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Author: Subject: Diethylamine as catalyst in henry reaction?
Racconized
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Diethylamine as catalyst in henry reaction?

Hi, stupid question here.
I attempted (2 times) a henry reaction with benzaldehyde (from benzyl alcohol and manganese dioxide, shity and possibly impure*), 1-nitroPROPANE and bad unknown concentration of aqueous methylamine (from hexamine hydrolysis). Eitherway this is besides the point, I was just bored and wanted to try it.

Since I dont wanna boil down the methylamine and recrystallize it due to the strong smell of cat piss of the methylamine/hexamine solution, I was wondering if there is any reason why not the secondary amine, diethylamine should work, that is the only alkylamine I have atm. Could only find one paper mentioning using diethylamine as a sole catalyst in henry reaction.

doi.org/10.2478/s11696-010-0047-1

Found another somewhat relevant article +-
https://doi.org/10.1016/j.tetlet.2017.12.050

I also ordered some technical grade benzaldehyde, which I will try on. Hoping to avoid having to buy butylamine or some other amine, since shipping is too expensive for only 1 chemical.

*Didn't have anything to make a bisulfite solution and purify by adduct.

Thanks for any input or redirection to useful academic paper or sciencemadness topic

[Edited on 18-6-2020 by Racconized]
draculic acid69
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Interesting experiment. I've wondered why it hasn't been done before. I think every different substrate works differently with different amines.you just have to find the right one for this rxn. Have u thought about trying phenethylamine? It's like $5 a bag off eBay.its worth trying I think. I'm pretty sure someone tried nitroethane with benzaldehyde using phenethylamine on here Racconized Harmless Posts: 22 Registered: 27-11-2016 Member Is Offline Mood: Yes  Quote: Originally posted by draculic acid69 Interesting experiment. I've wondered why it hasn't been done before. I think every different substrate works differently with different amines.you just have to find the right one for this rxn. Have u thought about trying phenethylamine? It's like$5 a bag off eBay.its worth trying I think. I'm pretty sure someone tried nitroethane with benzaldehyde using phenethylamine on here

I don't know starting to doubt if secondary amines can do it, seems more like it only works as a base in the papers I linked, with the major product being the nitro-alcohol. Same thing seems to be the case with tertiary amines.1

1https://pubs.acs.org/doi/abs/10.1021/ja01215a038

But I will try it once I get my benzaldehyde, but I also ordered some n-butylamine (edit: nope, no shipping of primary amines and pickup unavailable due to covid) and ammonium acetate anyway.

I'm thinking i'll try diethylamine as a sole base and possible catalyst, and also in combination of glacial acetic acid as solvent. Seen some info here and in studies using different acetate salts (besides ammonium acetate) and acetic acid.

Interesting study: Influence of base on nitro-aldol (Henry) reaction
products for alternative clandestine pathways

http://dx.doi.org/10.1080/00450618.2015.1112429

I also just realized I actually have aniline, but for some reason doubt that will work as a catalyst here.

[Edited on 18-6-2020 by Racconized]
draculic acid69
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Yes that's the post I was talking about
Pumukli
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If a primary amine can catalyse it, a strong base (NaOH) can catalyse it, even NaOAc can catalyse it then I'd expect a reaction with diethylamine too.

Isn't the nitro-alcohol is formed at first then it dehydrates in the following step? Strong acids (HCl e.g.) catalyse the dehydration.

Aniline - I think it is too weak a base for this. But who knows until someone tries? :-)
draculic acid69
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I read somewhere that iso,sec and tert butyl amine don't work so im guessing that the type of amines used isn't so flexible.
karlos³
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I used diethylamine for that reaction, but with the intended goal of a nitroalcohol.
It works pretty good, you would have to dehydrate the nitroalcohol afterwards though if you want the nitroalkene.
Racconized
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 Quote: Originally posted by karlos³ I used diethylamine for that reaction, but with the intended goal of a nitroalcohol. It works pretty good, you would have to dehydrate the nitroalcohol afterwards though if you want the nitroalkene.

Nice, nitroalcohols are also cool. Did you use it without any solvent, besides the the nitroalkane i.e. Did you take note of what yield you ended up with?

