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azo
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reductive amination with triacetoxyborohydride
Has anyone used triacetoxyborohydride for the reductive amination of aromatic ketones with primary amines i understand that it is selective towards
imine formation without forming the imine first with very little reduction of the ketone to the alcohol but i have also read that it is sluggish with
aromatic ketones and has limitations with aromatic ketones. Is nacnbh3 a better choice or does it give poor yields on non substituted ketones
does this pass your stringent rules nicodem
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Magpie
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Standard English is the official language of this forum. You know, capitalize the first letter of a sentence, use a period at the end of a sentence,
capitalize the pronoun I, etc. This should all be familiar from grade school. We have many contributors whose first language is not English who do a
fine job with grammar and punctuation. Why is it so difficult for you? You basically just show laziness and disrespect when you don't follow
standard forms. Also remember that the first letter of the symbols for chemical elements is also capitalized. Using standard punctuation makes it so
much easier on the reader. After all, why are you posting if not to successfully communicate with your readers?
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vulture
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Given the fact that NaCNBH3 (how hard is it to use capitals appropriately?) is less nucleophilic, it should work better with unsubstituted ketones
(which is an incorrect term anyway), as they are more electrophilic.
BTW, if you want help and expect your stay to be extended on this forum ,stop being an ass and learn how to capatalize properly, ie NOT ALL THE TIME,
but also not never! And how about some punctuation? You really think people are going to help you if they get a headache from reading your posts?
Did you always shout at your teachers when you wanted an answer?
| Quote: |
We have many contributors whose first language is not English |
And I happen to be one of them, FYI.
[Edited on 25-3-2008 by vulture]
[Edited on 25-3-2008 by vulture]
One shouldn't accept or resort to the mutilation of science to appease the mentally impaired.
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azo
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If i have made it hard to read i am sorry. I didnt think it was so important !.
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MagicJigPipe
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Right, communicating so others can understand you and respect what you say has never been important *sarcasm*. How well one can write is indicative
of ones motivation, responsibility and general intelligence. For example, if you can't apply things you learned in 3rd grade to your everyday life
then what the hell else can you be expected to do properly? Work in a respectable manner at a decent job? Be trusted with simple tasks (as simple as
capitalizing the pronound "I")? Of course not. It may be wrong but people get the impression that you are lazy, ignorant, apathetic, lazy and
(around this forum) a typical meth cook (I mean, your question is about aromatic ketones. I could have guessed) when you can't take the time or
muster up the wherewithal to type correctly. Also, do you know part of the reason bad grammar and ingorance is associated with meth cooks? Because
over at WetDreams that's how most of the people type. I mean, that forum probably wouldn't have such a bad rap if the people there communicated
themselves properly. To put it bluntly, it makes you look like an idiot when most people who speak English as their second language can write it
better than you.
What's funny is even after we told you about it you still didn't capitalize your "Is"! Not to mention "didn't" is a contraction and needs an
apostrophe. And I'm sure, at this point, commas would be way too much to ask for. Even if you don't have PERFECT grammar that requires high school
education you should at least know punctuation, capitalization and basic sentence structure. That's literally elementary shit.
If you really are still in the 3rd grade let us know so we can understand. Otherwise, stop being so lazy! And if you don't know this basic shit go
LEARN it and then come back and worry about how to manufacture methamphetamine from phenylacetone. The former is obviously more important.
As you can see guys, this kind of thing really pushes my buttons and I'm sorry for the rant.
[Edited on 25-3-2008 by MagicJigPipe]
"There must be no barriers to freedom of inquiry ... There is no place for dogma in science. The scientist is free, and must be free to ask any
question, to doubt any assertion, to seek for any evidence, to correct any errors. ... We know that the only way to avoid error is to detect it and
that the only way to detect it is to be free to inquire. And we know that as long as men are free to ask what they must, free to say what they think,
free to think what they will, freedom can never be lost, and science can never regress." -J. Robert Oppenheimer
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azo
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You no what makes me sick as soon as you ask a simple question? you get accused of being some meth cook where I live you wouldn't be able to get
the chemicals needed anyway.
