Author Topic: High-yielding nitrostyrene catalyst  (Read 9162 times)

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Barium

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Old wine
« Reply #20 on: March 26, 2003, 12:07:00 PM »
Why did I go trough the trouble to evaluate the applicability of using aqueous methylamine as a generally good knoevenagel catalyst together with the lower alcohols?
I was sick and tired of seeing ammonium acetate, n-butylamine or cyclohexylamine in refluxing toluene with a Dean-Stark trap being used in article after article and patent after patent. Looong reaction times and somewhat high temperatures awakens the improvment oriented spirit in me.

Ethylenediamine is a great catalyst for some substrates but for others it doesn't work very well at all. Methylamine gives a good yield with all the substrates I tried. I haven't seen any of the other catalysts giving a cosistent good yield with such a vide range of substrates. Have you?
I have also seen methylamine being used before, but always in dry reactions. In

Post 319830

(Barium: "Knoevenagel with various catalysts", Methods Discourse)
I wrote a list of various catalysts, conditions a yields. The reaction times are still quite long and dry solvents are used. I just discovered that aqueous enviroment is ok and the reaction time can be decreased by a mile by warming a bit.

I don't mind rain since I have an umbrella.


Antoncho

  • Guest
!!!!!!
« Reply #21 on: March 26, 2003, 12:59:00 PM »
Hey, Barium, what you discovered is the most important improvement in nitroalkene chemistry since Shulgin!

I'm shocked to see that still not everyone realizes this! :)


Awesome, man, this is awesome! I am _personally_ grateful to you for this :)





Antoncho

Barium

  • Guest
Not so wet methylamine
« Reply #22 on: March 27, 2003, 03:22:00 PM »
If someone wants to reduce the amount of water present in the reaction there is a easy way to do so. Make the methylamine freebase by mixing alcoholic solutions of KOH and methylamine HCl. KOH is preferable over NaOH since it is more soluble in alcohols. When the two solutions are mixed KCl falls out immediately and can be separated from the solution by filtration. The result is an alcoholic solution of methylamine containing only an equimolar amount of water.


Bandil

  • Guest
Sounds like a neat plan Barium.
« Reply #23 on: March 27, 2003, 04:29:00 PM »
Sounds like a neat plan Barium. I'll try that out, once i master the original procedure.


josef_k

  • Guest
Hmm.. maybe this isn't the right thread to ask
« Reply #24 on: March 27, 2003, 08:14:00 PM »
Hmm.. maybe this isn't the right thread to ask this, but nevermind. I saw in a patent about 3,4-dimethylamphetamine, that they used p-toluenesulphonic acid in the condensation between the aldehyde, nitroethane and n-butylamine. They used something like 1g for 100g aldehyde. The yield they got for that step was very high, 87% if I remember correctly. Is p-toluenesulphonic acid some catalyst for this reaction?

GC_MS

  • Guest
yes
« Reply #25 on: March 27, 2003, 08:39:00 PM »

Is p-toluenesulphonic acid some catalyst for this reaction?




Yes, it is a "general" catalyst for dehydration reactions.




slappy

  • Guest
What about...
« Reply #26 on: March 31, 2003, 04:20:00 PM »
Barium,

I notice that you add GAA to salt the methylamine at the end of the reaction before crystalization. But what if your aldehyde has a tertiary amine in it? Like say... 4-(Dimethylaminomethylene)-2,5-Dimethoxybenzaldehyde?

Bandil

  • Guest
Verification of Bariums research
« Reply #27 on: March 31, 2003, 11:28:00 PM »
Hi!

Bariums method is now tested and has proved very succesfull:

The following was added in succession to a 50 mL RBF, placed in a waterbath:

5,5 g (33 mmole, MW=166 g/mole) 2,5-dimethoxybenzaldehyde
2,7 g (35 mmole, MW=75 g/mole) nitroethane
½ mL (6,5 mmole, MW=31 g/mole) 40% aqueus methylamine

Finally methanol was added to take everything into the solution. It took roughly 10 mL's with swirling.

