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peach
Bon Vivant
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Methyl aryl ether demethylation of 4-Allyl-2-methoxyphenol - a LONG discussion
Before we go any further, anyone who's thinking of pointing me to the designer-drugs articles on demethylation as a reference, shut up and get back to
theorizing whilst the rest of us actually experiment.
To cut a long, long story short, the hard acid method of demethylation doesn't seem to want to work with 4-Allyl-2-methoxyphenol
A friend and I have spent a lot of time and notes playing around with this cock teaser and are beginning to draw some conclusions; like that we should
spend more time outside.
You can also add some soft base to the mix, but that doesn't actually seem necessary. There are a number of journal entries that just go straight to
it with the acid and yield, not great, but decent amounts of the catechol.
What sticks out in all of these papers is that they often use substrates that feature the ether moiety as their only major functional group.
4-Allyl-2-methoxyphenol is an entirely different thing, and I believe it's all down to that double bond floating around on the tail.
As far as my chemistry knowledge goes (which is simply destroyed by some of you on here), the hard acid attacks the ether by going after the pair of
spare electrons floating around on it. And so it also seems to lust after the electrons in the double bond as a bronsted acid would go after them in
hydrogenation.
4-Allyl-2-methoxyphenol is fairly well known for that tail doubling back on it's self in an attempt to form a cyclic in a few other reactions I've
seen, not involving demethylation if I remember rightly.
Our theory is that the acid may attack the ether, but also be messing around at the double bond, bringing with it the possibility of dimers.
Pyridine is fishy to have around, and the superbly supervised sublimated iodine equally so. Both are a pain in the ass and expensive. At least iodine
is purdy, when it's not on the carpet.
I found a particularly interesting paper on demethylation using the super simple AlCl3/DCM system. They didn't bother with any soft base or even a
PTC. Having the two lying around, as you do, I thought I'd give it a whurl and see what happens.
I hadn't actually opened the bottle of AlCl3 up to that point, but noted that in the time I'd had it, it had already tried to eat it's way out of the
seal and had gotten on to rotting the label and turning the sealed bag yellow. I instantly upped my level of respect for it on cracking the seal,
releasing the magical genie trapped within in a puff of smoke.
I ran the workup.
First thing I noted was that the AlCl3 really didn't seem interested in dissolving, even in an excess of DCM with the stir bar battering it around at
full speed. It did like turning into a kind of gummy plastic mess that smeared all over the flask and stuck to the walls, causing me to have to sit
with the plate constantly tweaking the stir bar and reattaching it when it bounced off a lump.
After about half an hour, I added a little of the substrate to see what would happen and a good pinch of PTC; for any cookalong chemists going for an
A to B, try shampoo... 
Anyway... back to the cloud base of endor, wookies and ewokes and all, and the experiment.
I noticed the AlCl3 starting to go into solution, at first I put this down to the presence of the substrate, but I doubt that's correct. It was
strange however that it seemed to reluctant to dissolve at first and then sped up through a somewhat exponential curve. When it started out with the
full dose of lewis acid there, it sounded like someone was grinding rocks up in a mortar and pestle. By the time everything was running smoothly, it
was all in solution.
Any advice on that, why was it taking so long? I also don't 'get' why it sped up the way it did, since the DCM didn't really get hot, it barely warmed
up, which is the usual explanation for increased rate. And the higher solution content as things went on should have slowed it down I'd have thought.
I'm rambling...
As it went into solution, the DCM turned a delightful yellow, gradually darkening to a deep, tarry orange; much like how I imagine my lungs look after
yet another 20 pack. It was deep enough I couldn't really see through the 500ml erlenmeyer flask.
I began dripping the 4-Allyl-2-methoxyphenol in as slowly as my shite funnel would allow - my very expensive pressure equalizing funnel is now overdue
for some repairs (glass blowing is on the list of things I'd like to have a go at). The stopcocks on both the bastards had seized, as usual. I've now
started 'taking apart' the cocks after use, leaving them loose, to prevent that (I've lost quite a lot of money learning that lesson, damn welded
together tapers). If I was doing this seriously, I'd 100% go for one of the funnels with a micro tap on it, the kind with a screw thread, the dropping
rate on a normal tap is too difficult to get down to controlled drips.
As the substrate went into the system, I noticed effervescence. Perhaps it was damp. Either way, I was greeted by the familiar stench of something
chloriney. It was concentrated enough that inhaling within a foot or two of the flask wasn't possible; I just coughed the air back out. Early on in
this discovery, I inhaled and immediately coughed the air back out, to find a plume of white 'smoke' on my breath, like I'd just inhaled through
ciggy; splendid. I took this as an indicator that it was time to leave the room, having suffered chlorine irritation to the lungs once before when
sterilising a room with 15% industrial bleach one day.
But, with the window open, the room never reached the point that it was painful to enter. It did reek of the substrate though, which quickly grates on
the soul. I'm also not entirely sure how safe it is to be inhaling vast quantities of the substrate vapours, as I'm sure I've read somewhere that it's
carcinogenic if ingested. So it could be worse than whatever was bubbling out of the DCM. However, I have a healthy respect for chlorine and from my
previous experience with the bleach I know that it's very easy to become acclimatised to low levels and not realise it's doing a number on your lungs
until a few hours later. So off I left...
If you're about to reply without reading the rest and tell me to get a fume hood. I know, and there are better, cheaper ways of fixing the problem
anyway; more on that later.
Two chilli burgers and some boxing of eBay good later, I returned.
During the addition, I'd momentarily checked back a few times to see how my downstairs mix up was progressing.
The solution appeared to be gradually changing to a blood red colour (which I think is just the AlCl3). I did notice the solution taking on a slightly
purplish hue as the substrate went in. I didn't noticed any exothermic heating, it was only as warm as the motor from the stir bar was making it.
Which was good, because I was worried this might be one of those ones that goes into thermal runaway.
Addition complete, I let it run for a while. In total it was probably running for about two hours.
I didn't bother applying reflux. Firstly, because my beautiful 400mm coil condenser sadly died, and my ultra cheap (virtually broken on arrival) high
school condenser had gone awol.
Secondly, and more scientifically, the journal entry I'd read stated that the workup was fine at room temperature.
Thirdly, I don't think heat is a good idea around the intermediate or product - it's prone to all those annoying cyclic attempts, dimerization and
thermal degradation I believe.
Beside, the subtle change in color on addition indicated that a reaction may have taken place already, so I didn't want to cook it just for the sake
of it.
