Literature DB >> 24764894

5-Propyl-6-(p-tolyl-sulfan-yl)pyrimidine-2,4(1H,3H)-dione.

Fatmah A M Al-Omary¹, Hazem A Ghabbour¹, Ali A El-Emam¹, C S Chidan Kumar², Hoong-Kun Fun¹.

Abstract

In the title pymiridine-2,4-dione derivative, C14H16N2O2S, the dihedral angle between the six-membered rings is 66.69 (10)°. The mol-ecule is twisted about the Cp-S (p = pyrimidine) bond, with a C-S-C-N torsion angle of -19.57 (16)°. In the crystal, adjacent mol-ecules form inversion dimers through pairs of strong N-H⋯O hydrogen bonds, generating an R 2 (2)(8) ring motif. The dimers are connected into chains extending along the c-axis direction through additional N-H⋯O hydrogen bonds.

Entities: Chemical Disease Species

Year: 2014 PMID： 24764894 PMCID： PMC3998333 DOI： 10.1107/S1600536814000749

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For the pharmacological activity of pyrimidine-2,4-dione derivatives, see: Al-Abdullah et al. (2011 ▶); El-Emam et al. (2004 ▶); Hopkins et al. (1996 ▶); Klein et al. (2001 ▶); Miyasaka et al. (1989 ▶); Nencka et al. (2006 ▶); Russ et al. (2003 ▶); Tanaka et al. (1995 ▶); For related pyrimidine-2,4-dione structures, see: El-Brollosy et al. (2009 ▶); Wang et al. (2006 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For reference bond lengths, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C14H16N2O2S M = 276.35 Monoclinic, a = 11.8356 (3) Å b = 10.3040 (2) Å c = 13.3999 (3) Å β = 119.850 (2)° V = 1417.37 (6) Å3 Z = 4 Cu Kα radiation μ = 2.03 mm−1 T = 293 K 0.82 × 0.71 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.287, T max = 0.855 9643 measured reflections 2658 independent reflections 2450 reflections with I > 2σ(I) R int = 0.024

Refinement

R[F 2 > 2σ(F 2)] = 0.044 wR(F 2) = 0.126 S = 1.06 2658 reflections 180 parameters H atoms treated by a mixture of independent and constrained refinement Δρmax = 0.33 e Å−3 Δρmin = −0.39 e Å−3 Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶). Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814000749/sj5382sup1.cif Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814000749/sj5382Isup2.hkl Click here for additional data file. Supporting information file. DOI: 10.1107/S1600536814000749/sj5382Isup3.cml CCDC reference: Additional supporting information: crystallographic information; 3D view; checkCIF report

C₁₄H₁₆N₂O₂S	F(000) = 584
M_r = 276.35	D_x = 1.295 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 5622 reflections
a = 11.8356 (3) Å	θ = 3.8–69.5°
b = 10.3040 (2) Å	µ = 2.03 mm⁻¹
c = 13.3999 (3) Å	T = 293 K
β = 119.850 (2)°	Needle, colourless
V = 1417.37 (6) Å³	0.82 × 0.71 × 0.08 mm
Z = 4

Bruker APEXII CCD diffractometer	2658 independent reflections
Radiation source: fine-focus sealed tube	2450 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.024
φ and ω scans	θ_max = 69.9°, θ_min = 4.3°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −14→14
T_min = 0.287, T_max = 0.855	k = −12→10
9643 measured reflections	l = −16→16

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.126	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ²(F_o²) + (0.0707P)² + 0.439P] where P = (F_o² + 2F_c²)/3
2658 reflections	(Δ/σ)_max < 0.001
180 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.39 e Å⁻³