The color of the solution was slightly yellow tinted. To avoid the methanol escaping, a vigreux column was used as an air cooled reflux condensor. This worked just fine because of the low temperatures. It was warmed up to 65 degrees on the waterbath and held there for about one hour. At this point the reaction mixture was nicely canary yellow. When the reaction was done(60 mins), ½ mL 85% formic acid was added(no GAA available).

The mixture was put into the fridge and cooled. After 30 mins, the whole lot had crystallized into a canary yellow mess. It was filtered on suction, but only very few crystals remained. They where washed with IPA, but it was quite soluble, so a lot of product got lost here. After a few days, the solvent was stripped on a hotplate, and the remaining oil was dissolved in chloroform and washed two times with water, which was back extracted with chloroform a final time. The collected chloroform mixtures was evaporated and a dark yellow/red oil remained. This was cooled down in a fridge, but alas no crystals formed. After scraping for 10 secs with a glass rod, the whole mess crystallized into beatifull yellow crystals.

The final yeild of 2,5-dimethoxynitropropene was 4,0 grammes(18 mmol, MW=223 g/mole) which is 55% yeild calculated from the benzaldehyde. A lot where lost because the solvent was not stripped straight away and wash with water, but the yeild is still very nice. Next time i suspect the yeild to go even higher!

Way to go Barium!

Now lets see what some LAH can do to this bugger molecule :D

Regards
Bandil


Barium

  • Guest
Great
« Reply #28 on: April 01, 2003, 10:14:00 AM »
Nice work, thank you Bandil  :)
This is the reason I post my results here. To see others using the methods. Otherwise I'd just fill my lab book with methods only I could use.

Bandil, don't be afraid to add some water to the alcohol solution before cooling. This effectively kicks out the nitrostyrene. Add just enough water to cause a permanent turbidity while it's hot. Then you won't lose as much.


GC_MS

  • Guest
test test
« Reply #29 on: April 01, 2003, 09:17:00 PM »
A 50 mL RB flask was charged with 15 mL IPA, 15 mmol home-made 2,5-dimethoxybenzaldehyde (ca 95% pure, not recrystallized yet), and 1 mL nitromethane. This mixture was stirred at room temperature till all benzaldehyde was dissolved. At that point, 1 mL 20% aqueous MeNH2 was added. The colour of the mixture became dark yellow and switched to yellow-orange withing fifteen minutes. After 30 minutes, the mixture was clearly orange in colour. At exactly the 1 hour mark, the mixture suddenly solidified and as such made any further magnetic stirring impossible. The solid mass was filtered off and washed with cold dH2O (4°C). The orange mass was dissolved in warm IPA and allowed to cool down to room temperature, after which it was put in the fridge. A cloud of tiny orange crystals filled the beaker. The crystals were filtered off and washed with a small amount of cold IPA (4°C). The crystals are verified to be MeNH2-free by smell. The crystalline mass is air-dried to constant weight. Yield: 80% (not taking into account the +/- 95% purity of the benzaldehyde). The filtrate is currently warmed up to evaporate some IPA and will be put in the fridge later to harvest some residual 2,5-dimethoxynitrostyrene which is still in solution.

I also verified Ba's procedure for 3,4,5-trimethoxybenzaldehyde and anisaldehyde with nitroethane, and for 3,4,5-trimethoxybenzaldehyde with nitromethane. Seems to work OK. My yields are ca 5% less than Bariums.
I also tried benzaldehyde with nitroethane, but my nitrostyrene is refusing to crystallize. But it's there, I see it.
Props to Ba!


