Final Word on the HI/RP Mechanism

[Rhodium]

Regenerative role of the red phosphorus in the couple 'Hydriodic Acid-Red Phosphorus'

J. Organomet. Chem. 529, 295-299 (1997)

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/hi-rp.mechanism.html)

[halfkast]

whoa would you look at that
thats so beautiful, I'm pretty sure I don't have the mind at present to appreciate it and the rationale fully.

but I do know it's beautiful and something special.

wow again.

you must bee happy with that Rh, you don't come across as someone who likes uncertainties. So have you learnt anything from this reference for yourself or is it confirming your past beliefs?

WizardX are you going to make this your wallpaper for a while?

it's a beauty.

[WizardX]

I disagree with the term, "catalytic cycle".

[Osmium]

Funny, no PH3 mentioned on the left, "wet" scheme.

[Rhodium]

I disagree with the term, "catalytic cycle".

Why? It is certainly a cycle for the production of hydrogen and phosphoric acid from red P and water, the cycle being catalytic in iodine.

you must bee happy with that Rh, you don't come across as someone who likes uncertainties. So have you learnt anything from this reference for yourself or is it confirming your past beliefs?

Yes, I'm very happy with finding this article, as finally I have hard data to point to whenever someone posts any misinformation again, as well as the article itself being full of useful things.

New things I've learned myself is that formation of toxic phosphine gas is unavoidable when insufficient water is present (and as phosphine self-ignites in air, this is thus the culprit of all "flask fires"), and that P₂I₄ can be an intermediate, rather than PI₃.

[BOS]

Thats lovely and all,But what kind of pretty paterns does one
get when ephedrine is bought into the equation?
What bearing would this have on how one would determine if someone is presenting misinformation ,following this scheme?

[mr_pyrex]

Well I would like to say THANKS as well, cause it was just the last weekend I was sitting around rehashing old theories and ideas and trying to figure out the exact way by which the "dry setup" or push/pull runs its course.  Reason being is I was reading the posts from back around January or at least a recent link you had in a post that referred back to when you discussed using Phosphorus Acid in place of Red and using HI instead of using the push/pull setup and was trying to figure out if there might be a benefit in doing a push/pull setup with a condensor on top of the reaction vessel and then the push/pull setup coming off the condensor.  Reason is I figured that if push pull works good even when it is slowly but progressively dumping the HI into the tanks wouldn't it be a good idea to keep the continually being made, high concentration HI in the pot and thereby maybe have it run more efficiently and end up with a better end product.  I haven't figured out exactly the details yet but will be in the near future...and once again thanks for the very useful info Rhodium.  Pyrex out of theories

[WizardX]

Red Phosphorus involvement in a catalytic cycle for the generation of hydriodic acid in ...

This can be interpreted that Red Phosphorus has a catalyst mechanism.

It would be better if it was written maybe like this.

Red Phosphorus involvement in a reactant cycle for the generation of hydriodic acid in ...

An iodide ion I- acts as a catalyst on the catalytic decomposition of H2O2.

H2O2 ==[ I- ]==> H2O + 1/2 O2

[Rhodium]

BOS: Very simplistic, one could say that the hydrogen (H₂) given off in the above depicted cycle reacts with (pseudo)ephedrine forming methamphetamine and water.

More detailed:

1. (pseudo)Ephedrine + HI -> Iodoephedrine + H₂O
2. Iodoephedrine + HI -> Methamphetamine + I₂

Overall: (pseudo)Ephedrine + 2 HI -> Methamphetamine + I₂ + H₂O

[Osmium]

> Very simplistic, one could say that the hydrogen (H2) given off in the above
> depicted cycle reacts with (pseudo)ephedrine forming methamphetamine and water.

That's of course VERY simplistic, since bubbling H2 through a pseudo or ephedrine solution will of course NOT produce meth. Just thought I'd say that before someone starts a new urban legend.

