organic compounds
5-[(4-Fluoroanilino)methyl]-6-methyl-N-(4-methylphenyl)-2-phenylpyrimidin-4-amine
aDepartment of Organic Chemistry, Medical Academy, 9 Grodzka St, 50-137 Wrocław, Poland, bFaculty of Chemistry, University of Wrocław, 14 Joliot-Curie St, 50-383 Wrocław, Poland, and cDepartment of Bioorganic Chemistry, Faculty of Engineering and Economics, Wrocław University of Economics, 118/120 Komandorska St, 53-345 Wrocław, Poland
*Correspondence e-mail: isai@o2.pl
In the title compound, C25H23FN4, the pyrimidine ring makes dihedral angles of 11.3 (2), 24.5 (2) and 70.1 (2)° with the phenyl and two benzene rings, and the molecular conformation is stabilized by an intramolecular N—H⋯N hydrogen bond with an S(6) ring motif. In the crystal, a pair of weak C—H⋯F hydrogen bonds link two molecules into an inversion dimer with an R22(16) motif. In the dimer, there is also an intermolecular π–π stacking interaction [centroid–centroid distance = 3.708 (4) Å] between the fluorinated benzene rings. The dimers are further linked by a C—H⋯π interaction, so forming a column along the c axis.
Related literature
For the antibacterial activity of 6-methyl-2-phenyl-5-substituted pyrimidine derivatives, see: Cieplik et al. (2003, 2008); Cieplik, Stolarczyk et al. (2011). For related structures, see: Cieplik et al. (2006, 2012); Cieplik, Pluta et al. (2011).
Experimental
Crystal data
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Data collection
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Refinement
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Data collection: CrysAlis CCD (Oxford Diffraction, 2007); cell CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2007); 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.
Supporting information
https://doi.org/10.1107/S160053681203783X/is5187sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S160053681203783X/is5187Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S160053681203783X/is5187Isup3.cml
The title compound was obtained by adopting the procedure described previously by Cieplik et al. (2003). 4 g (0.0125 mmol) of 5-(chloromethyl)-6-methyl-N-(4-methylphenyl)-2-phenylpyrimidin-4-amine was dissolved in 50 ml of chloroform, and 2 g of 4-fluoroaniline was added. The reaction mixture was refluxed for 4 h with vigorous stirring, then was cooled and poured into 100 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
on silica gel (200–400 mesh) using CHCl3 as the and by crystallization from methanol to give single crystals (yield: 3.74 g, 76.0%, m.p. 423–425 K).The N-bonded H atoms were found in a difference Fourier map and their positions were refined with Uiso(H) = 1.2Ueq(N). The remaining H atoms were treated as riding on their carrier atoms, with C—H distances in the range 0.95–0.99 Å, and with Uiso(H) = 1.2Ueq(C), except methyl groups where Uiso(H) = 1.5Ueq(C).
The pyrimidine core attracts attention as natural products and pharmacologically active compounds. In our ongoing research on an immunomodulating agent, we have synthesized some of 6-methyl-2-phenyl-5-substituted pyrimidine derivatives and their antibacterial and antifungal activities have been reported (Cieplik et al., 2003, 2008; Cieplik, Stolarczyk et al., 2011). As part of our study, we previously characterized structures of 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-alloxyphenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amines (Cieplik, Pluta et al., 2011; Cieplik et al., 2012). In the continuation of our search for more potent antibacterial agent, the title compound, 5-[(4-fluoroanilino)methyl]-6-methyl-2-N-(4-methylphenyl)-phenylpyrimidin-4-amine, was also prepared.
The title compound crystallizes in P1 with one molecule in the (Fig. 1). There is an intramolecular N—H···N hydrogen bond between N4—H4 and N5, which closes a six-membered ring (Table 1). The N4···N5 distance [2.982 (2) Å] is longer than its conterparts in other similar compound (Cieplik, Pluta et al., 2011; Cieplik, Stolarczyk et al., 2011), compared with 2.940 (3) Å for the polymorphic form of N-(4-chlorophenyl)-5-[(4-chlorophenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amine (denoted as Ia, Cieplik et al., 2006). The conformation of the title molecule is best defined by dihedral angles formed between the pyrimidine ring and the planes of the phenyl ring attached to atom C2 and two other aryl rings of the (4-methylphenyl)amino and the (4-fluorophenyl)aminomethyl groups attached, respectively, to atoms C4 and C5 of the pyrimidine ring. These dihedral angles are 11.3 (2), 24.5 (2) and 70.1 (2)°, respectively.
