硼氢化钠,氰基硼氢化钠,三乙酰氧基硼氢化钠还原 使用总结

如何正确使用三乙酰氧基硼氢化钠？

是要还原胺化吧，这东西我记得是无毒的。还原胺化反应是指将羰基化合物转变为胺的重要有机合成反应。先形成亚胺，然后被硼氢化钠还原；无论是硼氢化钠，还是三乙酰氧基硼氢化钠、氰基硼氢化钠，还是醋酸硼氢化钠，差别没有这么大，只要你形成了亚胺，下一步就是简单的还原。

将羰基跟胺反应生成亚胺（西弗碱），然后用硼氢化钠或者氰基硼氢化钠还原成胺。反应应在弱酸条件下进行，因为弱酸条件一方面使羰基质子化增强了亲电性促进了反应，另一方面也避免了胺过度质子化造成亲核性下降的发生。用氰代硼氢化钠比硼氢化钠要好，因为氰基的吸电诱导效应削弱了硼氢键的活性，使得氰代硼氢化钠只能选择性地还原西弗碱而不会还原醛、酮的羰基，从而避免了副反应的发生。用NaBH(OAc)3作还原剂，用ClCH2CH2Cl做溶剂可以缩短反应时间并显著提高产率。

我在做一类“胺基还原烷基化反应”，其中用到上述还原剂，我想求助以下几个问题：

1）这三种还原剂分别都在什么溶剂中进行反应？

2）它们中哪些是可以还原醛或者酮的？因为据说三乙酰氧基硼氢化钠在甲醇中反应很快，而且可以将醛还原掉。那么其他的会不会？

3）如果不考虑毒性、成本等因素，单从化学性质上说，氰基硼氢化钠与三乙酰氧基硼氢化钠，它们的用法有什么区别？

4）我的反应体系pH值接近中性偏碱，据说氰基硼氢化钠在酸性条件下还原能力不错，而在中性时候不行，那么三乙酰氧基硼氢化钠呢？它的适用pH范围是多少？

J. Org. Chem. 1996, 61, 3849-3862

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive aminationof aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH3CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)3 gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines

where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH4.

氰基硼氢化钠会产生有毒副产物，用三乙酰氧基硼氢化钠的话反应液不能有水。

这两种还原剂都比较常用，个人认为做还原氨化时主要考虑两个因素（溶剂，还原剂，是否加酸）。一般假如是酮的还原氨化，建议你加一点醋酸；醛多数情况下可不加；在用氰基硼氢化钠做还原剂时建议用甲醇作溶剂，尤其是反应物溶解性不好时；三乙酰氧基硼氢化钠做还原剂时一般用二氯，二氯乙烷或乙腈作溶剂。