Literature DB >> 25161558

6-[(2-Methyl-phen-yl)sulfan-yl]-5-propyl-pyrimidine-2,4(1H,3H)-dione.

Nadia G Haress¹, Hazem A Ghabbour¹, Ali A El-Emam², C S Chidan Kumar³, Hoong-Kun Fun⁴.

Abstract

In the title pyrimidine-2,4-dione derivative, C14H16N2O2S, the dihedral angle between the six-membered rings is 77.81 (10)°. The mol-ecule is twisted about the Cp-S (p = pyrimidine) bond, with a C-S-C-N torsion angle of -59.01 (17)°. An intramolecular C-H⋯S hydrogen bond generates an S(5) ring motif. In the crystal, bifurcated acceptor N-H⋯O and C-H⋯O hydrogen bonds generate inversion-related dimers incorporating R 2 (1)(9) and R 2 (2)(8) loops. These dimers are connected into a chain extending along the a-axis direction by a second pair of inversion-related N-H⋯O hydrogen bonds, forming another R 2 (2)(8) loop. The crystal structure is further stabilized by weak inter-molecular C-H⋯π inter-actions, generating a three-dimensional network.

Entities: CellLine Chemical Disease Species

Year: 2014 PMID： 25161558 PMCID： PMC4120546 DOI： 10.1107/S1600536814013269

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 ▶, 2014 ▶); Tanaka et al. (1995 ▶); Hopkins et al. (1996 ▶); Russ et al. (2003 ▶); Al-Deeb et al. (2013 ▶); Nencka et al. (2006 ▶); El-Emam et al. (2004 ▶); El-Brollosy et al. (2009 ▶, 2011 ▶). For related pyrimidine-2,4-dione structures, see: Al-Omary et al. (2014 ▶); Wang et al. (2006 ▶). For reference bond lengths, see: Allen et al. (1987 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C14H16N2O2S M = 276.36 Monoclinic, a = 10.3434 (8) Å b = 5.3355 (3) Å c = 24.4948 (18) Å β = 91.171 (3)° V = 1351.52 (16) Å3 Z = 4 Mo Kα radiation μ = 0.24 mm−1 T = 293 K 0.42 × 0.11 × 0.06 mm

Data collection

Bruker APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.906, T max = 0.986 32195 measured reflections 4165 independent reflections 2968 reflections with I > 2σ(I) R int = 0.088

Refinement

R[F 2 > 2σ(F 2)] = 0.063 wR(F 2) = 0.134 S = 1.08 4165 reflections 182 parameters H atoms treated by a mixture of independent and constrained refinement Δρmax = 0.56 e Å−3 Δρmin = −0.37 e Å−3 Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶). Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814013269/sj5409sup1.cif Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814013269/sj5409Isup2.hkl Click here for additional data file. Supporting information file. DOI: 10.1107/S1600536814013269/sj5409Isup3.cml CCDC reference: 1007120 Additional supporting information: crystallographic information; 3D view; checkCIF report

C₁₄H₁₆N₂O₂S	F(000) = 584
M_r = 276.36	D_x = 1.353 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 7715 reflections
a = 10.3434 (8) Å	θ = 2.6–30.3°
b = 5.3355 (3) Å	µ = 0.24 mm⁻¹
c = 24.4948 (18) Å	T = 293 K
β = 91.171 (3)°	Plate, colourless
V = 1351.52 (16) Å³	0.42 × 0.11 × 0.06 mm
Z = 4

Bruker APEXII CCD diffractometer	4165 independent reflections
Radiation source: fine-focus sealed tube	2968 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.088
φ and ω scans	θ_max = 30.7°, θ_min = 2.6°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −14→14
T_min = 0.906, T_max = 0.986	k = −7→7
32195 measured reflections	l = −34→35

