(Hive Bee)
02-14-01 20:35
No 173322
      TMA2-P2NP: an alternative approach
(Rated as: excellent)

There was around in the Hive a lengthly and comprehensive thread on the preparation of the 2,4,5 trimethoxy-phenyl-2-nitropropene based on the nitrosite approach [1]. The nitrosite rxn is a bit 'picky' and alternatives could be dreamed. The following is a summary on a different route to the TMA2-P2NP. Starting point is the asarone, which can be obtained via fractional destillation of Indian calmus oil.

2,4,5-trimethoxy-benzaldehyde [2]
58g Sodium-hydrogencarbonate (NaHCO3) are disolved in 800 ml tap water with magnetic stirring in a 2l beaker. 30g KMnO4 are dissolved in 500ml tapwater under strirring and kept warm at 50DegC on a water bath in a seperate beaker.
The NaHCO3 solution is heated up to 90DegC (max temp of heater plate) and 20ml of asarone are added. The magnetic stirring is set to 700rpm (heavy stirring). From a dropping funnel the 500ml warmed KMnO4 are added continously to the almost boiling and stirred mixture during 35 minutes. For each drop MnO2 immediately appears, the steam of the mixture smells heavily from asarone, later from the aldehyde as well, vent the steam out (or use a fume head).
During the addition of the oxidizer, prepare approx 500ml boiling water, get thick gloves and setup for a hot-buchner vacuum filtration. When the addition of the KMnO4 solution has been completed, the dark brown mixture is immediately vacuum filtered as hot as possible. It is essential to filter the mixture hot (as hot as possible) and to prevent any MnO2 coming into the filtrate. Use two filter papers and wet well before pouring the hot mix into the funnel. [3] A clear hot yellow filtrate is collected. The first filtration (about one liter) is poured in a clean beaker and set aside. Into the funnel 300ml boiling hot water is added, carefully mixed with the dark MnO2 and vacuum is applied again. The second filtrate is again poured in a different beaker and set aside. A second wash may follow with the rest of the hot water. Use a third beaker for the little yellow filtrate.
The three beakers are allowed to cool down over night, most of the product appears in the first filtrate as yellow nice needles. The first wash contains normally a reasonable amount of aldehyde, the second wash mostly give no product anymore. In the morning the aldehyde is vacuum filtered and dried in a desicator (no vac required) or on a clay plate. It can be used for the next rxn as it is. Re-cristalisation fron little hot EtOH gives an almost white pure product of long needles. A 1:1 mix of dH2O and EtOh can also be used for recristallisation.
Yield varies considerably [4]. Expect something between 25% and 45%. mp. is 110-111DegC

2,4,5-trimethoxy-phenyl-2-nitropropene [5]
7.6g 2,4,5-trimethoxy-benzaldehyde is disolved in 27ml nitroethan in a 100ml flask under mag strirring. 1.7g ammonium acetate anhydrous is added and the flask is heated for 2.5 hours in a boiling water bath. The mixture turns from yellow to orange and to red. After the 2.5 hrs has been elapsed, a vacuum destillation follows. The remaining nitroethane is removed under moderate pressue (110Torr). It comes over cloudy together with the seperated water.
After cooling the vacuum is removed, the oily orange content of the flask poured into a beaker and the flask is washed three times with 8ml boiling MeOH each. The combined washes together with the oily residue are stirred with a glas rod. Under heating the p2np cristallises as dark yellow cristalls. [6] The are filtered off, the mother liquor is kept cool over night to get a second cristallisation. mp is 100-101 degc. Re-cristallisation is done with little hot MeOH if needed.
Yield something around 50-60% based on the aldehyde.

[1] See Novel Discourse, 'Low down on Nitrosites' from Antibody2
[2] Ber. 39, 1211, (1906) Fabinyi
[3] If any MnO2 comes with the filtrate, continue! Do not abort the filtration. The MnO2 can be removed later during a recristallisation.
[4] Fabinyi (2) gives 50%. When Uemuras 'Karma' was optimal, he got 45%.  This rxm seems to be sensitive on temp, stirring and other factors TBD.
[5] Shulgin, #158, Pihkal
[6] This p2np is much more dense than the one from the nitrosite route.

Several experiments are under investgation for alternative condensations of the aldehyde with the nitroethane.

Carpe Diem!
( )
02-14-01 21:32
No 173335
      Re: TMA2-P2NP: an alternative approach  Bookmark   

Wow, nice write-up Uemura. That 1st step looks like a killer, though. Where do think the losses are occuring? Is it simply unreacted asarone or destroyed arsarone.

What I am wondering is, if there is asarone that can be recovered and reprocessed? As we know, this cannot be done with the nitrosite rxn. Be a sweet way to increase the yeilds here if it could could be recovered.

Also if a chemist were impatient perhaps the aldehyde could also be extracted as a bisulfite adduct, possibly negating the need to crystallize overnight and recrystallize.
(Hive Bee)
02-14-01 22:33
No 173351
      Re: TMA2-P2NP: an alternative approach  Bookmark   

uemura, since you seem to have asarone in relatively large amounts, could you give the oxidation with dichromate a try?