[bloosh]

[BOS]

Sure,But doesnt such a simplification follow along the lines of RP + I + H20 = HI?
And nothing else realy matters?

I find it hard to accept that all of these rxns can occur
and yet only the H and the I from the formed HI have any bearing on what happens to the ephedrine e.g forming the intermediate iodo-compounds and then the reduction itself.
If this was the case, what would be the reasoning behind such a sluggish,low yielding rxn when a only massive excess of premade HI is used (no regenerative agent) as aposed to it being formed in situ?

Are we now saying that the wet rxn and the dry rxn both
follow the same mechanism in regards to reducing ephedrine
e.g follow your statement above?
If so,what makes one better then the other,seeing as it is only a matter of HI production that counts,and that by accounting for enough reactants ,both schemes will produce HI and a full reduction should occur no matter what.

I see no mention of PI3,no mention of iodic or periodic acids and many other inorganic by-products or side rxns which I have read about in relation to these rxns.

Why do we have to accept such a simplistic version of events when it comes to using these schemes in a reduction.

I have no problem with what your find tells us,but to me it merely points out an order of rxns which have been common knowledge all along.
I feel the real issue is how such proceedings,effect the rate/degree/by-products of the halogenation and reduction of organic compounds,and that the simplistic reasoning you have used above with the old HI + Ephedrine = Water and meth quote, is how the abundance of misinformation/misinterpritation has come about.

It is obviously not so simple is it?

Rhod` Im sorry if I sound belligerent.
I dont want to seem like I know the answers.
It just frustrates me so much, when I have personally sought
a simple explination for the myriad of different results we encounter when talking about this rxn, and all I ever seem to get back is this simplification, which would be lovely if it was so simple(I simply dump my ephedrine in a bucket of hydriodic acid and be done ),but if translated to real world findings leaves a whole lot more blanks than the reasoning behind the regenerative role of Phosphorus in HI production could ever dream of leaving.

Surely you have a paper or simular,depicting these rxns in as much detail as the one above.This would be nice.
All the lit` I have scanned pretty much pumps out the same chemical equations and leavs it at that.


End rant.

[Rhodium]

If this was the case, what would be the reasoning behind such a sluggish,low yielding rxn when a only massive excess of premade HI is used (no regenerative agent) as aposed to it being formed in situ?

How massive an excess of HI has been tested under controlled conditions?

The concentration is very important, if the HI concentration drops below 50% the reaction grinds to a halt (ref:

Post 344019 (missing)

(foxy2: "US Pat 5516960", Stimulants)), and it is easily extrapolated that the higher the concentration, the faster the reaction (up to a certain point, where byproducts may form instead, due to elimination/hydrolysis to form P2P, followed by a cascade of other reactions, see the links below).

If so,what makes one better then the other,seeing as it is only a matter of HI production that counts,and that by accounting for enough reactants ,both schemes will produce HI and a full reduction should occur no matter what.

A very important factor is temperature control. Without acetic acid, water or toluene as solvent, localized hot-spots may easily form and high temp leads to byproduct formation.

Why do we have to accept such a simplistic version of events when it comes to using these schemes in a reduction.

Because beyond this, we lack hard facts and we have only idle speculation without proofs. Also, this model explains the majority of observed events pretty good, and at the moment there is no competing model.

I have no problem with what your find tells us,but to me it merely points out an order of rxns which have been common knowledge all along.

By those in the know, yes, but many people have also been refusing to accept even this simple theory, for example by claiming that RP is a catalyst rather than a reactant.

I feel the real issue is how such proceedings,effect the rate/degree/by-products of the halogenation and reduction of organic compounds

That is also a very important aspect of the reaction when applied to real-world reductions. That is however discussed in other articles, and is not the main topic of the article I posted, which is mainly focused on the interaction of Iodine, Hydriodic acid and phosphorous-based regeneration agents.