The N—H···N hydrogen bonds involving the amine atom N5 as a donor are commonly observed in previously described structures (Cieplik et al., 2006, 2012; Cieplik, Pluta et al., 2011). However, in the structure of the title compound, atom H5 is not involved in any interactions. The π and π–π stacking interactions. The molecules are linked by a C—H···F interaction involving atom C57 as a donor and atom F5 (-x, -y + 1, -z + 2) as an acceptor. This results in the formation of an inversion dimer with an R22(16) ring motif. Between aryl rings of (4-fluorophenyl)aminomethyl groups of molecules forming the dimer there is also an aromatic π–π stacking interaction. The distance between the centroids of C51–C56 ring at (x, y, z) and (-x, -y + 1, -z + 2) is 3.708 (4) Å, and the and the centroid offset are 3.429 (4) Å and 1.41 Å, respectively. Additionally, the C57—H572 group acts as a donor of C—H···π(arene) interaction to the pyrimidine N1/C2/N3/C4–C6 ring (-x, -y + 1, -z + 1). The combination of C—H···F and C—H···π interactions generates a column running along the [001] direction (Fig. 2).
of the title compound is stabilized by weak C—H···F, C—H···For the antibacterial activity of 6-methyl-2-phenyl-5-substituted pyrimidine derivatives, see: Cieplik et al. (2003, 2008); Cieplik, Stolarczyk et al. (2011). For related structures, see: Cieplik et al. (2006, 2012); Cieplik, Pluta et al. (2011).
Data collection: CrysAlis CCD (Oxford Diffraction, 2007); cell
CrysAlis CCD (Oxford Diffraction, 2007); data reduction: CrysAlis RED (Oxford Diffraction, 2007); 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 (Sheldrick, 2008).C25H23FN4 | Z = 2 |
Mr = 398.47 | F(000) = 420 |
Triclinic, P1 | Dx = 1.304 Mg m−3 |
Hall symbol: -P 1 | Melting point: 424 K |
a = 8.306 (4) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 10.070 (4) Å | Cell parameters from 9708 reflections |
c = 12.234 (5) Å | θ = 4.8–35.0° |
α = 88.78 (4)° | µ = 0.09 mm−1 |
β = 89.12 (4)° | T = 85 K |
γ = 82.75 (5)° | Needle block, light yellow |
V = 1014.8 (8) Å3 | 0.36 × 0.18 × 0.14 mm |
Oxford Xcalibur PX diffractometer with Onyx CCD | 4334 reflections with I > 2σ(I) |
Radiation source: normal-focus sealed tube | Rint = 0.033 |
Graphite monochromator | θmax = 35.0°, θmin = 4.8° |
φ and ω scans | h = −11→13 |
17245 measured reflections | k = −15→16 |
8461 independent reflections | l = −19→19 |
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)] = 0.049 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.093 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | w = 1/[σ2(Fo2) + (0.030P)2] where P = (Fo2 + 2Fc2)/3 |
