Sciencemadness Discussion Board

1,3-Diaminoacetone(1,3-diamino-2-propanone) problems

divinyl - 16-1-2019 at 06:20

Hello, there!
This is my first post, but I visit this forum from time to time since years. You guys are great!

I really need this chemical. I could order it but it is EXTREMELY expensive!
I also have access to 1,3-dichloroacetone(also the dibromo one), 1,3-dihalo-2-propanOL and even 1,3-diamino-2-propanol.
I know that a simmilar topic was brought up recently but it didn't answer my questions.

I know that the 1,3-dihalo-2-propanols can be reacted with ammonia or subjected to a delepine rxn to transform them to the diamino product.
In the patent, for which I need this substance(https://patents.google.com/patent/WO2016146049A1/en), they have a paragraph in the experimantal section, where they use dichloroacetone and NH3 gas but here start my questions:

In the procedure in the patent, the diaminoacetone produced is costantly removed by reaction, and I ask myself:

1:) Would the diaminoacetone self-condensate (the keto functionality reacting with the amino groups of the other molecules or the NH3 to for immines, if I wanted to produce the target molecule from 1,3-dihalo-2-propanone? Would a delepine reaction minimize this risk(especially when using ethanolic HCl)? Or do I have to protect the ketone functionality as a ketal/acetal? Maybe dimethoxy or protect with ethylenglycol?

EDIT: I think the large amount of water present in the patent that uses 2,3-dibromo-2-propanOL to produce 1,3-diamino-2-propanol, would in this case shift the equilibrium far away from the formation of the immine in the case dihaloalcetone is used instead to produce the diaminoacetone (Patent: https://patents.google.com/patent/US1985885A/en)

Diaminoacetone as said is really, really, expensive.

2.) Could I oxidise the 1,3-diamino-propanol to diaminoacetone? Which oxidizer could be used that would leave the amino groups alone?

If the answer is no for both questions, I came across more exotic methods(reacting with phtalimide, NaNO2, starting from acetonedicarboxylic acid....) of producing the target compound but I wanted to keep it simple for the beginning. I made my research but don't have Scifinder etc right now.

So what route would you suggest I take?


I would greatly apprechiate any help.
Greets
divinyl

(Just that you understand what I mean with the wildly different costs:
Prices at sigma(swiss francs ~ US $): 100 SFr = 100.95$
1,3-dichloroacetone (>=95%): 10g: 20.70.-, 50g: 62.60.-
1,3-dichloro-2-propanol(98%): 100g: 28.-, 500g: 72.-
1,3-dibromo-2-propanol(95%): 5g: 27.70.-, 25g: 95.50.-
1,3-diamino-2-propanol(95%) 5g: 58.10.- 25g: 181.-
As you can see, If I could one of the dihalo compounds, I would save a lot of cash. The site removed a listing for diaminoacetone, the oly one left is 305.-!!! The one they took of the list was much less expensive though, but still very expensive.)
[Edited on 16-1-2019 by divinyl]

[Edited on 16-1-2019 by divinyl]

[Edited on 16-1-2019 by divinyl]

Tsjerk - 16-1-2019 at 09:35

Do you have a proper fumehood? Halo-acetones are terrible lacrimators.

divinyl - 16-1-2019 at 11:59

Yes, fortunately I do.
Before I had one, I made my experiences with haloketones and tear gas is a good description of them. Fortunately I never messed around with halogenated acetophenone before I had a decent installation, as I heard that this is one of the worst. Although I messed around with 1-bromoacetone which was, as I understand used as a military tear-gas in the past. Luckily, I didn't experience something like the sudden boilover of bromo-butyrophenone as the guy who wrote: Learning to respect NBS the hard way
Do you think that self-condensation would be a problem with all the water in aq ammonia that pushes the equilibrium away from formation of immines?

