Methyl 6-methoxy-carbonyl-methyl-2-oxo-4-phenyl-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

The title compound, C(15)H(16)N(2)O(5), belongs to the class of monastrol-type anti--cancer agents and was selected for crystal structure determination in order to determine the conformational details needed for subsequent structure-activity relationship studies. The central tetra-hydro-pyrimidine ring has a flat-envelope conformation. The 4-phenyl group occupies a pseudo-axial position and is inclined at an angle of ca 90° to the mean plane of the heterocyclic ring. Of the two methyl ester groups, one (in the 5-position) is in a coplanar and the other (in the 6-position) in a perpendicular orientation with respect to the heterocyclic plane. The coplanar 5-ester group has its carbonyl bond oriented cis with respect to the pyrimidine C=C double bond. By comparison of the structural results for the present compound with those determined previously for its diethyl analogue, we have identified the mol-ecular factors which control the dual course of the Biginelli reaction with salicylaldehyde. The crystal structure is dominated by two hydrogen bonds which link the mol-ecules into chains of dimers.

Related literature

For related literature, see: Haggarty et al. (2000 ▶); Hirshfeld (1976 ▶); Kettmann et al. (2008 ▶); Klein et al. (2007 ▶); Mayer et al. (1999 ▶); Světlík et al. (2008 ▶).

Experimental

Crystal data

C15H16N2O5

M = 304.35

Monoclinic,

a = 23.498 (5) Å

b = 12.072 (2) Å

c = 10.933 (5) Å

β = 99.15 (2)°

V = 3061.9 (16) Å3

Z = 8

Mo Kα radiation

μ = 0.10 mm−1

T = 296 (2) K

0.30 × 0.25 × 0.20 mm

Data collection

Siemens P4 diffractometer

Absorption correction: none

5187 measured reflections

4466 independent reflections

2308 reflections with I > 2σ(I)

R int = 0.040

3 standard reflections every 97 reflections intensity decay: none

Refinement

R[F 2 > 2σ(F 2)] = 0.046

wR(F 2) = 0.118

S = 0.90

4466 reflections

201 parameters

54 restraints

H-atom parameters constrained

Δρmax = 0.13 e Å−3

Δρmin = −0.27 e Å−3

Data collection: XSCANS (Siemens, 1991 ▶); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808026135/bv2102sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808026135/bv2102Isup2.hkl

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

C15H16N2O5	F000 = 1280
Mr = 304.35	Dx = 1.320 Mg m−3
Monoclinic, C2/c	Melting point: 454 K
Hall symbol: -C 2yc	Mo Kα radiation λ = 0.71073 Å
a = 23.498 (5) Å	Cell parameters from 20 reflections
b = 12.072 (2) Å	θ = 7–18º
c = 10.933 (5) Å	µ = 0.10 mm−1
β = 99.15 (2)º	T = 296 (2) K
V = 3061.9 (16) Å3	Prism, colourless
Z = 8	0.30 × 0.25 × 0.20 mm

Siemens P4 diffractometer	Rint = 0.040
Radiation source: fine-focus sealed tube	θmax = 30.0º
Monochromator: graphite	θmin = 1.9º
T = 296(2) K	h = −1→32
ω/2θ scans	k = −1→16
Absorption correction: none	l = −15→15
5187 measured reflections	3 standard reflections
4466 independent reflections	every 97 reflections
2308 reflections with I > 2σ(I)	intensity decay: none

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)] = 0.046	H-atom parameters constrained
wR(F2) = 0.118	w = 1/[σ2(Fo2) + (0.0575P)2] where P = (Fo2 + 2Fc2)/3
S = 0.90	(Δ/σ)max = 0.001
4466 reflections	Δρmax = 0.13 e Å−3
201 parameters	Δρmin = −0.27 e Å−3
54 restraints	Extinction correction: none
Primary atom site location: structure-invariant direct methods