8461 reflections | (Δ/σ)max = 0.001 |
279 parameters | Δρmax = 0.38 e Å−3 |
0 restraints | Δρmin = −0.31 e Å−3 |
C25H23FN4 | γ = 82.75 (5)° |
Mr = 398.47 | V = 1014.8 (8) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.306 (4) Å | Mo Kα radiation |
b = 10.070 (4) Å | µ = 0.09 mm−1 |
c = 12.234 (5) Å | T = 85 K |
α = 88.78 (4)° | 0.36 × 0.18 × 0.14 mm |
β = 89.12 (4)° |
Oxford Xcalibur PX diffractometer with Onyx CCD | 4334 reflections with I > 2σ(I) |
17245 measured reflections | Rint = 0.033 |
8461 independent reflections |
R[F2 > 2σ(F2)] = 0.049 | 0 restraints |
wR(F2) = 0.093 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | Δρmax = 0.38 e Å−3 |
8461 reflections | Δρmin = −0.31 e Å−3 |
279 parameters |
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 | ||
N1 | 0.10445 (10) | 0.79035 (8) | 0.41851 (7) | 0.01576 (19) | |
C2 | 0.20919 (12) | 0.71729 (10) | 0.35266 (8) | 0.0140 (2) | |
C21 | 0.25288 (12) | 0.78216 (10) | 0.24794 (8) | 0.0146 (2) | |
C22 | 0.16726 (13) | 0.90318 (10) | 0.21321 (9) | 0.0202 (2) | |
H22 | 0.0795 | 0.9441 | 0.2565 | 0.024* | |
C23 | 0.20876 (14) | 0.96450 (11) | 0.11618 (9) | 0.0249 (3) | |
H23 | 0.1488 | 1.0466 | 0.0930 | 0.030* | |
C24 | 0.33733 (13) | 0.90659 (11) | 0.05289 (9) | 0.0232 (3) | |
H24 | 0.3651 | 0.9485 | −0.0139 | 0.028* | |
C25 | 0.42520 (13) | 0.78748 (11) | 0.08714 (9) | 0.0223 (2) | |
H25 | 0.5144 | 0.7482 | 0.0443 | 0.027* | |
C26 | 0.38325 (13) | 0.72516 (10) | 0.18414 (8) | 0.0185 (2) | |
H26 | 0.4438 | 0.6432 | 0.2071 | 0.022* | |
N3 | 0.28386 (10) | 0.59329 (8) | 0.37320 (7) | 0.01478 (18) | |
C4 | 0.25062 (12) | 0.53878 (10) | 0.47043 (8) | 0.0142 (2) | |
N4 | 0.32494 (10) | 0.41352 (8) | 0.49809 (7) | 0.01661 (19) | |
H4 | 0.3281 (13) | 0.3965 (11) | 0.5680 (9) | 0.020* | |
C41 | 0.42036 (12) | 0.31806 (10) | 0.43411 (8) | 0.0152 (2) | |
C42 | 0.50900 (12) | 0.21177 (10) | 0.49004 (9) | 0.0173 (2) | |
H42 | 0.5058 | 0.2087 | 0.5677 | 0.021* | |
C43 | 0.60151 (12) | 0.11080 (10) | 0.43404 (9) | 0.0191 (2) | |
H43 | 0.6628 | 0.0406 | 0.4741 | 0.023* | |
C44 | 0.60703 (12) | 0.10953 (10) | 0.32041 (9) | 0.0197 (2) | |
C47 | 0.70423 (14) | −0.00354 (12) | 0.26030 (10) | 0.0290 (3) | |
H473 | 0.7735 | −0.0592 | 0.3120 | 0.043* | |
H472 | 0.7721 | 0.0333 | 0.2040 | 0.043* | |
H471 | 0.6303 | −0.0582 | 0.2259 | 0.043* | |
C45 | 0.51525 (13) | 0.21488 (10) | 0.26533 (9) | 0.0207 (2) | |
H45 | 0.5153 | 0.2158 | 0.1877 | 0.025* | |
C46 | 0.42383 (12) | 0.31843 (10) | 0.31983 (8) | 0.0183 (2) | |
