Literature DB >> 21582221

5-Acetyl-4-(4-chloro-phen-yl)-6-methyl-3,4-dihydro-pyrimidine-2(1H)-thione.

N Anuradha, A Thiruvalluvar, K Pandiarajan, S Chitra, R J Butcher.

Abstract

In the title mol-ecule, C(13)H(13)ClN(2)OS, the heterocyclic ring adopts a flattened boat conformation, and the plane through the four coplanar atoms makes a dihedral angle of 87.92 (10)° with the benzene ring. The thione, acetyl and methyl groups have equatorial orientations with respect to the attached heterocyclic ring. The chloro-phenyl group has an axial orientation. Inter-molecular N-H⋯O, N-H⋯S and C-H⋯O hydrogen bonds are found in the crystal structure.

Entities: CellLine Chemical Disease Gene

Year: 2009 PMID： 21582221 PMCID： PMC2968427 DOI： 10.1107/S1600536809005029

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

Related literature

For dihydropyrimidin-2(1H)-ones as anti-oxidant agents, see: Stefani et al. (2006 ▶), and for their biological activity, see: Patil et al. (1995 ▶). For dihydropyrimidinones as calcium channel blockers, see: Rovnyak et al. (1995 ▶); Atwal et al. (1990 ▶) and as antihypertensive agents, see: Atwal et al. (1991 ▶); Grover et al. (1995 ▶). For the biological activity of marine alkaloids possessing a dihydropyrimidine-5-carboxylate core, see: Patil et al. (1995 ▶). For the biological activity of dihydropyrimidin-2(1H)-thiones, see: Kappe (1993 ▶).

Experimental

Crystal data

C13H13ClN2OS M = 280.77 Triclinic, a = 7.2389 (6) Å b = 8.2304 (7) Å c = 12.9038 (11) Å α = 73.366 (7)° β = 89.373 (7)° γ = 72.613 (7)° V = 700.62 (11) Å3 Z = 2 Cu Kα radiation μ = 3.72 mm−1 T = 295 K 0.42 × 0.25 × 0.22 mm

Data collection

Oxford Diffraction Gemini R diffractometer Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008 ▶) T min = 0.182, T max = 1.000 (expected range = 0.080–0.441) 6666 measured reflections 2878 independent reflections 2105 reflections with I > 2σ(I) R int = 0.036

Refinement

R[F 2 > 2σ(F 2)] = 0.071 wR(F 2) = 0.202 S = 1.03 2878 reflections 173 parameters H atoms treated by a mixture of independent and constrained refinement Δρmax = 0.53 e Å−3 Δρmin = −0.23 e Å−3 Data collection: CrysAlis CCD (Oxford Diffraction, 2008 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2008 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶). Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809005029/hg2476sup1.cif Structure factors: contains datablocks I. DOI: 10.1107/S1600536809005029/hg2476Isup2.hkl Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C₁₃H₁₃ClN₂OS	Z = 2
M_r = 280.77	F(000) = 292
Triclinic, P1	D_x = 1.331 Mg m⁻³
Hall symbol: -P 1	Melting point: 529.5 K
a = 7.2389 (6) Å	Cu Kα radiation, λ = 1.54184 Å
b = 8.2304 (7) Å	Cell parameters from 2326 reflections
c = 12.9038 (11) Å	θ = 5.9–77.2°
α = 73.366 (7)°	µ = 3.72 mm⁻¹
β = 89.373 (7)°	T = 295 K
γ = 72.613 (7)°	Prism, colourless
V = 700.62 (11) Å³	0.42 × 0.25 × 0.22 mm

Oxford Diffraction Gemini R diffractometer	2878 independent reflections
Radiation source: fine-focus sealed tube	2105 reflections with I > 2σ(I)
graphite	R_int = 0.036
Detector resolution: 10.5081 pixels mm^-1	θ_max = 77.4°, θ_min = 5.9°
φ and ω scans	h = −9→5
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008)	k = −10→9
T_min = 0.182, T_max = 1.000	l = −16→16
6666 measured reflections

