Diazomethane is among the most versatile and useful reagents for introducing methyl or methylene groups in organic synthesis. However, because of its explosive nature, its generation and purification by distillation are accompanied by a certain safety risk. This protocol describes how to construct a configurationally simple tube-in-flask reactor for the in situ on-demand generation of anhydrous diazomethane using membrane separation technology and thus avoiding distillation methods. The described reactor can be prepared from commercially available parts within ∼1 h. In this system, solutions of Diazald and aqueous potassium hydroxide are continuously pumped into a spiral of membrane tubing, and diazomethane is generated upon mixing of the two streams. Pure diazomethane gas diffuses out of the reaction mixture through the membrane tubing (made of gas-permeable Teflon AF-2400). As the membrane tubing is immersed in a flask filled with the substrate solution, diazomethane is instantly consumed, which minimizes the risk of diazomethane accumulation. For this protocol, the reaction of diazomethane with benzoic acid on a 5-mmol scale has been selected as a model reaction and is described in detail. Methyl benzoate was isolated in an 88-90% yield (597-611 mg) within ∼3 h.

中文翻译：

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使用膜分离技术的实验室规模的无水重氮甲烷生产。

重氮甲烷是在有机合成中引入甲基或亚甲基的最通用和最有用的试剂之一。然而，由于其爆炸性，其通过蒸馏的产生和纯化伴随着一定的安全风险。该协议描述了如何使用膜分离技术构建一个结构简单的烧瓶内反应器，用于现场按需生成无水重氮甲烷，从而避免了蒸馏方法。所描述的反应器可以在约1小时内由可商购的部件制备。在该系统中，将Diazald和氢氧化钾水溶液连续泵入螺旋状的膜管中，并在两种物流混合后生成重氮甲烷。纯的重氮甲烷气体通过膜管（由透气的Teflon AF-2400制成）从反应混合物中扩散出来。由于将膜管浸入装有底物溶液的烧瓶中，因此重氮甲烷会立即被消耗掉，从而使重氮甲烷积聚的风险降到最低。对于此方案，已选择重氮甲烷与苯甲酸在5 mmol规模的反应作为模型反应，并对其进行了详细描述。在约3小时内以88-90％的收率（597-611 mg）分离出苯甲酸甲酯。重氮甲烷与苯甲酸在5 mmol规模的反应已被选作模型反应并进行了详细描述。在约3小时内以88-90％的收率（597-611 mg）分离出苯甲酸甲酯。重氮甲烷与苯甲酸在5 mmol规模的反应已被选作模型反应并进行了详细描述。在约3小时内以88-90％的收率（597-611 mg）分离出苯甲酸甲酯。