Sciencemadness Discussion Board

desulfuration

romanceliu - 23-6-2010 at 08:40

now we synthesis the chemicals

5-AMINO-4-CHLOROPYRIMIDINE from chemcal 1,

process:

1 was added to 3L flask and added NH3.H2O and EtOH was added subsequence. The mixture was stirred and Raney-Nickel was added portions, then stirred the mixture overnight. the mixture reflux for 2 hours. TLC show reaction completed, cooled to rt and filter to remove solid, concentrated filtrate and purified by silica-gel got yellow solid

but Raney-Nickel need a lot

1:Raney-Nickel=1:5

i want to find another method to desulfurate , i search a lot of Literatures , but i do not good method except Raney-Nickel

pls gei me some advice , i want to find to good method to
desulfurate

thanks

12.jpg - 13kB

Nicodem - 23-6-2010 at 09:07

Is that the minimum amount of Raney nickel to obtain complete conversion? Does lowering the Ni loading and prolonging reaction time still give incomplete conversion? What is the ratio of the dehalogenated product? Your post lacks the most basic information.

You might be able to dramatically reduce the amount Raney nickel if you use it as catalyst instead of reagent, but this would require a hydrogenation apparatus in order to supply external hydrogen. Rate of dehalogenation might increase though. Also, the activity of Raney nickel is highly dependent on the method of preparation (type of catalyst). Which Raney nickel version do you use? Try another one.
Otherwise, there is a method where aluminium-nickel (50:50, the alloy used to prepare Raney Ni) and the substrate is refluxed in formic acid. This might require less Al-Ni alloy and avoids the tedious preparation and handling of the pyrophoric Raney nickel. If you truly did a literature search, you surely already know about this, so I will not bother searching for the reference. Though I do not know whether such method leads to increased dehalogenation or not.

PS1: Are you aware that this is a forum for amateur chemists and that your industrial profit related question is - besides being non hygienic - also considered a form of parasitism? If you insist on exploiting us, then at least have the decency to make a forum donation, or at least start contributing to the community!

PS2: Start using a spell checker!

Barium - 23-6-2010 at 12:54

My general protocol for nickel desulfurisations is to reflux the substrate with 2-3 mol eq. raney nickel in acetone or methyl ethyl ketone until TLC indicates complete conversion. The metal quality required is the oldest and crappiest nickel possible since I do NOT want any hydrogen left in the pores of the catalyst. To make absolutely sure the catalyst is dead dump it in some acetone and reflux the shit out of it for about thirty minutes. Then change solvent and start the reaction. I prefer not to use alcohols as solvents in this reaction since they can activate the catalyst again.

DJF90 - 23-6-2010 at 14:46

The catalyst needs adsorbed hydrogen, otherwise it is unable to replace the C-S bonds with C-H ones. Raney Nickel is the traditionally used reagent, but Urushibara Nickel and "Nickel boride" also remove sulfur from organic molecules. Urushibara nickel in particular is worth looking into, as it could be a much cheaper alternative to Raney Nickel, and is supposedly easier to prepare.

If the Raney Nickel is not freshly prepared (so as to contain adsorbed hydrogen gas), then the reaction must be performed under hydrogen atmosphere.

Oxydro - 23-6-2010 at 16:29

DJF90, I read the first post, thought, "Hey! U-Ni sounds ideal here"... scroll down and you got here first.


http://www.erowid.org/archive/rhodium/chemistry/urushibara.h...