I set the flask aside and let it cool from it's luke warm temperature to room temperature whilst I got on with some more shipping related issues (I've
been trying to ship this box for literally weeks).
On standing, I noticed the splashes of solution near the neck of the flask had turned purple and that the solution had a disappointingly black
appearance. I wasn't hopeful.
WE WILL NOW BE GOING ON WITH THE HYDROLYSIS I AM THINKING YES?
Again, not much heat evolved at all, but the nasty fumes returned.
On to the fume hood...
You don't need one, just run it in a two neck flask or fit a claisen head and stick a wash bottle head or vent on one of them, the funnel on the
other. Route the evolved gas off through another wash bottle with some alkali in it or some other scrubber.
Oh right! I am forgetting some numbers. I wasn't being very precise, this was just to see if I could yield anything. I had around 50ml of the
substrate to 50g of AlCl3 in about 200ml of DCM. I used around half a teaspoon of PTC; which is more than enough. I hydrolysed with around a liter of
water.
I was using roughly equimolar amounts of substrate to acid, but the journal entry used something like a ten fold excess of acid. I only got the entry
after I'd run the workup, to see if there was anything helpful in there about the cleanup.
Once the first 250ml of water is in, the rest can go in quickly since it's basically done.
As I hydrolysed, the solution turned a much more promising tan color.
The DCM, naturally, split from the aqueous phase perfectly on standing. The aqueous layer is a muddy orange pond water color. The DCM, a heart
breaking filthy black; I've seen that more times than I'm happy with.
Bedtime, and the mess got to stay in the guest bedroom, more commonly known to the layman as the sep funnel. I split the two the next morning and
retained both. This gave me some time to have a good think about how to proceed.
I drove the DCM off the organic phase with evaporation, sitting it on the hotplate with it on the 'you may as well turn me off' setting. I was trying
to determine if it was worth going any further and was looking for a smoky smell as an indicator, but the overpowering stench of DCM had to go first.
Whilst my DCM evaporates, I get on with watching girlies hula hooping; a highly productive activity I think you'll agree on browsing.
On completion, I was left with a dark, dark tarry orange, tacky, sticky liquid. With careful smelling, it does smell a little different to the raw
substrate, but it's tricky to describe. It had a slightly smoky / burnt smell to it, slightly more aggressive than the substrate.
Since the product is a solid at room temperature, I stuck it in the fridge overnight to see if any solid would form. No, it didn't. The liquid has,
however, turned so thick I can turn the dish upside down and it won't move. If I dip a finger in it, it's tacky and sticks to my finger.
The fact the product is supposed to be white, and I have a horrible mess, suggests it's either in need of a serious clean up or it's gone wrong,
again. I'm sick to death of tar clogging up all my glass, which has so far been part and parcel of experimenting with this substrate.
I've read a few comments about how to go about cleaning the workup. Some of them suggested that the product would be in the aqueous phase, or that it
should be taken up in that phase by treating it with HCl and washing it out of the aqueous layer with ethyl acetate. That's curious to me, as both the
DCM and ethyl acetate are polar aprotics, so it'll be in the DCM anyway I'd have thought.
Compounded by the journal entry using exactly the same system as mine doing nothing of the sort. The product is a waxy material and will dissolve in
water, but it's going to prefer the DCM.
I measured the aqueous phase pH and it came out as something like 3.228, so it's acidic anyway from all the AlCl3 shenanigans.
In the entry, they simply wash the DCM phase with HCl to remove byproducts, dry it and then stick it on the Buchi.
Here ends my adventure. I now have a flask of pond water waiting on my desk and a filthy orange, tarry dish of sticky mess in the fridge. It looks
remarkably akin to a certain yeast based health food, so I think it's safe to say no one will be eating it anytime soon. Oooooo, controversy! 
http://img413.imageshack.us/i/controversy.jpg/
My sticky mess will undoubtedly have unreacted substrate in there and a host of other delightful byproducts, which may be masking any product. Before
I give up and ditch either, I'm having a think about how I might recover any product that is lurking in there.
I decided to post this up to the gods of chemistry not only to let you know how this ran in my version of reality but I'd also be very grateful for
any advice on how to claw any possible product out of the two.
DISCUSSION TIME!
After much worrying about the activity of the double bond being a problem, we (mainly I), had a long think about what might be going on.
First of all, the fact it's even there is going to be a problem.
The fact it's on the primary position of a decent tail makes it worse, since it'll be even less stable than it would with the isomerized version.
Indeed, one of us made attempts to isomerize the substrate, but found cleaning it up to be a tricky one. As far as I know, no attempts were made to
run such a demethylation against the isomer. Or, if they were, I think it ended with a purple substance. I can't remember the details of that though,
so it could have just been in need of hydrolysis.
Yes, I know isomerization of similar substrates is a walk in the park, there was much struggling with the one in question.
My pigeon chemistry skills tell me the AlCl3 forms some kind of conjugate ligand that needs hydrolysing to break it up.
I then explored the possibility of protecting the double bond, ironic considering the workup it's going into is for deprotection.
The most fitting and easily accessible method I could think of was to stabilize some of that double bond freedom by tying it up with the
electronegativity of an oxygen stuck on there; a ketone.
The substrate DOES NOT like the wacker. I ran it through numerous times trying various oxidation methods, including the renowned ketone reaction
vessel method that sees one yanking off thin air for an hour or two; like one of those pornstars who has no idea what's going on.
I then found a patent that had run the wacker against a huge array of similar substrates and, amazingly, the protagonist in question.
The oxidizer in this case was methyl nitrite. I love the way that stuff goes from colorless to brown, bleachy fumes on exposure to the air. Generating
it is also produces some pretty blue solutions.
Needless to say, IT'S A TRAP! The patent had lied, or at least not been very clear about how they'd followed and assayed for the ketone.
It was claiming excellent yields, 80% or higher I think; might have even been over 90.
The results of my attempts? FAIL!
I ran it all dead on the workup described.
I stripped the 'product' from the workups with xylene and then vacuum distilled. At one point, I obtained what must have been 5ml of an oil that
seemed to be a kind of neon yellow color; a good sign, especially as my substrate was lab grade and essentially colorless. But that was a long, long
way from the yields claimed given that I was putting in an order of magnitude more substrate than I was getting as product.
In a last ditch attempt, I tried using H2O2 and sodium nitrite as oxidizers.
