Adding a certain compound to certain chemical reactions, such as: 22236-10-8, name is 4-(Difluoromethoxy)aniline, belongs to ethers-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 22236-10-8, Quality Control of 4-(Difluoromethoxy)aniline
General procedure: Step-1:4-amino-2,6-dichloro pyrimidine: 2,4,6-trichloro pyrimidine (1.0 mmol) in ethanol (5 mL) was treated with an aromatic amine (1.1 mmol) in the presence of Na2CO3 (1.1 mmol) at rt. The mixture was stirred at reflux for 2-4 h until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, an equal volume of water was added with cooling. The resulting white precipitate was filtered, washed with water, and dried in vacuum over night to yield 4-substituted 2,6-dichloro pyrimidine. In case of no precipitation, ethanol was removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 4-amino-2,6-dichloro pyrimidines in 85-95% yield. Step-2: 2,4-diamino-6-chloropyrimidine: 4-amino-2,6-dichloro pyrimidine (1.0 mmol) prepared from the above procedure was treated with another aliphatic amine or aromatic amine (2.0 mmol) in the presence of DIEPA (5.0 mmol) in n-BuOH (5 mL) at rt. For an aliphatic amine the reaction mixture was stirred at rt for overnight. For an aromatic amine the reaction mixture was refluxed for 24-72 h or placed in microwave (150 C, 2-7 h) until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, solvents were removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography (EtOAc/hexane) to afford the 2,4-diammino-6-chloropyrimidines in 85-90% yield. Step-3: 2,4,6-triaminopyrimidine: 2,4-diamino-6-chloropyrimidine (1.0 mmol) prepared from the above procedure was treated with another suitable aliphatic amine or aromatic amine (3.0 mmol). For an aliphatic amine, 2,4-diamino-6-chloropyrimidine (1.0 mmol) was treated with aliphatic amine (3.0 mmol) and DIPEA (5.0 mmol) in n-BuOH (5 mL) and placed in microwave (150 C) for 3-7 h. After the completion of the reaction (monitored by TLC), solvents were removed and the residue was dissolved in EtOAc. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 2,4,6-triaminopyrimidines 90-95% yield. For aromatic amine; 2,4-diamino-6-chloropyrimidine (1.0 equiv) was dissolved in dioxane under argon and to that were added Pd2(dba)3 (10 mol %), Xantphos (10 mol %), aromatic amine (1.2 mmol), t-BuOK (1.2 mmol). The resulting solution was degassed with argon for 5 min and heated to 85 C for overnight. The reaction mixture was filtered through a pad of celite, washed with CH2Cl2 (2 × 10 mL) and the resulting filtrate was concentrated. The resulting crude was purified by flash column chromatography to yield 2,4,6-triaminopyrimidines in 90-95% yield.
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 4-(Difluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see.
Reference:
Article; Sagi, Vasudeva Naidu; Liu, Tianyu; Lu, Xiaoying; Bartfai, Tamas; Roberts, Edward; Bioorganic and Medicinal Chemistry Letters; vol. 21; 23; (2011); p. 7210 – 7215;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem