Sciencemadness Discussion Board - Experimental: Alternative to Al/Hg - the Al/Cu

Experimental: Alternative to Al/Hg - the Al/Cu

Pages: 1 2

TheCopperMan - 4-5-2014 at 10:51

References
There has been some talks before about using copper to activate Al:

- Woelens site talks about activating Al using CuSO4 and NaCl.
- Klute successfully reduced nitromethane to methylamine with a solution of CuSO4 and NaCl.
- On the hyperlab forums, it has been used for reductions of other compounds than nitromethane, but generally the results were unconclusive and/or low yielding.

Now, after lots of experimenting with this method (Lots of time, resources, and at least 40 test reactions ran), a general method has been found that produces approx. the same yields as one would expect from an Al/Hg. So far it's been ran successfully on a various set of nitrostyrenes. (including aromatic nitroalkenes)

Experimental
15g regular Al-foil (folded 4x, in flat strips, 2in long, 0.8in wide) was added into a 2-necked, 2L RBF. The Al-strips were made as flat as possible to avoid them floating to the surface later. 300ml EtOH, 120ml water, 45ml GAA was added in. Lastly 20g of nitrostyrene was added in. A condenser was mounted to the flask, along with a stirring rod attached on the 2nd neck, with a PTFE seal. Contents of the flask were heated to 60C. A solution of 10g CuSO4, 20g NaCl and 40ml hot water was mixed together separately. This was then added all at once to the 2L RBF, and the flask was immediately swirled around to ensure even distribution of the copper solution. Immediately, a vigorous reaction set in. During this, some Al floated to the surface. The stirring rod was lifted up by hand (without moving the PTFE seal) then pushed down on the Al in the flask, in order to keep the Al below the surface as best as possible. After 10 minutes or so, the reaction slowed down, and some Al was still left. Reflux was turned on for 1 hr, under overhead stirring. (If one does not have an overhead stirring motor, simply give the stirring rod an occasional swirl with your hands, to move the flask contents around. If one stirrs enough, then after 1 hrs, most of the Al should be gone.) The reaction was now finished and 300-400ml hot water was added whilst it was still at reflux temperature. It was then quickly re-rigged for distillation, and the alcohol was taken off. The solution was then cooled, ~130g NaOH added under mixing, and it was extracted 3x with DCM (or any solvent of choice). One can also do an in-situ steam distillation, then add acid of choice directly to the distilled water, and evaporate it in the open to be left with the salt. No need to worry about mercury fumes.

Some notes
• Generally, this reaction is a bit milder than the Al/Hg. So a larger surface area of Al can be used, and the reaction contents need to be heated a bit before the copper is added, to make it vigorous.
• It can be scaled up easily, and the amounts of CuSO4 / NaCl needed do not increase.
• It is efficient and environmentally friendly in terms of chemicals used. The alcohol is recycled, the amount of GAA used is small (45ml per 20g styrene), even the water can be recycled. If it's steam distilled, it's not neccessary to add anymore NaOH than what it takes to reach the correct PH, and no solvents would need to be used either. A lot of this possible, because one needs not worry about mercury which would otherwise contaminate everything.
• It is believed (although not 100% sure) that most copper will remain as an insoluble solid.
• It can probably be used for reductive aminations, but the CuSO4 and NaCl would possibly react with methylamine. Use of CuCl2 in place of CuSO4 and NaCl is possible.

Lastly, it should be noted that the reaction seems very tolerant and consistently produces the same yields, despite large changes in variables. For instance, in the beginning, this reaction was ran with 20g styrene in 250ml water, 250ml GAA, 250ml EtOH in an open beaker, with 50g CuSO4 and 100g NaCl dissolved in. This reaction was a mess, and there was a large amount of green precipitate at the bottom even before it began. Then 5g Al foil at a time, packed together by hand, was held into the reaction with a metal tool. The aluminum was eaten up with vengance, and the solution was boiling hard and solvent actively escaped into the open, and had to be replaced constantly. Nontheless, a total of 40g Al was consumed. And even here, yields were the same (~70%) as with the above reaction.

[Edited on 4-5-2014 by TheCopperMan]

[Edited on 4-5-2014 by TheCopperMan]

[Edited on 4-5-2014 by TheCopperMan]

blogfast25 - 4-5-2014 at 11:45

Welcome.

That is a very nice write-up but to the uninitiated like me it isn't clear what you've produced?

Zyklon-A - 4-5-2014 at 12:09

Very interesting, I have a few questions:
Exactly what are all the reactions happening here?
Excuse my apparent ignorance, but what is GAA?
What is the main reaction product? You just said reduction of aluminum, (Al → Al^3- + 3e^-) what is the anion?

[Edited on 4-5-2014 by Zyklonb]

TheCopperMan - 4-5-2014 at 12:44

Quote: Originally posted by Zyklonb

Very interesting, I have a few questions:
Exactly what are all the reactions happening here?
Excuse my apparent ignorance, but what is GAA?
What is the main reaction product? You just said reduction of aluminum, (Al → Al^3- + 3e^-) what is the anion?

[Edited on 4-5-2014 by Zyklonb]

Please see the reference to Woelens site, where he explains the reactions between aluminum and the tetrachlorocuprate.

In short:

2Al(s) + 3[CuCl4]2-(aq) → 2[AlCl4]–(aq) + 4Cl–(aq) + 3Cu(s)

2Al(s) + 6H2O(aq) → 2Al(OH)3(s) + 3H2(g)

The exact mechanism isn't too well understood. It seems that aluminum and copper also works as an electrolytic couple, which oxidizes the aluminum and produces hydrogen from the water at the copper site.

GAA is glacial acetic acid.

As for the last one, the main text has been corrected. Aluminum was not reduced obviously, but consumed in the reaction...

Quote: Originally posted by blogfast25

Welcome.

That is a very nice write-up but to the uninitiated like me it isn't clear what you've produced?

Amines, following the reduction from various nitrostyrenes...

[Edited on 4-5-2014 by TheCopperMan]

[Edited on 4-5-2014 by TheCopperMan]

blogfast25 - 4-5-2014 at 13:18

What's the reduction half reaction of the nitrate?

R-NO2 + 6 H+ + 6 e- === > R-NH2 + 2 H2O

... by any chance?

TheCopperMan - 4-5-2014 at 13:58

blogfast25: Think so

Al oxidation half-reaction:
2Al ------> 2Al3+ + 6e-

Also there might be reactions between any unreacted CuSO4 and the activated Al itself:

2Al + 3CuSO4 → Al2(SO4)3 + 3Cu
Ox: Al(0) → Al(2+) + 2e-
Red: Cu(2+) + 2e- → Cu(0)

Also in solution, Na2SO4 formed from the reaction between CuSO4 and NaCl.

Not sure if CuCl2 and CuCl3- might also be present.

To be fair, these reactions between copper salts and aluminum have always been confusing...there is a lot going on.

[Edited on 4-5-2014 by TheCopperMan]

eidolonicaurum - 5-5-2014 at 02:32

Forgive my ignorance, and the noobishness of the question, but what is the purpose of the glacial acetic acid? I've seen it used before in reactions, but I can never understand its purpose. Is acting as a solvent? If so, why ethanol and glacial acetic acid?

blogfast25 - 5-5-2014 at 04:20

By nitrostyrene, must we understand 2-nitrovinylbenzene?

Did you characterise your product (presumably 2-aminovinylbenzene)?

Have you tried other reductions with this tetrachlorocuprate/Al reducing agent?

[Edited on 5-5-2014 by blogfast25]

Metacelsus - 5-5-2014 at 04:47

I would think it would be reduced all the way to 2-phenylethylamine.

Wouldn't 2-aminovinylbenzene tautomerize to the imine?

Nicodem - 6-5-2014 at 09:50

Thank you for you contribution. Besides the reports in the long thread at the Hyperlab, I think this is the only other such report confirming this system is able to reduce beta-nitrostyrenes.

Quote: Originally posted by TheCopperMan

• It can be scaled up easily, and the amounts of CuSO4 / NaCl needed do not increase.

