What am I doing wrong? (P2NP)

[Rabidreject]

So iv tried to synthesise this a couples times now, using both ethylenediamine/GAA and more recently using cyclohexylamine/ GAA.

The first time I tried using EDA as the catalyst, I don’t think I refluxed for long enough. It changed colour from essentially clear to slightly yellow but I couldn’t ever get anything to crash out of it.

This time I used 1.2 mol eq of nitroethane, catalytic quantities of cyclohexylamine with a bit more GAA and then a little methanol as a solvent.
I attached a condenser and put it in a water bath with stirring for 12.5h at reflux. Then I turned the heat down to around 30 and left it for another 6 or so hours (I was asleep and the pump was making an annoying sound). Probably could have just turned it off but I didn’t.
It’s now in the freezer but I doubt anything will crash out.
What am I doing wrong?

Should I just use a huge excess of nitroethane as both solvent and reagent to push it forward according to le Chatlier’s principle? Or what’s the deal why am I never seeing anything crystallise?

If I come back and it has crystallised I will obviously update this but I’d be really surprised.

I have done quite a few successful Henry reactions but almost always with electron donating methoxy groups on the aromatic ring, so they have been pretty easy compared to regular benzaldehyde.

 

[Rabidreject]

Huh okay - it looks like a got an oil crash out instead. Do I just separate it, re-x and hope for the best?
I think I ended up with an oil when I made 3,4,5-trimethoxynitropropene…

 

[Rabidreject]

One last thing; how do I know if im using enough/ too much solvent when recrystallising an oil?
obviously when you start with a solid you can dissolve in a minimal amount of solvent but you can’t really see that with an oil. Any recommendations?

Or maybe it isn’t even crude p2np that’s dropped out - does it ever crash out as an oil?

 

[FQ-BB]

I'll help you solve it

 

[FQ-BB]

If the following helped you out, please donate to the bb forums and thank them for giving you the platform to provide a solution!!!!
1. The reaction may not have been fully carried out:
Reaction time: 12.5 h reflux, additional 6 h low temp, although longer, may not have reached full conversion. Color change: from clear to slightly yellowish, indicating that the reaction is proceeding, but has not reached the deep orange/red stage, possibly low conversion. Oil precipitation: may be unpurified P2NP, or a by-product. 2.
2. P2NP nitroalkene may form an oily by-product: if the polarity of the reaction solvents do not match (e.g., more methanol is used), this may result in the target product failing to crystallize, another possibility is that the P2NP still contains unreacted aldehydes or intermediates causing it to precipitate out in liquid form. The solvent system may not be suitable for recrystallization: Recrystallization Requirements: The correct solvent pair needs to be found, e.g., methanol + water / ethanol + ethyl acetate, to ensure that the P2NP can be solubilized and slowly cooled to crystallize. If P2NP is still oily, it may be necessary to remove impurities (e.g. unreacted benzaldehyde, alcoholization by-products) before attempting crystallization.
Suggested adjustments:
1. Use a stronger catalyst (e.g., ethylenediamine EDA + acetic acid GAA) Cyclohexylamine is a weak base, and EDA is more suitable as a base catalyst, which promotes P2NP formation faster. Reagent ratio optimization:
Benzaldehyde: 1.0 isomole
Nitroethane: 1.2-1.5 equimolar (moderate excess, not extreme excess)
EDA: catalytic amount (5-10 mol%)
Acetic acid (GAA): catalytic amount (5-10 mol%)
Solvent: methanol / ethanol / isopropanol (moderate amount to ensure dissolution of reactants)
2. Improved reflux temperature: 80-90°C
Time control: 6-8 hours (12+ hours not required) During this time, the color should change from clear → yellow → orange → red or deep red (indicating nitroalkene formation).
When the reaction is complete, neutralize the reaction solution with carbonic acid (Na₂CO₃) or sodium hydroxide (NaOH) to remove excess acetic acid.
If an oily P2NP has been produced, do not put it directly into the freezer, but: try extraction and purification with dichloromethane (CH₂Cl₂) or ethyl acetate (EtOAc). The organic phase is dried with anhydrous sodium sulfate (Na₂SO₄) and filtered to remove water. The solvent was evaporated at low temperature and observed for solid precipitation. Add a small amount of anhydrous hexane or n-hexane, stir and cool to -10°C. Allow to stand for 24 h. Observe for crystal precipitation. Try directly Methanol (small amount) + water (dropwise) for recrystallization: Heat to dissolve P2NP (50-60°C). Cool slowly to room temperature and then to 0°C to promote crystal formation.

🫢🫢🫢

 

[w2x3f5]

5 percent of the excess nitroetan is enough more than. Do you understand the difference between ethylendiamine and cyclohexylamine? It is advisable to distill the excess of nitroethan. Washing is carried out with clean cold water, neither soda nor alkali are used. For crystallization, a crystal is used.

 

[Rabidreject]

Oh brilliant suggestions. Thanks a bunch for that.
It’s infuriating because iv done this reaction so many times with substituted benzaldehyde’s and always got great results but with p2np it’s a different story!

Okay yeh I did realise I screwed up the mol ratios and realised this morning I should not have added methanol at all.
Will try again with these mol eq’s:

benzaldehyde - 1
Nitroethane - 1.4
EDA - 0.1
GAA - 0.71

I just put it on and my EDA (or the open bottle of EDA) was pretty orange and discoloured. Thought I would try it anyway and got more of a colour shift in the first few minutes than in the 18h I was messing about with the last one.