H46 | 0.3638 | 0.3893 | 0.2797 | 0.022* | |
C5 | 0.14131 (12) | 0.60620 (10) | 0.54702 (8) | 0.0146 (2) | |
C57 | 0.09810 (12) | 0.53600 (11) | 0.65109 (8) | 0.0181 (2) | |
H571 | 0.0099 | 0.5926 | 0.6897 | 0.022* | |
H572 | 0.0578 | 0.4507 | 0.6332 | 0.022* | |
N5 | 0.23857 (11) | 0.50820 (9) | 0.72329 (7) | 0.0198 (2) | |
H5 | 0.2891 (13) | 0.5843 (11) | 0.7280 (9) | 0.024* | |
C51 | 0.20720 (12) | 0.45585 (10) | 0.82908 (8) | 0.0171 (2) | |
C52 | 0.11769 (13) | 0.34826 (11) | 0.84171 (9) | 0.0210 (2) | |
H52 | 0.0775 | 0.3099 | 0.7790 | 0.025* | |
C53 | 0.08662 (13) | 0.29654 (11) | 0.94486 (9) | 0.0215 (2) | |
H53 | 0.0245 | 0.2239 | 0.9535 | 0.026* | |
F5 | 0.11487 (8) | 0.30347 (6) | 1.13620 (5) | 0.02904 (17) | |
C54 | 0.14766 (13) | 0.35259 (10) | 1.03413 (8) | 0.0197 (2) | |
C55 | 0.23850 (13) | 0.45671 (11) | 1.02485 (9) | 0.0228 (2) | |
H55 | 0.2808 | 0.4927 | 1.0880 | 0.027* | |
C56 | 0.26771 (13) | 0.50879 (11) | 0.92156 (9) | 0.0215 (2) | |
H56 | 0.3298 | 0.5815 | 0.9140 | 0.026* | |
C6 | 0.07285 (12) | 0.73425 (10) | 0.51736 (8) | 0.0154 (2) | |
C61 | −0.03893 (13) | 0.82245 (11) | 0.59100 (9) | 0.0211 (2) | |
H611 | −0.1495 | 0.7992 | 0.5855 | 0.032* | |
H612 | −0.0375 | 0.9164 | 0.5687 | 0.032* | |
H613 | −0.0025 | 0.8093 | 0.6667 | 0.032* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0161 (4) | 0.0172 (4) | 0.0143 (4) | −0.0035 (3) | 0.0008 (4) | 0.0001 (4) |
C2 | 0.0141 (5) | 0.0158 (5) | 0.0124 (5) | −0.0035 (4) | −0.0012 (4) | 0.0000 (4) |
C21 | 0.0174 (5) | 0.0145 (5) | 0.0125 (5) | −0.0040 (4) | −0.0001 (4) | −0.0001 (4) |
C22 | 0.0250 (6) | 0.0162 (5) | 0.0187 (6) | 0.0000 (4) | 0.0028 (5) | 0.0003 (4) |
C23 | 0.0348 (7) | 0.0175 (6) | 0.0213 (6) | 0.0001 (5) | 0.0004 (5) | 0.0055 (5) |
C24 | 0.0314 (7) | 0.0247 (6) | 0.0150 (6) | −0.0107 (5) | 0.0014 (5) | 0.0041 (5) |
C25 | 0.0221 (6) | 0.0271 (6) | 0.0177 (6) | −0.0042 (5) | 0.0058 (5) | 0.0010 (5) |
C26 | 0.0199 (6) | 0.0186 (5) | 0.0162 (5) | −0.0006 (4) | 0.0014 (4) | 0.0017 (4) |
N3 | 0.0156 (4) | 0.0157 (4) | 0.0135 (4) | −0.0038 (3) | 0.0003 (3) | 0.0012 (3) |
C4 | 0.0147 (5) | 0.0149 (5) | 0.0138 (5) | −0.0042 (4) | −0.0007 (4) | −0.0001 (4) |
N4 | 0.0215 (5) | 0.0166 (5) | 0.0109 (4) | 0.0002 (4) | 0.0017 (4) | 0.0023 (4) |
C41 | 0.0152 (5) | 0.0138 (5) | 0.0169 (5) | −0.0040 (4) | 0.0016 (4) | 0.0005 (4) |
C42 | 0.0192 (5) | 0.0178 (5) | 0.0156 (5) | −0.0052 (4) | −0.0016 (4) | 0.0012 (4) |
C43 | 0.0176 (5) | 0.0160 (5) | 0.0236 (6) | −0.0022 (4) | −0.0036 (5) | 0.0017 (4) |
