138786-86-4 4-硝基-1H-吡唑-3-甲酸甲酯

危险性质：非危险化学品

化学合成。

化学合成

合成路线 1（1. 合成：138786-86-4）

产率：100% 合成条件：Stage #1: at 20℃; for 16 h; Stage #2: With water; sodium hydrogencarbonate In methanol; ethyl acetate 实验步骤：参考例1 4-硝基-1H-吡唑-3-羧酸甲酯将乙酰氯（9mL）滴加到甲醇（90mL），4-硝基-1H-吡唑-3-羧酸（9.00g，57.3mmol）中 加入混合物中。 将混合物在室温下搅拌16小时，并减压浓缩。 向残余物中加入甲醇，并将混合物减压浓缩，重复该操作两次。 将残余物用甲醇和乙酸乙酯稀释。 加入5％碳酸氢钠水溶液，将pH调节至8-9。 用乙酸乙酯萃取混合物。 萃取液用水，盐水洗涤，用无水硫酸镁干燥，减压蒸发溶剂，得到标题化合物（9.83g，收率100％）。 1H-NMR（DMSO-d6,200MHz）：δ3.98（3H，s），8.28（1H，s）。 参考文献：

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合成路线 2（3. 合成：138786-86-4）

产率：99.5% 合成条件：at 0 - 25℃; for 16 - 48 h; 实验步骤：向装有数字温度计和搅拌器的20L反应容器中加入A-硝基-1H-吡唑-3-羧酸（1.117Kg，7.11mol，1wt）和甲醇（8.950L，8vol）。将反应混合物在氮气下搅拌，冷却至0至50℃，在180分钟内加入亚硫酰氯（0.581L，8.0mol，0.52vol），将所得混合物温热至18-25℃搅拌过夜，之后时间1H NMR分析（d6-DMSO）表明反应完成。将反应混合物在40至45℃下减压浓缩，将残余物用甲苯处理并在40至45℃下减压浓缩（3×2.250L，3×2体积），得到4-硝基-1H-吡唑-3。 - 羧酸甲酯，为灰白色固体（1.210Kg，99.5％）。在环境温度下将亚硫酰氯（2.90ml，39.8mmol）缓慢加入到4-硝基-3-吡唑甲酸（5.68g，36.2mmol）的MeOH（100ml）混合物中，并将混合物搅拌48小时。将混合物真空浓缩，通过与甲苯共沸干燥，得到4-硝基-1H-吡唑-3-甲酸甲酯，为白色固体。阶段1：4-硝基-1H-吡唑-3-羧酸甲酯4-硝基-1H-吡唑-3-羧酸（1.350Kg，8.59mol，1.0wt）和甲醇（10.80L，8.0vol）的制备将其装入装有机械搅拌器，冷凝器和温度计的法兰烧瓶中。在氮气下将悬浮液冷却至0至5℃并在该温度下加入亚硫酰氯（0.702L，9.62Mol，0.52体积）。将混合物在16至24小时内温热至15至25℃。通过1H NMR分析（d6-DMSO）测定反应完成。将混合物在35至45℃下真空浓缩，并将甲苯（2.70L，2.0体积）加入到残余物中，并在35至45℃下真空除去。用甲苯（2.70L，2.0体积）重复甲苯共沸物两次，得到4-硝基-1H-吡唑-3-羧酸甲酯[1.467Kg，99.8％，108.7％w / w，1H NMR（d6-） DMSO）与结构一致，没有夹带的溶剂]，为灰白色固体。 参考文献：

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