In the experimental example, you used a huge and over-stoichiometric amount of CuSO₄ (pentahydrate, I assume). Here you imply that this amount could be reduced (without affecting yields?). Did you evaluate the effect of the CuSO4 loading during your experiments?
In the reductions of nitrostyrenes with Hg activated aluminium, reducing the amount of Hg(MeCOO)₂ or other Hg salts (e.g., <15 mg / g Al) can result in the nitrostyrenes or oximes not being effectively reduced all the way to the amines (losing yields and build up of the N-hydroxyamines). Did you observe any such lower limit for Cu(II) that would dramatically affect yields and purity?

Quote:

Lastly, it should be noted that the reaction seems very tolerant and consistently produces the same yields, despite large changes in variables.

Did you try different substrates, ring substituted beta-nitrostyrenes, beta-substituted nitrostyrenes, oximes, or others? In what range were the yields?

I'm moving this thread to the Organic chemistry section. Though the main issue is about an alternative aluminium surface activation, the discussion is about a new organic synthetic method.

Chemosynthesis - 6-5-2014 at 14:08

Quote: Originally posted by blogfast25

By nitrostyrene, must we understand 2-nitrovinylbenzene?

I'm assuming it's actually a phenethylamine product, possibly an amphetamine. Maybe it's because I get paid to think about this kind of thing all day, but it seems very similar to some clandestine writeups with a new catalyst.

TheCopperMan - 6-5-2014 at 18:45

Sorry for the late replies,

Regarding the exact needed amounts of CuSO4, it has been researched a bit but no sure conclusion yet. What is interesting is that after the initial reaction is over, if one is to add more CuSO4 / NaCl solution, this will not speed up the reaction substantially. It was at some points tried adding at least 10g more CuSO4 and 20g more NaCl, after the initial reaction with 10g CuSO4 / 20g NaCl, and this did not change the speed at all (okay maybe a tiny bit, but nothing compared to the speed of the initial reaction).

However, the initial amounts added seem to matter to the initial speed. It was tried adding as little as 2g CuSO4 / 4g NaCl one time, and the initial speed was substantially less than from 10g CuSo4 / 20g NaCl. If more is added initially, this seems to make it more vigorous.

As for scaling, the only thing certain is that the amnt. of CuSO4 / NaCl needed do not increase proportionaly to scale. A 10x scale was ran at least once, and it was was ran with around 25g CuSO4 / 50g NaCl. It created a dangerous situation where BOTH the ice-cooled Allihn condensers attached clogged with alcohol halfway up. Here, the amounts of copper solution could preferrably be reduced, or perhaps the initial temperature of the reaction could be reduced.

Regarding substrates, the entire list won't be posted. Nitroalkanes (from NaBH4 C=C red) were reduced. Aromatic nitroalkenes were reduced. At least one oxime of an aromatic nitroalkene was reduced successfully. (Oxime prepared previously with SnCl2 in ethyl acetate). Substituted, yes. The bottom line is, everything that an Al/Hg is expected to go work for, the Al/Cu worked for in similar or slightly lower yields.

An interesting sidenote to this, is that SnCl2 was also tried as an aluminum activating agent (SnCl2 has very good solubility in EtOH unlike CuSO4) and in fact it works. It was tried for only one experiment, which did indeed produce an amine. However the amounts needed seem to be much greater than with the copper. In the future, gallium chlorides will be tried as well to activate the aluminum.

[Edited on 7-5-2014 by TheCopperMan]

[Edited on 7-5-2014 by TheCopperMan]

[Edited on 7-5-2014 by TheCopperMan]

DraconicAcid - 6-5-2014 at 20:34

I'd expect copper(II) chloride to be a bit more soluble in alcohol than the sulphate- perhaps that would work.

I'm not much into organic chemistry; would this work for reducing aldehydes to alcohols?

Chemosynthesis - 6-5-2014 at 23:41

Quote: Originally posted by DraconicAcid

I'm not much into organic chemistry; would this work for reducing aldehydes to alcohols?

I would expect it to as Al/Hg can produce alcohols and pinacols from aldehydes and ketones, respectively.

TheCopperMan - 7-5-2014 at 00:41

Quote: Originally posted by DraconicAcid

I'd expect copper(II) chloride to be a bit more soluble in alcohol than the sulphate- perhaps that would work.

I'm not much into organic chemistry; would this work for reducing aldehydes to alcohols?

The CuSO4 and NaCl already produces copper chlorides though. Unsure if it produces just [CuCl4]2- or also CuCl3- and CuCl2. It seems these complexes exist in an equilibrum according to:

CuCl2 + Cl− <--> CuCl3-
CuCl2 + 2Cl- <--> [CuCl4]2-
Source

Unsure of the solubility of CuCl3- and [CuCl4]2- in alcohol, but it seems these are formed either way also when using just CuCl2 instead of CuSO4 and NaCl.

Copper(II) chloride would still be the best choice, at least for reductive aminations, because the less salts in solution the better or methylamine might get salted out.

Nicodem - 7-5-2014 at 05:49

Quote: Originally posted by Chemosynthesis

Quote: Originally posted by DraconicAcid

I'm not much into organic chemistry; would this work for reducing aldehydes to alcohols?

I would expect it to as Al/Hg can produce alcohols and pinacols from aldehydes and ketones, respectively.

Aluminum amalgam has been used sporadically to reduce aldehydes and ketones, but it has a relatively narrow scope. Many ketones are quite inert toward it while some give almost exclusively the pinacol coupling product.
A good study on this topic is DOI: 10.1016/S0040-4039(00)80139-2. It was found that simple aliphatic ketones do not reduce significantly (only few % conversions), while 4-7 membered cycloaliphatic ketones do reduce as long as there is no significant steric hindrance at the carbonyl group. Unhindered cyclohexanones are reduced with best yields. Aromatic ketones and benzaldehydes give pinacols only and in excellent yields. One aliphatic aldehyde was tried (n-heptanal) and it reduced with only 20% yield.

Of course, it would be a nice scientific contribution, if someone applied this Al-Cu system on ketones or aldehydes. It might be quite suitable for pinacol couplings.

I should add that all this is quite new and not yet described in the scientific literature - an excellent achievement by the amateur chemistry community and is now becoming a combined Hyperlab-Sciencemadness effort.

Chemosynthesis - 7-5-2014 at 11:05

Quote: Originally posted by Nicodem

I should add that all this is quite new and not yet described in the scientific literature - an excellent achievement by the amateur chemistry community and is now becoming a combined Hyperlab-Sciencemadness effort.

Really fascinating. If anyone has spare time and interest, they may track down citations 82-84 of Organic Electrochemistry, Fourth Edition edited by Ole Hammerich and Henning Lund, page 1161. They appear relevant.
It was reviewed here: J. Am. Chem. Soc., 2001, 123 (36), pp 8880–8880 DOI: 10.1021/ja015214a

Jesse Pinkman - 11-5-2014 at 14:42

Perhaps using this method one can produce aluminium isopropoxide for the Meerwein-Ponndorf-Verley reduction from the activated aluminium and isopropanol. CuCl2 can be used instead CuSO4+NaCl and is more soluble in alcohols.

Dan Vizine - 12-5-2014 at 12:48

Quote: Originally posted by Chemosynthesis

Quote: Originally posted by blogfast25

By nitrostyrene, must we understand 2-nitrovinylbenzene?

I had the same thought. Then I looked at the number of posts and saw only 5 and all about the same thing. Interesting. Didn't the beta-nitrostyrene reduction and the nitromethane to methylamine reduction in the same post seem funny? Once you have the beta nitrostyrene you don't need MeNH2 unless you were going to go back to phenylacetone (from the styrene) first? Of course, depends if you want the monomethyl or are happy with the plain amine. Or, just maybe he is after various substituted phenethylamines? Maybe he's the new Shulgin? There's talent there for sure.

