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Melgar
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You should look into getting ninhydrin, for detecting the presence of amines and ammonia. Ammonia turns red, primary amines turn blue, and secondary
amines (or primary amine salts) turn yellow. It's a lot more reliable than "nose chromatography".
Adding the sodium carbonate is more of a test than anything else. If there's no reaction, then there apparently is not an excess of acid. I've
always had it react, but I've never tried to make an amine that sterically hindered. I do know that the sodium carbonate was essential for making
TBAB though, which is a quaternary salt.
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alking
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Thanks, ninhydrin sounds useful indeed, I'll look into that.
Am I correct that normally you would add the Na2CO3 (or more commonly I actually see K2CO3) into the reaction in the beginning which encourages it to
go forward as opposed to when it's seemingly over? That would make sense as it should react driving it forward and the slow rate of reaction due to
low solubility wouldn't matter since the alkylation is slow anyway. I don't think that would work in a closed vessel due to the CO2 buildup though.
Current Progress:
The Na2CO3 was filtered off and washed with MeOH. The filtrate was acidified to PH 7.5 with H2SO4 and the solution was distilled until the still head
reached 100C. The Na2CO3 was dissolved into the solution, some NaOH was added to ensure the amines had been liberated, and distilled again. To my
dissapointment only about 20-30ml of distillate was collected between 60-100C, 2-4ml of which was 2-BrPr which could be seen forming a lower layer.
The majority of the distillate seemed to be concentrated between 75-85C, presumably my target amine, but it never held at any one point and I did not
do a careful fractionation as I knew I would still have to redistill to remove any alcohol or 2-BrPr anyway.
If I had gotten a quantitative yield on the starting ammonium chloride I should have almost 300ml of DIPA so I'm no where close. I do still have about
~300ml of an organic layer which has not been worked up or extracted though, hopefully there is more there. If there is though it would be as a
dissolved HBr salt however since there is no amine smell which doesn't seem too likely given its poor solubility so I don't know. I'll probably work
that up later today, if nothing else I need to recover my remaining 2-BrPr to try again. If this doesn't work I'll probably try to start from roundup
since I have no more NH3:MeOH.
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Melgar
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Quote: Originally posted by alking  | Thanks, ninhydrin sounds useful indeed, I'll look into that.
Am I correct that normally you would add the Na2CO3 (or more commonly I actually see K2CO3) into the reaction in the beginning which encourages it to
go forward as opposed to when it's seemingly over? That would make sense as it should react driving it forward and the slow rate of reaction due to
low solubility wouldn't matter since the alkylation is slow anyway. I don't think that would work in a closed vessel due to the CO2 buildup though.
|
There shouldn't be any acid in solution at the beginning, so you're probably better off adding the alkyl halide, waiting, and then adding your base in
small portions. Remember, the alkyl halide can react at least once without an acid scavenger. Not to mention, you don't want your reaction vessel
erupting all over your table.
If you have potassium carbonate, that would probably be better to use, mainly because it has some desiccant activity, whereas sodium carbonate doesn't
until after it reacts. If a small amount doesn't react, then you just don't add any more. Considering only two molecules of isopropyl bromide can
alkylate one ammonia molecule, the second one might actually take some time and heat to get to react. I really don't know why it didn't react though,
maybe you need a stronger base like potassium carbonate?
When I alkylated ammonia with bromobutane, I just added 28% aqueous ammonia to my alkyl halide. An aqueous layer formed, of course, with a white salt
in it. I added sodium carbonate in order to get any amines out of the aqueous layer, and to neutralize any acids that formed. Incidentally, I've
never experienced amine carbonate salts forming except at temperatures below the freezing point of water, although I can't guarantee that they don't
exist.
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alking
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I'm revisting this synthesis starting from isopropylamine. I've successfully made n-ethyl-n-isopropylamine, but I could not get 2-bromopropane to
react with it while refluxing in i-PrOH for ~40hr or so, bp 62-64C. I am thinking more i-PrOH, or even a higher boiling solvent if necessary, might
help raise the temperature and thus drive it forward. I'm also reconsidering using a catalyst, I did not for this one.
