Synthesis
The general procedure for synthesizing 3-hydroxy-4-methoxybenzonitrile from isovanillin was as follows: 14.2 g of isovanillin was dissolved in 75 mL of formic acid, 15 g of sodium formate was added, and stirred at 85 °C. Subsequently, 9 g of hydroxylamine hydrochloride was added in batches, and the reaction mixture was kept at 85 °C and continued to be stirred for 4 hours. Upon completion of the reaction, the mixture was poured into a nearly saturated sodium chloride solution and a precipitate was precipitated. The precipitate was separated by filtration, washed sequentially with water and petroleum ether, and dried to give the product. The yield was 14.2 g. The yield was 93% of the theoretical value. The product was analyzed by HPLC-MS (Method D) with a retention time (Rt) of 1.18 min.
References
[1] Patent: WO2011/92128, 2011, A1. Location in patent: Page/Page column 37
[2] Patent: US2012/28939, 2012, A1. Location in patent: Page/Page column 18
[3] Patent: CN105330586, 2016, A. Location in patent: Paragraph 0055; 0056
[4] Patent: CN105461602, 2016, A. Location in patent: Paragraph 0049; 0050
[5] Molecules, 2017, vol. 22, # 10,
[6]
Semenov, V. V., Kiselyov, A. S., Titov, I. Y., Sagamanova, I. K., Ikizalp, N. N., Chernysheva, N. B., Tsyganov, D. V., Konyushkin, L. D., Firgang, S. I., Semenov, R. V., Karmanova, I. B., Raihstat, M. M., Semenova, M. N. (2010). Synthesis of Antimitotic Polyalkoxyphenyl Derivatives of Combretastatin Using Plant Allylpolyalkoxybenzenes. Journal of Natural Products, 73(11), 1796–1802.
https://doi.org/10.1021/np1004278
