Author Topic: Proposal for reduction of nitroalkenes to aminoalkanes sans LAH (Read 475 times)

Tsathoggua · « **on:** March 14, 2012, 01:09:51 AM »

Before he loses the idea cooking up in his brain...Toady had a thought, for reduction of nitroalkenes to aminoalkanes for those with no LAH connections and designs on certain substances known to honey producers the world over.

Since dithionite is known to reduce double bonds, first a nitroalkene be treated with dithionite, which could be accessed easy enough from bisulfite if somebody got desperate enough

Makes ol' toady wonder if a neat way to reduce nitroalkenes, might not be to treat first with dithionite, then with diborane (Thus avoiding the use of LAH).

B2H6 should bee accessible from borax or boric acid, roasting the crap out of the hydrates until only the boric oxide remains, thermite to boron (elemental) and treatment of the resulting element with aluminium or magnesium to form the boride, which would liberate the pyrophoric diborane gas on acidification. Toxic stuff though, but a whole bunch easier to source borax than LAH...

pyramid · « **Reply #1 on:** March 14, 2012, 01:44:15 AM »

Or after isolating the nitroalkane you can just use Zn or Al metal. But I thought dithionite will reduce nitro groups as well? Not that I believe it will work for total reduction of nitroalkenes... But who has tried?

Regardless, it should not be necessary to try to produce diborane since many easier methods exist for the second step of reduction.

Edit:

Well, I don't believe that sodium dithionite will reduce a nitroalkene all the way, but it's possible I guess you can reduce first the double bond, maybe someone with more knowledge than me can add some information and insight. Either way, I've never seen it tried. Since experimentation is the name of the game and the only way to find out, I may try this on a simple nitrostyrene like 4-methoxy-beta-nitrostyrene.
My guess is maybe it can work for the double bond, and once the nitroalkane is in hand, continue with zinc metal.
Thanks for this topic reminding me of a little idea I had ages ago but dismissed.

Any thoughts on conditions? I have seen reflux in aqueous solution used or RT in DMF as a cosolvent with water...Of course some Na2CO3 is also used for pH control, I need to research this all again anyway.
I'll add more here in a little while.

lugh · « **Reply #2 on:** March 14, 2012, 02:21:17 AM »

Quote

Or after isolating the nitroalkane you can just use Zn or Al metal. But I thought dithionite will reduce nitro groups as well? Not that I believe it will work for total reduction of nitroalkenes... But who has tried?

Barium thought it was possible:

http://parazite.nn.fi/hiveboard/novel/000427794.html

but got the oxime as other researchers had in the last century

pyramid · « **Reply #3 on:** March 14, 2012, 03:21:33 AM »

Well those are nitropropenes and all that seemed to be tried was straight dithionite THEN adding Na2CO3. Examples I've seen elsewhere for reductions of nitro compounds/double bonds using sodium dithionite use a basic solution already containing the sodium carbonate, but I have only just begun reading about it again and maybe I am just stupid and missing something obvious.

Regardless it's going to be tried with some different conditions to see where it goes, on a nitroethene. Unless of course, as I said, I missed something obvious and it's worthless to try.

Tsathoggua · « **Reply #4 on:** March 14, 2012, 07:19:36 AM »

Its a nitroalkene that needs reducing. Toady got LAH connects. He needs to reduce the nitro group.

Hells, toady has LAH, he just is looking for something non-pyrophoric, that will reduce both a nitro and an aliphatic C=C without in one step. Diborane is for sure, but as a gas, that can be generated on tap, it has its advantages over using LAH, in this particular case. More convenient to burn off any borane gas bubbling out as it forms, than require constant inert gas flow.

java · « **Reply #5 on:** March 14, 2012, 08:40:44 AM »

http://en.wikipedia.org/wiki/Diborane

......having read and never used the gas in question, it doesnt seem to be a very friendly route to go....what's wrong with the tried and true reduction with AlHg, it will reduce the double bond and convert the nitro to an amine in one shot......java

pyramid · « **Reply #6 on:** March 14, 2012, 02:03:06 PM »

Yes now you rephrase what you want Tsathoggua I think you are making it too complicated as many, many method exist to reduce nitroalkenes.
I've said it to you before that NaBH4 then Zn or CTH or some other normal nitro group reduction works fine and is easy. NaBH4/I2, hydrogenation, Al/Hg (for some it's been proven you can utilize CuSO4/NaCl).
Electrochemical, the methods continue.

