Sciencemadness Discussion Board

Catalytic Hydrogenation

jamjam - 22-1-2007 at 18:10

I met a guy on the weekend who was telling me about a catalytic hydrogenation process, undertaken with varous precursors, including a common amine used in bodybuilding 'stacks':

Anyway his process was fairly basic, but he laid it on me with detail regardless, and I was curious as to whether it would work -

He had extracted the amine from an herb, although it is sold in apparently pure form. The herb contains more than one alkaloid so his 'starting point' was possibly impure.

He said he had reacted magnesium ribbon with hydrochloric acid in the equation of 1 mole of magnesium ribbon, to 2 moles of 30% hydrchloric acid, to produce 1 mole of hydrogen gas and magnesium chloride in solution: he had completed this reaction in a flask with a pipe running from the top into another flask.

The other flask contained the amine (or alkaloid or whatever it was, extracted from the plant), as well as elemental palladium std. Both were in solution of alcohol (ethanol). This occurred at standard pressure.

Now I was wondering, was this guy just going on, or was his synthesis a feasible one? Out of curiosities sake, I got most of the details out of him. However, I'm still unsure as to the entire process.

Would the hydrogen yielded by reaction of Mg ribbon and Hcl acid, reduce an impure sympathomimetic amine, with elemental palladium as catalyst, or would a Palladium/Carbon catalyst be required?

I'm not one to tell him his process is wrong, as shabby as it is, but I wouldn't mind knowing for curiosities sake, just as to the theoretical feasability of this process.

Thank you

Sauron - 22-1-2007 at 18:26

So he's doing a dissolving metal rxn and then using the H2 at 1 atmosphere.

1. Is he scrubbing wahter vapor and HCl out of his H2? Doesn't sound like it.

2. What is his catalyst in the 2nd flask? Sounds like "none".

I'd bet the fellow is a flake. However it is hard to be precise when you have not told us what the amine might be or just what functional group or groups are supposed to be reduced.

There are atmospheric catalytic hydrogenations (cf. cleavage of the benzoyloxycarbonyl Z-protecting group from peptides in methanol or ethanol) but that requires Pd on C usually 5-10%. See Bergmann-Zervas rxn, the Z is for Zervas.

But you aren't talking a PG removal, sounds like you are talking the deoxygenation of a well known component of ma huang.

If you tell us exactly what transformation he is claiming to accomplish, we can tell you whether a 1-atm hydrogenation in presence of a Pd standard solution might effect it (but I am dubious.) Pd on C is prepared from palladium chloride, the point of the carbon being high surface area support.

Is he trying to cleave off a -OH group to -H?

Reduce a carbonyl?

Reduce a double bond?

Or what exactly?

You really have not provided sufficient information to make a really unqualified answer. By unqualified I mean without hemming and hawing.

[Edited on 23-1-2007 by Sauron]

jamjam - 22-1-2007 at 23:56

Hi Sauron,

Thanks for the detailed response:

Yeah, he's trying to change the -OH group to H on that compound which you mentioned:

He says he has palladium chloride or elemental palladium in Hcl matrix, either of which I assume he might possibly be able to prepare a Pd/C catalyst.

And yep, spot on with the reaction: he's attempting to react magnesium with Hcl acid in order to produce H2 gas, funnel that through to the impure ma huang extract (fairly impure, perhaps 50% at a guess), in the presence of a palladium catalyst.

The desired result, according to him, without chlorination of the ma huang compound, would be, among other things, a racemic, reduced form of that compound.

I'm inclined towards telling him any problems with the procedure, including pressure, or as to whether the method of H2 production is erroneous.

Thanks again

garage chemist - 23-1-2007 at 00:14

What matters is which catalyst he is using. In what form is the palladium? Pd on charcoal, Pd on BaSO4, or what?
It must be finely divided and on a carrier.

But then it might just work. HCl and water vapor aren't detrimental to the hydrgenation.
The hydrogen will have to be bubbled extremely slowly though. Hydrogenations at atmospheric pressure take very long.
Also, the system shoul be closed so that a constant atmosphere of hydrogen is over the reactant solution and the reactant solution must also be vigorously stirred.

