organic compounds
5-[(1,3-Dimethyl-5-oxo-2-sulfanylideneimidazolidin-4-ylidene)amino]-2-methylisoindoline-1,3-dione
aDepartment of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India
*Correspondence e-mail: srk@chem.iitb.ac.in
The title N,N-dimethylthiohydantoin containing an N-methylated pthalimide group, C14H12N4O3S, arose from an unexpected reaction in a deep eutectic dimethylthiourea–tartaric acid solvent system. The mean planes of the ring systems are twisted at an angle of 73.84 (17)°. In the crystal, weak C—H⋯O hydrogen bonds connect the molecules.
CCDC reference: 1847293
Structure description
Thiohydantoins are effective in treating various biological disorders (Spicer et al., 2013; Wang et al., 2021; Huang et al., 2018; Manzanaro et al., 2006). In an attempt to synthesize 5-amino-substituted hydantoins and thiohydantoins (Kotha et al., 2019), we unexpectedly obtained the title imino-substituted thiohydantoin 1.
The 1H NMR spectrum confirmed the absence of two H atoms (CH—NH grouping) and the 13C spectrum showed the downfield shift for the carbon atom of the C—N bond. To establish its structure unambiguously, the was determined, which confirmed the presence of the C10=N3 double bond [1.252 (4) Å] (Fig. 1). The remaining geometrical parameters are comparable with those of a 5-aniline-substituted thiohydantoin reported by our group (Kotha et al., 2019; Cambridge Structural Database refcode FOWGOQ).
The molecular structure of 1 has an angular shape and the mean planes defined by the C10–C12/N1/N2 imidazole ring and C1–C9/N4 pthalimide ring system subtend a dihedral angle of 73.84 (17)°. The bond angle of the C8—N3—C10 linker , which connects the thiohydantoin ring with the N-phenyl substituent is 120.6 (3)°, some 4° less than the corresponding angle in FOWGOQ (Fig. 2).
The N1 and N2 nitrogen atoms in the imidazole ring are protected by methyl groups, which rules out the possibility of classical hydrogen bonding in the packing (Fig. 2), but several weak C—H⋯O links occur (Table 1).
Synthesis and crystallization
Initially, a deep eutectic mixture was obtained by mixing dimethylthiourea and L-tartaric acid (DMTU:L–(+)TA) in 70:30 ratio at 80°C. After obtaining the melt, aniline 2 (100 mg, 0.57 mmol) and ethylglyoxalate 3 (0.12 ml, 1.14 mmol) were added and the mixture was stirred at the same temperature for 6 h. After completion of the reaction (TLC monitoring), the product was concentrated and purified by silica-gel using petroleum ether and ethyl acetate as the to afford the title compound 1 (Fig. 3). Yellow plates were recrystallized from chloroform solution (Kotha et al., 2019).
