Sciencemadness Discussion Board - Does this seem a safe and effective way to alkylate ammonia?

Does this seem a safe and effective way to alkylate ammonia?

alking - 18-6-2017 at 18:01

I'd like to make n,n-diisopropylamine by alkylating ammonia in methanol by reacting it with 2-bromopropane. From what I understand alkylations of ammonia are normally done at elevated temperatures in a pressure vessel to prevent the ammonia from out gassing. I assume it can be done at room temperature as well and it may take a day or two as opposed to a number of hours, but I haven't found a specific reference to confirm that.

My plan is to use an autoclavable media bottle such as these to perform the reaction in. I would assume there would be no dangerous pressure build up if I were to heat it in a water bath to at least 40C or so but I'd like to have a more definite idea before trying it.

I have various ideas to ensure safety and to test it if I don't have anywhere to start from, but I want to hear some input from those more knowledgeable or experienced before I waste my time or do something dumb. My main worry isn't exploding glass or getting physically hurt, that's easy to control and the bottle should vent before that, but releasing concentrated and pressurized ammonia and bromopropane would be a big mess and health hazard to clean up, even if it were confined in a containment vessel.

UC235 - 18-6-2017 at 18:19

http://www.sciencemadness.org/talk/viewthread.php?tid=28429

alking - 18-6-2017 at 20:45

I came across that earlier, I know that's a feasible route, but I'm wondering if this would specifically work. Being able to aminate ammonia from alcohols would simply be useful in general too. I already have NH3 saturated MeOH, i-PrOH, NaBr, and H2SO4 and I do not have any round up from which to extract the starting precursor monoisopropylamine.

If this does work it would also be a better route anyway because you're only performing a single alkylation opposed to buying something else just for this and extracting it only to run the very same alkylation. You may have to create the NH3:MeOH depending on your resources however, but you're likely to have those on hand and I've already done so in this case anyway.

Actually I'm not sure if you're linking that to encourage me to start from roundup or for the information contained within otherwise, you didn't give context. I assumed the former. If the later however I'll point out that I'm specifically asking about ammonia because of it's tendency to outgas, thus you can't simply use a reflux condensor for the reaction. With monoisoporpylamine that is not an issue since it's bp is above RT.

alking - 20-6-2017 at 14:56

Well I'm giving it a shot right now, wish me luck. I've got it heating in a water bath inside a sealed pressure cooker. A thermometer probe was run in under the lid and a bleed hose has been put in place of the rocker.

The probe's wire is small enough that I can close and latch it down. Though I'd imagine it doesn't form a complete seal because of it, it should be enough to contain any blow outs and the majority of the fumes should go out the bleed hose. I have not measured my ammonia concentration but I estimate that there's about 1.5-2eq of 2-BrPr to 1eq of NH3. I used approximately 80ml of 2-BrPr with about 35ml of MeOH that *should* be saturated with NH3 at around ~5C, so it should be over saturated at RT. These were put into a 100ml autoclavable media bottle w/about 10ml of empty space remaining and the lid tightened with vice grips, but not excessively as I'm concerned I may not be able to get it off.

alking - 20-6-2017 at 15:51

I came across this while doing some more research.

https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/p...

I'd like to quote it, but the formatting gets messed up. Basically it cites an example that n-butylamine can be made by reacting butylbromide at RT in a 47% yield with excess ammonia (to favor the primary amine). So that's confirmation enough that it should work at RT, though no mention of time and I wonder what % of secondary and tertiary amines were formed. More interesting however:

http://s3.amazonaws.com/academia.edu.documents/39847168/Gree...

Quote:

In order to ascertain the comparative effectiveness of microwave
heating with respect to conventional heating, a few representative
reactions were conducted using conventional heating in an oil bath.
Mixtures of alkyl halides and amines, in the presence of one
equivalent of aqueous NaOH, were heated in a round-bottom flask
for a period of 12 hours. On the other hand, the same reactions
proceeded to completion under microwave irradiation condition
within 20 minutes (Table 1). Further, it was observed that under
conventional heating mixtures of products were formed (entry 1) in
addition to small amounts of side products such as benzyl alcohol
(entries 1 and 3) as a result of hydrolysis of the alkyl halides in
alkaline medium.

I need to find a spare microwave!

