1-[1-(2-Hydroxy­ethyl)-6-methyl-2-phenyl-4-thioxo-1,4-dihydro­pyrimidin-5-yl]-1-ethanone

Sabino, J.R.; Lariucci, C.; Bastos, R.M.; Cunha, S.

doi:10.1107/S1600536807019940

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1-[1-(2-Hydroxyethyl)-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidin-5-yl]-1-ethanone

J. R. Sabino, C. Lariucci, R. M. Bastos and S. Cunha

The title compound, C₁₅H₁₆N₂O₂S, is of interest with respect to antibacterial and anticancer activity and shows some trypanocidal activity. The crystal structure displays O—H

N hydrogen bonding, forming a chain along [001]. A weak non-classical hydrogen bond of type C—H

S connects molecules across an inversion centre. The packing is also mediated by an intermolecular C=O

π ring interaction connecting centrosymmetrically related molecules. Steric effects are responsible for the molecular conformation.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807019940/cf2101sup1.cif Contains datablocks global, I
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807019940/cf2101Isup2.hkl Contains datablock I

CCDC reference: 601661

checkCIF report

Key indicators

Single-crystal X-ray study
T = 297 K
Mean (C-C) = 0.004 Å
R factor = 0.054
wR factor = 0.212
Data-to-parameter ratio = 13.3

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT029_ALERT_3_B _diffrn_measured_fraction_theta_full Low .......       0.94

Alert level C
REFLT03_ALERT_3_C  Reflection count < 95% complete
           From the CIF: _diffrn_reflns_theta_max           67.15
           From the CIF: _diffrn_reflns_theta_full          67.15
           From the CIF: _reflns_number_total               2465
           TEST2: Reflns within _diffrn_reflns_theta_max
           Count of symmetry unique reflns         2609
           Completeness (_total/calc)             94.48%
PLAT022_ALERT_3_C Ratio Unique / Expected Reflections too Low ....       0.94

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

Thioxopyrimidine is an essential structural unit of several heterocycles, which displays a wide range of interesting biological, and pharmacological properties, such as anticancer and antimicrobial activities (Cocco et al., 2001, Cocco et al., 1995). Despite these characteristics, solid-state studies of such 4-thioxopyrimidines are scarce. Recently, we described our results concerning the formal aza-[3 + 3] cycloaddition reaction of acyclic N-alkyl-substituted enaminones with benzoyl isotiocyanate for direct 4-thioxopyrimidines synthesis (Cunha et al., 2007). Compound (I) showed some level of trypanocidal activity.

This is the first of a series of three papers devoted to the structural analisys of 4-thioxopyrimidines, Ethyl 1-(2-hydroxyethyl)-6-methyl-2-phenyl-4-thioxo-1,4-dihydro-5- pyrimidinecarboxylate and Ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydro-5-pyrimidinecarboxylate will be presented in Part 2 and Part 3.

The molecule of (I) is depicted in Fig. 1. The conformation is defined by steric effects, which force a rotation of the phenyl ring relative to the mean plane though the pyrimidine group (r.m.s. 0.032 Å) by 84.19 (8) °, and keep the torsion angles C20–C19–N1–C6 of -92.1 (3)° and C4–C5–C14–O15 of 104.8 (3) °. The observed bond distances C4═S, C14═O15, C2═N3 and C5═C6 are indicative of doubly bonded atoms. The bonds C2–C7 and C5–C14 are longer than the expected formal single bond distance by 0.033 and 0.052 Å, respectively, a consequence of the phenyl ring and acetyl group rotations relative to the pyrimidine ring plane and lack of π-orbital overlap on these bonds.

The packing (Fig. 2) is stabilized by an intermolecular H-bond of type O21–H21···N3ⁱ and a non-classical intermolecular interaction of type C13–H13C···Sⁱⁱ [Symmetry codes: (i) x, -y + 3/2, z + 1/2; (ii) -x, -y + 1, -z + 1]. The former connects molecules in linear chains along to the [0 0 1] direction and the later connects parallel molecules about an inversion center. Also, a non-H weak intermolecular C14═O15···π-ring interaction mediates the molecular packing between molecules related by an inversion center with distances O15···C2ⁱⁱ and O15···N1ⁱⁱ of 3.173 (3) and 2.922 (3) Å, respectively.