[Edited on 12-5-2014 by Dan Vizine]

TheCopperMan - 12-5-2014 at 16:20

A little update, the same exact reaction was ran as in the original post, but this time using 1.5g CuCl2 instead. That was the only changing variable. It gave the exact same results as with the 10g CuSO4 and 20g NaCl, in fact it seemed to react even more vigorous and Al dissolved more easily. It's possible the amount of CuCl2 can be reduced even further. Note that this has only been tried for one reaction, but so far yields are the same as with the CuSO4 and NaCl. I see no reason why CuCl2 shouldn't produce the same results on all substrates.

CuCl2 also has very good alcohol solubility, so it's fully possible that one can use regular Al/Hg solvent ratios and writeups, and in them, simply just substitute CuCl2 for HgCl2 and get the same results.

[Edited on 13-5-2014 by TheCopperMan]

[Edited on 13-5-2014 by TheCopperMan]

kmno4 - 13-5-2014 at 13:43

Something interesting to read:
Reductive Ring Cleavage of Nonconjugated Δ²-Isoxazolines to β-Hydroxy Ketones with Aluminum and Copper(II) Chloride
Very a propos

Attachment: s-0031-1290310.pdf (103kB)
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blogfast25 - 14-5-2014 at 04:58

Would this system (Al/Cu) stand even the remotest chance of reducing phenol to benzene? My guess, based on the bond strength of C-O, would be 'no'. In the Clemmensen reduction Zn/Hg reduces ketones to alkanes but the C=O bond is weaker than the C-O bond.

madscientist - 14-5-2014 at 07:47

Usually to do that you have to turn the phenol into an aryl triflate, oxidatively add it onto a metal, and throw a proton source at it.

Nice find kmno4. I'd like to point out (for those who only skim articles) that they randomly include two examples of reduction of nitroarenes at the end and report good yields.

This is a method that deserves further investigation. The biggest gap in the amateur chemist's arsenal has long been access to selective reducers, ones that won't convert nearby lakes into toxic dumps as mercury so easily can.

Have you tried running this reaction in neutral media, as they did in the SynLett posted by kmno4? (Or gradually adding AcOH merely to maintain acidic pH). Extractions are (obviously) easier with less AcOH to deal with. Might not be such a bad idea either to quench with aqueous ammonia, to displace any of your product that may be coordinating to copper and complicating extraction.

Quote: Originally posted by Jesse Pinkman

Perhaps using this method one can produce aluminium isopropoxide for the Meerwein-Ponndorf-Verley reduction from the activated aluminium and isopropanol. CuCl2 can be used instead CuSO4+NaCl and is more soluble in alcohols.

Definitely worth a shot.

Regarding CuCl2, this is trivial to prepare: CaCl2 is available in 50lb bags for melting ice, and CaSO4 is almost completely insoluble in water. Hence, all you have to do is mix equamolar quantities in aqueous solution and filter out the precipitate, and you will have a solution of CuCl2.

CuSO4 + CaCl2 ----> CuCl2 + CaSO4 (insoluble)

[Edited on 14-5-2014 by madscientist]

Burner - 14-5-2014 at 10:00

A bit off topic, but would the Al/Cu approach be an environmentally friendly method for generating LARGE quanties of H2 gas?

madscientist - 14-5-2014 at 10:32

Better than many of the alternatives, that's for sure. But don't let any copper salts go down the drain - they're rather toxic.

Aluminum sulfate is a lot less soluble in alcohols than aluminum chloride, so that's another possible answer to why chloride seems to be needed.

I'm not convinced aluminum is actually effecting the reduction directly - it may be, but there's reason to believe otherwise. I think it would be worth looking at a few other metals, such as cobalt and nickel - looking at the SI from the third reference below suggests they may prove to be superior. It's also worth considering running these reactions in straight alcohol, or even aprotic solvents such toluene with the alcoholic proton source being added gradually.

I'm wondering if an alternative reagent could be used to generate copper nanoparticles - maybe ascorbic acid would do the trick? It's certainly effective at generating copper colloids (which soon begin dumping out precipitate). And of course, it's probably worth trying Zn or Mg dust as well.

The first paper attached reports reduction of a lot of functional groups with Cu(II) + NaBH4 systems that don't occur easily with NaBH4 alone. Hence my thoughts on this matter. Nitriles, esters, nitro groups can all be reduced (they make phenethylamine, for example). Amides seem to be inert.

Highly Chemoselective Reduction of Aromatic Nitro Compounds by Copper Nanoparticles/Ammonium Formate
A highly chemoselective reduction of aromatic nitro compounds to the corresponding amino derivatives has been achieved by a combination of copper nanoparticles and ammonium formate in ethylene glycol at 120 °C. The reductions are successfully carried out in presence of a wide variety of other reducible functional groups in the molecule, such as Cl, I, OCH2Ph, NHCH2Ph, COR, COOR, CN, etc. The reactions are very clean and high yielding.
http://pubs.acs.org/doi/abs/10.1021/jo800863m?journalCode=jo...

Highly Chemo- and Regioselective Reduction of Aromatic Nitro Compounds Catalyzed by Recyclable Copper(II) as well as Cobalt(II) Phthalocyanines
Copper/cobalt phthalocyanines were established for the first time as catalysts for the very efficient chemo- and regioselective reduction of aromatic nitro compounds to generate the corresponding amines. The selective reduction of nitro compounds was observed in the presence of a large range of functional groups such as aldehyde, keto, acid, amide, ester, halogen, lactone, nitrile and heterocyclic functional groups. Furthermore, the present method was found to be highly regioselective towards the reduction of aromatic dinitro compounds in a short time with high yields. In most of the cases the conversion and selectivity were >99% as monitored by GC-MS. The reduction mechanism was elucidated by UV-vis and electrospray ionization quadrupole time-of-flight tandem mass spectrometry.
http://onlinelibrary.wiley.com/doi/10.1002/adsc.201000191/ab...

Room-Temperature Chemoselective Reduction of Nitro Groups Using Non-noble Metal Nanocatalysts in Water
Purely aqueous-phase chemoselective reduction of a wide range of aromatic and aliphatic nitro substrates to the respective amines has been achieved in the presence of inexpensive Ni and Co metal nanocatalysts, with a high tolerance to other highly reducible groups present in close proximity to the targeted nitro groups, using hydrous hydrazine as a reducing agent at room temperature.
http://pubs.acs.org/doi/abs/10.1021/ic402674z

Preparation of fine Ni powders from nickel hydrazine complex
Fine nickel powders with narrow size distribution have been prepared from the reduction of nickel hydrazine complexes in aqueous solution. The pure nickel hydrazine complexes, [Ni(N2H4)3]Cl2 were prepared with the molar ratio of N2H4/Ni2+ = 4.5, while a mixture of complexes, such as Ni(N2H4)2Cl2, [Ni(N2H4)3]Cl2, and [Ni(NH3)6]Cl2 were formed with N2H4/Ni2+ < 4.5. By the X-ray diffraction (XRD), FT-IR, and scanning electron microscopy (SEM) analyses, it was found that the reduction of Ni2+ to metallic Ni powder proceeded via the formation of nickel hydroxide which was reduced by hydrazine liberated from the ligand exchange reaction between the nickel hydrazine complex and NaOH. The standard deviation of the particle size decreased with the decreasing molar concentration of nickel hydrazine complex while the mean particle size increased. As the amount of hydrazine increased, the surface roughness of the particles was improved significantly due to the catalytic decomposition of the excess hydrazine at the surface of the nickel particle. It was found that average particle size could be controlled from 150 to 380 nm by adjusting the reaction molar ratio and temperature.
http://www.sciencedirect.com/science/article/pii/S0254058405...

Attachment: Reduction of Organic Compounds with Sodium Borohydride-Copper(II) Sulfate System.pdf (132kB)
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Attachment: Preparation of Copper Nanoparticles and Catalytic Properties for the Reduction of Aromatic Nitro Compounds.pdf (389kB)
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[Edited on 14-5-2014 by madscientist]

Burner - 14-5-2014 at 10:58

Quote: Originally posted by madscientist

Better than many of the alternatives, that's for sure. But don't let any copper salts go down the drain - they're rather toxic.