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)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.134	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	w = 1/[σ²(F_o²) + (0.0398P)² + 1.8642P] where P = (F_o² + 2F_c²)/3
4165 reflections	(Δ/σ)_max < 0.001
182 parameters	Δρ_max = 0.56 e Å⁻³
0 restraints	Δρ_min = −0.37 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	0.06364 (5)	−0.09820 (10)	0.09629 (2)	0.01784 (14)
O1	0.14557 (13)	0.6290 (3)	−0.02258 (6)	0.0174 (3)
O2	0.50699 (13)	0.2361 (3)	0.04241 (6)	0.0185 (3)
N1	0.12191 (17)	0.2935 (3)	0.03381 (7)	0.0144 (4)
N2	0.32504 (16)	0.4210 (4)	0.00837 (7)	0.0141 (4)
C1	0.0464 (2)	0.3038 (4)	0.16726 (9)	0.0199 (5)
H1A	0.1358	0.3149	0.1645	0.024*
C2	−0.0179 (2)	0.4673 (5)	0.20078 (9)	0.0239 (5)
H2A	0.0274	0.5909	0.2199	0.029*
C3	−0.1512 (2)	0.4459 (5)	0.20570 (10)	0.0262 (5)
H3A	−0.1952	0.5532	0.2288	0.031*
C4	−0.2185 (2)	0.2647 (5)	0.17622 (10)	0.0237 (5)
H4A	−0.3075	0.2514	0.1801	0.028*
C5	−0.1558 (2)	0.1012 (4)	0.14083 (9)	0.0195 (4)
C6	−0.0214 (2)	0.1221 (4)	0.13752 (8)	0.0163 (4)
C7	−0.2318 (2)	−0.0789 (5)	0.10612 (10)	0.0247 (5)
H7A	−0.2013	−0.2463	0.1128	0.037*
H7B	−0.2214	−0.0378	0.0683	0.037*
H7C	−0.3217	−0.0684	0.1150	0.037*
C8	0.17527 (19)	0.1011 (4)	0.06450 (8)	0.0139 (4)
C9	0.19324 (18)	0.4591 (4)	0.00465 (8)	0.0136 (4)
C10	0.38780 (19)	0.2403 (4)	0.03944 (8)	0.0140 (4)
C11	0.30560 (19)	0.0645 (4)	0.06833 (8)	0.0136 (4)
C12	0.3691 (2)	−0.1357 (4)	0.10241 (8)	0.0154 (4)
H12A	0.4479	−0.1886	0.0849	0.018*
H12B	0.3119	−0.2795	0.1039	0.018*
C13	0.4024 (2)	−0.0509 (4)	0.16085 (9)	0.0220 (5)
H13A	0.4635	0.0867	0.1597	0.026*
H13B	0.3246	0.0095	0.1780	0.026*
C14	0.4602 (3)	−0.2630 (5)	0.19489 (10)	0.0304 (6)
H14A	0.4831	−0.2017	0.2306	0.046*
H14B	0.5362	−0.3257	0.1776	0.046*
H14C	0.3980	−0.3955	0.1979	0.046*
H1N2	0.367 (2)	0.530 (5)	−0.0072 (10)	0.017 (6)*
H1N1	0.042 (3)	0.304 (5)	0.0290 (10)	0.024 (7)*

