Ethyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate: a triclinic polymorph

Novina, J.J.; Vasuki, G.; Suresh, M.; Viswanathan, V.; Velmurugan, D.

doi:10.1107/S2414314616019374

organic compounds

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ISSN: 2414-3146

Volume 1| Part 12| December 2016| x161937

https://doi.org/10.1107/S2414314616019374

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Ethyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate: a triclinic polymorph

J. J. Novina,^a G. Vasuki,^b ^* M. Suresh,^c Vijayan Viswanathan ^d and Devadasan Velmurugan ^e

^aDepartment of Physics, Idhaya College for Women, Kumbakonam-1, India, ^bDepartment of Physics, Kunthavai Naachiar Govt. Arts College (W) (Autonomous), Thanjavur-7, India, ^cDepartment of Chemistry, College of Engineering, Guindy, Anna University, Chennai-25, India, ^dCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai-25, India, and ^eCentre of Advanced study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai-25, India
^*Correspondence e-mail: vasuki.arasi@yahoo.com

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 30 November 2016; accepted 3 December 2016; online 9 December 2016)

The title compound, C₁₂H₁₄N₂O₄, crystallizes in the triclinic space group P-1. The previously reported polymorph occurs in the monoclinic space group P2₁/c, and has two independent molecules in the asymmetric unit [Wang (2010 ). Acta Cryst. E66, o2822]. The dihydropyrimidine ring adopts a screw-boat conformation. The furan ring is positioned axially and makes a dihedral angle of 85.94 (7)° with the mean plane through the pyrimidine ring. In the crystal, molecules are linked via pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R₂²(8) ring motif. The dimers are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming chains propagating along the a-axis direction.

Keywords: crystal structure; pyrimidine; dihydropyrimidines; Biginelli compounds; hydrogen bonding.

CCDC reference: 1520574

Structure description

In recent years, dihydropyrimidines (DHPMs, `Biginelli compounds') and their derivatives have attracted considerable attention in synthetic organic chemistry because of their wide range of biological activities, such as antiviral, antitumor, antibacterial and anti-inflammatory properties (Kappe 2000 ; Kulkarni et al., 2009 ; Patil et al., 2011 ). The Biginelli reaction is a well-known multi-component reaction involving a one-pot cyclocondensation of an aldehyde, β-ketoester and urea/thiourea. Multi-component reactions (MCRs) have recently gained tremendous importance in organic and medicinal chemistry (Kulkarni et al., 2009). They are also very potent calcium channel modulators (Kappe 1998 ; Jauk et al., 2000 ). Furthermore, apart from synthetic DHPM derivatives, several marine natural products with interesting biological activities containing the dihydropyrimidine-5-carboxylate core have also been isolated. Most notable among these are the batzelladine alkaloids A and B, which inhibit the binding of HIV envelope protein gp-120 to human CD4 cells and, therefore, are potential leads for AIDS therapy (Kappe, 2000). As part of our studies in this area, we have determined the crystal structure of the title compound presented herein. It is one of the analogues of our previously reported DHPM structures (Suresh et al., 2015a ,b ; Novina et al., 2015 ).

In the title compound, Fig. 1, the furan ring at the chiral carbon atom C4 is positioned axially and bisects the pyrimidine ring with a dihedral angle of 85.94 (7)°. The pyrimidine ring adopts a screw-boat conformation with atoms N1 and C4 displaced by −0.1674 (10) and 0.1603 (9) Å, respectively, from the mean plane of the other atoms (C1/N2/C2/C3). The puckering parameters are q2 = 0.2446 (16) Å, q3 = 0.1048 (16) Å, Q = 0.2661 (16) Å, θ = 66.8 (3)° and φ = 327.6 (4)°. The ethyl acetate group attached to the pyrimidine ring shows an extended conformation [C3—C6—O3—C7 = −179.29 (12)°].

Figure 1
The molecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

In the crystal, molecules are linked via pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R₂²(8) ring motif (Fig. 2 and Table 1). The dimers are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming chains propagating along the a–axis direction (Fig. 2 and Table 1).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O1ⁱ	0.86	2.00	2.855 (2)	176
N1—H1⋯O2ⁱⁱ	0.86	2.34	3.142 (2)	156
C5—H5A⋯O1ⁱⁱⁱ	0.96	2.52	3.141 (2)	122
Symmetry codes: (i) -x+1, -y+2, -z+1; (ii) x-1, y, z; (iii) x+1, y, z.

