organic compounds
1,3-Bis(2-oxopropyl)thymine
aDepartamento de Química, Universidade Federal Rural de Pernambuco, 52171-900 Recife, PE, Brazil, and bChemistry Department, State University of New York, College at Buffalo, 1300 Elmwood Ave, Buffalo, NY 14222-1095, USA
*Correspondence e-mail: nazareay@buffalostate.edu
In the title compound [systematic name: 5-methyl-1,3-bis(2-oxopropyl)pyrimidine-2,4(1H,3H)-dione], C11H14N2O4, the two 2-oxopropyl groups are nearly perpendicular to the planar thymine unit. One methyl group of oxopropyl substituent is disordered. In the crystal, C—H⋯O interactions help to connect the molecules into (001) layers.
Keywords: crystal structure; thymine; substituted nucleobase; 2-oxopropyl.
CCDC reference: 1986083
Structure description
Nucleoside analogs play an important role in combating viral diseases and neoplasms; this is demonstrated by the pharmacological success of drugs such as Zidovudine, Stavudine, Lamivudine, and around 20 others belonging to this group of compounds (Adamska et al., 2016; Krim et al., 2012; Negrón-Silva et al., 2013; Thakur et al., 2014). We performed the transformation of N1,N3-bispropargyl thymine and uracyl, which furnished N1,N3-bis-(2-oxopro-1-yl) derivatives; these compounds offer ample possibilities of further functionalization via C or O alkylation of their or via reductive amination, among others.
In the title compound (Fig. 1), the thymine unit is nearly planar, with the largest deviation from the mean plane being less than 0.03 Å. The two essentially planar 2-oxopropyl substituents are almost perpendicular to the thymine unit; the dihedral angles between the mean plane of the six-membered ring and those of the 2-oxopropyl fragments with atoms C1 and C7 are 77.96 (1) and 82.92 (1)°, respectively. Rotational disorder was observed for the C1 methyl group of the 2-oxopropyl substituent.
There are no usual hydrogen bonds in this structure. Attractive C—H⋯O interactions (Table 1), involving all oxygen atoms of the molecule, help to organize the molecules in a layer parallel to the (001) plane. These layers are packed in the three-dimensional crystal by mainly between hydrogen atoms (Fig. 2).
Synthesis and crystallization
As N1,N3-bispropargyl thymine can be prepared in yields exceeding 80%, we used it as a starting material to obtain the title compound (1) via addition of water catalyzed by silica-supported HgSO4/H2SO4 (Mello et al., 2010). This furnished the necessary 1 (Rf 0.30, EtOAc neat, more polar than N1,N3-bis-propargylthymine, Rf 0.70, hexane-EtOAc) by simple filtration of the solids and crystallization from ethyl acetate. The product formed well-resolved crystals suitable for X-ray analysis. Compound 1: m.p. 408–412 K (EtOAc). 1H NMR (300 MHz, DMSO-d6): 7.47 (broadened s, 1H, H6), 4.66 and 4.64 (two s, total of 4H, NCH2), 2.16 and 2.14 (two s, total of 6H, COCH3), 1.80 (broadened s, 3H, C5CH3). 13C NMR (75 MHz, DMSO-d6): 201.8 and 201.3 (two COCH3), 162.0 and 150.6 (C2, 4), 140.8 (C6), 107.3 (C5), 56.9 and 49.7 (two CH2), 27.1 and 26.8 (two COCH3), 12.4 (C5CH3).
Refinement
Crystal data, data collection and structure . Methyl group C1 is disordered.
