organic compounds
2-[(4,6-Diaminopyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
aCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India, and bDepartment of Pharmaceutical Science and Technology, Birla Institute of Technology, Mesta, Ranchi 835215, Jharkhand, India
*Correspondence e-mail: shirai2011@gmail.com
In the title compound, C13H15N5O2S, the acetamide N—C(=O)—C plane makes dihedral angles of 30.51 (11) and 51.93 (11)°, respectively, with the benzene ring and the pyrimidine ring. The dihedral angle between the benzene and pyrimidine rings is 43.40 (6)°. There is an intramolecular N—H⋯N hydrogen bond with an S(7) ring motif. In the crystal, molecules are linked by pairs of intermolecular N—H⋯N hydrogen bonds, forming inversion dimers with an R22(8) ring motif. The molecules are further linked by intermolecular N—H⋯O hydrogen bonds, forming a C(9) chain along [100]. Intermolecular C—H⋯π and N—H⋯π interactions are also observed.
Keywords: crystal structure; 2; 4-diaminopyrimidine derivative.
CCDC reference: 1838329
Structure description
2,4-Diaminopyrimidine derivatives are reported to be potent antimalarial and anti-filarial agents because of their inhibition of dihydrofolate reductase (DHFR) (Neekhara et al., 2006; Sharma et al., 2013). Furthermore, they have also exhibited anti-retroviral activity (Hocková et al., 2004), antibacterial (Kandeel et al., 1994) and potential anti-microbial properties (Holla et al., 2006). As part of our own studies in this area, we report herein the synthesis and of the title compound.
The title molecule has an intramolecular N—H⋯N hydrogen bond with an S(7) ring motif (Table 1 and Fig. 1). The methyl group (C1) is oriented syn-periplanar to atom C7 [C7—C2—O2—C1 = 5.7 (3)°] and anti-periplanar to atom C3 [C3—C2—O2—C1 = −174.8 (2)°]. The pyrimidine ring makes a dihedral angle of 43.40 (6)° with the benzene ring. The acetamide N5/C8/O1/C9 plane makes dihedral angles of 30.51 (11) and 51.93 (11)°, respectively, with the benzene and pyrimidine rings. The bond lengths C10—S1 [1.7664 (17) Å] and C9—S1 [1.808 (2) Å] are comparable with the values reported in the literature (1.751 and 1.813 Å, respectively; Allen et al., 1987).
In the crystal, the molecules are linked into inversion dimers with an R22(8) ring motif by pairs of N—H⋯N hydrogen bonds (Table 1, Fig. 2). Adjacent molecules are further linked via N—H⋯O hydrogen bonds, forming a C(9) chain along [100]. The crystal packing also features C—H⋯π and N—H⋯π interactions (Table 1 and Fig. 3).
