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【结 构 式】 
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【分子编号】59339 【品名】(1S,3aS,4R,6aS)-4-(nitrooxy)octahydro-1-pentalenyl 4-nitrobenzoate 【CA登记号】 |
【 分 子 式 】C15H16N2O7 【 分 子 量 】336.30132 【元素组成】C 53.57% H 4.8% N 8.33% O 33.3% |
合成路线1
该中间体在本合成路线中的序号：(V)1. The nitration of isosorbide (I) with fuming HNO3 in acetic acid/acetic anhydride gives the dinitrate (II), which is selectively monoreduced by means of diisopropyltitanium tetrahydroborate (obtained by reaction of disopropyltitanium dichloride with benzyltriethylammonium borohydride) in dichloromethane to afford the isosorbide 5-nitrate. 2. The reduction of dinitrate (II) can also be performed with benzyl triethyl ammonium tetrathiomolibdate in DMF. 3. The reduction of dinitrate (II) can also be performed with H2 over PtO2/C in methanol. 4. The reduction of dinitrate (II) can also be performed with cobalt phthalocyanine and NaBH4 in methanol. 5. The reduction of dinitrate (II) can also be performed with Zn and HOAc in ethanol/water. 6. The reduction of dinitrate (II) can also be performed with H2 over Pd/C and NiCl2 in ethanol/water. 7. The reaction of isosorbide (I) with 4-nitrobenzoyl chloride (III) and pyridine in dichloromethane gives the isosorbide 2-O-(4-nitrobenzoate (IV), which is nitrated with HNO3 in acetic acid/acetic anhydride to yield the isosorbide 5-O-nitrate-2-O-(4-nitrobenzoate) (V). Finally, this compound is selectively hydrolyzed with KOH in methanol/dichloromethane.
| 【1】 Bhar, D.; Chandrasekaran, S.; A highly chemoselective reduction of isosorbide-2,5-dinitrate mediated by tetrathiomolybdate. Indian J Chem 1997, 36B, 9, 793. |
| 【2】 Ravikumar, K.S.; Chandrasekaran, S.; Highly chemoselective reduction of 2,5-dinitro-1,4:3,6-dianhydro-D-glucitol with titanium(III) tetrahydroborates: Efficient synthesis of isomerically pure 2- and 5-nitro-1,4:3,6-dianhydro-D-glucitols. Synthesis (Stuttgart) 1994, 10, 1032. |
| 【3】 Brown, C.; et al.; New preparative routes to isosorbide 5-mononitrate. J Chem Soc - Perkins Trans I 2000, 12, 1809. |
| 【4】 Camera, E.; Filipuzzi, F.; De Lucchi, O.; Modena, G. (Consiglio Nazionale delle Ricerche); Process for the preparation of isosorbide-5-mononitrate. EP 0201067; US 4713466 . |
| 【5】 Gallardo Carrera, A. (Fordonal SL); Process for the preparation of isosorbide-5-nitrate. ES 8402305 . |
| 【6】 Roberts, S.M.; Marston, R.W.; Quigley, P.F.; Brown, C.M.; Cross, S.J.; Synthesis of isosorbide mononitrate. EP 1248788; WO 0149692 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 59337 | (1R,3aS,4S,6aS)octahydro-1,4-pentalenediol | C8H14O2 | 详情 | 详情 | |
| (II) | 59338 | (1R,3aS,4S,6aS)-1,4-bis(nitrooxy)octahydropentalene | C8H12N2O6 | 详情 | 详情 | |
| (III) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |
| (IV) | 59340 | (1R,3aR,4R,6aR)-1,3a,6a-trimethyl-4-[2-(4-methylphenyl)-2-propenyl]octahydropentalene | C21H30 | 详情 | 详情 | |
| (V) | 59339 | (1S,3aS,4R,6aS)-4-(nitrooxy)octahydro-1-pentalenyl 4-nitrobenzoate | C15H16N2O7 | 详情 | 详情 |