details are summarized in Table 2
|
Structural data
CCDC reference: 1986083
https://doi.org/10.1107/S2414314620002576/zq4039sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314620002576/zq4039Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314620002576/zq4039Isup3.cdx
Supporting information file. DOI: https://doi.org/10.1107/S2414314620002576/zq4039Isup4.cml
Data collection: APEX2 (Bruker, 2013); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); 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).C11H14N2O4 | Dx = 1.360 Mg m−3 |
Mr = 238.24 | Melting point: 412 K |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 13.9490 (9) Å | Cell parameters from 2683 reflections |
b = 4.9891 (3) Å | θ = 3.0–25.8° |
c = 17.3647 (11) Å | µ = 0.11 mm−1 |
β = 105.693 (4)° | T = 173 K |
V = 1163.41 (13) Å3 | Plate, colourless |
Z = 4 | 0.2 × 0.15 × 0.08 mm |
F(000) = 504 |
Bruker PHOTON-100 CMOS diffractometer | 2458 independent reflections |
Radiation source: sealedtube | 1889 reflections with I > 2σ(I) |
Detector resolution: 10.4 pixels mm-1 | Rint = 0.051 |
ω scans | θmax = 26.7°, θmin = 3.0° |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | h = −17→17 |
Tmin = 0.769, Tmax = 0.862 | k = −6→6 |
18736 measured reflections | l = −21→21 |
Refinement on F2 | Primary atom site location: dual |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.042 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.103 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0421P)2 + 0.5355P] where P = (Fo2 + 2Fc2)/3 |
2458 reflections | (Δ/σ)max < 0.001 |
163 parameters | Δρmax = 0.21 e Å−3 |
0 restraints | Δρmin = −0.18 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. Methylene hydrogen atoms are refined with riding coordinates and with Uiso(H) = 1.2 Uiso(C); methyl hydrogen atoms are refined as rotating idealized methyl groups and with Uiso(H) = 1.5 Uiso(C). |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
O1 | 0.83624 (10) | 0.9143 (2) | 0.36977 (7) | 0.0433 (3) | |
O2 | 0.63791 (8) | 1.2059 (2) | 0.24695 (7) | 0.0361 (3) | |
O3 | 0.92187 (8) | 0.9349 (2) | 0.18756 (7) | 0.0378 (3) | |
O4 | 0.50121 (8) | 1.2301 (2) | 0.06408 (7) | 0.0364 (3) | |
N1 | 0.62809 (9) | 0.8661 (3) | 0.15811 (7) | 0.0258 (3) | |
N2 | 0.78007 (9) | 1.0765 (3) | 0.21574 (7) | 0.0244 (3) | |
C1 | 0.35466 (13) | 1.0758 (5) | 0.09457 (13) | 0.0579 (6) | |
H1A | 0.333498 | 1.262010 | 0.097365 | 0.087* | 0.43 (3) |
H1B | 0.343268 | 0.974481 | 0.139636 | 0.087* | 0.43 (3) |
H1C | 0.316192 | 0.995262 | 0.044202 | 0.087* | 0.43 (3) |
H1D | 0.328474 | 0.892492 | 0.090103 | 0.087* | 0.57 (3) |
H1E | 0.318704 | 1.180021 | 0.047833 | 0.087* | 0.57 (3) |
H1F | 0.345780 | 1.159240 | 0.143267 | 0.087* | 0.57 (3) |
C2 | 0.46300 (11) | 1.0691 (3) | 0.09839 (9) | 0.0285 (4) | |
C3 | 0.52141 (11) | 0.8459 (3) | 0.14837 (10) | 0.0291 (4) | |
H3A | 0.50906 (19) | 0.8483 (3) | 0.2009 (7) | 0.035* | |
H3B | 0.4978 (3) | 0.675 (2) | 0.1234 (3) | 0.035* | |
C4 | 0.67906 (11) | 1.0595 (3) | 0.20955 (9) | 0.0252 (3) | |
C5 | 0.83796 (11) | 1.2601 (3) | 0.27622 (8) | 0.0261 (3) | |