Every attempt ended in tar. Tar that I had to beat the shit out of with saturated, boiling KOH to get it back off the glass; it'd often take hours of
washing. The KOH was strong and hot enough it dissolved the bristles on my impressive collection of bottle cleaning brushes.
On further investigation, I discovered there is actually a journal entry describing 'anomalies of [substrate] in the wacker oxidation'. From what I
gather, the complex that forms get's distracted and doesn't bind properly to the site, leaving the oxidizer to uncontrollably incinerate the
substrate. Any money says it's the darn OH group dangling off the other end. It's like chasing your own tail with this whore, you try and fix one end
of it and get harassed by the other.
I am left wondering how the patent came up with the yield claims. I gave them the benefit of the doubt and thought they might have perhaps not
actually extracted the product but have just been following it on TLC or something similar. But then, the solution turning a dirty solid brown color
on each occasion makes me think otherwise. Otherwise being, did they just make this stuff up?
Another option would be to try a peracid oxidation, as that won't rely on the catalyst-substrate complex forming.
I don't have any isosubstrate handy, and I haven't been in the mood to start cooking any up, so I haven't been able to try it.
END!
That was fairly long, and I'm expecting a slap from some members for some error in my working, but remember that I'm only trying to pass up some
information to save you some time or give you ideas about how you might like to proceed.
I also can't keep up with the amount of experimenting this is taking, so I'd welcome any help from those inspired. And if you find anything promising,
you HAVE to pm me after that typing session and the amount of effort, time & $$$ that's gone into the experiments to produce it; if you just post
it up I might miss it, since I don't frequent the board as often as I should.
Another thing interested me. Referring to the designer-drugs article, one guy seems to have tried it with AlI3 and produced a tan colored solid on
hydrolysis. He was using the entirely nonpolar cyclohexane, which may be why it appeared so easily, as opposed to my more aggressive DCM.
I'm still curious. The manner in which he reports the workup suggests he did actually run it. But for the life of me, I'm struggling to think of such
a product hanging around in my bowl of muck.
Of coarse, anyone familiar with this topic will know that I'm not the first to suggest an idea like this, psychokitty and drone had a similar
discussion a long time ago, but didn't seem to follow it up.
I also realize that this workup functions better on more stable substrates. The problem with those substrates is that any subsequent alkylation
requires you first sign yourself into jail via your invoices.
I have some photos of the workup, but I don't think they'll be of much use at the moment.
I'm still new to the boards so I don't know the exact etiquette of posting, I know you don't like certain material on here so I've tried to follow a
similar line as I found in the Wang / Hendrickson; I like the way you've reversed the names there 
If I've gone too far, let me know and I'll clean the message up. I'd prefer that to it being deleted, I think I'm giving myself carpal tunnel syndrome
with all this typing.
There it is my busy bumble bees. More may be to follow.
[Edited on 1-5-2010 by peach]
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Nicodem
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Please open referenceless threads only in the Beginners section where I'm moving this. Not taking even the slightest effort to use the search engine
is also not particularly welcome. Also, it is pointless to post beginners odes about idle experiments, that could be otherwise described in few
sentences, but instead go on for pages and pages. Surely you don't expect people to read looooong posts that bear no interesting information and don't
even provide the reference they are based on? Myself, I'm still trying to figure out what your post is about and I read nearly all of it.
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Nicodem
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Thread Moved
2-5-2010 at 10:58 |
peach
Bon Vivant
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Fair enough on the references point. I've purposely missed them out since I've purchased the obscure articles the references come from and I doubt
anyone, including yourself, would be happy with opening the potential of people finding out your address. I also respect the work of the journalists
enough to not copy and paste their effort onto the web. And I don't see much point in posting the references given that they contain absolutely
nothing in addition to what I've said. Indeed, they lack some of the points I've made. I notice there are posts in the organics forum lacking any
references or even a description of what the workup is being run against, that still remain given horrifically poor experimental methods.
I'm a little more bothered about;
"that bear no interesting information"
I think there are people here that would quite easily be able to find useful information in there, and I'm purposefully not making it easy to find
given the implications of how this could be used.
As for idle experiments, the level of accuracy used was perfectly in line with what was needed to demonstrate if the demethylation even functions. I'm
not trying to perform any precision analysis or work out optimized ratios. Are you not applying excessive decimal points to something that wasn't
intended in that way? Seems a little like suggesting I should HPLC water to check salt dissolves in water.
But it's your forum, and I respect the quality of the information and attitude on here and, so I'm fine with you moving it to where ever your judgment
suggests. I do doubt that this is a beginner topic however; if you're about to suggest something like HBr or Pyridine, you're far off the mark. I am
routinely referenced to articles that explain how easy it is, with those doing the referring failing to understand why their references are useless.
Please point me to some examples of where I've entirely failed with the search engine. Have no fear, I will be genuinely embarrassed if they're
relevant.
[Edited on 2-5-2010 by peach]
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DJF90
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Take note of what Nicodem says. I also have some advice for you:
Don't run a new reaction on such a large scale, 5-10mmol is ideal to check for the possibility of exotherms and the like.
Get the paper BEFORE doing the experiment - this way you can save yourself alot of hassle. If it says reflux the reaction mixture for 30minutes, do
so, but follow by TLC because its pretty uncommon for the timescale they give to effect complete conversion to product
If AlCl3 can coordinate and activate the alkene, you might have cyclised your material in a Freidel-Crafts type reaction, although such a case would
be (off the top of my head) a 5-endo-trig cyclisation, disfavoured by the rules of Baldwin, so you may be fine.
If BBr3 doesn't react with the alkene, then this is the ideal (probably most widely used) reagent for this reaction. Also I seem to recall one of the
silver oxides doing the same, but the product in this case is the quinone.
Check your AlCl3 - if it's not anhydrous it won't work. Anhydrous material is a pale yellow amorphous powder. White crystals and its no good.
The only reason why you might wish to demethylate such a compound is to methylenate it afterwards. If this is the case, it would seem somewhere along
the line you'll be ingesting this stuff. Don't do it; it sounds as if your practical skills leave alot to be desired!
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peach
Bon Vivant
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| Quote: |
Don't run a new reaction on such a large scale, 5-10mmol is ideal to check for the possibility of exotherms and the like. |
I did this. See the part about adding a small amount of AlCl3 to the DCM and then a few drops of the substrate. My reagents and substrate are also not
expensive, and my lack of precision analytical equipment means running above average molar amounts for a trial run is fair; the cost of purchasing
that equipment is higher than the cost of running it in larger amounts that'll be easier to assay. The logic within should appeal to truly scientific
minds.
