Ethyl 2-allylsulfanyl-4-(4-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate.

In the title compound, C(18)H(22)N(2)O(3)S, the pyrimidine ring is not planar. It adopts a half-chair conformation The crystal structure is characterized by classical N-H⋯O and C-H⋯O inter- and intra-molecular hydrogen bonds, respectively. The title compound exhibits a wide spectrum of biological activities.

Related literature

For related literature, see: Allen et al. (1987 ▶); Biginelli (1893 ▶); Cremer & Pople (1975 ▶); Gurskaya et al. (2003a ▶,b ▶); Kappe (1993 ▶); Kappe et al. (1997 ▶); Li (2006 ▶); Nardelli (1983 ▶); Nizam Mohideen et al. (2008 ▶); Overman et al. (1995 ▶); Snider et al. (1996 ▶).

Experimental

Crystal data

C18H22N2O3S

M = 346.44

Monoclinic,

a = 28.325 (5) Å

b = 7.410 (2) Å

c = 20.202 (4) Å

β = 121.61 (3)°

V = 3610.9 (18) Å3

Z = 8

Mo Kα radiation

μ = 0.20 mm−1

T = 293 (2) K

0.4 × 0.2 × 0.1 mm

Data collection

Bruker Kappa APEXII CCD diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T min = 0.954, T max = 0.983

16675 measured reflections

3183 independent reflections

2722 reflections with I > 2σ(I)

R int = 0.025

Refinement

R[F 2 > 2σ(F 2)] = 0.045

wR(F 2) = 0.140

S = 1.04

3183 reflections

220 parameters

H-atom parameters constrained

Δρmax = 0.47 e Å−3

Δρmin = −0.33 e Å−3

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808026664/pv2100sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808026664/pv2100Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C18H22N2O3S	F000 = 1472
Mr = 346.44	Dx = 1.275 Mg m−3
Monoclinic, C2/c	Mo Kα radiation λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 7889 reflections
a = 28.325 (5) Å	θ = 2.6–25º
b = 7.410 (2) Å	µ = 0.20 mm−1
c = 20.202 (4) Å	T = 293 (2) K
β = 121.61 (3)º	Needle, yellow
V = 3610.9 (18) Å3	0.4 × 0.2 × 0.1 mm
Z = 8

Bruker Kappa APEXII CCD diffractometer'	3183 independent reflections
Radiation source: fine-focus sealed tube	2722 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.026
T = 293(2) K	θmax = 25.0º
ω and φ scan	θmin = 1.7º
Absorption correction: Multi-scan(SADABS; Bruker, 2004)	h = −33→33
Tmin = 0.954, Tmax = 0.983	k = −8→8
16675 measured reflections	l = −24→24