Figure 2
The crystal packing of the title compound, showing the R₂²(8) ring motif, viewed normal to the bc plane. Hydrogen bonds are shown as dashed lines (see Table 1

Synthesis and crystallization

A mixture of ethylacetoacetate (1.3 ml, 0.01 mol), furfural (1 ml, 0.01 mol), and urea (1.8 g, 0.03 mol) in ethanol (5 ml) was heated under reflux in the presence of CeCl₃·7H₂O (25 mol %) for 8 h (monitored by TLC). The reaction mixture, after being cooled to room temperature, was poured onto crushed ice and stirred for 5–10 min. The precipitate was then washed with water, filtered, dried and again washed with petroleum ether (40–60%) and dried in a vacuum. The compound was recrystallized from absolute ethanol giving colourless block-like crystals [m.p. 435–438 K, yield 88%].

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₄N₂O₄
M_r	250.25
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	296
a, b, c (Å)	7.4670 (2), 8.8307 (3), 10.5426 (3)
α, β, γ (°)	106.833 (2), 108.557 (2), 99.420 (2)
V (Å³)	605.20 (3)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.19 × 0.16 × 0.13

Data collection
Diffractometer	Bruker Kappa APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2008 )
T_min, T_max	0.980, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections	9061, 2458, 2116
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.624

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.123, 1.08
No. of reflections	2458
No. of parameters	166
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.31, −0.36
Computer programs: APEX2, SAINT and XPREP (Bruker, 2008), SIR92 (Altomare et al., 1993 ), SHELXL97 (Sheldrick, 2008 ), ORTEP-3 for Windows (Farrugia, 2012 ) and PLATON (Spek, 2009 ).

Structural data

CCDC reference: 1520574

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314616019374/su4105sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616019374/su4105Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314616019374/su4105Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: APEX2 and SAINT (Bruker, 2008); data reduction: SAINT and XPREP (Bruker, 2008); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2009).

Ethyl 4-(furan-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate top

Crystal data top

C₁₂H₁₄N₂O₄	Z = 2
M_r = 250.25	F(000) = 264
Triclinic, P1	D_x = 1.373 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.4670 (2) Å	Cell parameters from 2458 reflections
b = 8.8307 (3) Å	θ = 2.2–26.3°
c = 10.5426 (3) Å	µ = 0.10 mm⁻¹
α = 106.833 (2)°	T = 296 K
β = 108.557 (2)°	Block, colourless
γ = 99.420 (2)°	0.19 × 0.16 × 0.13 mm
V = 605.20 (3) Å³

Data collection top

Bruker Kappa APEXII CCD diffractometer	2458 independent reflections
Radiation source: fine-focus sealed tube	2116 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
ω and φ scan	θ_max = 26.3°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −9→9
T_min = 0.980, T_max = 0.987	k = −10→10
9061 measured reflections	l = −13→12

Refinement top

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)] = 0.042	H-atom parameters constrained
wR(F²) = 0.123	w = 1/[σ²(F_o²) + (0.0596P)² + 0.1739P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max < 0.001
2458 reflections	Δρ_max = 0.31 e Å⁻³
166 parameters	Δρ_min = −0.36 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.010 (5)

Special details top

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 > 2sigma(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.

