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

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ISSN: 2414-3146

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

Edited by O. Blacque, University of Zürich, Switzerland (Received 15 February 2020; accepted 24 February 2020; online 28 February 2020)

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.

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

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[Adamska, A., Rumijowska-Galewicz, A., Ruszczynska, A., Studzińska, M., Jabłońska, A., Paradowska, E., Bulska, E., Munier-Lehmann, H., Dziadek, J., Leśnikowski, Z. J. & Olejniczak, A. B. (2016). Eur. J. Med. Chem. 121, 71-81.]; Krim et al., 2012[Krim, J., Taourirte, M. & Engels, J. W. (2012). Molecules, 17, 179-190.]; Negrón-Silva et al., 2013[Negrón-Silva, G. E., González-Olvera, R., Angeles-Beltrán, D., Maldonado-Carmona, N., Espinoza-Vázquez, A., Palomar-Pardavé, M. E., Romero-Romo, M. A. & Santillan, R. (2013). Molecules, 18, 4613-4627.]; Thakur et al., 2014[Thakur, R. K., Mishra, A., Ramakrishna, K. K. G., Mahar, R., Shukla, S. K., Srivastava, A. K. & Tripathi, R. P. (2014). Tetrahedron, 70, 8462-8473.]). 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 enolates, or via reductive amination, among others.

In the title compound (Fig. 1[link]), 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.

[Figure 1]
Figure 1
Numbering scheme for the title compound, shown with 50% probability displacement ellipsoids.

There are no usual hydrogen bonds in this structure. Attractive C—H⋯O inter­actions (Table 1[link]), 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 van der Waals forces, mainly between hydrogen atoms (Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) x, y-1, z; (iii) [-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iv) x, y+1, z.
[Figure 2]
Figure 2
Packing of the title compound, viewed along [010].

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[Mello, R., Alcalde-Aragonés, A. & González-Núñez, M. E. (2010). Tetrahedron Lett. 51, 4281-4283.]). 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 refinement details are summarized in Table 2[link]. Methyl group C1 is disordered.

Table 2
Experimental details

Crystal data
Chemical formula C11H14N2O4
Mr 238.24
Crystal system, space group Monoclinic, P21/c
Temperature (K) 173
a, b, c (Å) 13.9490 (9), 4.9891 (3), 17.3647 (11)
β (°) 105.693 (4)
V3) 1163.41 (13)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.11
Crystal size (mm) 0.2 × 0.15 × 0.08
 
Data collection
Diffractometer Bruker PHOTON-100 CMOS
Absorption correction Multi-scan (SADABS; Krause et al., 2015[Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3-10.])
Tmin, Tmax 0.769, 0.862
No. of measured, independent and observed [I > 2σ(I)] reflections 18736, 2458, 1889
Rint 0.051
(sin θ/λ)max−1) 0.632
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.103, 1.03
No. of reflections 2458
No. of parameters 163
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.21, −0.19
Computer programs: APEX2 (Bruker, 2013[Bruker (2013). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]) SAINT (Bruker, 2016[Bruker (2016). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Structural data


Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: 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).

5-Methyl-1,3-bis(2-oxopropyl)pyrimidine-2,4(1H,3H)-dione top
Crystal data top
C11H14N2O4Dx = 1.360 Mg m3
Mr = 238.24Melting point: 412 K
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 13.9490 (9) ÅCell parameters from 2683 reflections
b = 4.9891 (3) Åθ = 3.0–25.8°
c = 17.3647 (11) ŵ = 0.11 mm1
β = 105.693 (4)°T = 173 K
V = 1163.41 (13) Å3Plate, colourless
Z = 40.2 × 0.15 × 0.08 mm
F(000) = 504
Data collection top
Bruker PHOTON-100 CMOS
diffractometer
2458 independent reflections
Radiation source: sealedtube1889 reflections with I > 2σ(I)
Detector resolution: 10.4 pixels mm-1Rint = 0.051
ω scansθmax = 26.7°, θmin = 3.0°
Absorption correction: multi-scan
(SADABS; Krause et al., 2015)
h = 1717
Tmin = 0.769, Tmax = 0.862k = 66
18736 measured reflectionsl = 2121
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.103H 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 parametersΔρmax = 0.21 e Å3
0 restraintsΔρmin = 0.18 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.