Yes, I realize that, but since it is not consumed in the rxn I felt that it could be (re)used until the Al(OH)3 slurry got pretty thick. It would sure beat the typical process of using strong base and would make it much safer for children to use.

Reductive amination

organichem - 15-5-2014 at 04:49

I tried a reductive Al/Cu amination like Al/Hg with a ketone and nitromethane at 25 mmol scale but received no amine (only evolution of MeNH₂ vapor when adding conc. NaOH)

Quote: Originally posted by madscientist

It's also worth considering running these reactions in straight alcohol, or even aprotic solvents such toluene with the alcoholic proton source being added gradually.

I suppose it's due to too much water (+ acid) in the reaction preventing effective imine formation. What about the HOAc?
Probably the reaction could be tried in anhydrous MeOH/EtOH/IPA (of course CuCl₂ has to be used then) and without any acid added (analogue Al/Hg)?

Another idea: why in general is a mixture of ketone/nitromethane added (with Al/Hg) - couldn't pre-formation of methylamine from nitromethane and subsequent addition of the carbonyl compound in alcohol give better conversion?

lullu - 15-5-2014 at 06:48

Quote:

why in general is a mixture of ketone/nitromethane added (with Al/Hg) - couldn't pre-formation of methylamine from nitromethane and subsequent addition of the carbonyl compound in alcohol give better conversion?

I guess using nitromethane is more an "to kill two birds with one stone"-approach.

I assume using methanol+methylamine and molsieves while forming the imine first and reduce it afterwards would give better results, although there are reports on formation of imines in water and isolating them in good yield.

EdMeese - 15-5-2014 at 13:53

Highly meso-Diastereoselective Pinacol Coupling of Aromatic Aldehydes Mediated by Al Powder/Copper Sulfate in Water

Yoshiharu Mitomaa, Iwao Hashimotob, Cristian Simionc*, Masashi Tashirod & Naoyoshi Egashiraa

Synthetic Communications. 2008, Vol. 38 Issue 19, p3243-3250.
http://www.tandfonline.com/doi/full/10.1080/0039791080211019...

nothing is new

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[Edited on 15-5-2014 by EdMeese]

RingoStarr - 15-5-2014 at 15:24

Quote: Originally posted by eidolonicaurum

Forgive my ignorance, and the noobishness of the question, but what is the purpose of the glacial acetic acid? I've seen it used before in reactions, but I can never understand its purpose. Is acting as a solvent? If so, why ethanol and glacial acetic acid?

I've often wondered the same thing but Nicodem has given a clue given here.

Quote: Originally posted by Nicodem

<snip>
In the reductions of nitrostyrenes with Hg activated aluminium, reducing the amount of Hg(MeCOO)₂ or other Hg salts (e.g., <15 mg / g Al) <snip>

Is this Hg/acetic acid "coupling" the reason acetic acid is needed?

madscientist - 16-5-2014 at 02:55

While cursing at some stubbornly slow reactions yesterday (that needed to be done the day before yesterday) I decided to dig into the inorganics cabinet and flail away.

It appears the counterion is important in ways beyond mere solubility.

CuCl2 (hydrate) and CuBr2 (anhydrous) both afforded rapid reaction with aluminum foil or aluminum powder in water or dry methanol. Cu(OAc)2, Cu(NO3

2, CuCl, CuI in MeOH had no effect on Al. CuF2 did, but was only tested in MeOH, where solubility was poor. Discoloration of shredded Al foil was noted after several hours.

Aqueous solutions of nickel chloride and cobalt chloride had no effect on Al foil.

CuCl2 in MeOH generated an amazing amount of hydrogen gas with Mg powder, while Zn dust afforded none - the solution simply turned colorless and Cu(0) dropped out of solution (though eventually it regained the copper color as, assumedly, atmospheric oxygen helped oxidize it and bring it back into solution - don't ask for details on how this would occur, because this is not my expertise

).

I also tried chucking a couple obvious reduction candidates at CuCl2 in MeOH, using either Al or Mg. At this point, I only have TLC results (I am one busy bee these days), but it appears Mg is not the way to go. Nitromethane, nitrobenzene, and 3,4-dimethoxyphenylacetonitrile were all exposed to these conditions - the reactions with nitrobenzene and Al powder were violently exothermic, and I returned from my desk to find a bit of a mess.

I also (very sloppily and hastily) prepared an imine condensed from benzylamine and benzaldehyde, and pitched it in - it's going to need GCMS data to sort out, but the crude NMR with Cu still hanging around (which will cause chemical shift drift - really, very low on time, hence the sloppiness) suggests some reduction occured, but it's not enough to justify popping champagne quite yet. I've been deceived before.

blogfast25 - 17-5-2014 at 06:27

Quote: Originally posted by madscientist

It appears the counterion is important in ways beyond mere solubility.

CuCl2 (hydrate) and CuBr2 (anhydrous) both afforded rapid reaction with aluminum foil or aluminum powder in water or dry methanol. Cu(OAc)2, Cu(NO3

2, [...]

Well, yes. That's what woelen found (see link in OP's first post). Interesting that you found the same activity with copper (II) bromide, though...

kmno4 - 18-5-2014 at 23:10

Quote: Originally posted by blogfast25

Quote: Originally posted by madscientist

2, [...]

Well, yes. That's what woelen found (see link in OP's first post). Interesting that you found the same activity with copper (II) bromide, though...

Yeah - I love these woelen's amateur descriptions:
....small pieces of household aluminium foil
...put some table salt
....add some water
....add a few drops
.....then a small amount of hydrochloric acid may be added, but not too much.

In general, it makes the experiment unreproducible, moreover addition of any acid leads to false conclusions.
Below my version of this experiment.
Mix (at r.t.) 3g of NaCl + 12g of H2O + 0,3g CuSO4x5H2O. It gives green solution. Add 70mg piece of Al foil (about 0,04 mm thick) and swirl all with glass rod.
Nothing interesting happens, Cu slowly precipitates as spongy brown-red deposit (especially on foil edges). Very tiny amount of H2 goes off from Al (and it lasts many hours - tested in one run).
One drop (~60 mg) of ~50% H2SO4 was added (it was at hand), It gave slightly faster H2 evolution, one more drop of conc HCl gave additional increase of H2, but still very slow.
Then additional 0,3g portion of CuSO4x5H2O was added - it caused more H2 evolution, another 0,3g - more H2, another 0,3g - more H2. Now H2 evolves quite violently. Cu deposit is now less spongy and more rose-coloured, the mixture becomes warm and deeply ("dirty" I would say) green. When more Al is added, reaction soon ends with colourless, milky (+Cu spong) solution.
When amount of Al is limited, reaction ends with deeply brown solution. I have seen seen such colours many times - clear indication of Cu(I) complex.
It also explains activity of Cl and Br anions and nonactivity of acatate, sulfate, nitrate... etc anions, because Cl or Br gives (relatively) stable and soluble complexes with Cu(I) in concentrated NaCl (or surely bromides also) solutions.
Clearly, mechnism of Al activation by Cu is more complex and most possibly includes Cu(I) species.

Continuing the off topic: Mg/methanol reducing system - unfortunately in German, old (1929) article from Annalen.
Über die Anwendung von Magnesium und Methylalkohol als Reduktionsmittel

Attachment: red_Mg.pdf (316kB)
This file has been downloaded 864 times

TheCopperMan - 19-5-2014 at 01:05

Quote: Originally posted by madscientist

Have you tried running this reaction in neutral media, as they did in the SynLett posted by kmno4? (Or gradually adding AcOH merely to maintain acidic pH). Extractions are (obviously) easier with less AcOH to deal with. Might not be such a bad idea either to quench with aqueous ammonia, to displace any of your product that may be coordinating to copper and complicating extraction

Actually yes it was tried without AcOH as well a couple of times, but the yield seem to come in a bit lower so it was given no further thoughts.

Quote: Originally posted by Burner

Quote: Originally posted by madscientist

Better than many of the alternatives, that's for sure. But don't let any copper salts go down the drain - they're rather toxic.

