Electric Literature of 583-68-6,Some common heterocyclic compound, 583-68-6, name is 2-Bromo-4-methylaniline, molecular formula is C7H8BrN, 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.
2-isocyano-5-methyl-biphenyl (1a):To a dry three necked flask, 2-bromo-4-methylaniline(S1,3.7 g, 20 mmol), phenylboronic acid (2.9 g, 24 mmol), aqueous solution of K2CO3 (2M, 15 mL) and DME (15 mL) were added,and the mixture was stirred for 30 min at room temperature under Ar atmosphere.To the stirred mixture, PdCl2 (PPh3)2 (280mg, 0.40 mmol) was added at room temperature, and the mixture was stirred for overnight at 80 C, under Ar. The reaction mixture was then cooled to room temperature and diluted with EtOAc. The organic layer was washed with water and dried over anhydrous MgSO4. After removing the solvent in vacuo, the residue was purified by flash column chromatography on silica gel(petroleum ether/EtOAc = 30/1) to afford 4-methyl-2-phenylaniline as yellow oil (S2, 3.2 g, 87%). Acetic formic anhydride, which was prepared from the reaction of acetic anhydride (1.3 mL) with formic acid (0.6 mL) at 55 C for 2 h, was added dropwise to a stirred solution of S2 (1.10 g, 6 mmol) at 0 C in THF (10 mL) and the mixture was stirred for 2 h at room temperature. Then, the mixture was quenched by sat.aqueous solution of NaHCO3 and extracted with EtOAc three times. The extract was dried over Na2SO4 and concentrated under reduced pressure to give formamide S3 as pale yellow oil. This material was used for the subsequent dehydration without further purification. THF (10 mL), NEt3 (6 mL) and the whole amount of S3 obtained above were added and cooled to 0 C.Then, POCl3 (0.9 mL, 10 mmol) was added dropwise, and the mixture was stirred at 0 C for 2 h. After the reaction was completed, the mixture was quenched by sat. aqueous solution of Na2CO3 and stirred for 1 h. The mixture was extracted with CHCl3 three times, dried over MgSO4 and evaporated under reduced pressure. The compound was purified by column chromatography on Florisil (hexane/EtOAc = 20/1) to give 1a as a white solid (0.89 g, 77% yield from S2).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-4-methylaniline, its application will become more common.
Reference:
Article; Wang, Gao; Chen, Shan-Yong; Yu, Xiao-Qi; Tetrahedron Letters; vol. 55; 38; (2014); p. 5338 – 5341;,
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