UncleFester

  • Guest
home brew methylamine
« Reply #30 on: April 02, 2003, 05:13:00 AM »
Barium, I already gave you props for you work, and I salute your initiative. If one is making meth or MDMA, one would be looking at making homebrew methylamine anyway, but these other compounds that would not be the case, yet the need for homebrew methylamine would still be there. Was this research done with homebrew methylamine, and how do typical homebrew contaminats like ammonia, formaldehyde, dimethylamine, affect the yield... I know dimethylamine causes alcohols to be formed, so I would like more details on the prep part of the reaction

Barium

  • Guest
No homebrews
« Reply #31 on: April 02, 2003, 10:45:00 AM »
I buy all my methylamine from the chemical supply houses. The price is next to nothing so I would never bother to make it myself. But if one has to rely on home-made I'd say it's just a matter of purifying it properly. Follow the directions in Vogel's bible.


GC_MS

  • Guest
additional information
« Reply #32 on: April 02, 2003, 05:54:00 PM »
I found this recently via CA; it is a little bit related to Ba's find: SP Makarow. Ueber den Mechanismus der Kondensation aromatischer Oxyaldehyde mit Nitromethan in Gegenwart organischer Basen. J prakt Chem 141 (1934) 77-90

3-methoxy-4-hydroxy-5-bromo-w-nitrostyrene - 2.3 g (1 mol) 5-bromovanillin and 0.75 g MeNO2 are dissolved in 10 mL EtOH, together with one drop 20% alcoholic MeNH2 solution. The mixture is heated on the waterbath till the 5-bromovanillin goes into solution (ca 70-75°C) and kept at that temperature for 6 hours. The weakly yellow coloured solution slowly changes to deep cherry red. When the solution is cooled down, yellow needle-shaped crystals are formed. To recrystallize the 3-methoxy-4-hydroxy-5-bromo-w-nitrostyrene, EtOH with one drop AcOH is applied; mp 189-190°C. Yield: 2 g. Easily dissolved in aceton, almost insoluble in EtOH or carbohydrates. By addition of alkali or the salts of weak acids (bicarbonates), red salts are formed.[...]


Barium

  • Guest
A damn quick one
« Reply #33 on: May 09, 2003, 05:17:00 PM »
100 mmol 5-bromo-2,4-dimethoxybenzaldehyde (made by bromination of 2,4-dimethoxybenzaldehyde with elementar bromine in DCM, 92% yield) was added to 150 ml EtOH and 120 mmol nitromethane and heated to 55°C to dissolve it. About 50% of the aldehyde went into solution. 20 mmol methylamine as a 40% aq solution was added. Now the aldehyde went into solution during 5 minutes while swirling the solution by hand.

When all of the aldehyde had gone into solution I was just about to place the flask back into the heating bath when I noticed that the solution became a bit cloudy. As I watched the solution went from slightly cloudy to a unstirrable mass of bright yellow crystals within 20 seconds. 200 ml EtOH was added and the suspension was heated to 50°C with stirring. 10 minutes later it, once again, had become a unstirrable paste. The crystals are drying right now. it will be interesting to see the yield.

Never ever have I seen a nitrostyrene formation going at this speed. Amazing!!  :o


Barium

  • Guest
Thanks Lego
« Reply #34 on: May 29, 2003, 03:58:00 PM »
That procedure looks quite nice and I'll bet it is improveble. It's amazing that this article was out on review and apparently nobody reacted to the lack of nitromethane information. Or was it even reviewed?


Xicori

  • Guest
High! Swim is really impressed from the yeilds
« Reply #35 on: May 29, 2003, 09:11:00 PM »
High!

Swim is really impressed from the yeilds you got, Barium!! Very nice work, indeed!!

Does anybee know if homemade Methylamine is also useable in this reaction? (Because of the NH4Cl/Dimethylamine impurities)

Can the aqueous solution be made by just adding Mathylamine-HCl and NaOH to cold water?

greetings,
xicori

Barium

  • Guest
Ammonia again
« Reply #36 on: July 03, 2003, 11:40:00 AM »
A quick test gave this result:

2,5-Dimethoxybenzaldehyde, 50 mmol
Nitromethane, 60 mmol
Ammonia, 15 mmol as a 25% aqueous solution
IPA, 25 ml

The aldehyde was added to IPA and the ammonia solution added.
The mixture was heated to 40° and stirred to dissolve the aldehyde.
When all was dissolved the nitromethane was added and the yellow
solution heated to 60° for 4 hours. The solution now had a
dark color consistent with the nitrostyrene but no crystals visible.
When cooled to 5°C crystals begun to grow. These was removed by
filtration and washed sparingly with ice-cold IPA and dried to constant weight.

