stoichiometric_steve
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Titanium Isopropoxide Reductive Amination
The Reference
While this reaction looks pretty nice, the workup is annoying:
"The reaction was quenched by pouring into aq. ammonia (30 ml, 2M), resulting inorganic precipitate filtered off"
and thats where the reference is lacking quite some detail, because a pretty much unfilterable solid - Ti2O(OiPr)2 - is formed, which took ~1.5h for
vac. filtration of 500ml. Even the attempted filtration through a 2cm pad of celite didn't help much.
Would it maybe be helpful to make a slurry with celite and then filter through a celite pad?
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Klute
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Good to see you are trying this out!
Can you get the solid to settle down afetr a while, and decant most of it out, or does make a suspension sludge?
How about directly steam distilling out the freebase after quenching/basifying? This works with aluminium sludge IIRC.
Or maybe quenching with Na2SO4.10H2O if that neutralizes the Ti(iPr)4.. It works well the LAH, although the hydride is more reactive.
How much eq of the isopropoxide did you use? wasn't the consumption too excessive?
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stoichiometric_steve
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for now, i used 2eq. of Isopropoxide/MeNH2*HCl/Et3N vs. substrate.
the stuff makes a pretty ugly suspension because it's so finely divided.
i was thinking about steam distillation, but in my case the product amine has a bp. of 300-310 °C@760mmHg and thus a pretty low volatility, which
will probably make steam distillation an unfeasible process.
i don't think the Na2SO4 decahydrate trick will work here.
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chemrox
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JCS paper
I pulled the paper down so we can all have a 'more legit' reference for this. The way I read it you did everything according to the paper including
the molar ratio and filtration. What if you filtered through spun glass to get rid of the more bulky crap and then used Celite? or paper? What if
you pulled it off with a strong vac? like 1-2mm?
I edited to ask about the cost. How does this reagent compare with using STAB in terms of cost? (STAB generally 3:1). When you get through this I
want to ask you guys for help with my reductive am. It's going to be about some details in using inert gas that I still have a few questions about.
The rhodium rendition didn't mention Ar as the article did in the general procedure. Did you use inert conditions? If not could oxidations have lead
to more inorganic ppt?
[Edited on 11-5-2008 by chemrox]
Attachment: Ti-propoxide technique_Perkin(16).pdf (89kB)
This file has been downloaded 3144 times
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stoichiometric_steve
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| Quote: | Originally posted by chemrox
What if you filtered through spun glass to get rid of the more bulky crap and then used Celite? or paper? |
I thought about using glass wool, but didnt have the time then. I will probably try again. I dont see how this could be advantageous since Celite is
supposed to do just that.
| Quote: | Originally posted by chemrox
What if you pulled it off with a strong vac? like 1-2mm?
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Your solvent will boil off and be sucked right into your vac pump. What you had in mind is pressure filtration! I almost bought a Sartorius pressure
filtration apparatus a few months back on ebay, but didnt have the necessary 300 EUR for it. 300 EUR for such a device is dirt cheap, although i think
a hardware shop can make one pretty easily for you.
| Quote: | Originally posted by chemrox
How does this reagent compare with using STAB in terms of cost?
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STAB is about 45 times as expensive for me compared to the Isopropoxide, taking into account the price of 100g STAB (largest size i can get) vs. 500g
Isopropoxide (can get up to 2kg sizes) and the needed molar ratio of 3 STAB : 2 Isopropoxide.
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synapse
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Why would you not just form the STAB in-situ from 3 equivs of GAA & NaBH4?
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stoichiometric_steve
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| Quote: | Originally posted by synapse
Why would you not just form the STAB in-situ from 3 equivs of GAA & NaBH4? |
why not go elsewhere with questions totally unrelated to the topic.
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Bolt
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| Quote: | Originally posted by stoichiometric_steve
"The reaction was quenched by pouring into aq. ammonia (30 ml, 2M), resulting inorganic precipitate filtered off"
and thats where the reference is lacking quite some detail, because a pretty much unfilterable solid - Ti2O(OiPr)2 - is formed, which took ~1.5h for
vac. filtration of 500ml. Even the attempted filtration through a 2cm pad of celite didn't help much.
