硼氢化钠作为还原剂，是工艺中的常客，直接还原醛、酮、席夫碱；直接或搭配其他物质还原酯；特定组合还可以还原氰基和酰胺等。
从文献的总结上看，硼氢化钠参与反应的加料方式一般有如下几种
把硼氢化钠固体分批加到待还原底物的体系中
把甲醇（作为引发剂）滴加到待还原底物/硼氢化钠/THF的悬浊体系中
把待还原底物滴加到硼氢化钠/THF的体系中
把硼氢化钠的甲醇溶液（加催化量甲醇钠或者氢氧化钠为稳定性剂）滴加到待还原底物的甲醇或者THF中
把硼氢化钠的冷水溶液短时间内滴加到待还原底物的体系中
分享文献案例前，先分享一个小编经历的案例
硼氢化钠还原羰基，加料方式是滴加甲醇，到底物/硼氢化钠/THF的悬浊液中
案例一：还原酮
加料方式：滴加底物到硼氢化钠/乙醇的悬浊液中
淬灭方式：先丙酮，后盐酸
实验操作
To 17.4 kg (98.2 mol) of 6-nitro-1-indanone (8), that contained approximately 20% of the 4-nitroisomer, was added 35 L of THF. In a separate tank, 155 L of 2B-3 EtOH (denatured with toluene) was cooled to -15 °C, and 1.02 kg (27.0 mol, 1.1 equiv) of NaBH4 was added. The nitroindanone/THF solution was added over 30 min to the cold NaBH4/EtOH slurry. The nitroindanone tank was rinsed with 25 L of THF.
After 1 h, acetone (3.5 L) was added to quench excess NaBH4, followed by 4.0 kg of concentrated HCl as necessary to adjust the pH to 3
案例二：还原酯
加料方式：滴加底物到硼氢化钠/THF的悬浊液中
淬灭方式：先甲醇，后盐酸
化合物3先双酯化，然后硼氢化钠还原酯得到化合物25
实验操作
A 5000 L reactor was charged with NaBH4 (72.7 kg, 1922 mol, 250 mol %) and THF (974 kg, 1096 L, 8.40 L/kg) at 20 °C. A solution of dimethyl ester 24 (131 kg, 779 mol) in THF (438 kg, 493 L, 3.75 L/kg) was then slowly added to the reactor at 20 °C over 6 h.
The resulting reaction mixture was stirred at 20 °C for 24 h and then quenched with MeOH (210 kg, 265 L, 2.02 L/kg) over 4 h at −5 °C. A solution of HCl in MeOH (6 mol/L, 1150 L, 6900 mol, 882 mol %) was then added to the solution at −5 °C over 3 h to adjust the pH to 2.
案例三：还原酰胺
加料方式：滴加底物/三氟化硼到硼氢化钠/THF的悬浊液中
淬灭方式：水
实验操作
12 (11.3 kg, 34.6 mol) was dissolved in THF (33.9L). BF3·OEt2 (12.3 kg, 86.4 mol) was added.
The solution was slowly transferred to a heated (55 °C) suspension of NaBH4(2.45 kg, 64.8 mol) in THF (28.2 L) over 3 h while the temperature of the receiving reactor was maintained between 50 to 60 °C.
The mixture was stirred at 60 °C for 3 h and then cooled to 5 °C. A 10:1 (w/w) mixture of water and THF (20.6kg) was slowly added, while the temperature of the receiving reactor was maintained between 5 to 20 °C. After the mixture stirred at 20 °C for 2 h, water (45.2 L) was slowly added over 30 min, and the mixture was extracted with 2-methyl THF (45.2 L).
案例四：还原羧酸
加料方式：分批加入硼氢化钠
淬灭方式：甲醇
实验操作
A reactor was charged with THF (300 kg) and 16 (27.7 kg, 132.13 mol, 1.0 equiv). To this suspension was added NaBH4 (14.96 kg, 395.45 mol,3.0 equiv) in batches every 5 min. Then, the internal temperature was raised to 40°C, and BF3·THF (36.96 kg, 264.26 mol, 2.0 equiv) was added dropwise over 150 min. The reaction was heated to 70 °C for 24 h.
The reaction was cooled to 45 °C, and MeOH (97 kg)was added dropwise over 2 h. The internal temperature was raised to 66 °C and held for 12 h. Upon completion, the volume of the solution was reduced to approximately 60 L under reduced pressure at 50 °C.
案例五：还原席夫碱
加料方式：滴加硼氢化钠的甲醇溶液（催化量甲醇钠为稳定剂）
淬灭方式：丙酮
实验操作
To a 30 L reactor was charged 20 (5.39 mol)diluted in methanol (9.5 L, 5.6 mL/g). A freshly prepared solution of sodium borohydride (163 g, 4.31 mol, 0.8 equiv) containing sodium methanolate at 0.01 N in methanol (3.4 L, 2 mL/g) was added at 20 °C over 2 h maintaining the process temperature below 25 °C during the addition. The mixture was then stirred at 20 °C for 1 h. The excess of sodium borohydride was quenched by addition of acetone (1.4 L, 18.8 mol, 3.5 equiv) over 30 min, maintaining the process temperature below 25 °C during the addition.
