重氮盐的安全性,是桑德迈尔反应很少应用于放大的原因。桑德迈尔反应其实就是SNAr反应,只是离去的基团不是常见的卤素,而是氮气,典型的SNAr1反应。 案例一 实验操作Compound 18 was prepared according to a literature procedure.18 In a roundbottom flask, methyl 4-amino-2-bromobenzoate (7.786 g, 30mmol) was weighed, the flask was cooled to 0 °C and H2SO4 (13.6 mL in 92 mL H2O) was added dropwise. After the resulting solution was stirred at 0 °C for 20 min, NaNO2 (3.5g, 51 mmol) in 35 mL water was added dropwise and the reaction mixture was allowed to stir for an additional 30 min at0 °C before refluxing at 100 °C for 45 min. 参考文献DOI: 10.1021/acs.oprd.9b00199案例二 实验操作A freshly prepared solution of NaNO2 (137.5 g, 1.2 equiv) in water (270mL) was added to a mixture of 30% H2SO4 (5 kg), aniline 31(266.6 g, 1.66 mol, 1.0 equiv) and acetonitrile (270 mL) at 50−55 °C over 35 min. [CAUTION: evolution of nitrogen gas!]Residual nitrite salt can be decomposed by treating the end reaction mixture with urea (0.3 equiv) for 10 min at 50 °C. 参考文献 Org. Process Res. Dev. 2012, 16, 595−604