PNP’s into P2P’s using SnCl2

tetraedr · Sun Mar 20, 2005 2:05 am

Because the discussion in topic "PNP's into amphetamines via reduction on alu foil was expanded to the other reductions I have decided to make the new topic, dedicated to the problem of reduction/hydrolisis into P2P's.

2 Moderator: could you to move the posts, related to this theme, to this topic, thnx.

-------------------------
PROCEDURE
-------------------------
This is General Procedure for synthesis of different kind of P2P’s (see appendix after procedure).

To the 250 mL flask was placed 13.84 g (61.4 mmol, 2.2 eq) SnCl2.2H2O, added 8 mL (2.1 g, 2 eq) of conc. HCl, stirred on magnet stirrer until the salt complete dissolved. Then were added by turns 10 mL of water, corresponding nitropropene (28 mmol, 1 eq) and 15 mL of toluene. Obtained mixture was refluxed with intensive stirring for 4-6 h. During this time the mixture becomes lighter and thick. After complete reaction the mixture was cooled down, moved into 0.5 L glass and big amount of potassium carbonate was added with strong mix by stick until the rmx turn into the “mash potato” state (very thick). The ketone was extracted with ethylacetate (several times, with strong mix by stick and decantation resulting yellow liquid), combined organic phases were dried over sodium sulfate, evaporated with yield of light-brown oil with purity is enough for using on next stage (reductive methylamination) without distillation or purification via bisulfite adduct. But yield for next stage will be, of course lower, than for the purified (e.g. distilled) P2P.

Substrate................................................scale............yield of crude product
--------------------------------------------------------------------------------------------------
3,4-methylenedioxyphenylnitropropene.......5.8 g.............98%
4-methoxyphenylnitropropene....................2.7 g.............99%
phenylnitropropene....................................16 g..............87%

(note: yields are approximate: the liquid product did not dried over high vacuum from the rest of volatiles)

IndoleAmine · Dreamreader Deluxe

When nitropropenes are reduced to P2Ps with SnCl2 under aequous conditions, some nitropropene becomes cracked up into aldehyde and other garbage.

If this wasn't the case, toluene/H2O biphasic system would be the ideal choice, but sadly this is not the case....

But when done right, the SnCl2 method produces ultra-pure ketone. You just have to take care that the oxime is first formed under anhydrous conditions, then hydrolyze it with lots of water and HCl.

If you'd like learn more about it, you should read this:
1) http://12.162.180.114/dcd/chemistry/p2p.sncl2.html
(original procedure as tested by Barium)

2) http://12.162.180.114:90/synthetika/hiveboard/methods/000503137.html
(and a discussion of the pros and cons of having water present when reducing nitropropenes with SnCl2)

greets

i_a

ApprenticeCook · DILLIGAF

Cant merge selected posts from threads as far as i can see so this is the best i can do tetraedr... thats all you wanted right?

-AC

Merged posts----------------------------------------------------------------->

brain: Posted: Fri Mar 18, 2005 4:39 pm
I have bad experiences with that method
-used, powder not dust
-when temperature is low-the reaction is fealing like "dont react" in 20h,, in water bath-cold-easy to control
-when temp, is rised 40-50C, the reaction is wiolen and tem is still rising-not easy to cool it down !! than, the iron begin to swin on surface!! and dont reduce the p2np...
-i done these 3 times, 1 was some kind of succes-but still low yelded...
use CrCl2,SnCl2,,, maybe FeCl2? -i didnt try it.

IndoleAmine: Posted: Sat Mar 19, 2005 12:46 pm
I experienced something similar when I once tried to reduce nitromethane to methylamine using Zn/HCl - violent exotherm, volcano of boiling HCl, ZnCl2 and nitromethane/methylamine - and the whole thing even started to burn, it actually catched fire (dunno why the nitromethane didn't explode, don't wanna know)....

Icecool: if you do an Al/Hg on MDP2P with nitromethane, the Al/Hg will reduce nitromethane to methylamine immediately, and this methylamine will condense directly with the MDP2P to give an imine - and this imine is reduced also by Al/Hg to 3,4-methylenedioxyphenyl-2-methylaminopropane (aka MDMA)...

So: if you are dreaming about making methylated amphetamines, you should dream about making the P2P ketone intermediate with any method you like (reduction of nitropropenes with SnCl2, Fe/HCl, Fe/GAA etc; or a percarboxylic acid oxidation of propenylbenzenes like you described for example) and use Al/Hg to make methylamine "just in time" and condense that with your ketone (during the Al/Hg) to give final product.

