Shvos catalyst

[41Dxflatline]

Would Shvo's catalyst be suitable for reducing P2NP via catalytic transfer hydrogenation?

 

[OrgUnikum]

Probably not.
P2NP is not polar enough for it to work and generally catalytic hydrogenation of unsaturated nitrostyrenes is very difficult, better use other methods. I believe a two step reduction scheme would be better then the NaBH4/Cu mostly used, say first reduce the double bond, the Alkene to an Alkane and then the nitro to an Amine.

 

[41Dxflatline]

NaBH4/Cu is what I've been using but I'm not comfortable purchasing NaBH4 constantly or in large amounts since lately its been getting some attention due to the FDA putting it on their special surveilance list.
What about Urushibara nickel as the catalyst in a microwave assisted hydrogenation as detailed here: https://www.designer-drug.com/pte/12.162.180.114/dcd/chemistry/mw.cth.html if Raney nickel works so should Urushibara?

 

[OrgUnikum]

Urushibara is a ghost whining through the dusty chambers of chemistry, together with Akabori and some others he is elusive maybe even mythical . Unicorns have been seen more often then a working Urushibara thats all I know.

IIRC you can reduce the double bound of the Alkene with SnCl2/HCl in Ethyl Acetate in excellent yields to the Nitro-Alkane and THIS should be reduceable with noble metal catalysts without trouble.

Please regard the second one as an educated guess, I have to look it up to be sure. SnCl2 works 100% as told though.

Problem generally is that in the double bond reduction a Michael addition reaction on the intermediate is competing with the reduction, if conditions are neutral or alkaline.

You are right that the amounts of NaBH4 used in the CuSO4 reduction are a disgrace. There must be a way to reduce this.

 

[41Dxflatline]

Urushibara is a ghost whining through the dusty chambers of chemistry, together with Akabori and some others he is elusive maybe even mythical . Unicorns have been seen more often then a working Urushibara thats all I know.

IIRC you can reduce the double bound of the Alkene with SnCl2/HCl in Ethyl Acetate in excellent yields to the Nitro-Alkane and THIS should be reduceable with noble metal catalysts without trouble.

Please regard the second one as an educated guess, I have to look it up to be sure. SnCl2 works 100% as told though.

Problem generally is that in the double bond reduction a Michael addition reaction on the intermediate is competing with the reduction, if conditions are neutral or alkaline.

You are right that the amounts of NaBH4 used in the CuSO4 reduction are a disgrace. There must be a way to reduce this.

OrgUnikumApparently you can do a Urushibara-like reduction in situ using a nickel salt dissolved in an ammonia solution and powdered zinc. There's also Al/Ni thats reported to work without the ammonia just a non-mineral acid. Yields are low though (30%) but thats not a major issue for me. I'll try the Al/Ni first.

 

[OrgUnikum]

Apparently you can do a Urushibara-like reduction in situ using a nickel salt dissolved in an ammonia solution and powdered zinc

I tried this reaction method for P2P to Amph several times as I was told it would give up to 80 % yields and I can tell you this apparently is utter bullshit and yields are ridiculously low. I am sure it will not work well on P2NP as alkaline conditions as told before a not favorable for the first step.
Acidic Al/Hg works of course and with ok yields but reaction volume is large and the reaction is so violent that I know nobody who dared tp process more then for 100 g Amph at a time (and those reported also that sometimes it just blows everything to the ceiling - they only did it outsides for this reason),
Al/Ni and acid, thats just another Urushibara variation, the acid makes hydrogen from the Al which is supposed to charge the Ni which is supposed to be in the form of nanoparticles and theoretically it works of course but honestly, I cannot see it working without a pressure vessel and high purity reagents and a big piece of plain luck.

So any reaction to reduce P2NP which starts out basic (alkaline) will have very low yields (except the situation is remedied by addition of a huge amount of SiO in form of silica gel which has been calcified at up to 800 °C before use. Strictly anhydrous conditions. This will be a reaction in a slurry but it prevents the Michaels side-reaction from taking place. (800 °C for SiO are easy in a microwave btw.)
Left is the question if this system will reduce the resulting Nitro-Alkane. I do not know.
But it would be worth a shot, orecipitating CuCl2 or the Sulfate onto SiO and calcinating this and then adding P2NP in methanol/xylene, heat to boiling and add NaBH4 in portions, 4 to 5 molar equivalents at all.
I think this works as NaBH4 at elevated temps forms an addition compound with methanol which is perfectly suited for the double bond reduction, the silica gel prevents the side reaction and the Copper makes the Nitro reduction possible.
To use Cu2FeO4 nanoparticles on silica gel (prep is simple) would be the better choice though.

