Author Topic: different routes starting from nitropropenes  (Read 7501 times)

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armageddon

  • Guest
different routes starting from nitropropenes
« on: April 07, 2004, 05:41:00 PM »
Hi Bees!

I have just tried to remember all possibilities for going from a nitropropene to an aminopropane that explicitly don't use mercury amalgams, lithium aluminium hydride, pressurized hydrogen or other hazardous reagents. I also wanted to exclude reactions using ferromagnetic metal catalysts like iron, nickel or magnesium etc. because they can't be performed without adequate overhead stirring equipment.

But as there are so many methods known to the hive, I got confused. So I decided to write down a "reaction scheme"...  ;D  and ended up with this diagram (made using ChemDraw).
It is only an overview of possible routes using certain easy-to-handle chemicals, for further details on reactions use TFSE, it's all there. If you think something important is missing, please tell me! And I named it "ketones, imines, oximes" because most of the possible ways I remember include these as intermediate products.  :)







[EDIT]
1.

Post 392067 (missing)

(Aurelius: "P2P from Tin (II) and nitropropene", Methods Discourse)

2.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#p2np


   ("Reduction with iron powder")
3.

Post 465461

(Bandil: "Proof of concept!", Novel Discourse)

   

Post 483260

(SpicyBrown: "4-Fluoroamphetamine: A full report.", Methods Discourse)

4.

Post 427794

(Barium: "Nitrostyrenes to oximes with sodium dithionite", Novel Discourse)

5.

https://www.thevespiary.org/rhodium/Rhodium/pdf/nitroalkene-stannite-1.pdf


   

https://www.thevespiary.org/rhodium/Rhodium/pdf/nitroalkene-stannite-2.pdf


6.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdaoxime.html


   

Post 319296

(Rhodium: "P2P oxime in quantitative yield", Novel Discourse)

7.

Post 382254

(Barium: "A great CTH method", Novel Discourse)
   
    (although Barium uses potassium formate, the procedure is essentially the same)
8.

Post 460139

(Bandil: "Formic acid reduction - comments", Methods Discourse)

9.

Post 477266 (missing)

(Lego: "Reduction of oximes with zinc/ammonium formate", Novel Discourse)

10.

https://www.thevespiary.org/rhodium/Rhodium/pdf/cth.oximes.formate.pdf


11. + 12.

Post 455901

(Sunlight: "Ammonium salts for imine", Methods Discourse)

   

Post 335851

(Sunlight: "MDA and MDMA from CTH reductive amination", Novel Discourse)

11. + 13.

Post 461926

(cublium: "NaBH4 is just amazing.", Newbee Forum)

[/EDIT]

As I said already, this is only a short overview over the possibilities  starting with phenyl-2-nitropropenes, and if someone knows something that should bee added, go ahead!

Greetz A


Rhodium

  • Guest
Suggestion
« Reply #1 on: April 07, 2004, 07:51:00 PM »
Number the different reactions, and collect links to different procedures to effect that particular transformations, then post those link lists to the various methods as a little lexicon to aid yourself and others to learn about the multitude of routes possible.


armageddon

  • Guest
reaction references
« Reply #2 on: April 07, 2004, 09:19:00 PM »
Ok, (although I wanted to avoid it because of being too lazy  ;) ) it still seems a good idea. So here are links for every of the above reactions (the picture and post have been edited and the reactions were numbered).

(As imine formation from the ketone and following reduction are best perfomed immediately after each other, I have just included routes that involve preparing the imine in situ...)


Hope this will help some bees in getting a better overview of these reactions (including me  :) ).

Greetz A


Nicodem

  • Guest
Nice scheme and links!
« Reply #3 on: April 08, 2004, 02:24:00 AM »
Nice scheme and links!
It is always lovely to see somebee trying to make some order in the chaos, but I miss the reactions from 1-phenyl-2-nitropropenes directly to amphetamines ;) .


armageddon

  • Guest
several nitropropene CTH failures are the reason
« Reply #4 on: April 08, 2004, 03:20:00 AM »
Hi Nicodem!

THX, I like it too (I just like looking at pictures.. ;)  ;D )

But I didn't include nitropropene to amine conversions as they all require pressurized hydrogen and/or ferromagnetic (and for sure pyrophoric, but that's ok) catalysts (raneyNi = ferromagnetic = not mag.stirrer compatible), or if you think of a Pd/C catalysed CTH w/NH4COOH, then I'm sorry to have to tell you but for SWIA this direct reduction didn't work although he tried it several times (w/variations of course), and therefore I didn't include them, too. (SWIA told me he followed instructions found in a document by dreamer,

https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitropropene.cth.txt

) Of course, if you have better knowledge than I do, please post a writeup or a link to one, I would appreciate it. (but remember, NO pressurized H2, NO Fe/Ni/Co/Mg, LiAlH4 and of course no "T+"-style Hg-X things) :)

Greetz A


Lilienthal

  • Guest
LiALH4
« Reply #5 on: April 08, 2004, 05:24:00 AM »
LiALH4 [hint]

nightshade

  • Guest
electrochemical
« Reply #6 on: April 08, 2004, 09:11:00 AM »
electrochemical

armageddon

  • Guest
re: LiALH4 [hint]
« Reply #7 on: April 08, 2004, 10:15:00 AM »
Lilienthal: Sure, metal hydrides are capable of reducing nitropropenes to primary amines, but they also react violently with water if no really anhydrous solvent is used. And the solvents used are ethers and THF... :o

So I didn't include this reducing agent (the goal was to collect routes that don't use Fe/Mg/Ni/Co, pressurized hydrogen, no metal hydrides and no mercury salts, remember)

Nightshade: could you please point out what kind of electrochemical reaction you mean? Perhaps with a link?
That would bee nice!