Suggested reading:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/meth.hi-p.impurities.html

https://www.thevespiary.org/rhodium/Rhodium/chemistry/meth.forensic.html

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

[Chewbacca]

"the hydrogen (H2) given off in the above depicted cycle reacts with (pseudo)ephedrine forming methamphetamine and water"

"bubbling H2 through a pseudo or ephedrine solution will of course NOT produce meth"

why is it that the H2 produced from the reaction b/w I2 and P4 in the HI reaction mechanism will reduce (pseudo)ephedrine to methamphetamine whilst exposing the same (pseudo)ephedrine to the same H2 molecules will not? is it that the (pseudo)ephedrine must be converted to an iodo intermediate before the H2 will reduce it?

[Rhodium]

why is it that the H2 produced from the reaction b/w I2 and P4 in the HI reaction mechanism will reduce (pseudo)ephedrine to methamphetamine whilst exposing the same (pseudo)ephedrine to the same H2 molecules will not?

The H₂ shown in the mechanistic schemes above is only evolved as hydrogen gas at higher temperatures without any reducible substrate present (like iodoephedrine). When there is, the mechanism is slightly different, the HI and iodoephedrine more or less reacting directly with each other (possibly by a radical mechanism) forming I₂ and methamphetamine.

Therefore, the H₂ is not to be taken literally, but rather seen as an entity available for reducing a substrate (this is obvious if you bother to read the entire article).

[Organikum]

"impurities through higher HI concentrations" - thats nowhere in the references and plain nonsense.
Impurities by free I2 - yes.


The whole thread is just not on the point as it answers no open questions on the reaction. WHY must the concentration be higher as XXX? (the answer is in the hydrates of HI -> Gmelin) Why takes HI so much longer as PI3 to halogenate a benyzlic alcohol? (HI halogenation is reversible - a equilibrium forms similar to esterifications -> Gattermann Wieland).

The industry in the old times used fuming HI plus some phosphorus in pressure vessels. They did this for sure not to maximise byproducts and impurities.

Fuming HI and pressure vessels are not appropriate now and here.

But in the days of safrole bromination Uncle Fester presented a way how to make 48%HBr aqueous work. By dehydrating the HBr with HCl-gas bubbled into the reaction. (confirmed by Ritter)
This works perfect with HI also.
(confirmed by me)
Dehydrate the HI by HCl - fast and complete iodination takes place - the reduction is cake, this is well known. HI reduces iodoephedrine quick and complete in (almost)any concentration. The reduction is well known to be far predominant.(Skinner)


hey, some real answers and an advice how to bring this to real world!




I accept any rating except the insulting "Good Idea"
delete the post instead.

ORG


PS: the ratios from the synths from Rhodiums page where the authors boast with 100% yield PRODUCE ALL AN HI SPITTING VOLCANO! Read it. Try it. Enjoy.

[Rhodium]

"impurities through higher HI concentrations" - thats nowhere in the references and plain nonsense.

It is because that article did not deal with vicinal amino alcohols as substrates. My references are these:

Acid Hydrolysis of Ephedrine Derivatives to P2P

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#ephedrine)

Profiling of impurities in illicit methamphetamine by HPLC

(https://www.thevespiary.org/rhodium/Rhodium/pdf/meth.impurity.profiling.pdf)

Investigations of the Impurities Found in Methamphetamine Synthesized from Pseudoephedrine by Reduction with Hydriodic Acid and Red Phosphorus

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/meth.hi-p.impurities.html)

Impurities by free I2 - yes.

Refs please (out of interest, not disbelief).

The industry in the old times used fuming HI plus some phosphorus in pressure vessels.

For the reduction of vicinal amino alcohols?

the ratios from the synths from Rhodiums page where the authors boast with 100% yield PRODUCE ALL AN HI SPITTING VOLCANO! Read it. Try it.

Could you specify where this is written so that I can re-evaluate it? This synth will never be quantitative.