Yield 108 mg, 60%, m.p. 268–270°C, Rf = 0.76 (60% EtOAc–petroleum ether),1H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H), 7.20 (dd, J = 8.0, 1.5 Hz, 1H), 3.42 (s, 3H), 3.15 (s, 3H), 3.03 (s, 3H) p.p.m., 13C NMR (125 MHz, CDCl3) δ 180.7, 168.3, 168.3, 154.3, 151.9, 141.4, 133.7, 128.3, 125.3, 124.1, 115.3, 29.6, 28.1, 24.2 p.p.m., HRMS (ESI) calculated for C14H12N4NaO3S [M + Na] 339.0522, found 339.0526, IR (neat) 3376, 3028, 1767, 1749, 1738, 1712, 1615, 1405, 1383 cm−1.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1847293
https://doi.org/10.1107/S2414314621003229/hb4377sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314621003229/hb4377Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314621003229/hb4377Isup3.cml
Data collection: CrysAlis PRO (Rigaku OD, 2015); cell
CrysAlis PRO (Rigaku OD, 2015); data reduction: CrysAlis PRO (Rigaku OD, 2015); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C14H12N4O3S | F(000) = 656 |
Mr = 316.34 | Dx = 1.513 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 5.4887 (9) Å | Cell parameters from 2419 reflections |
b = 9.2470 (12) Å | θ = 2.3–31.0° |
c = 27.457 (2) Å | µ = 0.25 mm−1 |
β = 94.75 (1)° | T = 150 K |
V = 1388.7 (3) Å3 | Plate, yellow |
Z = 4 | 0.31 × 0.27 × 0.22 mm |
Rigaku Oxford Diffraction Saturn724+ diffractometer | 2343 independent reflections |
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source | 1624 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.105 |
Detector resolution: 28.5714 pixels mm-1 | θmax = 25.0°, θmin = 2.3° |
ω scans | h = −6→6 |
Absorption correction: multi-scan (CrysalisPro; Rigaku OD, 2015) | k = −9→10 |
Tmin = 0.340, Tmax = 1.000 | l = −32→32 |
8048 measured reflections |
Refinement on F2 | Primary atom site location: dual |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.061 | H-atom parameters constrained |
wR(F2) = 0.153 | w = 1/[σ2(Fo2) + (0.0624P)2 + 0.3068P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
2343 reflections | Δρmax = 0.38 e Å−3 |
202 parameters | Δρmin = −0.34 e Å−3 |
0 restraints |
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 | ||
S1 | 0.6276 (2) | 0.57457 (11) | 0.24925 (3) | 0.0309 (3) | |
O3 | 0.5648 (5) | 0.8470 (2) | 0.40427 (8) | 0.0257 (7) | |
O2 | 0.9716 (5) | 0.9678 (3) | 0.63093 (8) | 0.0257 (7) | |
O1 | 0.4516 (5) | 0.6022 (3) | 0.57964 (8) | 0.0316 (7) | |
N4 | 0.6704 (5) | 0.7946 (3) | 0.61393 (9) | 0.0209 (7) | |
N2 | 0.5470 (6) | 0.7361 (3) | 0.32835 (9) | 0.0221 (7) | |
N1 | 0.8657 (6) | 0.5885 (3) | 0.33889 (9) | 0.0220 (7) | |