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).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.83624 (10)0.9143 (2)0.36977 (7)0.0433 (3)
O20.63791 (8)1.2059 (2)0.24695 (7)0.0361 (3)
O30.92187 (8)0.9349 (2)0.18756 (7)0.0378 (3)
O40.50121 (8)1.2301 (2)0.06408 (7)0.0364 (3)
N10.62809 (9)0.8661 (3)0.15811 (7)0.0258 (3)
N20.78007 (9)1.0765 (3)0.21574 (7)0.0244 (3)
C10.35466 (13)1.0758 (5)0.09457 (13)0.0579 (6)
H1A0.3334981.2620100.0973650.087*0.43 (3)
H1B0.3432680.9744810.1396360.087*0.43 (3)
H1C0.3161920.9952620.0442020.087*0.43 (3)
H1D0.3284740.8924920.0901030.087*0.57 (3)
H1E0.3187041.1800210.0478330.087*0.57 (3)
H1F0.3457801.1592400.1432670.087*0.57 (3)
C20.46300 (11)1.0691 (3)0.09839 (9)0.0285 (4)
C30.52141 (11)0.8459 (3)0.14837 (10)0.0291 (4)
H3A0.50906 (19)0.8483 (3)0.2009 (7)0.035*
H3B0.4978 (3)0.675 (2)0.1234 (3)0.035*
C40.67906 (11)1.0595 (3)0.20955 (9)0.0252 (3)
C50.83796 (11)1.2601 (3)0.27622 (8)0.0261 (3)
H5A0.8008 (5)1.422 (2)0.27574 (8)0.031*
H5B0.8985 (8)1.3054 (7)0.26324 (18)0.031*
C60.86268 (11)1.1388 (3)0.35899 (9)0.0266 (3)
C70.91998 (12)1.3150 (3)0.42473 (9)0.0316 (4)
H7A0.8774 (5)1.456 (2)0.4341 (5)0.047*
H7B0.9756 (8)1.392 (2)0.4098 (3)0.047*
H7C0.9440 (8)1.2108 (12)0.4727 (6)0.047*
C80.67438 (11)0.7030 (3)0.11540 (9)0.0259 (3)
H80.6350 (7)0.574 (2)0.0796 (7)0.031*
C90.77188 (11)0.7166 (3)0.12144 (8)0.0250 (3)
C100.83202 (11)0.9100 (3)0.17581 (9)0.0254 (3)
C110.82282 (13)0.5375 (4)0.07549 (10)0.0347 (4)
H11A0.7752 (6)0.398 (2)0.0469 (7)0.052*
H11B0.8811 (8)0.449 (2)0.1132 (4)0.052*
H11C0.8461 (8)0.6461 (12)0.0358 (6)0.052*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0613 (9)0.0324 (7)0.0357 (7)0.0108 (6)0.0122 (6)0.0031 (5)
O20.0298 (6)0.0419 (7)0.0409 (7)0.0006 (5)0.0169 (5)0.0137 (6)
O30.0215 (6)0.0471 (8)0.0452 (7)0.0015 (5)0.0095 (5)0.0046 (6)
O40.0377 (7)0.0335 (7)0.0383 (7)0.0051 (5)0.0108 (5)0.0024 (5)
N10.0200 (6)0.0270 (7)0.0309 (7)0.0016 (5)0.0079 (5)0.0025 (6)
N20.0212 (6)0.0294 (7)0.0234 (6)0.0016 (5)0.0073 (5)0.0028 (5)
C10.0299 (10)0.0888 (17)0.0564 (12)0.0140 (10)0.0142 (9)0.0332 (12)
C20.0279 (8)0.0338 (9)0.0241 (7)0.0036 (7)0.0075 (6)0.0053 (7)
C30.0213 (8)0.0303 (9)0.0366 (9)0.0047 (6)0.0093 (6)0.0001 (7)
C40.0221 (7)0.0288 (8)0.0260 (7)0.0009 (6)0.0086 (6)0.0001 (6)
C50.0242 (8)0.0285 (8)0.0255 (8)0.0042 (6)0.0064 (6)0.0023 (6)
C60.0237 (8)0.0296 (8)0.0278 (8)0.0008 (6)0.0091 (6)0.0004 (7)
C70.0313 (9)0.0361 (9)0.0262 (8)0.0022 (7)0.0058 (6)0.0011 (7)
C80.0302 (8)0.0248 (8)0.0227 (7)0.0013 (6)0.0074 (6)0.0010 (6)
C90.0295 (8)0.0249 (8)0.0217 (7)0.0038 (6)0.0087 (6)0.0028 (6)
C100.0222 (8)0.0304 (8)0.0246 (7)0.0038 (6)0.0081 (6)0.0050 (6)
C110.0383 (9)0.0361 (10)0.0340 (9)0.0054 (8)0.0168 (7)0.0022 (8)
Geometric parameters (Å, º) top