[Organikum]

Old days industry reduced with fuming pressurized HI everything with a HO group and most with an oxygene including ether cleavage.
Was for some time the universal hammer of some kind....

By dehydrating the HI with HCl-gas, the HI can be hold in a hydrated stage of the 1,71 density acid or preferable slightly above this point (this would be nearly fuming so no HCl would fume anyways) with ease and almost only HCl will escape. Temperatures may as low as 50°C to 60°C (so in advance prepared HI is used) the HCl also provides the agitation. Reaction time 4 to 6 hours. Yields up to quantitative.
This say I.
 
Are ya all blind methcooks or has Geezmeister first to certify this in not less than 4000 words? (hey Geez, peace, a joke a joke this is!)

Rhodium the ratios I refered to by the fuming volcano werer taken from the two H3PO2 pdfs on your page (from memory: 4mmol substrate, 4mmol iodine, called catalyst, shit, 16 or more mol 50percnt H3PO2 all in GAA - 100percent yield - ho! try! fumes! and not only a lil fuming - no.)

I am still onlinecrippeled, I beg for excuse not to link this stuff.
I will reread the refs posted by you Rhodium but I stand to my post before in principle. Of course can you get overreduction by fuming 1,96 density HI pressurized at high temps for example.
You can also lower temperatures and stop after 10minutes.
The time factor was important in those days long gone as such a fast reaction made it possible to run one complete reaction including prep and workup on one working-day 12 to 14 hours.
Not being pressed by such economic forces the pressure may stay history as HCl dehydration does the same in just a lil. more time.

REMARK:
if you are new to chemical engineering - I talk engineering not chemistry - dont think on using density 1,96 fuming HI under pressure. First you wont be able to prepare it and second you will hurt - hopefully yourself and nobody else.
No, thats not exactly what a pressurecooker was made for.


Hey Rhodium! Dont get dogmatic in your young days already, there is enough time left when you get older!
Realy, you want: low temperature, high HI concentration and aa not to long reaction time over all.
The last simply, because if I heat almost any organic compound long enough in the presence of strong HI I will get some uncalculable reactions, thats in the nature of HI I guess, we shouldnt blame it for being this way, ok?

Somebody starts thinking and talking on the hydrates of HI and the salt formed with the amine (what I forgot to mention before) and the influence of this on the reaction, and ratios to use - or why stochiometry is not exactly what we want and need here - some call iodine a catalyst only - heresy?

[Rhodium]

Yields up to quantitative. This say I.
 
Are ya all blind methcooks or has Geezmeister first to certify this in not less than 4000 words?

Well, it has probably a lot to do with a general cynism against novel ideas which has not been backed up by references, or at least a credible-looking writeup from the person advertising it. There has been too many instances in the past where people have gotten "great ideas" which did not work at all in practice, so due to too many failures people nowadays demand some kind of proof that it really works, and that one person simply say it does is not enough.

Rhodium the ratios I refered to by the fuming volcano werer taken from the two H3PO2 pdfs on your page (from memory: 4mmol substrate, 4mmol iodine, called catalyst, shit, 16 or more mol 50percnt H3PO2 all in GAA - 100percent yield - ho! try! fumes! and not only a lil fuming - no.)

You are probably talking about

https://www.thevespiary.org/rhodium/Rhodium/excellent.ideas/

The volcano effect, did it occur at the scale used by the original authors (4 mmol) or the one in my suggestion (20 mmol)? In any way, this should be possible to eliminate by the use of more solvent, slower hypo addition, or more efficient stirring.

[Organikum]

I wasnt referring to your "...ideas" but to the two pdfs you have on your server which talk on H3PO2 reactions. I am no coward - if I mean you I tell this, ok?

Actually I cannot find the information on impurities by high HI concentration in the references you provided - the forensic ones are also suspicious per se - or do you you think they provide correct ratios for cookie cookie?

