity for a pair of elements X and Y indicates a high likelihood of forming X⋯Y contacts in the crystal packing. The favourable O⋯H and H⋯π contacts in the crystal packing are reflected in the enrichment ratios E_OH of 1.24 and E_CH of 1.23 for these contacts. The slight E_SH enrichment (1.11) refers to the multiple S⋯H contacts between S1 and neighbouring methyl groups (S⋯H distances ranging from 3.01 to 3.50 Å). However, the high enrichment ratio E_NH must be interpreted with caution as it results from the quotient of two small numbers (Jelsch et al., 2014).

Table 2
Enrichment ratios for the title compound

Parameter	Ratio
H⋯H	0.94
C⋯H	1.23
O⋯H	1.24
N⋯H	1.30
S⋯H	1.11
S⋯C	0.96
S⋯O	0.82

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.40, update of May 2019; Groom et al., 2016 ) for diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives with a ring substituent at C4 results in 70 hits for which coordinates are available. Most similar to the title compound is the 4-(2-thienyl) derivative (refcode QIWWEY; Caignan et al., 2000 ; refcode QIWWEY01; Huang & Cui, 2016 ). In these compounds the thienyl group is disordered over two sets of sites with an occupancy ratio of 0.51:0.49. An overlay between the title compound and QIWWEY excluding the thiophene ring gives an r.m.s. deviation of 0.318 Å. In QIWWEY, the 1,4-dihydropyridine and thiophene rings make an angle of 83.19 (17)°. Fig. 6 shows the four possible orientations of the two C=O substituents on the 1,4-dihydropyridine ring. Most popular are the s-trans/s-cis (35%), the s-cis/s-cis (31%) and the s-cis/s-trans conformation (29%). The s-trans/s-trans conformation occurs only for 5% of the derivatives. In the title compound, both C=O substituents are present in an s-trans/s-cis conformation.

Figure 6
Four possible orientations of the C=O groups for diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives with a ring substituent (R) at C4.

5. Synthesis and crystallization

The reaction scheme for the synthesis of the title compound is given in Fig. 7.

Figure 7
Reaction scheme for the synthesis of the title compound.

Synthesis of diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate:

A mixture of thiophene-3-carbaldehyde (3 mmol), ethyl acetoacetate (6 mmol) and NH₄OAc (3 mmol) in ethanol (10 mL) was exposed to microwave radiation for 3 min. at a power of 450W. The reaction mixture was cooled down and the solid product was separated by filtration and purified by recrystallization in ethanol to give the compound as yellowish transparent crystals (yield 82%), m.p. 423 K. IR (KBr, cm⁻¹): 3346, 3244 (NH), 3099, 2979 (C–H), 1699 (C=O), 1490 (C=C). ¹H NMR [Bruker XL-500, 500 MHz, d₆-CDCl₃, δ (ppm), J (Hz), see Fig. 7 for numbering scheme]: 7.12 (m, 1H, J = 4.5, H⁴), 6.99 (m, 1H, J = 4.5, H⁵), 6.91 (d, 1H,, J = 2.5, H²), 5.93 (s, 1H, H⁹), 5.14 (s, 1H, H⁶), 4.13 (m, 4H, J = 7.5Hz, H^13,13′), 2.30 (s, 6H, H^10,10′), 1.25 (m, 6H, J = 7.25 H^14,14′). ¹³C NMR [Bruker XL-500, 125 MHz, d₆-CDCl₃, (ppm)]: 19.4 (C^10,10′), 14.3 (C^14,14′), 34.6 (C⁶), 59.7 (C^13,13′), 103.4 (C^7,7′), 120.3 (C²), 124.6 (C⁴), 127.6 (C⁵), 144.4 (C³), 147.9 (C⁸,C^8′), 167.7 (C^11,11′). Calculated for C₁₇H₂₁NO₄S: M^[+H] = 335.4 au.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. H atom H6 was found in a difference electron-density map and refined freely. The other H atoms were placed in idealized positions and included as riding contributions with U_iso(H) values of 1.2U_eq or 1.5U_eq of the parent atoms, with C—H distances of 0.93 (aromatic), 0.98 (CH), 0.97 (CH₂) and 0.96 Å (CH₃). In the final cycles of refinement, four outlying reflections were omitted.