The copper salt does get used (not a catalyst) and at the very end of the reactions as all is poured out, one can observe solid copper particles in the bottom of the flask.

polsaer - 1-6-2014 at 06:59

To good to be true, but i gave it a run.
2,5 gr Al
50 ml water
2 gr phenyl-2-nitropropene
100 ml AcOH
1,5 gr CuCl2
Long story short - after workup i got 70mg of phenyl-2-aminopropane.
So it's waste of time/=

[Edited on 2-6-2014 by polsaer]

Crowfjord - 1-6-2014 at 16:34

So quick to discredit a method! It's good to be skeptical, but one run is scant evidence. Some reactions are finicky and need some fine adjustments an attention to detail to get to go properly. Did you forget to use alcohol as solvent, or did you just forget to mention it? I haven't worked with nitrostyrenes or phenyl nitropropenes before, but I doubt that they are appreciably soluble in water. I imagine that would put a big kink in things.

polsaer - 1-6-2014 at 23:13

They are soluble in AcOH for some extent, and Al/Hg works perfectly without using alcohol as a co-solvent.
There are posts on hyperlab about Al/Cu - also with unsatisfactory results.
It certainly works but personally i don't believe in 70% yields

P.S Maybe it works only on nitrostyrenes like Zn/Hcl.

[Edited on 2-6-2014 by polsaer]

madcedar - 2-6-2014 at 00:57

Quote: Originally posted by polsaer

...
There are posts on hyperlab about Al/Cu - also with unsatisfactory results.
...

Can someone with better Internet search skills than myself please post a link to the hyperlab thread.

Nicodem - 2-6-2014 at 09:58

In the Hyperlab post [540004] from 21. Sept. 2010, the member ruzer describes what is a method most similar to that reported by TheCopperMan. He reduces 2-(2,5-dimethoxyphenyl)nitroethene in a no less than about 70% yield (the exact yield cannot be determined because he did not analyse the crude product for purity, instead he derivatized the crude product as such).

All the previous attempts reported misserable yields or no isolated yield whatsoever. It is hard to say if this is due to the substrate used or due to the different method. In some reported failures, the inapropriate isolation might be the cause. Only few members at Hyperlab worked on this problem since the first mention in 2006 (see post [498996] and follow up) and very little progress was made before ruzer's report. The fact is, that if it were not for the lack of interest, the reduction method would have been well research till now.

PS: I find it interesting that the articles using this metal dissolving system appeared only after the initial 2007 publication at Sciencemadness, yet none of them cites it. Looks like those academic snobs refuse to cite us. If I weren't one of them I would spite at them!

madcedar - 2-6-2014 at 16:22

Nicodem, thank you for the references and above all, your commentary (as always).

polsaer - 3-6-2014 at 06:48

Somebody should try it on various phenyl-2-nitropropenes(plain, 2,5-, 3,4- e.t.c)
We clearly have not enough information.

TheCopperMan - 3-6-2014 at 11:05

Quote: Originally posted by polsaer

To good to be true, but i gave it a run.
2,5 gr Al
50 ml water
2 gr phenyl-2-nitropropene
100 ml AcOH
1,5 gr CuCl2
Long story short - after workup i got 70mg of phenyl-2-aminopropane.
So it's waste of time/=

[Edited on 2-6-2014 by polsaer]

Please try it as per the original writing. Use 300ml EtOH, 120ml water, 45ml or more GAA for every 20g styrene. Pre-heat it to 60C along with 15g Al, then add in the CuCl2 and it should start a vigorous reaction for 10+ minutes, then reflux for one hour under stirring and at the end, preferrably steam distill it in-situ. A lot of people (yes A LOT) mess up the solvent extractions one way or another.

Crowfjord - 3-6-2014 at 12:26

Well, my interest is sufficiently raised. I will see if I can form the nitrostyrene from vanillin, and give the reduction a try with that.

polsaer - 4-6-2014 at 01:05

Quote: Originally posted by TheCopperMan

All my p2np is gone now, can you try this reduction by yourself on nitroPROPENE? In my opinion it certainly works for nitrostyrenes, but propenes are matter for discuss.

Crowfjord - 6-6-2014 at 19:55

@TheCopperMan - when you say steam distill, do you mean external (live) steam with a steam generator, or internal steam distillation? My 3-methoxy-4-hydroxy-betanitrostyrene is crystallizing, so I should be able to try this method tomorrow.

TheCopperMan - 7-6-2014 at 10:44

@Crowfjord Steam distill it internally. Just add a bunch of water and heat it, re-add water occasionally, take readings of distillate coming over (PH or etc) to check when everything has been distilled out. Works like a charm.

@polsaer It works on nitropropenes. That is all that can be said. Re-try it as per the writeup, it will work.

Nicodem - 8-6-2014 at 02:26

Crowfjord, 3-methoxy-4-hydroxy-beta-nitrostyrene is a terribly bad choice for a model substrate. The corresponding reduction product will be very difficult to isolate. It's partition will require very efficient solvents (MeTHF, n-BuOH, etc.) otherwise it will not get extracted from water. You will also have to correct the pH to 8-9, but not more than that (the product is an acid as well as a base).
You would have done better to first alkylate vanillin with some easy to make or acquire (O-ethyl or anything higher would make the product nicely hydrophobic and easier to isolate).

Quote: Originally posted by TheCopperMan

@Crowfjord Steam distill it internally. Just add a bunch of water and heat it, re-add water occasionally, take readings of distillate coming over (PH or etc) to check when everything has been distilled out. Works like a charm.

It is not possible to steam distil compounds that are relatively well soluble in water unless they form an azeotrope with water.

Crowfjord - 8-6-2014 at 10:16

Good points, Nicodem. I did figure that it would be a bit of a challenge. I want to give it a try anyway, but maybe I'll see if I can methylate some vanillin to veratraldehyde as well, and go from there. Hmm, I wonder if the vanillin nitrostyrene can be O-alkylated in a facile manner?

Crowfjord - 9-6-2014 at 17:22

I would be stupid not to follow your advice, Nicodem. This weekend I will make some ethyl bromide to alkylate with, rather than the methyl. No need to aggravate myself working with gasses (though I'm getting the hang of it) just to verify a procedure, when a simpler solution is available.

(Please pardon the double post)

Nicodem - 10-6-2014 at 12:09

Quote: Originally posted by Crowfjord

I would be stupid not to follow your advice, Nicodem. This weekend I will make some ethyl bromide to alkylate with, rather than the methyl. No need to aggravate myself working with gasses (though I'm getting the hang of it) just to verify a procedure, when a simpler solution is available.

I'm not saying that 4-hydroxy-3-methoxy-beta-nitrostyrene is useless. If you had access to an HPLC then it might be just fine as a substrate (provided you had a column suitable for polar amines - not all work). However, for an amateur situation where you need to tediously isolate the product in order to do an optimization study, you would do better with a more suitable substrate. 3,4-Dimethoxy-beta-nitrostyrene might be OK, depending on the work up method and extraction solvent (it would not do well with toluene, but ethyl acetate after reaction mixture filtration, concentration, dilution and basification should be OK). Higher homologues 4-alkoxy-3-methoxy-beta-nitrostyrenes where the alkyl is ethyl, propyl, isopropyl, benzyl (etc.) would be best for a rudimentary setting as you are at least sure there are only insignificant losses during the isolation.

Ethyl bromide is quite volatile, but doable with a good condenser. If you have n-propanol it would be more practical to do the less volatile bromopropane. 2-Bromopropane from 2-propanol sounds attractive, but it is poorly reactive and O-isopropylation of vanillin would optimally require DMF or NMP as a solvent. Benzyl chloride from toluene is also very simple and reactive enough. It would also say something about a possible debenzylation issue under the reaction conditions (I don't really expect any, but it is good to verify this possibility).

pepsimax - 11-6-2014 at 09:01

I tried this, I wasn't expecting how vigorously it would react! A great deal of my ethanol was boiled away within seconds, my condenser was a crude home built job just to try this as it was dropped a few weeks back. I performed the reaction at half scale, it seemed to go well. Except the solvent loss. I would have expected to receive at least a 50% yeild. Should have left it at that but I added more substrate, more GAA, more ethanol, more Al and ended up with a 10% yield and a lot of polymerised crap.

