Author Topic: High-yielding nitrostyrene catalyst  (Read 7719 times)

0 Members and 1 Guest are viewing this topic.

Barium

  • Guest
High-yielding nitrostyrene catalyst
« on: March 20, 2003, 12:40:00 PM »
I have been searching and searching and trying and trying for years to find a cheap  condensation/dehydration catalyst which doesn't require refluxing GAA or nitromethane to get good yields. Finally I have found it. Methylamine.


A general method for nitrostyrenes is as follows:

100 mmol of a aromatic aldehyde
105 mmol nitromethane or nitroethane
15-20 mmol methylamine as a 10-20% aqueous solution
Enough MeOH, EtOH or IPA to make the mixture stirable. Usually about 25 ml

To a 250 ml rb-flask equipped with a magnetic stirbar is added the aromatic aldehyde, nitromethane and the alcohol. Sirring is started and the aqueous methylamine solution is added in one portion. The reaction flask is placed in a water bath and heated to 40-50°C. The reaction progress can be monitored by TLC to see when the aldehyde is consumed. In most cases 45 minutes in the water bath is enough.
When the reaction is over 25 mmol GAA is added to the reaction mixture and the flask is placed in the freezer until the crystallisation is complete [1]. The solids are then broken up with a spatula, transferred to a filter funnel and washed with water to remove most of the methylamine acetate. The nitrostyrene is then recrystallised from MeOH, EtOH or IPA.



1-phenyl-2-nitroethene, 92%
1-phenyl-2-nitropropene, 93%
1-(4-ethoxyphenyl)-2-nitroethene, 88%
1-(4-ethoxyphenyl)-2-nitropropene, 90%
1-(2-methoxyphenyl)-2-nitroethene, 94%
1-(2-methoxyphenyl)-2-nitropropene, 89%
1-(4-methoxyphenyl)-2-nitroethene, 92%
1-(4-methoxyphenyl)-2-nitropropene, 88%
1-(2,4-dimethoxyphenyl)-2-nitroethene, 97%
1-(2,4-dimethoxyphenyl)-2-nitropropene, 74%
1-(2,5-dimethoxyphenyl)-2-nitroethene, 97%
1-(2,5-dimethoxyphenyl)-2-nitropropene, 89%
1-(2,4,5-trimethoxyphenyl)-2-nitroethene, 89%
1-(2,4,5-trimethoxyphenyl)-2-nitropropene, 94%
1-(2,4,6-trimethoxyphenyl)-2-nitroethene, 95%
1-(2,4,6-trimethoxyphenyl)-2-nitropropene, 96%
1-(3,4,5-trimethoxyphenyl)-2-nitroethene, 92%
1-(3,4,5-trimethoxyphenyl)-2-nitropropene, 93%


3-(2-nitrovinyl)-1H-indole, 79%
3-(2-nitropropenyl)-1H-indole, 72%
5-methoxy-3-(2-nitrovinyl)-1H-indole, 83%
5-methoxy-3-(2-nitropropenyl)-1H-indole, 91%

[1] In case of 1-(2,5-dimethoxyphenyl)-2-nitroethene crystallisation occurs during the reaction. After 20 minutes at 50°C the reaction mixture becomes a bright neon-orange solid cake.


pHarmacist

  • Guest
wow! Thanks a lot Barium!
« Reply #1 on: March 20, 2003, 02:11:00 PM »
Thank you sooo much for telling us about methylamine's use! Personally I'm going to have a lot of benefit from this in Henry's condensation. You've just opened my eyes! Are you actually talking about isolated yields, that YOU got?

If Barium does it, it will work!


Sunlight

  • Guest
Take a look
« Reply #2 on: March 20, 2003, 07:11:00 PM »
To this Rhodium's link:

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



They used four methods to prepare nitrostyrenes, methanolic methylamine 16-20 %, aqueous ethylamine 70 %, ethanol KOH and ammonium acetate acetic acid. Results show that using methods first or second, an apparent 90 % + yield of nitrostyrenes from piperonal and veratraldehyde are really 50-60 % due nitrostyrene is contaminated with high molecular mass products.
Anyway in Michael Valentine' Psychedelic Chemistry methanolic methylamine is proposed to get the 3,4,5 nitro, with an unespecefied yield. It's not a very good book.
And for example, 3,4,5 trimethoxy benzaldehyde condensation with cyclohexylamine in methanol yield a strange product that it is not the styrene. TLC aids almost nothing in this case because this product is not soluble in methanol.
Have you performed any analytical procecure to determine the purity of the products you got with this attractive method ?