Is there some law against research into this field?
Since being on this site I have had nothing but abuse
And accused of doing things I have not done and will not do
One day someone will need my help and I will not reply.
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grind
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As far as I can remember there is an article in which is made a comparison between NaCNBH3 and NaBH(AcO)3 in reductive amination. And if I remember
rightly, they say NaBH(AcO)3 is of great advantage and gives much higher yields in virtually all cases.
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MagicJigPipe
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If it looks like a duck and smells like a duck...
Really, I don't care whether you're a "meth cook" or not. You should be able to do what you want in your home. It's just that you are acting like a
stereotypical methcook by typing like a monkey and asking questions about chemical processes that could be used in the manufacture of amphetamines.
WHAT THE HELL ELSE are you going to get from reductive alkylation of "aromatic ketones with primary amines"? You might as well just come out and say
it "for the reductive animation of [methylenedioxy]phenyl-2-propanone with methylamine". Anyway, I apologize for contributing to the clogging of this
thread but I think we have enough P2Pish threads already.
Shall we continue?
"There must be no barriers to freedom of inquiry ... There is no place for dogma in science. The scientist is free, and must be free to ask any
question, to doubt any assertion, to seek for any evidence, to correct any errors. ... We know that the only way to avoid error is to detect it and
that the only way to detect it is to be free to inquire. And we know that as long as men are free to ask what they must, free to say what they think,
free to think what they will, freedom can never be lost, and science can never regress." -J. Robert Oppenheimer
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pantone159
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I'm actually interested in STAB, it seems like an actual chemistry question, I really don't care much (as far as reading and understanding) what the
legality of the substrates are.
That doesn't excuse silly capitalization games however.
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Klute
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Isn't an aromatic ketone by definition a ketone of the type: Ar-CO-R? In that case phenypropanones are not aromatic ketones, even though they contain
aromatic ring.
Thus, the limitations in that JACS 1996 article on STAB your are surely talking about don't apply to phenypropanones.
An aromatic ketone is going to form a stable imine, even if it can take a while. Depending on the bp of the amine you plan on using, refluxing
toluene in a dean stark trap is going to get you your imine. Remove most of the toluene under vacuum, add methanol or another alcohol, and use NaBH4
to reduce your imine. STAB only has 1 hydride to react, so you will need 4x the amount of NaBH4, which is a waste if you make it from NaBH4 in GAA.
STAB is really only needed when good yield are crucial, wxith expensive products, the more delicate substrates or for the N-alkylations mentionned.
Again, CTH or catalytic hydrogenations could get you were you want. You good give dissolving metals a look too: Al, Mg, Na...
Don't get pissed so quickly. This forum is the way it is, but can bring much is you make the effort to have a correct attitude. I will stop here for
the political/social aspect.
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Nicodem
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Azo, thank's for improving your grammar, though you still have much space for improvement (at the moment that "nacnbh3" was indeed the most annoying
mistype while the rest was almost readable).
MagicJigPipe, phenylacetone is not an aromatic ketone so don't jump to conclusion and divert every thread that you can into some meth-discussion.
Now, please let us continue with the topic of using STAB in reductive aminations. There is almost an entire page of posts added an nothing
scientifically useful yet. I'm too tired at the moment to do a literature search, so someone else please post some reviews on this reagent so to give
this thread some meaning.
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stoichiometric_steve
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i'd say, experiment is king.
the up-side of STAB is its easy preparation from cheap NaBH4 with 3.05eq glacial acetic acid in toluene.
its down-side is that you only have one hydride equivalent per mol.
it is indeed the case that aromatic ketones react sluggishly, whereas it would be preferred to use a preformed imine (which can be accomplished by
drying the reaction mix with molecular sieves or silica gel) and subsequently adding NaBH4.
