Author Topic: Easy NaBH4 amination  (Read 3178 times)

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XrLeap

  • Guest
Easy NaBH4 amination
« on: September 17, 2004, 08:46:00 AM »
SWIM received a PM on doing the NaBH4 amination easy way.

The method has been mentioned all over bee hive, but there is no detailed description on it. SWIM is now posting this in NewBee forum for sharing. Please bear with it if this has been described in detail before.

This is the LabTop's methanol method with easy generation of methylamine gas.

Materials:

MDP2P 1 weight unit
Methylamine.HCl 0.7 weight unit
NaOH 0.42 weight unit
Methanol 3 weight unit
NaBH4 0.1 weight unit

3A molecular sieves 0.5 unit

1) Dissolved all methylamine.hcl in warm methanol.
2) Dissolved all NaOH in the previous solution, while applying cooling with ice/salt bath.
3) Filtered the NaCl formed after methylamine gas generation in situ completed. One can see that all NaOH has been dissolved.
4) Throw in some amount of 3A mol sieves to hopefully dry the methanol. Stir for 1 hour. 24 hours would be good.
5) Added the PMK cooled.
6) Added NaBH4 a la LabTop.
7) Removed cooling, stirred for 21 hours.

Workup as usual. The standard workup for SWIM:
1) Throw in 3x or 4x volume of 10% NaOH into the solution. PH as high as possible.
2) Let settle, meaning there are 2 layers formed.
3) Seperate the lower layer in this case.
4) Add in DCM(low boiling point, good extraction) to extract more freebase, 3 times would be enough. Now the aqeous solution should look very clear.
5) Make the soluion acidic, pH 3 is good, by adding dilute acid solution.
6) Discard the DCM layer now. This contains maybe unreacted PMK.
7) Make the aqeous solution alkaline.
8) Extract with DCM 3 times.
9) Distill off DCM, residual Methanol or other lower boiling stuff. Under atm pressure, stirring is applied for distilling very volatile solvent like DCM.
10) Apply vacuum to distill the lovely smell free base.
11) To squeeze over the last drops, turn off the vaccum, bring the flask's temperature higher by 15C to 20C. Then apply the vaccum again. Red or grey tar forms in the flask.

This is nothing new, but SWIM just wishes to share what he received from fellow helpful bees.


XrLeap

  • Guest
Oops, SWIM forgot to indicate yield.
« Reply #1 on: September 18, 2004, 02:47:00 PM »
Oops, SWIM forgot to indicate yield. 85% m/m can be achieved repeatedly. MDP2P used was obtained thru benzo wacker, 1 time distilled.

1 way to improve further is to add the 3A mol sieves after PMK addition, to remove H2O from imine formation.


XrLeap

  • Guest
Help needed
« Reply #2 on: October 23, 2004, 11:17:00 AM »
SWIM is using this method to aminate his ketone:

Post 531792

(XrLeap: "Easy NaBH4 amination", Newbee Forum)


In the cooling part, SWIM tried to use dry ice to cool the methanol solution and it became below -20C. This was during addition of NaBH4, the temaperature stayed below 0c until all NaBH4 was added. Lowest was way below what a normal thermometer could indicate.

However, there was problem. When SWIM returned the next day, there was still a lot of NaBH4 undissolved(teampurature @ 21C), the methanol solution(methanol, methylamine, ketone, NaBH4) looked very concentrated. SWIM went on to work up(A/B extraction plus distill) and obtained only about 50% yeild.

Is adding of NaBH4 needed to be between 0 to 150C? SWIM started from below -20C. This was done on multi mol scale.

Could imine formation be done under -20C?

Could amine formation be done under -20C?

Or could it be that methylamine.HCL and NaOH could not react to produce methylamine(free base) + NaCL + H20 under -20C?

If it was possible to produce methylamine(free base) + NaCL + H20, will the H20 become solid(ice) under that temperature?

Allow SWIM to say thank you for taking your precious time in reading this. Thank you.

XrLeap


LaBTop

  • Guest
You are confused with 3 procedures.
« Reply #3 on: October 23, 2004, 04:24:00 PM »
Making 10% MeAm-gaseous/MeOH, Imine-forming, and Amination !