Would it maybe be helpful to make a slurry with celite and then filter through a celite pad? |
Experiment 2 might help you.
Gravimetric Determination of Calcium as CaC2O4 . H2O
Calcium ion can be analyzed by precipitation with oxalate in basic solution to form CaC2O4 . H2O. The precipitate is soluble in acidic solution
because the oxalate anion is a weak base. Large, easily filtered, relatively pure crystals of product will be obtained if the precipitation is carried
out slowly. Slow precipitation is achieved by dissolving Ca(2+) and C2O4(2-)
in acidic solution and gradually raising the pH by thermal decomposition of urea.
http://bcs.whfreeman.com/exploringchem3e/content/cat_060/exp...
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stoichiometric_steve
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thanks, bolt! thats probably the best idea. although this is quite hard to accomplish when doing bigger batches, when the rxn. mix has to be slowly
poured into another liquid - the main problem being that there is already a (fine) precipitate in the original reaction mix.
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not_important
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Might try adding a strong solution of ammonium alum to the ammonia quenched solution. This should form Al(OH)3, often used as a flocculating agent in
water clarification. The sulfate ions may also aid in clumping the fine particles.
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stateofhack
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| Quote: | Originally posted by not_important
Might try adding a strong solution of ammonium alum to the ammonia quenched solution. This should form Al(OH)3, often used as a flocculating agent in
water clarification. The sulfate ions may also aid in clumping the fine particles. |
For water treatment, "fluctuation" actually i remember studying that Calcium oxide and Aluminum Sulphate are used, although i do not know how that
could be used here 
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not_important
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Aluminium sulfate in dilute slightly alkaline solution gives Al(OH)3, as does ammonium alum in aqueous ammonia or other alkaline solution.
floc·cu·late
v., -lat·ed, -lat·ing, -lates.
v.tr.
1. To cause (soil) to form lumps or masses.
2. To cause (clouds) to form fluffy masses.
v.intr.
To form lumpy or fluffy masses.
n.
Something that has formed lumpy or fluffy masses.
flocculation floc'cu·la'tion n.
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stoichiometric_steve
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the stuff is lumpy and fluffy, and with the right equipment (like pressure filtration in water treatment, the precipitate is no problem. just vac
filtration is a pain in the ass...
i don't see how NH4Al(SO4)2 would be of any help here, all it would probably do is make lots more solids to filtrate.
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not_important
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The point is to a the solids more filterable, like adding celite and like boiling which tends to make larger, faster filtering particles. If you are
saying there's too much already, rather than what is formed is difficult, try adding just plain ammonium sulfate to yhr aqueous ammonium on a roughly
equal molar basis with the Ti.
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stoichiometric_steve
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after the workup (i didnt bother washing the precipitate again, which probably trapped a lot of the product), i got about 12ml of product prior to
final distillation. this ain't much more than 60%...
Next time i'm gonna use 0.3 eq. of the Ti compound along with 1eq of the amine, probably as a solution in MeOH or EtOH.
[Edited on 16-5-2008 by stoichiometric_steve]
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Klute
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Hum, it's a pity....
Do you think potassium sodium tartrate would complexe the Ti salt, hopefully forming a soluble complex, as it does with quenced LiAlH4? Or maybe
another ligand complexing Ti easily...
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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LSD25
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I am looking seriously at how to isolate a product which appears to be semi-immune to my favourite workup procedure - which is how I found this
It examines the use of ion-exchange resins (both acidic & basic - cationic & anionic) to allow for the simplification of multi-step solution
based work-up techniques. They simply stir the post-reaction mix with the resin, then filter out the resin in a lot of cases, alternatively, where the
neutralization of the reaction mix causes problems, it is possible that by neutralizing with a strong-base resin it would be that the Ti precipate
would be attached to the amine group of the resin? Thus aiding filtration?