I have no doubt that this reaction works and can be fine tuned to be one of the greats.

Few Q's, EtOH is expensive here and precious. Would any other alcohols work? Would adding the copper and salt solutions in portions slow it down a little? It's a little hard to keep everything together when it's reacting so hard.

IPA is cheap, as is MeOH. Would I be wasting my time using them? If not would simply distilled meths be ok, mostly ethanol I guess.

[Edited on 11-6-2014 by pepsimax]

Trying with IPA now. Reaction seemed to go ok, slightly less intense on addition of copper though. All the Al chunks have gone after 10 mins, I'll refulx for an hour and see what comes out.

[Edited on 11-6-2014 by pepsimax]

IPA : 0% yeild.

[Edited on 11-6-2014 by pepsimax]

TheCopperMan - 12-6-2014 at 18:27

A little update, this reaction was ran again with 10x scale, and this time it was used only 5g CuCl2 and it was heated to 60C initially. And despite using two Allihn condensers, both condensers actually clogged all the way up, that means condensed alcohol was escaping top of condensers and dripping everywhere. Pretty crazy and an extreme fire hazard, and not good for the heart either. Definitely recommend to use some serious high-powered condensers and icewater, this is no joke for sure.

It should be said that initially only 1-2g of the CuCl2 was added. But as nothing much happened and impatience set in, all the 5g of the CuCl2 was just dumped in. Maybe should have waited a bit more. Anyways there seems to be two ways to regulate the initial reaction. 1. regulate the initial temperature. 2. regulate amount of copper solution added.

@ pepsimax
MeOH has been tried and works as well. IPA has not been tried. For regulating reaction, see above points. Oh yes, and denaturated EtOH works well. Should have written that in the original post actually, but yeah, it works just fine.

EDIT:

Another possibility, is to regulate the sizes of the Al-bits. Maybe thicker Al-foil, or crunching it together rather than adding it in flat strips? Just thinking out loud.

[Edited on 13-6-2014 by TheCopperMan]

EDIT 2:
A little appeal. For anyone wanting to attempt this reaction, please do it exactly as per the initial writeup first. Then try any modifications after you get to know it. As already said, if done like that, it should produce more or less the same yield as an Al/Hg. And yes, extractions are a bitch. Many people screw it up. Do it on something that can be steam distilled. Just add NaOH, add water, and boil the water off. Then extract the water, or just add acid directly and boil it off in the open. No mercury worries. No need for pressure cookers. Steam distillation is easy , pure, simple and calming for the nerves instead of messing around with solvens, filtration, gahh...you get a headache just from thinking about it

[Edited on 13-6-2014 by TheCopperMan]

[Edited on 13-6-2014 by TheCopperMan]

[Edited on 13-6-2014 by TheCopperMan]

chemrox - 12-6-2014 at 20:02

Outstanding! sorry couldn't help myself

pepsimax - 14-6-2014 at 04:25

I checked my reaction with IPA and realised I hadn't based it properly - pH 8 (whoops)! Plenty of NaOH has just gone in and I'll update again. The alcohol layer was blood red though so I'm not expecting much.

pepsimax - 14-6-2014 at 11:24

Still nothing unfortunately. Could be crappy extraction because I can't steam distill it at the moment due to lack of still head but I doubt it'd be fruitful anyway.

polsaer - 14-6-2014 at 13:20

Kinda strange - why it is working with EtOH but not IPA?
Also what is the role of alcohol in this reaction? Al/Hg can be perfectly run without it.

pepsimax - 15-6-2014 at 06:26

Could have been dirty substrate, I didn't recrystallise it before use. Impure substrate can lead to a sharp drop in yield in other reactions. The first time I tried it my starting material was very pure, second not so much but would have been fine for general use. I shall up the purity and try again with IPA then report back.

pepsimax - 15-6-2014 at 06:46

Also i'm getting a lot of black powder in both reactions, copper oxide I presume? Is this normal? Seems to favour hanging around in the organic phase (hexane in my case) making extraction difficult - another reason for steam distillation. Lots of metallic copper particles too.

TheCopperMan - 15-6-2014 at 13:19

Yeah, there has sometimes been observed particles hanging around in the interface between organic/inorganic layer after reaction is over. Best tip is to use a minimal amount of CuCl2 to avoid copper creating any problems during extraction. As demonstrated above, 5g was enough for a reaction at 10x scale.

BTW pepsimax, could you post a detailed writeup of how the reaction was ran? Even with the EtOH instead of IPA, 10% is just way too low. When you say 10% yield, this is from the initial amount of substrate added, or the total amount added? (Since you say you added more afterwards)

[Edited on 15-6-2014 by TheCopperMan]

pepsimax - 15-6-2014 at 22:33

10% was from the total amount added the first reaction, around 22g. 10g was added to begin with and as it boiled off the alcohol, I added more of everything creating a big mess. As above I think it would have been around 50% if i'd just left it alone. From what I remember.. Half the EtOH, GAA, water and 7.5g thick Al foil folded as you said were added to a 2 neck 1ltr rbf. No overhead stirrer available so a very weighty egg shaped bar was added and set to 1000 rpm, enough turbulence to keep the foil under. 10g substrate was added and heated to excatly 60'c and held there stirring for 5-10 mins. In 2x 50ml flat bottom flasks the copper sulphate and salt solutions were prepared, again to half what you said, salt and water then added through a funnel in the second neck at the same time. Reaction kicked in, within 30 seconds a thick cloud of alcohol shot out the condenser but it looked good. Temp rose to about 93 and i'd lost most my solvent so panicked and added more ethanol and cooling. Everything looked well again so I stupidly added more of everything else hoping to obtain more product but in turn I just ruined what I had. IPA was run the same but without the boilover and extra additions. I'm going to try it with minimal copper chloride instead. Perhaps i'm using way to much sulphate, is it possible it's causing polymerisation like a strong acid could?

TheCopperMan - 16-6-2014 at 19:01

Some of the copper sulphate is prepared from H2SO4 and can have a very acidic effect. So best is probably to use CuCl2.

That being said, the reaction was once ran with 50g sulphate and 100g NaCl in an open beaker (as mentioned in original post), and even then yields were on par. So it's dubious that the copper sulphate will affect the reaction negatively.

Nontheless, would recommend to re-run it in denat. EtOH (not sure about IPA, never tried it), use CuCl2 just in case, make sure to avoid solvent escape during the reaction, reflux under stirring for 1 hour and make sure most Al is gone, then add NaOH and preferrably steam distill it out.

[Edited on 17-6-2014 by TheCopperMan]

pepsimax - 19-6-2014 at 11:06

Yeah, not in a hurry to try IPA again so waiting on more EtOH, reagent grade. Should be here soon, made a few hundred G's of copper chloride anyway. E- reagent EtOH is taking too long, distilling some purple denat now. Simple distillation is so damned slow! At least i'll end up with some pretty pyridine sulphate crystals to add to the pile.

2.5h later, 287ml...

Close

[Edited on 20-6-2014 by pepsimax]

[Edited on 20-6-2014 by pepsimax]

Ok, reaction run again. 20g, 300ml EtOH, 45 GAA, 15g thick foil folded as asked. Heated to exactly 60'c, 10g copper (ii) chloride and 20g table salt introduced through second neck.

A fantastic fireworks display ensued. T+10 seconds, Al strips are rapidly and very visibly 'rusting', huge deposits of copper are plating them - very exciting!

T + 15 seconds, everything is bubbling up rapidly. Uh oh, cooling needed.

T + 30 seconds, half the contents of the flask have shot out of the condenser and hit the ceiling over 4 foot above. The flask and condenser are shoved in a bucket of ice water and left to cool. The ice is quickly melted as the reaction stays above 75 but thankfully in the flask.