Synthesis and crystallization
To a solution of 4,6-diamino-pyrimidine-2-thiol (0.5 g, 3.52 mmol) in 25 ml of ethanol was added (0.2g, 3.52 mmol) potassium hydroxide and the mixture was refluxed for about 30 min. An equimolar quantity of 2-chloro-N-(4-methoxyphenyl)acetamide (3.52 mmol) was then added and reflux was continued for 4 h. Evaporation of the organic layer in a vacuum provided the title compound. After purification, single crystals were obtained from an ethanol solution by slow evaporation of the solvent.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2
|
Structural data
CCDC reference: 1838329
https://doi.org/10.1107/S2414314618006004/is4027sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618006004/is4027Isup3.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314618006004/is4027Isup3.cml
Data collection: APEX2 (Bruker, 2008); cell
APEX2 (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2015).C13H15N5O2S | Dx = 1.458 Mg m−3 |
Mr = 305.36 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pbca | Cell parameters from 3471 reflections |
a = 18.2763 (6) Å | θ = 2.0–28.3° |
b = 7.5909 (2) Å | µ = 0.25 mm−1 |
c = 20.0571 (6) Å | T = 293 K |
V = 2782.59 (14) Å3 | Block, yellow |
Z = 8 | 0.30 × 0.25 × 0.20 mm |
F(000) = 1280 |
Bruker SMART APEXII area-detector diffractometer | 2119 reflections with I > 2σ(I) |
ω and φ scans | Rint = 0.043 |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | θmax = 28.3°, θmin = 2.0° |
Tmin = 0.753, Tmax = 0.823 | h = −24→15 |
14130 measured reflections | k = −10→8 |
3471 independent reflections | l = −13→26 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.042 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.110 | w = 1/[σ2(Fo2) + (0.0494P)2 + 0.2859P] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
3471 reflections | Δρmax = 0.25 e Å−3 |
211 parameters | Δρmin = −0.27 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. |
Refinement. The C-bound H atoms were placed in calculated positions with C—H = 0.93–0.97 Å and refined as riding with Uiso(H) = 1.5Ueq(C) for methyl group or Uiso(H) = 1.2Ueq(C) for other groups. The N-bound H atoms were located in a difference Fourier map and refined freely. |
x | y | z | Uiso*/Ueq | ||
H1D | −0.0645 (12) | 0.581 (3) | 0.0150 (12) | 0.064 (7)* | |
H1E | −0.1267 (12) | 0.591 (3) | 0.0632 (11) | 0.052 (7)* | |
H2A | −0.0275 (12) | 0.190 (3) | 0.2877 (11) | 0.048 (7)* | |
H2B | −0.1027 (12) | 0.269 (3) | 0.2704 (10) | 0.045 (6)* | |