C44 | 0.0181 (5) | 0.0182 (5) | 0.0234 (6) | −0.0042 (4) | 0.0015 (5) | −0.0026 (5) |
C47 | 0.0305 (7) | 0.0249 (6) | 0.0308 (7) | 0.0006 (5) | −0.0008 (5) | −0.0067 (5) |
C45 | 0.0249 (6) | 0.0218 (6) | 0.0159 (6) | −0.0048 (5) | 0.0018 (5) | −0.0018 (4) |
C46 | 0.0210 (6) | 0.0180 (5) | 0.0156 (5) | −0.0016 (4) | −0.0014 (4) | 0.0028 (4) |
C5 | 0.0149 (5) | 0.0180 (5) | 0.0115 (5) | −0.0040 (4) | 0.0002 (4) | 0.0008 (4) |
C57 | 0.0190 (6) | 0.0212 (5) | 0.0137 (5) | −0.0020 (4) | 0.0031 (4) | 0.0019 (4) |
N5 | 0.0186 (5) | 0.0262 (5) | 0.0154 (5) | −0.0067 (4) | −0.0006 (4) | 0.0043 (4) |
C51 | 0.0148 (5) | 0.0206 (5) | 0.0148 (5) | 0.0018 (4) | 0.0020 (4) | 0.0033 (4) |
C52 | 0.0225 (6) | 0.0257 (6) | 0.0151 (6) | −0.0042 (5) | −0.0026 (5) | 0.0000 (5) |
C53 | 0.0222 (6) | 0.0212 (6) | 0.0210 (6) | −0.0032 (4) | 0.0015 (5) | 0.0044 (5) |
F5 | 0.0398 (4) | 0.0301 (4) | 0.0151 (3) | 0.0018 (3) | 0.0043 (3) | 0.0068 (3) |
C54 | 0.0239 (6) | 0.0205 (6) | 0.0122 (5) | 0.0055 (4) | 0.0039 (4) | 0.0053 (4) |
C55 | 0.0299 (6) | 0.0221 (6) | 0.0155 (6) | 0.0007 (5) | −0.0028 (5) | −0.0020 (5) |
C56 | 0.0243 (6) | 0.0195 (6) | 0.0209 (6) | −0.0030 (4) | 0.0002 (5) | 0.0000 (5) |
C6 | 0.0137 (5) | 0.0188 (5) | 0.0140 (5) | −0.0035 (4) | 0.0001 (4) | −0.0011 (4) |
C61 | 0.0224 (6) | 0.0212 (6) | 0.0190 (6) | −0.0009 (4) | 0.0057 (5) | −0.0012 (4) |
N1—C2 | 1.3377 (14) | C47—H473 | 0.9800 |
N1—C6 | 1.3598 (14) | C47—H472 | 0.9800 |
C2—N3 | 1.3427 (14) | C47—H471 | 0.9800 |
C2—C21 | 1.4865 (15) | C45—C46 | 1.3867 (16) |
C21—C22 | 1.3928 (16) | C45—H45 | 0.9500 |
C21—C26 | 1.3955 (16) | C46—H46 | 0.9500 |
C22—C23 | 1.3853 (16) | C5—C6 | 1.3853 (15) |
C22—H22 | 0.9500 | C5—C57 | 1.5037 (15) |
C23—C24 | 1.3845 (17) | C57—N5 | 1.4692 (15) |
C23—H23 | 0.9500 | C57—H571 | 0.9900 |
C24—C25 | 1.3835 (16) | C57—H572 | 0.9900 |
C24—H24 | 0.9500 | N5—C51 | 1.4199 (14) |
C25—C26 | 1.3908 (15) | N5—H5 | 0.922 (11) |
C25—H25 | 0.9500 | C51—C56 | 1.3884 (16) |
C26—H26 | 0.9500 | C51—C52 | 1.3940 (16) |
N3—C4 | 1.3389 (13) | C52—C53 | 1.3879 (15) |
C4—N4 | 1.3705 (14) | C52—H52 | 0.9500 |
C4—C5 | 1.4173 (15) | C53—C54 | 1.3726 (17) |
N4—C41 | 1.4091 (15) | C53—H53 | 0.9500 |
N4—H4 | 0.869 (11) | F5—C54 | 1.3694 (13) |
C41—C42 | 1.3932 (15) | C54—C55 | 1.3688 (16) |
C41—C46 | 1.3980 (15) | C55—C56 | 1.3876 (16) |
C42—C43 | 1.3820 (16) | C55—H55 | 0.9500 |
C42—H42 | 0.9500 | C56—H56 | 0.9500 |
C43—C44 | 1.3905 (16) | C6—C61 | 1.5043 (16) |
C43—H43 | 0.9500 | C61—H611 | 0.9800 |
C44—C45 | 1.3935 (16) | C61—H612 | 0.9800 |
C44—C47 | 1.5081 (17) | C61—H613 | 0.9800 |