Related literature top

Thioxopyrimidine is an essential structural unit of several heterocycles and displays a wide range of interesting biological and pharmacological properties, such as anticancer and antimicrobial activities (Cocco et al., 1995, 2001). 4-Thioxopyrimidine was obtained by the formal aza-[3 + 3] cycloaddition reaction of acyclic N-alkyl-substituted enaminones with benzoyl isothiocyanate (Cunha et al., 2007).

Experimental top

Compound (I) (m.p. 508.7–509.6 K) was prepared according to a known procedure (Cunha et al., 2007). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution in CHCl₃ at room temperature.

Structure description top

Computing details top

Data collection: CAD-4-PC Software (Enraf–Nonius, 1993); cell refinement: CAD-4-PC Software; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. A view of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A packing diagram for (I). Intermolecular contacts are shown as dashed lines. Only the H atoms involved in hydrogen bonds are shown.

1-[1-(2-Hydroxyethyl)-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidin-5-yl]- 1-ethanone top

Crystal data top

C₁₅H₁₆N₂O₂S	F(000) = 608
M_r = 288.37	D_x = 1.316 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54180 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 11.3833 (14) Å	θ = 18.4–43.4°
b = 10.4303 (17) Å	µ = 2.00 mm⁻¹
c = 12.8157 (14) Å	T = 297 K
β = 106.944 (9)°	Prism, colourless
V = 1455.6 (3) Å³	0.35 × 0.25 × 0.2 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.016
non–profiled ω/2θ scans	θ_max = 67.2°, θ_min = 4.1°
Absorption correction: ψ scan (North et al., 1968)	h = −13→13
T_min = 0.525, T_max = 0.669	k = 0→12
2832 measured reflections	l = −1→15
2465 independent reflections	2 standard reflections every 120 min
2293 reflections with I > 2σ(I)	intensity decay: 2%

Refinement top

Refinement on F²	H-atom parameters constrained
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.1484P)² + 0.5327P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.054	(Δ/σ)_max < 0.001
wR(F²) = 0.212	Δρ_max = 0.45 e Å⁻³
S = 1.14	Δρ_min = −0.42 e Å⁻³
2465 reflections	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
185 parameters	Extinction coefficient: 0.049 (4)
0 restraints

Crystal data top

C₁₅H₁₆N₂O₂S	V = 1455.6 (3) Å³
M_r = 288.37	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 11.3833 (14) Å	µ = 2.00 mm⁻¹
b = 10.4303 (17) Å	T = 297 K
c = 12.8157 (14) Å	0.35 × 0.25 × 0.2 mm
β = 106.944 (9)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	2293 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.016
T_min = 0.525, T_max = 0.669	2 standard reflections every 120 min
2832 measured reflections	intensity decay: 2%
2465 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.054	0 restraints
wR(F²) = 0.212	H-atom parameters constrained
S = 1.14	Δρ_max = 0.45 e Å⁻³
2465 reflections	Δρ_min = −0.42 e Å⁻³
185 parameters