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	U_iso*/U_eq
S1	0.28497 (6)	0.53022 (5)	0.47950 (5)	0.0610 (2)
O1	0.45217 (15)	0.07980 (13)	0.58320 (11)	0.0594 (4)
N1	0.38171 (14)	0.28614 (14)	0.53086 (12)	0.0434 (3)
C1	0.35088 (16)	0.38803 (16)	0.45499 (14)	0.0426 (4)
O2	0.44741 (15)	0.24368 (14)	0.26889 (11)	0.0584 (4)
N2	0.45477 (15)	0.16770 (15)	0.42914 (12)	0.0441 (3)
C2	0.43133 (16)	0.17195 (16)	0.51850 (13)	0.0418 (4)
C3	0.42669 (17)	0.26374 (17)	0.34806 (14)	0.0438 (4)
C4	0.37290 (17)	0.38287 (17)	0.36542 (14)	0.0460 (4)
C5	0.3446 (2)	0.49234 (19)	0.28137 (16)	0.0529 (4)
H5A	0.4150	0.4980	0.2642	0.063*
H5B	0.3424	0.5733	0.3173	0.063*
C6	0.2176 (2)	0.4763 (2)	0.17021 (19)	0.0625 (5)
H6A	0.1478	0.4628	0.1872	0.075*
H6B	0.2225	0.4002	0.1300	0.075*
C7	0.1865 (3)	0.5949 (3)	0.0927 (2)	0.0891 (8)
H7A	0.1054	0.5816	0.0229	0.134*
H7B	0.2547	0.6076	0.0746	0.134*
H7C	0.1800	0.6702	0.1317	0.134*
C8	0.22523 (18)	0.47959 (18)	0.57142 (16)	0.0489 (4)
C9	0.1270 (2)	0.3881 (2)	0.53692 (18)	0.0586 (5)
H9A	0.0937	0.3477	0.4657	0.070*
C10	0.0791 (2)	0.3573 (2)	0.6090 (2)	0.0669 (6)
H10A	0.0149	0.2941	0.5866	0.080*
C11	0.1244 (2)	0.4185 (3)	0.7138 (2)	0.0694 (6)
C12	0.2192 (2)	0.5123 (3)	0.74454 (19)	0.0720 (6)
H12A	0.2485	0.5565	0.8136	0.086*
C13	0.2718 (2)	0.5423 (2)	0.67553 (18)	0.0587 (5)
H13A	0.3376	0.6040	0.6990	0.070*
C14	0.0734 (3)	0.3817 (4)	0.7929 (3)	0.1124 (13)
H14A	0.0086	0.3151	0.7575	0.169*
H14B	0.0353	0.4564	0.8074	0.169*
H14C	0.1438	0.3501	0.8643	0.169*
H2N2	0.483 (2)	0.096 (2)	0.4206 (19)	0.055 (6)*
H1N1	0.3791 (19)	0.291 (2)	0.5883 (19)	0.046 (5)*

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0879 (4)	0.0444 (3)	0.0701 (4)	0.0183 (2)	0.0541 (3)	0.0103 (2)
O1	0.0977 (10)	0.0498 (7)	0.0494 (7)	0.0248 (7)	0.0507 (7)	0.0134 (6)
N1	0.0588 (8)	0.0447 (8)	0.0356 (7)	0.0101 (6)	0.0303 (6)	0.0027 (6)
C1	0.0483 (8)	0.0411 (9)	0.0399 (8)	0.0035 (7)	0.0231 (7)	0.0013 (7)
O2	0.0888 (9)	0.0579 (8)	0.0487 (7)	0.0058 (7)	0.0494 (7)	0.0040 (6)
N2	0.0609 (8)	0.0421 (8)	0.0392 (7)	0.0091 (6)	0.0323 (7)	0.0029 (6)
C2	0.0523 (8)	0.0434 (9)	0.0335 (7)	0.0081 (7)	0.0243 (7)	0.0018 (7)
C3	0.0545 (9)	0.0461 (9)	0.0367 (8)	−0.0002 (7)	0.0271 (7)	0.0009 (7)
C4	0.0560 (9)	0.0443 (9)	0.0414 (8)	0.0019 (7)	0.0270 (7)	0.0026 (7)
C5	0.0677 (11)	0.0465 (9)	0.0514 (10)	−0.0021 (8)	0.0348 (9)	0.0033 (8)
C6	0.0705 (12)	0.0537 (11)	0.0591 (12)	0.0046 (9)	0.0291 (10)	0.0076 (9)
C7	0.108 (2)	0.0711 (16)	0.0669 (14)	0.0175 (14)	0.0272 (14)	0.0261 (12)
C8	0.0557 (10)	0.0460 (10)	0.0498 (10)	0.0145 (7)	0.0299 (8)	0.0031 (7)
C9	0.0604 (11)	0.0551 (11)	0.0600 (11)	0.0097 (9)	0.0298 (9)	−0.0052 (9)
C10	0.0603 (11)	0.0616 (12)	0.0860 (15)	0.0110 (9)	0.0417 (11)	0.0096 (11)
C11	0.0625 (12)	0.0885 (16)	0.0680 (13)	0.0275 (12)	0.0407 (11)	0.0210 (12)
C12	0.0752 (14)	0.0937 (17)	0.0485 (11)	0.0216 (13)	0.0318 (10)	−0.0030 (11)
C13	0.0596 (11)	0.0623 (12)	0.0544 (11)	0.0090 (9)	0.0285 (9)	−0.0054 (9)
C14	0.099 (2)	0.167 (4)	0.102 (2)	0.038 (2)	0.0731 (19)	0.044 (2)