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)] = 0.071	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.202	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ²(F_o²) + (0.1275P)² + 0.1258P] where P = (F_o² + 2F_c²)/3
2878 reflections	(Δ/σ)_max = 0.001
173 parameters	Δρ_max = 0.53 e Å⁻³
0 restraints	Δρ_min = −0.23 e Å⁻³

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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 > 2σ(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
Cl1	0.5516 (3)	0.8292 (2)	−0.08141 (12)	0.1388 (8)
S2	1.30462 (11)	0.38375 (11)	0.46485 (8)	0.0548 (3)
O15	0.6554 (3)	0.0586 (3)	0.3317 (3)	0.0656 (9)
N1	1.2495 (3)	0.1540 (3)	0.3701 (2)	0.0469 (8)
N3	0.9758 (3)	0.3326 (3)	0.4163 (2)	0.0449 (8)
C2	1.1665 (4)	0.2871 (4)	0.4144 (3)	0.0429 (8)
C4	0.8486 (4)	0.2810 (4)	0.3534 (3)	0.0418 (8)
C5	0.9546 (4)	0.1023 (4)	0.3372 (3)	0.0410 (8)
C6	1.1509 (4)	0.0490 (4)	0.3417 (2)	0.0410 (8)
C15	0.8251 (4)	0.0061 (4)	0.3157 (3)	0.0467 (9)
C16	0.8904 (5)	−0.1503 (5)	0.2717 (4)	0.0669 (13)
C41	0.7733 (5)	0.4234 (4)	0.2449 (3)	0.0486 (9)
C42	0.8999 (6)	0.4851 (5)	0.1744 (3)	0.0681 (12)
C43	0.8321 (8)	0.6118 (6)	0.0741 (4)	0.0832 (16)
C44	0.6360 (9)	0.6762 (6)	0.0464 (4)	0.0843 (16)
C45	0.5095 (8)	0.6201 (7)	0.1132 (5)	0.0967 (19)
C46	0.5777 (6)	0.4951 (6)	0.2145 (4)	0.0738 (16)
C61	1.2863 (4)	−0.1154 (4)	0.3226 (3)	0.0563 (12)
H1	1.367 (5)	0.131 (4)	0.361 (3)	0.040 (8)*
H3	0.910 (5)	0.415 (5)	0.448 (3)	0.058 (10)*
H4	0.73685	0.26846	0.39490	0.0500*
H16A	0.78061	−0.18685	0.25915	0.1003*
H16B	0.98424	−0.24715	0.32324	0.1003*
H16C	0.94799	−0.11707	0.20472	0.1003*
H42	1.03260	0.44097	0.19439	0.0819*
H43	0.91806	0.65179	0.02692	0.0998*
H45	0.37713	0.66430	0.09217	0.1159*
H46	0.48960	0.45990	0.26195	0.0886*
H61A	1.25700	−0.21851	0.36724	0.0843*
H61B	1.41785	−0.12402	0.34080	0.0843*
H61C	1.27086	−0.10909	0.24764	0.0843*