Table 3
Experimental details

Crystal data
Chemical formula	C₁₇H₂₁NO₄S
M_r	335.41
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	15.6801 (8), 7.4311 (3), 15.5968 (8)
β (°)	111.424 (6)
V (Å³)	1691.77 (16)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.21
Crystal size (mm)	0.5 × 0.2 × 0.05

Data collection
Diffractometer	Rigaku Oxford Diffraction SuperNova, single source at offset/far, Eos
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.555, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	19775, 3446, 2805
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.061, 0.187, 1.05
No. of reflections	3446
No. of parameters	216
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.53, −0.47
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT2014 (Sheldrick, 2015a ), SHELXL2016 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC references: 1964486; 1964486

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989019015081/sj5585sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019015081/sj5585Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989019015081/sj5585Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate top

Crystal data top

C₁₇H₂₁NO₄S	F(000) = 712
M_r = 335.41	D_x = 1.317 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 15.6801 (8) Å	Cell parameters from 8195 reflections
b = 7.4311 (3) Å	θ = 3.1–27.9°
c = 15.5968 (8) Å	µ = 0.21 mm⁻¹
β = 111.424 (6)°	T = 293 K
V = 1691.77 (16) Å³	Block, colourless
Z = 4	0.5 × 0.2 × 0.05 mm

Data collection top

Rigaku Oxford Diffraction SuperNova, single source at offset/far, Eos diffractometer	3446 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Mo) X-ray Source	2805 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.027
Detector resolution: 15.9631 pixels mm^-1	θ_max = 26.4°, θ_min = 2.6°
ω scans	h = −19→19
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2018)	k = −9→9
T_min = 0.555, T_max = 1.000	l = −19→19
19775 measured reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.061	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.187	w = 1/[σ²(F_o²) + (0.0981P)² + 1.416P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
3446 reflections	Δρ_max = 0.53 e Å⁻³
216 parameters	Δρ_min = −0.46 e Å⁻³