This pretty much covers it. Note that:
A) catalyst is easy to produce, and quite cheap.
B) is recoverable and easy to regenerate.
C) is suitable (allegedly) for all applications of Raney nickel.

romanceliu - 24-6-2010 at 04:26

thanks , i will try ,

DJF90 - 24-6-2010 at 06:55

Sorry Oxydro, you just gotta be quicker ;)

Barium - 26-6-2010 at 05:21

Quote: Originally posted by Nicodem  
You might be able to dramatically reduce the amount Raney nickel if you use it as catalyst instead of reagent, but this would require a hydrogenation apparatus in order to supply external hydrogen. Rate of dehalogenation might increase though. Also, the activity of Raney nickel is highly dependent on the method of preparation (type of catalyst). Which Raney nickel version do you use? Try another one.
Otherwise, there is a method where aluminium-nickel (50:50, the alloy used to prepare Raney Ni) and the substrate is refluxed in formic acid. This might require less Al-Ni alloy and avoids the tedious preparation and handling of the pyrophoric Raney nickel. If you truly did a literature search, you surely already know about this, so I will not bother searching for the reference. Though I do not know whether such method leads to increased dehalogenation or not.


I have never seen Raney nickel being used in hydrodesulurization since the mechanism behind the activity of nickel here is the irreversible formation of NiS. Can you please give an example of the catalytic use of nickel in hydrodesulfurization?
If using 50:50 Ni-Al with formic acid as hydrogen source, doesn't that give a raney-type of nickel as residue with all the pyrophoric properties as ordinary raney nickel?

DJF90 - 26-6-2010 at 07:32

Nicodem mentions the formation of the Raney Nickel in situ and so there is no pyrophoric properties to have to deal with (at least until work up).

Barium - 26-6-2010 at 08:26

DJF90, What makes you think that wasn't pretty obvious when I wrote "If using 50:50 Ni-Al with formic acid as hydrogen source"?
It is in the work up the pyrophoric properties becomes a problem.

DJF90 - 27-6-2010 at 03:22

Of course, but thats 50% less pyrophoricity you have to deal with, if there is none whilst setting up the reaction.

[Edited on 27-6-2010 by DJF90]

Nicodem - 28-6-2010 at 00:02

Quote: Originally posted by Barium  
I have never seen Raney nickel being used in hydrodesulurization since the mechanism behind the activity of nickel here is the irreversible formation of NiS. Can you please give an example of the catalytic use of nickel in hydrodesulfurization?

I was completely wrong here. The nickel catalysts used for catalytic desulfurizations are very different from Raney nickel (Ni, NiS or Ni/Co molybdates on alumina) and the reaction requires temperatures above 200 °C, so this is something else altogether and not applicable to sensitive substrates. Like you say, at any lower temperature than that, NiS should always be the end product instead of H2S, so that catalysis or use of less than 1 eq of nickel is out of question.
Quote:
If using 50:50 Ni-Al with formic acid as hydrogen source, doesn't that give a raney-type of nickel as residue with all the pyrophoric properties as ordinary raney nickel?

I don't think formic acid is used as the hydrogen source here. It is probably just the acid for etching Ni-Al and forming hydrogen saturated Ni in situ. I should check the original paper, but I can't remember where I saved it (my collection of files is getting too chaotic to handle). It might have even been acetic acid and my memory confused them. The residue in my opinion should not be pyrophoric as the conditions are not such to form the Raney nickel type of material. But that is just an opinion and I'll rather not claim anything this time, because when it comes to this topic you surely have more experience. I never did any desulfurisations and my experience with Raney nickel is limited to its use in catalytic hydrogenation of alkenes and nitriles for which I used it only 5 times, of which I managed to get it to burn one time while filtering it of after the hydrogenation. :D Luckily the fire did not spread to any nearby solvent, but the hazards of Raney nickel should never be underestimated. If I compare that incident with the only similar incident with Pd-C which occurred to me only once in about 100 hydrogenations it soon becomes obvious that palladium on charcoal is a piece of cake for handling when compared to Raney Ni. Another incident with Pd-C that I had was the typical consequence of loosening the safety protocols due to lowered fears (one of the most common reasons of all fuck ups!). Seeing it is (seemingly) no big deal, I soon begun to skip the argon flushing of the vessel before adding 5% Pd-C to the methanolic solution of the reaction mixture and one time the contact with Pd-C ignited it. Luckily the neck of the vessel is not wide enough and the flames extinguished by themselves as soon as the air could not sufficiently access the solvent any more, but the experience was scary enough to get me back to religiously stick to the safer practice. Hope this little account helps others in avoiding similar accidents.