Corrosive Joeseph - 20-6-2017 at 20:23

Here is the citation for the n-Butylamine prep - Ref 84

Frank C. Whitmore, D. P. Langlois. J. Am. Chem. Soc. , 1932, 54 (8), pp 3441–3447

And is attached in full. Page 3............

/CJ

Attachment: whitmore1932.pdf (435kB)
This file has been downloaded 376 times

alking - 20-6-2017 at 22:43

The vessel was held in a water bath between 60-64C for 4 hours after which heating was stopped and it was allowed to come down to RT over approx 2 additional hours. The reaction vessel was taken out and put into the freezer for a few minutes to ensure there was no pressure build up prior to opening it.

Clusters of small to medium white needle like HBr crystals were observed on the bottom, however an ethereal odor was still noted. It did seem minor in comparison to before, but little ammonia smell could be detected either so it's possible there was not as much present as I thought or much was salted out as the HBr. It also may have simply not been allowed to run to completion or there was ether contamination from the 2-BrPr synthesis, which there likely was as I did not take any steps to remove it.

If anyone has tips on separating NH3, monoisopropylamine, and diisopropylamine they would be very welcome. I'd like to primarily get the DIPA, but the MIPA is desirable as well, and both should be ammonia free. I can boil off most of the ammonia, I'm not sure how pure that would get it or if there's a more efficient way though. Fractional distillation is the only idea I have to separate the two amines, but I'd imagine I'll have a nasty azeotrope to deal with. If I did this again I would use more 2-BrPr to ensure the secondary amine (unless I find out that's what happened), but I was limited on the 2-BrPr and was mostly just testing if this would work at all.

Melgar - 20-6-2017 at 23:58

Since triisopropylamine doesn't easily form due to steric effects (I'm like 90% sure, anyway), the diisopropyl version is actually the major product when you akylate ammonia with 2-bromopropane. Also, alking, have you seen the alkyl halide syntheses that use sulfur and elemental bromine? A small amount of water needs to be there initially, but it's replaced as its used from the alcohols. It doesn't work for ethyl bromide, but does for methyl and butyl. Basically, bromine reacts with sulfur to form sulfur bromide, then that reacts with water to form HBr and H2SO4. The net reaction oxidizes sulfur to sulfuric acid, while halogenating alcohols. Useful if you have access to lots of NaBr, and somewhere that you can avoid the smell of it.

edit: Yes, it is actually extremely difficult to produce triisopropylamine because alkylation of ammonia with isopropyl halides stops at diisopropylamine due to steric effects. Which is great if that's what you're trying to produce, though.

[Edited on 6/21/17 by Melgar]

alking - 21-6-2017 at 07:21

I wasn't aware of that, but it makes sense. No sulfur on hand for now though and plenty of old drain cleaner (which surprisingly is crystal clear).

You're definitely right about DIPA being too hindered to further alkylate, that's one of the main appeals of allylation here to me as it doesn't suffer from the normal issue if you're desired product is the most saturated one that can form. My end goal is actually hunigs reagent, diisopropylethylamine, to use in general alkylations in the future. I'm sure I'll be using this to produce other amines in the future if it works well though.

Right now I'm thinking of making some more 2-BrPr tonight to fully alkylate all of my ammonia and any primary amine instead of working it up now, it should save me time in the long run as I expect to have to run this again based on my presumable low yield and incomplete reaction at present. I'm starting with about 2M of NH3 and I'd like to end up with at least 1M of DIPEA, which is only a 25% yield on the NH3, that should be doable. I suspect a lot of my NH3 is likely being consumed by the HBr however since it also serves as the base in the reaction.

Melgar - 21-6-2017 at 09:05

Well, then throw in some sodium carbonate. That's what I did to make TBAB. The sodium carbonate is a strong enough base to pull HBr away from your amines, which will either form a separate organic layer or stay in the organic layer. The sodium carbonate, on the other hand, can only be reactive in the aqueous layer, and if there is none, it will form an aqueous layer from the oxygen in CO3(-2) and the H+ ions, so I just added it dry. Sodium bromide (formed in situ) works well enough as a desiccant, at least well enough to salt out water, and then you just separate the layers when you're done.