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C2	0.2055 (2)	0.6771 (2)	0.4151 (2)	0.0379 (6)
C4	0.0370 (2)	0.5648 (2)	0.3104 (2)	0.0398 (6)
C5	−0.0344 (2)	0.6197 (2)	0.37357 (19)	0.0381 (6)
C6	0.0206 (2)	0.6935 (2)	0.4626 (2)	0.0380 (6)
C7	0.3353 (2)	0.7183 (3)	0.4316 (2)	0.0432 (7)
C8	0.3584 (3)	0.8187 (3)	0.3714 (3)	0.0565 (8)
H8	0.2934	0.8627	0.3241	0.068*
C9	0.4788 (3)	0.8549 (4)	0.3811 (3)	0.0719 (10)
H9	0.4944	0.9229	0.3401	0.086*
C10	0.5744 (3)	0.7899 (4)	0.4511 (4)	0.0773 (11)
H10	0.6549	0.8139	0.4574	0.093*
C11	0.5523 (3)	0.6903 (4)	0.5115 (4)	0.0806 (12)
H11	0.618	0.6469	0.5587	0.097*
C12	0.4323 (3)	0.6526 (3)	0.5036 (3)	0.0620 (9)
H12	0.4174	0.5851	0.5455	0.074*
C13	−0.0490 (3)	0.7478 (3)	0.5336 (3)	0.0534 (7)
H13A	−0.1354	0.7377	0.499	0.08*
H13B	−0.03	0.8372	0.5456	0.08*
H13C	−0.0266	0.7036	0.6023	0.08*
C14	−0.1707 (2)	0.5926 (3)	0.3418 (2)	0.0453 (7)
C16	−0.2484 (3)	0.6676 (3)	0.2491 (3)	0.0642 (9)
H16A	−0.3296	0.6318	0.2266	0.096*
H16B	−0.2135	0.6646	0.1894	0.096*
H16C	−0.2524	0.755	0.2713	0.096*
C19	0.2104 (2)	0.7881 (3)	0.5869 (2)	0.0453 (7)
H19A	0.2942	0.7566	0.6113	0.054*
H19B	0.1717	0.7682	0.6431	0.054*
C20	0.2126 (3)	0.9326 (3)	0.5732 (2)	0.0550 (8)
H20A	0.2487	0.9539	0.5155	0.066*
H20B	0.1296	0.9662	0.5534	0.066*
N1	0.14383 (18)	0.72046 (19)	0.48503 (16)	0.0379 (5)
N3	0.15686 (18)	0.6024 (2)	0.33238 (17)	0.0421 (6)
O15	−0.2127 (2)	0.5186 (2)	0.3936 (2)	0.0675 (7)
O21	0.2829 (2)	0.9875 (3)	0.67280 (19)	0.0693 (7)
H21	0.2486	0.9747	0.7199	0.104*
S	−0.02136 (6)	0.45695 (7)	0.21138 (6)	0.0530 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C2	0.0354 (12)	0.0382 (12)	0.0411 (12)	−0.0003 (9)	0.0126 (9)	0.0008 (10)
C4	0.0432 (13)	0.0375 (12)	0.0395 (12)	−0.0037 (9)	0.0134 (10)	0.0021 (10)
C5	0.0372 (12)	0.0360 (12)	0.0414 (13)	−0.0018 (9)	0.0120 (10)	0.0043 (10)
C6	0.0391 (12)	0.0341 (12)	0.0428 (13)	0.0000 (9)	0.0151 (10)	0.0027 (10)
C7	0.0329 (12)	0.0460 (14)	0.0508 (14)	−0.0029 (10)	0.0122 (10)	−0.0084 (12)
C8	0.0454 (15)	0.0673 (19)	0.0604 (17)	−0.0084 (13)	0.0209 (13)	0.0026 (15)
C9	0.0545 (18)	0.078 (2)	0.093 (3)	−0.0160 (16)	0.0357 (17)	−0.002 (2)
C10	0.0455 (17)	0.077 (2)	0.115 (3)	−0.0157 (16)	0.0323 (18)	−0.031 (2)
C11	0.0428 (16)	0.069 (2)	0.118 (3)	0.0060 (15)	0.0043 (18)	−0.015 (2)
C12	0.0437 (15)	0.0530 (16)	0.082 (2)	0.0007 (12)	0.0064 (14)	−0.0023 (16)
C13	0.0537 (15)	0.0545 (16)	0.0603 (17)	−0.0026 (12)	0.0296 (13)	−0.0078 (14)
C14	0.0394 (13)	0.0412 (13)	0.0556 (15)	−0.0030 (10)	0.0144 (11)	0.0005 (12)
C16	0.0471 (15)	0.0654 (19)	0.072 (2)	0.0039 (13)	0.0039 (13)	0.0128 (16)
C19	0.0489 (14)	0.0472 (14)	0.0395 (13)	−0.0029 (11)	0.0123 (11)	−0.0050 (11)
C20	0.0677 (18)	0.0490 (16)	0.0527 (16)	−0.0151 (13)	0.0244 (14)	−0.0123 (13)
N1	0.0388 (10)	0.0379 (11)	0.0378 (11)	−0.0003 (8)	0.0125 (8)	0.0000 (8)
N3	0.0411 (11)	0.0429 (11)	0.0452 (12)	−0.0041 (9)	0.0173 (9)	−0.0055 (10)
O15	0.0474 (12)	0.0666 (14)	0.0890 (17)	−0.0107 (10)	0.0209 (11)	0.0214 (13)
O21	0.0808 (16)	0.0743 (15)	0.0632 (14)	−0.0388 (12)	0.0376 (12)	−0.0265 (13)
S	0.0551 (5)	0.0535 (6)	0.0501 (5)	−0.0125 (3)	0.0146 (3)	−0.0143 (3)