C2—N1—C6 | 116.60 (9) | H472—C47—H471 | 109.5 |
N1—C2—N3 | 126.73 (9) | C46—C45—C44 | 122.35 (10) |
N1—C2—C21 | 116.67 (9) | C46—C45—H45 | 118.8 |
N3—C2—C21 | 116.55 (10) | C44—C45—H45 | 118.8 |
C22—C21—C26 | 118.70 (10) | C45—C46—C41 | 119.72 (10) |
C22—C21—C2 | 120.54 (10) | C45—C46—H46 | 120.1 |
C26—C21—C2 | 120.73 (10) | C41—C46—H46 | 120.1 |
C23—C22—C21 | 120.65 (11) | C6—C5—C4 | 116.38 (9) |
C23—C22—H22 | 119.7 | C6—C5—C57 | 123.37 (10) |
C21—C22—H22 | 119.7 | C4—C5—C57 | 120.15 (9) |
C24—C23—C22 | 120.24 (11) | N5—C57—C5 | 111.50 (9) |
C24—C23—H23 | 119.9 | N5—C57—H571 | 109.3 |
C22—C23—H23 | 119.9 | C5—C57—H571 | 109.3 |
C25—C24—C23 | 119.80 (11) | N5—C57—H572 | 109.3 |
C25—C24—H24 | 120.1 | C5—C57—H572 | 109.3 |
C23—C24—H24 | 120.1 | H571—C57—H572 | 108.0 |
C24—C25—C26 | 120.13 (11) | C51—N5—C57 | 116.18 (9) |
C24—C25—H25 | 119.9 | C51—N5—H5 | 110.7 (7) |
C26—C25—H25 | 119.9 | C57—N5—H5 | 109.2 (7) |
C25—C26—C21 | 120.47 (10) | C56—C51—C52 | 118.76 (10) |
C25—C26—H26 | 119.8 | C56—C51—N5 | 120.78 (10) |
C21—C26—H26 | 119.8 | C52—C51—N5 | 120.45 (10) |
C4—N3—C2 | 116.05 (9) | C53—C52—C51 | 120.76 (11) |
N3—C4—N4 | 119.36 (10) | C53—C52—H52 | 119.6 |
N3—C4—C5 | 122.42 (9) | C51—C52—H52 | 119.6 |
N4—C4—C5 | 118.22 (9) | C54—C53—C52 | 118.55 (11) |
C4—N4—C41 | 130.21 (9) | C54—C53—H53 | 120.7 |
C4—N4—H4 | 114.2 (7) | C52—C53—H53 | 120.7 |
C41—N4—H4 | 114.6 (7) | C55—C54—F5 | 118.87 (10) |
C42—C41—C46 | 118.41 (10) | C55—C54—C53 | 122.38 (10) |
C42—C41—N4 | 116.76 (10) | F5—C54—C53 | 118.75 (10) |
C46—C41—N4 | 124.71 (10) | C54—C55—C56 | 118.76 (11) |
C43—C42—C41 | 120.88 (10) | C54—C55—H55 | 120.6 |
C43—C42—H42 | 119.6 | C56—C55—H55 | 120.6 |
C41—C42—H42 | 119.6 | C55—C56—C51 | 120.78 (11) |
C42—C43—C44 | 121.60 (10) | C55—C56—H56 | 119.6 |
C42—C43—H43 | 119.2 | C51—C56—H56 | 119.6 |
C44—C43—H43 | 119.2 | N1—C6—C5 | 121.77 (10) |
C43—C44—C45 | 117.02 (10) | N1—C6—C61 | 114.84 (9) |
C43—C44—C47 | 121.06 (10) | C5—C6—C61 | 123.38 (9) |
C45—C44—C47 | 121.89 (10) | C6—C61—H611 | 109.5 |
C44—C47—H473 | 109.5 | C6—C61—H612 | 109.5 |
C44—C47—H472 | 109.5 | H611—C61—H612 | 109.5 |
H473—C47—H472 | 109.5 | C6—C61—H613 | 109.5 |
C44—C47—H471 | 109.5 | H611—C61—H613 | 109.5 |
H473—C47—H471 | 109.5 | H612—C61—H613 | 109.5 |
C6—N1—C2—N3 | 1.40 (15) | C44—C45—C46—C41 | −0.85 (16) |
C6—N1—C2—C21 | −175.79 (9) | C42—C41—C46—C45 | −0.49 (14) |
N1—C2—C21—C22 | −10.66 (14) | N4—C41—C46—C45 | −176.22 (9) |
N3—C2—C21—C22 | 171.85 (9) | N3—C4—C5—C6 | −1.67 (14) |
N1—C2—C21—C26 | 167.46 (9) | N4—C4—C5—C6 | 177.97 (9) |