If you are talking of the nitrostyrene for 2C-D or DOM (you have mentioned it a few times in the past) don't think about it this much.
And I'll also say again in hopes you will hear me, even wet THF can be used and add the LiAlH4 to it just use some excess. It's not that dangerous to use, unless you get it in lumps and have to powder it. You aren't going to have problems with peroxides (that you probably don't have), if you read too much about LiAlH4 it will scare you too much, until you do it and see its simple and no problem you will always be afraid and hence looking for alternatives when you have the simple option right in front of you. But its true some alternatives yield better than LiAlH4 itself.

You spun this from being looking for an alternate nitroalkene reduction (which are not universal by the way) into a method that you need for reduction. Nw I don't know if you want to reduce the whole thing at once or two step as proposed in your first post.

Give some substrate examples! I don't think dithionite is going anywhere honestly, and diborane is to much fucking work compared to everything else that been developed.
If you have the connections buy some other reagents then, such as NaBH4 which is extremely versatile.

lugh · « **Reply #7 on:** March 14, 2012, 05:00:10 PM »

The electrochemical reduction based on the work of Slotta would undoubtedly be best suited for someone who is under scrutiny:

http://www.sciencemadness.org/talk/viewthread.php?tid=4145

as easily available vehicle batteries aren't very suspicious to have around

Tsathoggua · « **Reply #8 on:** March 14, 2012, 06:40:04 PM »

Toady is most curious weather diborane will go all the way.

lugh · « **Reply #9 on:** March 15, 2012, 05:57:20 PM »

Quote

Toady is most curious weather diborane will go all the way.

Toady needs to request:

Reduction of organic compounds with diborane

Clinton F. Lane
Chem. Rev., 1976, 76 (6), pp 773–799
DOI: 10.1021/cr60304a005
Publication Date: December 1976

Reduction of oximes, oxime ethers, and oxime esters with diborane. Novel synthesis of amines

Henry Feuer, D. M. Braunstein
J. Org. Chem., 1969, 34 (6), pp 1817–1821
DOI: 10.1021/jo01258a062
Publication Date: June 1969

is attached

If you would have read the Wikipedia article java gave you a link to you could have answered your own question

These article citations were found using the search terms "diborane" and "reduction"

The end results from the effort applied

antibody2 · « **Reply #10 on:** April 19, 2012, 01:34:27 AM »

Ab2 was around when Barium proposed using sodium dithionite to reduce nitroalkenes to nitroalkanes. If memory serves it worked fine as a pathway to amphetamines, but for phenethylamines the nitroalkenes suffered hydrolysis. Specifically, 2,5-DMNP was hydrolyzed under the conditions Barium put forward. In the end NaBH4 did the trick.

An OTC source for sodium dithionite is the fabric whitener sold along with fabric dyes, if memory serves the brand name was RIT.

Sydenhams chorea · « **Reply #11 on:** April 19, 2012, 03:46:55 PM »

Dithionite reduces nitroalkenes to oximes, only NaBH4 will reduce to nitroalkanes.

I was just looking at some patents that I never got around to post in the days of the Hive, and found back under the dust.

Patent DE245523 describes 3,4-methylenedioxy-beta-nitrostyrene being reduced to the PEA by a two-step reduction, using Zn dust tot the oxime and then Na/Hg to the amine. In the first example the oxime is isolated, the second example does it in one pot.

This could be tweaked and Al/Hg would work instead of Na/Hg, dithionite instead of Zn dust.

The third example gives a one-pot reduction to the amine using Al/Hg. Freely translated it goes like this (parts are of course by weight):

15 parts 3,4-methylenedioxy-beta-nitrostyrene in 1000 parts hot ethanol were heated under reflux with 50 parts activated aluminium (=Al/Hg) for several hours. The aluminium salts and insoluble matter are filtered off and the alcohol is distilled off until 1/10th its volume. The residue was slightly acidified with acetic acid and diluted with 4 times its volume of water. After some standing the oxime crystallises out and is filtered off. The homopiperonylamine is isolated from the filtrate by basifying and extracting.

But in my opinion electroreduction is the only way.

Look at patent DE254861, the same substrate is used.

In the first example, the catholyte consists of a solution of 15 grams 3,4-methylenedioxy-beta-nitrostyrene in 230ml hot glacial AcOH is placed in the cathode chamber and with strong stirring 100 ml 30% H2SO4 is added. This causes the 3,4-methylenedioxy-beta-nitrostyrene to precipitate as a fine paste. The cathode is a 168 cm² lead cylinder. Anolyte is 30% H2SO4. Current density is about 20 A and the temperature of the catholyte is kept under 30°C.

After the electrolysis, the catholyte is diluted with water, filtered and basified. The precipitated oil is taken up in ether and HCl(g) is passed through the ether layer. The HCl salt of homopiperonylamine precipotates. This is washed with acetone, dissolved in water and basified. The base oil is extracted with ether, the ether evaporated and the base distilled in vacuo.