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

	x	y	z	U_iso*/U_eq
S1	0.23846 (6)	0.68160 (12)	0.53767 (5)	0.0587 (3)
C2	0.28608 (18)	0.6398 (4)	0.45764 (17)	0.0407 (6)
H2	0.340156	0.575481	0.470126	0.049*
C3	0.23681 (15)	0.7104 (3)	0.37324 (15)	0.0293 (5)
C4	0.15812 (17)	0.8010 (4)	0.37597 (18)	0.0405 (6)
H4	0.115977	0.858331	0.325101	0.049*
C5	0.14966 (17)	0.7959 (4)	0.46445 (18)	0.0393 (6)
H5	0.102525	0.847582	0.478796	0.047*
N6	0.32530 (15)	0.3391 (3)	0.28906 (16)	0.0406 (5)
H6	0.346 (2)	0.236 (5)	0.297 (2)	0.053 (9)*
C7	0.39001 (16)	0.4737 (3)	0.31863 (17)	0.0351 (5)
C8	0.36158 (15)	0.6465 (3)	0.31363 (16)	0.0302 (5)
C9	0.26034 (14)	0.6872 (3)	0.28729 (15)	0.0273 (5)
H9	0.246735	0.800269	0.252562	0.033*
C10	0.20195 (15)	0.5392 (3)	0.22653 (15)	0.0303 (5)
C11	0.23455 (16)	0.3689 (3)	0.23509 (17)	0.0359 (5)
C12	0.48666 (18)	0.4023 (4)	0.3531 (2)	0.0533 (8)
H12A	0.509780	0.397134	0.419186	0.080*
H12B	0.524659	0.480463	0.333367	0.080*
H12C	0.487105	0.283768	0.328792	0.080*
C13	0.42150 (16)	0.8049 (3)	0.33895 (17)	0.0348 (5)
O14	0.39447 (13)	0.9578 (2)	0.32155 (16)	0.0545 (6)
O15	0.50981 (12)	0.7683 (2)	0.38631 (16)	0.0516 (5)
C16	0.57344 (18)	0.9188 (4)	0.4152 (2)	0.0532 (7)
H16A	0.553963	1.002135	0.452336	0.064*
H16B	0.575719	0.982674	0.361883	0.064*
C17	0.6646 (2)	0.8441 (5)	0.4697 (3)	0.0831 (13)
H17A	0.683923	0.764533	0.431803	0.125*
H17B	0.661164	0.778721	0.521443	0.125*
H17C	0.707965	0.940521	0.491285	0.125*
C18	0.10811 (16)	0.5808 (4)	0.16274 (16)	0.0363 (5)
O19	0.05131 (14)	0.4733 (3)	0.11903 (16)	0.0646 (7)
O20	0.09182 (12)	0.7592 (2)	0.15614 (12)	0.0410 (4)
C21	0.00100 (19)	0.8172 (5)	0.0952 (2)	0.0525 (7)
H21A	−0.020354	0.738253	0.042024	0.063*
H21B	0.005081	0.938003	0.073416	0.063*
C22	−0.0661 (3)	0.8156 (6)	0.1416 (3)	0.0767 (11)
H22A	−0.124239	0.858116	0.099750	0.115*
H22B	−0.044950	0.892617	0.194641	0.115*
H22C	−0.072715	0.695134	0.160476	0.115*
C23	0.1849 (2)	0.2020 (4)	0.1900 (2)	0.0542 (8)
H23A	0.218986	0.098199	0.220459	0.081*
H23B	0.178354	0.200892	0.126401	0.081*
H23C	0.125325	0.199968	0.194332	0.081*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0677 (5)	0.0662 (6)	0.0442 (4)	0.0079 (4)	0.0228 (4)	0.0059 (3)
C2	0.0385 (13)	0.0430 (14)	0.0386 (13)	0.0084 (11)	0.0117 (10)	0.0040 (11)
C3	0.0288 (10)	0.0250 (11)	0.0327 (11)	−0.0019 (8)	0.0094 (9)	−0.0028 (8)
C4	0.0339 (12)	0.0462 (14)	0.0391 (13)	0.0080 (11)	0.0104 (10)	−0.0014 (11)
C5	0.0313 (12)	0.0424 (14)	0.0466 (14)	0.0033 (10)	0.0169 (11)	−0.0069 (11)
N6	0.0372 (11)	0.0225 (10)	0.0547 (13)	0.0035 (8)	0.0082 (10)	0.0007 (9)
C7	0.0298 (11)	0.0306 (12)	0.0422 (13)	0.0026 (9)	0.0101 (10)	0.0014 (10)
C8	0.0266 (11)	0.0267 (11)	0.0362 (11)	0.0012 (8)	0.0100 (9)	0.0014 (9)
C9	0.0269 (10)	0.0209 (10)	0.0333 (11)	0.0021 (8)	0.0098 (9)	0.0024 (8)
C10	0.0289 (11)	0.0289 (11)	0.0314 (11)	−0.0019 (9)	0.0091 (9)	0.0004 (9)
C11	0.0350 (12)	0.0312 (12)	0.0399 (12)	−0.0025 (10)	0.0116 (10)	−0.0027 (10)
C12	0.0359 (14)	0.0342 (14)	0.080 (2)	0.0093 (11)	0.0095 (13)	−0.0009 (14)
C13	0.0295 (11)	0.0292 (12)	0.0465 (13)	0.0007 (9)	0.0146 (10)	0.0007 (10)
O14	0.0375 (10)	0.0254 (9)	0.0918 (15)	0.0001 (7)	0.0134 (10)	0.0048 (9)
O15	0.0300 (9)	0.0301 (9)	0.0830 (15)	−0.0027 (7)	0.0068 (9)	0.0011 (9)
C16	0.0378 (14)	0.0339 (14)	0.081 (2)	−0.0091 (11)	0.0137 (13)	0.0000 (14)
C17	0.0435 (17)	0.056 (2)	0.124 (3)	−0.0095 (15)	0.0001 (19)	0.009 (2)
C18	0.0321 (11)	0.0432 (14)	0.0312 (11)	0.0001 (10)	0.0084 (9)	−0.0009 (10)
O19	0.0429 (11)	0.0552 (13)	0.0715 (14)	−0.0041 (10)	−0.0079 (10)	−0.0129 (11)
O20	0.0338 (9)	0.0420 (10)	0.0395 (9)	0.0080 (7)	0.0043 (7)	0.0042 (7)
C21	0.0391 (14)	0.0634 (19)	0.0449 (15)	0.0146 (13)	0.0035 (12)	0.0102 (13)
C22	0.055 (2)	0.091 (3)	0.084 (3)	0.0277 (19)	0.0258 (18)	0.005 (2)
C23	0.0489 (16)	0.0326 (14)	0.073 (2)	−0.0062 (12)	0.0128 (14)	−0.0139 (13)