I have provided refs to every point.
I wont provide an US-childrensbedroom methmaking writeup for 8 years old. (thats not addressed to you Geez ok?) Tell me what information you need to be able to bubble HCl into a reaction at 60°C. And I will tell you why I wont give this information to you.

Try it or leave it, but dont fuck around with me.
This is no idea of mine but basic chemistry. Answer with chemistry and not with throwing dirt and cheapo tricks. Of course ppl must be careful - at least when trying your stuff from TSII. But I am not you.

Obviously I am really the only one who has read the references.

Anotherone:
Hydriodic acid may be prepared by the action of iodine on stannic or stannous salts.
Huh?
Tin + conc. HCl(excess) + iodine = HI
says Gmelin.


I apologize for the harsh tone - but could anyone come over with FACTS?

[Rhodium]

no Rhodium - H3PO2 not H3PO3

I wasnt referring to your "...ideas" but to the two pdfs you have on your server which talk on H3PO2 reactions. I am no coward - if I mean you I tell this, ok?

Huh? On the page

https://www.thevespiary.org/rhodium/Rhodium/excellent.ideas/index.html

two PDF files are linked, namely these two:

https://www.thevespiary.org/rhodium/Rhodium/excellent.ideas/h3po2.i2.reduction-1.pdf

https://www.thevespiary.org/rhodium/Rhodium/excellent.ideas/h3po2.i2.reduction-2.pdf

The only thing discussed on that page is the Hypophosphorous acid–Iodine reducing system published in Tet. Lett. 2-3 years ago, and my only effort was to read those two docs and adapt their techniques for use with (pseudo)ephedrine instead of boring benzhydrols.

Actually I cannot find the information on impurities by high HI concentration in the references you provided - the forensic ones are also suspicious per se - or do you you think they provide correct ratios for cookie cookie?

If you check the GC outputs from each and every of those forensic articles, you can see that the main product very often is not methamphetamine, but rather phenylacetone (+ condensation products of that compound), especially in the reference where they analyze the remnants of a "dry reduction" (= high acid concentration, high temperature).

If you then on the other hand take a look at the german patents for the production of phenylacetone from ephedrine alkaloids, you see the same general trend - hydrolysis of ephedrine and its derivatives to the corresponding imine, and in the end phenylacetone from that - that reaction is favored by strong acid and high temperatures.

There is no need to believe the ratios published by the forensic chemists, as they have probably not made any effort towards optimizing the reaction even if they are telling the truth - the main point is to look at the product distibution in their spectra - as they have probably not drawn them by hand, those can be regarded as autenthig data.

I have provided refs to every point.

Except what I have been asking all the time - in what piece of literature can I find a high-yielding reduction of a vicinal amino alcohol to the hydrocarbon where stronger acid than the constant-boiling 57% HI is used (with or without recyclants).

Tell me what information you need to be able to bubble HCl into a reaction at 60°C.

That sentence is enough if taken as instructions, what I felt your description lacked was rather a compelling reason why anyone would go through the trouble of performing the experiment you suggested, as this far we have nothing but your word on that it is a "great modification" to the standard procedure. You have not provided any literature references, nor have you described a controlled trial where you tell us what the return is from the increased effort in terms of absolute yields, reaction times, product purity etc... Only that you describe your variation as "better".

[gluecifer69]

This may bee slightly off topic, but Gluecifer an't fraid of a some bad karma.

Gluecifers point is this, this is the greatest thread I have had the pleasure of learning alot of new info from!

Please Rhodium and Organkium, you are the two (in Glueys opinion in his reads on this site for the past year and Rhodium's for the past three) greatist minds in the hive and please don't get agressive Gluecifer senses that both Rh and Org should keep up the great info exchange, but back off on the personal emotions.

[Organikum]

For the flowers first and for the hint which is right on the point.