Sauron - 23-1-2007 at 00:51

We have by sheer coincidence a book on ephedrine in the forum library, another book on catalytic hydrogenation, and a bevy of exiled from The Hive around here who ought to be able to give a very certain and definite answer to the question.

@GC according to the original post the Pd or Pd salt soln is not on a carbon or barium sulfate or any other support. And that is why I suspect that the fellow is yanking his pud, if you will pardon the vulgarity.

Mg ribbon seems like a wasteful way to generate H2. Fe filings, or other muchless costly metal would work as well. Ideally he would start the H2 generation a while before adding the substrate soln in order to achieve a decently O2 free atm in the rxn flask. Otherwise his yield will suffer. The other main point is what else did he pull out of his ma huang, and did he actually get his target ephedrine at all? The details of the extraction were not furnished as the poster was being a little coy.

Also, the resulting phenylproptlamine wo't have a chiral center at the benzylic position, so it won't be racemic. If the reduction is succesful it will just be a plain vanila methylene adjacent to the ring. The -OH was what made it chiral, and the natural isomer of the alleged starting material is l-ephedrine. IIRC. :)

jamjam - 23-1-2007 at 04:22

The catalyst is according to this fellow yet to be prepared, from Palladium Chloride, 60% Pd - it is to be prepared by a particular means to form a Pd/C catalyst of unknown percentage (possibly 5%, though I am not sure, and can't advise him as to what will work best).

Material was extracted from ma huang by means of ethanol and is apparently gummy and brown - the reaction was expected to occur with just this substance, which despite obvious organic impurities, apparently has less alkaloidal impurities. However a steam distillation kit is available and again, I am not sure whether to tell him to proceed by means of steam distillation, which can be difficult, or attempt reaction in solution of impure extract - simpler, but could not work at all and pay result in much less pure outcome.

Thanks to Sauron very much and also to garage chemist.

Iron filings are to be used in the reaction, as I advised this guy, who was unaware of their reaction with Hcl to produce the gas. This is a small scale reaction using less than 200g of ma huang plant material; yields aren't being estimated at all for the actual outcome, but for the extraction and the material to be used in the reaction, a 30-40% purity would be aimed for but not expected.

Thanks again

Sauron - 23-1-2007 at 07:49

According to Merck Index 12th edition, ma huang contains 0.75% to 1% l-ephedrine along with a misture of other isomers.

So your (I mean your distant acquaintance's) 300 g herb at best contained 2-3 g l-ephedrine, along with norephedrine, pseudoephedrine etc.

My advice would be to heat the solution and stir with maybe 2-3 g Norit, then filter through a celite pad. You will then have a clear solution free of tarry plant crap. Then consider seperating the l-ephedrine from the isomers by whatever means the literature suggests.

Once you have oure l-ephedrine you can maybe get somewhere.

If not it's going to be GIGO (Garbage In, Garbade Out.)

Here's a short section out of the free book in the forum library which you ought to read. It will tell you how to isolate l-ephedrine from the crude alcoholic plant extract. Don't go do a Richard Pryor on us now.



[Edited on 23-1-2007 by Sauron]

Attachment: ephedrine.pdf (336kB)
This file has been downloaded 1138 times

Nicodem - 23-1-2007 at 11:20

The hydrogenation with Pd/C can not reduce benzylic alcohols (like the Ph-CH(OH)-R), it can however reduce protonated benzylic alcohols (like the Ph-CH(OH2(+))-R). So obviously it is not possible to reduce a benzylic alcohol in a neutral media since the pKa of protonated alcohols is less than -2. Esters and ethers of benzyl alcohols can however be reduced directly with H2 and Pd/C as catalyst.
Quote:
Originally posted by jamjam
Material was extracted from ma huang by means of ethanol and is apparently gummy and brown - the reaction was expected to occur with just this substance, which despite obvious organic impurities, apparently has less alkaloidal impurities.

That is crap, and reducing crap still gives you crap.

jamjam - 23-1-2007 at 18:10

Thanks again for the information.