Sandmeyer - 30-6-2010 at 19:17

Quote: Originally posted by DJF90  


If the Raney Nickel is not freshly prepared (so as to contain adsorbed hydrogen gas), then the reaction must be performed under hydrogen atmosphere.


That's bollocks, I have 10 years old RaNi containers and it works as good as new. I would never dare to run a reaction with RaNi under hydrogen atm... However, as long as it's wet it's perfectly safe to both store and handle... I've used it for a number of hydrodeselenizations and sometimes I've been sloppy so it catches fire (burns a bit like a sparkler, no problem), especially when I used magnet (Nickel is magnetic!) and had to clean it after the rxn. :)

[Edited on 1-7-2010 by Sandmeyer]

Nicodem - 1-7-2010 at 00:27

Quote: Originally posted by Sandmeyer  

That's bollocks, I have 10 years old RaNi containers and it works as good as new.

Good to know. It is annoying to prepare it every time when needed.
Quote:
I would never dare to run a reaction with RaNi under hydrogen atm... However, as long as it's wet it's perfectly safe to both store and handle...

It is actually perfectly safe all the way to the filtration step, as long as you don't do anything stupid. What I did was to prepare the W4 version, but rather than filtering, doing all the washing steps by decantation. This way you can never have it exposed dry and you end up with a thick slurry of Raney Ni in water. Then you just use a pipette to add it in the reaction vessel (you estimate the amount by volume and mass of the Al-Ni alloy used). It works beautifully for reducing nitriles. In one case I got complete reduction in matter of 30min, while it took 2 days using Pd-C! It is not only that Raney Ni is more active on certain functional groups, but also in that you can load as much catalyst as you want (it is dirt cheap!). Otherwise certain functional groups get reduced with RaNi while they practically don't with Pd-C (ketoximes are one such annoying example).
Quote:
I've used it for a number of hydrodeselenizations and sometimes I've been sloppy so it catches fire (burns a bit like a sparkler, no problem), especially when I used magnet (Nickel is magnetic!) and had to clean it after the rxn. :)

It is not the glowing and burning metal that is scary, it is the sparks flying around in the vicinity of highly flammable solvents that get me extremely nervous. Otherwise, I think the most common source of fires in organic labs is sodium. The metal burning, not the hydrogen explosions! That was the scariest experience I ever had and about a third of colleagues that I ask about say their worst fire accident was with sodium.

DJF90 - 1-7-2010 at 05:47

In your 10 year old containers, do you have 50:50 Ni/Al alloy, or the actual prepared Raney Nickel itself? I was using the term "freshly prepared" to mean "contains hydrogen", whilst Barium was advocating the use of purposely dehydrogenated Raney Nickel; Something that would not work without a hydrogen atmosphere for the hydrodesulfurisation of C-S bonds, which is what the OP requests.

Sandmeyer - 1-7-2010 at 06:05

Quote: Originally posted by DJF90  
In your 10 year old containers, do you have 50:50 Ni/Al alloy, or the actual prepared Raney Nickel itself?


Raney Nickel (RaNi) - as I already said.

DJF90 - 1-7-2010 at 08:36

Just wanted to be sure; I've seen Raney Nickel advertised before on ebay but it was just the alloy.

Barium - 1-7-2010 at 15:21

Quote: Originally posted by DJF90  
Barium was advocating the use of purposely dehydrogenated Raney Nickel; Something that would not work without a hydrogen atmosphere for the hydrodesulfurisation of C-S bonds, which is what the OP requests.


Can you please provide a reference in which RaNi is used as a catalyst to convert a C-S bond to C-H and H-S-H?