But you want something without NaBH4, ok, as told there is the SnCl2/HCl which works well and the SnCl2 can be prepared in situ from tin and HCl.
Then reduce the nitro with something else, there are several possible ways, but sadly reactions do not work just because somebody wrote they do or because one would really want them to work as they are so easy and use only whats on hand. I fell for this myself in the past and in the end I regretted the waste of money, time and precursors and cultivated a flaming hate for the armchair chemists who suck fictious reactions from thin air and a little knowledge but a lot of wishthinking and post the result on internet boards as if the actually did this (or wrote articles in second or third tier journals which often carry "communications" or "letters" in their names).

I hope you are aware that P2NP reduction can result in a whole plethora of different compounds depending on conditions and temps and solvents and whats the reducing agent. Like SnCl2 in methanol or ethanol gives a completely different product (alkylated) then doing it in ethyl acetate what gives the alkane. Troubleshooting without serious analytical equipment and skills is virtually not possible for this reason.

I have one other way in mind which I believe to be very promising for reducing nitroalkenes,alkanes oximes, nitriles and some more, but this I wwant to try myself first, sorry. I will make the results if noteable public anyways, I always did. I need some P2NP first though, if anybody in the EU wants to donate 50 g or 100 g, I would not say no. Its an expensive hobby if one does not sell anything and I do not sell. Not complaining just as matter of fact.

 

[41Dxflatline]

SnCL2/HCl is defintely the way to go to produce the oxime according to the paper I read (since my last post) yields are very high and all reagents are readily available . I'm aware about ethyl acetate being the key otherwise you'll get the ketoxime but it seems the reaction itself proceeds at room temp and you can just stick a reflux condenser on the top and not have to babysit it like Al/Hg.

There's 2 of the same aldoxime to amine reduction papers in Rhodium's archive which seem to good to be true:

Zinc/Ammonium Formate: Rapid and selective reduction of oximes to amines - [www.rhodium.ws]

Reduction of Nitro Groups With Zinc/Ammonium Formate - [www.rhodium.ws]

Again, easily available reagents (making ammonium formate is trivial) and high yields. If it works I wonder why this route doesn't seem to be popular. Even though its more labourious than Al/Hg it has some definite advantages.

 

[OrgUnikum]

SnCL2/HCl is defintely the way to go to produce the oxime according to the paper I read (since my last post) yields are very high and all reagents are readily available . I'm aware about ethyl acetate being the key otherwise you'll get the ketoxime but it seems the reaction itself proceeds at room temp and you can just stick a reflux condenser on the top and not have to babysit it like Al/Hg.

There's 2 of the same aldoxime to amine reduction papers in Rhodium's archive which seem to good to be true:

Zinc/Ammonium Formate: Rapid and selective reduction of oximes to amines - [www.rhodium.ws]

Reduction of Nitro Groups With Zinc/Ammonium Formate - [www.rhodium.ws]

Again, easily available reagents (making ammonium formate is trivial) and high yields. If it works I wonder why this route doesn't seem to be popular. Even though its more labourious than Al/Hg it has some definite advantages.

41DxflatlineYes, you get the oxime of course with SnCl2 in EtOAc, sorry I am a bit tired.
Oxime reduction with as you said Zinc/Ammonium Formate or any other of the known reductions, the important part is that you got rid of the double bond without Michael addition.
I must ahve a look why antibody2 did not use Zinc/Ammonium Formate but acidic Al/Hg for the MDP2P-Oxime reduction. Another way to rduce the Oxime in good yields is Na metal, molten and finely dispersed in xylene added to the Oxime in Xylene together with some alcohol. 3 to 4 molar equivalents of Na are needed and a little less alcohol (n-butyl, or EtOH).
Na metal is trivial, look for Nurdrage on YouTube. But use a SS vessel not glass. Na metal is dispersed by using an Hershberg stirrer - basically a SS egg-beater.
Everything should be pretty anhydrous for this, obviously.

As said I have to find out if there is not a prolem with the Zinc reduction, something does not add up.

 

[OrgUnikum]

SnCL2/HCl is defintely the way to go to produce the oxime according to the paper I read (since my last post) yields are very high and all reagents are readily available . I'm aware about ethyl acetate being the key otherwise you'll get the ketoxime but it seems the reaction itself proceeds at room temp and you can just stick a reflux condenser on the top and not have to babysit it like Al/Hg.

There's 2 of the same aldoxime to amine reduction papers in Rhodium's archive which seem to good to be true:

Zinc/Ammonium Formate: Rapid and selective reduction of oximes to amines - [www.rhodium.ws]

Reduction of Nitro Groups With Zinc/Ammonium Formate - [www.rhodium.ws]

Again, easily available reagents (making ammonium formate is trivial) and high yields. If it works I wonder why this route doesn't seem to be popular. Even though its more labourious than Al/Hg it has some definite advantages.