Hopefully the reaction will proceed on as pure a chemical as possible, as extracted according to the methods in the .pdf file.

jamjam - 24-1-2007 at 03:24

Could this reaction be achieved, possibly, under the conditions already described, with the use of a Nickel on Carbon rather than Palladium on Carbon catalyst?

Thanks

Nicodem - 24-1-2007 at 11:45

I suggest you to go to the library and read some books first.

Organikum - 24-1-2007 at 21:02

The extraction procedure as told in the article posted by Sauron is messy, lowyielding and therefor outdated. Quantitative ephedra extraction is done with dry plant powder (E. Sinica), sodium carbonate in water and DCM followed by a double A/B including filtration through sodium carbonate. Yields are significantly better then.
The recrystallized HCl-salt of the alkaloids from this extraction produces in a reduction a product at least equal to the one obtained with the other methods usually employed.

Overall the method of reduction as described is bullshit from the first to the last word, beginning with the ephedra extraction going on to the wrong solvent, etc. etc--

And why reinvent the wheel?

Sauron - 24-1-2007 at 23:55

Actually I suspect it was bullshit from "I met a guy on the weekend who was telling me about ..." which alongside all the obfuscation about the nature of the herb and the target to be extracted, was an insult to the intellgence of all who saw it.

But I figured, give the kid a break, let's play along.

The book is old but so are many of the books in the forum library. jamjam does not appear to be very inclined toward scholarship, so I fidures it was immaterial.

[Edited on 25-1-2007 by Sauron]

jamjam - 25-1-2007 at 01:52

Of course the way I address things unclearly aren't intended to insult anyone's intelligence, but they might be interpreted as bullshit.

As for my inclination towards scholarship: it's limited to the information I can dig up on the internet...considering the rurality of my location...

Anyway...if anyone could point me towards a more detailed descrption of the extraction procedure as Organikum outlined, that'd be well appreciated.

But in the interest of theory, why is the reduction procedure bullshit?

Back to inclination, I'm certainly inclined to learn and appreciative of answers I get here, but going to the library and digging up a book on the latest methods of hydrogenation in this regard isn't an option...and so perhaps my knowledge isn't as solid as it ought to be, nor are my skills at searching on the Internet for related information as effective..

So I ask in a way that doesn't intend to be brazen or suggest I know more than I do.

And I appreciate all answers, and suggestion or instruction.

Sauron - 25-1-2007 at 03:18

I'm in Bangkok, and have no access to any library, have only a few hardcopy references, and everything else I have I got on the Internet, which you have good access to. The forum library is accessible to all, not just members, and you're a member. The two FTP sites MadHatter and Axehandle) you need PWs for, just PM those teo siteowners (MadHatter and Axehandle) and eventually they will reply. You will then with a bit of time and effort have a library on your own desktop which you can access anytime offline.

Add to that formal chemical education if any, and Google, and your own native ingenuity in searching for information in cyberspace and you have a very powerful tool right in front of you this very moment. So, USE it.

BTW Nicodem already told you two ways to modify your procedure that would get you a chance of success. (1) alkylate that benzylic OH to an ether, which can be cleaved by Pd?C in neutral medium. (2) switch to an acid medium, -OH+ can be cleaved by Pd/C catalysis with hydrogen. Says Nicodem.

And BTW none of this Internet chemistry has cost me one thin dime, beyond the $65 a month or so I pay my ISP for 2MB broadband for a LAN.

solo - 25-1-2007 at 03:44

Note:.........Off topic ......link provided by whOre over at wetdreams.ws it's full of free info..............solo

http://www.eliteskills.com/free_education/?foo=x

[Edited on 25-1-2007 by solo]

Organikum - 25-1-2007 at 04:14

Quote:
Originally posted by Sauron
Actually I suspect it was bullshit from "I met a guy on the weekend who was telling me about ..." which alongside all the obfuscation about the nature of the herb and the target to be extracted, was an insult to the intellgence of all who saw it.

But I figured, give the kid a break, let's play along.

The book is old but so are many of the books in the forum library. jamjam does not appear to be very inclined toward scholarship, so I fidures it was immaterial.