In the cooling part, SWIM tried to use dry ice to cool the methanol solution and it became below -20C. This was during addition of NaBH4 (LT: that's the Imine to Amine forming step!), the temperature stayed below 0°C until all NaBH4 was added. Lowest was way below what a normal thermometer could indicate.



The first procedure you are confusing is to use Methanol as cold as can be, to obtain a 10% MeAm-gaseous/Methanol solution by introducing gaseous Methylamine from a gas cylinder or any other means in very cold Methanol.
You have to repeatably re-cool the Methanol, since adding of MeAm gas will quickly warm up the Methanol, thus you have to put your vessel back in a freezer a few times.
OR, instead of a freezer, you use a cooling vessel around your mixing vessel where you dropped chunks of dry-ice in f.ex. Acetone (stinks) or Methanol(you already have it at hand, and it doesn't stink), to force-cool your fast warming up MeAm/Methanol mixture during bubbling MeAm gas.


However, there was problem. When SWIM returned the next day, there was still a lot of NaBH4 undissolved(temperature @ 21°C), the methanol solution(methanol, methylamine, ketone, NaBH4) looked very concentrated. SWIM went on to work up(A/B extraction plus distill) and obtained only about 50% yeild.



That is caused by a much too low temperature of the NaBH4 addition step. What you were seeing when returning was a lot of decomposed NaBH4.
The NaBH4 addition step must be performed at temps between 0 and 5°C, so, cooling with simple COLD water from the tap with lots of icecubes in it, is sufficient to keep the temperature in that range.
Logical ofcourse, since you add only relatively very small portions (1:100) of NaBH4 to a huge motherliquid load of Methanol, and that big mass will never warm up as quickly as the other first step, the preparation of a 10% gaseous MeAm/Methanol solution (1:10).


1. Is adding of NaBH4 needed to be between 0 to 15°C? SWIM started from below -20°C. This was done on multi mol scale.
2. Could imine formation be done under -20°C?
3. Could amine formation be done under -20°C?
4. Or could it be that methylamine.HCL and NaOH could not react to produce methylamine(free base) + NaCL + H20 under -20°C?
5. If it was possible to produce methylamine(free base) + NaCL + H20, will the H20 become solid(ice) under that temperature?



1. That's the Editimine to amineEndEdit formation step! Between 0 and 5°C. Stay away from roomtemperature and freezing temps of the WHOLE stirred motherliquid, the cooling liquid however can and will have a MUCH lower temperature as the motherliquid, because it can only cool the walls of the motherliquid-vessel!!! That's why cooling liquid temperature indications of a 1000 liter vessel are VERY very different from a 2 liter vessel! The motherliquid load to be cooled is much smaller in the latter case, so you probably read my huge One-pot method and didn't realize that those are instructions for huge scale procedures. I expected those times, my readers to understand that Chemical Engineering is quite different from a research lab with a RotoVap with a 2 liter reaction flask.
So, always stirr fast and powerfull in big vessels and in small glass vessels in relation to the flask. And read the temperature of the MOTHERLIQUID, and only compare that to the reading of the COOLING LIQUID. Thus keeping a fine balance between extraction of energy from the motherliquid via the walls of your vessels, by your cooling liquid.
And do not throw chunks of dry ice INTO the motherliquid. Do you know the effect of CO2 on your reaction? No.
2. That's too cold. See 1.
3. EditNot advisable. See again 1., keep it between 0 and 5°C.EndEdit
When supposing you mean gassing of the amine-base fluid with HCl gas, again, don't overdo, cool the Acetone or Toluene in a freezer, that's the easiest way, and then bubble HCl gas in, and replace the vessel in the freezer when you can feel with your hands on the vessel wall that the temperature rose too high. This repeatingly cooling of the crystalizing process will in the end reward you with the highest yield of crystals.
4. You proved to yourself already that it greatly delays the process, so, you only needed someone else to tell you: Yes, not sufficiently.
5. If enough NaCl salt will be present and will form a saturated solution in the formed water, plus a portion of non soluted salt, you have to look up a freezing table of saturated salt solutions. But in your case, it is mixed with a freebase gas MeAmine, which will make that table useless. Only practice will tell you fast. But you can freeze a lot of solutions, when you go cold enough. But I do understand what you ask, can I separate the water and the salt, by freezing, from the freebase MeAm.
Or do you ask if you can salt out freebase Methylamine gas, out of the formed salty water? Then you must add the Methanol in your little list and the NaOH.
Practice will show you.
 :)

