Synthetic Route of 7006-52-2,Some common heterocyclic compound, 7006-52-2, name is N-Methyl-3-chloroaniline, molecular formula is C7H8ClN, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
General procedure: Ureas used in this project were prepared according to reaction equation (1)-(3) and related procedures given below. A 100 mL two-necked flask with a magnetic stir bar was evacuated and backfilled with argon three times. Amine (2 eq) was dissolved in THF. A solution of n-BuLi (2.5 M in hexane, 1.0 eq) was added slowly at ?40 °C and the resulting mixture was stirred for 15 min at the same temperature. After cooling to ?60 °C, iodomethane (1.0 eq) was added slowly and the mixture was allowed to warm to rt and stirred for additional 8 h at rt. The mixture was quenched by adding H2O and the organic phase was separated. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with sat. NaHCO3-solution, dried over Na2SO4 and the solvents were evaporated under reduced pressure. After purification by flash chromatography the pure product was obtained. A 100 mL two-necked flask with a magnetic stir bar was evacuated and backfilled with argon three times. Triphosgene (5.0 mmol) and CH2Cl2 (30 mL) were added to the flask. The mixture was cooled at ?30 °C and dry pyridine (3.0 mL) was slowly added to the flask (Caution: highly toxic phosgene was generated). After stirring for 15 min at ?30 °C, secondary amine (10 mmol) was slowly added to the mixture. The mixture was warmed to room temperature and stirred for 6 h at room temperature. The reaction mixture was carefully quenched by 1N HCl (10 mL) and was extracted with CH2Cl2 (5 mL x 3). The organic layer was washed with water and brine, then dried over Na2SO4. After the filtration, the solution was concentrated to dryness. The crude product was purified by silica gel column chromatography. Further purification was carried out by recrystallization or distillation under vacuum. MeNH2 methanol solution (33.3percent) (1.5 equiv.), acid chloride (1.0 equiv.), Et3N (2.0 equiv.) and CH2Cl2 (0.5 M) were added into a round bottom flask capped with a septum. The mixture was stirred at room temperature. After 2 h, the crude reaction mixture was extracted with CH2Cl2, purified by flash chromatography.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N-Methyl-3-chloroaniline, its application will become more common.
Reference:
Article; Wang, Yan; Zhou, Hao; Xu, Ke; Shen, Mei-Hua; Xu, Hua-Dong; Chinese Chemical Letters; vol. 28; 1; (2017); p. 92 – 96;,
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