Sciencemadness Discussion Board - Preparation of n-butylamine(consult)

Preparation of n-butylamine(consult)

B.D.E - 23-9-2020 at 00:33

Hey there, I'm in need for some n-butylamine and I would highly appreciate your consult and advice regarding to its preparation.
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Failed attempt:
I've tried running the Gabriel reaction by mixing 1.2eq of n-BuCl with 1eq of p.phthalimide, together with just enough DMF to partially dissolve everything into a fluid slurry.

I've heated the slurry for about an hour(with magnetic stirring), vacuumed filtered the solids, and washed 3 times with dH₂O. Unfortunately, all of the solids had dissolved during the washes, implying that none(/very little) of the n-butylphthalimide intermediate was formed.

Things I consider trying next:
As for the moment I'm thinking on maybe trying it again, this time with acetone as a solvent and a catalytic amount of NaI.

I'm also reconsidering sticking to the Gabriel route at all, as it seems like quite a pain in the keister. I do have some NaN₃, and I ponder if it might be easier for me to just make n-BuN₃ and reducing it with something like Fe/NH4Cl(I ain't got no zinc, but I can make some from ZnCl₂).
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Any thoughts/suggestions/relevant information or insights that you might have would be highly appreciated(!).
Much thanks, B.D.E

[Edited on 23-9-2020 by B.D.E]

stoichiometric_steve - 23-9-2020 at 02:13

Quote: Originally posted by B.D.E

I'm in need for some n-butylamine

…

(I ain't got no zinc, but I can make some from ZnCl₂).

Not to judge, but do you want to make the n-butylamine for fun? Seems kinda unlikely that someone who would consider making Zn from ZnCl2 can't get n-butylamine.

ArbuzToWoda - 23-9-2020 at 02:17

Maybe for synthesis of tetrabutylammonium salts as PTCs? Why would he/she buy ZnCl2 and pay for shipping if one has some zinc metal on hand?

ArbuzToWoda - 23-9-2020 at 02:22

Also, here is a thread about a successful synthesis of n-butylamine by someone quite renowned here. It has an experimental, too.

http://www.sciencemadness.org/talk/viewthread.php?tid=16444

B.D.E - 23-9-2020 at 04:08

Quote: Originally posted by stoichiometric_steve

Quote: Originally posted by B.D.E

...

do you want to make the n-butylamine for fun? Seems kinda unlikely that someone who would consider making Zn from ZnCl2 can't get n-butylamine.

Mostly for fun and practice, but I do actually have some use for it. as for reducing the ZnCl2 - I hoped to avoid this completely by using iron wool, but if I had to, I'd try to reduce it with some sodium metal(of which I have plenty). Seems like a neat experiment by itself

Quote: Originally posted by ArbuzToWoda

here is a thread about a successful synthesis of n-butylamine by someone quite renowned here. It has an experimental, too.

http://www.sciencemadness.org/talk/viewthread.php?tid=16444

Yes I saw it(this is where I got the idea). I actually pretty sure I'm going to give it a try, but I still hoped for some feedback on my failed attempt and also my NaI/acetone idea.

stoichiometric_steve - 23-9-2020 at 04:12

Quote: Originally posted by ArbuzToWoda

Maybe for synthesis of tetrabutylammonium salts as PTCs? [rquote]

that's why he used a Gabriel reagent, sure... could have just straight quaternized the amine.

Dr.Bob - 23-9-2020 at 04:43

If you can deprotonate the phthalimide NH first with NaH or such, that will speed up the reaction. Might work best in THF for NaH reaction.

karlos³ - 23-9-2020 at 08:29

You want to stick to the gabriel synthesis?
Then it is best if you forget about stupid phthalimide, this is one of the worst gabriel reagents really.

Can you make sodium methoxide, and can you get formamide?
Then I would highly suggest to you to make sodium diformylamide and react that with your butyl chloride, and then deprotect the resulting diformylimide with HCl(aq.) dissolved in ethanol, resulting in the hydrochloride of your desired primary amine.

I made quite a few primary amines with that useful reagent, for example benzylamine from benzyl chloride, and it works wonderful, clean and easy.
The yield could be a bit higher though... but the cleanliness of the reaction speaks for itself, as you get with little effort quite the clean butylamine HCl salt out of this reaction.

Here have a look at this thread of mine: http://www.sciencemadness.org/talk/viewthread.php?tid=155452

Corrosive Joeseph - 23-9-2020 at 09:19

https://www.sciencemadness.org/whisper/files.php?pid=560751&...

/CJ

ArbuzToWoda - 23-9-2020 at 10:54

I can't access that thread, CJ. Is it for veterans only?

karlos³ - 23-9-2020 at 11:21

You have to ask one of the moderators for access to the reference section, just like you have to for access to whimsy.
It is usually quickly granted, to anyone who asks, as this is only done to avoid google crawlers and such in those sections.