Sandmeyer - 1-7-2010 at 17:23

I think he means that RaNi with hydrogen completely removed from its surface is dead and incapable of hydrodesulfurization and I agree. The new hydrogen atom(s) on the product has to come from somewhere, and it comes from the RaNis surface. I have been unable to get hydrodesulfurization to work when I have boiled the RaNi in aceton for a while prior to adding it to a complex thiocompound dissolved in various solvents. Without boiling, it works great, well, too great, as I get other functional group reduced as well and I want it spared. There are many literature examples where they boil RaNi in various solvents to get it deactivated in order to make it more chemoselective, but I think there still must be at least some hydrogen present on the surface otherwise it dosen't work.

DJF90 - 1-7-2010 at 18:21

Yes this is exactly what it meant. Was my communication so poor that it took this long to understand?

Sandmeyer - 1-7-2010 at 20:32

Quote: Originally posted by DJF90  
Yes this is exactly what it meant. Was my communication so poor that it took this long to understand?


I understood you perfectly, but I also pointed out that you were wrong in saying that one needs freshly prepared RaNi for the reaction to work - no one in his right mind makes his own RaNi these days. RaNi dosen't have to be "freshly prepared" in order to contain hydrogen as you imply, mine is 10 years old and contains hydrogen, as I already mentioned. ;)

[Edited on 2-7-2010 by Sandmeyer]

Barium - 2-7-2010 at 05:22

Quote: Originally posted by Sandmeyer  
The new hydrogen atom(s) on the product has to come from somewhere, and it comes from the RaNis surface.

What happens with the old hydrogen atom(s) then?
In the example given by the originator of the thread a C-S-H functionality is to be converted to C-H and Ni-S, a reaction which doesn't need any additional hydrogen as it is only a removal of the sulfur.

DJF90 - 2-7-2010 at 06:13

Sorry, I was just assuming the OP didn't have access to Raney Nickel, and thus has to prepare it from the alloy. "Freshly prepared" was used in the wrong context; I'll be more careful in future.

Good point Barium. I forgot we were cosidering a thiol and not a sulfide. Its an interesting point, but I'm not sure it will work without additional hydrogen. I know this is slightly off topic, but thiols will react with gold surfaces in order to adhere the molecule to the surface via the sulfur atom. Nickel may react similarly, but I susppect you are correct in this instance.

Sandmeyer - 2-7-2010 at 08:35

Quote: Originally posted by Barium  
Quote: Originally posted by Sandmeyer  
The new hydrogen atom(s) on the product has to come from somewhere, and it comes from the RaNis surface.

What happens with the old hydrogen atom(s) then?
In the example given by the originator of the thread a C-S-H functionality is to be converted to C-H and Ni-S, a reaction which doesn't need any additional hydrogen as it is only a removal of the sulfur.



Yes, I agree with you, there is enough hydrogen atoms (equal amount in reactants as well as products) in the case of thiols. The hydrogen atom on that C-S-H is just acidic and AFAIK you can't treat dead RaNi with an acid to make it active - it has to be hydrogen gas, which is absorbed onto the surface of nickel by providing one electron per hydrogen atom to the d-orbital (where the juicy valence electrons are) of nickel. So for example, I think that attempted hydrodesulfurization with dead RaNi conducted in acetic acid would fail. However, I should also add that I'm just guessing. :)

[Edited on 2-7-2010 by Sandmeyer]

Barium - 2-7-2010 at 10:57

I don't think I have ever seen a desulfurization using Raney nickel using hydrogen from external sources. It has alvays been a intramolecular donation. If not, then why isn't nickel used in catalytical amounts? I believe the reason for using nickel in the form of Raney nickel is due to the very high surface area compared to other forms of nickel. Since the end product is NiS and not H2S, high loadings of metal is needed in order to provide enough nickel to bind all sulfur.