N3—C2—C21—C26 | −10.03 (14) | N3—C4—C5—C57 | 175.03 (9) |
C26—C21—C22—C23 | 1.20 (16) | N4—C4—C5—C57 | −5.32 (14) |
C2—C21—C22—C23 | 179.36 (10) | C6—C5—C57—N5 | −116.78 (12) |
C21—C22—C23—C24 | −0.62 (17) | C4—C5—C57—N5 | 66.75 (13) |
C22—C23—C24—C25 | −0.41 (17) | C5—C57—N5—C51 | 173.10 (9) |
C23—C24—C25—C26 | 0.82 (17) | C57—N5—C51—C56 | −132.72 (11) |
C24—C25—C26—C21 | −0.22 (16) | C57—N5—C51—C52 | 48.62 (14) |
C22—C21—C26—C25 | −0.78 (15) | C56—C51—C52—C53 | 1.29 (15) |
C2—C21—C26—C25 | −178.94 (10) | N5—C51—C52—C53 | 179.98 (10) |
N1—C2—N3—C4 | −0.86 (15) | C51—C52—C53—C54 | −0.79 (16) |
C21—C2—N3—C4 | 176.34 (9) | C52—C53—C54—C55 | −0.40 (16) |
C2—N3—C4—N4 | −178.66 (9) | C52—C53—C54—F5 | 178.85 (9) |
C2—N3—C4—C5 | 0.98 (14) | F5—C54—C55—C56 | −178.21 (9) |
N3—C4—N4—C41 | −9.67 (16) | C53—C54—C55—C56 | 1.04 (16) |
C5—C4—N4—C41 | 170.67 (10) | C54—C55—C56—C51 | −0.50 (16) |
C4—N4—C41—C42 | 166.24 (10) | C52—C51—C56—C55 | −0.64 (15) |
C4—N4—C41—C46 | −17.97 (17) | N5—C51—C56—C55 | −179.32 (10) |
C46—C41—C42—C43 | 1.63 (14) | C2—N1—C6—C5 | −2.09 (14) |
N4—C41—C42—C43 | 177.70 (9) | C2—N1—C6—C61 | 177.06 (9) |
C41—C42—C43—C44 | −1.47 (15) | C4—C5—C6—N1 | 2.23 (14) |
C42—C43—C44—C45 | 0.12 (15) | C57—C5—C6—N1 | −174.35 (9) |
C42—C43—C44—C47 | −178.02 (10) | C4—C5—C6—C61 | −176.85 (9) |
C43—C44—C45—C46 | 1.03 (15) | C57—C5—C6—C61 | 6.56 (15) |
C47—C44—C45—C46 | 179.16 (10) |
Cg1 is the centroid of the N1/C2/N3/C4–C6 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···N5 | 0.869 (11) | 2.294 (11) | 2.9820 (18) | 136.2 (9) |
C57—H571···F5i | 0.99 | 2.54 | 3.440 (2) | 151 |
C57—H572···Cg1ii | 0.99 | 2.60 | 3.467 (7) | 147 |
Symmetry codes: (i) −x, −y+1, −z+2; (ii) −x, −y+1, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C25H23FN4 |
Mr | 398.47 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 85 |
a, b, c (Å) | 8.306 (4), 10.070 (4), 12.234 (5) |
α, β, γ (°) | 88.78 (4), 89.12 (4), 82.75 (5) |
V (Å3) | 1014.8 (8) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.36 × 0.18 × 0.14 |
Data collection | |
Diffractometer | Oxford Xcalibur PX diffractometer with Onyx CCD |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 17245, 8461, 4334 |
Rint | 0.033 |
(sin θ/λ)max (Å−1) | 0.807 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.049, 0.093, 1.00 |
No. of reflections | 8461 |
No. of parameters | 279 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.38, −0.31 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2007), CrysAlis RED (Oxford Diffraction, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008).