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.045	H-atom parameters constrained
wR(F2) = 0.140	w = 1/[σ2(Fo2) + (0.0785P)2 + 3.5811P] where P = (Fo2 + 2Fc2)/3
S = 1.05	(Δ/σ)max = 0.002
3183 reflections	Δρmax = 0.48 e Å−3
220 parameters	Δρmin = −0.33 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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	Uiso*/Ueq
S1	0.15041 (3)	0.63300 (8)	0.44134 (3)	0.0551 (2)
O1	0.33272 (7)	1.1779 (2)	0.34204 (10)	0.0580 (4)
O2	0.06407 (7)	1.4020 (2)	0.24877 (9)	0.0522 (4)
O3	0.01426 (7)	1.2100 (2)	0.15153 (9)	0.0617 (5)
N1	0.14728 (7)	0.9848 (2)	0.40787 (9)	0.0385 (4)
N2	0.09759 (7)	0.7816 (2)	0.30377 (10)	0.0387 (4)
H2	0.0954	0.6715	0.2889	0.046*
C1	0.23063 (8)	1.2512 (3)	0.39532 (11)	0.0399 (5)
H1	0.2280	1.3171	0.4325	0.048*
C2	0.27875 (9)	1.2591 (3)	0.39437 (13)	0.0456 (5)
H2A	0.3082	1.3292	0.4308	0.055*
C3	0.28341 (8)	1.1622 (3)	0.33898 (12)	0.0406 (5)
C4	0.23922 (9)	1.0596 (3)	0.28488 (12)	0.0424 (5)
H4	0.2418	0.9951	0.2474	0.051*
C5	0.19079 (8)	1.0533 (3)	0.28672 (11)	0.0387 (5)
H5	0.1611	0.9844	0.2499	0.046*
C6	0.18558 (8)	1.1467 (2)	0.34195 (11)	0.0331 (4)
C7	0.13489 (8)	1.1274 (2)	0.34918 (11)	0.0334 (4)
H7	0.1298	1.2415	0.3692	0.040*
C8	0.13171 (8)	0.8265 (3)	0.38169 (11)	0.0359 (4)
C9	0.06696 (8)	0.9154 (3)	0.25004 (11)	0.0355 (4)
C10	0.08227 (8)	1.0897 (3)	0.27177 (11)	0.0341 (4)
C11	0.02055 (9)	0.8432 (3)	0.17415 (13)	0.0484 (5)
H11A	−0.0117	0.9173	0.1562	0.073*
H11B	0.0123	0.7217	0.1813	0.073*
H11C	0.0315	0.8444	0.1365	0.073*
C12	0.05336 (8)	1.2485 (3)	0.22475 (12)	0.0382 (5)
C13	−0.01773 (13)	1.3590 (4)	0.10104 (16)	0.0718 (8)
H13A	0.0067	1.4473	0.0989	0.086*
H13B	−0.0387	1.4178	0.1204	0.086*
C14	−0.05525 (19)	1.2832 (6)	0.0238 (2)	0.1255 (18)
H14A	−0.0341	1.2191	0.0066	0.188*
H14B	−0.0755	1.3789	−0.0120	0.188*
H14C	−0.0807	1.2017	0.0261	0.188*
C15	0.33997 (12)	1.0703 (4)	0.28976 (19)	0.0700 (8)
H15A	0.3327	0.9462	0.2949	0.105*
H15B	0.3774	1.0823	0.3016	0.105*
H15C	0.3147	1.1098	0.2374	0.105*
C16	0.19334 (12)	0.7289 (4)	0.53535 (15)	0.0662 (7)