Edit: I think now, that basically, you ask in point 5, perhaps this:
If adding extra salt from an extern source (a pot of NaCl) to the motherliquid of Methanol, MeAm.HCl, NaOH beads, AFTER the NaCl + H2O formed , aiming to end up at a thoroughly saturated salt solution of the WATER, formed as a reaction product of the .HCl from the Methylamine.HCl salt with the NaOH (which also forms the water as a second reaction product), will salt out the Methyl amine GAS freebase, out of the formed water, so it stays SOLELY soluted in the Methanol. But Methanol mixes indefinitely with water, your first problem.
Your second problem, you indicated that all NaOH soluted, and that you filtered off the rest of the non-soluted NaCl, which means, that your water part was already saturated, otherwise you would have not seen any solid NaCl.
You better do the stochiometric calculations, to find out for yourself, how much, in grams, water will be formed with the amounts in grams you took for the reaction participants.
You will see that there is not that much water formed, and that it is saturated with NaCl salt, making it more difficult for Methanol to mix with that water.
Let's look at your first steps:


1) Dissolved all methylamine.hcl salt in warm methanol.
2) Dissolved all NaOH in the previous solution, while applying cooling with ice/salt bath.
3) Filtered the NaCl formed after methylamine gas generation in situ completed. One can see that all NaOH has been dissolved.
4) Throw in some amount of 3A mol sieves to hopefully dry the methanol. Stir for 1 hour. 24 hours would be good.



Freezing the water out instead of step 3 to safe time, will be complicated or not possible, practice will proof it, because you have a Methanol/saltwater mixture, which mixtures are notorious for lowering their freezing points, compared to the sole constituents of the mixture.
So, try freezing the water out after step 3, but without filtering the precipitated NaCl salt. Because if you succeed, you only have to separate the ice and the NaCl from the MeAm/Methanol mix.

I still think using dried silicagel beads from Merck will do the trick, sucking up the water, in one to two hours under strong mixing in a closed vessel, so no new water from the air can be added.
And I also assume that perhaps Bariums wet boro method will avoid a lot of these problems.
However, if you feel comfortable with this method, after finetuning it with the temps I gave you, this will be just as easy, since you indicated that before you used that far too strong cooling during imine forming (with CO2 dry-ice chunks, perhaps even thrown in the motherliquid, which is wrong), everything worked out fine, with a 80 to 85% yield molar/molar.
I hope you meant that by giving yield in m/m.

EndEdit.

You really all need to read this thread first, before attempting testruns:

Post 439864

(Vibrating_Lights: "Imine reduction", Newbee Forum) .
And then try first to understand all implications of what is posted there.
An example of more extensive knowledge, obtainable from that thread is from this post:

Post 440189

(LaBTop: "Excellent Boro info I page 1", Newbee Forum)
:


Sodium borohydride reductions are generally conducted in solvents such as methanol or ethanol due to its high solubility in them. However, the efficiency of sodium borohydride in these solvents is very poor due to the high rate of decomposition. Conducting the reaction in two phases using non-polar aprotic solvents such as hydrocarbons and a phase transfer catalyst can alleviate this problem. In hydrocarbon solvents sodium borohydride is stable and does not undergo decomposition reaction and thus its complete utilization can be realized.



Because of that high rate of decomposition, we add very small portions of NaBH4 to very big amounts of 10%MeAm/Methanol, at such a highest possible temperature (ca.+5°C), that the inevitable decomposition has the smallest chance to occure!
And look for posts of Barium for his use of hydrocarbons and a phase transfer catalyst( PTC ) like Alliquat, in his wet methods.