H5A | 0.8008 (5) | 1.422 (2) | 0.27574 (8) | 0.031* | |
H5B | 0.8985 (8) | 1.3054 (7) | 0.26324 (18) | 0.031* | |
C6 | 0.86268 (11) | 1.1388 (3) | 0.35899 (9) | 0.0266 (3) | |
C7 | 0.91998 (12) | 1.3150 (3) | 0.42473 (9) | 0.0316 (4) | |
H7A | 0.8774 (5) | 1.456 (2) | 0.4341 (5) | 0.047* | |
H7B | 0.9756 (8) | 1.392 (2) | 0.4098 (3) | 0.047* | |
H7C | 0.9440 (8) | 1.2108 (12) | 0.4727 (6) | 0.047* | |
C8 | 0.67438 (11) | 0.7030 (3) | 0.11540 (9) | 0.0259 (3) | |
H8 | 0.6350 (7) | 0.574 (2) | 0.0796 (7) | 0.031* | |
C9 | 0.77188 (11) | 0.7166 (3) | 0.12144 (8) | 0.0250 (3) | |
C10 | 0.83202 (11) | 0.9100 (3) | 0.17581 (9) | 0.0254 (3) | |
C11 | 0.82282 (13) | 0.5375 (4) | 0.07549 (10) | 0.0347 (4) | |
H11A | 0.7752 (6) | 0.398 (2) | 0.0469 (7) | 0.052* | |
H11B | 0.8811 (8) | 0.449 (2) | 0.1132 (4) | 0.052* | |
H11C | 0.8461 (8) | 0.6461 (12) | 0.0358 (6) | 0.052* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0613 (9) | 0.0324 (7) | 0.0357 (7) | −0.0108 (6) | 0.0122 (6) | 0.0031 (5) |
O2 | 0.0298 (6) | 0.0419 (7) | 0.0409 (7) | −0.0006 (5) | 0.0169 (5) | −0.0137 (6) |
O3 | 0.0215 (6) | 0.0471 (8) | 0.0452 (7) | 0.0015 (5) | 0.0095 (5) | −0.0046 (6) |
O4 | 0.0377 (7) | 0.0335 (7) | 0.0383 (7) | −0.0051 (5) | 0.0108 (5) | 0.0024 (5) |
N1 | 0.0200 (6) | 0.0270 (7) | 0.0309 (7) | −0.0016 (5) | 0.0079 (5) | −0.0025 (6) |
N2 | 0.0212 (6) | 0.0294 (7) | 0.0234 (6) | −0.0016 (5) | 0.0073 (5) | −0.0028 (5) |
C1 | 0.0299 (10) | 0.0888 (17) | 0.0564 (12) | 0.0140 (10) | 0.0142 (9) | 0.0332 (12) |
C2 | 0.0279 (8) | 0.0338 (9) | 0.0241 (7) | −0.0036 (7) | 0.0075 (6) | −0.0053 (7) |
C3 | 0.0213 (8) | 0.0303 (9) | 0.0366 (9) | −0.0047 (6) | 0.0093 (6) | −0.0001 (7) |
C4 | 0.0221 (7) | 0.0288 (8) | 0.0260 (7) | −0.0009 (6) | 0.0086 (6) | 0.0001 (6) |
C5 | 0.0242 (8) | 0.0285 (8) | 0.0255 (8) | −0.0042 (6) | 0.0064 (6) | −0.0023 (6) |
C6 | 0.0237 (8) | 0.0296 (8) | 0.0278 (8) | 0.0008 (6) | 0.0091 (6) | 0.0004 (7) |
C7 | 0.0313 (9) | 0.0361 (9) | 0.0262 (8) | −0.0022 (7) | 0.0058 (6) | 0.0011 (7) |
C8 | 0.0302 (8) | 0.0248 (8) | 0.0227 (7) | −0.0013 (6) | 0.0074 (6) | −0.0010 (6) |
C9 | 0.0295 (8) | 0.0249 (8) | 0.0217 (7) | 0.0038 (6) | 0.0087 (6) | 0.0028 (6) |
C10 | 0.0222 (8) | 0.0304 (8) | 0.0246 (7) | 0.0038 (6) | 0.0081 (6) | 0.0050 (6) |
C11 | 0.0383 (9) | 0.0361 (10) | 0.0340 (9) | 0.0054 (8) | 0.0168 (7) | −0.0022 (8) |
O1—C6 | 1.2093 (19) | C2—C3 | 1.508 (2) |
O2—C4 | 1.2191 (18) | C3—H3A | 0.972 (12) |
O3—C10 | 1.2205 (18) | C3—H3B | 0.972 (12) |
O4—C2 | 1.2066 (19) | C5—H5A | 0.958 (12) |
N1—C3 | 1.4551 (19) | C5—H5B | 0.958 (12) |
N1—C4 | 1.3749 (19) | C5—C6 | 1.511 (2) |
N1—C8 | 1.3742 (19) | C6—C7 | 1.491 (2) |
N2—C4 | 1.3864 (18) | C7—H7A | 0.962 (10) |
N2—C5 | 1.4612 (19) | C7—H7B | 0.962 (10) |
N2—C10 | 1.4027 (19) | C7—H7C | 0.962 (10) |
C1—H1A | 0.9800 | C8—H8 | 0.959 (17) |
C1—H1B | 0.9800 | C8—C9 | 1.337 (2) |
C1—H1C | 0.9800 | C9—C10 | 1.449 (2) |
C1—H1D | 0.9800 | C9—C11 | 1.499 (2) |
C1—H1E | 0.9800 | C11—H11A | 0.997 (11) |
C1—H1F | 0.9800 | C11—H11B | 0.997 (11) |
