硼氫化鈉,氰基硼氫化鈉,三乙酰氧基硼氫化鈉還原使用總結(jié)

如何正確使用三乙酰氧基硼氫化鈉？

是要還原胺化吧，這東西我記得是無(wú)毒的。還原胺化反應(yīng)是指將羰基化合物轉(zhuǎn)變?yōu)榘返闹匾袡C(jī)合成反應(yīng)。先形成亞胺，然后被硼氫化鈉還原；無(wú)論是硼氫化鈉，還是三乙酰氧基硼氫化鈉、氰基硼氫化鈉，還是醋酸硼氫化鈉，差別沒(méi)有這么大，只要你形成了亞胺，下一步就是簡(jiǎn)單的還原。

將羰基跟胺反應(yīng)生成亞胺（西弗堿），然后用硼氫化鈉或者氰基硼氫化鈉還原成胺。反應(yīng)應(yīng)在弱酸條件下進(jìn)行，因?yàn)槿跛釛l件一方面使羰基質(zhì)子化增強(qiáng)了親電性促進(jìn)了反應(yīng)，另一方面也避免了胺過(guò)度質(zhì)子化造成親核性下降的發(fā)生。用氰代硼氫化鈉比硼氫化鈉要好，因?yàn)榍杌奈娬T導(dǎo)效應(yīng)削弱了硼氫鍵的活性，使得氰代硼氫化鈉只能選擇性地還原西弗堿而不會(huì)還原醛、酮的羰基，從而避免了副反應(yīng)的發(fā)生。用NaBH(OAc)3作還原劑，用ClCH2CH2Cl做溶劑可以縮短反應(yīng)時(shí)間并顯著提高產(chǎn)率。

我在做一類(lèi)“胺基還原烷基化反應(yīng)”，其中用到上述還原劑，我想求助以下幾個(gè)問(wèn)題：

1）這三種還原劑分別都在什么溶劑中進(jìn)行反應(yīng)？

2）它們中哪些是可以還原醛或者酮的？因?yàn)閾?jù)說(shuō)三乙酰氧基硼氫化鈉在甲醇中反應(yīng)很快，而且可以將醛還原掉。那么其他的會(huì)不會(huì)？

3）如果不考慮毒性、成本等因素，單從化學(xué)性質(zhì)上說(shuō)，氰基硼氫化鈉與三乙酰氧基硼氫化鈉，它們的用法有什么區(qū)別？

4）我的反應(yīng)體系pH值接近中性偏堿，據(jù)說(shuō)氰基硼氫化鈉在酸性條件下還原能力不錯(cuò)，而在中性時(shí)候不行，那么三乙酰氧基硼氫化鈉呢？它的適用pH范圍是多少？

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.

氰基硼氫化鈉會(huì)產(chǎn)生有毒副產(chǎn)物，用三乙酰氧基硼氫化鈉的話(huà) 反應(yīng)液不能有水。

這兩種還原劑都比較常用，個(gè)人認(rèn)為做還原氨化時(shí)主要考慮兩個(gè)因素（溶劑，還原劑，是否加酸）。一般假如是酮的還原氨化，建議你加一點(diǎn)醋酸；醛多數(shù)情況下可不加；在用氰基硼氫化鈉 做還原劑時(shí)建議用甲醇作溶劑，尤其是反應(yīng)物溶解性不好時(shí)；三乙酰氧基硼氫化鈉做還原劑時(shí)一般用二氯，二氯乙烷或乙腈作溶劑。