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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
N1	0.44833 (5)	0.44128 (9)	0.38217 (11)	0.0509 (3)
H1	0.4615	0.4278	0.4587	0.061*
C2	0.44596 (5)	0.55052 (11)	0.34279 (13)	0.0477 (3)
O1	0.47167 (4)	0.62359 (8)	0.40833 (10)	0.0628 (3)
N3	0.41662 (5)	0.56699 (9)	0.23011 (11)	0.0536 (3)
H3	0.4214	0.6292	0.1948	0.064*
C4	0.37661 (5)	0.48718 (11)	0.16121 (13)	0.0479 (3)
H4	0.3779	0.4979	0.0728	0.058*
C5	0.39764 (5)	0.37090 (11)	0.19483 (12)	0.0458 (3)
C6	0.43076 (5)	0.35337 (10)	0.30560 (12)	0.0444 (3)
C7	0.31513 (5)	0.50992 (12)	0.18200 (12)	0.0473 (3)
C8	0.28364 (7)	0.59098 (14)	0.11197 (16)	0.0676 (4)
H8	0.2998	0.6291	0.0520	0.081*
C9	0.22800 (7)	0.61558 (16)	0.13099 (19)	0.0827 (5)
H9	0.2069	0.6696	0.0827	0.099*
C10	0.20409 (7)	0.56203 (17)	0.21879 (18)	0.0825 (5)
H10	0.1669	0.5795	0.2314	0.099*
C11	0.23487 (7)	0.48198 (19)	0.28903 (18)	0.0894 (6)
H11	0.2185	0.4444	0.3491	0.107*
C12	0.29047 (6)	0.45678 (16)	0.27056 (15)	0.0714 (5)
H12	0.3113	0.4028	0.3193	0.086*
C13	0.37881 (6)	0.28141 (13)	0.10727 (13)	0.0535 (3)
O2	0.39408 (5)	0.18597 (10)	0.11528 (11)	0.0759 (4)
O3	0.34141 (5)	0.31856 (10)	0.01108 (10)	0.0760 (4)
C14	0.32059 (10)	0.23753 (17)	−0.08185 (17)	0.1000 (7)
H14A	0.3526	0.2055	−0.1139	0.150*
H14B	0.2951	0.2726	−0.1480	0.150*
H14C	0.3001	0.1805	−0.0457	0.150*
C15	0.45308 (6)	0.24370 (11)	0.35961 (13)	0.0513 (3)
H15A	0.4440	0.1867	0.2971	0.062*
H15B	0.4947	0.2478	0.3805	0.062*
C16	0.42908 (6)	0.21132 (11)	0.47094 (14)	0.0522 (3)
O4	0.39511 (5)	0.26165 (9)	0.51997 (10)	0.0646 (3)
O5	0.45077 (6)	0.11392 (10)	0.51199 (14)	0.0996 (5)
C17	0.43033 (14)	0.0714 (2)	0.6208 (3)	0.1504 (12)
H17A	0.4401	0.1224	0.6882	0.226*
H17B	0.4481	0.0011	0.6430	0.226*
H17C	0.3892	0.0623	0.6035	0.226*