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.2014 (19)	0.0993 (10)	0.0671 (8)	−0.0081 (12)	−0.0255 (10)	0.0105 (7)
S2	0.0423 (4)	0.0610 (5)	0.0724 (6)	−0.0201 (3)	0.0039 (3)	−0.0325 (4)
O15	0.0355 (11)	0.0666 (14)	0.105 (2)	−0.0201 (10)	0.0099 (12)	−0.0365 (14)
N1	0.0286 (11)	0.0521 (14)	0.0644 (17)	−0.0132 (10)	0.0056 (10)	−0.0232 (12)
N3	0.0377 (12)	0.0493 (13)	0.0526 (15)	−0.0123 (10)	0.0049 (10)	−0.0238 (12)
C2	0.0392 (14)	0.0462 (14)	0.0448 (16)	−0.0147 (12)	0.0011 (12)	−0.0141 (12)
C4	0.0353 (13)	0.0450 (14)	0.0465 (16)	−0.0120 (11)	0.0055 (11)	−0.0164 (12)
C5	0.0373 (13)	0.0388 (13)	0.0467 (16)	−0.0110 (10)	0.0029 (11)	−0.0133 (12)
C6	0.0368 (13)	0.0406 (13)	0.0465 (16)	−0.0135 (11)	0.0033 (11)	−0.0126 (11)
C15	0.0375 (14)	0.0459 (15)	0.0549 (18)	−0.0152 (12)	−0.0018 (12)	−0.0094 (13)
C16	0.0512 (18)	0.064 (2)	0.098 (3)	−0.0223 (16)	0.0000 (19)	−0.038 (2)
C41	0.0530 (16)	0.0433 (15)	0.0510 (18)	−0.0114 (12)	0.0036 (14)	−0.0200 (13)
C42	0.065 (2)	0.067 (2)	0.063 (2)	−0.0151 (18)	0.0140 (18)	−0.0108 (18)
C43	0.114 (4)	0.070 (2)	0.059 (2)	−0.027 (3)	0.019 (2)	−0.011 (2)
C44	0.120 (4)	0.059 (2)	0.054 (2)	−0.006 (2)	−0.010 (2)	−0.0086 (18)
C45	0.081 (3)	0.095 (4)	0.082 (3)	0.000 (3)	−0.025 (3)	−0.005 (3)
C46	0.055 (2)	0.078 (3)	0.069 (3)	−0.0081 (18)	−0.0066 (18)	−0.005 (2)
C61	0.0390 (15)	0.0486 (16)	0.085 (3)	−0.0129 (12)	0.0042 (15)	−0.0259 (16)

Cl1—C44	1.747 (5)	C41—C42	1.386 (6)
S2—C2	1.686 (3)	C42—C43	1.392 (6)
O15—C15	1.211 (4)	C43—C44	1.370 (9)
N1—C2	1.359 (4)	C44—C45	1.343 (9)
N1—C6	1.395 (4)	C45—C46	1.397 (8)
N3—C2	1.320 (4)	C4—H4	0.9800
N3—C4	1.461 (4)	C16—H16A	0.9600
N1—H1	0.83 (4)	C16—H16B	0.9600
N3—H3	0.90 (4)	C16—H16C	0.9600
C4—C41	1.525 (5)	C42—H42	0.9300
C4—C5	1.515 (5)	C43—H43	0.9300
C5—C6	1.353 (4)	C45—H45	0.9300
C5—C15	1.469 (4)	C46—H46	0.9300
C6—C61	1.498 (5)	C61—H61A	0.9600
C15—C16	1.501 (5)	C61—H61B	0.9600
C41—C46	1.374 (6)	C61—H61C	0.9600