41DxflatlineAh yes. Those are another example of strange Indian chemistry which seems to work only in India, same as Mg for reductive Aminations. Must have some magic Zinc there.

They also call the Zinc a catalyst in the article what is clearly wrong and tells a lot of the level of understanding of organic chemistry the authors must have. If I had to guess I would say they probably studied in Australias diploma mills err, Universities

So sorry I am quit sure that you will not get anywhere with zinc when reducing Oximes.

 

[OrgUnikum]

SnCL2/HCl is defintely the way to go to produce the oxime according to the paper I read (since my last post) yields are very high and all reagents are readily available . I'm aware about ethyl acetate being the key otherwise you'll get the ketoxime but it seems the reaction itself proceeds at room temp and you can just stick a reflux condenser on the top and not have to babysit it like Al/Hg.

There's 2 of the same aldoxime to amine reduction papers in Rhodium's archive which seem to good to be true:

Zinc/Ammonium Formate: Rapid and selective reduction of oximes to amines - [www.rhodium.ws]

Reduction of Nitro Groups With Zinc/Ammonium Formate - [www.rhodium.ws]

Again, easily available reagents (making ammonium formate is trivial) and high yields. If it works I wonder why this route doesn't seem to be popular. Even though its more labourious than Al/Hg it has some definite advantages.

41DxflatlineKabalka, G. W., Laila, G. M. H., & Varma, R. S. (1990). Selected reductions of conjugated nitroalkenes. Tetrahedron, 46(21), 7443–7457. doi:10.1016/s0040-4020(01)89059-1

Sci-Hub | Selected reductions of conjugated nitroalkenes. Tetrahedron, 46(21), 7443–7457 | 10.1016/S0040-4020(01)89059-1

Kabalka and his team are first class reliable.

The synthesis of 9-anthracenylacetaldoxime is representative. w-(Nitrovinyl)anthracene (1.25 g, 5 mmol), SnC12.2H20 (2.25 g, 10 mmol) and ethyl acetate (25 ml) were placed in a 50 ml Erlenmeyer flask and the mixture stirred at room temperature. A mildly exothermic reaction ensued which was accompanied by the gradual disappearance of the yellow coloration (nitroalkene). The reaction mixture was carefully poured into ice water and the solution made slightly basic (pH 7-8) by addition of 5% aqueous sodium bicarbonate. The product was extracted into ether, washed with brine, dried (Na2S04) and the solvent removed under reduced pressure to yield essentially pure E/Z mixture of 9-anthracenylacetaloxime, mp 177-18O'C; (1.05 g, 90%)

Not shabby, 90%. I would suggest to prepare the SnCl2 beforehand as the in situ preparation is quite exothermic and easily leads to runaways as the onset of the SN - HCl reaction is delayed. If you want to do it in situ add a pinch of mercury salt what solves the problem of delayed reaction and makes it instantly. A pinch, a knifes tip suffices.

Why those Indian nonsense articles? No, they are not SO stupid. It is about patent laws. In India one cannot patent a compound only its synthesis. Of course western Pharmacompanies file patents in India which try to cover ALL existing and a few non-existing ways to make the new drug. So sometimes Indians are barred from making a generic just for they have no own synthesis they can say they use. And so they built themselves an arsenal of unheard of, simple synths for basic stuff which is good enough for a patent. In the factory they use the best way to do it of course. And thats why one must be REALLY careful with Indian and Malayian Articles in special.

 

[41Dxflatline]

Kabalka, G. W., Laila, G. M. H., & Varma, R. S. (1990). Selected reductions of conjugated nitroalkenes. Tetrahedron, 46(21), 7443–7457. doi:10.1016/s0040-4020(01)89059-1

Sci-Hub | Selected reductions of conjugated nitroalkenes. Tetrahedron, 46(21), 7443–7457 | 10.1016/S0040-4020(01)89059-1

Kabalka and his team are first class reliable.

Not shabby, 90%. I would suggest to prepare the SnCl2 beforehand as the in situ preparation is quite exothermic and easily leads to runaways as the onset of the SN - HCl reaction is delayed. If you want to do it in situ add a pinch of mercury salt what solves the problem of delayed reaction and makes it instantly. A pinch, a knifes tip suffices.

Why those Indian nonsense articles? No, they are not SO stupid. It is about patent laws. In India one cannot patent a compound only its synthesis. Of course western Pharmacompanies file patents in India which try to cover ALL existing and a few non-existing ways to make the new drug. So sometimes Indians are barred from making a generic just for they have no own synthesis they can say they use. And so they built themselves an arsenal of unheard of, simple synths for basic stuff which is good enough for a patent. In the factory they use the best way to do it of course. And thats why one must be REALLY careful with Indian and Malayian Articles in special.