[Edited on 25-1-2007 by Sauron]
Well actually the information on the ephedra extraction comes from the practical training of chemistry students at a well reputed german university. In this course also black pepper was extracted - interesting that is....

@jamjam: This topic was discussed at the Hive (you should be able to dig up the archives on the net) ad nauseum and in the beginning I myself believed that catalytic hydrogenation would be a feasible, yes the best way to do this kind of reduction. It is not. If one has not access to serious lab equipment and high quality catalysts like made by DEGUSSA (best of the best) then this is plain not doable. And even more: It is far from being the best way to do this, in truth, without sophisticated workup catalytic hydrogenation results in product contaminated with ephedrine and halogenated ephedrine ("chloro-methamphetamine").

Whereas reduction with red phosphorus/iodine (HI) or preferably the Birch (anhydrous ammonia/lithium) are simple, quick, highest yielding even on a rather impure substrate and give after a simple workup pure methamphetamine.

I have translated the ephedra extraction times ago, but I think I posted it on another board. Maybe I can find it and then I will post it here at SCM.

@Sauron: Why are you such a loud bigmouth? I always have to plug my ears reading your selfrighteous posts and look, you are doing your reputation no good postin such halfassed stuff which you quickly pulled from standard literature labeled as the ultimate wisdom. I suppose you only want to be helpful but for some personality deficits you always come over as a jerk dont you realize this?

@jamjam: The only trustworthy procedure to reduce ephedrine by means of direct catalytic hydrogenation is the the one found in an old (1944?) german article by Rosenmund (yeah! THIS Rosenmund!) . GAA as solvent, 70% perchloric acid as activator, 10% Pd/BaSO4 as catalyst preloaded with hydrogen. 3atm pressure IIRC (or was it even STP?).
Funny, This procedure was actually already described by Yogi on ADC in the very early times of the internet, but he didnt reference it.

And jamjam: Meth is a damned bad drug it brings almost as much bad karma as cocain.

/ORG

Sauron - 25-1-2007 at 04:43

@Orgy, why do you feel the need to engage in ad hominem attacks in public? Are you frustrated that I put your name as the very first one in my short but sweet PM Ignore list?

I will not lower myself to your level. Have a nice life.

Organikum - 25-1-2007 at 15:19

Quote:
Originally posted by Sauron
@Orgy, why do you feel the need to engage in ad hominem attacks in public? Are you frustrated that I put your name as the very first one in my short but sweet PM Ignore list?

I will not lower myself to your level. Have a nice life.
Really? I didnt know for I didnt PM you sice your last PM to me. Why should I? Because of the insults? Na, I am to old for this and you are taking yourself for to important.

Funny! :D

Ozone - 25-1-2007 at 17:26

mmmmKay...

Unless you chromatograph (Si(OH)x), recrystallize (not so hot with a gummy herbal extract) or otherwise purify your feed, you'll not get very far.

Look up "balloon hydrogenation" which is, I think, the most facile amateur route, and for catalysis, "Pt/C from chloroplatinic acid"; this should bring up a bevy of lists including E&W, which is probably what you are looking for.

In general, polar protic solvents increase the kinetics seen in catalytic hydrogenations, which is why most of mine have taken place in glacial AcOH.

For the sake of you, your house, and your friends, I *highly* recommend avoiding the synthesis of illicit pharmies.

Regards,

O3

chemrox - 27-1-2007 at 00:50

Could the extraction of dried leaves be done with less gummy stuff being produced using a soxhlet and n-hexane? Just wondering.

Reduction of benzillic hydroxyls is always a challenge. I appreciated the comment about the need for protonating it in atmospheric conditions. In the US a lot is done with dissolving metals and a very old technique using in situ generation of hydriodic acid with P and I2 or HI and I2 (or is it HI and P?) anyway, much info can be had by surfing these meth-ods. Dissolving metal came to be called "Nazi" becaue it was a modification of the Birch reduction leaving out the protic solvent that causes the reduction to occur on the pi bonds instead of the desired OH.