Yield 4,7 g 1-(2,5-dimethoxyphenyl)-2-nitroethene (22 mmol, 45%)

Comments: Higher yields would possibly be achieveble if the ammonia is generated in situ in IPA from e.g. NH4Cl and KOH. Aromatic imines are very stable compared to aliphatic imines, but the water present in the 25% aq NH4OH solution might interfer too much. Anyway, this clearly shows that cheap and simple to get ammonia can be used to make, at least, 2,5-DMNS.


hest

  • Guest
nuuking 2,5-DMBA, nitomethane (mole to mole)...
« Reply #37 on: July 03, 2003, 04:32:00 PM »
nuuking 2,5-DMBA, nitomethane (mole to mole) and some amine (cyclohexylamine, butylamine ect.) gives yeald close to 100%

Sunlight

  • Guest
Mmm
« Reply #38 on: July 03, 2003, 05:26:00 PM »
I used to make 2,5 DMNS with cyclohexylamine. That rxn is sensitive to amine concentration, and I've got yields of 100 % whith no solvent, but some of the product was a polymeric byproduct not much soluble in boiling IPA. Using methanol as solvent the rxn works better, but yield was about 77 % and sometimes it has a spot in the TLC of a contaminant. Finally I tried the ethylenediammonium diacetate (making it in situ) and yield is always 90+ %, and only one spot.
3,4,5 TMB in methanol and cyclohexylamine yields a polymer not soluble in boiling methanol.
Not always the product recovered is just the desired product. I posted this link as an example of this in the beginning of the tread.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenethylamines.dibah.html


Sunlight

  • Guest
Test with 3,4,5 TMB failure
« Reply #39 on: July 09, 2003, 03:40:00 AM »
Acording with Barium's instructions, 5 gr of 3,4,5 TMB was mixed with repective amounts of aqueous methylamine and nitromethane in 20 ml of methanol, and it was kept at 50 C for 1 hour. Then it was put in the freezer, and filtered. The filtrate was a yellow and amorphous solid, and a TLC showed three spots, one on the bottom line, other in the place of the aldehyde an the third one in the place ot the nitrostyrene.
I tried to recrystallize a sample of 1.9 grams in ethanol. It was posted a reference it the Hive in wich this recrystallization was done using 7:1 of ethanol, but this substance refused to dissolve even in 18:1 boiling ethanol. I filtered it immediatly and recovered about 1.2 grams of the product, a sample of that couldn't be dissolved even in a large excess of boiling acetone, while a sample of the nitrostyrene made with Shulgin's procedure (one spot TLC) was easily dissolved in a bit of acetone at room temperature. The procedure yield a mixture in wich the main part corresponds to this not soluble product, that appears in the bottom line in the TLC because it is in suspension. I got the same product when I tried to make 3,4,5 TMNS with cyclohexylamine in methanol at room temp as I've said before, then I was confused thinking it was the styrene, because it has a yellowish aspect.
So I don't recommend this method if you want to get this particular nitrostyrene. It probably will work fine with some aldehydes, but others will produce byproducts, as in this case and in the others tested in the paper in Rhodium's page. (Link above).
I guess Barium didn't verified that the product he got in his test was the desired product.

By the way, I guess there is a typo in PIHKAL in the entry of mescaline, the nitrostyrene is recrystallized using 15 ml/g but in fact 5 ml it's enough, I've done it. There's another one in the dose, the amount of the sulfate and the hydrochloride doesn't match.