N3 | 1.0073 (6) | 0.6355 (3) | 0.41971 (9) | 0.0248 (8) | |
C4 | 0.8759 (7) | 0.8769 (4) | 0.60409 (11) | 0.0207 (9) | |
C3 | 0.9437 (7) | 0.8266 (4) | 0.55580 (11) | 0.0203 (9) | |
C2 | 0.7823 (7) | 0.7184 (4) | 0.53916 (11) | 0.0227 (9) | |
C10 | 0.8555 (7) | 0.6584 (4) | 0.38396 (11) | 0.0213 (9) | |
C1 | 0.6097 (7) | 0.6926 (4) | 0.57754 (11) | 0.0216 (9) | |
C12 | 0.6818 (7) | 0.6322 (4) | 0.30574 (11) | 0.0214 (9) | |
C11 | 0.6395 (7) | 0.7596 (4) | 0.37603 (11) | 0.0221 (9) | |
C8 | 0.9789 (7) | 0.7009 (4) | 0.46559 (11) | 0.0250 (9) | |
C5 | 0.5476 (7) | 0.8074 (4) | 0.65885 (11) | 0.0289 (10) | |
H5A | 0.664931 | 0.840036 | 0.685427 | 0.043* | |
H5B | 0.481137 | 0.713115 | 0.667237 | 0.043* | |
H5C | 0.414137 | 0.877738 | 0.654078 | 0.043* | |
C7 | 1.1494 (7) | 0.8039 (4) | 0.48344 (11) | 0.0268 (10) | |
H7 | 1.279648 | 0.829387 | 0.464394 | 0.032* | |
C9 | 0.7927 (7) | 0.6529 (4) | 0.49413 (11) | 0.0247 (9) | |
H9 | 0.680360 | 0.579570 | 0.483004 | 0.030* | |
C6 | 1.1326 (7) | 0.8698 (4) | 0.52850 (11) | 0.0238 (9) | |
H6 | 1.246289 | 0.941822 | 0.540186 | 0.029* | |
C14 | 0.3422 (7) | 0.8152 (4) | 0.30389 (12) | 0.0284 (10) | |
H14A | 0.403902 | 0.886751 | 0.281610 | 0.043* | |
H14B | 0.251819 | 0.864661 | 0.328326 | 0.043* | |
H14C | 0.233247 | 0.747504 | 0.285278 | 0.043* | |
C13 | 1.0409 (8) | 0.4761 (4) | 0.33055 (13) | 0.0360 (11) | |
H13A | 1.175975 | 0.479863 | 0.356201 | 0.054* | |
H13B | 1.104667 | 0.490714 | 0.298611 | 0.054* | |
H13C | 0.960755 | 0.381459 | 0.331176 | 0.054* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0393 (8) | 0.0339 (7) | 0.0201 (5) | 0.0062 (5) | 0.0060 (4) | −0.0072 (4) |
O3 | 0.0335 (18) | 0.0206 (15) | 0.0247 (12) | 0.0004 (12) | 0.0136 (12) | −0.0036 (11) |
O2 | 0.0278 (17) | 0.0253 (15) | 0.0248 (12) | −0.0008 (12) | 0.0064 (11) | −0.0070 (11) |
O1 | 0.0362 (19) | 0.0289 (16) | 0.0305 (13) | −0.0074 (14) | 0.0077 (13) | −0.0029 (12) |
N4 | 0.024 (2) | 0.0215 (17) | 0.0180 (13) | 0.0009 (14) | 0.0059 (13) | −0.0003 (12) |
N2 | 0.025 (2) | 0.0213 (17) | 0.0200 (14) | 0.0033 (14) | 0.0048 (13) | −0.0030 (13) |
N1 | 0.028 (2) | 0.0238 (18) | 0.0148 (13) | 0.0072 (14) | 0.0045 (14) | −0.0038 (12) |
N3 | 0.032 (2) | 0.0265 (19) | 0.0169 (14) | 0.0020 (15) | 0.0070 (15) | −0.0017 (13) |
C4 | 0.024 (2) | 0.017 (2) | 0.0221 (17) | 0.0047 (16) | 0.0056 (17) | −0.0017 (16) |
C3 | 0.026 (2) | 0.016 (2) | 0.0191 (16) | 0.0056 (16) | 0.0027 (16) | 0.0020 (14) |
C2 | 0.028 (3) | 0.022 (2) | 0.0189 (16) | 0.0036 (17) | 0.0056 (16) | 0.0011 (15) |
C10 | 0.027 (2) | 0.019 (2) | 0.0197 (17) | 0.0010 (17) | 0.0116 (17) | −0.0003 (15) |