So I apologize explicitely for the "below the belt" expressions in my last post, also I was highly pissed - and not without reason - it was unnecessary.
I hope Rhodium you will accept my excuse on this.

Back on topic:
- Rhodium, high HI concentrations AND high temperatures, you name it by yourself. Whereby the high HI concentration is necessary for the reaction and concentrations on the edge of workability lead to unnecessary prolonged reactiontimes which also must lead to byproducts by the timefactor alone, the temperatures are the point you can move something.
- By reading the Gmelin and the old threads on safrole bromination you will find in the end some similarities:
- 48percent aqueous HBr is hardly able to brominate safrole 
- HI with less than 50percent is not able to iodinate ephedrine - you tell this
A working solution was found by Fester, Ritter confirmed it several times:
Dehydration of the HBr by gaseous HCl. As dehydration works the problem will be related to the hydrates formed by HBr as HI. For the HI hydrates see the Gmelin.

There is some logic in this.
I thought.
I tried.
And the proof is in the pudding.

The dehydration fights also another probable problem, which I guess to exist but here I have no direct proof: I believe a part of the the HI is trapped as salt on the aminegroup - a equilibrium with the HCl salt form may be formed. But thats a guess.

I also tried a reaction after the old german reference using a catalytic amount of iodine (10percent of theory) - no reduction at all also at 140°C+. TLC was run using 48/48/2 - ethylalcohol/chloroform/ammonia on standard TLC plates.

I read and learned a lot the last years.


So Rhodium, your interpretation of the data in the references is by will and not by facts, sorry - you cannot blame something on one factor if already two factors are provided, thats unscientific. But usual I know.
The information in the references is unconsistant and contradictary in parts - sometimes HI is produced from the GAA even.... why not, who minds...?
So I refer mainly to physical data and hopefully proofen knowledge:
- Gattermann-Wieland
- Gmelin
- Vogels

In addition - please think through the reaction by my way once - you will see how things suddenly fit together and how a certain (not complete) amount of predictibility is gained all of a sudden - and the predicted changes match with the known facts.
Of course a rather high developed ability of imagination of complex things is needed to do so....
(sorry - couldnt behave..... )


hey - a present for the chief at last:
- the hexamine to methylamine reaction is NOT always the same as ammoniumchloride + formaldehyde to methylamine one. These french chemists in these days were not so stupid and paper to publish was expensive.
The funny thing is you have the answer also pointed out but never followed it experimental: "....if enough water is present" The frenchies did never say stochiometric amounts are enough, how do you come to think so? Try 4l water for 100gram hexamine and use less HCl - if you add some zinc or Al or tin a 40th of theory HCl and roomtemperature is good to go..... or you get ammoniumchloride en masse.
(ever heard of chloropicrin? Thats where I took the trace to haunt this down)

I once tried to spoonfeed the biosynth to the masses.
I swore to myself never ever to spoonfeed something again.

Happy experimenting!

[Rhodium]

There is some logic in this.

Most definitely, it has been a good theory all the time. Hopefully the reaction rate increase by using this modification wins out over the unavoidable increase in hydrolysis rate gotten at the same time.

I thought. I tried. And the proof is in the pudding.

Is this to be read as you did try out this suggestion of yours? If so, then was was the yield difference?

The dehydration fights also another probable problem, which I guess to exist but here I have no direct proof: I believe a part of the the HI is trapped as salt on the aminegroup - a equilibrium with the HCl salt form may be formed. But thats a guess.

Does any amine salts precipitate during the reaction? If not, then all the HI is available for reduction, as in a homogenous solution, the amine nitrogen is merely protonated and not present as a tight RR'NH₂⁺I^- ion pair holding on to the iodide ion.

I also tried a reaction after the old german reference using a catalytic amount of iodine (10percent of theory) - no reduction at all also at 140°C+. TLC was run using 48/48/2 - ethylalcohol/chloroform/ammonia on standard TLC plates.