I'd still love to see a reference in which nickel is used as a catalyst in a desulfurization or hydrodesulfurization.

Sandmeyer - 2-7-2010 at 11:45

I have no such example, 1 eq. NiS is irreversibly formed so I don't understand how the process could be catalytic. Anyway, I should have been more specific couple posts up, by a thiocompound I mean a thione (a keton with sulfur instead of oxygen) because deactivated RaNi failed to hydrodesulfurize it - I got back the thione again and again. I tried to partly deactivate it by boiling it in acetone but it is very difficult to do this, sometimes I got RaNi unable to hydrodesulfurize C=S, sometimes I got RaNi being able to do this, but it also started reducing other functional group - so I gave up. Well, I wonder if there is an example of completely dehydrogenated RaNi being able to dehydrosulfurize thiols? Maybe with thiols it does work, but for thiones it dosen't.

Nicodem - 2-7-2010 at 12:32

Quote: Originally posted by Sandmeyer  
The hydrogen atom on that C-S-H is just acidic and AFAIK you can't treat dead RaNi with an acid to make it active - it has to be hydrogen gas, which is absorbed onto the surface of nickel by providing one electron per hydrogen atom to the d-orbital (where the juicy valence electrons are) of nickel. So for example, I think that attempted hydrodesulfurization with dead RaNi conducted in acetic acid would fail. However, I should also add that I'm just guessing. :)

Interesting bone to chew on that Barium served us. I must admit that I completely missed the point in his post about deactivating Raney nickel first, so I did not understood what DJF90 was asking about.

If you think about it, it is perfectly plausible that hydrogenless nickel can desulfurize thiols if you consider that the electrons for the reduction come from Ni(0) and H from the thiol group.
I don't know the mechanism of the desulfurization or whether if any was ever demonstrated, but already if you chose just any of the most likely ones you can see this is possible. For example, if you take an organometalic mechanism and chose either oxidative insertion of Ni(0) into the Hetaryl-S bond or S-H bond, you get a Ni(II) intermediate which can rearrange in a Hetaryl-NiS-H intermediate which upon reductive elimination gives Hetaryl-H and NiS. If you take a radical anion formation folowed by the capturing of aryl radical by the metal (similar to the proposed mechanism of the Ullmann condensations) you still get a viable route to the desulfurization, because at the last stage you get to the same reductive elimination as in the purely organometalic mechanism.

The obvious question that arises from the consideration of these two mechanisms is: Does treating diaryl tioethers with such hydrogenless Raney nickel gives biaryls? This should happen if any of the two mechanisms is valid, yet I have not heard of any such example. I was intrigued about this possibility and went to do a SciFinder search. Indeed there are some examples with the NiCRA or other Ni(0) reagents, either as the desired reaction or just a side reaction observed, but all cases are for the ring contraction of tricyclic systems containing endocyclic sulfur:
Journal of Heterocyclic Chemistry, 22 (1985) 1547-1550. (with Ni(cod)2)
Journal of Organometallic Chemistry, 139 (1977) C51-C55, DOI: 10.1016/S0022-328X(00)85477-7. (with Ni(cod)2)
Journal of Organic Chemistry, 54 (1989) 4848-4853. (with NiCRA, this paper also proposes the radical anion mechanism)

I already thought that there would be no paper where deactivated Raney Ni was tried when I stumbled upon a carbazole synthesis from phenothiazine which uses degassed Raney Ni (Molecules, 13 (2008) 1345-1352) and gives reference to Aust. J. Chem., 17 (1964) 366-370. So not only it seems plausible that deactivated/hydrogenless Raney Ni can desulfurize thiols, but also that it can induce ring contraction in some endocyclic sulfur containing systems. I must say that I'm quite surprised about this last property.

BTW, the Molecules paper gives warning: "Caution! Degassed Raney nickel is explosive!". Anybody knows what is this about?
Quote: Originally posted by Barium  
I'd still love to see a reference in which nickel is used as a catalyst in a desulfurization or hydrodesulfurization.