Its just the reaxys document on butylamine, and as usual most entries aren't suitable for an amateur anyways.

[Edited on 23-9-2020 by karlos³]

Cou - 23-9-2020 at 12:19

The Delephine reaction looks good. It's run in chloroform, and the hexamethylenetetramine salt precipitates out. https://www.organic-chemistry.org/namedreactions/delepine-re...

Staudinger reaction https://www.organic-chemistry.org/namedreactions/staudinger-...

[Edited on 9-23-2020 by Cou]

karlos³ - 23-9-2020 at 13:24

Although I've seen an example of the preparation of ethylamine with the delepine once, back on versuchschemie.de(so sadly now lost), my own experiments with the delepine have turned out to require far more effort and an extensive purification of the final product.
While not even being higher yielding than the gabriel synthesis with sodium diformylamide.

I can only recommed that gabriel reagent strongly, it is such a neat reagent and works very well under relatively mild conditions.
And the reagent is prepared in quantitative yields too, with a rather simple and cheap procedure.

I am a huge fan of sodium diformylamide, one just needs to react his haloalkane in DMF or MeCN with the powdered Na-diformylamide in suspension for a few hours, and the diformylamide is precipitated as oil with water, taken up in DCM and then washed and dried.
The DCM is stripped of, and the oily residue is then stirred for two days at RT in ethanol containing 5% of conc. HCl.
Or a higher percentage under heating, for a shorter time.
Then all the volatiles are distilled off, and to the residue is given some dry acetone.
The products HCl salt will precipitate sooner or faster, depending on the product, and will often be obtained already in a very satisfying purity.

Can't get much easier, honestly, the ease of using this stuff is hardly beaten by any other method to prepare primary amines.
Its not even as simple if done via NaN3 followed by reduction with zinc powder/ammonium formate, nor higher yielding.

E: accidentally wrote "2h" instead of two days

[Edited on 23-9-2020 by karlos³]

Corrosive Joeseph - 24-9-2020 at 11:27

Quote: Originally posted by ArbuzToWoda

I can't access that thread, CJ. Is it for veterans only?

A preparation of butylamine from butanol via butyl bromide and ammonia is contained within Whitmore '32.... And here is the REAXYS.... As Karlos says, most preps are useless and use unobtanium reagents, but there are usually at least a couple of golden nuggets contained inside these documents and they are always my first port of call when confronted with a new molecule.
How can anyone make any decisions unless they know what has gone before.

/CJ

Attachment: whitmore1932 - (n-BUTYLAMINE).pdf (435kB)
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Attachment: REAXYS - n-Butylamine.pdf (1.2MB)
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B.D.E - 26-9-2020 at 02:48

Thanks for all the ideas and information! It really expanded my mind and knowledge on the matter, which is awesome

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Quote: Originally posted by Dr.Bob

If you can deprotonate the phthalimide(...)

I actually used potassium phthalimide for the rxn. I was just lazy and wrote p.phthalimide instead(my bad). For the record, there's much simpler way to deprotonate phthalimide. I personally followed Chemplayer prep. video.

Quote: Originally posted by karlos³

You want to stick to the gabriel synthesis?(...)

Thanks for the very cool info. Sound much simpler than p.phthalimide yet somehow much less known. Unfortunately I have no formamide in hand(I can make some, but it feels like too much work).

Quote: Originally posted by Cou

The Delephine reaction(...)

Thanks, but I don't have any hexamine nor phosphine derivatives :)

Quote: Originally posted by Corrosive Joeseph

A preparation of butylamine from butanol via butyl bromide and ammonia is contained within Whitmore(...)

Although very surprising(I would have guessed it would form lots of di/tributylamines as byproducts), it's still a bit complicated to perform(gaseous ammonia, glass packed column, long rxn times etc).
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For the time being I decided going with the azide reduction route, merely because it's the most appealing method to me(in terms of simplicity, reagents availability, and yield).

I actually planned running the rxn yesterday, so I could share photos and observations today(alongside with this comment). Unfortunately my hotplate just died. So it got delayed until I'll get it fixed.

B.D.E

[Edited on 26-9-2020 by B.D.E]

B.D.E - 7-10-2020 at 04:41

So after about 40 hours at ~60-65C(with s.stirring) - almost none of my n-chlorobutane converted to n-azidobutane...
I roughly followed the instructions from the pic below, only with n-BuCl instead of n-BuBr. I also done none of the weird workup steps, instead I just separated the layers and continued to distillation.

The prep I've roughly followed:

I recoverd most of the BuCl and NaN3, hoping to try it again in DMSO. But it came to my attention that Cl^- has the same nucleophilic strength as N₃^- in aprotic solvents, so it probably ain't gonna work too.