GC_MS

  • Guest
Must
« Reply #3 on: March 20, 2003, 08:13:00 PM »
Must...find...benzaldehydes...Start...synthesis...aaaargh! Nice to hear you're still alive Ba  ;)


Barium

  • Guest
Tests
« Reply #4 on: March 21, 2003, 10:40:00 AM »
The following nitrostyrenes has been reduced to the corresponding nitroalkanes using the EtOAc/EtOH/NaBH4 method followed by reduction to the amines using the IPA/KCOOH/Pd-C system.

1-(4-ethoxyphenyl)-2-nitroethene, 89% nitroalkane*, 85% amine hydrochloride*, 97% by HPLC**.
1-(4-ethoxyphenyl)-2-nitropropene, 86% nitroalkane*, 85% amine hydrochloride*, 98% by HPLC**.
1-(2,5-dimethoxyphenyl)-2-nitroethene, 94% nitroalkane*, 82% amine hydrochloride*, 98% by HPLC**.
1-(2,4-dimethoxyphenyl)-2-nitropropene, 90% nitroalkane*, 91% amine hydrochloride*, 98% by HPLC**.
1-(2,4,6-trimethoxyphenyl)-2-nitropropene, 96% nitroalkane*, 94% amine hydrochloride*, 98% by HPLC**.

* Isolatetd yield
** Purity by HPLC, calculated as area %.


Sunlight

  • Guest
Good
« Reply #5 on: March 22, 2003, 02:47:00 AM »
Very good, congratulations !!! I hope I can try it soon with my own hands.

Chimimanie

  • Guest
Barium
« Reply #6 on: March 22, 2003, 10:06:00 AM »
Barium you are the best :)

Very good work, thank you man ;)

cattleprodder

  • Guest
Barium,
« Reply #7 on: March 24, 2003, 03:31:00 PM »

Bandil

  • Guest
skip this post
« Reply #8 on: March 24, 2003, 03:38:00 PM »

cattleprodder

  • Guest
Free acid for the school kids!
« Reply #9 on: March 24, 2003, 08:00:00 PM »

Bandil

  • Guest
To return to the topic
« Reply #10 on: March 24, 2003, 10:43:00 PM »
I don't know if this is a dumb question, but here goes:

The reaction is a condensation reaction, where water is from the two molecules, when reacting. In order to improve yeilds it has been proposed to remove the water via a dean stark trap during the reaction according to le chaleliers principle. 

This variant of the reaction is "swamp like" wet and yet provides high yeilds. Does anyone have an explanation of this? Could the yeilds go even higher if anhydrous methylamine dissolved in IPA was used?

Regards
Bandil


Megatherium

  • Guest
That is a rather interesting question.
« Reply #11 on: March 24, 2003, 11:19:00 PM »
That is a rather interesting question.

But if you use anhydrous MeNH2 in i-PrOH, what keeps the methylamine from reacting with the benzaldehyde to form an imine?

And, since the reaction temperature is 40 - 50 °C, anhydrous methylamine in an alcohol will jump out of the liquid phase and fill your room with a huge cloud of noxious gas  :) .

Bandil

  • Guest
Well, you have the methylamine in it's ...
« Reply #12 on: March 24, 2003, 11:27:00 PM »
Well, you have the methylamine in it's freebase form in the water aswell. Don't know the solubility in the different alcohols, but its quite high in water(959cc/100ml). Imagine it's high in alcohol aswell.

Regards
Bandil


Rhodium

  • Guest
Nitroalkene catalysis
« Reply #13 on: March 24, 2003, 11:38:00 PM »
But if you use anhydrous MeNH2 in i-PrOH, what keeps the methylamine from reacting with the benzaldehyde to form an imine?

That is the mechanism of the amine catalysis. The imine is more readily attacked by nitroalkanes than the aldehyde itself.

Megatherium

  • Guest
Hmm, cool. Then should the anhydrous...
« Reply #14 on: March 25, 2003, 12:07:00 AM »
Hmm, cool.  Then the anhydrous methylamine reaction should work fairly well  :)  (provided that the solubility doesn't cause any problems ... i-PrOH isn't as good as water in hydrogen bond formation).