Geometric parameters (Å, º) top

C4—S	1.680 (3)	C19—C20	1.519 (4)
C14—O15	1.205 (4)	C20—O21	1.415 (4)
C2—N3	1.302 (3)	C8—H8	0.93
C4—N3	1.368 (3)	C9—H9	0.93
C19—N1	1.483 (3)	C10—H10	0.93
C2—C7	1.493 (3)	C11—H11	0.93
C6—C13	1.482 (4)	C12—H12	0.93
C14—C16	1.480 (4)	C13—H13A	0.96
C2—N1	1.367 (3)	C13—H13B	0.96
C4—C5	1.424 (4)	C13—H13C	0.96
C5—C6	1.368 (4)	C16—H16A	0.96
C5—C14	1.511 (3)	C16—H16B	0.96
C6—N1	1.377 (3)	C16—H16C	0.96
C7—C8	1.370 (4)	C19—H19A	0.97
C7—C12	1.396 (4)	C19—H19B	0.97
C8—C9	1.393 (4)	C20—H20A	0.97
C9—C10	1.371 (6)	C20—H20B	0.97
C10—C11	1.362 (6)	O21—H21	0.82
C11—C12	1.396 (5)

N3—C2—N1	123.6 (2)	C10—C9—H9	120.1
N3—C2—C7	117.1 (2)	C8—C9—H9	120.1
N1—C2—C7	119.2 (2)	C11—C10—H10	119.8
N3—C4—C5	117.9 (2)	C9—C10—H10	119.8
N3—C4—S	119.93 (19)	C10—C11—H11	119.6
C5—C4—S	122.20 (19)	C12—C11—H11	119.6
C6—C5—C4	120.2 (2)	C7—C12—H12	120.7
C6—C5—C14	120.9 (2)	C11—C12—H12	120.7
C4—C5—C14	118.9 (2)	C6—C13—H13A	109.5
C5—C6—N1	118.7 (2)	C6—C13—H13B	109.5
C5—C6—C13	122.1 (2)	C6—C13—H13C	109.5
N1—C6—C13	119.2 (2)	C14—C16—H16A	109.5
C8—C7—C12	120.2 (3)	C14—C16—H16B	109.5
C8—C7—C2	119.0 (2)	C14—C16—H16C	109.5
C12—C7—C2	120.8 (3)	N1—C19—H19A	109
C7—C8—C9	120.1 (3)	C20—C19—H19A	109
C10—C9—C8	119.8 (4)	N1—C19—H19B	109
C11—C10—C9	120.4 (3)	C20—C19—H19B	109
C10—C11—C12	120.9 (3)	O21—C20—H20A	109.9
C7—C12—C11	118.6 (3)	C19—C20—H20A	109.9
O15—C14—C16	122.7 (3)	O21—C20—H20B	109.9
O15—C14—C5	120.8 (2)	C19—C20—H20B	109.9
C16—C14—C5	116.4 (2)	C20—O21—H21	109.5
N1—C19—C20	113.0 (2)	H13A—C13—H13B	109.5
O21—C20—C19	108.7 (3)	H13A—C13—H13C	109.5
C2—N1—C6	118.9 (2)	H13B—C13—H13C	109.5
C2—N1—C19	120.4 (2)	H16A—C16—H16B	109.5
C6—N1—C19	120.6 (2)	H16A—C16—H16C	109.5
C2—N3—C4	120.1 (2)	H16B—C16—H16C	109.5
C7—C8—H8	119.9	H19A—C19—H19B	107.8
C9—C8—H8	119.9	H20A—C20—H20B	108.3