But I entirely respect and understand the point you're getting at. I've even given the same advice to others with a lot of heart. I'm all too familiar
with people trying to jump straight to multi-molar quantities having never tried what they're attempting before.
| Quote: |
Get the paper BEFORE doing the experiment - this way you can save yourself alot of hassle. If it says reflux the reaction mixture for 30minutes, do
so, but follow by TLC because its pretty uncommon for the timescale they give to effect complete conversion to product |
The paper's title explains the system and temperatures used. I only needed it to check how they'd washed it. I'd predicted the paper wouldn't have run
it against it anything similar to my own substrate, and my prediction was 100% correct. As I will say lower down, my intention was nothing to do with
optimizing the reaction or even to produce any significant amount of product, the only goal was to see if it even worked in the first place.
| Quote: |
If AlCl3 can coordinate and activate the alkene, you might have cyclised your material in a Freidel-Crafts type reaction, although such a case would
be (off the top of my head) a 5-endo-trig cyclisation, disfavoured by the rules of Baldwin, so you may be fine. If BBr3 doesn't react with the
alkene, then this is the ideal (probably most widely used) reagent for this reaction. Also I seem to recall one of the silver oxides doing the same,
but the product in this case is the quinone. |
Genuinely, thanks.
| Quote: |
Check your AlCl3 - if it's not anhydrous it won't work. Anhydrous material is a pale yellow amorphous powder. White crystals and its no good.
|
Thanks again, however, as I also suggested in the post, the AlCl3 came from a genuine supplier and was most definitely not the hydrated form;
evidenced not only by the by the color and form but also by it's response to the atmosphere and severe hatred of being near anything aqueous; I also
noted those responses in the original post, which should have been enough alone to tell you that it's not the hydrated form.
| Quote: |
The only reason why you might wish to demethylate such a compound is to methylenate it afterwards. |
That's a good, and easy, guess given the nature of what I'm doing, however it's not the only reason. And there are, indeed, genuine legal alternatives
that have nothing to do with remethylation.
I'd like to hear some genuine responses from those posting in Sauron's thread on the Wang / Hendrickson synth on what legal and useful things they
hoped to achieve from messing around with what they are. Arguments about the racemic nature of the product are a thousand miles away from the
mentality of the people reading that kind of thing; who are happy to have anything that doesn't require thousand liter bioreactors or lb's of organic
matter to extract. Let's not be getting picky about our substrates and products now given that the products of my own may land people in a state of
depression and the products of that particular workup, psychiatric hospitals.
And yes, I fully appreciate and respect Sauron's admiration for the original author attempting to form derivatives that would make illegal use next to
impossible. But I also see numerous posts in that thread that would lead to the less medicinally powerful uses; speaking as someone who suffers from
routine headaches that Sauron's post may be able to help.
Be brave boys. Skirting the edges isn't good enough to keep you out of jail. Read and understand the laws regarding assumed intention. You're just
tripping on your own feet on the way to the cell; which impresses the authorities even less. The police -always- win, they've been jailing people for
decades on the same logic. Have a look into ALD-52, Orange Sunshine and the Analogs Act if you think you're smarter. The international ban on the
distribution of narcotics and psychotropics will take care of people even as advanced as Sauron himself. If this is news to you, you shouldn't be
anywhere near this kind of organic chemistry.
The products of that workup, even the harder to transform variations, will land you in jail.
Incidentally, there is already an even more simplified version of getting there. Some of my own posts hint at ways of getting there. But you can find
that yourselves I guess... with the search engine.
Also keeping in mind that those interested in the Wang / Hendrickson are competing with billion dollar pharmaceutical companies who have literally
hundreds of millions of dollars to throw at the R&D of a single drug, orders and orders of magnitude greater than anyone on here. I doubt any of
the better chemists on here would be willing to taste anything they produced and thusly, lacking any means to test the compounds biological activity,
the entirety of their 'legal and noble' work is rendered useless. I would go further and suggest that whilst many of them be godlike in terms of their
chemistry knowledge, a lot of them probably don't understand receptor sites, neuroscience, psychiatry, in vitro complications with other
pharmaceuticals, pharmacodynamics or kenetics very well. Step away from the high horse, sirs, you're not ready to jump.
I see ZERO explanation of how anyone in these discussions, Sauron included, intends to put their work to any serious use. They don't even have lab
rats to test it on, let alone the computer modeling or correct medical procedures and authority to test it in humans. You're not even close to a
pre-clinical phase capacity, let alone phase 0 and upwards.
I don't see any discussion of ANY biological activity of the products they're excusing their posts with; even the very beginnings, like receptor
sites.
| Quote: |
If this is the case, it would seem somewhere along the line you'll be ingesting this stuff. Don't do it; it sounds as if your practical skills leave
alot to be desired! |
See my reply to Nicodem stating what my intentions of running this workup were in the first place.
I'm not picking holes in your responses, if that's the way it comes across I'm sorry and it's not intentional. I'm just trying to justify the
responses.
I am also not doing this with any intentions of becoming rich. I've known people who were and, universally, they're got themselves into trouble. I've
also known a lot of people who would be interested in the results of this kind of work and I am blown away by the attitudes of so many of them; I
don't want to be involved with them.
I am also now concerned that I am soon to be banned from the forum. And if you're considering that, please be sure to delete all of my posts as well;
where I'm trying to help beginners when no one else can be bothered.
Reading my own post back now, I can see that, despite it being so long, it breaks one of my own rules of trying to stay as far away as possible from
an A to B recipe book for idiots. I'm sorry about that and, again, didn't intend it to be that way. I post on a lot of forums and each one has very
different levels of knowledge, making it tricky to find the correct way of wording posts. I obviously underestimated Sci-Mad.
[Edited on 3-5-2010 by peach]
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Fleaker
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Seemingly, quite a few have some degree of fixation and dare I say morbid interest on eugenol's demethylation and subsequent methylenation. Quite a
few seem to eschew the use of an inert atmosphere. Why I wonder? The double bond is indeed problematic as well. Best save it for your toothaches! And
if people are really so hard up for it, go get a chainsaw, shovel, and wood chipper or move to Mexico. Probably easier and considerably better
smelling that putzing around with AlCl3 and incurring Nicodem's wrath.