Over the next 10 mins as much of the mixture as possible is collected with a syringe and replaced in the main flask. A lot is lost. The stuff collected is oily and grey, seems to be multiple phases. It is not known whether this laborious task will be of any use to the total yeild collected which again isn't looking so good.

So from this I've learnt - copper chloride reacts much quicker and violently in EtOH than sulphate. My flask was probably too small. I used the 1 ltr RBF again, next size I have is 5ltr unfortunately. Should have run half scale again.

Either much less copper chloride should be used or less heating to begin with and shoved in the ice bath right before the addition.

Refluxing now, I'll boil off the alcohol then steam distil. I'll report back as always whether I get anything or not!

Good luck anyone who's going to try!

[Edited on 20-6-2014 by pepsimax]

pepsimax - 20-6-2014 at 07:02

All the Al has gone. It should be noted this particularly violent reaction could have been because of something in the quickly distilled purple methylated spirits, though unlikely. My first boilover was with reagent grade ethanol.

[Edited on 20-6-2014 by pepsimax]next attempt will be thick foil rolled into fairly tight balls and submerged in ice water immediately.

[Edited on 20-6-2014 by pepsimax]

kmno4 - 20-6-2014 at 11:01

↑
this is pure amateurishness. Why not to try this experiment with 1/5 or 1/10 amoutnt of reagents ?

pepsimax - 20-6-2014 at 11:36

Well, first things first I am an amateur. I'm posting excatly what I did in the hope others will not make the same mistakes and hopefully get some advice myself! Secondly i'm sticking to copper mans original procedure as close as possible as he asked. Isn't it the point to report results good or bad? I will scale down greatly the next few tries as it doesn't seem as simple as one imagined.

TheCopperMan - 20-6-2014 at 18:00

10g copper chloride and 20g table salt? Damn. That is a lot! Notice in the two posts that was made about using CuCl2, a very small amount was used only and still created a very vigorous reaction. As mentioned above, a 10x scale reaction was ran with only 5g CuCl2 and a nervous breakdown ensued. Would DEFINITELY not substitute 1:1 CuSO4 for CuCl2. The amounts of CuCl2 need to be much less. Sorry, should have written this more clearly.

Primarily there needs to be used less copper chloride, for 20g reaction only 1-2g should do. OR you could probably use the same amount you did, but then definitely the initial temperature needs to be lower, however not sure how low exactly. Or use thicker Al grit, again however, this has not be tried so can't really be helpful with how exactly this needs to be ran. But please, if you do it would be extremely interesting to see the results and a possible writeup! Currently have not access to Al grit so can't run it.

Oh yeah regarding the alcohol. The denat. alcohol used here at least contains MEK or something that is reduced to isobutanol. However it did never interfere with reaction.

[Edited on 21-6-2014 by TheCopperMan]

pepsimax - 21-6-2014 at 01:35

Ah my mistake, should have read that better. Finished the steam distil. I took the first 70mls off, there was a strange oil that sunk to the bottom. It appears to be chloroform by the vapours I accidentaly caught and there was a lot of product dissolved in it. The rest of the exected product remained floating on top of the water in the second jar with a few gloops of the presumed chloroform at the bottom. Not sure how any chloroform got in there, is it a common denaturant? When I boiled off the alcohol everything came off at 82 instead of 78 so there was some strange azeotrope, I left it running until nothing would come over at all. I'm quite confused by this "chloroform" or whatever it may be, I don't think i'll use anything other than reagent ethanol next time.

TheCopperMan - 21-6-2014 at 02:06

Chloroform? Hmm, that's weird. What exactly is the substrate you are reducing?

If you have access to it, pls check the MSDS for your denaturated alcohol and you could post the ingredient list here so we could see if there's anything that might disturb the reaction. But honestly don't see what that should be. Has tried numerous different denaturated EtOHs and they have all worked successfully.

Also possibility, the quick reaction rate caused some kind of decomposition. Although again, very unlikely unless the substrate you're using is super-sensitive.

Main tip though, re-run reaction w/ less CuCl2, maybe even lower initial temperature. From the experiences with CuCl2 as have been posted, would recommend start temperature of maybe 40 or 50C instead. For the CuSO4 can probably still use 60C.

[Edited on 21-6-2014 by TheCopperMan]

pepsimax - 21-6-2014 at 03:13

beta nitrostyrene to PEA. Here's the ingredient lest on the alcohol.

3. COMPOSITION/INFORMATION ON INGREDIENTS

INGREDIENT NAME CAS No CONTENT RISK PHRASE CLASS

Ethanol 64 – 17 – 5 90-93% R11 F
Methanol 67 – 56 – 1 5-10% R11, 23/24/25, 39/23/24/25 F,T
Pyridine 110 – 86 – 1 <1% R11, 20/21/22 F, Xn

I simply distilled it with a few drops of H2SO4 in there to turn the pyridine into a salt.

This chloro solvent must have been formed in situ, I can't see anywhere else where it would come from. Everything reeks of chlorine, the water, flasks etc. Some amine has definitely formed though, in what looks like an ok yeild. Due to potential toxicity of this unknown addition, I'm not going to try and refine it though to get a weight. It worked though definitely.

[Edited on 21-6-2014 by pepsimax]
On second thoughts perhaps it didn't work as intended if chloroform was formed, I might have produced a chlorinated version of PEA, who knows? Wish I had access to proper analysis equipment (and the the knowledge to use it

)

[Edited on 21-6-2014 by pepsimax]

TheCopperMan - 21-6-2014 at 04:24

Interesting, well, it's definitely not the denat EtOH.

PEA has been tried before and this has never been experienced. Only explanation seen is the excess heat and excess NaCl/CuCl2 messin something up.

If re-ran with less CuCl2 (1-2g per 20g) and/or a bit lower initial starting temp it should probably be better.

[Edited on 21-6-2014 by TheCopperMan]

pepsimax - 21-6-2014 at 05:16

Do you recommend still using the same amount of nacl with the copper? Ie 1g cu 20g na, or adjust accordingly?

TheCopperMan - 21-6-2014 at 06:09

Use only CuCl2...no NaCl is neccessary.

So only 1-2g CuCl2.

pepsimax - 21-6-2014 at 08:20

Ah, no salt. Thanks, perhaps that contributed to my 'chloroform'. I was looking at a prep for chloroform from ethanol using bleaching powder, I guess something similar must have happened in my flask. Thanks again copper man, although I haven't been entirely successful at least i've been entertained this last week or so ;-)

Crowfjord - 22-6-2014 at 09:02

Presence or formation of chloroform doesn't make sense to me, assuming you aren't leaving out anything important. But... How pure was the nitrostyrene? If there was a fair amount of benzaldehyde contamination, it could have been reduced to benzyl alcohol, which in turn may have been chlorinated to benzyl chloride. It has been a while since I had any benzyl chloride, but if I remember correctly, it smells vaguely "chloroformish."

Also, impure starting material would at least partially explain the low yields

pepsimax - 22-6-2014 at 13:36

Hey that makes absolute perfect sense, I think you're dead on there. The nitrostyrene was recrystalised but does still have the almond odour. The description on wiki matches.. war gas indeed. The stuff is incredibly harsh on the throat, that's why I presumed chloroform as i've never actually smelt it, just going by appearance and knockout stench, thanks!

[Edited on 22-6-2014 by pepsimax]

TheCopperMan - 22-6-2014 at 22:16

Benzyl chlorides main effect should be a massive amount of tears in your eyes. If you smell it, you should also tear up almost immediately. If not then it's something else. Have worked with it before and that was the first and last time. Need a full face mask to just be near it, and even then it can hydrolyze with sweat on your skin and cause burns which was also experienced. The stuff is vicious.

[Edited on 23-6-2014 by TheCopperMan]

pepsimax - 23-6-2014 at 05:11

Is benzyl chloride soluble in xylene? According to wiki it shouldn't be, where as this stuff is. I poured some in and the gloops quickly dissolved in it when swirled around. does anyone know the density of 4-chlorophenethylamine? Perhaps this is actually my free base oil and it's heavier than water and extremely stinky.

