Sciencemadness Discussion Board

NaBH4 ester reduction to alcohol ?'s

German - 13-5-2009 at 00:33

I have been trying to reduce amino acid esters to it's alcohol using NaBH4 and I had a few questions.

The first is that the chemist describing the procedure of reducing the ester to it's alcohol via NaBH4 suggests putting the NaBH4 in a flask, add several hundred ml of alcohol (he says either alcohol is fine even though I have found out that methanol actually acts as a catalyst), then over 15 minutes slowly add the ester. *I* found that the instant the alcohol is added the NaBH4 immediately starts reacting before even the ester is added. After 15 minutes or so of all the ester finally being added I imagine most of the hydrogen used for the reduction is already gone (even though it still gases for a good 5 minutes after all has been added). What I was thinking instead was putting the alcohol in the flask, add the ester, and then slowly add the NaBH4 over 15 minutes. This way every bit of NaBH4 would be contributing to the reduction. Does anyone forsee any safety problems with this variation if I am monitoring temperature and venting the gas properly?

The other question I had is through my research I found that hydrogen is not the only gas that is being released by NaBH4 during the reduction. Apparently diborane gas is released too. Does anybody know the amount that would be released? I assume that it is quite small since I never came across it before but I am concerned about it because diborane gas has an autoignition temp of 38 degree c. Not exactly stuff I like to be mixing with hydrogen gas as an exothermic reaction is taking place. (Even though an interesting thing I found about diobrane is that it is capable of reducing carboxylic acids to it's alcohol completely).

And also, I've been doing these reductions with 10g NaBH4 in 300ml alcohol with 500 ml ester solution but I would like to scale it up 10 fold and was wondering if anybody had any safety comments regarding 100g NaBH4, 3L alcohol, and 5L ester solution. I have had no problem with any kind of runaway reaction with the amount I've been doing but perhaps someone with NaBH4 experience could give insight if this should be a concern with greater amounts.


Edit by Nicodem: "Swiming" is strictly forbidden on this forum. The next time you do it, your post will be removed. Also discussing upscaling and "swiming" at the same time is incredibly stupid, so keep in mind that profit related discussion is not tolerated.

[Edited on 13/5/2009 by Nicodem]

German - 13-5-2009 at 12:37

What are you talking about? I am talking about reducing an amino ester to it's alcohol. What in the world is wrong about that???? We can not discuss simple amino acid reductions here?

DJF90 - 13-5-2009 at 12:48

NaBH4 is typically used in ethanol solution. In my experience NaBH4 reductions are fairly benign, at least that of fluorenone was. And it was small scale. However there was practically no heat evolution at all and so I can see no problem in this respect with scaling up.

[Edited on 13-5-2009 by DJF90]

Arrhenius - 14-5-2009 at 20:08

Sodium borohydride in ethanol won't reduce your ester. I'm not well versed in its use in methanol to reduce esters, but if this actually works, it probably first converts the salt into borane (diborane) which can reduce esters. You may be able to reduce the ester with NaBH4 in ethanol + sulfuric acid, but i don't have a procedure for you. I see no danger in adding a solution of NaBH4 to a solution of your ester. You could even slowly add the solid to your reaction, but I would NOT advise this on a large scale. If you want to scale up, put a thermometer in your reaction and make sure it doesn't run away. Add the reducing agent slowly.

Just don't say "swim". Mind stating your exact amino acid? Chemistry is difficult when poorly described.

solo - 14-5-2009 at 21:00

"Sodium borohydride in ethanol won't reduce your ester. I'm not well versed "

...........said Arrhenius

.....you are right , you aren't well versed, so why do you make sweeping statements like that , read more before you stick your foot in your mouth, amino acid esters are easily reduced with NaBH4 in 50% ethanol/water with yields of 80%+, but I won't give you the reference as you need to eat your words...and learn to respect the forum.....read!.....solo

Arrhenius - 14-5-2009 at 22:37

OK Solo. First, that quote takes my words out of context. So thank you for that.

So let me return the favor:
"amino acid esters are easily reduced with NaBH4 in 50% ethanol/water with yields of 80%+"
REALLY Solo. Where in your suggestion have you mentioned methanol, since that's where German's problem arises? I and one other person just suggested that he try ethanol, and so did you. Yet you're upset.

Give me a reason why I should help this guy by taking MY time to find him a reference on how to use an oddball method to prepare something that is obviously not just amateur experimentalism. No one here is making this quantity of shit just to prove that it works.

You're right, I'm not well versed in this forum. I do, however, have a formal education in chemistry. Does that count for anything? Or shall I keep my mouth shut when someone's looking for help.

I'll continue reading more credible sources than this forum. But as long as folks like you and Sauron continue to bash others for trying to offer information, then I see no reason why anyone would want to post here.

Thank you kindly for your input. I'm sure German appreciates it.