Curiously, everyone forgets vanillin which is *considerably* more easily demethylated.
Sad thing is, this is interesting chemistry. Too bad that much of it seems to go to questionable ends...
Why not try it with p-anethole?
Neither flask nor beaker.
"Kid, you don't even know just what you don't know. "
--The Dark Lord Sauron
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Sedit
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If the goal is to achieve ring formation as the final product why not discuss something that has not been done to death like the use of Diacetoxy
iodobenzene and iodine as a means of demethylation when the methoxy is next to a phenol function. This proceeds first by closing the ring thru free
radical mechanism then is followed with hydrolysis to form the demethylated catechol. My guess is hydrolysis wouldn't be on your agenda though.
There are quite a few other reagents other then DIB that form alkoxyl radicals needed to perform the closure of the ring as well many more avalible
substances such as Lead(IV)acetates and a few others like insitu Fe persulfate. It should work as long as the hydroxy and methoxy functions are within
the 2.4-2.8 Amstrongs range of each other from what the papers state. I do not know if this is the case in vanillin since molecular geometry was
something I am not to good at calculating.
Someone performing this reaction successfully would be interesting but plain 'ol demethylation.... not nearly as much.
Knowledge is useless to useless people...
"I see a lot of patterns in our behavior as a nation that parallel a lot of other historical processes. The fall of Rome, the fall of Germany — the
fall of the ruling country, the people who think they can do whatever they want without anybody else's consent. I've seen this story
before."~Maynard James Keenan
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querjek
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Quote: Originally posted by Sedit  | | If the goal is to achieve ring formation as the final product why not discuss something that has not been done to death like the use of Diacetoxy
iodobenzene and iodine as a means of demethylation when the methoxy is next to a phenol function. This proceeds first by closing the ring thru free
radical mechanism then is followed with hydrolysis to form the demethylated catechol. |
Do you have a reference for this?
it's all about chemistry.
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Sandmeyer
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I specially like the introduction:
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zed
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Sometimes less is more. The production of interesting intermediates via benzodioxazole, is fairly straightforward.
For those of you without library access, The ACS site, wants 30 bucks to view this paper online. Catch it while you can.
http://www.erowid.org/archive/rhodium/pdf/md-mandelic2pipero...
If you really gotta have that dihydroxy allyl material, and you are in the US. The easiest thing might be to drive South. Florida, the Gulf Coast
States, and Southern California, have large, unwanted populations, of Camphor trees. Cut one down, grind it up, and steam distill the wood pulp. The
wood oil so obtained, once the camphor has crystalized out, contains a high percentage of Safrole.
Dihydroxy- allyl material can be easily obtained from Safrole, owing to the fragility of the 3,4-methylenedioxy ring.....
In fact, commercial availability of 3,4-Methylenedioxy-Phenyl 2 propanone, is probably due to the ease of cleavage of the methylenedioxy ring. Which
might be cleaved, as the last step in the production of Parkinson's medications.
[Edited on 23-6-2010 by zed]
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transformer
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Have you ever thought of trying iodocyclohexane for demethylation purposes?
ref: doi:10.1016/j.tetlet.2008.04.070
(enjoyed your post btw  )
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turd
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 10.0 eq of iodocyclohexane. I hope you can recover most of that, otherwise
synthesis from catechol is probably significantly cheaper.
Edit: It says HI in the abstract - incompatible with the double bond.
[Edited on 24-6-2010 by turd]
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zed
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Perhaps you would find iso-Eugenol easier to de-methylate.
If a Wacker type reaction is to be applied eventually to the substrate, I can recall discussions wherein it was stated that the Wacker isn't finicky.
Either Allyl or Propenyl Benzenes, react to produce the identical product.....A methyl ketone.
Now, I did in fact, ferret something unexpected out of this industrial processes article, generously supplied by erowid/rhodium.
http://www.erowid.org/archive/rhodium/pdf/md-mandelic2pipero...
There is a suggestion that Vanillin is somewhat difficult to de-alkylate....While Ethyl Vanillin, might not be! I'll read up on it.
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peach
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Avast thar ship maties! It be strange that you be digging this topic up from the watery depths of Davy Jones' locker, as I just be trying an AlI3
method and yielding me gold... arrr.
Even stranger, I just be about to type it up with pictures when I see you fishing me topic back.
I can be telling yars that the Wacker does not appear to work against eugenol, due to a failure of the catalytic complex to correctly form ---->
tetrahedron be noting this, despite a certain patent claiming it be functioning (which I be trying many times and yielding wet rope with).
The wacker also be an outdated and likely poor choice for protecting the tail. I be saying it be easier to double chlorinate that thar tail by gassing
the monkey with Cl2 and then demethylate. This not only be tying up the charge in thar double bond, it makes the structure more susceptible to
microwave irradiation and softer acid methods by creating a highar polarization in the ring. This thar double chlorinated bond can be transformed to a
ketone, if that be what yar after, by simple work up with KOH.
Me gold be smelling smokey, flowing at room temperature, solidifying on cooling, oxidizing easily on standing and performing in a phenol test. I can
inform yars that I suspect brown is not necessarily all tar where this be concerned. I be having some more observations, but I'll let yar salty sea
dogs know these when I post again, near high tide.
Vanillin be easy to demethylate, it also be lacking much of eugenol's tail. And yes, I be knowing of methods for reconnection if that be important.
But 'tis it not better to get yar gold first, rather than silver and then trade over and over for yar gold? I nots be living in Amer-reka, and I nots
be digging up any trees.
Stop yar talking about illegal moleculars, yar evil scoundrels yar, this be not the discussion!
I be winning this game. And now the land lubber wenches be all over me for thar results and I be laughing in thar faces of the ney sayers, arrr.....
Arrr... and now I be liking the tangible results yars only be discussing thar theory of 
[Edited on 13-7-2010 by peach]
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Sedit
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Yup, a bunch.
Knowledge is useless to useless people...
"I see a lot of patterns in our behavior as a nation that parallel a lot of other historical processes. The fall of Rome, the fall of Germany — the
fall of the ruling country, the people who think they can do whatever they want without anybody else's consent. I've seen this story
before."~Maynard James Keenan
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peach
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Here it's is whores, the first attempt at this method I'm aware of. My rough notes and photos;
Aluminum Triiiodide preparation
1 mol Al turnings (or foil or powder all work well, powder is the quickest closely followed by foil then turnings a distant third) is combind with
1.5mol (note the excess of Al) of Iodine in 1000mL of cyclohexane (exchange solvent as needed but not diethyl ether!). This mix is stirred under
reflux until the red colour has turned to a grey (about 1.5hrs with powder, 2-3 with foil, 4+ with turnngs). At this point the heat is turned off and
the AlI3 in solvent allowed to cool to room tempeature with stirring.