Cg1 is the centroid of the N1/C2/N3/C4–C6 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···N5 | 0.869 (11) | 2.294 (11) | 2.9820 (18) | 136.2 (9) |
C57—H571···F5i | 0.99 | 2.54 | 3.440 (2) | 151 |
C57—H572···Cg1ii | 0.99 | 2.60 | 3.467 (7) | 147 |
Symmetry codes: (i) −x, −y+1, −z+2; (ii) −x, −y+1, −z+1. |
References
Cieplik, J., Pluta, J., Bryndal, I. & Lis, T. (2006). Acta Cryst. C62, o259–o261. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Cieplik, J., Pluta, J., Bryndal, I. & Lis, T. (2011). Acta Cryst. E67, o3162. Web of Science CSD CrossRef IUCr Journals Google Scholar
Cieplik, J., Pluta, J. & Gubrynowicz, O. (2003). Boll. Chim. Farm. 142, 146–150. PubMed CAS Google Scholar
Cieplik, J., Raginia, M., Pluta, J., Gubrynowicz, O., Bryndal, I. & Lis, T. (2008). Acta Pol. Pharm. Drug Res. 65, 427–434. CAS Google Scholar
Cieplik, J., Stolarczyk, M., Bryndal, I. & Lis, T. (2012). Acta Cryst. E68, o1729–o1730. CSD CrossRef CAS IUCr Journals Google Scholar
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Oxford Diffraction (2007). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abington, England. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
The pyrimidine core attracts attention as natural products and pharmacologically active compounds. In our ongoing research on an immunomodulating agent, we have synthesized some of 6-methyl-2-phenyl-5-substituted pyrimidine derivatives and their antibacterial and antifungal activities have been reported (Cieplik et al., 2003, 2008; Cieplik, Stolarczyk et al., 2011). As part of our study, we previously characterized structures of 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-alloxyphenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amines (Cieplik, Pluta et al., 2011; Cieplik et al., 2012). In the continuation of our search for more potent antibacterial agent, the title compound, 5-[(4-fluoroanilino)methyl]-6-methyl-2-N-(4-methylphenyl)-phenylpyrimidin-4-amine, was also prepared.
The title compound crystallizes in P1 space group, with one molecule in the asymmetric unit (Fig. 1). There is an intramolecular N—H···N hydrogen bond between N4—H4 and N5, which closes a six-membered ring (Table 1). The N4···N5 distance [2.982 (2) Å] is longer than its conterparts in other similar compound (Cieplik, Pluta et al., 2011; Cieplik, Stolarczyk et al., 2011), compared with 2.940 (3) Å for the polymorphic form of N-(4-chlorophenyl)-5-[(4-chlorophenyl)aminomethyl]-6-methyl-2-phenylpyrimidin-4-amine (denoted as Ia, Cieplik et al., 2006). The conformation of the title molecule is best defined by dihedral angles formed between the pyrimidine ring and the planes of the phenyl ring attached to atom C2 and two other aryl rings of the (4-methylphenyl)amino and the (4-fluorophenyl)aminomethyl groups attached, respectively, to atoms C4 and C5 of the pyrimidine ring. These dihedral angles are 11.3 (2), 24.5 (2) and 70.1 (2)°, respectively.
The N—H···N hydrogen bonds involving the amine atom N5 as a donor are commonly observed in previously described structures (Cieplik et al., 2006, 2012; Cieplik, Pluta et al., 2011). However, in the structure of the title compound, atom H5 is not involved in any interactions. The crystal structure of the title compound is stabilized by weak C—H···F, C—H···π and π–π stacking interactions. The molecules are linked by a C—H···F interaction involving atom C57 as a donor and atom F5 (-x, -y + 1, -z + 2) as an acceptor. This results in the formation of an inversion dimer with an R22(16) ring motif. Between aryl rings of (4-fluorophenyl)aminomethyl groups of molecules forming the dimer there is also an aromatic π–π stacking interaction. The distance between the centroids of C51–C56 ring at (x, y, z) and (-x, -y + 1, -z + 2) is 3.708 (4) Å, and the interplanar spacing and the centroid offset are 3.429 (4) Å and 1.41 Å, respectively. Additionally, the C57—H572 group acts as a donor of C—H···π(arene) interaction to the pyrimidine N1/C2/N3/C4–C6 ring (-x, -y + 1, -z + 1). The combination of C—H···F and C—H···π interactions generates a column running along the [001] direction (Fig. 2).