S1—C1	1.7658 (17)	C6—H6B	0.9700
S1—C8	1.7766 (19)	C7—H7A	0.9600
O1—C2	1.225 (2)	C7—H7B	0.9600
N1—C2	1.361 (2)	C7—H7C	0.9600
N1—C1	1.378 (2)	C8—C13	1.379 (3)
N1—H1N1	0.79 (2)	C8—C9	1.385 (3)
C1—C4	1.350 (2)	C9—C10	1.378 (3)
O2—C3	1.220 (2)	C9—H9A	0.9300
N2—C2	1.358 (2)	C10—C11	1.381 (4)
N2—C3	1.382 (2)	C10—H10A	0.9300
N2—H2N2	0.84 (3)	C11—C12	1.378 (4)
C3—C4	1.454 (2)	C11—C14	1.508 (3)
C4—C5	1.509 (2)	C12—C13	1.383 (3)
C5—C6	1.509 (3)	C12—H12A	0.9300
C5—H5A	0.9700	C13—H13A	0.9300
C5—H5B	0.9700	C14—H14A	0.9600
C6—C7	1.526 (3)	C14—H14B	0.9600
C6—H6A	0.9700	C14—H14C	0.9600

C1—S1—C8	104.50 (8)	C6—C7—H7A	109.5
C2—N1—C1	122.71 (14)	C6—C7—H7B	109.5
C2—N1—H1N1	114.1 (16)	H7A—C7—H7B	109.5
C1—N1—H1N1	122.9 (16)	C6—C7—H7C	109.5
C4—C1—N1	121.90 (15)	H7A—C7—H7C	109.5
C4—C1—S1	119.78 (13)	H7B—C7—H7C	109.5
N1—C1—S1	118.30 (12)	C13—C8—C9	120.23 (19)
C2—N2—C3	126.53 (15)	C13—C8—S1	117.82 (16)
C2—N2—H2N2	114.9 (16)	C9—C8—S1	121.72 (15)
C3—N2—H2N2	118.3 (16)	C10—C9—C8	119.5 (2)
O1—C2—N2	122.78 (15)	C10—C9—H9A	120.3
O1—C2—N1	122.06 (14)	C8—C9—H9A	120.3
N2—C2—N1	115.16 (14)	C9—C10—C11	121.3 (2)
O2—C3—N2	119.25 (16)	C9—C10—H10A	119.3
O2—C3—C4	125.16 (16)	C11—C10—H10A	119.3
N2—C3—C4	115.59 (14)	C12—C11—C10	118.1 (2)
C1—C4—C3	117.98 (15)	C12—C11—C14	121.2 (3)
C1—C4—C5	124.38 (16)	C10—C11—C14	120.8 (3)
C3—C4—C5	117.64 (15)	C11—C12—C13	121.8 (2)
C4—C5—C6	113.39 (16)	C11—C12—H12A	119.1
C4—C5—H5A	108.9	C13—C12—H12A	119.1
C6—C5—H5A	108.9	C8—C13—C12	119.0 (2)
C4—C5—H5B	108.9	C8—C13—H13A	120.5
C6—C5—H5B	108.9	C12—C13—H13A	120.5
H5A—C5—H5B	107.7	C11—C14—H14A	109.5
C5—C6—C7	111.6 (2)	C11—C14—H14B	109.5
C5—C6—H6A	109.3	H14A—C14—H14B	109.5
C7—C6—H6A	109.3	C11—C14—H14C	109.5
C5—C6—H6B	109.3	H14A—C14—H14C	109.5
C7—C6—H6B	109.3	H14B—C14—H14C	109.5
H6A—C6—H6B	108.0

