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]

Genuinely, thanks.

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.

Quote: Originally posted by peach

To cut a long, long story short, [Edited on 1-5-2010 by peach]

Have you ever thought of trying iodocyclohexane for demethylation purposes?

ref: doi:10.1016/j.tetlet.2008.04.070

(enjoyed your post btw )

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]

Quote: Originally posted by Sandmeyer

I specially like the introduction:

Arrr... and now I be liking the tangible results yars only be discussing thar theory of



[Edited on 13-7-2010 by peach]

Quote: Originally posted by querjek

Do you have a reference for this?

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]

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

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]

Quote: Originally posted by iwillgetthere

wadup peachy watching and learning... x

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]

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

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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.

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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]