(see http://rhodium.lycaeum.org/chemistry/aldehyde.txt )
(Hive Bee)
02-15-01 16:30
No 173525
      Re: TMA2-P2NP: an alternative approach  Bookmark   

That was done. Problem is that under neutral or basic conditions there seems to be no reaction of the bichromate with the asarone. As soon as you do it in acid conditions you are hit by the acid sensivity of the asarone. Polymerisation takes place immediately.

Does any bee know of other oxidation methods under basic conditions?
Carpe Diem
(Hive Bee)
02-15-01 16:43
No 173526
      Re: TMA2-P2NP: an alternative approach  Bookmark   

Antibody, to your questions:
1) the asarone is oxidised to the aldehyde and to the 2,4,5trimethoxybenzoeacid (and perhaps smaller pieces like CO2). There will no asarone be left, some escape with the steam.
2) the bisulfit compound could surely be formed, but there is so much water involved in this rxn, that Uemura doubts the bislfite compund can be easily cristallised.
Carpe Diem. 
02-15-01 17:34
No 173529
      Re: TMA2-P2NP: an alternative approach  Bookmark   

Just an idea for an alternate workup:

Extract the aldehyde with your favorite NP solvent, recrystallise residue.
Problem: Big amounts of water to extract.
(Hive Bee)
02-18-01 11:20
No 174074
      Re: TMA2-P2NP: an alternative approach
(Rated as: excellent)

Aldehyde after filtration and drying:

Aldehyde after recristallisation from EtOH

(Hive Bee)
02-22-01 06:51
No 174794
      Re: TMA2-P2NP: an alternative approach  Bookmark   

why did the potassium permanganate oxidation step result in an aldehyde instead of a ketone?

If pacman influenced us, we'd glide around dark rooms eating pills and listen to repetitive music.
(Stonium's Main Man)
02-22-01 17:09
No 174881
      Re: TMA2-P2NP: an alternative approach  Bookmark   

The KMnO4 oxidation rips the whole side chain of the asarone away, leaving the benzaldehyde and the benzoic acid (side-product).

Ar-CH=CH-CH3 --KMnO4--> Ar-COH and Ar-COOH
(Chief Bee)
02-23-01 21:21
No 175084
      Re: TMA2-P2NP: an alternative approach  Bookmark   

I think the question rather is why is the aldehyde formed in such a "high" yield when the basic KMnO4 evidently is able to oxidize it further to the aldehyde? Could the reaction conditions be altered to give an even higher yield, and in that case how?

Someone really should extract the final solution with DCM and rotovap it down and run a gc/ms on it to see what is formed besides the aldehyde. It is probably not only the acid, as the authors of the orignal article notied that very little of the acid could be isolated from the filtered mixture.

(Hive Bee)
02-24-01 02:18
No 175150
      Re: TMA2-P2NP: an alternative approach  Bookmark   

current run just seems to indicate high temp improves the yield. Compared with the previous run where overall temp was 2-5 degC lower, gives higer yields(measured on the wet product, stuff is in desic now over night...) than with lower temp

Making the mother liquid acid is a bit time consuming, if you do it too fast, polymeristaion takes place, boils over and so on... After 30min carefully adding HCl to the theor. amount needed (ph now something at ph 4), you end up with a 'cloudy' mix which is still cloudy after 3 hrs. Wait for the morning.

Good Night....
06-19-02 03:50
No 322891
      Uemura, you say hotter, is that reflux then?  Bookmark   

Uemura, you say hotter, is that reflux then? Your initial write up says near boiling, or is it the KMnO4 solution which is heated more?

Making the mother liquid acid is a bit time consuming i'm confused now, there was no mention of this in the write-up, what am i missing here?
(Hive Bee)
07-03-02 20:26
No 328392
      Why not scrap that and directly nitrate?  Bookmark   

Why bother with product losses and multiple steps, just go directly to nitration with silver nitrite and iodine.
That's a lot easier than messing with the psuedonitrosite, and probably a lot easier than what your doing there.
(Chief Bee)
07-03-02 20:50
No 328402
      Silver nitrite is expensive and very light ...  Bookmark   

Silver nitrite is expensive and very light sensitive.

Better use sodium nitrite/iodine in ethylene glycol under an inert atmosphere. Details at my site.
(Hive Photographer)
07-06-02 18:13
No 329331
      Picking up from brain...  Bookmark   

Hi ab2,
Uemura is still alive - just was absent a bit, PM me if you want to know why -
2 your question: 'almost reflux' -- no, it was heated in an open beaker, it was  just the heater plate which isn't powerful enough to bring 1-2 liters to boil (as requested by the 1906 article). That's why uemura said 'as hot as possible'. The rxn isn't really picky, just the yield is a bit unpredictable. Anyway Rhod is right, surprising are the 'HIGH' yields anyway. 

To get the asarone-acid ONLY acidify the filtrate
To get the acid the time consuming thingy is to calm down the CO2 evolution and getting finish the job in reasonable time...

Carpe Diem
(Bee without a Title)
07-06-02 20:45
No 329372
      thanx uemura, thats what i thought.  Bookmark   

thanx uemura, thats what i thought. with the addition done at BP a yeild of 51% of the aldehyde from iso-dillapiole was realized. i'm intrigued by alumina supported KMnO4 oxidations too, but the volumes are a bit outlandish.

to scale the one Rhod has on his site would be a 3.5litre volume of DCM for 20g of starting material, i wonder if that could be halved?