Reaction with Eugenol
In a dropping funnel, eugenol (1 mol), tetra n-butyl ammonium iodide (1/360 mol) and a little cyclohexane are combined. This is slowly dripped into
the AlI3/cyclohexane mixture made in the previous step with vigourous stirring and inert gas sheilding. After all the eugenol has been added the
solution is brought to reflux (it is a tan coloured slurry at this point, but upon refluxing turns less viscous) for 1 hour. The solution is then
cooled in an ice bath and hydrolysed with ~600mL of water, slowly.
The resultant mix is filtered under nitrogen and the solid collected immersed in ethyl acetate, this is swirled for a couple of minutes, then
filtered. The ethyl acetate is seperated from the water (collected through the filtration) and removed and what you have left is a tan coloured solid
with a charactistic 'smoke' smell and a melting point 45-51°C, althought this range could be tightened by recrystalisation or vac distillation with
hot water in the condenser.
A few notes:
* If you are quick then maybe you can not bother with the inert atmoshpere in the workup, however the filtering takes a long time (don't even
consider using gravity) beacause the Al is very finely divided and clogs up the filter paper.
* It seems the reactant ratios are critical so get them right.
* The workup is a shit for large quantities, any suggested impovements would be appreciated.
----------------------------------------------------------------------------
Peach's attempt
Theoretical scaled to 100ml of cyclohexane.
0.1mol (2.69g) atomized Al
0.15 mol (19.04g) sublimated and pelleted I2
0.1 mol (16.42g / 15.49ml) eugenol (pharmacopedia grade)
0.28 mmol (0.09g) TBAB
CaCl2 drying agent
Silica drying agent
KOH exhaust wash
60ml refridgerator cooled deionized Water
Acetone for washing out equipment
Actual measurements:
~110ml cyclohexane
2.70g atomized Al
19.05g I2
15.5ml eugenol
0.09g TBAB
71ml deionized, cooled water for hydrolysis
Atmosphere: 99.998% oxygen free nitrogen thru silica drying agent
Equipment:
Hotplate / stirrer
~75mm stir bar
B24 500ml Erlenmyer flask
B24 Claisen adapter
B24 Coil condenser (150mm effective path)
B24 Inline drying tube x2
B24 wash head x4
B24 test tube for KOH wash
Neoprene tubing
Ice
Plastic bowl
100ml Erlenmyer flask
Plastic funnel
25ml grade A pipette
Pipette filler
0.01g readable balance
B24 glass stopper
PTFE tape for tapers
B24 vacuum receiving bend
Buchner filter
110mm qualitative slow flow paper, porosity fine, 1um particle retention
Time line:
4:44 I2 added
4:46 N2 purge started
5:03 recirulating condenser started
5:05 hotplate set to 10
5:06 hotplate set to 1
5:09 most I2 pellets in solution
5:10 constant refluex achieved - the glassware looks beautiful!
5:12 increase plate to 2
5:16 increase plate to 3
5:20 increase plate to 4
5:26 fumes leaving the condenser, add ice to the chiller and set plate to 1
5:29 N2 purge shut off, fuming immediately ceases, condeser clears
5:30 plate set back to 4
5:31 solvent refluxing down sides of flask with I2
5:40 return & find flask walls clear and solution pinky / purple grey
5:53 no more change in solution, switch of stir bar to solvent wash walls
6:00 heat shut off, begin fan cooling to RT, constant N2 purge
6:03 shut off N2 and disconnect KOH wash flask
6:14 I'm preparing the eugenol in 100ml Erlenmyer, 100ml cyclo + PTC
6:24 I note that TBAB is slow to dissolve even in excess cyclo + vigorous shaking, so give it time to go into solution. I have removed the condeser,
capped it's ends with film and replaced it with the addition funnel.
6:26 Plate is cool to the touch, I purge the system again
6:27 stir bar restarted and allowed to break up sludgy acid
6:28 TBAB appears to have dissolved, vigorously shake again and add to funnel, purging again. KOH wash reconnected
6:32 dropwise addition begins
6:33 solution is becoming opaque and stir bar is grinding
6:34 solution is becoming an opaque tan slurry. It was browny but, a hint of yellow appeared and it's now like curry
6:35 a very small quantity of bubbles are going through the KOH wash, 2-4 every 4-5s
6:59 return and bubbling thru KOH wash has stopped, addition near complete
7:02 addition complete
7:04 funnel removed, condenser replaced, system purged
7:07 purge ends, plate set to 10
7:08 plate set to 1
7:16 plate set to 2
7:19 plate set to 3
7:23 plate set to 5
7:32 reflux has begun in my abscence
8:03 no visible sign of change in opacity, color, viscosity or slurry. heat such off, fan cooling with N2 purge
8:06 purge off, KOH wash disconnected, the system is close off to the atmosphere to prevent O2 back syphon
8:32 the plate is at room temperature, preparing for hydrolysis, condenser removes and funnel put in place, flask in ice bath, purged with nitrogen
8:43 purge is turned off, addition begins
8:54 addition complete, flask repurged and stoppered
Filtering the cyclohexane off. The cake looks virtually identical to sand.
This filtration works fine and I recover the cyclohexane and cake. Then something falls and hits my buchner. I am devastated to be within one
filtration and have this happen. I'm walking around swearing, wondering how I'll get it filtered before it oxidizes. Previously, I'd been filtering
under nitrogen.
I scrape out the cake, extract with ethyl acetate and put it back in another funnel. Now I have to filter through a wad of tissue, which takes 24h,
literally. By the time it's done, the cake has started to oxidize.
The result is attempting to solidify at room temperature. I suspect it's contaminated with substrate and oxidized byproduct
FeCl3 hydrate grain, that looks like a sweety
A 1% solution of FeCl3
A few mg of eugenol are dissolved in methanol and one or two drops of the solution are added
Same test. A few mg of the product are dissolve in methanol and one or two drops of 1% FeCl3 are added. Starts out looking the same as above, then
immediately changes to...
The product, severely oxidized. It needs care when demethylating and filtering. It doesn't look like this when first extracted with acetate. It will
look like this if you leave it open to the atmosphere and light for 24h. Once I have a pure, tan / beige sample, I will determine which factors are
important (heat / atmosphere / illumination etc).