If you're not distilling the results, the sulfur + bromine method has a better yield, since its steps are much less reversible, and thus you don't have to worry about having as much alcohol as alkyl halide in your organic layer, which always seemed to happen when I did it. My guess is that there's always a small amount of water in the organic layer due to the presence of HBr and alcohols, both of which water is attracted to. And there's always bromine in the organic layer too, which can probably form radicals on exposure to light and mess with your reaction results. Right now, I finding space to set up a distillation rig isn't easy, and so I'm always trying to find methods that avoid distilling, when I can.

alking - 21-6-2017 at 09:59

Are you referring to the 2-BrPr synthesis or the amine alykation? I was talking about the later, but it sounds like maybe you're talking about the former, or maybe you just mean after the rxn to liberate the amines from the HBr?

AJKOER - 21-6-2017 at 10:54

Here is a possible small scale direct path to an impure mix containing the targeted amine starting with an alkane via UV photolysis with ammonia, water vapor and laughing gas:

N2O + H2O + UV --) N2 + .OH + OH-

Now, with methane, for example:

CH4 + .OH --) .CH3 + H2O
NH3 + .OH --) .NH2 + H2O
.CH3 + .NH2 --) CH3NH2

Other possible side products:

.NH2 + .OH --) NH2OH
.NH2 + .NH2 --) N2H4
......
Similarly with propane C3H8:

C3H8 + .OH --) .C3H7+ H2O
NH3 + .OH --) .NH2 + H2O
.C3H7 + .NH2 --) C3H7NH2

Other possible side products include again:

.NH2 + .OH --) NH2OH
.NH2 + .NH2 --) N2H4
......

and a much larger number of other products involving C3Hn where n = 7, 6,...

Related source (absent the benefical effect of N2O to create more hydroxyl radicals) see K. Ogura, "Photolysis of CH4, NH3, H2O mixture: formation of methylamine and ethylenediamine", in Journal of Photochemistry and Photobiology A: Chemistry, Volume 49, Issues 1–2, September 1989, Pages 53-61, https://doi.org/10.1016/1010-6030(89)87105-9, link: http://www.sciencedirect.com/science/article/pii/10106030898... . Here is the abstract:

"The photolysis of the mixture CH4, NH3, H2O was performed with a low pressure mercury lamp at 100 °C and atmospheric pressure. Of the products, the major nitrogen-containing compounds were methylamine and ethylenediamine; the maximum selectivity of the two amines exceeded 99% in the mol per cent of N-containing products. The other products were methanol, ethane and hydrogen, but the formation of methanol and ethane decreased rapidly with an increase in the amount of added ammonia. This was attributed to the preferential reactivity of methyl radicals with NH2 rather than with OH and/or CH3. The formation rates of NH2, CH3NH2 and NH2C2H4NH2 are discussed."

[Edited on 21-6-2017 by AJKOER]

Melgar - 21-6-2017 at 12:53

Quote: Originally posted by alking

Are you referring to the 2-BrPr synthesis or the amine alykation? I was talking about the later, but it sounds like maybe you're talking about the former, or maybe you just mean after the rxn to liberate the amines from the HBr?

No, during the second reaction. Alkyl halides won't attack protonated amines, but but deprotonated amines will often steal their protons, opening them up to alkylation. This will continue to happen until either all the amines are in salt form, or another base is introduced that can deprotonate amine salts. If your goal is maximum alkylation, then you need another base to neutralize the acids that are formed from alkylation, to open the amines up to further alkylation. Hence, sodium carbonate. Use a slight excess of your alkyl halide, add sodium carbonate until bubbling ceases, then discard aqueous layer that formed, and extract the amines with an appropriate quantity of HCl/water solution. Ammonia would be used up and so should no longer be in solution. Evaporate off the excess alkyl halides, and what's left should be your crude diisopropanolamine salt.

If you wanted to alkylate with ethyl bromide, you could probably just add it to the diisopropylamine solution after you give the reaction with the isopropyl bromide enough time to complete. I doubt it could be alkylated to the quaternary, though I could be wrong. I know that usually quaternary amines are harder to form than tertiary ones for any alkylation other than methyl, especially for one like this that's excessively hindered, sterically.

I'm not sure who AJKOER is, and thought he was actually AJOKER until recently, but he tends to find the most obscure syntheses possible that are borderline theoretical-only and recommend them to beginning chemists, for some reason that nobody here can comprehend. Most people just ignore him now.

edit: Here's a pretty good explanation for alkylation of ammonia with alkyl halides, written in a good teaching tone.

http://www.masterorganicchemistry.com/2017/05/26/alkylation-...