That's interesting, but do you remember the ratios of reagents/solvents? I believe the problem boils down to an insufficient HI concentration rather than any other factor in this case.

I think this will be my last post regarding this HI hydrate discussion, as my expertise lies in knowledge of the theory and the published literature rather than me having any practical experience with this reaction (something I believe I would need to discuss this further), as I have said before, I have never extracted a single pill and never run a single PIE reaction. I'll wait for others to take up this suggestion and publish more details regarding yield improvement using this procedure.

I'm not sure I understood what you said regarding the HMTA reaction, but let's take that discussion in an appropriate forum in case you want to clarify through what alternative mechanism the reaction would proceed - this is no place for that.

Thanks for your input in this case, hopefully others will embrace your suggestion or at least have learned a thing or two by reading our discussion here - it probably contains a lot of things we know about the reaction but which we haven't written down elsewhere for people to see.

[Organikum]

Please point me in the direction so I can verify this - I cant remember to have up to now read of this being named as a problem in this reaction.

"Does any amine salts precipitate during the reaction? If not, then all the HI is available for reduction, as in a homogenous solution, the amine nitrogen is merely protonated and not present as a tight RR'NH2+I- ion pair holding on to the iodide ion."

Are you sure on this? The HI and the hydrates are also completely dissociated and on the other side bound quite strong together. I believe this a simplified and misleading way to see things - this atoms swimming in a soup picture - I prefer to see it as a interacting assemblation of probabilities.

I told this being science and not fiction.
Now guess if tried it.
And I told about yields already.

nuff now.
anything else would be forced spoonfeeding.

[Rhodium]

Hydrolysis? Please point me in the direction so I can verify this - I cant remember to have up to now read of this being named as a problem in this reaction.

This is the acid-catalyzed hydrolysis of ephedrine alkaloids to phenylacetone and methylamine I have mentioned and linked to repeatedly above.

In regards to ion pair bonding, I am completely sure of the iodide ions not being taken out of the reaction equilibriums by salt formation as long as 1) no precipitation occur, and 2) at least 1 equivalent of H⁺ from another source being present (such as using an amine hydrochloride as starting material).

[Organikum]

As told - I am not sure on the salt formation as problem.
As told - I am sure acid hydrolysis almost not to take place at the low temperatures recommended - for boiling ephedrine in HCl only leads to razemisation on the alpha-carbon and a ephedrine/pseudoephedrine equilibrium is formed, this may be seen as strong hint in this direction. A stronger hint might be the fact that TLC showed no byproducts in my related experiments - but an almost quantitative reduction in several runs.

thats all.

[elfspice]

could it bee that the relative solubility of the various salts that can form in the reaction flask affects the reaction - specifically, if HI is the majority acid in the reaction (well, about 2x as much HI as the HCl from using E.HCl) then the logical conclusion is that the e.HI would tend to form a lot, and perhaps this salt is less prone to reaction somehow, and let's not forget that if it's ionised, stuck to the ephedrine, then it can't be reducing anything. In fact, you want to optimise conditions so that the least ionised acid in the mix is the HI, and the simplest way i can see of doing that is to eliminate water, use anhydrous acetic acid (which will greatly tilt the balance in favour of the formation of E.acetate and away from E.HI) and adding anhydrous HCl for good measure... if we want every drop of un-ionised HI to be available for reaction, we want to make the HI content about 1% of total acid content, which will mean that virtually none of the ephedrine forms E.HI

As far as i can tell, the reaction depends on un-ionised hydriodic acid coming into contact with the hydroxyl. Water ionises HI. HI in high concentrations at higher temps tears everything up, but what say we created conditions where it was virtually 100% HI (ie no water), and temperatures very low so as to keep the reaction intensity low and reduce side products.

how does this sound:

mix ascorbic acid with iodine with both dry, add small amounts of water to initiate the reaction and agitate it to get it to keep mixing and reacting.

minimal water: if minimal water is used the concentration of HI that forms will rapidly come to saturation and this will lead to fuming. The fumes are bubbled through a solution of anhydrous acetic acid.