Do you mean Raney Nickel or just any nickel catalyst? I have not found any example with Raney Ni, but there are plenty with other nickel catalysts. Catalytic desulfurization with external hydrogen and H2S as the end product is the most common form of desulfurization, though admittedly only because it is used in just about any petroleum processing plant. Just google "catalytic desulfurization". Ni or NiS on alumina was used in the old times (the book Organic chemistry of bivalent sulfur. Volume 1, available in References, has a chapter on these early catalysts). Nowadays more effective catalysts exist, particularly some cobalt molybdates and who knows what else.

Sandmeyer - 4-7-2010 at 15:59

Quote: Originally posted by Nicodem  


If you think about it, it is perfectly plausible that hydrogenless nickel can desulfurize thiols if you consider that the electrons for the reduction come from Ni(0) and H from the thiol group.
I don't know the mechanism of the desulfurization or whether if any was ever demonstrated, but already if you chose just any of the most likely ones you can see this is possible. For example, if you take an organometalic mechanism and chose either oxidative insertion of Ni(0) into the Hetaryl-S bond or S-H bond, you get a Ni(II) intermediate which can rearrange in a Hetaryl-NiS-H intermediate which upon reductive elimination gives Hetaryl-H and NiS. If you take a radical anion formation folowed by the capturing of aryl radical by the metal (similar to the proposed mechanism of the Ullmann condensations) you still get a viable route to the desulfurization, because at the last stage you get to the same reductive elimination as in the purely organometalic mechanism.


Well, Barium already pointed out the intramolecular donation leading to hydrodesulfurization. Treating Ar-SH with degased RaNi might as well give Ar-S-S-Ar and in that case no hydrodesulfurization has happened.

[Edited on 5-7-2010 by Sandmeyer]

Sandmeyer - 5-7-2010 at 16:16

Quote: Originally posted by Sandmeyer  



Yes, I agree with you, there is enough hydrogen atoms (equal amount in reactants as well as products) in the case of thiols. The hydrogen atom on that C-S-H is just acidic and AFAIK you can't treat dead RaNi with an acid to make it active - it has to be hydrogen gas, which is absorbed onto the surface of nickel by providing one electron per hydrogen atom to the d-orbital (where the juicy valence electrons are) of nickel. So for example, I think that attempted hydrodesulfurization with dead RaNi conducted in acetic acid would fail. However, I should also add that I'm just guessing. :)

[Edited on 2-7-2010 by Sandmeyer]


Well, what I’m saying here is bollocks, if degassed Raney nickel can insert between H-H it might as well do the same between S-H. And indeed it does, but if it then leads to hydrodesulfurization is the question here - and I would like to see an example that this is the case. Meanwhile, W. Bonner has published a study entitled: “The source of hydrogen in reductive desulfuraton”. This gentleman did some interesting experiments, notably he took naphtalene-2-thiol and refluxed together with “hydrogen-free” Raney nickel and got naphthalene disulfide (i.e Naphtyl-S-S-Naptyl), interestingly desulfurization was not observed, and he did the experiments in both ethanol (hydrogen donor) and benzene. Most conclusions of paper can be seen on the first page which is free of charge from AC$: http://pubs.acs.org/doi/abs/10.1021/ja01124a047

I should also correct myself in saying that I worked with a thione, in fact I attempted a chemoselective hydrodesulfurization on a highly substituted methylthioether where sulfur is connected to a sp2 carbon (isolated), if anyone cares.

DJF90 - 6-7-2010 at 14:50

Fieser shows a Raney Nickel desulfurisation similar to what is requested. However, a few pages back the book says that halogens are also displaced from aromatic systems under alkaline conditions. Find attached the mentioned pages.

Attachment: Raney Nickel - Fieser extract.pdf (148kB)
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