If you would like to dream about "normal" phenylisopropylamines, you should try to reduce phenyl-2-nitropropenes directy. This can be done with Al/Hg, LAH/THF, NaBH4/ZnCl2, 2-step with NaBH4 and then CTH with Pd/C-KCOOH.

(or you could make the oxime from your MDP2P and reduce that with Al/Hg and a bit GAA - it gives MDA too, and maybe a good option if one already has ketone..)

Just a few ideas (of course purely fictional - and they shouldn't be attempted under any circumstances, as they are pretty illegal to perform without the proper license).

i_a

IndoleAmine: Posted: Sat Mar 19, 2005 1:01 pm
Oh, and brain: try using SnCl2 dihydrate, 2.1x molar excess to (substituted) phenyl-2nitropropene - suspend the SnCl2 in EtOAc, stir to dissolve as much as possible, then slowly add the nitropropene in small amounts while stirring, the temperature of the solution shouldn't rise above 30°C (addition may take a while; please be patient here!). If it gets too hot, use an ice/water bath to cool to below 30°C.
After all P2NP has been added, stir for 30 minutes, until the color doesn't change anymore (it is yellow, but becomes almost white at the end). Now add 8x molar excess of HCl as 20% aequous solution, remove the EtOAc using aspirator vacuum, then reflux the whole thing for 1 hour, and steam distill the P2P (or extract with DCM when working with substituted nitropropenes, as they often cannot be steam distilled). Yield is 70-80% of theory.
(procedure courtesy of Barium - was just too lazy to look it up, but its in the hive archives somewhere...)

End------------------------------------------------------------------------------->

64bandil · Busy Bee

A small warning about the reaction...

When using EthylAcetate as the solvent, and following Bariums method, approximately 5% benzaldehyde will show up in the product. This has to be removed somehow. Either by complexing it with bisulfite (using very low concentrations of bisulfite to avoid getting the ketone) ot fractionally distilling it.

When using acetone, the amount of benzaldehyde is roughly 40%...

The only method that gives consistently good yields is IME the iron / acid one...

Kind regards
Bandil

tetraedr · Tue Mar 22, 2005 10:02 am

I just forgot to say, that main problem of this method - the separation of the phases. If you simple basified the reaction mixture after reaction - you will get the mono-phase liquid subsance. Addition of big amount of potassium carbonate is necessary for separation the organic and water phase.
Then the reaction mixture moved into glass, and you can make the decantation. Using separate funnel is not possible.
Other way to solve this problem - is maximal dilution (with water) of mixture.

This method is good for small amounts (till 5-10 g) of starting nitropropenes. But for big amounts you should use the huge glasses, liters of extracing solvent and kilos of K2CO3.

Maybe somebody know, how to separate the phases?
I agree also not a universal method, but only useful for one particular substrate.

IndoleAmine · Dreamreader Deluxe

What are u talking about - neutralizing with na2co3?? I don't remember this part of the procedure, although I used to know this rxn very well, and have thought about reducing nitropropenes with SnCl2 many times..... Very Happy

You mean perhaps neutralizing after hydrolysis, right? Not necessary: steam distill the ketone, it is very pure directly, can be easily separated, at least most of it (and the remainder is extracted completely from the distillate within 2 toluene pulls with little solvent), and you would have to distill anyway, so take the time, read a book in the meantime - and steam it out...

hAzzBEEn · Fri Jun 03, 2005 1:31 am

I have a few basic questions about Barium's SnClxH2O procedure. Here it is so it need not be looked up:

IndoleAmine · Dreamreader Deluxe

EtOAc does form azeotropes, and further decomposes slowly into EtOH and AcOH upon prolonged contact with H2O..

Just dry your solvent with an inert drying agent (MgSO4? Silica? Na2SO4? Drierite? etc.), then neutralize excess acetic acid with anhydr. Na2CO3 and redistill (if you're using recycled/degraded EtOAc), then proceed with carrying out your reaction as described.

As long as you use a nonpolar like EtOAc, water is excluded quite well, in contrast to using Me2CO or THF for example...

hAzzBEEn · Wed Jun 22, 2005 9:04 pm

Is there a reason that EtOAc was chosen for this reaction? Can any non-polar be used?