Melgar, do you have experiencing using Na2CO3 or the like in this? I'm just wondering what the best way to add it and how much, did you do any testing
to determine such variables or were you just guessing yourself? I know we discussed that last, but I'm just trying to get more information. It seems
it could go a lot of different ways and there's quite a few variables at play. Without using a catalyst I got about a 35-45% yield on the
isopropylamine -> n-ethyl-n-isopropylamine and no appreciable amount of n,n-diisopropylethylamine.
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clearly_not_atara
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I think you are making it too hard for yourself. It should be much easier to add ethyl iodide to diisopropylamine than to add isopropyl iodide to
ethylisopropylamine. Reason being, EtI has a larger dipole moment than iPrI and ethylene is a less stable elimination product than propylene. As such
it makes more sense to carry out the difficult alkylation first, by reacting isopropyl bromide with monoisopropylamine.
For any preparation of DIPEA, the final alkylation must be carried out with an iodide or a dialkyl sulfate, at least in every version I've ever heard
of. Diethyl sulfate is the most common reagent.
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alking
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I do not have access to iodine in sufficient quantities, so bromides are my only route. I could possibly make dialkyl sulfates, but it's a lot more
work (~3-4 steps opposed to one rather simple one) and much more toxic, I'd really like to avoid them if I can.
I did the ethylation first for two reasons. The first is actually that I heard the opposite of what you're saying, that adding an isopropyl group to
ethylisopropylamine is easier than adding an ethyl group to diisopropylamine because the later is so hindered already. Was that source mistaken? The
second reason is that according to this post ethylating diisopropylamine with bromoethane does not really work and results in a bunch of unsaturated side products. I do recall
reading a thread elsewhere on here that suggested and performed the route I am taking although I'm unable to find it now, that's the same thread I
believe that made the claim that EtPrNH3 -> Pr2EtNH3 is easier than Pr2NH3 -> Pr2EtNH3.
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clearly_not_atara
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| Quote: | | The second reason is that according to this post ethylating diisopropylamine with bromoethane does not really work and results in a bunch of
unsaturated side products. |
What do you mean it doesn't work? The post states:
" Diisopropylamine can be ethylated with ethyl bromide to produce Hünig's base using mild reaction conditions in a ~50% conversion after a 26hr
reaction time."
The post mentions that a patent says it doesn't work, but patents always claim alternative methods don't work (it's the whole point of the patent
system), and while 50% yield may not be economical for Sigma-Aldrich it's probably more than enough for you.
| Quote: | | The first is actually that I heard the opposite of what you're saying, that adding an isopropyl group to ethylisopropylamine is easier than adding an
ethyl group to diisopropylamine because the later is so hindered already. Was that source mistaken? |
Yes. Both reactions are "easy" at high enough temperature; what's "hard" is not generating an alkene, and the best thing to do for that is to use the
least stable alkene possible, in this case, ethylene. Diisopropylamine looks very hindered on paper, but if you remember that the nitrogen is
pyramidal, it makes more sense why it's not that much more hindered than ethylisopropylamine.
The alkyl halide attacks the nitrogen at the carbon atom (which bears an induced positive charge) so you want this atom to be unhindered as
much as possible. So if I look at isopropyl bromide, it has an extra methyl group in the way attached to the atom that reacts; with diisopropylamine
versus ethylisopropylamine, the extra methyl group is attached to an atom which does not react.
[Edited on 12-9-2017 by clearly_not_atara]
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Melgar
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| Quote: Originally posted by alking | | Melgar, do you have experiencing using Na2CO3 or the like in this? I'm just wondering what the best way to add it and how much, did you do any testing
to determine such variables or were you just guessing yourself? I know we discussed that last, but I'm just trying to get more information. It seems
it could go a lot of different ways and there's quite a few variables at play. Without using a catalyst I got about a 35-45% yield on the
isopropylamine -> n-ethyl-n-isopropylamine and no appreciable amount of n,n-diisopropylethylamine. |
I've used it to make TBAB from n-bromobutane, but that's much less subject to steric effects.
The first step in the process of learning something is admitting that you don't know it already.
I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
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