Barium

  • Guest
Nope
« Reply #8 on: April 08, 2004, 10:55:00 AM »
Red-Al can be used to reduce nitrostyrenes directly to amines in decent to good yields. The only solvent needed is toluene and if the toluene at hand is a bit wet, just use some Red-Al as a drying agent.

Nicodem

  • Guest
Zn/HCl,EtOH
« Reply #9 on: April 08, 2004, 01:30:00 PM »
I have never done any but there are alternatives to H2/cat and LiAlH4. Besides the already mentioned electrochemical reduction on a Pb cathode, there are also a few reductions on amalgamated metals (Al/Hg for example, but you said no Hg, right?) and the most surprising one, a simple reduction with Zn in HCl/EtOH (

https://www.thevespiary.org/rhodium/Rhodium/chemistry/leminger.html

). BTW, does anybody know why this one never gained popularity?


Vitus_Verdegast

  • Guest
Zn/HCl route
« Reply #10 on: April 08, 2004, 02:18:00 PM »
It works well, but the workup is horrible, extracting the Zn(OH)2 sludge feels like extracting a can of paint.  ::)


armageddon

  • Guest
"can-of-paint"-route for nitrostyrenes
« Reply #11 on: April 08, 2004, 03:55:00 PM »
Vitus: Besides from the disadvantages you mentioned, the Leminger rxn works only for nitrostyrenes, alpha-methylnitrostyrenes (P2NPs) give mainly the ketone and only minor amine, see also

Post 470515

(GC_MS: "Zn/HCl doesn't work for alfa-methylnitrostyrenes", Chemistry Discourse)

Post 439548

(GC_MS: "Zn/HCl reductions", Newbee Forum)


And Vitride is very hard to get, harder than NaBH4... >:(

Nicodem: could you pleeease give me a link to a electroreduction with a lead electrode? And what is being reduced? P2NP or intermediate (imine?)?

THX A


Rhodium

  • Guest
complex with ammonia?
« Reply #12 on: April 08, 2004, 06:18:00 PM »
It works well, but the workup is horrible, extracting the Zn(OH)2 sludge feels like extracting a can of paint.

Did anyone ever try to complex the Zn2+ with ammonia? It should solubilize the sludge well.


armageddon

  • Guest
sodium hypophosphite as reducing agent
« Reply #13 on: April 08, 2004, 11:22:00 PM »
I just found something I missed previously: nitropropenes (especially the 2,4,6-triMeO from asarone) are reduced to the ketoxime with Pd/C and sodium hypophosphite in high yields (90%+), but piperonal and P2NP give mixtures of the oxime and the ketone, depending on amount of catalyst used and acidity of rxn. here's the link:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tma-2.oxime.html



What about just hydrolysing the oxime part completely to the ketone, which can then be separated by steam distillation? That would give a nice route to ketones using hypophosphite.

Barium, which reducing agent for getting oximes would you prefer: sodium dithionite or hypophosphite/catalyst? (or what about rhodiums suggestion of using NH3 for basifying tin suspensions? stannite reduction would become alot more attractive - perhaps somebee has xperience with it?)

Thanks!


Nicodem

  • Guest
electroreduction
« Reply #14 on: April 09, 2004, 04:04:00 AM »
Nicodem: could you pleeease give me a link to a electroreduction with a lead electrode? And what is being reduced? P2NP or intermediate (imine?)?

I guess the electrochemical bee would bee Uemura:

Post 47461

(uemura: "Electrochemical Reduction of Nitrostyrenes", Novel Discourse)

There is also

Post 219827 (missing)

(Bandil: "Tin instead of lead as cathode", Methods Discourse)
and probably more threads if you take some more time to UTFSE than I did.

I only have these two papers at home:

Masui and Yijima. Controlled-potential Electrolysis. Part IX. Reduction of two nitro-indolyl-esters in acid solution. ?JACS? (1963) 1101-1105.
(it is about the reduction of ethyl alpha-nitro-beta-indolyl-propionates to DL-tryptophan on Pb or Hg cathode)

Niazimbetova et al. Cathodically promoted addition of nitromethane to aldehydes and exploratory studies of the mechanism of the electrochemical reduction of the nitroolefins so produced. J. Electrochem. Soc. 145 (1998) 2768-2774.
(it is mostly about the electrochemicaly promoted Ph-CHO + MeNO2 => Ph-CH(OH)-CH2NO2, much less on the nitro->amine reduction, there is also a lot on the theory, lots of polarograms and studies of side products)

I can scan them if anybee is interested, but I think there are also better papers out there.