C1 | 0.024 (2) | 0.023 (2) | 0.0182 (16) | 0.0041 (18) | 0.0024 (16) | 0.0017 (15) |
C12 | 0.023 (2) | 0.017 (2) | 0.0257 (17) | 0.0012 (16) | 0.0101 (17) | 0.0025 (15) |
C11 | 0.026 (2) | 0.019 (2) | 0.0225 (16) | −0.0058 (16) | 0.0115 (16) | −0.0010 (15) |
C8 | 0.037 (3) | 0.021 (2) | 0.0177 (16) | 0.0078 (18) | 0.0074 (17) | 0.0006 (15) |
C5 | 0.037 (3) | 0.032 (2) | 0.0193 (16) | 0.0032 (19) | 0.0157 (17) | −0.0030 (16) |
C7 | 0.035 (3) | 0.026 (2) | 0.0208 (17) | 0.0046 (19) | 0.0112 (17) | 0.0000 (16) |
C9 | 0.027 (3) | 0.024 (2) | 0.0228 (17) | 0.0017 (17) | 0.0048 (17) | 0.0029 (15) |
C6 | 0.026 (3) | 0.021 (2) | 0.0243 (17) | 0.0019 (17) | 0.0055 (17) | 0.0022 (15) |
C14 | 0.031 (3) | 0.026 (2) | 0.0290 (18) | 0.0074 (18) | 0.0048 (17) | 0.0010 (17) |
C13 | 0.047 (3) | 0.032 (2) | 0.0284 (18) | 0.020 (2) | 0.0041 (19) | −0.0047 (18) |
S1—C12 | 1.644 (3) | C2—C1 | 1.493 (4) |
O3—C11 | 1.215 (4) | C2—C9 | 1.382 (4) |
O2—C4 | 1.209 (4) | C10—C11 | 1.512 (5) |
O1—C1 | 1.210 (4) | C8—C7 | 1.395 (5) |
N4—C4 | 1.405 (5) | C8—C9 | 1.410 (5) |
N4—C1 | 1.394 (4) | C5—H5A | 0.9800 |
N4—C5 | 1.459 (4) | C5—H5B | 0.9800 |
N2—C12 | 1.390 (4) | C5—H5C | 0.9800 |
N2—C11 | 1.382 (4) | C7—H7 | 0.9500 |
N2—C14 | 1.458 (5) | C7—C6 | 1.389 (4) |
N1—C10 | 1.401 (4) | C9—H9 | 0.9500 |
N1—C12 | 1.363 (5) | C6—H6 | 0.9500 |
N1—C13 | 1.448 (4) | C14—H14A | 0.9800 |
N3—C10 | 1.252 (4) | C14—H14B | 0.9800 |
N3—C8 | 1.417 (4) | C14—H14C | 0.9800 |
C4—C3 | 1.481 (4) | C13—H13A | 0.9800 |
C3—C2 | 1.389 (5) | C13—H13B | 0.9800 |
C3—C6 | 1.387 (5) | C13—H13C | 0.9800 |
C4—N4—C5 | 123.6 (3) | C7—C8—N3 | 118.9 (3) |
C1—N4—C4 | 112.1 (3) | C7—C8—C9 | 121.0 (3) |
C1—N4—C5 | 124.1 (3) | C9—C8—N3 | 119.9 (3) |
C12—N2—C14 | 124.0 (3) | N4—C5—H5A | 109.5 |
C11—N2—C12 | 111.4 (3) | N4—C5—H5B | 109.5 |
C11—N2—C14 | 124.5 (3) | N4—C5—H5C | 109.5 |
C10—N1—C13 | 123.1 (3) | H5A—C5—H5B | 109.5 |
C12—N1—C10 | 111.8 (3) | H5A—C5—H5C | 109.5 |
C12—N1—C13 | 124.9 (3) | H5B—C5—H5C | 109.5 |
C10—N3—C8 | 120.6 (3) | C8—C7—H7 | 119.3 |
O2—C4—N4 | 125.1 (3) | C6—C7—C8 | 121.4 (3) |
O2—C4—C3 | 129.4 (3) | C6—C7—H7 | 119.3 |
N4—C4—C3 | 105.5 (3) | C2—C9—C8 | 116.4 (3) |
C2—C3—C4 | 108.7 (3) | C2—C9—H9 | 121.8 |
C6—C3—C4 | 130.4 (3) | C8—C9—H9 | 121.8 |
C6—C3—C2 | 121.0 (3) | C3—C6—C7 | 117.5 (3) |
C3—C2—C1 | 107.9 (3) | C3—C6—H6 | 121.2 |
C9—C2—C3 | 122.5 (3) | C7—C6—H6 | 121.2 |
C9—C2—C1 | 129.6 (3) | N2—C14—H14A | 109.5 |
N1—C10—C11 | 104.3 (3) | N2—C14—H14B | 109.5 |
N3—C10—N1 | 122.8 (3) | N2—C14—H14C | 109.5 |
N3—C10—C11 | 132.9 (3) | H14A—C14—H14B | 109.5 |
O1—C1—N4 | 124.3 (3) | H14A—C14—H14C | 109.5 |