In the second example, the catholyte consists of a solution of 15 grams 3,4-methylenedioxy-beta-nitrostyrene suspended in 225 ml ethanol and 75 ml 50% H2SO4 is added. Current density is about 20A. Electrolysis is performed at 50-60°C for 8 hours, cathode (lead) surface was 168 cm².

In the third example, the catholyte consists of a solution of 15 grams 3,4-methylenedioxy-beta-nitrostyrene in hot glacial AcOH is placed in the cathode chamber and with strong stirring 100 ml dilute acetic acid was added. Again, this causes the 3,4-methylenedioxy-beta-nitrostyrene to precipitate as a fine paste, which is easily electrolysed. Current density was 5A, the temperature doesn't rise above 40°C, cathode (lead) surface was 168 cm², after 5 hours the reaction has ended.

My 2 cents to add to this: always use a clean lead cathode with a freshly precipitated layer of spongy lead. This is done by using the cathode-to-be as an anode in a dilute H2SO4 solution, so a layer of PbO2 is deposited. This is then reduced when the polarity is switched.

The old chemists used unglazed porcelain as a diaphragm (which can be a flowerpot or a designed cup from the local pottery), modern substitutes are car battery diaphragms (semipermeable PE or PP) or Tyvek.

Polonium · « **Reply #12 on:** April 19, 2012, 04:02:31 PM »

The electro reduction does indeed look very clean. Have you tried this yourself, Sydenhams chorea? If you have, what power supply did you use? Also for the anode did you just use regular lead sheeting that you activated as described?

Sydenhams chorea · « **Reply #13 on:** April 19, 2012, 04:11:44 PM »

Quote from: Polonium on April 19, 2012, 04:02:31 PM

The electro reduction does indeed look very clean. Have you tried this yourself, Sydenhams chorea? If you have, what power supply did you use? Also for the anode did you just use regular lead sheeting that you activated as described?

Yes, lugh gave the link a couple of posts above.

As a power supply, a car battery charger or a PC power supply can be used. Regular "roofing" grade lead sheeting were indeed used for the cathode, after cleaning with sandpaper and rubbing the surface with alcohol or acetone. Then it was coated electrochemically as described, which is absolutely essential to get reliable and reproducable results.

Sydenhams chorea · « **Reply #14 on:** April 19, 2012, 04:13:15 PM »

I forgot to add: yields are modest, around 50% But considering the ease of the setup, the reduction and the work-up, I'd take it any day of the week.

Electro´S · « **Reply #15 on:** May 11, 2012, 09:26:03 AM »

lately I've been dreaming with a very special cat. it is interested in the theorycal proce of this topic.
it found this reducction on the net.
______________________________________________________
hxxp://www.sciencemadness.org/talk/viewthread.php?tid=3576
Phenyl-2-nitropropene reduction

I recently had a dream of reducingp2np to the amine with sn and hcl
Procedure went like this.
in a 2 litre beaker was 30 grams of recristlized p2np , 120 grams granulated tin with just enough water to cover contents.
A mechanical stirrer was fitted and the contents was heated to 50c
added dropwise was 200ml of 37% hcl over a period of 8 hours
the contents upon conpletion of the reduction had gone from a yellow p2np colour to to clear water
I then carefully basified water to ph13 which percipertated out tin hydroxide whitch i filtered out
I then had a yellow as water phase with a little bit of sodium cloride in it from reaction
Next i evaperated down the water to yeild a yellow product mixed with sodium cloride
When it was dry i added 250ml dry ethanol which dessolved the organic phase but not the nacl i then had a nice yellow alcohol phase
Dropwise i added conc h2so4 which percipertated out a very white powder
I then filtered to collect 26 grams of product wich i thought was amphetamine sulphate but was not did it go to the oxime or some other intermediate could somewone with more knowledge tan me help
I would be much apprecaited thank you:o
____________________________________

the cat read the topic a lot of times but nothing concrete about the product yielded is definite.

Is possible than the end product was the amine? Or the oxime?
If is the amine (it doubts it), it´s a easy goal.
And if is the oxime, a good proccess to end would be "Zn/amonium formate".

hxxp://www.erowid.org/archive/rhodium/chemistry/oxime2amine.zn-af.html
_____________________________________________________
Reduction of oximes to amines, general procedure:

To a solution of the substrate (5 mmole) in methanol (10 ml) was added ammonium formate (10-20 mmole) [or ammonium chloride (10-20 mmol)] and zinc dust (10 mmol). The mixture was stirred under reflux. After the completion of the reaction (monitored by TLC), the reaction mixture was filtered through celite. The filtrate was evaporated under vacuum and the residue was taken into chloroform or ether, washed twice with 80% saturated brine solution and finally with water. The organic layer was dried over anhydrous sodium sulphate and evaporation of the organic layer was followed by purification either by preparative TLC, or by column chromatography, to yield the desired product.
________________________________________________________

Can anyone show some light about this (Tin metal/HCl) reduction?