However, the yields of this reaction itself are very good.  It probably won't bee worth the trouble preparing an isopropanolic methylamine solution.

UncleFester

  • Guest
old wine in a new bottle
« Reply #15 on: March 26, 2003, 02:35:00 AM »
In some of the original work done on the Knoevenagel condensation (see JACS vol. 56, pages 1556-8 (1934)), the catalyst they used for their studies was methylamine. I sited this work in SOMM 5 years ago, and noted the use of methylamine.
When I go to Org Syn, the amines preferred are higher boiling amines so they can boil the mixture without driving out the catalyst, and run a Dean Stark trap to get out the water.
I laud your work on this subject, but it seems that higher boiling amines are preferred by people doing the reactions.
The most easily available higher amine is ethylenediamine, used as a component for nickel stripping solutions. I could pick up drums or pails without so much as a howdy-do, and the Russians claim it is great for making phenylacetone from benzaldehyde. I don't want to rain on the parade, but it is really old news.

Rhodium

  • Guest
What catalyst for which benzaldehyde?
« Reply #16 on: March 26, 2003, 03:24:00 AM »
But there is something I have never understood, and that is why there is no obvious pattern to which catalyst gives the best yields with what substrate - Ethylenediamine works wonders with most things, but fails miserably with fluorine-substituted benzaldehydes, 3,4,5-trimethoxybenzaldehyde and piperonal. The latter two gives great yields with cyclohexylamine though, but not the fluorine ones, they "need" ammonium acetate...

Why this randomness?

lugh

  • Guest
Knoevenagel Catalysts
« Reply #17 on: March 26, 2003, 04:04:00 AM »
From the Organic Reactions article by Jones  :)

Selection of Experimental Conditions

The most generally used catalyst is still pyridine with or without added piperidine, while for the production of arylidenemalonic acids alcoholic ammonia is preferred. Piperidine or other secondary amines are suitable for the condensations which involve malonic esters, malononitrile, beta-diketones, beta-ketonic esters, and methyl groups activated by attachment to a heterocyclic or nitro aromatic system. A study of condensations between ketones and ethyl cyanoacetate led to the suggestion that ammonium acetate is the best catalyst for condensations with hindered ketones, and primary amines, especially benzylamine, for unhindered ketones and aldehydes. A startling increase in yield in condensations involving ketones carrying other functional groups (notably ester groups) was obtained by the use of piperidine containing a little benzylamine. The cyclopentanone condensed with ethyl cyanoacetate to give the unsaturated compound in 55% yield with piperidine as catalyst. With added benzylamine the yield was 89%. Secondary amines are on the whole less successful in condensations involving aliphatic nitro compounds, where the catalyst of choice is a primary amine or ammonium acetate in boiling benzene. In a comparative study the latter was found superior. The Schiff bases can be used without catalysts.