H5 | 0.1243 (11) | 0.295 (3) | 0.2612 (9) | 0.042 (6)* | |
C1 | 0.11212 (15) | 0.6519 (4) | 0.56365 (12) | 0.0726 (8) | |
H1A | 0.1009 | 0.7542 | 0.5375 | 0.109* | |
H1B | 0.1226 | 0.6868 | 0.6086 | 0.109* | |
H1C | 0.0710 | 0.5731 | 0.5634 | 0.109* | |
C2 | 0.16810 (11) | 0.5039 (3) | 0.47250 (9) | 0.0387 (5) | |
C3 | 0.22722 (11) | 0.4076 (3) | 0.44951 (9) | 0.0399 (5) | |
H3 | 0.2665 | 0.3864 | 0.4778 | 0.048* | |
C4 | 0.22885 (10) | 0.3426 (3) | 0.38539 (9) | 0.0375 (5) | |
H4 | 0.2690 | 0.2781 | 0.3707 | 0.045* | |
C5 | 0.17026 (10) | 0.3739 (3) | 0.34272 (9) | 0.0337 (5) | |
C6 | 0.11077 (10) | 0.4671 (3) | 0.36636 (10) | 0.0404 (5) | |
H6 | 0.0710 | 0.4867 | 0.3383 | 0.049* | |
C7 | 0.10898 (11) | 0.5321 (3) | 0.43086 (10) | 0.0425 (5) | |
H7 | 0.0684 | 0.5942 | 0.4460 | 0.051* | |
C8 | 0.22034 (10) | 0.2696 (3) | 0.23446 (9) | 0.0363 (5) | |
C9 | 0.19429 (11) | 0.1899 (3) | 0.16929 (9) | 0.0406 (5) | |
H9A | 0.1574 | 0.1017 | 0.1791 | 0.049* | |
H9B | 0.2352 | 0.1303 | 0.1482 | 0.049* | |
C10 | 0.06326 (9) | 0.3615 (3) | 0.13367 (9) | 0.0299 (4) | |
C11 | −0.04605 (9) | 0.4777 (3) | 0.10243 (9) | 0.0325 (4) | |
C12 | −0.07491 (10) | 0.4288 (3) | 0.16389 (9) | 0.0349 (5) | |
H12 | −0.1223 | 0.4598 | 0.1760 | 0.042* | |
C13 | −0.03109 (10) | 0.3332 (3) | 0.20616 (9) | 0.0325 (5) | |
N1 | −0.08541 (11) | 0.5584 (3) | 0.05502 (9) | 0.0468 (5) | |
N2 | −0.05566 (11) | 0.2679 (3) | 0.26481 (8) | 0.0457 (5) | |
N3 | 0.04068 (8) | 0.3016 (2) | 0.19228 (7) | 0.0335 (4) | |
N4 | 0.02461 (8) | 0.4414 (2) | 0.08647 (7) | 0.0339 (4) | |
N5 | 0.16624 (9) | 0.3033 (2) | 0.27763 (8) | 0.0366 (4) | |
O1 | 0.28525 (7) | 0.2957 (2) | 0.24536 (7) | 0.0565 (5) | |
O2 | 0.17327 (8) | 0.5664 (2) | 0.53655 (7) | 0.0524 (4) | |
S1 | 0.15638 (2) | 0.34642 (8) | 0.11078 (2) | 0.03976 (17) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.091 (2) | 0.083 (2) | 0.0438 (14) | 0.0218 (17) | 0.0071 (13) | −0.0136 (14) |
C2 | 0.0467 (11) | 0.0393 (13) | 0.0301 (10) | −0.0042 (10) | 0.0000 (9) | 0.0051 (9) |
C3 | 0.0375 (11) | 0.0489 (14) | 0.0331 (10) | −0.0014 (10) | −0.0062 (8) | 0.0058 (10) |
C4 | 0.0302 (9) | 0.0455 (13) | 0.0368 (10) | 0.0031 (9) | 0.0001 (8) | 0.0029 (10) |
C5 | 0.0320 (10) | 0.0369 (12) | 0.0322 (10) | −0.0021 (9) | −0.0023 (8) | 0.0037 (9) |
C6 | 0.0361 (10) | 0.0487 (14) | 0.0365 (10) | 0.0056 (10) | −0.0048 (8) | 0.0044 (10) |
C7 | 0.0446 (11) | 0.0403 (13) | 0.0425 (11) | 0.0078 (10) | 0.0043 (9) | 0.0003 (10) |