Geometric parameters (Å, º) top

S1—C2	1.701 (3)	C12—H12C	0.9600
S1—C5	1.674 (3)	C13—O14	1.208 (3)
C2—H2	0.9300	C13—O15	1.338 (3)
C2—C3	1.364 (3)	O15—C16	1.456 (3)
C3—C4	1.420 (3)	C16—H16A	0.9700
C3—C9	1.525 (3)	C16—H16B	0.9700
C4—H4	0.9300	C16—C17	1.479 (4)
C4—C5	1.434 (4)	C17—H17A	0.9600
C5—H5	0.9300	C17—H17B	0.9600
N6—H6	0.82 (4)	C17—H17C	0.9600
N6—C7	1.379 (3)	C18—O19	1.205 (3)
N6—C11	1.381 (3)	C18—O20	1.347 (3)
C7—C8	1.352 (3)	O20—C21	1.459 (3)
C7—C12	1.507 (3)	C21—H21A	0.9700
C8—C9	1.518 (3)	C21—H21B	0.9700
C8—C13	1.468 (3)	C21—C22	1.479 (5)
C9—H9	0.9800	C22—H22A	0.9600
C9—C10	1.521 (3)	C22—H22B	0.9600
C10—C11	1.353 (3)	C22—H22C	0.9600
C10—C18	1.477 (3)	C23—H23A	0.9600
C11—C23	1.496 (3)	C23—H23B	0.9600
C12—H12A	0.9600	C23—H23C	0.9600
C12—H12B	0.9600

C5—S1—C2	94.05 (12)	H12B—C12—H12C	109.5
S1—C2—H2	123.5	O14—C13—C8	123.8 (2)
C3—C2—S1	113.10 (19)	O14—C13—O15	121.5 (2)
C3—C2—H2	123.5	O15—C13—C8	114.7 (2)
C2—C3—C4	110.2 (2)	C13—O15—C16	118.0 (2)
C2—C3—C9	124.8 (2)	O15—C16—H16A	110.2
C4—C3—C9	124.9 (2)	O15—C16—H16B	110.2
C3—C4—H4	123.1	O15—C16—C17	107.4 (2)
C3—C4—C5	113.8 (2)	H16A—C16—H16B	108.5
C5—C4—H4	123.1	C17—C16—H16A	110.2
S1—C5—H5	125.6	C17—C16—H16B	110.2
C4—C5—S1	108.88 (18)	C16—C17—H17A	109.5
C4—C5—H5	125.6	C16—C17—H17B	109.5
C7—N6—H6	115 (2)	C16—C17—H17C	109.5
C7—N6—C11	123.8 (2)	H17A—C17—H17B	109.5
C11—N6—H6	120 (2)	H17A—C17—H17C	109.5
N6—C7—C12	112.6 (2)	H17B—C17—H17C	109.5
C8—C7—N6	118.9 (2)	O19—C18—C10	126.2 (2)
C8—C7—C12	128.5 (2)	O19—C18—O20	121.9 (2)
C7—C8—C9	119.7 (2)	O20—C18—C10	111.8 (2)
C7—C8—C13	125.5 (2)	C18—O20—C21	117.0 (2)
C13—C8—C9	114.60 (19)	O20—C21—H21A	109.2
C3—C9—H9	108.4	O20—C21—H21B	109.2
C8—C9—C3	110.47 (18)	O20—C21—C22	112.2 (3)
C8—C9—H9	108.4	H21A—C21—H21B	107.9
C8—C9—C10	110.90 (18)	C22—C21—H21A	109.2
C10—C9—C3	110.21 (18)	C22—C21—H21B	109.2
C10—C9—H9	108.4	C21—C22—H22A	109.5
C11—C10—C9	119.68 (19)	C21—C22—H22B	109.5
C11—C10—C18	120.6 (2)	C21—C22—H22C	109.5
C18—C10—C9	119.6 (2)	H22A—C22—H22B	109.5
N6—C11—C23	113.4 (2)	H22A—C22—H22C	109.5
C10—C11—N6	118.6 (2)	H22B—C22—H22C	109.5
C10—C11—C23	128.0 (2)	C11—C23—H23A	109.5
C7—C12—H12A	109.5	C11—C23—H23B	109.5
C7—C12—H12B	109.5	C11—C23—H23C	109.5
C7—C12—H12C	109.5	H23A—C23—H23B	109.5
H12A—C12—H12B	109.5	H23A—C23—H23C	109.5
H12A—C12—H12C	109.5	H23B—C23—H23C	109.5