The most significant modification of the Knoevenagel reaction has been the introduction by Cope of ammonium and amine acetates as catalysts. They are used with a solvent mixture of acetic acid (minor component) and some water-immiscible solvent such as benzene, chloroform, or toluene (major component).  By boiling the reaction mixture and using a Dean-Stark water separator the reaction can be accelerated and the progress of the reaction observed. Raja has studied the yields obtained with a variety of second solvents and has found the most effective to be benzene and toluene, followed by chloroform and hexane. The Cope modification has proved most valuable for condensations involving cyanoacetic esters, but it has been used successfully for reactions with malononitrile, malonic esters, cyanoacetamide, acetoacetic esters, alkyl- and aryl-sulfonylacetic esters, and aliphatic nitro compounds. Variations in the acid component include the use of benzoic and caproic acids to minimize the loss of amine salt by amide formation during prolonged reactions. Increase in yield by reduction in acetamide formation has also been achieved by adding the ammonium acetate catalyst at intervals during lengthy reactions. In some cases, however, this has been reported to be without effect. The suggestion that amine salts are active catalysts has led to the use of amino acids. An extensive range of amino acids has been tested and four selected as superior. All give yields of the same order as piperidinium acetate under Cope conditions in the condensation between acetone and ethyl cyanoacetate. The four selected (para-aminophenol, alpha-aminophenyl-acetic acid, beta-alanine, and epsilon-aminocaproic acid) were used with acetic acid and benzene; it was found that with increasing amounts of p-aminophenol the acetic acid became unnecessary. A number of successful conden-sations have been performed with weakly basic resins such as Amberlite IR-4B and Dowex 3, preferably in the acetate or benzoate form. The resins have the advantage of easy removal by filtration after completion of the reaction. The use of triethanolamine to obtain high yields of beta, gamma-unsaturated acid in the malonic acid condensation has been mentioned. No general rules regarding temperature of reaction can be given,. although it has been reported that a number of aromatic aldehydes failed to condense with malonic acid at -10° to -6°. The proportion of catalyst used varies considerably from a large excess (as with pyridine in the Verley-Doebner modification of the cinnamic acid synthesis) to a few drops, as commonly with piperidine. A number of studies of individual reactions with the intention of discovering the optimum amount of catalyst have not led to any general rule. In some cases 0.1 to 0.2 mole of catalyst to each mole of aldehyde has been used; in others a 1: 1 ratio; in others a large excess of catalyst. The usual proportion of ammonium acetate or amine acetate in the Cope modification is 0.2 mole to each mole of active methylene component. Variations in concentration of the acetic acid alter the yield in the condensation between ethyl pyruvate and ethyl cyanoacetate, the maximum yield being attained with a concentration of 0.075-0.1 M.  In the condensation of furfural with acetylacetone in water using glycine as catalyst the yield of condensation product rose with increasing concentration of catalyst, but this may have been due in part to a salting-out effect. A considerable increase in yield and in rate of reaction was achieved by application of high pressures (15,000 atmospheres) to the condensation between cyclopentanone and ethyl cyanoacetate. Using cyclohexanone the condensation could be achieved without the piperidine catalyst.

Catalysts Other Than Amines or Their Salts

Catalysts other than amines or their salts have been used frequently in condensation between aldehydes or ketones and active methylene compounds. Among the more common catalysts are caustic alkalies or sodium carbonate, the latter in what amounts to an extension of the aldol condensation; and, less often, quaternary ammonium hydroxides or strongly basic resins. An example of the use of quaternary ammonium hydroxide resins is the formation of the coumarin from ethyl acetoacetate and o-hydroxyacetophenone. Catalysis by sodium hydroxide is as common as the use of amines in the condensation of cyanoacetic acid with aldehydes. Sodium cyano-acetate, as synthesized in aqueous alkaline solution, can be used directly in the condensation. Condensations involving malonic esters have been performed with acetic anhydride or zinc chloride as catalyst, and a number of cases have been recorded for which the yields were higher with acetic anhydride than with piperidinium acetate. Potassium fluoride has been used extensively in recent years as a catalyst for condensations involving malonic esters and cyanoacetic esters. Most of the yields reported are lower than those obtained by using conventional Knoevenagel catalysts. Titanium tetrachloride has been used to catalyze the condensation of aldehydes with ethyl malonate, ethyl acetoacetate, and ethyl cyanoacetate.

Acta Chem Scand 3 (1949)
Bull Soc Chim France 797 (1956)
Ber 37 4502 (1904)
Chem Rev 32 373 (1943)
Compt Rend 246 3079 (1958)
Ind Eng Chem 44 2867 (1952)
JACS 56 1556 (1934)
JACS 59 2327 (1937)
JACS 63 3452 (1941)
JACS 80 4949 (1958)
J Ind Chem Soc 9 311 (1932)
J Ind Chem Soc 30 206, 665 (1953)
J Ind Chem Soc 34 537 (1957)
J Sci Res Inst 52 99 (1958)
J Sci Res Inst 52 105 (1958)
J Sci Res Inst 52 112 (1958)
J Sci Res Inst 52 151 (1958)
J Sci Res Inst 53 19 (1959)
JCS 844 (1927)
JCS 74 (1931)
JCS 876 (1937)
JCS 3155 (1951)
JOC 15 388 (1950)
JOC 18 3 (1953)
JOC 26 4874 (1961)
JOC 27 3505 (1962)
Proc Acad Sci, Agra Oudh 4 290 (1934/5)


UncleFester

  • Guest
don't add too much!
« Reply #18 on: March 26, 2003, 04:18:00 AM »
While we are on the topic, the original works also covered the effect of adding more than the prescribed dose of catalyst. It was not favorable, so it is not season to taste.

