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Topic: Reductive amination, DCE  (Read 2941 times)

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Offline jimimissel90

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Reductive amination, DCE
« on: November 30, 2016, 09:29:06 AM »
Carrying out a couple of reductive aminations on an isoprenoid tail and most of the methods use 1,2-Dichoroethane as the solvent along with some acetic acid as catalyst. I've been using DCM with no problems just interested in why DCE is the preferred solvent. I couldn't think of any reasons why DCM couldn't be used as in this prep and was wondering if my that was affecting my yields.
Any ideas?

"Sodium triacetoxyborohydride is a general, mild, and selective reducing agent for the reductive amination of various aldehydes and ketones. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions. Acid sensitive functional groups such as acetals and ketals, and reducible functional groups such as C-C multiple bonds and cyano and nitro groups are tolerated.
A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C. A. Maryanoff, R. D. Shah, J. Org. Chem., 1996, 61, 3849-3862 "


Offline rolnor

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Re: Reductive amination, DCE
« Reply #1 on: November 30, 2016, 10:23:15 AM »
I have many times found that people use the solvent that was used in the original paper but many other solvents can often also be used with good result.

Offline Dan

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Re: Reductive amination, DCE
« Reply #2 on: November 30, 2016, 11:53:08 AM »
A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C. A. Maryanoff, R. D. Shah, J. Org. Chem., 1996, 61, 3849-3862 "

I'm sure it says somewhere else in that paper that they wanted to avoid DCM because it can (very slowly) react with some amines. This is from memory though, I could be wrong.

I've found this reaction generally works very well, but we have occasionally had reactions that were much cleaner in THF than DCE. Also, we've generally found the yields are better if you prepare the triacetoxyborohydride in situ using NaBH4 + 3 eq AcOH rather than using commercially supplied NaBH(OAc)3.
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Offline orgopete

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Re: Reductive amination, DCE
« Reply #3 on: November 30, 2016, 03:05:59 PM »
I'm sure it says somewhere else in that paper that they wanted to avoid DCM because it can (very slowly) react with some amines. This is from memory though, I could be wrong.

That was my first thought as well. I haven't done this reaction, but I also wondered whether the reaction might be moderately heated as an option?
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Offline jimimissel90

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Re: Reductive amination, DCE
« Reply #4 on: December 01, 2016, 04:34:04 AM »
I'm sure it says somewhere else in that paper that they wanted to avoid DCM because it can (very slowly) react with some amines. This is from memory though, I could be wrong.

That was my first thought as well. I haven't done this reaction, but I also wondered whether the reaction might be moderately heated as an option?

Ah, that would explain some of the faint dots on the TLC. I heat mine to 30°C and it seems to help speed up the reaction. I also found that if I have it extremely dry, the reaction doesn't work as well.

I think I'll use dry THF (depending on solubility), as I don't want to buy in 1,2-dichloroethane for one one small step in my synthesis. I'll try making the triacetoxyborohydride in situ as well. The commercial triacetoxyborohydride is very hygroscopic, which is a pain when trying to slowly add the powder.

Cheers for the help guys


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