C8 | 0.0305 (10) | 0.0429 (13) | 0.0356 (10) | 0.0038 (10) | −0.0027 (8) | 0.0036 (9) |
C9 | 0.0361 (10) | 0.0468 (14) | 0.0390 (11) | 0.0108 (10) | −0.0029 (9) | −0.0053 (10) |
C10 | 0.0272 (9) | 0.0354 (12) | 0.0270 (9) | −0.0013 (8) | −0.0012 (7) | −0.0045 (8) |
C11 | 0.0310 (9) | 0.0356 (12) | 0.0309 (9) | 0.0021 (8) | −0.0030 (8) | −0.0060 (9) |
C12 | 0.0268 (9) | 0.0479 (14) | 0.0300 (10) | 0.0044 (9) | 0.0009 (7) | −0.0046 (9) |
C13 | 0.0305 (9) | 0.0394 (13) | 0.0278 (9) | −0.0027 (9) | 0.0014 (7) | −0.0060 (9) |
N1 | 0.0378 (10) | 0.0685 (15) | 0.0341 (10) | 0.0194 (10) | 0.0001 (8) | 0.0072 (10) |
N2 | 0.0324 (10) | 0.0698 (15) | 0.0349 (10) | −0.0007 (10) | 0.0029 (8) | 0.0128 (10) |
N3 | 0.0267 (8) | 0.0445 (11) | 0.0292 (8) | −0.0003 (8) | −0.0001 (6) | 0.0015 (7) |
N4 | 0.0293 (8) | 0.0437 (11) | 0.0286 (8) | 0.0028 (8) | 0.0006 (6) | 0.0013 (8) |
N5 | 0.0261 (8) | 0.0518 (12) | 0.0319 (8) | −0.0013 (8) | −0.0032 (7) | −0.0015 (8) |
O1 | 0.0273 (7) | 0.0955 (13) | 0.0466 (8) | −0.0007 (8) | −0.0033 (6) | −0.0068 (9) |
O2 | 0.0659 (10) | 0.0570 (11) | 0.0343 (7) | 0.0039 (9) | −0.0024 (7) | −0.0048 (7) |
S1 | 0.0274 (2) | 0.0607 (4) | 0.0311 (3) | 0.0034 (2) | 0.00268 (19) | 0.0036 (2) |
C1—O2 | 1.402 (3) | C9—S1 | 1.808 (2) |
C1—H1A | 0.9600 | C9—H9A | 0.9700 |
C1—H1B | 0.9600 | C9—H9B | 0.9700 |
C1—H1C | 0.9600 | C10—N3 | 1.326 (2) |
C2—O2 | 1.373 (2) | C10—N4 | 1.328 (2) |
C2—C7 | 1.382 (3) | C10—S1 | 1.7664 (17) |
C2—C3 | 1.384 (3) | C11—N1 | 1.341 (2) |
C3—C4 | 1.378 (3) | C11—N4 | 1.359 (2) |
C3—H3 | 0.9300 | C11—C12 | 1.391 (2) |
C4—C5 | 1.391 (2) | C12—C13 | 1.373 (3) |
C4—H4 | 0.9300 | C12—H12 | 0.9300 |
C5—C6 | 1.381 (3) | C13—N2 | 1.353 (2) |
C5—N5 | 1.413 (2) | C13—N3 | 1.362 (2) |
C6—C7 | 1.385 (3) | N1—H1D | 0.91 (2) |
C6—H6 | 0.9300 | N1—H1E | 0.81 (2) |
C7—H7 | 0.9300 | N2—H2A | 0.91 (2) |
C8—O1 | 1.222 (2) | N2—H2B | 0.87 (2) |
C8—N5 | 1.339 (2) | N5—H5 | 0.84 (2) |
C8—C9 | 1.517 (3) | ||
O2—C1—H1A | 109.5 | S1—C9—H9A | 108.6 |
O2—C1—H1B | 109.5 | C8—C9—H9B | 108.6 |
H1A—C1—H1B | 109.5 | S1—C9—H9B | 108.6 |
O2—C1—H1C | 109.5 | H9A—C9—H9B | 107.6 |
H1A—C1—H1C | 109.5 | N3—C10—N4 | 128.54 (16) |
H1B—C1—H1C | 109.5 | N3—C10—S1 | 120.52 (13) |
O2—C2—C7 | 124.45 (19) | N4—C10—S1 | 110.91 (13) |
O2—C2—C3 | 116.15 (17) | N1—C11—N4 | 115.81 (17) |
C7—C2—C3 | 119.40 (18) | N1—C11—C12 | 123.17 (17) |
C4—C3—C2 | 121.13 (18) | N4—C11—C12 | 121.00 (16) |
C4—C3—H3 | 119.4 | C13—C12—C11 | 117.83 (17) |
C2—C3—H3 | 119.4 | C13—C12—H12 | 121.1 |
