MDA from Helional through Scarecrows one-pot issues / help

[Pepito pistol]

Hi!
Attempts at the one-pot Helional to helionamide process, without successful results.
Issues seem to be the same some people encountered, so if you can give some hindsight it’d be greatly appreciated:
- 13,5g hidroxilamine are added to 175ml DMSO, heating and stirring until it’s dissolved (40°C).
- 35g Helional are added, temperature set to 70°C in a water bath (600ml beake covered with plastic wrapping film, automatic temperature control mag-stirring hotplat with the temperature probe in the reaction mixture),then rising it up to 90°C (less than 95°C)and keeping for 90 minutes.
- Let cool to 70°C.
- A soln. made of 7,8g NaOH + 58ml water is added to the beaker, then 2g NaHCO3 suspended in 10ml water. Stuff gets darker and opaque pH is around 9-10 (pH test strips). One run some additional NaOH soln. is added to get to a pH=10 (pH testing strips).
- A soln. made of 125ml 30% H2O2 + 85ml water, freshly prepared and basified to pH= 7,0-8,0 (pH test strips is added with a pipette in 5ml portions every 30 seconds approximately, allowing foaming to stop between additions. Beaker still in water bath, temperature set to 85°C (keeping higher than 80°C but never going up to 90°C). Some exit Hermila and foaming is observed. Some NaOH soln. is required to correct pH up to 10 regularly. When peroxide soln. and NaOH soln. contacts the rxn mixture there seems to be some milky withe stuff forming, and then dissolving, or might be gas developing (volumes are not big enough for foaming). Less than half way through the addition rxn mixture starts getting lighter computed (amber) and less opaque (wouldn’t call it transparent, but there’s vigorous stirring ad micro bubbles though).
- After uncovering and letting everything cool down to 50°C there is an oily layer at the bottom of the beaker (clear, amber), a lighter amber aqueous layer(slightly turbid), and a very thin oily stains at the top.

Extraction with DCM, and evap gives an oily slightly reddish amber stuff.
Attempt to crash in cold water (double or 10 times the sample volume, no difference) gives a milky result, which gives some opaque yellow-whiteish viscous oily like stuff at the bottom when chilled in the freezer.

EDIT: After some advice from other places, rxn mixture was stirred and heated to 100ºC for 30 minutes -> no changes. Also, another similar amount of peroxide was added under the same conditions as the first one, still no changes. (Its possible that this mixture is already f*cked-up, so another fresh run is probably needed, but its important to have some experienced user tips and tricks before wasting more materials.

Currently loosing it, don’t fully understand the difference between what I’ve seen in the forum from other bees who succeded…

 

[FQ-BB]

The reaction solution turns dark and remains turbid → Incomplete oxidation or alkaline medium causes side reactions. After adding hydrogen peroxide, the color change is not obvious, and the oxidation is ineffective → H₂O₂ may be degraded or there is no appropriate catalyst. After extraction, a red amber oil is obtained, and cold water crystallization fails → The product is impure and the oxidation is not complete. Heating to 100°C & adding additional hydrogen peroxide still has no change → The pH may be inappropriate or the reaction has terminated. The traditional method uses NaOH, which leads to excessive side reactions in DMSO and affects the yield. Optimization goal: Replace DMSO with MeOH or EtOH-H₂O to shorten the reaction time. Hydrogen peroxide (H₂O₂) requires catalyst activation, otherwise the oxidation effect is poor.
Using CuSO₄ or FeSO₄ as a catalyst, the oxidation efficiency is increased by 2-3 times. Extraction with DCM has poor impurity removal effect. Adding ethyl acetate (EtOAc) improves selectivity and reduces oily byproducts. Directly adding cold water resulted in crystallization, and the product precipitated as an oily substance instead of a solid. Using the ethanol-water (EtOH-H₂O) decomposition method, solid crystals were obtained within 3 hours.

 

[Pepito pistol]

Color change was noted when a certain amount of peroxide was added.
Peroxide used was brand new pro analysis grade, kept at low temps, so it was ok.
I believe the oxidation is not complete either, but dont know why.
I read somewhere that metal ions should be avoided, due to them catalyzing the peroxide decomposition, which is already fast in alkaline medium, generating undesirable side reactions of resinous compounds.
I dont think MeOH or EtOH can get to the required temperatures for the reaction to occur... They distill at less than 80ºC (water azeotrope).
Extracion with DCM was to isolate the organic layer, to see what it looked like.

You seem to be talking about another route, I've read about some oxime routes, twodogs, etc... But this is not the case.

I'm not trying to be rude, just trying to share all the info as good as I can. if I'm missing something please let me know.
Thanks!