2,5-Disubstituted furans are frequently found in pharmaceuticals and bioactive natural products. Nucleophilic substitution reactions on the carbon atom adjacent to the furan ring are useful for producing various furan derivatives. However, the formation of 5-substituted 2-halomethylfuran and the subsequent nucleophilic substitution reactions are often limited by severe undesired reactions caused by the highly reactive halomethylfurans. This paper reports the successful rapid synthesis of various 2,5-disubstituted furans using microflow technology, which suppresses undesired reactions including dimerization and ring opening of the furans. We observed that Brønsted acids had a significant effect on the nucleophilic substitution reaction and the use of HBr and HI gave the best results. A plausible mechanism of the Brønsted acid-mediated nucleophilic substitutions in the developed approach was proposed.

中文翻译：

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在微流反应器中快速原位生成 2-(卤甲基)-5-苯基呋喃并进行亲核加成

2,5-二取代呋喃常见于药物和生物活性天然产物中。与呋喃环相邻的碳原子上的亲核取代反应可用于生产各种呋喃衍生物。然而，5-取代的2-卤代甲基呋喃的形成和随后的亲核取代反应常常受到高反应性卤代甲基呋喃引起的严重不良反应的限制。本文报道了利用微流技术成功快速合成各种2,5-二取代呋喃，抑制了呋喃二聚和开环等不良反应。我们观察到布朗斯台德酸对亲核取代反应有显着影响，并且使用 HBr 和 HI 给出了最好的结果。提出了所开发方法中布朗斯台德酸介导的亲核取代的合理机制。