O1—C61.2093 (19)C2—C31.508 (2)
O2—C41.2191 (18)C3—H3A0.972 (12)
O3—C101.2205 (18)C3—H3B0.972 (12)
O4—C21.2066 (19)C5—H5A0.958 (12)
N1—C31.4551 (19)C5—H5B0.958 (12)
N1—C41.3749 (19)C5—C61.511 (2)
N1—C81.3742 (19)C6—C71.491 (2)
N2—C41.3864 (18)C7—H7A0.962 (10)
N2—C51.4612 (19)C7—H7B0.962 (10)
N2—C101.4027 (19)C7—H7C0.962 (10)
C1—H1A0.9800C8—H80.959 (17)
C1—H1B0.9800C8—C91.337 (2)
C1—H1C0.9800C9—C101.449 (2)
C1—H1D0.9800C9—C111.499 (2)
C1—H1E0.9800C11—H11A0.997 (11)
C1—H1F0.9800C11—H11B0.997 (11)
C1—C21.495 (2)C11—H11C0.997 (11)
C4—N1—C3117.21 (12)H3A—C3—H3B107.8
C8—N1—C3120.74 (13)O2—C4—N1122.08 (13)
C8—N1—C4122.02 (12)O2—C4—N2122.48 (14)
C4—N2—C5116.53 (12)N1—C4—N2115.44 (13)
C4—N2—C10125.13 (13)N2—C5—H5A109.2
C10—N2—C5117.87 (12)N2—C5—H5B109.2
H1A—C1—H1B109.5N2—C5—C6111.84 (13)
H1A—C1—H1C109.5H5A—C5—H5B107.9
H1A—C1—H1D141.1C6—C5—H5A109.2
H1A—C1—H1E56.3C6—C5—H5B109.2
H1A—C1—H1F56.3O1—C6—C5121.18 (14)
H1B—C1—H1C109.5O1—C6—C7123.40 (14)
H1B—C1—H1D56.3C7—C6—C5115.42 (13)
H1B—C1—H1E141.1C6—C7—H7A109.5
H1B—C1—H1F56.3C6—C7—H7B109.5
H1C—C1—H1D56.3C6—C7—H7C109.5
H1C—C1—H1E56.3H7A—C7—H7B109.5
H1C—C1—H1F141.1H7A—C7—H7C109.5
H1D—C1—H1E109.5H7B—C7—H7C109.5
H1D—C1—H1F109.5N1—C8—H8118.5
H1E—C1—H1F109.5C9—C8—N1122.96 (14)
C2—C1—H1A109.5C9—C8—H8118.5
C2—C1—H1B109.5C8—C9—C10118.83 (14)
C2—C1—H1C109.5C8—C9—C11123.13 (14)
C2—C1—H1D109.5C10—C9—C11118.03 (13)
C2—C1—H1E109.5O3—C10—N2120.12 (14)
C2—C1—H1F109.5O3—C10—C9124.33 (14)
O4—C2—C1122.64 (16)N2—C10—C9115.55 (12)
O4—C2—C3122.26 (14)C9—C11—H11A109.5
C1—C2—C3115.10 (14)C9—C11—H11B109.5
N1—C3—C2113.07 (13)C9—C11—H11C109.5
N1—C3—H3A109.0H11A—C11—H11B109.5
N1—C3—H3B109.0H11A—C11—H11C109.5
C2—C3—H3A109.0H11B—C11—H11C109.5
C2—C3—H3B109.0
O4—C2—C3—N16.9 (2)C5—N2—C4—O26.5 (2)
N1—C8—C9—C100.5 (2)C5—N2—C4—N1173.64 (13)
N1—C8—C9—C11179.45 (14)C5—N2—C10—O35.4 (2)
N2—C5—C6—O10.6 (2)C5—N2—C10—C9175.01 (12)
N2—C5—C6—C7178.80 (12)C8—N1—C3—C2103.59 (16)
C1—C2—C3—N1173.11 (16)C8—N1—C4—O2179.34 (15)
C3—N1—C4—O21.3 (2)C8—N1—C4—N20.5 (2)
C3—N1—C4—N2178.54 (13)C8—C9—C10—O3178.02 (15)
C3—N1—C8—C9179.04 (14)C8—C9—C10—N22.5 (2)
C4—N1—C3—C274.43 (17)C10—N2—C4—O2178.41 (14)
C4—N1—C8—C91.1 (2)C10—N2—C4—N11.7 (2)
C4—N2—C5—C679.50 (16)C10—N2—C5—C693.04 (15)
C4—N2—C10—O3177.28 (14)C11—C9—C10—O31.0 (2)
C4—N2—C10—C93.2 (2)C11—C9—C10—N2178.53 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3A···O2i0.97 (1)2.56 (1)3.304 (2)134 (1)
C3—H3B···O4ii0.97 (1)2.45 (1)3.3820 (19)160 (1)
C5—H5B···O3iii0.96 (1)2.50 (1)3.353 (2)148 (1)
C7—H7A···O1iv0.96 (1)2.54 (1)3.2576 (19)131 (1)
C7—H7B···O3iii0.96 (1)2.50 (1)3.370 (2)150 (1)
C8—H8···O4ii0.96 (1)2.50 (1)3.3213 (19)144 (1)
Symmetry codes: (i) x+1, y1/2, z+1/2; (ii) x, y1, 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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