I'd stay clear of all this if I were you. I understand the attitude in Thailand toward making pharms is even more intense than in the US which is pretty bad.

Sauron - 27-1-2007 at 04:56

@chemrox, I'm in no danger of making illegal substances or having anything else to do with them. A former associate used to be deputy director of national police and he was fond of summarily executing drug dealers "extrajudicially" as we say here.

A very nice fellow and former police escort to HM the King.

Before he left office the Asian Wall Street Journal (or maybe it was Far Eastern Economic Review) interviewed him, he had asked for written questions. He passed the list to me, and I wrote his answers for them. :)

[Edited on 27-1-2007 by Sauron]

Levi - 27-1-2007 at 07:13

"extrajudicially" hehe. we call it murder here ;)

Ozone - 27-1-2007 at 07:40

Hmm,

Extrajuris prudence?

Anyway, @Chemrox, a preliminary extraction with hexane will remove waxes and oils nicely (freon would be *much* better). Followed with your extraction of choice, your 2° extract will be much cleaner (florasil is also excellent for this). I'd still chromatograph the stuff from Si(OH)x with a non-polar solvent (like, maybe, ligroin:EtOAc or THF). Routine drying of a drop of eluate onto a glass plate (and viewing under LWUV) can tell you if your stuff has finished eluting. The LWUV is also useful for examining bands on the column directly.

Cheers,

O3

[Edited on 27-1-2007 by Ozone]

LWUV

chemrox - 10-2-2007 at 01:20

How many thing show up under LW v. SW? (UV)

zed - 11-10-2008 at 21:57

Ah, my memory IS accurate after all. I recalled, that About forty years ago, my buddy Alex Palmiter (RIP), told me about his preferred method of making Methamphetamine from Ephedrine. It was reacting the alcoholic functional group of Ephedrine with Thionyl Chloride and reducing the resultant 1-chloro-1-phenyl-N-methyl-isopropylamine to Methamphetamine via Hydrogenation.

Oddly enough, at that time, making Meth was very illegal, and in most quarters it was considered highly immoral. How times have changed. (Sarcasm)

Anyway, there is an interesting reference to this method on the DEA's "Microgram" website. A place I like to visit occasionally, as a reality check. I sometimes forget how stressful the game of cops and clandestine chemists, actually is.

http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg04...

Oh man! Caught in lab with 28 Kilos of Meth. That has to rate some serious prison time.


[Edited on 11-10-2008 by zed]

JohnWW - 12-10-2008 at 03:30

Or some serious bribery! The DEA is as corrupt as hell.

zed - 13-10-2008 at 02:09

John,

Microgram is a website constructed by the U.S. DEA. And, while men are mere flesh, and thereby are corruptible......Here in the States, in general, if the DEA has a good case against you, you will not be bribing your way out of trouble.

Across our Southern Border in Mexico, dealers can hire platoons of Federales, to guard their drug shipments during transport. Not so in the U.S..

That being said, the aforementioned link is full of tasty tidbits of information....Like, how much meth the Mexican Mafia smuggled into California, last year.....And, How adultrated common illegal drugs are, and with what.

Also full of mystery. Why were these Asian chemists intentionally making L-Methamphetamine? Is this material superior in some way to the supposedly stronger D-Methamphetamine? I do not plan to make any, but it makes you think.
What were they up to?

And, since this is a link on catalytic hydrogenation......Of further interest, was their non-chalantly mentioning "Activatiing" the substrate via Nitric Acid or Sodium Acetate. I did not know of those methods.

madcease - 13-10-2008 at 03:28

Are catalytic hydrogenations better suited when shaken or stirred?
Since when using certain catalyst they can auto ignite if not dilute maybe im going down the stir path. Anyone had experience with the stirring instead of shaken?

stoichiometric_steve - 13-10-2008 at 14:11

Quote:
Originally posted by zedWhy were these Asian chemists intentionally making L-Methamphetamine?


They obviously didnt know that their precursor was the wrong stuff ;)

Alternatively, they were trying to make some Vicks inhalers.

zed - 13-10-2008 at 18:34

Steve,

With a 30 liter Hydrogenator, and 28 kilos of product? Not likely. I'm inclined to think that those boys knew something that we don't.