UncleFester

  • Guest
understanding this stuff
« Reply #19 on: March 26, 2003, 05:33:00 AM »
I've been studying this field for about 25 years now. Damnded if I can understand why one molecular structure wants to dive into a catalyst, while another turns up its nose. I just attempt to catalog and be a happy cooker.

Barium

  • Guest
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.

GC_MS

  • Guest
Imine
« Reply #40 on: July 09, 2003, 07:59:00 AM »
Could the amorph substance be an imine?

I have used MeNH as a 5-20% aqueous solution in several cases of which some have and some have not been confirmed by analytical testing. Those which have been confirmed are:

phenyl-2-nitropropene
4-methoxyphenyl-2-nitroethene
4-methoxyphenyl-2-nitropropene
4-ethoxy-3-methoxyphenyl-2-nitropropene
5-bromo-4-hydroxy-3-methoxyphenyl-2-nitropropene
2,5-dimethoxyphenyl-2-nitroethene
3,4,5-trimethoxyphenyl-2-nitropropene

I have tried other substances as well, but I took their identify "for granted". I'll see if I can find some space in my schedule to elucidate the amorphous solid's identity, if it appears not to be 3,4,5-trimethoxyphenyl-2-nitroethene.


GC_MS

  • Guest
GC-MS
« Reply #41 on: July 09, 2003, 09:30:00 AM »
I just found the chromatogram and MS of a recent experiment, viz anisaldehyde + nitroethane with 10% aqueous MeNH2 catalyst. The obtained 4-methoxyphenyl-2-nitropropene has not been analyzed, but has been subjected to Ba's toluene/PTC/NaBH4 reduction procedure. The resulting pale yellow oil has been analyzed and gave the following MS:



Since the M+ is 195 (which is the MW of 4-methoxyphenyl-2-nitropropene +2), I accept this to be 4-methoxyphenyl-2-nitropropane. This also means that the MeNH2 catalyzed reaction did work for this specific compound.


Sunlight

  • Guest
Ok
« Reply #42 on: July 09, 2003, 02:31:00 PM »
I'm not saying the methylamine procedure doesn't work. Just that it doesn't work in this specific case. Anyway I can repeat it, but I'm sure it is not the imine, the imine will be soluble, an in any case it will be less than a 20 % of the initial product (methylamine content), while I got a lot more of that thing. Furthermore we know that this particular aldehyde doesn't work well with EDDA and nitromethane, while 2,5 DMB works fantastically.
I think that doubts should be solve with a corporative work, so someone should try to repeat the procedure with a samll amount, fridge filter and try to solve the product in acetone.
I made the respective nitropropene with cyclohexylamine too (with no solvent) time ago, and I still have the product, that was good. May be that like with the NaBH4 reductions, the nitropropenes are easier to work with.

armageddon

  • Guest
nitroethane problem
« Reply #43 on: April 20, 2004, 05:31:00 PM »
Hi bees!

Deemtermined: I once thought GAA just served as a solvent in Henry condensations, but I heard from my buddy SWIA that he recently tried using ammonium acetate catalyst with GAA/iPrOH solvent system, and got VERY ugly, red tar-like nitrostyrene (went down the toilet..). And then the question: why is the acetate made when ethylene diamine is used as catalyst (ED+2GAA=EDDA)? Perhaps the thought behind it is to avoid evaporating the catalyst (methylamine is even more volatile than ethylenediamine). Adding GAA to nitrostyrene crystals makes no sense to me. But as you got nice nitrostyrene w/o GAA, may I suggest you simply don't add any...  ;D  :P
(seriously, I suggest using EDDA)

Perhaps the following is a bit off-topic (I apologize) but the FSE is down at the moment, so I can't find the appropriate thread an have to ask here: SWIA has an OTC source for nitroethane, but the product in question contains ~40-60% NE, the rest being ethyl formate, ethyl acetate and butylalcohol. Although fractionally distilling several times, he hasn't managed to get high purity (at least all knoevenagel rxns gave him constantly 50-60% of the expected yield, with aldehydes, solvents and catalysts being lab-grade, and SWIA thinks the reason is his nitroethane) Since I wanted to help the poor guy, I suggested to make the nitronate salt by adding NE to aequ. KOH, then heating to remove EtOAc etc. (perhaps wash with nonpolar) and finally acidify and salt out the NE again.
Do you think my advice was right?  :P  Or is there a simpler method for removing said impurities?

