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

The title compound (C18H13ClF3N3O) were synthesized and recrystallized from CH3OH. The compound was characterized by NMR, MS, HRMS, and X-ray diffraction. The compound crystallized in the monoclinic space group with (14), (2), (3)？ , (3), , (5)？ , and for 1933 observed reflections with 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 , B3LYP/6-31G . The full geometry optimization was carried out using 6-31G 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. 1. Introduction Heterocyclic compounds are commonly used as scaffolds on which pharmacophores are arranged to provide potent and selective medicines or pesticides [1–3]. Usually, pyrimidine and their derivatives have been proved to be effective biological activities [4]. Some of them had been developed to commercial agrochemicals and medicines, such as Sulfometuron-Methyl, Bensulfuron-Methyl, Chlorimuron-Ethyl, Pyrazosulfuron-Ethyl, Nicosulfuron, Flazasulfuron, Azimsulfuron, Primisulfuron-Methyl, Amidosulfuron, Flumetsulam, Metosulam, diclosulam, florasulam, Penoxsulam, and 5-FU. Also phenoxy group always exhibited diversity activities, such as antibacterial, antifungal, anti-HIV, antioxidant, and anti-inflammatory activities [5, 6]. 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 NMR, FTIR, MS, and HRMS. The single crystal structure of the title compound was determined by X-ray diffraction. 2. 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, SnCl2 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 (K2CO3, NaOH, Et3N, 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 4-methylbenzenesulfonic acid. The proton magnetic