| Molecular Formula | C12H10O3 |
| Molar Mass | 202.21 |
| Density | 280.32°C (rough estimate) |
| Melting Point | 102-104° (Kawada); mp 106-107° (Watanabe) |
| Boling Point | 280.32°C (rough estimate) |
| Refractive Index | 1.5080 (estimate) |
| Physical and Chemical Properties | Chemical properties crystallize from ethanol, melting point 102~104 ℃;106~107 ℃. Acute toxicity LD50 male and female mice, male and female rats (mg/kg):1810,1740,5630,5640 oral administration. |
| Use | Use for gastric ulcer. |
Method l: At room temperature and under stirring, add methyl 5-acetyl-2-hydroxybenzoate (8.0mol) to 1.32kg of potassium carbonate in the suspension of 2.0L dimethylformamide. After heating at 60 ℃ for 1h, add 1.32kg α-bromo-& gamma;-butyrolactone within 5 ℃ and 3h. After adding, stir at 45 ℃ for 10 hours. Cooling, filtering to remove insoluble inorganic matter. The filtrate is concentrated under reduced pressure, and the remainder is vacuum distilled to remove unreactive methyl 5-acetyl-2-hydroxybenzoate. The residue (crude compound (I), recrystallized with methanol, melting point 112~113 ℃) is dissolved in 2L methanol and 2L 50% sodium hydroxide aqueous solution. And heated at 60 ℃. After cooling, the reaction liquid was poured into 1.5L ice water and acidified with 2.2L concentrated hydrochloric acid. Filter to collect precipitated precipitate, wash with water and dry. Soluble in 1L dioxane and 1L toluene. 400g p-toluenesulfonic acid was added and heated and refluxed for 8.5h in a device equipped with a water separator. Concentrate under reduced pressure, and the remainder is poured into 10L of ice water. Filtered to collect the precipitated precipitate, washed with water, dried, and dissolved in ethyl acetate. After drying, it was concentrated and recrystallized with acetone-methanol to obtain compound (II) with a total yield of 45% and a melting point of 155~158 ℃.
1.26mol compound (II) was heated and refluxed in 2.8L acetic anhydride solution and 560ml triethylamine. Decompression and concentration, the remaining material is poured into 3L of ice water. The precipitate was filtered and collected, washed and recrystallized with methanol to obtain compound (Ⅲ) with 55% yield and melting point of 132~134 ℃.
7.4mol compound (Ⅲ) and 94g sodium chloride were dissolved in 1.5L dimethyl sulfoxide and stirred at 150 ℃ for 1.5h. After cooling, pour into the ice water. The precipitate was filtered and collected, washed with water, dried, and recrystallized with ethanol to obtain spirozofurone with 88% yield and melting point. 102~104 ℃.
Compound (III) can also be obtained directly from compound (I). Compound (I)(4.7mmol) was heated and refluxed for 10h in 15ml of acetic anhydride solution and 3ml of triethylamine. Concentrate under reduced pressure, the remainder is poured into ice water and extracted with ethyl acetate. The extract is washed, dried and concentrated under reduced pressure. The residue was eluted with silica gel chromatography and carbon tetrachloride-acetone (5:1, volume ratio). The second component eluent was collected and recrystallized with methanol to obtain compound (Ⅲ) with 47% yield.
Method 2: One-step synthesis. Using 5-acetyl -2-[(tetrahydro-2-oxo-3-furyl) oxygen] methyl benzoate (compound (I)) as raw material, snazofurone can be obtained by one-step reaction, but the reagent requirements are higher.
4.17 g1, 5-diazobicyclo [5.4.0] undecene -5(DBU) and 67g of sodium chloride were dissolved in 1L dimethylformamide, 5-acetyl -2-[(tetrahydro-2-oxo-3-furan)] methyl benzoate (278g,lmo1) was added dropwise in a solution of 1.8L dimethylformamide at 150 ℃ and stirred for 2h. The solvent is distilled under reduced pressure, and the residue is diluted with water and extracted with dichloromethane. The extract is washed, dried, and decolorized by silica gel. Dichloromethane solution was concentrated under reduced pressure, and the resulting crystals were recrystallized with ethanol to obtain 136g of spirozofone with 67% yield and melting point of 106-107 ℃.