THX for your help!

A


Rhodium

  • Guest
Solubility reasons
« Reply #44 on: April 20, 2004, 05:42:00 PM »
And then the question: why is the acetate made when ethylene diamine is used as catalyst (ED+2GAA=EDDA)?

Solubility reasons. Other salts like the hydrochloride and the nitrate are a lot less soluble in IPA.


armageddon

  • Guest
re: solubility reasons
« Reply #45 on: April 20, 2004, 05:54:00 PM »
Hi!

Rhodium: Perhaps I should have said "Why is a salt made at all?"  ;D

I would like to know what is the reason behind the fact that isopropylamine, butylamine and methylamine are used as free bases, whereas ethylenediamine is not?

(BTW ethylenediamine diacetate is also used without any solvent, luckily someone at the hyperlab decided to post in english  :)  

Post 412716 (missing)

(Hellowin: "Condensation of benzaldehyde and nitroethane", Russian HyperLab)
I wonder why acetate is used here.. is the free amine not soluble in aldehyde/nitroalkane??)

Greetz A  :)


starlight

  • Guest
Nef reaction
« Reply #46 on: April 20, 2004, 05:55:00 PM »
If you acidify a nitronate salt with an excess of mineral acid, the Nef reaction occurs, making a carbonyl compound.

To regenerate the original nitro compound it is necessary to acidify very slowly by dripping weak acid (e.g. 50% acetic) into the nitronate solution whilst stirring vigorously.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/nef.html


Daphuk_up

  • Guest
I get it, now.
« Reply #47 on: April 21, 2004, 07:03:00 AM »
Oh.  Oh crap, thats where SWID's nitroethane went.  Nef reaction, huh? :-[  :(  ::)   A good fifty mL of nitroethane wasted. >:(  

Hmm, does that mean that ethylnitronate forms acetaldehyde on decompisition with strong HCl?


starlight

  • Guest
acetaldehyde
« Reply #48 on: April 21, 2004, 11:47:00 AM »
does that mean that ethylnitronate forms acetaldehyde on decompisition with strong HCl

Yes. The yeild and purity of the acetaldehyde will probably depend on the temperature. Best results for the Nef are often achieved with quite concentrated acids and freezing temperatures. Some substances form a lot of blue/green by-products if the temperature is too high.

armageddon

  • Guest
EDDA preparation
« Reply #49 on: May 15, 2004, 03:59:00 AM »
Hi bees!

Recently, I wondered why the acetate of ethylenediamine is made in nonpolar solvent...

As EDDA should be recrystallized from alcohol (MeOH, iPrOH) anyway, my idea was to mix GAA with alcohol, cool to below 0°C, slowly add (precooled) alcoholic solution of 0.5x molar amount ethylenediamine, chill to below 0°C, suction filter the formed crystals, and perhaps concentrate mother liquor with vac and cool again to get 2nd precipitation.

My experience is that it works fine as long as addition of the diamine solution is done slowly, with cooling to avoid evaporating the diamine, the so obtained EDDA is very pure and ready to use (after being dried) - and again one step less to perform! 8)

(and it avoids using nonpolar solvents)

But still I wonder why this alkylamine needs to be converted to its salt when being used as knoevenagel catalyst? BuNH2, iPrNH2, MeNH2 - all are used pure or in solution, but not as salts!! Does any bee know the reason?

Greetz A


Rhodium

  • Guest
lower yields with the freebase?
« Reply #50 on: May 15, 2004, 04:03:00 AM »
I believe it is the ethylenediamine which isn't stable, it turns dark and yucky upon storage.

Are you getting much lower yields with the freebase?


hest

  • Guest
neff
« Reply #51 on: May 15, 2004, 01:40:00 PM »
Hi vertus. This has been an ongoing discusion here at the hive. It's my impesion that the ammine is not so important, there are no 'golden' way to make the nitrostyrenes. Som aldehyde are har to work with, like 3,4,5-tmba and p-flurbenzaldehyde, and others work like a charm, lik 2,5-DMB.
My personal favorite is nitroethae/aldehyde 1:1 and methylamine in methanol(just enough to make a solution) at 25-50°C for some houers.
Barium ahve som exelent's post's abouth the subject.

armageddon

  • Guest
not tried yet
« Reply #52 on: May 17, 2004, 07:56:00 AM »
Hi!