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

	x	y	z	U_iso*/U_eq
O4	0.7408 (2)	0.90463 (16)	0.92870 (14)	0.0670 (4)
C10	0.5796 (3)	0.7209 (3)	0.9849 (2)	0.0647 (5)
H10	0.5005	0.6241	0.9791	0.078*
C11	0.6772 (3)	0.8695 (3)	1.1090 (2)	0.0699 (6)
H11	0.6753	0.8875	1.1999	0.084*
C12	0.7690 (3)	0.9745 (3)	1.0699 (2)	0.0725 (6)
H12	0.8433	1.0821	1.1296	0.087*
O1	0.32040 (15)	0.90923 (14)	0.55610 (13)	0.0463 (3)
N2	0.60593 (17)	0.84873 (15)	0.56522 (14)	0.0391 (3)
H2	0.6340	0.9242	0.5326	0.047*
O2	1.01790 (16)	0.58238 (15)	0.69053 (14)	0.0529 (3)
C3	0.71862 (19)	0.65870 (17)	0.66569 (15)	0.0346 (3)
O3	0.79382 (16)	0.45399 (13)	0.75180 (13)	0.0474 (3)
C6	0.8590 (2)	0.56456 (18)	0.70103 (16)	0.0378 (3)
N1	0.39886 (17)	0.70961 (15)	0.64088 (13)	0.0384 (3)
H1	0.2789	0.6658	0.6263	0.046*
C1	0.4345 (2)	0.82776 (18)	0.58816 (15)	0.0354 (3)
C2	0.73651 (19)	0.75677 (17)	0.59092 (15)	0.0350 (3)
C4	0.5541 (2)	0.65133 (17)	0.72213 (16)	0.0354 (3)
H4	0.4969	0.5358	0.7054	0.042*
C9	0.6239 (2)	0.74810 (18)	0.87951 (16)	0.0388 (3)
C7	0.9206 (3)	0.3533 (2)	0.7928 (2)	0.0510 (4)
H7A	1.0495	0.4230	0.8629	0.061*
H7B	0.9365	0.2840	0.7093	0.061*
C5	0.8859 (2)	0.7784 (2)	0.52603 (19)	0.0501 (4)
H5A	1.0055	0.8581	0.5979	0.075*
H5B	0.8361	0.8162	0.4486	0.075*
H5C	0.9118	0.6749	0.4900	0.075*
C8	0.8261 (4)	0.2502 (3)	0.8552 (3)	0.0700 (6)
H8A	0.8160	0.3200	0.9399	0.105*
H8B	0.9041	0.1790	0.8801	0.105*
H8C	0.6969	0.1848	0.7861	0.105*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.0817 (9)	0.0548 (8)	0.0514 (7)	−0.0049 (7)	0.0300 (7)	0.0097 (6)
C10	0.0792 (13)	0.0694 (12)	0.0645 (12)	0.0188 (10)	0.0445 (11)	0.0339 (10)
C11	0.0797 (14)	0.0946 (16)	0.0453 (10)	0.0336 (12)	0.0338 (10)	0.0241 (10)
C12	0.0817 (14)	0.0704 (13)	0.0480 (10)	0.0099 (11)	0.0246 (10)	0.0043 (9)
O1	0.0360 (6)	0.0589 (7)	0.0635 (7)	0.0228 (5)	0.0282 (5)	0.0348 (6)
N2	0.0326 (6)	0.0449 (7)	0.0532 (7)	0.0143 (5)	0.0248 (5)	0.0260 (6)
O2	0.0403 (6)	0.0607 (7)	0.0782 (8)	0.0246 (5)	0.0336 (6)	0.0363 (6)
C3	0.0303 (7)	0.0343 (7)	0.0405 (7)	0.0091 (5)	0.0179 (6)	0.0110 (6)
O3	0.0455 (6)	0.0469 (6)	0.0666 (7)	0.0214 (5)	0.0303 (5)	0.0300 (6)
C6	0.0362 (7)	0.0360 (7)	0.0431 (8)	0.0109 (6)	0.0196 (6)	0.0121 (6)
N1	0.0261 (6)	0.0458 (7)	0.0495 (7)	0.0094 (5)	0.0190 (5)	0.0215 (6)
C1	0.0292 (6)	0.0404 (7)	0.0383 (7)	0.0100 (6)	0.0157 (5)	0.0138 (6)
C2	0.0292 (7)	0.0371 (7)	0.0399 (7)	0.0091 (6)	0.0171 (6)	0.0116 (6)
C4	0.0320 (7)	0.0342 (7)	0.0470 (8)	0.0105 (5)	0.0211 (6)	0.0177 (6)
C9	0.0370 (7)	0.0426 (8)	0.0473 (8)	0.0155 (6)	0.0229 (6)	0.0214 (6)
C7	0.0530 (9)	0.0506 (9)	0.0620 (10)	0.0262 (8)	0.0265 (8)	0.0274 (8)
C5	0.0438 (9)	0.0659 (11)	0.0649 (10)	0.0250 (8)	0.0362 (8)	0.0357 (9)
C8	0.0852 (15)	0.0629 (12)	0.0862 (14)	0.0319 (11)	0.0446 (12)	0.0428 (11)

Geometric parameters (Å, º) top

O4—C9	1.3575 (19)	O3—C7	1.4528 (19)
O4—C12	1.366 (2)	N1—C1	1.3444 (19)
C10—C9	1.328 (2)	N1—C4	1.4702 (18)
C10—C11	1.432 (3)	N1—H1	0.8600
C10—H10	0.9300	C2—C5	1.4967 (19)
C11—C12	1.301 (3)	C4—C9	1.496 (2)
C11—H11	0.9300	C4—H4	0.9800
C12—H12	0.9300	C7—C8	1.481 (3)
O1—C1	1.2312 (17)	C7—H7A	0.9700
N2—C1	1.3700 (17)	C7—H7B	0.9700
N2—C2	1.3791 (18)	C5—H5A	0.9600
N2—H2	0.8600	C5—H5B	0.9600
O2—C6	1.2152 (18)	C5—H5C	0.9600
C3—C2	1.347 (2)	C8—H8A	0.9600
C3—C6	1.465 (2)	C8—H8B	0.9600
C3—C4	1.5258 (18)	C8—H8C	0.9600
O3—C6	1.3378 (18)