S1—C2—C3—C4	0.1 (3)	C9—C3—C4—C5	177.0 (2)
S1—C2—C3—C9	−177.09 (17)	C9—C8—C13—O14	−16.0 (4)
C2—S1—C5—C4	−0.1 (2)	C9—C8—C13—O15	161.9 (2)
C2—C3—C4—C5	−0.2 (3)	C9—C10—C11—N6	−9.6 (4)
C2—C3—C9—C8	−23.5 (3)	C9—C10—C11—C23	172.7 (3)
C2—C3—C9—C10	99.4 (3)	C9—C10—C18—O19	−170.8 (3)
C3—C4—C5—S1	0.2 (3)	C9—C10—C18—O20	10.6 (3)
C3—C9—C10—C11	−93.6 (3)	C10—C18—O20—C21	−179.8 (2)
C3—C9—C10—C18	82.7 (2)	C11—N6—C7—C8	15.7 (4)
C4—C3—C9—C8	159.7 (2)	C11—N6—C7—C12	−164.1 (3)
C4—C3—C9—C10	−77.4 (3)	C11—C10—C18—O19	5.5 (4)
C5—S1—C2—C3	0.0 (2)	C11—C10—C18—O20	−173.1 (2)
N6—C7—C8—C9	7.6 (4)	C12—C7—C8—C9	−172.6 (3)
N6—C7—C8—C13	−177.6 (2)	C12—C7—C8—C13	2.2 (4)
C7—N6—C11—C10	−14.7 (4)	C13—C8—C9—C3	−80.8 (2)
C7—N6—C11—C23	163.4 (3)	C13—C8—C9—C10	156.7 (2)
C7—C8—C9—C3	94.5 (3)	C13—O15—C16—C17	177.2 (3)
C7—C8—C9—C10	−28.0 (3)	O14—C13—O15—C16	−1.1 (4)
C7—C8—C13—O14	169.0 (3)	C18—C10—C11—N6	174.1 (2)
C7—C8—C13—O15	−13.1 (4)	C18—C10—C11—C23	−3.6 (4)
C8—C9—C10—C11	29.0 (3)	C18—O20—C21—C22	85.3 (3)
C8—C9—C10—C18	−154.6 (2)	O19—C18—O20—C21	1.5 (4)
C8—C13—O15—C16	−179.1 (2)

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the thiophene S1/C2–C5 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6···O14ⁱ	0.82 (4)	2.19 (4)	3.010 (3)	176 (3)
C5—H5···O19ⁱⁱ	0.93	2.52	3.220 (4)	133
C9—H9···O20	0.98	2.36	2.739 (3)	102
C12—H12B···O15	0.96	2.33	2.768 (3)	107
C23—H23C···O19	0.96	2.42	2.826 (4)	105
C17—H17C···Cg1ⁱⁱⁱ	0.96	2.79	3.720 (4)	162

Symmetry codes: (i) x, y−1, z; (ii) −x, y+1/2, −z+1/2; (iii) −x+1, −y+2, −z+1.

Enrichment ratios for the title compound top

Parameter	Ratio
H···H	0.94
C···H	1.23
O···H	1.24
N···H	1.30
S···H	1.11
S···C	0.96
S···O	0.82

Funding information

This research was funded by the Vietnam Ministry of Education and Training under grant No. B2019-SPH.562–05. LVM thanks the Hercules Foundation for supporting the purchase of the diffractometer through project AKUL/09/0035.

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