C2—N1—C1—C4	−2.7 (3)	N2—C3—C4—C5	178.08 (16)
C2—N1—C1—S1	179.11 (13)	C1—C4—C5—C6	−99.1 (2)
C8—S1—C1—C4	162.19 (15)	C3—C4—C5—C6	80.5 (2)
C8—S1—C1—N1	−19.57 (16)	C4—C5—C6—C7	174.6 (2)
C3—N2—C2—O1	175.69 (18)	C1—S1—C8—C13	123.21 (15)
C3—N2—C2—N1	−3.8 (3)	C1—S1—C8—C9	−62.23 (17)
C1—N1—C2—O1	−176.24 (17)	C13—C8—C9—C10	−2.0 (3)
C1—N1—C2—N2	3.3 (2)	S1—C8—C9—C10	−176.42 (15)
C2—N2—C3—O2	−176.34 (17)	C8—C9—C10—C11	1.8 (3)
C2—N2—C3—C4	3.4 (3)	C9—C10—C11—C12	0.3 (3)
N1—C1—C4—C3	2.1 (3)	C9—C10—C11—C14	−178.5 (2)
S1—C1—C4—C3	−179.72 (13)	C10—C11—C12—C13	−2.2 (3)
N1—C1—C4—C5	−178.32 (17)	C14—C11—C12—C13	176.6 (2)
S1—C1—C4—C5	−0.1 (2)	C9—C8—C13—C12	0.1 (3)
O2—C3—C4—C1	177.39 (17)	S1—C8—C13—C12	174.76 (16)
N2—C3—C4—C1	−2.3 (2)	C11—C12—C13—C8	2.0 (3)
O2—C3—C4—C5	−2.2 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N2···O1ⁱ	0.84 (2)	1.98 (2)	2.815 (2)	173 (2)
N1—H1N1···O2ⁱⁱ	0.79 (2)	2.17 (2)	2.8988 (18)	155 (2)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2N2⋯O1ⁱ	0.84 (2)	1.98 (2)	2.815 (2)	173 (2)
N1—H1N1⋯O2ⁱⁱ	0.79 (2)	2.17 (2)	2.8988 (18)	155 (2)

Symmetry codes: (i) ; (ii) .

11 in total

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Authors: Xiaowei Wang; Qinghua Lou; Ying Guo; Yang Xu; Zhili Zhang; Junyi Liu
Journal: Org Biomol Chem Date: 2006-07-28 Impact factor: 3.876

2. A short history of SHELX.

Authors: George M Sheldrick
Journal: Acta Crystallogr A Date: 2007-12-21 Impact factor: 2.290

3. Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors.

Authors: A L Hopkins; J Ren; R M Esnouf; B E Willcox; E Y Jones; C Ross; T Miyasaka; R T Walker; H Tanaka; D K Stammers; D I Stuart
Journal: J Med Chem Date: 1996-04-12 Impact factor: 7.446

4. A novel lead for specific anti-HIV-1 agents: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine.

Authors: T Miyasaka; H Tanaka; M Baba; H Hayakawa; R T Walker; J Balzarini; E De Clercq
Journal: J Med Chem Date: 1989-12 Impact factor: 7.446

5. Design and synthesis of novel 5,6-disubstituted uracil derivatives as potent inhibitors of thymidine phosphorylase.

Authors: Radim Nencka; Ivan Votruba; Hubert Hrebabecký; Eva Tloust'ová; Kveta Horská; Milena Masojídková; Antonín Holý
Journal: Bioorg Med Chem Lett Date: 2005-12-05 Impact factor: 2.823

6. Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as potential antimicrobial agents.

Authors: Ebtehal S Al-Abdullah; Abdul-Rahman M Al-Obaid; Omar A Al-Deeb; Elsayed E Habib; Ali A El-Emam
Journal: Eur J Med Chem Date: 2011-08-09 Impact factor: 6.514

7. Synthesis of novel uracil non-nucleoside derivatives as potential reverse transcriptase inhibitors of HIV-1.

Authors: Nasser R El-Brollosy; Omar A Al-Deeb; Ali A El-Emam; Erik B Pedersen; Paolo La Colla; Gabriella Collu; Giuseppina Sanna; Roberta Loddo
Journal: Arch Pharm (Weinheim) Date: 2009-11 Impact factor: 3.751

8. Synthesis and biological evaluation of 5-substituted derivatives of the potent antiherpes agent (north)-methanocarbathymine.

Authors: Pamela Russ; Pierre Schelling; Leonardo Scapozza; Gerd Folkers; Erik De Clercq; Victor E Marquez
Journal: J Med Chem Date: 2003-11-06 Impact factor: 7.446

9. Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

Authors: H Tanaka; H Takashima; M Ubasawa; K Sekiya; N Inouye; M Baba; S Shigeta; R T Walker; E De Clercq; T Miyasaka
Journal: J Med Chem Date: 1995-07-21 Impact factor: 7.446