Cl1···O15ⁱ	3.332 (4)	C16···H61C	2.8800
S2···N3ⁱⁱ	3.328 (3)	C16···H61A	2.7700
S2···H46ⁱⁱⁱ	2.9200	C42···H16A^iv	3.0800
S2···H61A^iv	3.0700	C43···H43^viii	2.9800
S2···H4ⁱⁱⁱ	3.1900	C61···H16B	2.7100
S2···H3ⁱⁱ	2.43 (4)	C61···H16C	2.9000
S2···H61B^v	3.0600	H1···O15ⁱⁱⁱ	2.06 (4)
O15···N1^vi	2.882 (3)	H1···H61B	2.1100
O15···C41	3.253 (4)	H3···S2ⁱⁱ	2.43 (4)
O15···C46	3.348 (6)	H4···S2^vi	3.1900
O15···C61^vi	3.405 (4)	H4···O15	2.3300
O15···Cl1ⁱ	3.332 (4)	H4···H46	2.3400
O15···H4	2.3300	H16A···C42^vii	3.0800
O15···H61B^vi	2.5800	H16B···C6	3.0900
O15···H1^vi	2.06 (4)	H16B···C61	2.7100
N1···O15ⁱⁱⁱ	2.882 (3)	H16B···H61A	2.1600
N3···S2ⁱⁱ	3.328 (3)	H16C···C61	2.9000
N1···H42	2.8200	H16C···H61C	2.4300
N3···H42	2.8100	H42···N1	2.8200
C2···C42	3.366 (5)	H42···N3	2.8100
C6···C42	3.549 (5)	H42···C2	2.8100
C16···C61	3.061 (5)	H42···C5	3.0800
C16···C42^vii	3.552 (6)	H43···C43^viii	2.9800
C41···O15	3.253 (4)	H46···S2^vi	2.9200
C42···C6	3.549 (5)	H46···H4	2.3400
C42···C2	3.366 (5)	H61A···S2^vii	3.0700
C42···C16^iv	3.552 (6)	H61A···C15	3.0900
C43···C43^viii	3.492 (7)	H61A···C16	2.7700
C46···O15	3.348 (6)	H61A···H16B	2.1600
C61···C16	3.061 (5)	H61B···O15ⁱⁱⁱ	2.5800
C61···O15ⁱⁱⁱ	3.405 (4)	H61B···H1	2.1100
C2···H42	2.8100	H61B···S2^v	3.0600
C5···H42	3.0800	H61C···C16	2.8800
C6···H16B	3.0900	H61C···H16C	2.4300
C15···H61A	3.0900

C2—N1—C6	124.2 (2)	C43—C44—C45	121.7 (5)
C2—N3—C4	124.3 (3)	Cl1—C44—C45	119.8 (5)
C2—N1—H1	118 (2)	C44—C45—C46	119.7 (5)
C6—N1—H1	118 (2)	C41—C46—C45	120.8 (4)
C2—N3—H3	122 (2)	N3—C4—H4	108.00
C4—N3—H3	113 (2)	C5—C4—H4	108.00
S2—C2—N3	123.2 (3)	C41—C4—H4	108.00
N1—C2—N3	116.3 (3)	C15—C16—H16A	109.00
S2—C2—N1	120.5 (2)	C15—C16—H16B	109.00
N3—C4—C5	110.0 (3)	C15—C16—H16C	110.00
N3—C4—C41	111.2 (3)	H16A—C16—H16B	109.00
C5—C4—C41	111.1 (3)	H16A—C16—H16C	110.00
C4—C5—C15	113.8 (3)	H16B—C16—H16C	110.00
C6—C5—C15	127.1 (3)	C41—C42—H42	119.00
C4—C5—C6	119.1 (3)	C43—C42—H42	119.00
N1—C6—C5	118.6 (3)	C42—C43—H43	121.00
N1—C6—C61	112.4 (3)	C44—C43—H43	121.00
C5—C6—C61	129.0 (3)	C44—C45—H45	120.00
C5—C15—C16	123.5 (3)	C46—C45—H45	120.00
O15—C15—C5	118.3 (3)	C41—C46—H46	120.00
O15—C15—C16	118.2 (3)	C45—C46—H46	120.00
C4—C41—C46	120.9 (3)	C6—C61—H61A	109.00
C42—C41—C46	118.0 (4)	C6—C61—H61B	109.00
C4—C41—C42	121.1 (3)	C6—C61—H61C	109.00
C41—C42—C43	121.2 (4)	H61A—C61—H61B	109.00
C42—C43—C44	118.5 (5)	H61A—C61—H61C	109.00
Cl1—C44—C43	118.5 (4)	H61B—C61—H61C	109.00