C1—C2 | 1.495 (2) | C11—H11C | 0.997 (11) |
C4—N1—C3 | 117.21 (12) | H3A—C3—H3B | 107.8 |
C8—N1—C3 | 120.74 (13) | O2—C4—N1 | 122.08 (13) |
C8—N1—C4 | 122.02 (12) | O2—C4—N2 | 122.48 (14) |
C4—N2—C5 | 116.53 (12) | N1—C4—N2 | 115.44 (13) |
C4—N2—C10 | 125.13 (13) | N2—C5—H5A | 109.2 |
C10—N2—C5 | 117.87 (12) | N2—C5—H5B | 109.2 |
H1A—C1—H1B | 109.5 | N2—C5—C6 | 111.84 (13) |
H1A—C1—H1C | 109.5 | H5A—C5—H5B | 107.9 |
H1A—C1—H1D | 141.1 | C6—C5—H5A | 109.2 |
H1A—C1—H1E | 56.3 | C6—C5—H5B | 109.2 |
H1A—C1—H1F | 56.3 | O1—C6—C5 | 121.18 (14) |
H1B—C1—H1C | 109.5 | O1—C6—C7 | 123.40 (14) |
H1B—C1—H1D | 56.3 | C7—C6—C5 | 115.42 (13) |
H1B—C1—H1E | 141.1 | C6—C7—H7A | 109.5 |
H1B—C1—H1F | 56.3 | C6—C7—H7B | 109.5 |
H1C—C1—H1D | 56.3 | C6—C7—H7C | 109.5 |
H1C—C1—H1E | 56.3 | H7A—C7—H7B | 109.5 |
H1C—C1—H1F | 141.1 | H7A—C7—H7C | 109.5 |
H1D—C1—H1E | 109.5 | H7B—C7—H7C | 109.5 |
H1D—C1—H1F | 109.5 | N1—C8—H8 | 118.5 |
H1E—C1—H1F | 109.5 | C9—C8—N1 | 122.96 (14) |
C2—C1—H1A | 109.5 | C9—C8—H8 | 118.5 |
C2—C1—H1B | 109.5 | C8—C9—C10 | 118.83 (14) |
C2—C1—H1C | 109.5 | C8—C9—C11 | 123.13 (14) |
C2—C1—H1D | 109.5 | C10—C9—C11 | 118.03 (13) |
C2—C1—H1E | 109.5 | O3—C10—N2 | 120.12 (14) |
C2—C1—H1F | 109.5 | O3—C10—C9 | 124.33 (14) |
O4—C2—C1 | 122.64 (16) | N2—C10—C9 | 115.55 (12) |
O4—C2—C3 | 122.26 (14) | C9—C11—H11A | 109.5 |
C1—C2—C3 | 115.10 (14) | C9—C11—H11B | 109.5 |
N1—C3—C2 | 113.07 (13) | C9—C11—H11C | 109.5 |
N1—C3—H3A | 109.0 | H11A—C11—H11B | 109.5 |
N1—C3—H3B | 109.0 | H11A—C11—H11C | 109.5 |
C2—C3—H3A | 109.0 | H11B—C11—H11C | 109.5 |
C2—C3—H3B | 109.0 | ||
O4—C2—C3—N1 | 6.9 (2) | C5—N2—C4—O2 | 6.5 (2) |
N1—C8—C9—C10 | 0.5 (2) | C5—N2—C4—N1 | −173.64 (13) |
N1—C8—C9—C11 | 179.45 (14) | C5—N2—C10—O3 | −5.4 (2) |
N2—C5—C6—O1 | 0.6 (2) | C5—N2—C10—C9 | 175.01 (12) |
N2—C5—C6—C7 | −178.80 (12) | C8—N1—C3—C2 | −103.59 (16) |
C1—C2—C3—N1 | −173.11 (16) | C8—N1—C4—O2 | 179.34 (15) |
C3—N1—C4—O2 | 1.3 (2) | C8—N1—C4—N2 | −0.5 (2) |
C3—N1—C4—N2 | −178.54 (13) | C8—C9—C10—O3 | 178.02 (15) |
C3—N1—C8—C9 | 179.04 (14) | C8—C9—C10—N2 | −2.5 (2) |
C4—N1—C3—C2 | 74.43 (17) | C10—N2—C4—O2 | 178.41 (14) |
C4—N1—C8—C9 | 1.1 (2) | C10—N2—C4—N1 | −1.7 (2) |
C4—N2—C5—C6 | 79.50 (16) | C10—N2—C5—C6 | −93.04 (15) |
C4—N2—C10—O3 | −177.28 (14) | C11—C9—C10—O3 | −1.0 (2) |
C4—N2—C10—C9 | 3.2 (2) | C11—C9—C10—N2 | 178.53 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
C3—H3A···O2i | 0.97 (1) | 2.56 (1) | 3.304 (2) | 134 (1) |
C3—H3B···O4ii | 0.97 (1) | 2.45 (1) | 3.3820 (19) | 160 (1) |
C5—H5B···O3iii | 0.96 (1) | 2.50 (1) | 3.353 (2) | 148 (1) |
C7—H7A···O1iv | 0.96 (1) | 2.54 (1) | 3.2576 (19) | 131 (1) |
C7—H7B···O3iii | 0.96 (1) | 2.50 (1) | 3.370 (2) | 150 (1) |
C8—H8···O4ii | 0.96 (1) | 2.50 (1) | 3.3213 (19) | 144 (1) |
Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) x, y−1, z; (iii) −x+2, y+1/2, −z+1/2; (iv) x, y+1, z. |
Acknowledgements
Financial support from the State University of New York for acquisition and maintenance of the X-ray diffractometer is gratefully acknowledged.
References
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