As I remember, the delepine reaction is specificially usefull for halo-ketones(and benzyl, allyl), It would seem to me that it would do a better job than NH3. (The ketone could also be protected with e.g. ethyleneglycol before the nucleophilic substitution)

If I go the oxidation route from 2,3-diamino-2-propanol to the ketone, which method would you suggest in order to minimise/eliminate protection deprotection steps.
Thanks for the answer

[Edited on 16-1-2019 by divinyl]

clearly_not_atara - 16-1-2019 at 13:23

Yes, self-condensation is an issue. The formation of a 2,5-dihydropyrazine makes the condensed product more stable than it would be otherwise. That's why this compound is so expensive! Additionally, exposure to air causes the dimer formation to become irreversible when the dihydropyrazine is oxidized to pyrazine.

The best method is to... pick an easier benzo. A blind horse could make diazepam.

I would not suggest using the "oxidation method". Instead the direct amination of 1,3-dichloroacetone is more likely to succeed. Avoiding oxidation of the product is essential; dimerization is reversible and unavoidable, but oxidation is irreversible and can be stopped by reducing exposure to O2. The Delepine reaction seems ok, but be sure to distill the product.

kmno4 - 17-1-2019 at 15:00

Quote:

So what route would you suggest I take?

Hard to say, it depends on time, money and amount.
If you need kilograms, I would try suppliers from PRC. Prices from sigma/aldrich are very often out of this world and reality, sellers from PRC may be much cheaper.

The most elegant preparation seems to be from dihaloacetone via ketal ->amination -> deprotection -> solution of salt of the product

Oxidation of 1,3-diamino-propanol looks promising, because when it is performed in acidic media, amino groups are protonated and are far less prone to oxidation.
So, proper oxidant may produce desired product.... Worth trying if you have mentioned substrate.

divinyl - 18-1-2019 at 16:55

Could you recommend me an oxydation method that doesn't affect the amines too much(SWERN etc.) or are the amines protected enough for harsher but acidic conditions like bichromate/H2So4? Also, the last example the give in the linked experimental section uses gaseous(and shurely anhydrous NH3 gas) for in-situ generation of the diaminoacetone and its reaction product with the precursor.
I don't know what would be worse, subjecting my "tear gas" dichloroacetone to aqueous NH3(degased with N2 optimally, I guess..), which are bad conditions for imine formation and I could neutralise afterwards, yielding the salt. Would you rather recommend the delepine reaction anyway?
Thanks again

Boffis - 19-1-2019 at 09:37

@divinyl, the preparation of diaminoacetone dihydrochloride is described in Shirley's "Preparation of synthetic intermediates" by the reduction of the 1,3-dioxime of propanone dialdehyde with stannous chloride in HCl. This compound is prepared from acetone dicarboxylic acid and sodium nitrite, the preparation of which is also described. The preparation of the dicarboxylic acid from citric acid and either conc sulphuric acid or oleum is described on the Org Synth web site. While the yield of the latter compound is not great with conc. sulphuric acid there is no need to isolate the pure compound before the reaction with sodium nitrite. While the yield might not be great it looks more do-able for the amateur chemist.

Let me know if you can't find a down load of Shirley's book.

CuReUS - 19-1-2019 at 10:05

Quote: Originally posted by divinyl  
Could you recommend me an oxydation method that doesn't affect the amines too much
https://en.wikipedia.org/wiki/Oppenauer_oxidation
Quote: Originally posted by kmno4  
Oxidation of 1,3-diamino-propanol looks promising, because when it is performed in acidic media, amino groups are protonated and are far less prone to oxidation.
So, proper oxidant may produce desired product.... Worth trying if you have mentioned substrate.
even I was thinking the same thing.I wonder if this would work -https://pubs.acs.org/doi/abs/10.1021/jo01298a066 (hope chloramines are not formed :( )

kmno4 - 19-1-2019 at 18:19

There are too many oxidation procedures to recommend any particular one, especially in case of mentioned aminoalcohol.
In general, I would avoid any transition metals - I am almost sure that some amino complexes will be generated and extraction of desired product could be problematic.
First, I would try oxidation with K2S2O8 or similar persulfate.
Of course, at start aminoalcohol should be converted to its salt (H2SO4 yes, HCl not).
Oxidation of alcohols is given, for example, here : Chinese Journal of Chemistry, 2007, 25, 836—838 (wiley)