Much apreciated!!!

Sydenhams chorea · « **Reply #16 on:** May 19, 2012, 10:25:59 AM »

P2NP reduction ~25% yield from electroreduction due to sloppiness and less suitable conditions. Catholyte consisted of 50ml conc H2SO4 (way to much)/50ml water/100ml ethyl acetate/100ml ethanol. Anolyte was 15% H2SO4. Lead cathode was pre-treated with a layer of PbO2 and subsequent reduction by switching polarity in 15% H2SO4. At a 12V car battery charger, 1.5A for about 10 hours (current density about 100-150mA/cm²) , then it was brought to 4A over the next 4 hours. Diaphragm was a flower pot from the local Turkish bazaar, the flower pot contained the catholyte and was placed in the anolyte. This setup was placed in a cooling bath. During the reduction an additional 100 ml ethanol was added to compensate for the loss by evaporation.

Uncrystallised P2NP (about 15 grams) was used. Lots of polymerisation was encountered towards the end of the reduction, which is noticed by the deep striking purple color of the solution and all subsequent washings. The catholyte was diluted with 50ml water. This was washed twice with ether and once with ethyl acetate. After basifying with cold concentrated NaOH sol (dark oil separates + fishy odor was noticed), it was extracted 3x with toluene. The pooled extract were washed thoroughly with distilled water 7x, after which no more purple hue was noticed in the washings and the organic layer became a yellow-orangish colour. Solvent was washed with brine, dried over MgSO4 and distilled off. The residue was diluted with acetone and amphetamine sulfate was precipitated using H2SO4 diluted in acetone.

This is a nice example of how not to do it. Results have been much better using recrystallised P2NP, higher current and thus shorter reaction time, and a much lower acid concentration (50ml 30% HCl instead of 50ml conc H2SO4). Still it shows how even in the most primitive conditions a very modest amount of product is still obtained by this route.

fresh1 · « **Reply #17 on:** May 19, 2012, 03:07:19 PM »

a very neat otc idea

Quote

, the flower pot contained the catholyte and was placed in the anolyte.

what a neat idea

You can get semi-fired pots from pottery places with no glaze on them called "greenware" They are basically preformed shapes of clay waiting to be glazed an fired again

There are pots of all sizes available and ones with wall much thinner than a plant pot so maybe they might allow for a more efficient electrolysis

I look forward to hearing how you go as I'm sure will be other wasps too

Wizard X · « **Reply #18 on:** May 20, 2012, 02:24:27 AM »

I have covered P2NP electroreduction in my X-Files. http://www.4shared.com/zip/Rxq35waK/X-Files.html

Sydenhams chorea · « **Reply #19 on:** May 20, 2012, 02:27:59 PM »

Thanks for the 'greenware' tip. I was thinking of asking the local pottery maker to make me a bunch of thin unglazed porcelain cylindric cups of specified sizes.

I agree the flowerpot is crude, but yields of 50% have been attained with several nitroalkene substrates using more carefully controlled conditions and recrystallized nitroalkene in a flowerpot.

I will give the size next time, but you should get a basic idea of it from these pics.

The setup:

Here you see (presumed) oxime crystallising on the cathode halfway into the reduction:

Note the colour of the catholyte solution in the pipette at that time.

It is also a good idea to make a couple of holes in the cathode to improve contact of the catholyte with the cathode.

Of course improvement could be had from adjustable voltage on the power supply with a reference electrode. A simple and cheap setup can be made with the LM338 adjustable voltage regulator (max 5A), a circuit example is given in the documentation:
http://www.jaycar.com.au/images_uploaded/LM138.PDF

This would allow the power to be adjusted so that competing hydrogen evolution could be minimized and even allow for selective reduction, if for example one only wants to obtain the oxime.

Author Topic: Proposal for reduction of nitroalkenes to aminoalkanes sans LAH (Read 475 times)

Tsathoggua

Proposal for reduction of nitroalkenes to aminoalkanes sans LAH

pyramid

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lugh

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pyramid

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Tsathoggua

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java

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pyramid

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lugh

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Tsathoggua

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lugh

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antibody2

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Sydenhams chorea

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Polonium

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Sydenhams chorea

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Sydenhams chorea

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Electro´S

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Sydenhams chorea

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fresh1

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Wizard X

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Sydenhams chorea

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