We’ll see, I have faith now iv adjusted the ratios to somewhere half sensible.

If I get lots of gunk or something then I would either redistil the EDA I have or just use the new bottle but looking good so far.

The other ‘oil’ wouldn’t crystallise on trying so I assume it didn’t go enough.

This reaction is a sort of orange colour before iv even really started. I’ll take the reflux up higher and do for less time this time also.

Thanks for the tips…

is there a reason you sent this to my messages BUT in Chinese? Lol

 

[FQ-BB]

Sorry, due to browser issues, my location appears as China, and itcurrently the Chinese New Year. Wishing you all a Happy New Year!





I made an error while using my phone. Please report to the forum administrator that I did not post any pre-sale content or promotional advertisements. Otherwise, my account may get banned.

 

[Rabidreject]

Do what now?

 

[w2x3f5]

The procedure for adding reagents?

 

[Rabidreject]

Oh wow.
I separated the oil and added hot methanol to it then put it in the freezer - nothing.
Then I decided to add water to it - with a view to throw it away as i am running another reaction.
Came back realised there was a fat leak under my kitchen sink, cleaned it up and then turn around and….

Beautiful clean P2NP. lovely.
Be interesting to see what happens with this reaction I’m doing now….and my sink

 

[FQ-BB]

pretty

 

[Rabidreject]

Reaction one (cyclohexylamine) - 65% yield (roughly). 15g reaction size and 14.5g of really pure looking crystals.

Reaction two (EDA) - 59.28% yield, 5ml quantity of benzaldehyde and I got 4.35g of a still fairly dirty looking p2np that i have re-crystallised once.
it looks mad though, it’s sort of a pink shade after the first re-x.

If I ever needed to make more I would just do the first reaction again but for just 6h instead of leaving it overnight.
Thanks for the help, I probably shouldn’t have even made this post as I didn’t even wait to see if what I had would crystallise…and it did so

 

[rampage]

check out this thread mate it might help you

http://bbzzzsvqcrqtki6umym6itiixfhni37ybtt7mkbjyxn2pgllzxf2qgyd.onion/threads/microwave-small-scale-1-phenyl-2-nitropropene-p2np.11823/

 

[Rabidreject]

Yeah that’s interesting. Trouble is I only have 1 microwave and I use it to eat - so I’ll probably pass…

It’s strange though, the second reaction using EDA clearly produced more biproducts that are hard to get rid of.
I recrystallised it twice from iso and they came out the same the second time.
They are like a pinky colour as opposed to the lovely pale yellow of my first reaction.

First reactions product…



second, discoloured product…



Is pretty annoying to be honest. The crystals form is right and nice shards formed but the colour is very odd!

Oh well, I’m good now. Iv done it once and can move on.
Thanks for all the help

 

[loadingST]

How much effort for such easy reaction, just use the plain cheap and available dry amonium acetate in gaa, boil hard in reflux to orange and crash out with ice, fast and easy way to get the crude p2np ...

 

[Rabidreject]

Yeah I have realised that now funnily enough.

So I had tried to make this before and now I have successfully done so, I realise that it wasn’t the actual reaction that was the issue before, it was the crystallisation.

So when I went to make some this time, I assumed it needed longer to react (which it didn’t) - I actually just needed to realise there was acid in the solution which was probably keeping the p2np dissolved. Washing with water, every time has lead to crystallisation so I assume that is what was going wrong when it wouldn’t crash out upon cooling.

Last night I made more in a much simpler manner.
I chucked everything into my round bottom (50ml benzaldehyde, 50ml nitroethane, 6-7ml of cyclohexylamine and 10ml GAA) and put it in a steam bath at 80c for 7 or so hours.
When I came back in the morning, there was a yellow oil layer on the bottom and a small clearer layer on top.
Yesterday I recrystallised my last batch of p2np and didn’t wash up the beaker so it had some crystals around the edge.
I poured my RM in and it instantly crystallised via seed nucleation.

When I filtered there was still some oil come through so I just washed it with more water and it eventually went solid. This happened a few times

So yeah a hot water bath with no condenser worked fine.

It is interesting how much extra heat and time it needs than working with substituted benzaldehyde’s.

 

[w2x3f5]

The bad tone mix benzaldehyde with amin. Either you make a ready -made amine acetate to the reaction, or first mix all the reagents and the last queue add benzaldehyde.

 

[Rabidreject]

Yeh okay that’s how iv been doing it anyway.

Iv done this a few times since actually on a 50g scale (because multiple subsequent reactions in a row were sloppy and yield was baaaaad)
I used it for two things, first I used HCl and iron to reduce to the ketone. Gross and yields suck but I had no other way really so that took up a load.
Then I spanked a load making D-amphetamine coz I tried to scale up my 10g NaBH4 reduction to 15g and it went really badly coz stirring wouldn’t work anymore. I wouldn’t be surprised if I get more on the one I just did which was 10g than how much R-amphetamine i got from the 15g one.
Anyway no one cares I’m sure but the resolution of enantiomers was the easy bit to be honest.

 

[rampage]

the microwave is much easier and quicker mate, if your gonna do p2np it is seriously worth it

 

[w2x3f5]

What I said concerns the reaction of Henry condensation