5-[(4-Eth­oxy­anilino)meth­yl]-N-(2-fluoro­phen­yl)-6-methyl-2-phenyl­pyrimidin-4-amine

Jerzy Cieplik; Marcin Stolarczyk; Iwona Bryndal; Tadeusz Lis

doi:10.1107/S1600536812021046

. 2012 May 16;68(Pt 6):o1729–o1730. doi: 10.1107/S1600536812021046

5-[(4-Ethoxyanilino)methyl]-N-(2-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine

Jerzy Cieplik ^a, Marcin Stolarczyk ^a, Iwona Bryndal ^b,^c,^*, Tadeusz Lis ^b

PMCID: PMC3379319 PMID: 22719517

Abstract

The asymmetric unit of the title compound, C₂₆H₂₅FN₄O, consists of two symmetry-independent molecules, denoted A and B. The conformation of each molecule is mainly determined by an intramolecular N—H⋯N hydrogen bond, which closes a six-membered ring. The dihedral angles between the pyrimidine ring and the phenyl, fluorophenyl and ethoxyphenyl rings are 15.4 (2), 28.4 (2) and 77.5 (2)°, respectively, in molecule A, and 15.9 (2), 2.7 (2) and 61.8 (2)° in molecule B. Intermolecular N—H⋯N hydrogen bonds and π–π stacking interactions between pyrimidine rings [centroid–centroid distance = 3.692 (4) Å] connect molecules A and B into dimers and C—H⋯O hydrogen bonds link the dimers into zigzag chains along [011]. The (4-ethoxyanilino)methyl group of the B molecule is disordered over two sets of sites, the occupancy factor for the major component being 0.900 (2).

Related literature

For the antibacterial activity of 6-methyl-2-phenyl-5-substituted pyrimidine derivatives, see: Cieplik et al. (1995 ▶, 2003 ▶, 2008 ▶); Pluta et al. (1996 ▶). For related structures, see: Cieplik et al. (2006 ▶); Cieplik, Pluta et al. (2011 ▶); Cieplik, Stolarczyk et al. (2011 ▶). graphic file with name e-68-o1729-scheme1.jpg

Experimental

Crystal data

C₂₆H₂₅FN₄O
M _r = 428.50
Triclinic,
a = 9.227 (4) Å
b = 10.085 (4) Å
c = 23.699 (9) Å
α = 81.92 (4)°
β = 87.52 (4)°
γ = 85.90 (4)°
V = 2176.6 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 85 K
0.55 × 0.05 × 0.05 mm

Data collection

Oxford Diffraction Xcalibur PX κ-geometry diffractometer
32959 measured reflections
18015 independent reflections
8365 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.079
S = 1.00
18015 reflections
620 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2007 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812021046/gk2480sup1.cif

e-68-o1729-sup1.cif^{(55.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812021046/gk2480Isup2.hkl

e-68-o1729-Isup2.hkl^{(880.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812021046/gk2480Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4A—H4A⋯N5A	0.894 (11)	2.093 (11)	2.8465 (17)	141.4 (10)
N5A—H5A⋯N1Bⁱ	0.879 (11)	2.265 (11)	3.1378 (19)	171.7 (11)
N4B—H4B⋯N5B	0.876 (11)	2.127 (11)	2.8460 (19)	138.9 (10)
N4B—H4B⋯N5C	0.876 (11)	2.184 (15)	2.824 (10)	129.7 (10)
N5B—H5B⋯N3Aⁱ	0.869 (13)	2.518 (13)	3.350 (2)	160.6 (11)
C46A—H46A⋯O5B	0.95	2.61	3.361 (2)	136
C23B—H23B⋯O5Aⁱⁱ	0.95	2.64	3.3437 (19)	132

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Symmetry codes: (i) Inline graphic ; (ii) .

supplementary crystallographic information

Comment

This work extends the biologial studies and structural data for 6-methyl-2-phenyl-5-substituted pyrimidine derivatives (Cieplik et al., 1995, 2003, 2008; Cieplik, Stolarczyk et al., 2011; Pluta et al., 1996) in connection with the previously characterized two polymorphic forms of N-(4-chlorophenyl)-5-[(4-chlorophenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amine (Cieplik et al., 2006) and N-(2-fluorophenyl)-5-[(4-methoxyphenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amine (Cieplik, Pluta et al., 2011).

As part of our ongoing studies of this class of derivatives, we have synthesized the title compound, namely N-(2-fluorophenyl)-5-[(4-ethoxyphenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amine, and present its structure here.

The asymmetric unit of title crystal consists of two independent molecules, hereafter referred to as A and B (C in case of disordered part attached to C5B), respectively (Fig. 1). The conformation of both molecules is dominated by the dihedral angles between the pyrimidine ring plane and those of the phenyl ring attached to the atom C2 and two other aryl rings of the (2-fluorophenyl)amino or (4-ethoxyphenyl)aminomethyl groups, attached to the atoms C4 or C5 of the pyrimidine ring, respectively (Table 1). These dihedral angles are 15.4 (2), 28.4 (2) and 77.5 (2)° in molecule A and 15.9 (2), 2.7 (2) and 61.8 (2)° in molecule B, respectively.

The molecules of title compound are linked by a combination of N—H···N and C—H···O hydrogen bonds and also the aromatic π–π stacking interactions (Table 2). The C—H···π(arene) hydrogen-bond interactions are absent. The N5 amine atom of molecule A acts as hydrogen-bond donor to the pyrimidine atom N1 of molecule B at (–x + 1, –y + 1, –z + 1). Simultaneously, the amine atom N5 of molecule B acts as hydrogen-bond donor to the pyrimidine atom N3 of molecule A at (-x + 1, -y + 1, -z + 1). This results in the formation of a dimer via a cyclic R²₂(14) ring motif. Between pyrimidine rings of molecules forming the dimer there is also an aromatic π-π stacking interaction (Fig. 2). The angle between the planes of these rings is 2.84 (8)°. The distance between the ring centroids of the molecules at (x, y, z) and (-x + 1, -y + 1, -z + 1) is 3.692 (4) Å with an interplanar spacing of 3.647 (4) Å and a centroid offset of 0.57 Å. The intermolecular N—H···N interaction was also observed in the polymorphic form of N-(4-chlorophenyl)-5-[(4-chlorophenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amine (denoted as Ia), but the propagation of such linkage generated a chain (Cieplik et al., 2006). In the structure of title compound, intermolecular C—H···O hydrogen bonds between the aryl atoms C46A and C23B and the ethoxy atom O5B and O5A at (x, y + 1, z + 1), respectively (Table 2, Fig. 2) links the molecules into extended zigzag chains which run parallel to the [011] direction and can be described by a C(15) motif.

Experimental

The title compound was obtained by adopting the procedure described previously by Cieplik et al. (2003). 4 g (0.0122 mmol) of 5-(chloromethyl)-N-(2-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine was dissolved in 50 ml of tetrahydrofuran, and 4.4 g of 4-ethoxyaniline. The reaction mixture was refluxed for 4 h with vigorous stirring, then was cooled and poured into 300 ml of water. The aqueous solution was extracted three times with chloroform (50 ml). The combined chloroform phases were dried over MgSO₄, filtered and concentrated under vacuum. The oily residue was purified by column chromatography on silica gel (200–300 mesh) using CHCl₃ as the eluent and by crystallization from methanol to give single crystals (yield: 4.1 g, 78.5%, m.p. 397–398 K).