LT/




LaBTop

  • Guest
I see that Aurelius
« Reply #4 on: October 23, 2004, 07:44:00 PM »
has changed that strange 4.16 % to 41.6 %, that seemed also a bit strange to me, when I read and reread that text.
(

Post 440349

(Aurelius: "JACS 74(9), 2346-2348 (1952)", Newbee Forum)
, the sup-text in blue halfway.)
In the same text, something interesting caught my attention while reading it, but I never saw anyone commenting on it:

Aqueous Metathesis with Lithium Borohydride.

Although lithium borohydride ordinarily reacts violently with water, it was discovered that if the pure compound is introduced anaerobically at or below 0*C, a solution results with but minor loss of activity.  Air-free distilled water is employedThe resulting solution is sufficiently stable to permit its use over a period of hours.



This could be an important yield promotor in Bariums wet boro method.
Why should sodium borohydride not act the same.
 
Can anybody, preferably Barium and those familiar with the latests methods, try the latest wet method imine forming procedure out under high vacuum? LT/




LaBTop

  • Guest
I inserted a quite long Edit
« Reply #5 on: October 24, 2004, 12:24:00 AM »
in post nr 537294. Please read that first, before commenting. LT/


indole_amine

  • Guest
evacuating would probably be counterproductive
« Reply #6 on: October 24, 2004, 12:59:00 AM »
Difficult - all imine reduction methods rely on shifting the equilibrium carbonyl + amine -> imine + water to the right by either removal of water and/or imine (its reduction to the amine is irreversible). If vacuum is applied, the commonly used primary amines (MeNH2, NH3) are continuously removed as gases, resulting in shifting the equation equilibrium towards the educts - I doubt it would improve anything...

Sodium and lithium don't react the same way: one slowly gets oxidized when coming in contact with air, while the other often explodes rather violently. I think this enhanced reactivity of lithium can be put on one level with that of sodium- vs. lithiumborohydride. (I would like to see someone throwing a big lump of lithium into a bucket of water!  :o )

To make water air-free, it also can be put under vacuum before dissolving the borohydride in it, isn't it? (at least as long as you immediately flush with inert gas right after air removal/before commencing with borohydride addition, it should be impossible for any air to enter the borohydride solution...  ;) )

(BTW slightly basifying the borohydride solution with NaOH does a very good job too in stabilizing the whole shebang... at least most of the manufacturers of aequous borohydride solutions believe in it!  ;) )


indole_amine

LaBTop

  • Guest
Yes,
« Reply #7 on: October 25, 2004, 05:01:00 AM »
you are right, I should have frased it as follows:

Can anybody try out Bariums wet method with 40% NaBH4 --in water--, where that water portion is then made airfree by applying high vacuum first.

Since the quote says that the resulting -airfree- 40% NaBH4/water solution stays fairly reactive during several hours, this should be tried asap.
And I read that "several hours" as under normal reaction circumstances, so without applying high vacuum during that reaction. The 40% NaBH4 in there will remain quite active during several hours.
He already uses a commercially obtained (basified with a pinch NaOH) 40% NaBH4 solution, but I like to see if the yield can be improved further by making that commercial solution also airfree.
I'm a yield-freak. ;)   LT/

PS: made a few edits extra in the long post, to clarify things which were typed wrong.


r2e3

  • Guest
ok
« Reply #8 on: October 25, 2004, 08:29:00 PM »
lithium and water is a slow reaction

i have made up my mind now ::)

indole_amine

  • Guest
Li is very reactive
« Reply #9 on: October 25, 2004, 08:35:00 PM »

hypo

  • Guest
huh?
« Reply #10 on: October 25, 2004, 09:04:00 PM »
i really don't want to annoy you, but usually Na is considered to be
more reactive than Li. because electronegativity decreases when you go
down in the periodic table. Li < Na < K. ever heard of Na-organyls?


indole_amine

  • Guest
Li > Na > K
« Reply #11 on: October 25, 2004, 10:44:00 PM »

hypo

  • Guest
google
« Reply #12 on: October 25, 2004, 10:51:00 PM »

http://jchemed.chem.wisc.edu/JCESoft/CCA/CCA2/MAIN/ALKALI/CD2R1.HTM


(note that this page is somewhat skewed, since the density probably has
an effect in this case too)

> Lithium is on top of the alkali metals, so if electronegativity decreases when
> going down the table, it should be Li > Na > K.

yes Li > Na > K for electronegativity,
but Li < Na < K for reactivity.  ;)
(they aren't active for attracting electrons, but for getting rid of their electron)

> Lithium has a lower bp than sodium, hence the reaction with water may be more violent.