Besides from the disadvantages you mentioned, the Leminger rxn works only for nitrostyrenes, alpha-methylnitrostyrenes (P2NPs) give mainly the ketone and only minor amine

I'm kind of convinced that it would work if instead of aq. HCl a solution of HCl gas in ethanol would bee used. It would form an intermediate Ar-CHCl-CHNO2-Me (no double bond!) and this gets reduced on Zn surface. And there would also bee less chances for the intermediate oxime to hydrolyze (no ketone product). Rhodium's idea of using ammonia in the work up instead of NaOH seams pretty good too.


Barium

  • Guest
Both dithionite and hypophosphite-Pd/C are...
« Reply #15 on: April 09, 2004, 03:43:00 PM »
Both dithionite and hypophosphite-Pd/C are good routes. They are about equally cost effective too. it is manly a matter of taste I guess. Some oximes are not hydrolysed by the dithionite route as they are by the hypophosphite route. If one is aiming for complete oxime hydrolysis I would add a good hydroxylamine acceptor. Basically any low molecular weight carbonyl compound which is not sterically hindered is just fine. Acetone is a good example.

Rhodium suggested ammonium complex forming with zinc not tin.

armageddon

  • Guest
re: acetone, tin
« Reply #16 on: April 10, 2004, 02:10:00 PM »
Thanks for your info, Barium. Just read that dithionite reduction gave you ~1% P2P contamination, compared to ~20% P2P resulting from hypophosphite-Pd/C rxn... Dithionite seems to work somewhat cleaner. Hm. Using acetone to affect complete hydrolysis sounds good, but I thought the purpose behind ketone formation was to bee able to separate via steam distillation and to avoid having to solvent xtract (unless the reason is that you NEED ketone, not oxime)? Wouldn't acetone interfer with this?

Oh, and about basifying tin with ammonia: I think tin will normally give a mess upon basification, too (read somewhere that workup of Na2SnO2 reductions to oximes is very hard, and I thought that was the reason why aurelius suggests hydrolyzing w/HCl - to simplify workup?) so I thought Rhodiums idea would perhaps solve the tin problem, too...  :-[
Does tin form complex salts with ammonia? Are they less soluble than hydroxides in nonpolars?

Nicodem:  8)  THX  8)  seems as this method isn't very popular at the hive, I really don't know why!?
And do you have any references for your idea of an anhydrous Zn/HCl reduction? I'm asking because I perhaps may have use for this doublbond-halogenation for some other, eeasy procedure if this really works...(secret) ;)

A


Nicodem

  • Guest
No ref’s, just theoretical bla, bla
« Reply #17 on: April 11, 2004, 04:53:00 AM »
And do you have any references for your idea of an anhydrous Zn/HCl reduction? I'm asking because I perhaps may have use for this doublbond-halogenation for some other, eeasy procedure if this really works...(secret)

Sorry, I don't have any references for the addition of HCl to nitrostyrenes (though I have a faint memory of actually seeing it somewhere). But HCl is known to easily add on the double bonds of Michael acceptors (I know of methyl acrylate as an example, but it is general to similar R-CH=CH-EWG where EWG is an electron withdrawing group). The addition is reversible, shifting completely left in basic conditions. I don’t know what your secret procedure is but if your compound fulfils the above conditions then HCl should add to the double bond. Especially if you have such a good Michael acceptor as a nitrostyrene is, which is perfect as it has a strong EWG (the nitro) and a carbocation stabilizing aryl on the other side.
I even think this could be an explanation for the Leminger’s reduction as well as the hydrogenating reductions that work only in the presence of HCl or H2SO4 (

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mescaline.cathyd.html

,

https://www.thevespiary.org/rhodium/Rhodium/chemistry/catalytic.html

).
It is known that H2/Pd does not easily reduce conjugated double bonds (as C=C-NO2) while it easily reduces benzylhalogenides and similar benzylic compounds. So I guess Ar-CHX-CHR-NO2 is the true intermediate in these reductions (where X = -Cl, -SO3H, -OAc, -OH2+ etc.). To me this is the easiest explanation on why these hydrogenations require HCl or H2SO4/AcOH as well as Zn/EtOH,HCl woks while Zn/AcOH does not.
But these are only guesses, though I hope they are of any use to your “secret” reaction.


armageddon

  • Guest
gosh - how could I forget?
« Reply #18 on: July 07, 2004, 10:07:00 PM »
As Antoncho's "92% yield"-Leuckart-thread became that popular recently (MANY views..), it came into my mind that I forgot this simple route via P2P to make an amph. from a nitropropene...

x-pheny-2-nitropropene __> x-phenyl-2-propanone __> x-formylaphetamine (x-amphetamine through hydrolysis)

..this major stupidity is now fixed!  ;D

A


Erny

  • Guest
One method is missing
« Reply #19 on: July 08, 2004, 04:16:00 AM »