[Edited on 15-5-2009 by Arrhenius]

Nicodem - 14-5-2009 at 23:35

Arrhenius, don't get so upset. Solo was just pointing out that what you find obvious (esters not being reduced by NaBH4 in alcohols) might not always be true. The things you learn at school as general are not always such (but you learn this only after some frustrating experience in the lab). For example, esters do get reduced by NaBH4 in protic media if there is a neighbouring group assistance. Thus, some esters of alpha-amino acids do get reduced under such conditions. There were several papers and/or references posted on this forum regarding this topic so I won't bother searching. However, what Solo missed is that nowhere did German mentioned his esters are esters of alpha-amino acids which essentially means that he was just as wrong as you in generalizing things, because it is generally not true that esters of amino acids get reduced under such condition. His claim that "amino acid esters are easily reduced with NaBH4 in 50% ethanol/water with yields of 80%+" is simply not true. It is true only for a very limited set of amino acid esters, but very far for being true in general.
Now you can both democratically "stick your foot in your mouth" if you please. :P

Also, diborane decomposes in protic media...

solo - 15-5-2009 at 21:15

........ok i was in a shit mood, women problems, my apologies to whomever i might insulted, but here is the reference,........solo

Studies on Optically Active Amino Acids. V. Synthesis of Optically Active α-Aminoalcohols by the Reduction of α-Amino Acid Esters with Sodium Borohydride
Seki Hedeo 1 Koga Kenji 2 Matsuo Hisayuki 3 Ohki Sadao 4 Matsuo Ichiro 5 Yamada Shun-ichi
Chemical & pharmaceutical bulletin Vol.13, No.8, pp. 995-1000,1965

Abstract
A facile reduction of optically active α-amino acid esters and their hydrochlorides took place with sodium borohydride in ethanol or aqueous ethanol to give the corresponding optically active α-aminoalcohols in fair yields. The reaction conditions were investigated.


.............also someone working on esters at WD posted this thread were the subject of ester reduction is discussed ....it may provide interesting reading,

http://gaussling.wordpress.com/2007/04/07/nabh4-reduction-of...

...and a thread here on this forum,

http://www.sciencemadness.org/talk/viewthread.php?tid=9023#p...

Attachment: Studies on Optically Active Amino Acids. V. Synthesis of Optically Active α-Aminoalcohols by the Reduction of &#945 (593kB)
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Arrhenius - 16-5-2009 at 10:20

Interesting paper. Thank you. I'd be interested to hear someone's results with it.

German - 16-5-2009 at 13:59

Edit by Nicodem: Post removed due to "swiming" (just as promised).

[Edited on 17/5/2009 by Nicodem]

solo - 16-5-2009 at 19:34

......why don't you just add some dilute NaOH solution to make it basic and go on with your reaction ....that might solve your problem......solo

DJF90 - 16-5-2009 at 22:00

Whats with the swim'ing? You've already been told it isnt welcome here :mad: In this very thread as well...

solo - 17-5-2009 at 06:48

SWIM; was something implemented at the former HIVE forum in order to keep annonimity and avoid self incrimination. It's still currently used at WD and other forums with the same concern in mind. There are topics which may insinuate some type of illegal chemistry or against the law in some country so it helps the forum and helps the members.
At this forum members feel they aren't doing anything questionalble, doubt that very much, but still, it's discussed openly without any concern of security and self preservation.......hence, my guess is that they don't want to be reminded with the use of the term ........of course this is my opinion ........solo

DJF90 - 17-5-2009 at 13:07

As soon as you see "swim" you know something funny is going on. It is an insult to our intellegence (we all know the swim'ers are talking about themselves...) and sometimes the swim'ers are so inconsistant that theres no point in involving swim in the first place! And I doubt it really lends any "protection" in a court of law.

turd - 17-5-2009 at 13:10

[OT]
Quote: Originally posted by solo  

At this forum members feel they aren't doing anything questionalble, doubt that very much, but still, it's discussed openly without any concern of security and self preservation.......hence, my guess is that they don't want to be reminded with the use of the term ........of course this is my opinion ........solo

No, I don't think this is the case. It's rather that anyone with common sense is probably aware that SWIMing will not protect you at all, since courts just aren't that dumb. For me it reeks of posers, tweakers and mindless people who think they are clever, when they clearly are not. And to make things worse, it makes postings hard to read.
[/OT]

[Edited on 17-5-2009 by turd]

setback - 17-5-2009 at 15:27
Quote:

No, I don't think this is the case. It's rather that anyone with common sense is probably aware that SWIMing will not protect you at all, since courts just aren't that dumb. For me it reeks of posers, tweakers and mindless people who think they are clever, when they clearly are not. And to make things worse, it makes postings hard to read.



More or less this, the real amusing part is that people actually believe swimming will save them. If Johnny Law wants you, they will get you.

vulture - 18-5-2009 at 09:47

Swimming is utterly useless. If you'd use your grey matter for a few milliseconds you'd realize that your username is in big letters next to your post. Not to mention the fact that it's tied to a IP address which any law organization will trace back to you with the help of a search warrant and your ISP. Unless you're smart ofcourse and use some way to cloak your identity. But then you'd also be smart enough to realize that swimming is both unnecessary and useless in that case.

Anyway, back on topic!

NaBH4 is also quite capable of reducing aromatic esters in my experience.

[Edited on 18-5-2009 by vulture]

solo - 18-5-2009 at 11:06

Reference Information

Sodium Borohydride: Carboxylic Acid Sodium Borohydride [in Japanese] Reaction of Sodium Borohydride. II. -Reduction of Carboxylic Acids and Esters with Sodium Borohydride
NOSE ATSUKO KUDO TADAHIRO
Journal of the Pharmaceutical Society of Japan 96(12) pp.1401-1406



Abstract
Reactions of carboxylic acids and esters with sodium borohydride were examined. With an equivalent mol of sodium borohydride, caproic acid (I) was reduced to 1-hexanol (II) in the absence of a solvent at 300°(bath temperature), and hexyl caproate (III) was obtained with 1/4 equivalent mol of sodium borohydride. Similarly, aliphatic and aromatic carboxylic acids were reduced to the corresponding alcohols with an equivalent mol of sodium borohydride. Reaction of esters with sodium borohydride gave the corresponding alcohols.


Attachment: Sodium Borohydride-Carboxylic Acid Sodium Borohydride [in Japanese] Reaction of Sodium Borohydride. II. -Reduction of Ca (742kB)
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