I probably just gonna make some n-BuBr instead and try again(this time in DMSO from the get-go).

B.D.E

Fantasma4500 - 16-7-2022 at 07:19

i would just like to report that i managed to create butylamine - or at least some amine from butanol made by NaOH + BuAcetate
this butanol was then reacted with sulfamic acid granules (yes really just granules, dont bother powdering it) for 24 lazy hours on sub100*C
subsequent reaction with NaOH in slight excess, distillation
its extremely sharp and im gonna try to react the amine or mix of amine/NH4OH with HCl, dry that out and EtOH extraction, NH4Cl is rather insoluble in EtOH
then ill once again NaOH it and now with my fancy setup test to see the boiling points, hopefully no diabolic azeotropes to hinder my life

i tested it positive on hotplate just about now simply by adding some NaOH to about 0.5mL of the solution (maybe 30% Butylamine?) then added in 20mL of milk, situated on hotplate this gradually changed its color towards pink, heatsetting 2, it takes about 5 minutes
when i performed this with NH4Cl instead or NH4OH i recall it giving me a brown solution/mush instead
lactose is what causes this reaction and pure lactose will give a more clear solution- i must attempt this in the future. maybe HAc+ milk followed by decantation can yield me some lactose solution to try with?

https://www.degruyter.com/document/doi/10.1515/cti-2019-0008...

with my limited knowledge i cant theorize whether i could have another amine, and i havent tested BP of it yet- but it was made with butanol and it gives a positive for amine and its like ammonia on steroids, distillation was very dreadful.

Boffis - 18-7-2022 at 02:00

@Antiswat; do you have a reference for the preparation of amines from alcohols with sulphamic acid? I would be interested to see some background and I can't find it in the Reaxys search posted above.

Tsjerk - 18-7-2022 at 02:29

I could find some references when looking for the preparation of methylamine from methanol and sulfamic acid, but they did state di- and trimethylamine are also formed. By adding the ammonium salt of benzene sulfonate they could up the yield a bit, but you still need to clean the primary amine from the secondary and tertiary and possibly even quartenary amines.

Although in this reference they talk about thermal isomerization before freebasing, I don't know what happens when you do an aqueous hydrolysis directly on the alkyl

I will upload the reference if I find it again.

Edit: William Smith, 1920

@Antiswat: Are you sure it is not ammonia? I don't see how ammonium alkyl sulfate would yield an alkyl amine just by adding NaOH.

[Edited on 18-7-2022 by Tsjerk]

Keras - 18-7-2022 at 02:56

IMHO, the only reliable way to get primary amines is to use sodium azide, the preparation of which Chemplayer has a video on.

[Edited on 18-7-2022 by Keras]

Fantasma4500 - 18-7-2022 at 03:40

i would like to see replication of it, i tested some ethylamine with milk yesterday and it gave same result

it seems that sulfamic acid and EtOH doesnt work

and yes it does rely on the compound re-arranging

unfortunately ammonia and amines smell the same to me- im not sure how else to test it than with lactose
the sulfamic method is typically used with methanol, i truly dont understand the chemistry behind

i think when youre at sodium azide that you need to look for an alternative route, thats very exotic and toxic, and can with a few oops form explosives

as for ethylamine- reacting with HCl and distilling off EtCl, then reacting this with +10% NH4OH solution along with emulsifier (0.5% oleic acid; resulting in ammonium oleate) but also at increased temperature and pressure, likely it does work at atmospheric pressure- the butyl variant should be much more doable as the boiling point would be higher
maybe soaking the whole deal into cotton wool would act the same as emulsifier?

another route that should be considered is through aminoacids, alanine and theanine can yield ethylamine, glycine can yield methylamine, and i did some guessing with a fellow chemist on what could yield butylamine
now- butylamine would have 4 carbons? i believe it was valine we ended up on guesstimating for

https://gyazo.com/99fe329a85af1cb2e3a361d803bed2f5

otherwise butyl alcohol could be made into nitrate or nitro, butylnitrite should be possible to re-arrange by isomerization or however its called by leading it through a substrate (rock wool was used for ethylnitrite, non catalytic?) and then have that reduced- unless if you can directly reduce butylnitrite
NOx could be lead directly into butyl alcohol, resulting in a mix of nitrite and nitrate

Tsjerk - 18-7-2022 at 05:03

You can try the lactose test with ammonia to see whether the color is different. But if you did thermally isomerize the salt, I expect a mixture of mono-, di- and tri alkyl amines.

DocX - 21-7-2022 at 05:27

Quote: Originally posted by B.D.E

Hey there, I'm in need for some n-butylamine

I understand the joy of making your own precursors, and once one gets started it becomes something that HAS to be solved. But if you're in Europe, I can always recommend THIS seller. Not the cheapest, but fast and reliable shipping.