Rhodium, I never tried ethylenediamine freebase as catalyst in condensations, but I don't think it'll give lower yields than if EDDA is used. Contrary, maybe yields could be raised in some cases: Barium references to Zh. Prikl. Khim., 31, 663 (1958) (a paper which I don't have acess to  :( ). But with interesting yields:

- Benzaldehyde/Nitroethane/Ethylenediamine, 50°C; 76% yield

- p-MeO-BA/NE/ED, 80°C; 100% yield(QUANTITATIVE!?)

- m-MeO-p-OH-BA/NE/ED, 20°C; 95%

And yields with simple benzaldehyde and paramethoxybenzaldehyde are both lower if EDDA is used!

Experiments to be done...

Greetz A


armageddon

  • Guest
Thanks!!!!!!!!!!!!!!!!
« Reply #53 on: May 21, 2004, 03:53:00 AM »
Thanks a lot for translating it!

I could kiss you for that!

(and I thought that putting the nitrostyrene solution under high vac over silica gel to get higher yield was MY idea!  :) )

And they REALLY distill their b-methyl-nitrostyrene!?! Twice?!

BTW (now that I read it again) I think the thermostat temperature for P2NP would bee somewhere between 60-80°C, like they mention it for 4MeOP2NP (example VII), but it's just a guess...

And to check if the diamine or its benzoate is the catalyst - well, distill your aldehyde (maybe over some carbonate salt) prior to use, use clear, non-coloured diamine (it sucks CO2 from the air and forms carbonates, becoming yellowish) and you'll see if the benzoic/carboxylic salt or the freebase is the "real" catalyst... ;)

THX A


Rhodium

  • Guest
Ethylenediammonium diacetate (EDDA) (lit. prep.)
« Reply #54 on: October 02, 2004, 08:08:00 AM »
Ethylenediammonium diacetate (EDDA) is prepared as follows:

A 250-mL, round-bottomed flask with a stirring bar and a pressure-equalizing addition funnel with a calcium-sulfate-filled drying tube is charged with dry ethylenediamine (12.0 g. 0.20 mol) and dry ether (100 mL). Acetic acid (24.0 g, 0.40 mol) in dry ether (20 mL) is added through the dropping funnel to the stirred solution. The reaction mixture is left at 4°C for 14 hr and the crystals are collected by filtration and washed with ether. Recrystallization from methanol provides 19.8 g (83%) of pure EDDA, mp 114°C, as white needles;

IR (KBr) cm?1: 3500–2000 (NH), 2180 (MH3+), 1650 (C=O), 1600–1400 (CO2-);
1H NMR (CDCl3) ?: 1.90 (s, 6 H, CH3), 3.20 (s, 4 H, CH2), 5.75 (s, 6 H, NH3+).


Source:
L. F. Tietze, G. v. Kiedrowski, K.-G. Fahlbusch, and E. Voss,

Organic Syntheses, CV 8, 353

(http://www.orgsyn.org/orgsyn/prep.asp?prep=cv8p0353)
Which in turn references the procedure to:
Tietze, L. F.; Eicher, T.; "Reaktionen und Synthesen im Org. Chem. Praktikum"; Thieme: Stuttgart, New York, 1981, p. 387;
Tietze, L. F.; Eicher, T.; "Reactions and Syntheses in the Organic Chemistry Laboratory"; University Science Books: Mill Valley, CA, 1989, p. 403.

Can anyone find any of the latter publications to see if there's any related information of value?


Saddam_Hussein

  • Guest
EDDA
« Reply #55 on: October 02, 2004, 03:00:00 PM »
Do you think it is necessary to synthesize EDDA in advance? Maybe it is sufficient to use ethylenediamine as catalyst and using acetic acid as co-solvent.

From azole's post in this thread: 4-Methoxy-?-nitrostyrene (I). A solution of  anisaldehyde (5 g, 0.0368 mol), nitromethane (2.9 g, 0.0368 mol), ethanol (5 ml), and ethylenediamine (2 drops) was allowed to stand in a closed vessel in the dark at 8-10 °C. After 10 days the nitroolefin I was filtered off and washed with small portions of alcohol. Yield 6.4 g (97.3%), m. p. 86 °C.

So maybe you could add 2 drops of ethylenediamine to a solvent mixture of ethanol and GAA, or add the corresponding quantity of GAA to ethanol?