	U11	U22	U33	U12	U13	U23
N1	0.0531 (6)	0.0410 (5)	0.0532 (6)	−0.0021 (5)	−0.0084 (5)	0.0027 (5)
C2	0.0392 (6)	0.0429 (7)	0.0574 (8)	−0.0001 (6)	−0.0032 (6)	0.0048 (6)
O1	0.0607 (6)	0.0434 (5)	0.0749 (7)	−0.0039 (5)	−0.0177 (5)	−0.0015 (5)
N3	0.0486 (6)	0.0447 (6)	0.0619 (7)	−0.0066 (5)	−0.0078 (5)	0.0122 (5)
C4	0.0415 (6)	0.0464 (7)	0.0527 (8)	−0.0022 (5)	−0.0022 (5)	0.0035 (6)
C5	0.0368 (6)	0.0455 (6)	0.0530 (7)	0.0002 (5)	0.0010 (5)	0.0003 (5)
C6	0.0360 (6)	0.0407 (6)	0.0548 (7)	0.0011 (5)	0.0017 (5)	0.0003 (5)
C7	0.0390 (6)	0.0490 (7)	0.0490 (7)	0.0024 (5)	−0.0080 (5)	−0.0046 (6)
C8	0.0557 (8)	0.0689 (11)	0.0743 (10)	0.0115 (7)	−0.0019 (7)	0.0143 (8)
C9	0.0596 (9)	0.0825 (12)	0.0996 (14)	0.0289 (9)	−0.0070 (8)	0.0080 (10)
C10	0.0446 (8)	0.1046 (15)	0.0955 (13)	0.0202 (9)	0.0028 (8)	−0.0154 (10)
C11	0.0569 (9)	0.1245 (17)	0.0893 (13)	0.0169 (10)	0.0190 (9)	0.0189 (11)
C12	0.0502 (8)	0.0883 (12)	0.0746 (11)	0.0138 (8)	0.0064 (7)	0.0244 (9)
C13	0.0462 (7)	0.0525 (8)	0.0594 (8)	−0.0017 (6)	0.0006 (6)	−0.0029 (6)
O2	0.0868 (8)	0.0517 (6)	0.0811 (8)	0.0034 (6)	−0.0118 (6)	−0.0112 (5)
O3	0.0810 (8)	0.0686 (7)	0.0670 (7)	0.0045 (6)	−0.0236 (6)	−0.0132 (5)
C14	0.1211 (17)	0.0911 (14)	0.0731 (11)	−0.0022 (13)	−0.0300 (11)	−0.0234 (10)
C15	0.0430 (7)	0.0420 (7)	0.0655 (8)	0.0065 (6)	−0.0020 (6)	0.0002 (6)
C16	0.0445 (7)	0.0347 (7)	0.0735 (9)	−0.0071 (6)	−0.0023 (6)	0.0033 (6)
O4	0.0629 (6)	0.0556 (6)	0.0764 (7)	−0.0047 (5)	0.0143 (5)	0.0000 (5)
O5	0.1040 (10)	0.0554 (7)	0.1434 (12)	0.0181 (7)	0.0316 (9)	0.0462 (8)
C17	0.172 (3)	0.1040 (19)	0.187 (3)	0.0252 (18)	0.065 (2)	0.0924 (19)