Noteworthy points;
I need a needle valve to control gas flow rate. The welding regulator is terrible. I had to keep turning it on and off to ensure the glass was purged,
but literally creeping it open, over and over again, it'd blow the solvent straight through the ice cooled coil condenser. It has to be an absolutely
tiny flow rate. My regulator's smallest increment is 5cfh, and the needle didn't even move off the pin when I opened it.
The product oxidizes very quickly in the atompshere, within hours it'll be going from beige / yellow to brown. You can not leave it exposed to the
atmosphere. This makes me question if some of my other failures were actually true failures, or do to improper atmosphere control.
I suspect this method may work with AlCl3, which is far cheaper and far cleaner to work with. It's interesting, because it demonstrates the importance
of phase differences and modes of attack. A double chlorinated version of eugenol, I suspect, would be more resistance to side product formation.
I know that looks like tar but, having experienced a lot of it, I can assure you that's due to unstoppable oxidation. I think the inert atmosphere is
a major factor in this reaction and workup. It's not tar, I'm virtually certain that's the catechol.
The end;
I will rerun this. I now have some better filtration methods. Once I have tens of mls, I'll vacuum distill it to see if I can get the tan solid. I did
see the yellow / tan ethyl acetate filtrate early on, just before the funnel broke.
Hope you liked it, start making your AlI3 / AlCl3 now if you'd like to participate. I am.
[Edited on 13-7-2010 by peach]
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mnick12
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Nice post I enjoy the pics,
I was thinking could aluminum tribromide be used instead? I think it could be which would be nice since alkai bromides are much cheaper than iodides.
Sorry to hear about your buchner, I had the same thing happen to be except mine only chipped even though it was a 5ft fall
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peach
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5 FEET tall? Jesus! I've seen large buchners, but never one 5ft tall.
[edit]Oh! FALL!
Yes, a variety of lewis acids are likely to function.
Lewis acids are grouped into soft, moderate and hard. Mainly soft and hard.
Selecting their 'hardness' is important, as Lewis acids and basis will attack like for like and ignore dissimilar conjugates (hard Lewis acids don't
attack soft Lewis bases). So a hard acid will attack a hard base site first. The ether linkage of the methyl group looks like a hard base on the
oxygen with a soft acid towards the ring. Which is why people usually try to break the linkage with a hard acid (to pull the group apart) and a soft
base (to help push it apart).
Essentially, you're looking for a metal with some halogens in an anhydrous state. If the trichloride worked, that'd be by far the cheapest and easiest
to prepare.
I have used the trichloride, but I'm not sure if that's functioning yet. Which is one of the reasons for me making a batch of my own in the other
thread, to see if it will function.
Boron trihalides are used quite a lot for demethylation, but they're way too tricky and nasty to work with.
Iron tri-iodide, bromide or chloride is another option.
If you scroll down on this page, there's a huge set of tables that group the various Lewis acids and bases
As I say, I'll give it another spin with some other acids when the rest of my glassware arrives. I just got a box full of flasks today, but was
disappointed to find some where looking a bit overly scratched for vacuum work.
The chemical supplier I buy other bits and pieces from is being a gimp, as usual. So far, they've smashed one order, sent me that horrible, dirty
AlCl3 and now... they've just sent me an invoice for an order I paid for, received last month and received multiple copies of the paperwork for,
rather than the one I actually ordered. All I want is a Liebig and a few flasks, nothing that special. God only knows what they're up to now. They're
probably about to send me a repeat of the last order. And BOC are sending me bills that seem to have random numbers written on them. I just paid for
my cylinder rental, then they send a bill for another £50 - 75, then another for £100+, for the smallest £15 cylinder of N2 they do... hmmmm...
something fishy is afoot nerds!
YAY! IT'S CHRISTMAS!
Multinecked, genuine Quickfit? That's just what I wanted! YAY!
Arrrr, more piratey wenches...
She not be looking in the mood shipmaties!
[Edited on 13-7-2010 by peach]
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iwillgetthere
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wadup peachy
watching and learning... x
I've arrived!
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zed
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So, the Wacker doesn't work on Eugenol. I'll remember that. Not that I would make that ketone again, or utilize the Wacker if I did.
The way I remember it, the Eugenol Methyl Ketone is very easy to make.
Just condense Vanillin and Nitroethane, to produce the Nitropropene......Then hydrogenate the Nitropropene in glacial acetic acid/with some H2SO4
present.
Bingo!
[Edited on 15-7-2010 by zed]
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peach
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Excellent!
| Quote: Originally posted by zed | So, the Wacker doesn't work on Eugenol. I'll remember that. Not that I would make that ketone again, or utilize the Wacker if I did.
The way I remember it, the Eugenol Methyl Ketone is very easy to make.
Just condense Vanillin and Nitroethane, to produce the Nitropropene......Then hydrogenate the Nitropropene in glacial acetic acid/with some H2SO4
present.
Bingo!
[Edited on 15-7-2010 by zed] |
PdCl2 isomerizes it to the iso, I think. I'm not sure if that's what's happening in oxidations via the Wacker. I have tried multiple oxidizing agents
and yielded something that looks identical to intractable tar in each case. I've tried that methyl nitrite patent entry, to the letter. Tar, I'm
reasonably sure. Tetrahedron also has a letter detailing complexes. I'm not sure if those complexes are correct, but I do think complexes are a
serious possibility with the phenol around and the tail bond having that catalytic oxidizer attached.
I've also heard peracids fail. Once I have some peroxide, I'll fire up the peracid method and see what happens. I don't really want to get involved
with nitroethane and all that.
The most hopeful method I seen for producing ketones from this is to double chlorinate the double bond with Cl2(g). I think that'll work okay, and it
can be transformed to a ketone easily enough. My main interested in halogenation is that it may help protect the substrate during demethylation.
I've seen so much tar around this substrate I'm relatively sure I can see when it's not working. Before the above was exposed to excessive atmospheric
contamination, heat and light, it didn't look like that. And it changed in a way that I would consider reasonable with regards to diffusion gradients
and exposure. Once I have my clamp stand back, I'll rerun it. I want enough to vacuum distill. I also want to try different Lewis acids, iodides are
an expensive mess. They either need to be hard or towards mild Lewis acid, I don't know precisely which as of yet, but soft acids only work under
microwave irradiation, with strong electron pulling groups on the tail side and with large excesses of the acid present. And I don't know how
important a soft base pusher is, yet. I do have a patented soft pusher method available, I'll run it when I have my gear back. I have far too many
options to run through on my own, and would love some help.