[Edited on 6/21/17 by Melgar]

AJKOER - 21-6-2017 at 13:58

Melgar:

Actually, in my opinion, you got your synthesis reviews reversed. Your classic schooled process is overly complex and the precise pathway is not clear or even understood, but nevertheless is usually ascribed a name (as if that really means anything).

It reflects a historical preference against a photolysis path as it is perceived as a non-standard lab technique, as was the use of microwaves to effect synthesis until more recently.

Of course, photolysis usually relies on radical chemistry which is also relatively new (which your described as obscure, really?), although its importance, especially in atomspheric chemistry, is of major significance.

You fail to note my process is published in a peer reviewed journal in 1989, not that you even known how dated your reputed 'science' is.

Let me give you a suggestion based on experience. A method that approaches a direct combination of elements should be a first consideration, if possible (maybe you can find that remark comprehensible).

But, who am I to give a review, as your last link goes to an article with the title, "Alkylation of Amines Tends To Be A Pretty Crappy Reaction" by JAMES in AMINES.

Also, lets just say I live in a jurisdiction where labs must have a license, so having a standard lab is not rationale behavior. However, things like a UV lamp, a microwave, ...are not problematic, and if their performance equals or exceeds classic methods, I am not complaining. Also, in many places, reagents are increasely restricted or subject to excessive scrutiny. So, one may need to expand ones horizon to radical chemistry, electrolysis, photolysis, sonolysis, fenton chemistry, surface chemistry, chemistry of aerosols,....just to fill the void.

[Edited on 22-6-2017 by AJKOER]

Melgar - 21-6-2017 at 16:54

AJKOER:

Any recommendations I give will be based on these factors:

Available information. If a reaction doesn't go like someone expects it to, I'd prefer to make sure that there are at least a few available examples of people doing the reaction successfully. Maybe the first authors left out some critical information that later experimenters added, for example.
Ease and cost of reagent acquisition. Reactions that are iridium-catalyzed, or use something that can only be purchased with a Sigma Aldrich account tend to not be well-received here, because this is a forum specifically for amateurs, that tend to be purchasing reagents using their own spending money. Ideally, it'd be better to recommend something that uses things the user already has on hand, or is likely to have on hand.
Ease of performing the synthesis, which includes acquiring, building, using, and cleaning the apparatus. Gas-phase reactions, like what you posted, tend to be low-yielding when done by amateurs, and often require high pressures when done in industrial settings. Also, how do you build the apparatus to do a gas-phase reaction in a commercial microwave? It certainly isn't easy, by any means, and would be far too time-consuming and expensive for something as simple as what he's trying to do.
Yield. The yield for what you listed would be comically low. You're producing all these side products that are probably going to have to be discarded, assuming limited storage space and storage vessels.

That being said, when saying "obscure", perhaps I should have said "difficult, time-consuming, low-yielding, and expensive"? Thinking about it more, "impractical" would have been the best word to use. And who cares how well a reaction is understood? If a reaction isn't well-understood, that's a GOOD thing! It means there's something to learn, some new scientific discovery to be made! Even I was able to discover a free-radical photolytic reaction that nobody had documented before! (This should at least help you realize that I have nothing against photolytic free-radical reactions, I fucking DISCOVERED one!

) Nicodem didn't believe me at first, then did the reaction himself and discovered not only that it did work, but posted a bunch of interesting aspects to the reaction that I would never have been able to test myself, being that I was doing it with test tubes, pool chemicals, and PVC tubing.

Quote:

A method that approaches a direct combination of elements should be a first consideration, if possible.

Uh, no. Let's say I want to make sodium acetate. You're saying I should get carbon, hydrogen, oxygen, and sodium, then thermally crack the carbon with the hydrogen and oxygen to form hydrocarbons and carbon monoxide (among a bunch of other things) then convert the ethylene to ethanol and oxide that to acetic acid, before reacting that with sodium? Or carbonylate methanol to form acetic acid, or acetic anhydride or whatever? I mean, it certainly is possible, since it's done industrially all the time. But don't you think it might be better to recommend mixing vinegar (or more-concentrated acetic acid) with baking soda (or sodium hydroxide) to an amateur?

