3-Amino-5-chlorophenol

Uses

3-Amino-5-chlorophenol is a useful compound for studying the recyclization with benzoxazinones.

Synthesis

General procedure for the synthesis of 3-amino-5-chlorophenol from 3-chloro-5-nitrophenol: 3-chloro-5-nitrophenol (3.00 g, 17.3 mmol) and zinc powder (5.65 g, 86.4 mmol) were dissolved in ethanol (80 mL) and heated to 60 °C. Subsequently, an aqueous solution of ammonium chloride (1.85 g, 34.6 mmol) was added dropwise to the reaction system (16 mL). The reaction temperature was maintained at 60 °C and stirring was continued for 3 hours. Upon completion of the reaction, the reaction mixture was filtered through Celite and the solvent was removed under vacuum. The residue was dissolved in water and extracted with ethyl acetate. The organic layer was dried with sodium sulfate and the solvent was again removed under vacuum. The residue was ground with dichloromethane and the precipitate was collected by filtration to give 1.97 g of 3-amino-5-chlorophenol in yellow crystalline form (77% yield). The product was characterized by 1H-NMR (400 MHz, DMSO-d6): δ= 5.25 (broad single peak, 2H), 5.92 (double peak, 2H), 6.03 (triple peak, 1H), and 9.29 (single peak, 1H).Results of the LC/MS (Method 4) analysis: retention time R1 = 1.07 min; MS (ESIpos): m/z = 144 [M + H]+.

References

[1] Patent: WO2009/33581, 2009, A1. Location in patent: Page/Page column 95-96
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 12, p. 5162 - 5192
[3] Patent: CN106831614, 2017, A. Location in patent: Paragraph 0484-0486
[4] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 1964 - 1978
[5] Biochemical Journal, 1956, vol. 64, p. 38,39