H16A	0.2215	0.6410	0.5676	0.079*
H16B	0.2122	0.8324	0.5304	0.079*
C17	0.16579 (19)	0.7873 (5)	0.57661 (19)	0.0867 (10)
H17	0.1891	0.8174	0.6287	0.104*
C18	0.1139 (2)	0.8017 (6)	0.5498 (3)	0.1070 (13)
H18A	0.0884	0.7736	0.4981	0.128*
H18B	0.1015	0.8404	0.5820	0.128*

	U11	U22	U33	U12	U13	U23
S1	0.0785 (5)	0.0335 (3)	0.0492 (4)	−0.0010 (3)	0.0305 (3)	0.0058 (2)
O1	0.0468 (9)	0.0614 (11)	0.0707 (11)	−0.0059 (8)	0.0342 (8)	−0.0012 (9)
O2	0.0615 (10)	0.0249 (8)	0.0522 (9)	0.0007 (7)	0.0174 (8)	−0.0004 (7)
O3	0.0692 (11)	0.0348 (9)	0.0446 (9)	0.0068 (8)	0.0045 (8)	0.0012 (7)
N1	0.0498 (10)	0.0318 (9)	0.0347 (9)	−0.0012 (7)	0.0226 (8)	0.0015 (7)
N2	0.0510 (10)	0.0219 (8)	0.0409 (9)	0.0009 (7)	0.0224 (8)	−0.0030 (7)
C1	0.0456 (11)	0.0325 (11)	0.0356 (10)	−0.0020 (8)	0.0171 (9)	−0.0050 (8)
C2	0.0414 (11)	0.0391 (12)	0.0444 (11)	−0.0100 (9)	0.0142 (9)	−0.0054 (9)
C3	0.0393 (11)	0.0361 (11)	0.0454 (11)	0.0010 (8)	0.0215 (9)	0.0083 (9)
C4	0.0521 (12)	0.0385 (11)	0.0400 (11)	−0.0019 (9)	0.0264 (10)	−0.0029 (9)
C5	0.0419 (11)	0.0337 (11)	0.0358 (10)	−0.0082 (8)	0.0171 (9)	−0.0065 (8)
C6	0.0395 (10)	0.0237 (9)	0.0313 (9)	0.0004 (7)	0.0151 (8)	0.0028 (7)
C7	0.0415 (10)	0.0240 (9)	0.0331 (9)	−0.0002 (8)	0.0184 (8)	−0.0013 (7)
C8	0.0436 (11)	0.0294 (10)	0.0383 (10)	0.0022 (8)	0.0239 (9)	0.0033 (8)
C9	0.0372 (10)	0.0307 (10)	0.0387 (10)	−0.0005 (8)	0.0200 (9)	−0.0024 (8)
C10	0.0376 (10)	0.0270 (10)	0.0359 (10)	0.0006 (8)	0.0180 (8)	−0.0002 (8)
C11	0.0488 (13)	0.0345 (12)	0.0484 (12)	−0.0045 (9)	0.0161 (10)	−0.0061 (9)
C12	0.0380 (10)	0.0333 (11)	0.0405 (11)	0.0007 (8)	0.0187 (9)	0.0004 (8)
C13	0.0752 (18)	0.0447 (15)	0.0550 (15)	0.0156 (13)	0.0063 (13)	0.0100 (12)
C14	0.133 (3)	0.085 (3)	0.065 (2)	0.022 (2)	−0.013 (2)	0.0010 (19)
C15	0.0728 (17)	0.0696 (18)	0.094 (2)	0.0004 (14)	0.0614 (17)	0.0047 (16)
C16	0.0784 (18)	0.0486 (15)	0.0485 (14)	−0.0047 (13)	0.0173 (13)	0.0134 (11)
C17	0.129 (3)	0.067 (2)	0.0587 (17)	−0.014 (2)	0.045 (2)	−0.0015 (15)
C18	0.141 (4)	0.098 (3)	0.103 (3)	0.017 (3)	0.078 (3)	0.004 (2)