C3—C4—C5 | 119.78 (18) | C11—C12—H12 | 121.1 |
C3—C4—H4 | 120.1 | N2—C13—N3 | 115.64 (17) |
C5—C4—H4 | 120.1 | N2—C13—C12 | 122.45 (17) |
C6—C5—C4 | 118.82 (18) | N3—C13—C12 | 121.89 (16) |
C6—C5—N5 | 118.06 (16) | C11—N1—H1D | 119.2 (15) |
C4—C5—N5 | 122.95 (18) | C11—N1—H1E | 119.7 (16) |
C5—C6—C7 | 121.46 (18) | H1D—N1—H1E | 121 (2) |
C5—C6—H6 | 119.3 | C13—N2—H2A | 119.3 (14) |
C7—C6—H6 | 119.3 | C13—N2—H2B | 116.0 (14) |
C2—C7—C6 | 119.38 (19) | H2A—N2—H2B | 120 (2) |
C2—C7—H7 | 120.3 | C10—N3—C13 | 114.85 (15) |
C6—C7—H7 | 120.3 | C10—N4—C11 | 115.47 (15) |
O1—C8—N5 | 124.76 (19) | C8—N5—C5 | 129.15 (17) |
O1—C8—C9 | 121.55 (17) | C8—N5—H5 | 114.1 (13) |
N5—C8—C9 | 113.67 (16) | C5—N5—H5 | 116.1 (14) |
C8—C9—S1 | 114.65 (15) | C2—O2—C1 | 117.90 (17) |
C8—C9—H9A | 108.6 | C10—S1—C9 | 104.07 (9) |
O2—C2—C3—C4 | −178.18 (19) | S1—C10—N3—C13 | 175.11 (14) |
C7—C2—C3—C4 | 1.4 (3) | N2—C13—N3—C10 | 177.94 (18) |
C2—C3—C4—C5 | 0.0 (3) | C12—C13—N3—C10 | −3.5 (3) |
C3—C4—C5—C6 | −1.3 (3) | N3—C10—N4—C11 | 5.3 (3) |
C3—C4—C5—N5 | −176.38 (19) | S1—C10—N4—C11 | −172.79 (14) |
C4—C5—C6—C7 | 1.1 (3) | N1—C11—N4—C10 | 179.97 (18) |
N5—C5—C6—C7 | 176.5 (2) | C12—C11—N4—C10 | −1.5 (3) |
O2—C2—C7—C6 | 178.01 (19) | O1—C8—N5—C5 | 0.2 (4) |
C3—C2—C7—C6 | −1.5 (3) | C9—C8—N5—C5 | 178.83 (19) |
C5—C6—C7—C2 | 0.3 (3) | C6—C5—N5—C8 | 152.0 (2) |
O1—C8—C9—S1 | −102.2 (2) | C4—C5—N5—C8 | −32.9 (3) |
N5—C8—C9—S1 | 79.2 (2) | C7—C2—O2—C1 | 5.7 (3) |
N1—C11—C12—C13 | 174.4 (2) | C3—C2—O2—C1 | −174.8 (2) |
N4—C11—C12—C13 | −4.0 (3) | N3—C10—S1—C9 | 15.55 (19) |
C11—C12—C13—N2 | −174.90 (19) | N4—C10—S1—C9 | −166.19 (14) |
C11—C12—C13—N3 | 6.7 (3) | C8—C9—S1—C10 | −86.82 (15) |
N4—C10—N3—C13 | −2.8 (3) |
Cg1 and Cg2 are the centroids of the N3/C10/N4/C11–C13 and C2–C7 rings, respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1D···N4i | 0.91 (2) | 2.17 (2) | 3.048 (2) | 164.2 (2) |
N2—H2B···O1ii | 0.87 (2) | 2.08 (2) | 2.922 (2) | 163.1 (2) |
N5—H5···N3 | 0.84 (2) | 2.06 (2) | 2.863 (2) | 160.3 (2) |
N2—H2A···Cg1iii | 0.91 (2) | 2.62 (1) | 3.533 (2) | 156.7 (2) |
C4—H4···Cg2iv | 0.93 | 2.76 | 3.623 (2) | 134 |
Symmetry codes: (i) −x, −y+1, −z; (ii) x−1/2, y, −z+1/2; (iii) −x, y−1/2, −z+1/2; (iv) −x+1/2, y−1/2, z. |
Acknowledgements
The authors the thank TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for data collection.
Funding information
MC thanks the CSIR, Government of India, for an SRF fellowship.
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