NaBH3CN is so exceedingly expensive that you dont really want to mess with it unless you have no, really NO other choice.
[Edited on 26-3-2008 by stoichiometric_steve]
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MagicJigPipe
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I apologize, I read it too quickly and didn't realize he was speaking of "aromatic ketones" as opposed to an aromatic with a ketone functional group.
Regardless, that was not the point of my post.
I have found 2 posts of mine that could be considered "diverting into a meth discussion". Please, do not generalize my posting habits as such.
"There must be no barriers to freedom of inquiry ... There is no place for dogma in science. The scientist is free, and must be free to ask any
question, to doubt any assertion, to seek for any evidence, to correct any errors. ... We know that the only way to avoid error is to detect it and
that the only way to detect it is to be free to inquire. And we know that as long as men are free to ask what they must, free to say what they think,
free to think what they will, freedom can never be lost, and science can never regress." -J. Robert Oppenheimer
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jizmaster
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Here's a nice article on some of the stuff that can be done with borohydrides. Had no idea about half of that stuff, reductions of amides, nitriles,
benzylic ketones and alcohols, deoxygenation of enones! Using 3 eq N-CO2iBu proline instead of acetic acid allows enantioselective imine reduction!
And lots of examples of plain reductive aminations here, some take a long time!:
http://taz4.erowid.org/archive/rhodium/pdf/sodium.triacetoxy...
I think the easiest way usually is to just make the imine and then reduce with NaBH4. Doesn't get much simpler, just stir in alcohol to form the
imine, add borohydride, wait 10 min, quench.
Attachment: Acyloxyborohydride review.pdf (434kB)
This file has been downloaded 939 times
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azo
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I supose one could do the reduction in acetic acid with NaBH4 using 1 mole NaBH4 and 1 mole acetic acid which would produce the more reactive
acyloxyborohydride. The acyloxyborohydride would have three hydride ions and would not reduce the ketone to the alcohol at all.
NaBH4 + 3RCO2H > NaBH(OCOR)3 + 3H2
NaBH4 + RCO2H > NaBH3OCOR + H2
By the way magic jig the reduction of a ketone with a amine is called a reductive amination the reduction of a amine with a alkyl group is reductive
alkylation
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jizmaster
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No, like you said the monoacetoxyborohydride is more reactive. Probably not as reactive as plain borohydride but it will still reduce ketones.
What i don't understand is how the borohydride/TFA combination appears even more reactive than plain borohydride. Electron withdrawing acyl groups
should increase the B-H bond strength, making it a weaker source of hydride. Is the hydride not able to full compensate for the electron withdrawal of
the acyl groups, maybe, resulting in a more acidic boron and less polarised B-H bond? This does seem to explain the increase in 'borane like'
behaviour with increasing substitution with EWG's.
Paper on hydroboration with 'sodium malonyl borohydride':
http://www.rsc.org/ej/NJ/2001/b100228g.pdf
Azo, maybe you could use this or another diacyl borohydride for intermediate reactivity? Though i'm still not sure if that's what you want, by
aromatic ketone do you mean the ketone is on the carbon atom connected to the aromatic ring? (the benzylic carbon) Or is it just an aliphatic ketone
with an aromatic system elsewhere in the molecule? Only if it's attached right next to the ring is it sometimes less reactive than an aliphatic
ketone.
[Edited on 27-3-2008 by jizmaster]
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Nicodem
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I don't think the trifluoroacetoxy anion is enough powerful ligand to form a stable NaBH3(CF3COO) type of borohydride. Instead this should further
decompose to diborane and CF3COONa. Hence the borane-type of reductions can be done with this combination. It is similar like the oxidation of NaBH4
with I2 which also results in the formation of diborane.
[Edited on 27/3/2008 by Nicodem]
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Phosphor-ing
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http://www.organic-chemistry.org/abstracts/literature/717.sh...