N3—C4—C5—C6	−8.8 (4)	C6—C5—C14—O15	−74.0 (4)
S—C4—C5—C6	171.19 (19)	C4—C5—C14—O15	104.8 (3)
N3—C4—C5—C14	172.4 (2)	C6—C5—C14—C16	102.4 (3)
S—C4—C5—C14	−7.6 (3)	C4—C5—C14—C16	−78.8 (3)
C4—C5—C6—N1	4.3 (3)	N1—C19—C20—O21	−177.2 (2)
C14—C5—C6—N1	−176.9 (2)	N3—C2—N1—C6	−5.7 (4)
C4—C5—C6—C13	−177.2 (2)	C7—C2—N1—C6	173.1 (2)
C14—C5—C6—C13	1.6 (4)	N3—C2—N1—C19	170.4 (2)
N3—C2—C7—C8	81.4 (3)	C7—C2—N1—C19	−10.8 (3)
N1—C2—C7—C8	−97.4 (3)	C5—C6—N1—C2	2.7 (3)
N3—C2—C7—C12	−95.9 (3)	C13—C6—N1—C2	−175.8 (2)
N1—C2—C7—C12	85.2 (3)	C5—C6—N1—C19	−173.4 (2)
C12—C7—C8—C9	0.7 (5)	C13—C6—N1—C19	8.1 (3)
C2—C7—C8—C9	−176.7 (3)	C20—C19—N1—C2	91.8 (3)
C7—C8—C9—C10	−0.1 (5)	C20—C19—N1—C6	−92.1 (3)
C8—C9—C10—C11	−0.2 (6)	N1—C2—N3—C4	1.1 (4)
C9—C10—C11—C12	−0.1 (6)	C7—C2—N3—C4	−177.7 (2)
C8—C7—C12—C11	−0.9 (5)	C5—C4—N3—C2	6.1 (4)
C2—C7—C12—C11	176.4 (3)	S—C4—N3—C2	−173.90 (19)
C10—C11—C12—C7	0.6 (6)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O21—H21···N3ⁱ	0.82	2.17	2.972 (3)	167
C13—H13C···Sⁱⁱ	0.96	2.84	3.789 (3)	172

Symmetry codes: (i) x, −y+3/2, z+1/2; (ii) −x, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₅H₁₆N₂O₂S
M_r	288.37
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	297
a, b, c (Å)	11.3833 (14), 10.4303 (17), 12.8157 (14)
β (°)	106.944 (9)
V (Å³)	1455.6 (3)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	2.00
Crystal size (mm)	0.35 × 0.25 × 0.2

Data collection
Diffractometer	Enraf–Nonius CAD-4
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.525, 0.669
No. of measured, independent and observed [I > 2σ(I)] reflections	2832, 2465, 2293
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.598

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.054, 0.212, 1.14
No. of reflections	2465
No. of parameters	185
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.45, −0.42

Computer programs: CAD-4-PC Software (Enraf–Nonius, 1993), CAD-4-PC Software, XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O21—H21···N3ⁱ	0.82	2.17	2.972 (3)	167.4
C13—H13C···Sⁱⁱ	0.96	2.84	3.789 (3)	171.9

Symmetry codes: (i) x, −y+3/2, z+1/2; (ii) −x, −y+1, −z+1.

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