Bandil (Hive Bee)
11-30-01 12:50
No 242648
      2,5-DMNS synth improvment  Bookmark   

Hi!

Swim has tried the 2,5-DMBA + NM + AmAc-> 2,5-DMNS route a couple of times, and this time he was going for yeild optimization.

25 g og 2,5-DMBA was placed in a RBF, filled with 50 g nitromethane and 2,5 g ammoniumacetate. This was refluxed on an oil bath for 4 hrs, whereafter the soln was deep-red/blackish. Vacuum was slowly applied to draw of the remaining NM. After a short while, only a large darkbrown/slightly orange mass remained. This was attempted to dissolve in IPA while warming on oilbath, but attempts to dissolve it was futile. After some chopping, cursing etcetc it was washed to the point where it was orange with a tint of brown. Swim got a yeild of about 66%

First of all:
Do you have any suggestions on how to improve the yeild?

Second:
The other times swim attempted the same reaction, he did in an erlenmeyerflask directly on the heating plate. There was not drawn of any NM afterwards, but the crystals was allowed to form, and was simply recrystallized in boiling IPA. The final NS looked a lot prettier(swim did not calculate the yeild though). Does anyone have an explanation for the discoloring the last time, when swim was working very neatly, to keep the product clean?

Thanks!

Regards
Peter
 
 
 
 
    Rhodium
(Chief Bee)
11-30-01 13:23
No 242660
      Re: 2,5-DMNS synth improvment  Bookmark   

2,5-DMNS in 96% yield: ../rhodium/chemistry /edda.html

 
 
 
 
    wolfx
(Hive Bee)
11-30-01 17:53
No 242795
      Re: 2,5-DMNS synth improvment  Bookmark   

I was thinking about doing it like Shulgin does it in the 2C-H synthesis in TIHKAL, seems an improvement over the 2C-B synthesis in PIHKAL, but I have never tried it, just guessing. He does only one re-crystalization, the workup looks better, the yields also. I think it can be done in a round bottom boiling flask, setup for reflux.

What Rhodium suggested is the best way, I think, if you can get the EDDA or make it.
 
 
 
 
    moo
(Hive Bee)
12-01-01 05:48
No 242984
      Re: 2,5-DMNS synth improvment  Bookmark   

I like this one: Tetrahedron Letters 39 (1998), 8013-8016, "The Ultrasound Promoted Knoevenagel Condensation of Aromatic Aldehydes"

In this paper several aromatic aldehydes are reacted with nitromethane in GAA at 22C for 3h using ammonium acetate catalyst. The reaction is done in an ultrasound cleaning bath. Yields of nitrostyrenes for the following aldehydes are: 2,3-diMeO-benzaldehyde 99%, piperonal 99%, 2,4,6-triMeO-benzaldehyde 85%, 4-AcNH-benzaldehyde 95%, 4-MeS-benzaldehyde 96%, indole-3-carboxaldehyde 93%, vanillin 89%. The reaction provided nitroalcohols instead of nitroalkenes in the case of: 4-Cl-benzahydehyde 70%, 4-nitrobenzaldehyde 61%, 3-nitrobenzaldehyde 51%. For these an additional diisopropylethylamine catalyst was needed. I bet the nitroalcohols could be dehydrated to the nitroalkenes.

The researchers also tried reacting several aldehydes with malonic acid to give the corresponding cinnamic acids in yields ranging from 61% to 99% (3-nitro being the worst, 4-Cl and plain benzaldehyde being the best ones). Pyridine was the solvent and piperidine the catalyst.

"General procedures. Nitromethane and pyridine were freshly distilled. Ultrasound reactions were peroformed using a branson 5510 ultrasound bath or a Crest Tru-Sweep ultrasonic cleaner with little difference. Method A:  A mixture of aldehyde (20.0 mmol), nitromethane (13.0 ml) and ammonium acetate (3.324 g), sonicated at 22C for 3h. After removal of nitromethane, partition between dichloromethane and water then brine gave crude product which was recrystallized from aq. ethanol (except 4-AcNH-benzaldehyde, AcOH). Method B: A solution of aldehyde (1.00 mmol), nitromethane (1.0 ml), ammonium acetate (2.5 mmol) and diisopropylethylamine (0.1 mmol) was sonicated at 22C for 3-6h, according to TLC. After removal of solvents , work-up as above gave crude product which was purified on silica gel. Method C: A solution of aldehyde (1.00 mmol), malonic acid (2.18 mmol) in pyridine (5.7 mmol) and piperidine (0.20 mmol) was sonicated at 22C for 3h. Solution added to 5% aq. HCl, chilled and filtered by suction. The precipitate was recrystallized from aq. ethanol."

They also mention that "...the 2,4,6-trimethoxy derivative 1c gave nitroalkene 5c (84%) demonstrating steric factors to be of little detriment." which is nice wink.

So, how about them 2,5-dimethoxybenzaldehyde or even 4-fluorobenzaldehyde? cool

understanding is everything
 
 
 
 
    hest
(Hive Bee)
12-01-01 08:40
No 243020
      Re: 2,5-DMNS synth improvment  Bookmark   

Mixing the aldehyde and the nitromethane (1:2 molar mass) and some amm.formiat and then nuke it in the mw for 5-10min. works great too. yeald high and reac. time fast.
 
 
 
 
    Rhodium
(Chief Bee)
12-01-01 09:58
No 243033
      Re: 2,5-DMNS synth improvment  Bookmark   

Hest: As in ../rhodium/chemistry /mw.nitroalkene.txt ?
 
 
 
 
    hest
(Hive Bee)
12-01-01 10:06
No 243036
      Re: 2,5-DMNS synth improvment  Bookmark   

Yes, i think i got the idear from exact that article.
It works greath, but by some reason it don't work with nitroethane and benzaldehyde or
2,4,5-trimethoxybenzaldehyde (at least not for mee:)