????


indole_amine

  • Guest
ah
« Reply #13 on: October 25, 2004, 10:56:00 PM »
Then call it reactivity, not electronegativity.

And although lithiums electronegativity is greater than that of sodium, it still reacts more vigorously with water: because it melts earlier, splatters earlier, gives smaller spots which heat up even quicker, and a fire is therefore set off much earlier than with sodium.

As you (hypo) are an experienced experimenter, I would advise you to take it to the test: Take two big buckets (preferably metal ones), fill with water. Take 500g of sodium which has been stored under petroleum previously, and 500g lithium which has been stored the same way. Make sure u use at least that much, else you won't notice any measurable effects. Also make sure you don't use any gloves here, it could cause imprecise results. Wash both lumps with plenty of alcohol, then quickly throw them both into a separate bucket (as you will realize later, it is VERY important to conduct the experiments at the same time and as close together as possible), take off your protection glasses and wait.

All others: DON'T TRY THIS! You *may* lack hypo's knowledge and therefore you most likely will cause a big explosion when attempting this. Don't do it.


indole_amine

Barium

  • Guest
Huh?
« Reply #14 on: October 26, 2004, 01:59:00 AM »
Indole; What are you talking about? The reactivity increases as you move down the table in that column. Compare potassium with sodium in water, then compare cesium with potassium. With cesium it is another dimension of reactivity. This is not from any book but from experience.

For comparison, why do you think that IPA or tert-butanol is the recomended solvent for the destruction of potassium? Sodium can be safely destroyed with EtOH if due precautions are taken. Sodium ethoxide is quickest made, according to Vogel's by adding ethanol to the metal...

"Place 1.5 mol sodium cut in small pieces in a 2 litre flask equipped with an efficient double surface condenser and a separatory funnel. Measure out 1 litre of super dry ethanol and place about 500 ml in the funnel. Place a large bowl beneath the flask and have a large wet towel in readiness to control the vigour of the reaction. Run in about 200 ml of the ethanol on to the sodium....."

Try that with potassium and you are in a world of trouble. Lithium wouldn't cause much in fuzz in comparison.


hypo

  • Guest
rotfl!! :)
« Reply #15 on: October 26, 2004, 12:45:00 PM »

As you (hypo) are an experienced experimenter, I would advise you to take it to the test: Take two big buckets (preferably metal ones), fill with water. Take 500g of sodium which has been stored under petroleum previously, and 500g lithium which has been stored the same way. Make sure u use at least that much, else you won't notice any measurable effects. Also make sure you don't use any gloves here, it could cause imprecise results. Wash both lumps with plenty of alcohol, then quickly throw them both into a separate bucket (as you will realize later, it is VERY important to conduct the experiments at the same time and as close together as possible), take off your protection glasses and wait.




do i smell a whiff of bitchiness, or what?  ;D
take it easy, everyone is wrong from time to time... that's an integral part of learning...




indole_amine

  • Guest
normally yes
« Reply #16 on: October 26, 2004, 04:24:00 PM »
At the risk of receiving a well-deserved "insignificant" rating:

You know, usually learning is fun - if it isn't based on the comments of someone who begins every reply with the intelligent and kind word "Huh?"...
(funny coincidence that this also includes Barium's last post; I realized it just after typing this..  :) )

And when I picked up the topic the first time, I originally just wanted to depict that different alkali metals have quite a different activity. And that alkali metal borohydrides therefore might posess different properties. So far about getting off-topic. Just to remember.  :)


indole_amine