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0144 (2)	0.0136 (3)	0.0258 (3)	−0.0032 (2)	0.00659 (19)	0.0002 (2)
O1	0.0098 (6)	0.0184 (8)	0.0241 (8)	−0.0012 (6)	0.0003 (6)	0.0051 (6)
O2	0.0089 (7)	0.0201 (8)	0.0264 (8)	−0.0011 (6)	0.0001 (6)	0.0052 (7)
N1	0.0064 (8)	0.0165 (9)	0.0202 (9)	−0.0015 (7)	0.0003 (7)	0.0019 (7)
N2	0.0070 (7)	0.0167 (9)	0.0185 (9)	−0.0019 (7)	0.0016 (6)	0.0028 (7)
C1	0.0178 (10)	0.0194 (11)	0.0226 (11)	−0.0012 (9)	0.0027 (9)	0.0026 (9)
C2	0.0301 (12)	0.0210 (12)	0.0207 (11)	−0.0014 (10)	0.0017 (10)	0.0004 (9)
C3	0.0282 (12)	0.0257 (13)	0.0249 (12)	0.0081 (10)	0.0072 (10)	0.0019 (10)
C4	0.0175 (10)	0.0287 (13)	0.0251 (12)	0.0053 (9)	0.0058 (9)	0.0032 (10)
C5	0.0165 (10)	0.0203 (11)	0.0219 (11)	−0.0011 (9)	0.0027 (8)	0.0051 (9)
C6	0.0146 (9)	0.0177 (10)	0.0166 (10)	0.0011 (8)	0.0034 (8)	0.0045 (8)
C7	0.0194 (11)	0.0250 (12)	0.0298 (12)	−0.0024 (10)	0.0006 (9)	0.0016 (10)
C8	0.0131 (9)	0.0126 (9)	0.0160 (9)	−0.0038 (8)	0.0015 (7)	−0.0006 (8)
C9	0.0077 (8)	0.0175 (10)	0.0156 (10)	−0.0031 (7)	0.0003 (7)	−0.0026 (8)
C10	0.0121 (9)	0.0143 (10)	0.0157 (10)	0.0004 (8)	−0.0001 (8)	−0.0013 (8)
C11	0.0127 (9)	0.0131 (10)	0.0150 (9)	−0.0019 (8)	0.0001 (7)	−0.0015 (8)
C12	0.0120 (9)	0.0131 (10)	0.0211 (10)	−0.0004 (8)	0.0010 (8)	−0.0004 (8)
C13	0.0250 (11)	0.0189 (12)	0.0221 (11)	0.0005 (9)	−0.0022 (9)	0.0010 (9)
C14	0.0389 (15)	0.0267 (13)	0.0253 (13)	0.0045 (11)	−0.0075 (11)	0.0032 (10)

S1—C8	1.763 (2)	C4—H4A	0.9300
S1—C6	1.792 (2)	C5—C6	1.399 (3)
O1—C9	1.223 (3)	C5—C7	1.496 (3)
O2—C10	1.234 (2)	C7—H7A	0.9600
N1—C9	1.362 (3)	C7—H7B	0.9600
N1—C8	1.381 (3)	C7—H7C	0.9600
N1—H1N1	0.83 (3)	C8—C11	1.363 (3)
N2—C9	1.380 (2)	C10—C11	1.459 (3)
N2—C10	1.382 (3)	C11—C12	1.499 (3)
N2—H1N2	0.82 (3)	C12—C13	1.534 (3)
C1—C2	1.379 (3)	C12—H12A	0.9700
C1—C6	1.394 (3)	C12—H12B	0.9700
C1—H1A	0.9300	C13—C14	1.521 (3)
C2—C3	1.391 (3)	C13—H13A	0.9700
C2—H2A	0.9300	C13—H13B	0.9700
C3—C4	1.386 (4)	C14—H14A	0.9600
C3—H3A	0.9300	C14—H14B	0.9600
C4—C5	1.398 (3)	C14—H14C	0.9600

C8—S1—C6	100.76 (10)	C11—C8—N1	121.85 (18)
C9—N1—C8	123.55 (17)	C11—C8—S1	122.60 (16)
C9—N1—H1N1	115.4 (19)	N1—C8—S1	115.52 (14)
C8—N1—H1N1	120.6 (19)	O1—C9—N1	123.35 (18)
C9—N2—C10	126.26 (18)	O1—C9—N2	122.14 (18)
C9—N2—H1N2	112.9 (17)	N1—C9—N2	114.51 (18)
C10—N2—H1N2	120.4 (17)	O2—C10—N2	120.18 (19)
C2—C1—C6	120.5 (2)	O2—C10—C11	123.46 (19)
C2—C1—H1A	119.7	N2—C10—C11	116.35 (17)
C6—C1—H1A	119.7	C8—C11—C10	117.37 (19)
C1—C2—C3	119.4 (2)	C8—C11—C12	124.19 (18)
C1—C2—H2A	120.3	C10—C11—C12	118.36 (17)
C3—C2—H2A	120.3	C11—C12—C13	113.39 (18)
C4—C3—C2	120.0 (2)	C11—C12—H12A	108.9
C4—C3—H3A	120.0	C13—C12—H12A	108.9
C2—C3—H3A	120.0	C11—C12—H12B	108.9
C3—C4—C5	121.6 (2)	C13—C12—H12B	108.9
C3—C4—H4A	119.2	H12A—C12—H12B	107.7
C5—C4—H4A	119.2	C14—C13—C12	111.74 (19)
C4—C5—C6	117.4 (2)	C14—C13—H13A	109.3
C4—C5—C7	120.6 (2)	C12—C13—H13A	109.3
C6—C5—C7	122.0 (2)	C14—C13—H13B	109.3
C1—C6—C5	121.0 (2)	C12—C13—H13B	109.3
C1—C6—S1	120.23 (16)	H13A—C13—H13B	107.9
C5—C6—S1	118.71 (17)	C13—C14—H14A	109.5
C5—C7—H7A	109.5	C13—C14—H14B	109.5
C5—C7—H7B	109.5	H14A—C14—H14B	109.5
H7A—C7—H7B	109.5	C13—C14—H14C	109.5
C5—C7—H7C	109.5	H14A—C14—H14C	109.5
H7A—C7—H7C	109.5	H14B—C14—H14C	109.5
H7B—C7—H7C	109.5