C6—N1—C2—S2	169.9 (2)	C4—C5—C6—C61	−176.4 (3)
C6—N1—C2—N3	−9.4 (5)	C15—C5—C6—N1	−176.0 (3)
C2—N1—C6—C5	13.7 (4)	C15—C5—C6—C61	2.4 (6)
C2—N1—C6—C61	−164.9 (3)	C4—C5—C15—O15	−12.9 (5)
C4—N3—C2—S2	166.0 (3)	C4—C5—C15—C16	165.2 (4)
C4—N3—C2—N1	−14.8 (5)	C6—C5—C15—O15	168.3 (4)
C2—N3—C4—C5	30.5 (4)	C6—C5—C15—C16	−13.7 (6)
C2—N3—C4—C41	−93.1 (4)	C4—C41—C42—C43	178.4 (4)
N3—C4—C5—C6	−24.4 (4)	C46—C41—C42—C43	−2.0 (6)
N3—C4—C5—C15	156.7 (3)	C4—C41—C46—C45	−177.3 (4)
C41—C4—C5—C6	99.1 (4)	C42—C41—C46—C45	3.1 (7)
C41—C4—C5—C15	−79.8 (4)	C41—C42—C43—C44	0.6 (7)
N3—C4—C41—C42	53.6 (4)	C42—C43—C44—Cl1	−177.8 (4)
N3—C4—C41—C46	−126.0 (4)	C42—C43—C44—C45	−0.1 (8)
C5—C4—C41—C42	−69.3 (4)	Cl1—C44—C45—C46	178.7 (4)
C5—C4—C41—C46	111.1 (4)	C43—C44—C45—C46	1.1 (8)
C4—C5—C6—N1	5.3 (5)	C44—C45—C46—C41	−2.7 (8)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O15ⁱⁱⁱ	0.83 (4)	2.06 (4)	2.882 (3)	175 (4)
N3—H3···S2ⁱⁱ	0.90 (4)	2.43 (4)	3.328 (3)	172 (3)
C61—H61B···O15ⁱⁱⁱ	0.96	2.58	3.405 (4)	144

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O15ⁱ	0.83 (4)	2.06 (4)	2.882 (3)	175 (4)
N3—H3⋯S2ⁱⁱ	0.90 (4)	2.43 (4)	3.328 (3)	172 (3)
C61—H61B⋯O15ⁱ	0.96	2.58	3.405 (4)	144

Symmetry codes: (i) ; (ii) .

7 in total

1. A short history of SHELX.

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

2. Dihydropyrimidine calcium channel blockers. 2. 3-substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines.

Authors: K S Atwal; G C Rovnyak; S D Kimball; D M Floyd; S Moreland; B N Swanson; J Z Gougoutas; J Schwartz; K M Smillie; M F Malley
Journal: J Med Chem Date: 1990-09 Impact factor: 7.446

3. Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators.

Authors: G C Rovnyak; S D Kimball; B Beyer; G Cucinotta; J D DiMarco; J Gougoutas; A Hedberg; M Malley; J P McCarthy; R Zhang
Journal: J Med Chem Date: 1995-01-06 Impact factor: 7.446

4. Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32,547 and SQ 32,926 [correction of SQ 32,946].

Authors: G J Grover; S Dzwonczyk; D M McMullen; D E Normandin; C S Parham; P G Sleph; S Moreland
Journal: J Cardiovasc Pharmacol Date: 1995-08 Impact factor: 3.105

5. Dihydropyrimidin-(2H)-ones obtained by ultrasound irradiation: a new class of potential antioxidant agents.

Authors: Hélio A Stefani; Carlindo B Oliveira; Roberta B Almeida; Claudio M P Pereira; Rodolpho C Braga; Rodrigo Cella; Vanessa C Borges; Lucielli Savegnago; Cristina W Nogueira
Journal: Eur J Med Chem Date: 2006-03-03 Impact factor: 6.514

6. Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents.

Authors: K S Atwal; B N Swanson; S E Unger; D M Floyd; S Moreland; A Hedberg; B C O'Reilly
Journal: J Med Chem Date: 1991-02 Impact factor: 7.446

7. Structure validation in chemical crystallography.

Authors: Anthony L Spek
Journal: Acta Crystallogr D Biol Crystallogr Date: 2009-01-20