Since you have tried diethylamine without solvent, I'm guessing I need to try it with acetic acid + diethylamine. Has been some talk on this forum about using the acetate salts of methylamine, Ethylenediamine and I think even cyclohexylamine. I'm expecting I will have my benzaldehyde in max 2 weeks or at least some bisulfite from a brewery e-shop in max 4 days to purify my current 5-8ml of benzaldehyde
Racconized
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Stumbled up on this and I was surprised to see the inventor's name "Alexander T. Shulgin"
He mentions the use of dimethylamine, and diethylamine in an alcohol, what I find quite contradictory is the product is a nitropropene and not an nitro-alcohol (maybe not right word, but you know what I mean).
Some other resources I found suggested that nitro-alcohol is the major product with tertiary or secondary amines

Such as https://patents.google.com/patent/EP0960876A1/en, however do note that in this patent the reaction conditions was -10 degress c and a reaction time of 45 min in the example with diethylamine (0.20 equiv)
Or (1) Worrall, D. E. The Knoevenagel Reaction and the Synthesis of Unsaturated Nitro Compounds. J. Am. Chem. Soc. 1934, 56 (7), 1556–1558. https://doi.org/10.1021/ja01322a030.
and (3) Chen, G.; Hao, X.-J.; Sun, Q.-Y.; Ding, J. Rapid Synthesis and Bioactivities of 3-(Nitromethylene)Indolin-2-One Analogues. Chemical Papers 2010, 64 (5). https://doi.org/10.2478/s11696-010-0047-1. (however do note that this paper used a "vastly" different substrate, i.e. not a benzaldehyde)

However there are other publications that support the claim that a nitro-propene is the major product using diethylamine as catalyst in similar conditions to Shulgin's patent
(3) Haszeldine, R. N.; Tipping, A. E.; Valentine, R. H. Perfluoroalkyl Derivatives of Nitrogen. Part L [1]. Synthesis of the Amphetamine 2-Amino-1-[(4-NN-Bistrifluoromethylamino)-Phenyl]Propane. Journal of Fluorine Chemistry 1982, 21 (3), 329–334. https://doi.org/10.1016/S0022-1139(00)81517-1.

I have also like I said in a previous post attempted diethylamine using acetic acid as solvent but the results were unsatisfactory and I failed to get some kind of indication that the reaction was on going even with the addition of more drops of diethylamine, there was no or very little change in color even after medium heating (no reflux, didnt use a three necked flask so wasn't able to get a temperature reading). Maybe I was too impatient, or possibly nitropropane is just a very bad or unreactive nitroalkane in the "nitro-aldol" reaction (which is a probability since nitropropane is known to be in general low-yielding based on pihkal entries and (6) Gallardo-Godoy, A.; Fierro, A.; McLean, T. H.; Castillo, M.; Cassels, B. K.; Reyes-Parada, M.; Nichols, D. E. Sulfur-Substituted α-Alkyl Phenethylamines as Selective and Reversible MAO-A Inhibitors: Biological Activities, CoMFA Analysis, and Active Site Modeling. J. Med. Chem. 2005, 48 (7), 2407–2419. https://doi.org/10.1021/jm0493109.

[Edited on 29-6-2020 by Racconized]

[Edited on 29-6-2020 by Racconized]
dextro88
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if you want to get the alcohol you need wet conditions and bases works good there was a table of the different isomers formed duo to base used, acidic invirnoment is meant duo for more easy and clean dehydration of the nitroalcohol to the double bond, im intrested coud one dehydrate the nitroalcohol formed with somethink like sulfuric acid to the nitroalkene as like borohydride woud reduce the phenyl2nitropropene ?
Racconized
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 Quote: Originally posted by dextro88 if you want to get the alcohol you need wet conditions and bases works good there was a table of the different isomers formed duo to base used, acidic invirnoment is meant duo for more easy and clean dehydration of the nitroalcohol to the double bond, im intrested coud one dehydrate the nitroalcohol formed with somethink like sulfuric acid to the nitroalkene as like borohydride woud reduce the phenyl2nitropropene ?

From what I have read, nitroalcohols are pretty prone to "decompose" or transform into nitroalkene. I do however re-call nitroalcohol of the nitromethane derivative being more prone to dehydration than the b-nitroalcohol of nitropropane

example: http://orgsyn.org/demo.aspx?prep=cv1p0413
Here Hydrochloric acid is enough to dehydrate, I however dont think this will for the the b-alcohol of nitropropane

I know and I'm sorry for not knowing the correct names for the b-nitroalcohol derivatives, I don't what they they are called.

Edit: ok I won't edit the text but what I meant with nitromethane derivative is 2-Nitro-1-phenylethenol, and nitroethane derivative being 2-Nitro-1-phenylprop-1-en-1-ol

Edit2: No I didn't, nitroethane derivative = 2-nitro-1-phenyl-1-propanol
However I'm unsure why the prepchem showed the beta-nitroalcohol with double bond since that doesnt seem to happen when nitroethane is used
https://cyber.sci-hub.tw/MTAuMTAyMS9qbzAxMTY4YTAwMw==/hoover...

I need to do some more research on this reaction, sorry for any of my post containing possible incorrect statements.

