Chemical Properties
white to light yellow crystal powde
Uses
6-Aminophthalide is used in the total synthesis of uncialamycin and its application to antitumor antibiotics. Also used in permethyl ningalin analogs as P-glycoprotein inhibitors.
Uses
It is used to produce 6-acetylamino-phthalide. It is also used as a starting material in the reduction reaction.
Definition
ChEBI: 6-Amino-1,3-dihydroisobenzofuran-1-one is a member of 2-benzofurans.
Synthesis
General procedure for the synthesis of 6-aminophthalide from 6-nitrotetrachlorophthalide: Commercially available 6-nitro-1(3H)-isobenzofuranone (9.9 g, 55 mmol) was dissolved in a solvent mixture of tetrahydrofuran (20 mL) and methanol (60 mL), and 5% palladium-carbon catalyst (1.5 g) was subsequently added. The reaction mixture was stirred at room temperature for 20 h under hydrogen atmosphere. Upon completion of the reaction, the mixture was filtered and the solid was washed sequentially with ethyl acetate and methanol. The filtrate and washings were combined and the resulting solution was concentrated under reduced pressure. The resulting solid was washed with ethyl acetate to give 6-aminophthalide (6.21 g) as a crystalline solid. The washings were concentrated and the residue was crystallized by mixed ethyl acetate-hexane solvent to obtain additional 6-aminophthalide (0.95 g, 87% total yield). The product was confirmed by NMR hydrogen spectrum (400 MHz, CD3OD): δ 5.225 (2H, s), 7.060 (1H, d, J = 2 Hz), 7.071 (1H, dd, J = 9, 2 Hz), 7.288 (1H, d, J = 9 Hz). Infrared spectra (KBr pressed) νmax cm-1: 3473, 3372, 3278, 1735, 1631, 1504, 1330, 1059, 992.
References
[1] Physical Chemistry Chemical Physics, 2005, vol. 7, # 24, p. 4070 - 4081
[2] Chemistry - A European Journal, 2016, vol. 22, # 13, p. 4600 - 4607
[3] ACS Catalysis, 2014, vol. 4, # 10, p. 3504 - 3511
[4] Patent: EP1362856, 2003, A1. Location in patent: Page/Page column 159
[5] Journal of Heterocyclic Chemistry, 2006, vol. 43, # 5, p. 1195 - 1204