O1—C1—C2 | 130.1 (3) | H14B—C14—H14C | 109.5 |
N4—C1—C2 | 105.7 (3) | N1—C13—H13A | 109.5 |
N2—C12—S1 | 125.7 (3) | N1—C13—H13B | 109.5 |
N1—C12—S1 | 126.9 (3) | N1—C13—H13C | 109.5 |
N1—C12—N2 | 107.4 (3) | H13A—C13—H13B | 109.5 |
O3—C11—N2 | 126.3 (3) | H13A—C13—H13C | 109.5 |
O3—C11—C10 | 128.5 (3) | H13B—C13—H13C | 109.5 |
N2—C11—C10 | 105.1 (3) | ||
O2—C4—C3—C2 | 179.0 (4) | C12—N2—C11—C10 | −0.3 (4) |
O2—C4—C3—C6 | −0.2 (7) | C12—N1—C10—N3 | −179.6 (3) |
N4—C4—C3—C2 | −0.5 (4) | C12—N1—C10—C11 | −1.4 (4) |
N4—C4—C3—C6 | −179.6 (4) | C11—N2—C12—S1 | 179.7 (3) |
N1—C10—C11—O3 | −176.8 (3) | C11—N2—C12—N1 | −0.6 (4) |
N1—C10—C11—N2 | 1.0 (3) | C8—N3—C10—N1 | −175.4 (3) |
N3—C10—C11—O3 | 1.1 (6) | C8—N3—C10—C11 | 7.1 (6) |
N3—C10—C11—N2 | 178.9 (4) | C8—C7—C6—C3 | 1.8 (6) |
N3—C8—C7—C6 | −179.0 (3) | C5—N4—C4—O2 | −1.0 (6) |
N3—C8—C9—C2 | 177.7 (3) | C5—N4—C4—C3 | 178.5 (3) |
C4—N4—C1—O1 | 174.2 (4) | C5—N4—C1—O1 | −1.3 (6) |
C4—N4—C1—C2 | −4.0 (4) | C5—N4—C1—C2 | −179.5 (3) |
C4—C3—C2—C1 | −1.9 (4) | C7—C8—C9—C2 | 3.1 (5) |
C4—C3—C2—C9 | 177.7 (3) | C9—C2—C1—O1 | 5.9 (7) |
C4—C3—C6—C7 | −179.1 (3) | C9—C2—C1—N4 | −175.9 (4) |
C3—C2—C1—O1 | −174.6 (4) | C9—C8—C7—C6 | −4.3 (6) |
C3—C2—C1—N4 | 3.6 (4) | C6—C3—C2—C1 | 177.4 (3) |
C3—C2—C9—C8 | 0.6 (5) | C6—C3—C2—C9 | −3.1 (6) |
C2—C3—C6—C7 | 1.9 (5) | C14—N2—C12—S1 | −3.3 (5) |
C10—N1—C12—S1 | −179.0 (3) | C14—N2—C12—N1 | 176.4 (3) |
C10—N1—C12—N2 | 1.3 (4) | C14—N2—C11—O3 | 0.6 (5) |
C10—N3—C8—C7 | −113.3 (4) | C14—N2—C11—C10 | −177.2 (3) |
C10—N3—C8—C9 | 72.0 (5) | C13—N1—C10—N3 | 4.7 (5) |
C1—N4—C4—O2 | −176.6 (3) | C13—N1—C10—C11 | −177.1 (3) |
C1—N4—C4—C3 | 2.9 (4) | C13—N1—C12—S1 | −3.4 (5) |
C1—C2—C9—C8 | −180.0 (4) | C13—N1—C12—N2 | 176.9 (3) |
C12—N2—C11—O3 | 177.6 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5C···O2i | 0.98 | 2.60 | 3.519 (5) | 157 |
C7—H7···O3ii | 0.95 | 2.37 | 3.302 (4) | 166 |
C9—H9···O1iii | 0.95 | 2.47 | 3.319 (4) | 149 |
C14—H14B···O2iv | 0.98 | 2.32 | 3.272 (5) | 164 |
Symmetry codes: (i) x−1, y, z; (ii) x+1, y, z; (iii) −x+1, −y+1, −z+1; (iv) −x+1, −y+2, −z+1. |
Acknowledgements
We thank Darshan S Mhatre for his help in collecting the X-ray data and the structure refinement.
Funding information
Funding for this research was provided by: Department of Science and Technology, Ministry of Science and Technology, India (grant No. SR/S2/JCB33/2010 to Prof. Sambasivarao Kotha); Council of Scientific and Industrial Research, India (scholarship to Naveen Kumar Gupta); University Grants Commission (scholarship to Saima Ansari).
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