I'd also like it to work with cosolvents that'd negate the PTC. At least, something easier than the ones I'm working with. Most of these work with
DCM. That'd be nice. No PTC, no odd solvents. I have worked with acetone, xylene and DCM before on this substrate, but I'm not happy enough with the
variables to report on it. But I do suspect that the biphasic nature of this method (odd solvents and a PTC) is intentionally, not to make things more
complicated. I think the PTC may be controlling how the Lewis acid attacks the substrate. This is similar to other methods that appear to work, e.g.
Pyridine and SIBX, which have structures that may hinder them from randomly attacking the tail or phenol. I think perhaps the PTC is doing something
similar. When I've dripped the substrate into AlCl3 in DCM before, under argon, it's turned a deeper brown with each drop and yielded something
looking like genuine tar.
[Edited on 16-7-2010 by peach]
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peach
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I've been rerunning, which has taken a long time (weeks), trying to work out what affects the demethylation on this multifunctional group substrate.
There appears, so far, to be a glaring error in the single reference to this method I've seen; which is potentially so bad, it will catastrophically
ruin the work.
Here are some results from the most recent look at it.
The samples under nitrogen and stored in the dark, in the freezer. The vials are spotting solutions, the RBF with the take off is some of the
substrate, but it's nothing much to do with this in particular, the red stoppered Erlenmeyer is the result of one of these runs (micro-vigreux, three
way distilled under nitrogen and vacuum), the RBF with the glass stopper is an undistilled result. The undistilled material is solid at room
temperature, the distilled result is when cooled, but flows at RT. For the plate work, the substrate I'm calling A (it's always on the left), the
undistilled potential result is B (and in the middle), the distilled result is C (and on the right). Keep in mind that B and C came from
different runs where I'd varied some of the parameters.
After performing a test tube ferric chloride test on the more recent results, the substrate was producing a lime / grassy green and the suspect
product a dark, extracted chlorophyll green. I then spotted some of the undistilled suspect product on bits of filter paper and looked at how they
were streaking with various solvents; the spots where simply tiny specs of the solid material around 10mm from the base of each paper. I chose a
solvent pair to run 60A, 250um Whatman TLCs, seen above the laminated paper filter papers , and ran them with 1-2% three drop spots. I've used some of the squiffy cut plates to consider each on it's own using more extreme polar /
none polar combinations to look for sidebands (they're also spotted 5 times more heavily than the others). Also notice that the filter papers show all
three materials are unacceptably streaking at the polar extremes (Xylene & DMSO). And that acetone has done a remarkably good job of lifting the
entire, undistilled, spot and shifting it up the paper, suggesting it would be a good replacement for e. acetate during the filtration extracting
stage of the cake; with it being cheaper, more readily available and boiling off at a lower point.
The ordering;
Single, polar elution, substrate and undistilled reaction product
Same, but with the distilled result spotted in addition
Next three plates, all three materials, sweeping towards none polar
Substrate, almost entirely none polar elution
Same, but with distilled result
Again, same but with undistilled result
FULL SIZE IMAGE
Here I'm sweeping the solvent polarities, and these are the more interesting of the plates. From left to right, the plates are getting less polar.
First plate (single, polar solvent);
The substrate, the left hand spot, is displaying a decent level of purity. The mid spot (the undistilled RT solid) is showing a considerably darker
spot with side banding and traces of the substrate (there's a slight purple band just above the main spot). That more defined spot half way down the
run may be some dimer or polymer side product. The streaking on B here may also be contamination from the sintered funnel, which has since been
piranha'd and acetoned to within an inch of detonation (I found a fair amount of 'gunk' in the sinter, despite being 98% sulphuric'd prior to this
run). I'll investigate next time. The distilled, RT flowing, spot is considerably cleaner in terms of side banding, but is also showing a substrate
spot.
Second plate;
Expanding the spots, I can't see any more sidebands appearing, but the substrate and product are RF'ing different values.
Third plate (halved polarity again);
Much of the same, but the substrate and suspect products have doubled their RF with respect to each other and with regards to the second plate.
FULL SIZE IMAGE
The results have an extremely odd smell. I've had a number of people look at them and describe them, so's not to skew the answers with my own bias. A
common theme for the distilled result is 'smoky antiseptic, hospital'. A lot of them also had a lot of difficulty actually describing it in terms of
aroma.
If anyone has better analytical equipment, any form of spectroscopy, I'd be perfectly happy to scrape some out of the flasks and post it out. The
TLC's seem to be giving good results, so I doubt it needs HPLC / GC. Vis/UV/IR would be good, along with MS or NMR.
May the winds be blowin' thar shipmates!
John
[Edited on 20-8-2010 by peach]
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ConorC96
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What does allyl chloride look like?
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Vogelzang
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If someone were to make a pharmaceutical from eugenoal how about this?
eugenol -> isoeugenol
isoeugenol -> methylvanillyl ketone
methylvanillyl ketone -> 3,4-dihydroxy P2P (using HBr, for example)
3,4-dihydroxy P2P -> 3,4-methylenedioxyP2P
See
http://www.google.com/patents?id=Q1YtAAAAEBAJ&printsec=a...
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Chordate
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@Vogelzang, thats not what this discussion is about, firstly.
Secondly, if you bothered to read it I'm sure you'll realize quickly that several of the methods listed in your source were being discussed, primarily
with an eye on troubleshooting failed demethylation.
@peach: you mentioned here:
| Quote: |
PdCl2 isomerizes it to the iso, I think. I'm not sure if that's what's happening in oxidations via the Wacker. I have tried multiple oxidizing agents
and yielded something that looks identical to intractable tar in each case. I've tried that methyl nitrite patent entry, to the letter. Tar, I'm
reasonably sure. Tetrahedron also has a letter detailing complexes. I'm not sure if those complexes are correct, but I do think complexes are a
serious possibility with the phenol around and the tail bond having that catalytic oxidizer attached. |
This might be a simple d'oh moment on my or your part, but if you're referring to a condensation I'm fairly sure you want a nitroalkane and not an
alkyl nitrite (which as far as I'm concerned is one the most perniciously confusing pieces of naming convention ever).
Would you mind citing your patents that I might have a looksie?
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