C9—O4—C12	106.82 (15)	N2—C2—C5	112.94 (12)
C9—C10—C11	106.66 (18)	N1—C4—C9	109.89 (11)
C9—C10—H10	126.7	N1—C4—C3	109.59 (11)
C11—C10—H10	126.7	C9—C4—C3	113.30 (11)
C12—C11—C10	106.67 (17)	N1—C4—H4	108.0
C12—C11—H11	126.7	C9—C4—H4	108.0
C10—C11—H11	126.7	C3—C4—H4	108.0
C11—C12—O4	110.45 (19)	C10—C9—O4	109.38 (15)
C11—C12—H12	124.8	C10—C9—C4	133.32 (16)
O4—C12—H12	124.8	O4—C9—C4	116.85 (12)
C1—N2—C2	124.35 (12)	O3—C7—C8	107.47 (15)
C1—N2—H2	117.8	O3—C7—H7A	110.2
C2—N2—H2	117.8	C8—C7—H7A	110.2
C2—C3—C6	121.82 (12)	O3—C7—H7B	110.2
C2—C3—C4	119.48 (12)	C8—C7—H7B	110.2
C6—C3—C4	118.62 (12)	H7A—C7—H7B	108.5
C6—O3—C7	117.05 (12)	C2—C5—H5A	109.5
O2—C6—O3	122.08 (14)	C2—C5—H5B	109.5
O2—C6—C3	126.50 (14)	H5A—C5—H5B	109.5
O3—C6—C3	111.41 (12)	C2—C5—H5C	109.5
C1—N1—C4	123.44 (11)	H5A—C5—H5C	109.5
C1—N1—H1	118.3	H5B—C5—H5C	109.5
C4—N1—H1	118.3	C7—C8—H8A	109.5
O1—C1—N1	123.84 (12)	C7—C8—H8B	109.5
O1—C1—N2	120.65 (13)	H8A—C8—H8B	109.5
N1—C1—N2	115.45 (12)	C7—C8—H8C	109.5
C3—C2—N2	119.95 (12)	H8A—C8—H8C	109.5
C3—C2—C5	127.10 (13)	H8B—C8—H8C	109.5

C9—C10—C11—C12	1.0 (3)	C1—N2—C2—C3	−12.1 (2)
C10—C11—C12—O4	−0.8 (3)	C1—N2—C2—C5	166.89 (14)
C9—O4—C12—C11	0.3 (3)	C1—N1—C4—C9	91.93 (16)
C7—O3—C6—O2	−0.7 (2)	C1—N1—C4—C3	−33.18 (18)
C7—O3—C6—C3	−179.29 (12)	C2—C3—C4—N1	20.23 (18)
C2—C3—C6—O2	12.9 (2)	C6—C3—C4—N1	−162.82 (12)
C4—C3—C6—O2	−163.98 (15)	C2—C3—C4—C9	−102.90 (15)
C2—C3—C6—O3	−168.65 (13)	C6—C3—C4—C9	74.05 (16)
C4—C3—C6—O3	14.48 (18)	C11—C10—C9—O4	−0.8 (2)
C4—N1—C1—O1	−159.14 (14)	C11—C10—C9—C4	−172.63 (17)
C4—N1—C1—N2	23.7 (2)	C12—O4—C9—C10	0.3 (2)
C2—N2—C1—O1	−176.44 (13)	C12—O4—C9—C4	173.67 (15)
C2—N2—C1—N1	0.8 (2)	N1—C4—C9—C10	96.8 (2)
C6—C3—C2—N2	−177.23 (12)	C3—C4—C9—C10	−140.24 (19)
C4—C3—C2—N2	−0.4 (2)	N1—C4—C9—O4	−74.56 (16)
C6—C3—C2—C5	4.0 (2)	C3—C4—C9—O4	48.40 (18)
C4—C3—C2—C5	−179.20 (14)	C6—O3—C7—C8	175.87 (15)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1ⁱ	0.86	2.00	2.855 (2)	176
N1—H1···O2ⁱⁱ	0.86	2.34	3.142 (2)	156
C5—H5A···O1ⁱⁱⁱ	0.96	2.52	3.141 (2)	122

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

Acknowledgements

We are grateful to the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection.

References

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