Is this what your talking about?
"The nine most terrifying words in the English language are: 'I'm from the government and I'm here to help.'" -Ronald Reagan
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Klute
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| Quote: | I supose one could do the reduction in acetic acid with NaBH4 using 1 mole NaBH4 and 1 mole acetic acid which would produce the more reactive
acyloxyborohydride. The acyloxyborohydride would have three hydride ions and would not reduce the ketone to the alcohol at all.
NaBH4 + 3RCO2H > NaBH(OCOR)3 + 3H2
NaBH4 + RCO2H > NaBH3OCOR + H2
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I'm not sure you can obtain monoacetoxyborohydride simply by adding 1 eq of AcOH, IIRC you will surely obtain a mixture of triacetoxy, a little
diacetoxy or less monoacetoxy, unless you use low temperatures. But i haven't checked the lit for this, i just remembered that monoacetoxyborohydride
isn't something you succesfully use as such, and obviously not isolate (although i guess you planned on making it insitu).
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grind
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You can add 4 or more moles of AcOH to 1 mol of NaBH4, in the cold only triacetoxyborohydride is formed. The last H is replaced at elevated
temperatures with an excess of acid.
You need very finely powdered NaBH4 and the complete conversion to triacetoxyborohydride takes a lot of time (min. 12 h) in the cold, even with an
excess of AcOH. The suspension becomes gel-like during the process.
[Edited on 27-3-2008 by grind]
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Klute
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So i could be wrong thinking mono- and di-acetoxyborohydride don't exist for long... My bad.
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azo
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hi klute
In relation to the formation of the imine in toluene i take it you ment a toluene and a aquous phase,. And if so do you need to use an acid catylist
to protonate the oxygen which would leave the carbon atom even more electron deficient and open for attack from the nucleophile. I am not so sure
about the removal of the water during the imine formation by forming an aziotrope with toluene is this good enough to drive the reaction in the
direction of imine formation.
regards azo
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Nicodem
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The most general method for the synthesis of imines is just that, an azeotropic removal of water with the Dean-Stark trap from the refluxing mixture
of the amine and ketone/aldehyde in the presence of catalytic amounts of TsOH. However, in most cases two or more days of reflux are used for complete
conversion.
Of course, by diluting such imine containing solution with MeOH and reducing with NaBH4 gives you the corresponding amine without the need to actually
isolate the imine intermediate. If this is the goal, the complete conversion to the imine (requiring days of azeotropic drying) in several cases is
not even necessary since protonated imines reduce at a much greater speed than ketones. This actually shifts the imine formation equilibrium and can
results in the amine being the main product. There are even rare cases where it is possible to do reductive aminations with NaBH4 directly on
methanolic solutions of an amine and ketone/aldehyde, though only in cases where the imine formation step is rapid enough.
The problem with any such approach is that its not predictable enough and only an experiment can tell you if it works at all and if it works what are
the yields. On the other hand using general STAB mediated aminations you can expect good results and less frustrations.
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azo
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Thank's nicodem that explains it well.
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Klute
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I haven't got much to add! 
The problem with toluene is that low boiling amines (NH3, MeNH2, etc) tend to evaporate off during the long reflux, or at least concentrate in the
trapped water ( no aq layer btw, the water is eliminated as it forms so you have a sometimes milky homogeneous phase). Besides using a very arge
excess of the amine, i haven't worked a way out of this... Maybe using the amine salt and slowly dripping trietylamine at RT, then refluxing would be
ok. For low boiling reflux, you can use pet ether as a solvant, i forms a ~5% azeotrope with water, i've used it for condensations and the pot temp
never went over 60°C. If I distilled the pentane fraction, or used pur pentane, the temp would be even less. I could take a few hours more though.
Have you considered the Ti isoproxide route? The "regular" grade isn't that expensive, and the reaction is said to work well with delicate
substrates...
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