[Edited on 29-6-2020 by Racconized]

[Edited on 29-6-2020 by Racconized]
Racconized
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Also I'm starting to doubt that my initial reactionS with shitty methylamine really failed, I just re-did the crappy methylamine catalysis but instead used nitroethane and the results were just like with nitropropane disappointing and ended up with a heavy thick yellow-orange oily layer but with somewhat solid / granulates / blobs at the bottom. However this time I decided to give it a chance and separated it after adding some acetic acid to neutralize the freebase methylamine. Dissolved it in minimal amount of methanol and put it in freezer, this was also a fail and only produced a solid round granulates at the bottom, so I removed it from freezer and put it in room temperature and then put it in fridge instead (today) and right now there is formation of fine crystals traveling from the bottom of the beaker.

Can't verify atm if the crystals really are nitropropene or perhaps the nitroalcohol, I mean it could just as well be the catalyst or the impurities from my methylamine but I doubt it since that should have gotten separated when I added a little water + acetic acid and decanted the aqueous layer

Anyway If this happens to be nitropropene, I'm obviously also gonna have to retry but with diethylamine with and without acetic acid as solvent (trying it with both nitropropane and nitroethane) , and just have some patience when it comes to re-crystallization (which appears to be rather difficult)
dextro88
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so you are tring to prepare the nitropropane with plain benzaldehyde and nitroethane, im intrested whats your intentions of usage of your nitropropane althrow the nitroalcohol is solution and you hardly will crystalize any p2np out of it.
Corrosive Joeseph
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https://www.erowid.org/archive/rhodium/chemistry/phenyl-2-ni...

/CJ

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karlos³
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Quote: Originally posted by Racconized
 Quote: Originally posted by karlos³ I used diethylamine for that reaction, but with the intended goal of a nitroalcohol. It works pretty good, you would have to dehydrate the nitroalcohol afterwards though if you want the nitroalkene.

Nice, nitroalcohols are also cool. Did you use it without any solvent, besides the the nitroalkane i.e. Did you take note of what yield you ended up with?

Acetic acid will stop this reaction.
Racconized
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 Quote: Originally posted by dextro88 so you are tring to prepare the nitropropane with plain benzaldehyde and nitroethane, im intrested whats your intentions of usage of your nitropropane althrow the nitroalcohol is solution and you hardly will crystalize any p2np out of it.

No sir, I have the nitroalkane, nitropropane. But I also have the nitroalkane nitroethane. So I am trying both.

Nitropropane should yield if successful nitrobutene

Not sure if a interpreted your post correctly, but I think my poorly written posts have confused you as to what my purpose is, and that is my bad and is due to my rambling.

My intention was to use diethylamine as a catalyst, to form a nitrobutene with nitropropane and to form a nitropropene with nitroethane. Which I still will try to do, however I'm gonna try using straight out diethylamine since the attempt with diethylamine and acetic acid failed. Most sources claim this will only yield nitroalcohol as the major product and that is what I also think and according to karlos, that seems to be the case. However Shulgin also reports using straight diethylamine in alcohol and apparently and surprisingly getting the nitropropene with substituted benzaldehydes.

I'm gonna attempt using diethylamine in alcohol to form phenyl-2-nitropropene (using of course nitroethane as my nitroalkane) either tomorrow or the day after. I think of course that I will get the nitroalcohol if anything, but eitherway I now have some phenyl-2-nitropropene crystals so in the event of it actually being successful crystallization should be easier now that I have some seed crystals.

Quote: Originally posted by karlos³
Quote: Originally posted by Racconized
 Quote: Originally posted by karlos³ I used diethylamine for that reaction, but with the intended goal of a nitroalcohol. It works pretty good, you would have to dehydrate the nitroalcohol afterwards though if you want the nitroalkene.

Nice, nitroalcohols are also cool. Did you use it without any solvent, besides the the nitroalkane i.e. Did you take note of what yield you ended up with?

Acetic acid will stop this reaction.

Yeah that explains why no color change occurred, it was plain transparent even after heating for several hours maybe a tint of light light yellow with heavy heating.

[Edited on 29-6-2020 by Racconized]

[Edited on 29-6-2020 by Racconized]

[Edited on 29-6-2020 by Racconized]

[Edited on 29-6-2020 by Racconized]

 Sciencemadness Discussion Board » Fundamentals » Organic Chemistry » Diethylamine as catalyst in henry reaction? Select A Forum Fundamentals   » Chemistry in General   » Organic Chemistry   » Reagents and Apparatus Acquisition   » Beginnings   » Responsible Practices   » Miscellaneous   » The Wiki Special topics   » Technochemistry   » Energetic Materials   » Biochemistry   » Radiochemistry   » Computational Models and Techniques   » Prepublication Non-chemistry   » Forum Matters   » Legal and Societal Issues