The xylene was separated and washed with sat NaOH then brine and dried with MgSO4. This was diluted a bit with acetone and 10% H2SO4 with IPA was dropped in and 13.4g of a sulphate salt was collected. that appears to be my yeild of this unknown compound!

[Edited on 23-6-2014 by pepsimax]

Ugh, I give up, apparently it is a dark solid.

[Edited on 23-6-2014 by pepsimax]

[Edited on 23-6-2014 by pepsimax]

TheCopperMan - 23-6-2014 at 06:39

Did you separate the other product from the steam distillate first, before you re-extracted it again with the Xylene? Or did you extract the entire water distillate only once with everything in it, then add the sulfate to get the salt? (in which case it'd be a mixture of unknown stuff, and phenetylamine)

[Edited on 23-6-2014 by TheCopperMan]

pepsimax - 23-6-2014 at 08:25

This was the gloopy stuff separated from the water distillate then put in fresh water to see if it sank again - it did, then dissolved in xylene. The water from the steam pull didn't seem to have anything in it, i'm not sure what the stuff floating on it was, it didn't salt out to anything. I could make the steam pull basic and try another solvent extraction, see what turns up

TheCopperMan - 23-6-2014 at 09:45

Hm, did you check the PH of the steam distillate?

Crypto - 27-6-2014 at 11:36

I tried to reduce nitromethane with Al/Cu today. I mixed 20ml of nitromethane with 50ml of IPA and 5ml of water. 1 gram of CuCl2 was dissolved in the mixture and 5 grams of pretty thick aluminum ribbon was dumped in. The reaction started after a minute and it was really slow. It took a faster pace after some heating was applied. Still, it was far from being vigorous. After about three hours no more action was observed. A lot of unreacted aluminum was still present. Unfortunately I could not smell any methylamine during or after the reaction.

Maybe I should try again with a proton donor present in the mix?

Or maybe I just could not smell it and should basify, separate the aluminum sludge, add acid and try to isolate the salt, to determine if the reaction occurred?

pepsimax - 29-6-2014 at 00:39

I didn't check the pH, too late now though as it has all been binned. I"ve found some aluminum swarf but it's pretty difficult to clean up. Washing in caustic solution seems the best way.

Crypto, try with foil and preheat your solution and that should help. I've run this twice with ipa and got zero yield both times, no idea why but it doesn't seem to work for me. Try ethanol maybe?

ChemicalCowboy84 - 29-6-2014 at 07:53

What about mixing a little gallium with the aluminum foil plus using the CuCl2

Burner - 29-6-2014 at 08:15

If you use the gallium you do not need the CuCl2.

ChemicalCowboy84 - 29-6-2014 at 09:00

So you think it would make the reaction run away ? I was just hypothesize that made it could help kick start the reaction with out the heating like a regular al/hg reaction ? I believe we have something great here

ChemicalCowboy84 - 29-6-2014 at 09:13

Also which CuCl2 should be used the anhydrous or dihydrate ?

pepsimax - 29-6-2014 at 09:41

Quote: Originally posted by Burner

If you use the gallium you do not need the CuCl2.

Have you got any experience with this? I've tried all sorts of attempts with gallium and never got anything whether it be gallium salts or alloys.

pepsimax - 29-6-2014 at 09:42

Quote: Originally posted by ChemicalCowboy84

Also which CuCl2 should be used the anhydrous or dihydrate ?

Doesn't matter you'll dissolve it in water anyway

TheCopperMan - 29-6-2014 at 09:53

Working on some gallium experiments now actually.

Gallium is awesome in that it allows complete control of reaction, because the amalgam is made beforehand and then added gradually into the reaction at a pace that you prefer.

The problem is, it's expensive, not all of it can be recycled (some dissolves), it's a pain in the ass to clean up the gallium post-reaction, and if you touch the amalgam, drop it on the floor or etc, it's a pain to remove the stains it leaves.

[Edited on 29-6-2014 by TheCopperMan]

Burner - 29-6-2014 at 10:33

Quote: Originally posted by pepsimax

Quote: Originally posted by Burner

If you use the gallium you do not need the CuCl2.

Have you got any experience with this? I've tried all sorts of attempts with gallium and never got anything whether it be gallium salts or alloys.

I have used gallium in place of mercury (mole for mole) and the reactions proceed quite similarly. I have not been able to recover the gallium easily, making this an expensive route for reductions.

Burner - 29-6-2014 at 10:35

Quote: Originally posted by TheCopperMan

Working on some gallium experiments now actually.

Gallium is awesome in that it allows complete control of reaction, because the amalgam is made beforehand and then added gradually into the reaction at a pace that you prefer.

The problem is, it's expensive, not all of it can be recycled (some dissolves), it's a pain in the ass to clean up the gallium post-reaction, and if you touch the amalgam, drop it on the floor or etc, it's a pain to remove the stains it leaves.

[Edited on 29-6-2014 by TheCopperMan]

I see someone else has explored this approach with similar results.

I do not recommend it, except for the learning experience, in which case it is excellent.

TheCopperMan - 29-6-2014 at 10:40

How much Ga did you use in place of mercury? Usually less than a gram mercury salt is used. Did you add it as a gallium salt or prepare amalgam beforehand?

pepsimax - 29-6-2014 at 11:11

Another run....

5g substrate, 75ml reagent EtOH, 4.5g Al (half strips like first post, half of the strips rolled into ball, 600mg copper chloride heated to 50c in a 500ml flask. Flask was dropped in cold water whilst stirring full throttle. Al dissolved after 20mins, temp rose to 73 and dropped slowly to 40 when the heat was turned on for gentle reflux. No nasty surprises this time. Just steaming it out now.

Gallium - are you using a salt? I made some gallium nitrate and that did nothing to foil when dropped in an aqueous solution of it, gallium chloride didn't do much either but I suspect I made that wrong (just dissolved the nitrate in hcl and evaporated)

[Edited on 29-6-2014 by pepsimax]

Burner - 29-6-2014 at 12:57

Quote: Originally posted by TheCopperMan

How much Ga did you use in place of mercury? Usually less than a gram mercury salt is used. Did you add it as a gallium salt or prepare amalgam beforehand?

I used the gallium metal and prepared the aluminum amalgam using some aluminum shot that I had. I then let it sit overnight before I used it. Quite simple really.

Burner - 29-6-2014 at 12:59

Quote: Originally posted by pepsimax

Gallium - are you using a salt? I made some gallium nitrate and that did nothing to foil when dropped in an aqueous solution of it, gallium chloride didn't do much either but I suspect I made that wrong (just dissolved the nitrate in hcl and evaporated)

[Edited on 29-6-2014 by pepsimax]

I used the metal, not the salt.

polsaer - 2-7-2014 at 12:47

So, nobody have tried it on nitropropenes?
And why it working in EtOH, but not in IPA?

Scr0t - 2-7-2014 at 13:00

Quote: Originally posted by polsaer

So, nobody have tried it on nitropropenes?
And why it working in EtOH, but not in IPA?

Probably some kind of solubility issue. I experienced something similar when attempting to reductively aminate cyclohexanone with aqueous NH3 and a Zn-Ni couple. Best yields were with EtOH but were horrible with IPA.

My own attempts to get GaCl3 to react with Al foil failed but then I read a reference (maybe from these boards) that applied an electrostatic potential to get a Ga salt to alloy.

[Edited on 2-7-2014 by Scr0t]

pepsimax - 25-7-2014 at 23:33

Been thinking, would this system run much smoother on nitrostyrene if the carbon carbon double bond was reduced with na borohydride first? Or is this essential and I've missed this!

TheCopperMan - 11-8-2014 at 08:45

NaBH4 was never used, so it should perform without it.

BTW what was the result of the steam distillation? If you check the PH of the distillate, it should be basic indicating amine. You can then add acid and evaporate the water to get the salt. Did you try this?

crystal - 12-8-2014 at 13:09

TheCopperMan, any attempts with gallium salts already? Gallium metal has been used before, and definitely works. As for the stains and recovery, I recommend using dilute HCl. It makes gallium form blobs that are easy to separate.

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