Quote:

Also, lets just say I live in a jurisdiction where labs must have a license, so having a standard lab is not rationale behavior. However, things like a UV lamp, a microwave, ...are not problematic, and if their performance equals or exceeds classic methods, I am not complaining. Also, in many places, reagents are increasely festricted or subject to excessive scrutiny. So, one may need to expand ones horizon to radical chemistry, electrolysis, photolysis, sonolysis, surface chemistry, chemistry of aerosols,....just to fill the void.

That's all fine and good. Most of us here use improvised equipment too. However, you posted a synthesis that uses nitrous oxide (restricted in many places), and also implied the necessary use of a gas-phase reactor capable of UV photolysis, which is virtually out of the scope of home chemistry for practical synthesis. He also wasn't asking about methylamine, but since you seem to have studied it quite extensively, you might be interested in knowing that the free-radical gas-phase reaction of propane and nitric acid at around 400˚C will give a number of products that would most likely interest you, among them being small nitroalkanes, like nitromethane and nitroethane! Dissolving-metal reductions can reduce nitromethane to methylamine and nitroethane to ethylamine. Continuing the dissolving metal reduction after the nitromethane has been reduced to an amine, and adding in the ketone that you used your nitroethane to synthesize, will give you a nice secondary amine that is probably one of the reasons that certain reagents have heavy restrictions placed on them in the first place. And really, by all means, if you have the apparatus, I encourage you to build a reactor for reacting propane and nitric acid. I tried about ten years ago, but only got a few mL of liquid that had a nitroalkane smell to it, after using a one-pound propane tank. For better efficiency, the unreacted propane should be collected and reacted again, but that would have required a huge amount of additional apparatus that would require more time and money than I had at the time.

I am actually curious though, what's the most success you've ever had at synthesizing a complex molecule? The proof is in the pudding, after all.

edit: also, regarding the link I posted, I selected it due to the fact that it was written to be easily understood. And it is. When starting out, chemists can have difficulty understanding some concepts, and this particular author is quite good at writing about chemistry in a way that's easily grasped. That is, I chose a source based on what I thought would be the most benefit to the person I was replying to. You, on the other hand, clearly did not, judging by the fact that the products were not the same as what was being sought, and by the sheer impracticality of using that reaction to synthesize ANYTHING in high yields.

[Edited on 6/22/17 by Melgar]

AJKOER - 21-6-2017 at 18:57

A few quick comments, "impractical" is more a matter of ingenuity. For example, filling a weather balloon with gases appears to mute the small scale label.

"A method that approaches a direct combination of elements should be a first consideration, if possible" in the current context refers to the convenient and workable radical reaction:

.C3H7 + .NH2 --) C3H7NH2

Understanding the mechanics of a reaction allows one to do things to increase efficiency. For example, when working with a Zn/Cu couple by pre treating the metal surface with HCl helps remove the oxide layer and improves performance of the couple. Another example is adding a touch of sea salt to a basically electrochemical process like the action of a weak acid and H2O2 on a transition metal.

Most of my prior reported experiments are in the realm of inorganic chemistry and I would claim many employ common household chemicals in original (or others would claim unconventional) procedures.

By the way, N2O has found its way into making more flavorful drinks and along with CO2 cartridges is sold in stores like Walmart at a nominal cost.

[Edited on 22-6-2017 by AJKOER]

alking - 22-6-2017 at 13:52

Quote: Originally posted by Melgar

Quote: Originally posted by alking

I understand what you're saying now. I thought of that, potassium carbonate is specifically mentioned in the wikipedia article on 2-BrPr as an activating agent (or w/e it would be called here). Wouldn't the CO2 that is released convert any amines to carbonates here though, resulting in the same issue? Maybe I have it wrong, but I thought it would go something like:

.....

Okay, nevermind, that works out. Once I started to write it out it didn't make sense. So it should proceed as:

Na2CO3 + RNRR*HBr -> NaBr + NaHCO3 + RNRR

I'm still cautious to do that though, I mean it's the best way available to encourage the reaction to go forward, but I'll have to add water to solvate the Na2CO3 which will form another layer as you say. That's not bad in itself, however wouldn't most of my ammonia also be pulled to that layer along with some of my alcohol? I would then either have to pull the water layer off which is wasting the ammonia anyway or I could leave it, but I would think it would significantly hinder the reaction since the two reactants are now in mixed phases, am I wrong? It may work just fine, and the alternative is of course to not bother and waste ammonia anyway, so I'll likely try it regardless, I'm just not so sure it will work as well as it sounds on paper.