C6—C1—C2—C3	1.5 (3)	C8—N1—C9—O1	179.84 (19)
C1—C2—C3—C4	−1.3 (4)	C8—N1—C9—N2	−0.4 (3)
C2—C3—C4—C5	−0.5 (4)	C10—N2—C9—O1	177.7 (2)
C3—C4—C5—C6	2.0 (3)	C10—N2—C9—N1	−2.1 (3)
C3—C4—C5—C7	−175.1 (2)	C9—N2—C10—O2	−174.9 (2)
C2—C1—C6—C5	0.1 (3)	C9—N2—C10—C11	3.9 (3)
C2—C1—C6—S1	−177.36 (17)	N1—C8—C11—C10	1.2 (3)
C4—C5—C6—C1	−1.8 (3)	S1—C8—C11—C10	179.05 (15)
C7—C5—C6—C1	175.2 (2)	N1—C8—C11—C12	177.94 (19)
C4—C5—C6—S1	175.71 (17)	S1—C8—C11—C12	−4.2 (3)
C7—C5—C6—S1	−7.3 (3)	O2—C10—C11—C8	175.5 (2)
C8—S1—C6—C1	−44.05 (19)	N2—C10—C11—C8	−3.3 (3)
C8—S1—C6—C5	138.44 (18)	O2—C10—C11—C12	−1.5 (3)
C9—N1—C8—C11	0.8 (3)	N2—C10—C11—C12	179.76 (18)
C9—N1—C8—S1	−177.26 (16)	C8—C11—C12—C13	−90.1 (2)
C6—S1—C8—C11	122.99 (18)	C10—C11—C12—C13	86.6 (2)
C6—S1—C8—N1	−59.01 (17)	C11—C12—C13—C14	177.06 (19)

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12B···S1	0.97	2.75	3.166 (2)	107
N2—H1N2···O2ⁱ	0.82 (2)	2.01 (2)	2.829 (2)	171 (2)
N1—H1N1···O1ⁱⁱ	0.83 (3)	1.98 (3)	2.805 (2)	173 (2)
C7—H7B···O1ⁱⁱ	0.96	2.58	3.289 (3)	131
C2—H2A···Cg2ⁱⁱⁱ	0.93	2.91	3.700 (2)	144
C7—H7B···Cg1^iv	0.96	2.85	3.632 (3)	140

Table 1

Hydrogen-bond geometry (Å, °)

Cg1 and Cg2 are the centroids of C1–C6 and C8–C11/N1/N2 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12B⋯S1	0.97	2.75	3.166 (2)	107
N2—H1N2⋯O2ⁱ	0.82 (2)	2.01 (2)	2.829 (2)	171 (2)
N1—H1N1⋯O1ⁱⁱ	0.83 (3)	1.98 (3)	2.805 (2)	173 (2)
C7—H7B⋯O1ⁱⁱ	0.96	2.58	3.289 (3)	131
C2—H2A⋯Cg2ⁱⁱⁱ	0.93	2.91	3.700 (2)	144
C7—H7B⋯Cg1^iv	0.96	2.85	3.632 (3)	140

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

11 in total

1. The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase.

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. 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

3. 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

4. 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

5. 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

6. 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

7. 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