S1—C8	1.766 (2)	C7—H7	0.9800
S1—C16	1.780 (3)	C9—C10	1.359 (3)
O1—C3	1.370 (3)	C9—C11	1.501 (3)
O1—C15	1.421 (3)	C10—C12	1.464 (3)
O2—C12	1.211 (2)	C11—H11A	0.9600
O3—C12	1.334 (3)	C11—H11B	0.9600
O3—C13	1.453 (3)	C11—H11C	0.9600
N1—C8	1.267 (3)	C12—O2	1.211 (2)
N1—C7	1.486 (2)	C13—C14	1.464 (4)
N2—C8	1.388 (3)	C13—H13A	0.9700
N2—C9	1.389 (3)	C13—H13B	0.9700
N2—H2	0.8600	C14—H14A	0.9600
C1—C2	1.374 (3)	C14—H14B	0.9600
C1—C6	1.395 (3)	C14—H14C	0.9600
C1—H1	0.9300	C15—H15A	0.9600
C2—C3	1.393 (3)	C15—H15B	0.9600
C2—H2A	0.9300	C15—H15C	0.9600
C3—C4	1.380 (3)	C16—C17	1.474 (5)
C4—C5	1.392 (3)	C16—H16A	0.9700
C4—H4	0.9300	C16—H16B	0.9700
C5—C6	1.385 (3)	C17—C18	1.277 (5)
C5—H5	0.9300	C17—H17	0.9300
C6—C7	1.524 (3)	C18—H18A	0.9300
C7—C10	1.517 (3)	C18—H18B	0.9300
C8—S1—C16	101.35 (11)	C9—C11—H11B	109.5
C3—O1—C15	117.37 (19)	H11A—C11—H11B	109.5
C12—O3—C13	117.77 (18)	C9—C11—H11C	109.5
C8—N1—C7	116.11 (16)	H11A—C11—H11C	109.5
C8—N2—C9	119.55 (16)	H11B—C11—H11C	109.5
C8—N2—H2	120.2	O2—C12—O3	122.22 (18)
C9—N2—H2	120.2	O2—C12—O3	122.22 (18)
C2—C1—C6	121.64 (19)	O2—C12—C10	123.91 (19)
C2—C1—H1	119.2	O2—C12—C10	123.91 (19)
C6—C1—H1	119.2	O3—C12—C10	113.86 (17)
C1—C2—C3	120.11 (19)	O3—C13—C14	107.1 (2)
C1—C2—H2A	119.9	O3—C13—H13A	110.3
C3—C2—H2A	119.9	C14—C13—H13A	110.3
O1—C3—C4	124.2 (2)	O3—C13—H13B	110.3
O1—C3—C2	116.34 (19)	C14—C13—H13B	110.3
C4—C3—C2	119.44 (19)	H13A—C13—H13B	108.5
C3—C4—C5	119.65 (19)	C13—C14—H14A	109.5
C3—C4—H4	120.2	C13—C14—H14B	109.5
C5—C4—H4	120.2	H14A—C14—H14B	109.5
C6—C5—C4	121.81 (18)	C13—C14—H14C	109.5
C6—C5—H5	119.1	H14A—C14—H14C	109.5
C4—C5—H5	119.1	H14B—C14—H14C	109.5
C5—C6—C1	117.34 (18)	O1—C15—H15A	109.5
C5—C6—C7	122.25 (17)	O1—C15—H15B	109.5
C1—C6—C7	120.26 (17)	H15A—C15—H15B	109.5
N1—C7—C10	112.63 (15)	O1—C15—H15C	109.5
N1—C7—C6	107.63 (15)	H15A—C15—H15C	109.5
C10—C7—C6	112.61 (15)	H15B—C15—H15C	109.5
N1—C7—H7	107.9	C17—C16—S1	116.9 (2)
C10—C7—H7	107.9	C17—C16—H16A	108.1
C6—C7—H7	107.9	S1—C16—H16A	108.1
N1—C8—N2	125.34 (17)	C17—C16—H16B	108.1
N1—C8—S1	123.53 (15)	S1—C16—H16B	108.1
N2—C8—S1	111.13 (14)	H16A—C16—H16B	107.3
C10—C9—N2	117.60 (18)	C18—C17—C16	128.1 (3)
C10—C9—C11	128.98 (19)	C18—C17—H17	115.9
N2—C9—C11	113.43 (17)	C16—C17—H17	115.9
C9—C10—C12	125.37 (18)	C17—C18—H18A	120.0
C9—C10—C7	118.86 (17)	C17—C18—H18B	120.0
C12—C10—C7	115.70 (16)	H18A—C18—H18B	120.0
C9—C11—H11A	109.5
C6—C1—C2—C3	0.3 (3)	C16—S1—C8—N2	179.62 (16)
C15—O1—C3—C4	−5.1 (3)	C8—N2—C9—C10	17.0 (3)
C15—O1—C3—C2	175.6 (2)	C8—N2—C9—C11	−163.18 (18)
C1—C2—C3—O1	179.86 (19)	N2—C9—C10—C12	−176.65 (17)
C1—C2—C3—C4	0.5 (3)	C11—C9—C10—C12	3.6 (3)
O1—C3—C4—C5	−179.79 (19)	N2—C9—C10—C7	6.3 (3)
C2—C3—C4—C5	−0.5 (3)	C11—C9—C10—C7	−173.39 (19)
C3—C4—C5—C6	−0.4 (3)	N1—C7—C10—C9	−29.8 (2)
C4—C5—C6—C1	1.2 (3)	C6—C7—C10—C9	92.1 (2)
C4—C5—C6—C7	−174.30 (18)	N1—C7—C10—C12	152.88 (16)
C2—C1—C6—C5	−1.2 (3)	C6—C7—C10—C12	−85.2 (2)
C2—C1—C6—C7	174.42 (18)	C13—O3—C12—O2	−2.9 (3)
C8—N1—C7—C10	31.2 (2)	C13—O3—C12—O2	−2.9 (3)
C8—N1—C7—C6	−93.6 (2)	C13—O3—C12—C10	178.3 (2)
C5—C6—C7—N1	93.2 (2)	C9—C10—C12—O2	171.3 (2)
C1—C6—C7—N1	−82.1 (2)	C7—C10—C12—O2	−11.6 (3)
C5—C6—C7—C10	−31.5 (2)	C9—C10—C12—O2	171.3 (2)
C1—C6—C7—C10	153.14 (17)	C7—C10—C12—O2	−11.6 (3)
C7—N1—C8—N2	−10.0 (3)	C9—C10—C12—O3	−10.0 (3)
C7—N1—C8—S1	170.98 (14)	C7—C10—C12—O3	167.10 (17)
C9—N2—C8—N1	−16.0 (3)	C12—O3—C13—C14	177.0 (3)
C9—N2—C8—S1	163.17 (14)	C8—S1—C16—C17	90.0 (2)
C16—S1—C8—N1	−1.2 (2)	S1—C16—C17—C18	−10.8 (5)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2i	0.86	2.16	2.990 (2)	161
C7—H7···O2	0.98	2.46	2.831 (3)	102

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O2i	0.86	2.16	2.990 (2)	161
C7—H7⋯O2	0.98	2.46	2.831 (3)	102

Symmetry code: (i) .