Barium (Hive Bee)
11-15-02 12:43
No 379935
      TMA-2, why oh why the low yield?  Bookmark   

First 1-(2,4,5-trimethoxyphenyl)-2-nitropropene was reduced to the oxime using low-pressure hydrogenation, then the isolated oxime was reduced to the amine using CTH (ammonium formate/Pd-C).
The yield sucks big time. 1,8 g TMA-2 HCl from 10 g oxime.

25,3 g 1-(2,4,5-trimethoxyphenyl)-2-nitropropene (100 mmol), 50 ml EtOAc, 18 ml (300 mmol) acetic acid and 125 mg 5%Pd/Al2O3 (0,5% w/w catalyst to substrate) was stirred under a 15 psig hydrogen atmosphere for about two hours. Celite (2 teaspoons) was added and the catalyst removed by vacuum filtration. The solvent was then removed to yield 22,5 g oxime (94%).

10 g 1-(2,4,5-trimethoxyphenyl)-2-propanone oxime (42 mmol), 1 g 5%Pd/C and 100 ml MeOH was added to a rb flask equipped with a condenser and a stirbar. Ammonium formate 13.25 g (210 mmol) was added in three portions over two hours time while the reaction temperature was kept at 55C. After about four hours the gas evolution had almost ceased. The catalyst was removed by vacuum filtration (celite) and the solvent removed by distillation. To the oily semi-crystalline residue was added 50 ml toluene and enough 5% HCl to bring the pH to 5. The organic layer was removed and the aqueous solution made alkaline (pH 12), saturated with NaCl and extracted twice with 30 ml toluene. The combined toluene extracts was dried over MgSO4 and dry HCl/IPA was added to pH 5.5 (damp universal pH paper). 1,8 g TMA-2 collected frown

Edit: Oops, forgot the acetic acid.....Now, there it is.



Catalytic hydrogenation freak
 
 
 
 
    Sunlight
(Pioneer Researcher)
11-15-02 17:31
No 380006
      Oxime with CTH ?  Bookmark   

I've read here in the Hive that a CTH rdxn of the nitropropene yields the oxime, so further CTH rdxn of the oxime should give the oxime, and yes, may be a bit of amine as byproduct. Not sure, it is what I've seen here.
 
 
 
 
    Barium
(Hive Bee)
11-15-02 18:20
No 380024
      Oxime reduction
(Rated as: excellent)
 Bookmark   

J. Prakt. Chem. 336 (1994), 695-697.

A mild and convinient reduction of aromatic and heteroaromatic aldoximes with ammonium formate/Pd


A number of oximes was reduced with this system in yields between 18-85%.

Typical procedure:

To a magnetically stirred suspension of the appropriate aldoxime (0,0025 mol) and 10%Pd/C (0,15 g) in MeOH (7 ml), anhydrous ammonium formate (0,01 mol) was added in one portion. The resulting mixture (slightly exothermic in some cases) was stirred at room temperature or at 50C for 10-50 minutes, when TLC indicated consumption of starting material. The catalyst was removed by filtration through celite and washed with MeOH (5 ml). The filtrate was then alkalized with saturated aqueous sodium carbonate and extracted with CHCl3 or DCM. The extract was dried over Na2SO4, the solvent evaporated and the residue purified by flash chromatography or vacuum distillation to give pure product.

Catalytic hydrogenation freak
 
 
 
 
    GC_MS
(Hive Bee)
11-15-02 19:09
No 380039
      ?  Bookmark   

TMA-2 is high on my to-do list... Currently taking preparations to start synth'ing it laugh.
What I'm interested in: do you have a (near) 100% conversion of your oxime (ergo alot of impurities), or a low conversion ratio (ergo the possibility to recycle the unreacted oxime again for a next run)?

Ave Hive, synthetisandi te salutant!
 
 
 
 
    Barium
(Hive Bee)
11-15-02 19:34
No 380050
      I`m running the reaction again and will check the ...  Bookmark   

I`m running the reaction again and will check the content of the acidic wash this time.

Catalytic hydrogenation freak