Background and overview[1]
1-(4-Nitrophenyl)-1,2,3-propanetriol can be used as a pharmaceutical intermediate, can prepare compounds with sulfamate, and can synthesize anticonvulsants, antibiotics and anti-tumor drugs , which has attracted much attention in drug research recently.
Structure
Application[1]
Armitage et al. reported that 1-(4-nitrophenyl)-1,2,3-propanetriol can be used to prepare sulfonamide 24d.
General steps: Add sulfamoylation reagent (44.23mmol) and acetonitrile (150mL) to a 500mL three-neck round-bottom flask. Alcohol (22.12 mmol) was then added via syringe at room temperature. After stirring for two minutes, hydrochloric acid (4M solution in 1,4-dioxane, 8.8 mmol) was added dropwise over 5 minutes. The resulting suspension was stirred at room temperature until LCMS or NMR analysis showed no unreacted residue. Filter to remove solids. Concentrate the filtrate to approximately 50 mL and cool to less than 10°C in an ice bath. Concentrated HCl (222 mmol) was added dropwise while keeping the reaction temperature below 25°C. After stirring for 2 hours, LCMS or NMR analysis showed no remaining tert-butoxycarbonyl sulfamate. The reaction mixture was extracted with ethyl acetate (3×30 mL). Wash the combined organic layers with water (3 x 50 mL). The organic layer was dried over sodium sulfate and then concentrated to obtain a crude mixture of the desired product sulfamate d and chloride c or sulfamate disalt e. When crude product purity was below 90% by NMR, sulfamate d was purified by silica gel column chromatography for characterization and yield determination.
24d: 2,3-dihydroxy-3-(4-nitrophenyl)propylsulfamate, white solid, 1.28g, yield 93%. Following general procedures, use 1-(4-nitrophenyl)-glycerol (1.00 g, 4.69 mmol, 1.0 equiv), sulfamoylation reagent (4.13 g, 9.38 mmol, 2.0 equiv) and 4 M HCl 1,4- A solution of dioxane (0.469 mL, 1.88 mmol, 0.40 equiv) was prepared for 24 days. After 6 hours, alcohol 24a was converted to tert-butoxycarbonyl sulfamate 24b. Taking off the BOC is 24d. M.p.117-119°C. 1HNMR (300MHz, CD3CN) δ8.37-8.07 (m, 2H), 7.76-7.50 (m, 2H), 5.69 (s, 2H), 4.76 (dd, J=6.8, 4.6Hz, 1H), 4.31-4.06 (m, 2H), 4.02-3.83 (m, 2H), 3.47 (d, J=5.9Hz, 1H). 13CNMR (75MHz, DMSO) δ151.44, 147.08, 128.82, 123.29, 73.13, 72.85, 71.11. HRMS calculated for C9H12N2O7S[M-H]: 291.0292, found 291.0291.
Main reference materials
[1]FromOrganicLetters,14(10),2626-2629;2012