Shaken, not Stirred?,

Either method works fine. Purge all air from the system and both work well. Many catalysts are pyrophoric however. The activated catalyst is full of adsorbed hydrogen. And, If you allow such a catalyst to dry out while in contact with air, that hydrogen will react with atmospheric O2, the catalyst will become very hot, and it will ignite itself and any nearby solvent. Might even cause an explosion. This is a bad thing.

Read up on the perils of such procedures. Even better, take a class, or find a mentor who is experienced with the relevant equipment.

Barium - 13-10-2008 at 19:20

I seriously doubt that Zed! The vast majority of these guys are far from rocket scientists and even less so, real chemists. There are no new unknown qualities of l-meth to be discovered. Don't you think the pharma industry has ben giving speed in all possible shapes and form to humans and animals alike in enough number of doses to make it perfectly clear which form gives you the best bang for your buck? Christ it has been known for about 120 years.

A stirred reactor always beats a shaken reactor in saturating the catalyst with hydrogen. By keeping the catalyst as saturated with hydrogen as possible less unwanted side reactions will occur.

stoichiometric_steve - 13-10-2008 at 23:37

And i'm inclined to think that these boys were just well trained, look at the product...

Apart from that, i have to agree with Barium. I have never done meth but for me and the various pharmacopoeias, the L-form is a vasoconstrictor and thats it.

zed - 14-10-2008 at 01:20

I will investigate this matter. I have heard counter claims.

Pause........

Well, I'm back. There were very interesting discussions on L versus D, versus D-L , out on the web.

For the moment, I'm going to surmise that those Asian chemists weren't through.

Has it occurred to you that those "wrong" isomers might be OTC in some parts of the world, and the chemists might have intended to racemize that L-Metamphetamine into D, L, Methamphetamine, via a further reaction?



[Edited on 14-10-2008 by zed]

Barium - 14-10-2008 at 04:01

Then why the trouble to recrystallize the product to make the "ice" appearance? Nah, those idiots simply had no clue about chirality. Then again, speed cooks aren't the top of the evolutionary ladder. And for the love of God Zed, calling them chemists is an insult to chemistry.

solo - 14-10-2008 at 06:18

...................I'd say they are in the business of making cut.....since it will crystallize and look like the d-isomer ...otherwise they would need the free base to either work it back to P2P or to do a metal recimization....but then who knows what their motive might be save use it as a pure chiral to help resolve something of more value to them......solo

solo - 10-1-2009 at 19:10

Quote:
Originally posted by zed


And, since this is a link on catalytic hydrogenation......Of further interest, was their non-chalantly mentioning "Activatiing" the substrate via Nitric Acid or Sodium Acetate. I did not know of those methods.


....does that mean they will recimize using those methods of activation .....the talk is refluxing the l,isomer with 37% HCl for 14 hours will recimize the isomer be it l, or d.....which is much easier than the involved pd. `zinc, iron to make a metal mix to do the recimization as noted on `patent -Recemization`- `improved method for converting l. amphetamine to d,l. amphetamine-pat-US2797243....`i would be interested if anyone has a working method to recimize active isomers besides those mentioned......solo

nolchmist - 21-9-2009 at 22:34

Quote: Originally posted by solo  
Quote:
Originally posted by zed


....does that mean they will recimize using those methods of activation .....the talk is refluxing the l,isomer with 37% HCl for 14 hours will recimize the isomer be it l, or d.....which is much easier than the involved pd. `zinc, iron to make a metal mix to do the recimization as noted on `patent -Recemization`- `improved method for converting l. amphetamine to d,l. amphetamine-pat-US2797243....`i would be interested if anyone has a working method to recimize active isomers besides those mentioned......solo


Are you sure about the information of racemizing l isomer with 37% HCL for 14 hours its true??:o

solo - 27-12-2009 at 09:41

......nothing is sure till it's tried, but i think the amine has to be in a phase transfer solvent such as acetone ...and in such a case perhaps an alkaline environment would work best as done with amides in patent US4918196.....solo