All that is needed now is a decent online source of small quantities of this shit (it is actually not to bad cost wise, especially as it can be
reused).
Attachment: Workup.strategies.for.High.throughput.soln.synthesis.pdf (88kB)
This file has been downloaded 983 times
Whhhoooppps, that sure didn't work
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stoichiometric_steve
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LSD25 - the scale i'm working on would need kilos of this shit - i'd rather go for steam distillation! thanks anyways 
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solo
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Reference Information (interesting reading)
---------------------------------------------------------------
One-pot reductive amination of aldehydes and ketones with α-picoline-borane in methanol, in water, and in neat conditions
Shinya Sato, Takeshi Sakamoto, Etsuko Miyazawa, Yasuo Kikugawa
TetrahedronVolume 60, Issue 36, 30 August 2004, Pages 7899-7906
Abstract
A one-pot reductive amination of aldehydes and ketones with amines using a-picoline-borane as a reducing agent is described.
The reaction has been carried out in MeOH, in H2O, and in neat conditions in the presence of small amounts of AcOH. This is a highly
efficient and mild procedure that is applicable for a wide variety of substrates. In particular, this is the first successful
demonstration that this
type of reaction can be carried out in water and in neat conditions.
Attachment: One-pot reductive amination of aldehydes and ketones with α-picoline-borane in methanol, in water, and in neat cond (219kB)
This file has been downloaded 4023 times
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solo
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I tried the above material on some phenylacetone and methylamine 40% in H2O, ....once without any solvents ....and the second time with only water
and acetic acid at the ration of 10:1 ....the reaction is a effervecent bubbling for 48 hours......phenylacetone was not dissolved in the mixture it
just stayed on top....doubt anything happened once post reaction rx with sodium carbonte solution was added and the organic extracted with
ethylacetate.....tried to chlorinate it but no show.....and the first reaction without any solvent did absolutely nothing.....added some methanol
after the reaction to silence the borane , then ph to 13, and extracted organic material with toluene....tried to chlorinate and nothing.....what
happenend, has anyone tried this reaction as I was hoping to also try it with L-Pac.... solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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chemrox
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@solo- I assume you'd already done this with Al amalgm and were looking for another way to do this? For instance I saw this one done with galvanized
steel as the catalyst and Meam in formic acid...high yields - larger scale..but back to the present: @ stoiciometric- this alternative workup would
use a benzaldehyde impregnated resin tube to separate 1* from 2* amines..(?) I need a way to do this too. Can you make your own tubes from
commercial resins and reagents? Did you find a workup yet? Did you try Na2SO4 solution to get better crystals? and I nearly forgot to ask: did you
make the Ti isoproxide reagent in situ? If not I take it it was pretty cheap (where from?).
I like both of these as alternatives to STAB. Does anyone know the cost of pic-BH? how it compares to STAB? I don't care for chromatographic
workups .. how to apply to a larger scale effort?
[Edited on 17-11-2008 by chemrox]
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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stoichiometric_steve
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chemrox:
- If you can buy GAA, then you're much better off preparing STAB yourself. I gather from the various preparations posted in other threads that it's
pretty easy.
- As posted earlier, the addition of huge amounts of water to the post reaction mixture indeed produces a filterable inorganic solid, making the
workup much more bearable. Still, you need huge amounts of the Titanium reagent on a larger scale. The cheapest source for me is about 200 USD for 2kg
of Ti(OiPr)4, that's roughly 7 moles.
- Ti(OiPr)4 was always bought, never prepared in situ since TiCl4 is equally expensive.
- Considering the cost of Picoline-BH3: IF you can get it, you can as well get NaBH4, so stick to that.
solo:
If your phenylacetone was never in solution, how did you expect that the imine formation/reduction should occur?
[Edited on 18-11-2008 by stoichiometric_steve]
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Klute
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Amine boranes are easily made by adding NaBH4 to a solution/suspension of the amine hydrochloride in THF or ether/H2O mixtures, filtering the NaCl and
evaporating the solvent under vacuum.