Also worth adding my little reaction vessel has been sitting at RT since the initial trial and it's still reacting, but quite slowly. There's now a rainbow of sparkles as you look through it due to all the tiny crystals on the sides of the walls. I read claims that it should take anywhere from 1-3 days at RT however and there's no way that's the case, maybe with other amines or haloalkanes, but not this. I'd imagine 1-3 weeks at this rate.

alking - 22-6-2017 at 14:16

I'm working up the 2-BrPr I made yesterday to finish this and it smells very strange, def not what I'm used to. I've smelled this odor before, but I've never been able to place it. I associate it with nitroalkanes as I've smelled it when synthing them as well as side products from reactions involving them. It smells very 'round' like extra pungent gasoline or something... hard to explain. Def not the familiar ether like odor though, this is way more pungent and headache inducing (I would imagine).

I stored it in the freezer overnight, the only other chemicals it could react with in there are some more 2-BrPr, some methylamine, and my NH3 in MeOH. They're all tightly bottled up too so I don't think they're the cause. I did reflux this for about an hour before distilling it and I poured in the exhausted contents of the flask from the last rxn, but otherwise it was done the exact same as before. Maybe my other 2-BrPr is contaminated with ether and that's why I associate it as smelling that way instead? I'm hesitant to use it until I figure this out, it could potentially be dangerous.

edit: I checked the other 2-BrPr in the freezer and it actually has a similar smell, which I did not detect before, although it is minor compared to this new batch. I suspect the same amount was produced both times and I smell it more here simply because there's more 2-BrPr and it's clearly quite volatile. It's also possible I do not actually know what ether smells like and odors I previously attributed to ethers was something else, or maybe it simply smells different in higher concentrations. I've never intentionally synthesized ethers so am basing my sense knowledge largely on assumptions made through practice.

[Edited on 22-6-2017 by alking]

[Edited on 22-6-2017 by alking]

alking - 22-6-2017 at 15:31

I just came across this too. No real need to click the link, it's a guy trying to overpressure an epoxied shut wine bottle until it explodes. It got all the way up to 260 psi before doing so! Holy shit that is a lot of pressure! I would have been impressed if it even made to 150psi, wine bottles are designed to take some pressure due to fermentation, but I wouldn't think but so much since wine isn't really pressurized. I wonder how a champagne bottle would fair? If one of those can get all the way up to 260psi then we should be able to do just about anything reasonable with these media bottles.

edit: Actually he does one with champagne too. It got to over 500psi! Wow, I am really impressed. Anyone have a guess at what the "weird crystals and brown slime" might be on the bottom of his two decade old bottle of unopened champagne?

[Edited on 22-6-2017 by alking]

DraconicAcid - 22-6-2017 at 15:38

Champagne bottles are much thicker than regular wine bottles because they are meant to be under pressure.

alking - 22-6-2017 at 17:28

I just realized the smell in this case may be from HBr, I did not wash the resulting product with a weak base and I would expect some to be present. I have no real idea what it smells like, but that is my guess as to the culprit.

Melgar - 23-6-2017 at 07:00

The "brown slime" would just be sediment from fermentation, and the "weird crystals" are almost certainly tartaric acid, which is most commonly found as crystals in wine.

If you want higher pressure still, get some SodaStream PETE bottles. They're plastic, rather than glass, so they can't take as high temperatures, but they're rated to over 1000 psi! They're also more resistant to shattering, obviously. I bought a few to do high-pressure hydrogenation in, as well as a pump that can get up to around 750 psi. Still have to find the time and the parts to put it all together though.

You don't have to add any water to the system, sodium carbonate makes its own water via the decomposition of carbonic acid. It's probably better to add sodium carbonate than bicarbonate, just because less water is produced by the reaction. Just drop it in dry, and it'll try to sink to the bottom, but will be held up for quite a while by all the bubbles that are forming. Sodium hydroxide is too strong of a base though, and can react with alkyl bromides to give alcohols. Ammonia and amines' solubility in aqueous solutions is highly dependent on pH. The higher the pH, the less will dissolve, and vice versa.

