Synthesis , Crystal Structure , and Theoretical Studies of N-( 4-( ( 4-chlorobenzyl ) oxy ) phenyl )-4-( trifluoromethyl ) pyrimidin-2-amine

The title compound (C 18 H 13 ClF 3 N 3 O) were synthesized and recrystallized from CH 3 OH.The compound was characterized by 1H NMR, MS, HRMS, and X-ray diffraction. The compound crystallized in the monoclinic space group P2(1)/n with a = 8.2354 (14), b = 12.686 (2), c = 16.633 (3) Å, α = 90, β = 97.951 (3), γ = 90, V = 1721.0 (5) Å3, Z = 4, and R = 0.0376 for 1933 observed reflections with I > 2σ(I). X-ray analysis reveals that intermolecular N–H⋅ ⋅ ⋅N interactions exist in the adjacent molecules. Theoretical calculation of the title compound was carried out with HF/6-31G (d,p), B3LYP/6-31G (d,p). The full geometry optimization was carried out using 6-31G (d,p) basis set and the frontier orbital energy. The optimized geometric bond lengths and bond angles obtained by using HF and DFT (B3LYP) showed the best agreement with the experimental data.

In view of these facts mentioned above, and also as a part of our work on the synthesis of bioactive lead compounds for drug discover, the title compounds were designed, synthesized, and characterized by 1 H NMR, FTIR, MS, and HRMS.The single crystal structure of the title compound was determined by X-ray diffraction.

Results and Discussion
2.1.Synthesis and Spectra.The 1-chloro-4-((4-nitrophenoxy)methyl)benzene was synthesized easily from the starting materials 4-nitrophenol and 1-chloro-4-(chloromethyl)benzene with mild condition.The 1-chloro-4-((4-nitrophenoxy)methyl)benzene was reduced by Raney Ni to regarding 4-((4-chlorobenzyl)oxy)aniline.We also used Fe/HCl, SnCl 2 to reduce, but the yield and purity are low.In the process of title compound, some conditions were tried, but the reaction can not work, such as different base (K 2 CO 3 , NaOH, Et 3 N, NaH), different solvent (EtOH, THF, Acetone), and different reaction temperature.Surprisingly, it is reported that acid can synthesize N-phenylpyrimidin-2-amine. So the title compound was synthesized under the catalyst 4methylbenzenesulfonic acid.The proton magnetic resonance spectra of the title compound have been recorded in CDCl 3 .The NH proton of chemical shift is at  7.24 as a singlet.The signal of CH 2 protons was observed at  5.02 ppm as a singlet.The chemical shifts at 8.58 and 6.97 ppm are the proton of pyrimidine.The ESI-MS spectrum showed that the m/z of  1 and 2. The molecular structure of the title compound is shown in Figure 1.The molecular packing of the molecule is shown in Figure 2. The hydrogenbond distances ( Á) of the title compound are listed in Table 3.

D-H⋅
The title compound has an extensive network of hydrogen bonding.In the  plane, they are linked together by N-H⋅ ⋅ ⋅N hydrogen bonds.This hydrogen-bonding sequence is repeated to form a ring.The ring is shaped like a decagon and has two N1 and two H1 atoms at the vertices, leading to a hydrogen-bond network defining cyclic motifs denoted  2 2 (8).The slight discrepancy of crystal structures is probably the consequence of the weakness of this hydrogen bond and van der Waals interactions in the solid-state structure.

Molecular Total Energies and Frontier Orbital Energy
Analysis.Molecular total energy and frontier orbital energy levels are listed in Table 4.It is seen that the results of HF and MP2 methods have good consistency.Energy gap between HOMO and LUMO calculated by B3LYP is smaller than those calculated by HF.
The HOMO and LUMO levels of title compound were deduced using DFT method, as shown in Figure 3.The HOMO and LUMO diagrams of title compound show that the compound is likely to exhibit an efficient electron transfer from the pyrimidine ring of HOMO to the whole pyrimidine molecular skeleton of LUMO if electronic transitions occur.The HOMO for the title compound is mainly localized at the benzene ring and pyrimidine ring, whereas the LUMO is localized at CF 3 group, benzene ring, and pyrimidine ring.Therefore, when electrons transfer from HOMO to LUMO, the electron density significantly decreases in the electrondonating benzene ring system, accompanied by an increase in the electron density of the electron accepting the whole molecule system.

Instruments.
Melting points were determined using an X-4 apparatus and uncorrected. 1H NMR spectra were measured on a Bruker AV-400 instrument using TMS as an internal standard and CDCl 3 as the solvent.Mass spectra were recorded on a Thermo Finnigan LCQ Advantage LC/mass detector instrument.Elemental analysis was performed on a Vario EL elemental analyzer.All the reagents are of analytical grade or freshly prepared before use.

Theoretical Calculations.
According to the above crystal structure, a crystal unit was selected as the initial structure, while HF/6-31G (d, p), DFT-B3LYP/6-31G (d, p), and MP2/6-31G (d, p) methods in Gaussian 03 package [7] were used to optimize the structure of the title compound.Vibration analysis showed that the optimized structures were in accordance with the minimum points on the potential energy surfaces, which means no virtual frequencies, proving that the obtained optimized structures were stable.All the convergent precisions were the system default values, and all the calculations were carried out on the Nankai Stars supercomputer at Nankai University.

General
Procedure.The title compounds were synthesized according to the route shown in Scheme 1, and the yields were not optimized.The pyrimidine 4 was synthesized according to the references.

Figure 1 :Figure 2 :
Figure 1: The molecular structure of the title compound.

Scheme 1 :
Scheme 1: The synthetic route of title compound.

Table 1 :
Selected bond lengths [ Å] and theoretical calculations for the title compound.

Table 2 :
Selected bond angles [ ∘ ] and theoretical calculations for the title compound.

Table 4 :
Total energy and frontier orbital energy.

Table 5 :
Crystal structure and data refinement parameters.