Coll. Czech. Chem. Commun., 1969,34, 3009
and
| Quote: |
The second major route to alkylamine-borane adducts is the reaction of an amine hydrochloride salt with a borohydride. The original investigators used
lithium borohydride in diethyl ether and obtained an 86% isolated yield of amine-borane based on equation 116 Sodium borohydride in THF is now the
reagent of choice for the synthesis of amine-boranes from amine-HCl and a few specific examples are given in Table 3.
LiBH4 + (CH3)3N●HCl → (CH3)3NBH3 + LiCl + H2 (9) |
http://www1.eere.energy.gov/hydrogenandfuelcells/pdfs/nbh_h2...
(jump to page 8 for the table)
This makes me wonder if it's not possible to simply use the amine used for the imine-formation (methylamine in Solo's case) to form the complex: add
NaBH to a solution of the amine hydrochloride, some base to liberate the rest of the amine as freebase, and add the carbonyl: no mixtures of amines.
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Organikum
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Quote: Originally posted by solo  | | I tried the above material on some phenylacetone and methylamine 40% in H2O, ....once without any solvents ....and the second time with only water
and acetic acid at the ration of 10:1 ....the reaction is a effervecent bubbling for 48 hours......phenylacetone was not dissolved in the mixture it
just stayed on top....doubt anything happened once post reaction rx with sodium carbonte solution was added and the organic extracted with
ethylacetate.....tried to chlorinate it but no show.....and the first reaction without any solvent did absolutely nothing.....added some methanol
after the reaction to silence the borane , then ph to 13, and extracted organic material with toluene....tried to chlorinate and nothing.....what
happenend, has anyone tried this reaction as I was hoping to also try it with L-Pac.... solo |
Your problem here was that you did not read the article well enough, it states that reductive aminations in water work only with water insoluble
amines and MeNH2 is water soluble as hell.
The advantage of picoline borane as of pyrindine borane is the solubility and the possibility to work in alkaline condtions. NaBH4 and STAB suffer
from solubility issues - they just do not dissolve well in organic solvents, an alkaline environment comes handy when working with Boc protected
compounds.
Ammonia borane is also an interesting one, it needs a Lewis acid to get anything going but thats true for many amine boranes - better to use one.
Titanium isopropoxide seems to works as Lewis acid somehow and it allows to get primary amines from a ketone and a salt of ammonia in good yields and
thats something for sure.
If I am not mistaken the propoxide can be easily made from Ti-tetra-halide and Iodine and bromine both form this by just adding the halide to Titanium
metal or TiO2. Adding the tetra-halide to IPA gives the propoxide, a base is added to scavenge the acid formed.
Funny enough: I wager this system would reduce a benzylic alcohol without problems if no scavenger is present. 
Also an alley worth exploring: If an chiral amine is used, chances are that the product of a reductive amination is chiral too, pre-chiral ketones
reduced to alcohols this way are enatiomeric pure.....
And chiral amines, well there are plenty.
I add some papers on the whole amine borane cosmos, maybe somebody will derive some inspiration from them....
The last one is about Magnetite nanoparticles as catalyst in Imine formations and I find it extraordinary interesting and will give it a shot quite
soon.
Attachment: Reductive_amination_using_ammonia_borane.pdf (90kB)
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Attachment: phpxB2VyN (238kB)
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Attachment: phpoYyIhQ (305kB)
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Attachment: Reductive Aminations of Ketones and Aldehydes using Borane-Pyridine .pdf (604kB)
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Attachment: Pyridine-Borane_redAmi.pdf (272kB)
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Attachment: phpladbM0 (226kB)
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Attachment: Onepot_reductive_amination_with_alphapicolineborane.pdf (171kB)
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Attachment: AMINE_BORANES_REDUCING_HYDROBORATING_AGENTS_REVIEW.pdf (1.2MB)
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Attachment: ramachandran2015.pdf (238kB)
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Attachment: phpflS7Jy (220kB)
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regards
/ORG
[Edited on 26-12-2022 by Organikum]
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