N1—C6	1.3739 (16)	C10—H10	0.9300
N1—C2	1.3856 (17)	C11—C12	1.387 (2)
N1—H1	0.8600	C11—H11	0.9300
C2—O1	1.2324 (16)	C12—H12	0.9300
C2—N3	1.3276 (17)	C13—O2	1.2058 (18)
N3—C4	1.4677 (16)	C13—O3	1.3362 (17)
N3—H3	0.8600	O3—C14	1.4388 (19)
C4—C5	1.5139 (19)	C14—H14A	0.9600
C4—C7	1.5228 (18)	C14—H14B	0.9600
C4—H4	0.9800	C14—H14C	0.9600
C5—C6	1.3480 (19)	C15—C16	1.473 (2)
C5—C13	1.464 (2)	C15—H15A	0.9700
C6—C15	1.5093 (17)	C15—H15B	0.9700
C7—C12	1.365 (2)	C16—O4	1.1957 (17)
C7—C8	1.3824 (19)	C16—O5	1.3308 (17)
C8—C9	1.388 (2)	O5—C17	1.446 (3)
C8—H8	0.9300	C17—H17A	0.9600
C9—C10	1.352 (3)	C17—H17B	0.9600
C9—H9	0.9300	C17—H17C	0.9600
C10—C11	1.368 (3)
C6—N1—C2	123.54 (11)	C10—C11—C12	119.97 (19)
C6—N1—H1	118.2	C10—C11—H11	120.0
C2—N1—H1	118.2	C12—C11—H11	120.0
O1—C2—N3	124.51 (13)	C7—C12—C11	121.07 (16)
O1—C2—N1	120.59 (12)	C7—C12—H12	119.5
N3—C2—N1	114.84 (12)	C11—C12—H12	119.5
C2—N3—C4	125.00 (11)	O2—C13—O3	121.92 (14)
C2—N3—H3	117.5	O2—C13—C5	127.01 (14)
C4—N3—H3	117.5	O3—C13—C5	111.07 (13)
N3—C4—C5	109.05 (10)	C13—O3—C14	115.78 (13)
N3—C4—C7	110.52 (11)	O3—C14—H14A	109.5
C5—C4—C7	114.30 (11)	O3—C14—H14B	109.5
N3—C4—H4	107.6	H14A—C14—H14B	109.5
C5—C4—H4	107.6	O3—C14—H14C	109.5
C7—C4—H4	107.6	H14A—C14—H14C	109.5
C6—C5—C13	122.87 (12)	H14B—C14—H14C	109.5
C6—C5—C4	118.89 (11)	C16—C15—C6	113.64 (12)
C13—C5—C4	118.18 (11)	C16—C15—H15A	108.8
C5—C6—N1	120.05 (12)	C6—C15—H15A	108.8
C5—C6—C15	127.18 (12)	C16—C15—H15B	108.8
N1—C6—C15	112.77 (11)	C6—C15—H15B	108.8
C12—C7—C8	118.39 (14)	H15A—C15—H15B	107.7
C12—C7—C4	122.75 (12)	O4—C16—O5	123.03 (15)
C8—C7—C4	118.80 (13)	O4—C16—C15	127.31 (13)
C7—C8—C9	120.14 (17)	O5—C16—C15	109.66 (14)
C7—C8—H8	119.9	C16—O5—C17	115.58 (17)
C9—C8—H8	119.9	O5—C17—H17A	109.5
C10—C9—C8	120.80 (17)	O5—C17—H17B	109.5
C10—C9—H9	119.6	H17A—C17—H17B	109.5
C8—C9—H9	119.6	O5—C17—H17C	109.5
C9—C10—C11	119.62 (17)	H17A—C17—H17C	109.5
C9—C10—H10	120.2	H17B—C17—H17C	109.5
C11—C10—H10	120.2
C6—N1—C2—O1	−166.61 (13)	C12—C7—C8—C9	−1.0 (2)
C6—N1—C2—N3	10.7 (2)	C4—C7—C8—C9	−178.35 (15)
O1—C2—N3—C4	−167.13 (13)	C7—C8—C9—C10	0.8 (3)
N1—C2—N3—C4	15.7 (2)	C8—C9—C10—C11	−0.6 (3)
C2—N3—C4—C5	−32.53 (18)	C9—C10—C11—C12	0.5 (3)
C2—N3—C4—C7	93.93 (15)	C8—C7—C12—C11	1.0 (3)
N3—C4—C5—C6	25.51 (17)	C4—C7—C12—C11	178.18 (16)
C7—C4—C5—C6	−98.74 (14)	C10—C11—C12—C7	−0.7 (3)
N3—C4—C5—C13	−157.16 (12)	C6—C5—C13—O2	−7.8 (2)
C7—C4—C5—C13	78.58 (16)	C4—C5—C13—O2	174.99 (14)
C13—C5—C6—N1	178.17 (13)	C6—C5—C13—O3	173.11 (13)
C4—C5—C6—N1	−4.6 (2)	C4—C5—C13—O3	−4.10 (18)
C13—C5—C6—C15	−1.0 (2)	O2—C13—O3—C14	0.1 (2)
C4—C5—C6—C15	176.17 (12)	C5—C13—O3—C14	179.23 (16)
C2—N1—C6—C5	−15.8 (2)	C5—C6—C15—C16	−114.21 (16)
C2—N1—C6—C15	163.47 (12)	N1—C6—C15—C16	66.54 (15)
N3—C4—C7—C12	−94.68 (17)	C6—C15—C16—O4	0.0 (2)
C5—C4—C7—C12	28.79 (19)	C6—C15—C16—O5	179.74 (12)
N3—C4—C7—C8	82.53 (15)	O4—C16—O5—C17	0.3 (3)
C5—C4—C7—C8	−154.00 (13)	C15—C16—O5—C17	−179.39 (18)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1i	0.86	2.06	2.8326 (17)	149
N3—H3···O4ii	0.86	2.32	3.0730 (17)	146

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1i	0.86	2.06	2.8326 (17)	149
N3—H3⋯O4ii	0.86	2.32	3.0730 (17)	146

Symmetry codes: (i) ; (ii) .