The anhydrous acetic acid now nicely saturated with HI is gassed this time with anhydrous HCL (CaCl+HCl) until saturated.

This fuming stinky mixture of acids can now have some pseudo freebase added to it, the whole thing in a flask with reflux running at a nice gentle 50 degrees C or so.

The hydriodic acid, without the water is able to react freely with whatever it finds most interesting (the hydroxyl) and with the lower temperatures, side reactions ring closures and decomposition reactions cannot easily occur, and there is no other reaction available to it, nothing to reduce in the whole reaction system except the hydroxyl

Couldn't this reaction be done in a sealed vessel that lacks a condenser anyway - i can see it working very well inside an earlenmeyer or volumetric flask with a cork held in place with a clamp or somesuch. with the fuming acids i don't think that a condenser would be enough, although i could be wrong... since the reaction works cold it doesn't need to breathe does it? i guess it doesn't matter, the condensing acetic acid will keep most of the HI in there.

I think this would make the reaction possible without using I2 recycling agents as well, since there is nothing but hydroxyls consuming the HI.


maybe i've got this all wrong, but i always remember from highschool chem that ions are different creatures to the un-ionised forms. when HI is dissolved in water it is really a H+ and an I- floating around. But anhydrous HI is exactly what the label says. Why, if it isn't the fact that the reaction requires un-ionised HI to occur, then i can't think what the hell else it could be, otherwise a very near to saturated (saturated enough to be smelly) solution of HI would not be needed. it could be done with a more mildly dissolved solution if it were the case.

HI in water is not HI, it is hydronium ions and iodide ions in equimolar quantities. this mixture of ions does not have the same chemical properties at all. the neccessity for conc HI solution points to this fact - that only the free HI can do the reducing, the iodide is almost unreactive. so clearly, water is the enemy here.

another point to add: ephedrine freebase is also a different beast to ephedrine ionised into a solution with excess acid countering the amine's addion of OH's. Which form of the ephedrine does the HI react more vigourously with? well, i would think that the salt is what you want, for the simple reason that the amine is a potential reductant for the HI.

[elfspice]

um, boiling ephedrine in HCl laden solution is gonna result in a lot of chiral rearrangement. so, no... keep the HCl out, maybe instead use an excess of anhydrous acetic acid

[CharlieBigpotato]

in a plastic bag.
a flask with a ballon on top is a sealed rxn, unless its leaking like a mother.
that 50 cent item (balloon) is evidently up to the task of containing the potential bomb within.

furthar more, there is no advantage in having air in the flask at the on-set

i'd like to see this post rated as dangerous, beecause heating up almost anything in a sealed containor is risky, especially if one doesn't know anything about anything.

heating up water in a sealed containor is just as risky, although not as corrosive on the 'seals'.
when liquids beecome gasses,generaly, ya'got pressure.
this is the secret to our lives, in america.
from wood fired , cast iron steam engines, to nuclear power plants.

[Rhodium]

Preparation of ?,?-Dimethyl- and N,?,?-Trimethyl-?-cyclohexylethylamine
Bernard L. Zenitz, Elizabeth B. Macks, Maurice L. Moore

J. Am. Chem. Soc. 70, 955-957 (1948)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/hi-rp.aminoalcohol2amine.pdf)

A reduction of ?-methyl-norephedrine to ?-methyl-amphetamine (Phentermine) with HI/P (80-88% yield).

They use 20g RP to 0.4 moles of the aminoalcohol (66g, it has the same molar weight as ephedrine) together with 170 mL 57% HI. The mixture is reacted for 25h at reflux and 12h at room temp before workup (filtration, thiosulfate addition, acid/base extraction, distillation, gassing w/ HCl).