I'm not actually sure what isopropyl bromide smells like though, to comment.

alking - 23-6-2017 at 15:02

True, I forgot to consider the Na2CO3 would likely push out most of the NH3 from the aqeous. That does sound pretty straight forward and clean.

Current status: The previous ~100ml of rxn mixture, ~30ml of unusued 2-BrPr from the previous batch along with an additional ~250ml from the new batch and the remaining ~100ml of NH3 in MeOH were combined last night into a 500ml media bottle and capped shut. The total volume was just over 400ml. It was held for approximately 14hr between 55 and 63C, most of the time in the high 50's.

Upon removing today the bottom ~80ml was completely covered in crystals. For comparison the first run for 4 hrs on 100ml of solution (different ratios however) I only had about 5-10ml of crystals. The odd smell is also still present, so it's not HBr as I had thought, I'd really like to identify this one day. There's also clearly a smell of NH3 and 2-BrPr still present so I can only guess the reaction still has yet to go to completion. There's a lot of waiting involved, but this is an extremely simple reaction to perform, all the ingredients are very cheap and accessible, and it seems to provide fairly good yields of saturated amines, though I won't know for sure until I work it up. If I get the courage to push this higher than 60C the reaction rate would likely increase pretty substantially I would imagine.

alking - 24-6-2017 at 07:08

Ran it for another 4hrs at 65C and it increased the yield from ~80ml to ~110 or so, not that that's a very accurate measurement of a salt, but it's all I have for now.

I just added ~30g of Na2CO3 and I'm not sure that was a good idea or not, I regret it because even if it was I now have to work this up to find out or discard the aqueous as intended and potentially throw away a lot of my product, I just created a lot more work for myself.

Initially there was no reaction at all, it just sat on the bottom as I had expected. So I added some water and there was still very little reaction, if any, even with a lot of stirring because the water floats on top. There was minor bubbling, but I can't say it wasn't simply from the vigorous stirring trying to get the Na2CO3 to interact with the water layer.

I added maybe 20ml of water (initially, not extra) and vigorously stirred until it seemed only Na2CO3 was on the bottom, but it's hard to really tell the difference between two white crystals. I added some more water until there was enough to suspend any solids, which was maybe 50ml more, and separated the two layers in a funnel. The organic layer is now 290ml, previously 410+, so I've lost 120ml+ of something. Some of it can be attributed to the HBr, but there's gotta be more than that gone. No amine smell is present in either so I have to assume it wasn't even liberated from the HBr and is sitting in the aqueous layer.

edit2: I added ~5g of NaOH to the aqueous to see if any amine smell was detected but still not. The aqeous layer does have a slight burn indicative of amines, but not much at all and nothing is detected in the organic besides an ethereal smell. I have to assume that both an amine or amines were made and that they are liberated however which leads me to think that maybe I cannot smell it because it has all been alkyated to the less volatile secondary amine. Prior to the reaction this would seriously burn your nose simply by opening it, well more than a standard concentrated ammonia solution (~29%) and now I can't even detect an odor at all. Regardless I do not think using Na2CO3 here provided any advantage, I now just have more work to do to hopefully get the same yield since my product is split between two layers and in order to distill off the 2-BrPr and MeOH I have to convert it back to a salt anyway.

edit2: Wait, I forgot I only added ~30g of the Na2CO3 I had weighed out so it's def still a salt. It would take ~250g to liberate it all...

[Edited on 24-6-2017 by alking]

karlos³ - 24-6-2017 at 07:30

Quote: Originally posted by alking

...
Anyone have a guess at what the "weird crystals and brown slime" might be on the bottom of his two decade old bottle of unopened champagne?

Not sure about the brown slime, which could be tannine, but the crystals are probably potassium bitartrate, so called "cream of tartar".

Edit: Haven´t seen that Melgar already has answered it.

[Edited on 24-6-2017 by karlos³]

Melgar - 25-6-2017 at 21:00

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.

alking - 26-6-2017 at 06:50

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.

Melgar - 27-6-2017 at 10:33

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.

alking - 11-9-2017 at 16:22

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.

clearly_not_atara - 12-9-2017 at 08:54

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.

alking - 12-9-2017 at 11:52

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.

clearly_not_atara - 12-9-2017 at 14:10

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]

Melgar - 13-9-2017 at 03:10

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.