OrgUnikumI'm purchasing the SnCl2 rather than making it (98% purity)

Yep, it's the same 2 Indians responsible for all the papers claiming Zinc/Ammonium formate can selectively reduce aldoximes. They're also responsible for claiming the same of Mg. There's papers not involving K. Abiraj and D. Gowda where azo compounds are reduced and one where imine was reduced to the secondary amine. Nothing that interests me currently. I was going to electroreduce the p2np all the way to the amine but I'll start with the oxime since it's an intermediate anyway. Can also form the imine I think by changing the ph.

Zn-Ni seems to work on p2p-oxime but the yields are garbage. I do have almost 1kg of p2p glycidic ester sitting around doing nothing though.

 

[OrgUnikum]

I'm purchasing the SnCl2 rather than making it (98% purity)

Yep, it's the same 2 Indians responsible for all the papers claiming Zinc/Ammonium formate can selectively reduce aldoximes. They're also responsible for claiming the same of Mg. There's papers not involving K. Abiraj and D. Gowda where azo compounds are reduced and one where imine was reduced to the secondary amine. Nothing that interests me currently. I was going to electroreduce the p2np all the way to the amine but I'll start with the oxime since it's an intermediate anyway. Can also form the imine I think by changing the ph.

Zn-Ni seems to work on p2p-oxime but the yields are garbage. I do have almost 1kg of p2p glycidic ester sitting around doing nothing though.

41DxflatlineP2P-Oxime is the problem. The reduction of the Oxime can be done by Al/Hg or NaBH4/Cu or those Copper/iron oxide nanos quite nicely. And with several variations of sodium metal reduction.
But on topic, we started with P2NP reduction here yes?

 

[41Dxflatline]

P2P-Oxime is the problem. The reduction of the Oxime can be done by Al/Hg or NaBH4/Cu or those Copper/iron oxide nanos quite nicely. And with several variations of sodium metal reduction.
But on topic, we started with P2NP reduction here yes?

OrgUnikumI was returning to Zn-Ni (that french patent) since we were talking about it before the ammonium formate tangent. I didn't mean p2p oxime I've just been typing oxime far too many times today. I had a good look through forum archives and theres a few saying it worked on p2np, you said it won't. I said I was going to try it but now I've concluded I'll save it for the P2P.

 

[OrgUnikum]

I was returning to Zn-Ni (that french patent) since we were talking about it before the ammonium formate tangent. I didn't mean p2p oxime I've just been typing oxime far too many times today. I had a good look through forum archives and theres a few saying it worked on p2np, you said it won't. I said I was going to try it but now I've concluded I'll save it for the P2P.

41DxflatlineThe Ni/Zinc/ammonia(salt) is even worse on P2P then on anything else as the di-alkylated Amphetamine is the main part of the very small amount of product. Ni/Zn works on easy substrates like hexanone or nitrobenzene I guess. But P2P and its derivatives, Imine, OOxime Nitro whatever is the biggest bitch as its completely saturated as molecule. It is kind of funny that what everybody believes to be simple, say making Amphetamine in good yields and quality, is actually by far the hardest one. Meth, MDA, MDMA and on, they are all much easier.

Whatever, I have wasted too much time and precursors on this last year (as somebody I thought to be true had assured me its good). And I am not the only one. But naturally everybody is entitled to his own experiences and I am not a preacher, I say what I know so others do not have to make the mistakes I and others made. I do this because I wish somebody had warned me back then. am not going to argue about anything, I have better things to do and I spent again too much time already talking about things which are known crap instead to read and talk about things which are untried and promising.
And thats what I will do now. Read about and try new stuff.
See you later

 

[41Dxflatline]

On a separate note: I can't send you 50g because I don't have 50g (this is all hobby/personal use) I can send you 10g but I'm not in the EU

 

[OrgUnikum]

On a separate note: I can't send you 50g because I don't have 50g (this is all hobby/personal use) I can send you 10g but I'm not in the EU

41DxflatlineThx a lot for the offer, but at the moment I want to avoid having this to come from outside the EU for personal reasons.

 

[OrgUnikum]

After a lot of experiments and research I want to warn everybody that my statements here should be taken for what they are, my opinion at the moment of posting and so often enough not correct.
What I know now for sure is that P2NP can be reduced in very good yields, first with 5 equivalent NaBH4 on silica gel in anhydrous IPA followed by addition of 0,2 equi. CuSO4.5H2O and two more equiv. Boro for the final step to the Amine. The reaction is well behaved and controllable and therefor can be scaled up into the kg range without problems.

I also want to thank the friendly member who made this research possible by providing me with the needed P2NP.