Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
 Pages:  1    3  
Author: Subject: Demethylation of Vanillin and Eugenol
S.C. Wack
bibliomaster
*****




Posts: 2069
Registered: 7-5-2004
Location: Cornworld, Central USA
Member Is Offline

Mood: Enhanced

[*] posted on 25-11-2018 at 14:26


PS For instance Allen's Commercial Organic Analysis (1910) tells of the method of Thoms that determines eugenol in clove oil by making the benzoate quantitatively (mp 70C.) and weighing it. The no-surprise method they give for ester hydrolysis in general (30 min. 0.5N ethanolic KOH reflux) is that sort of thing IDK how well plays with the allyl part, even though this isomerization isn't super easy...it sounds like a good place for inert gas in any case...obviously BzCl is not an obstacle except for expenses; homemade from BnH/Cl2 if nothing else...to determine total eugenol (free and combined such as eugenol acetate) Allen's says 5 g. of clove oil is heated for 30 min. with 20 ml. 15% NaOH, 6 g. BzCl is added, etc.

[Edited on 25-11-2018 by S.C. Wack]




"You're going to be all right, kid...Everything's under control." Yossarian, to Snowden
View user's profile Visit user's homepage View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 26-11-2018 at 06:41


Thanks for the feedback. So far I've tried both 1 hr NaOH (30%) aq reflux and dilute HCl reflux, with no discernible change at all. I can try in ethanolic KOH next. The AC solution (ethyl acetate extract of steam distillate, when evaporated the residue turns black when left exposed) I have turns red in alkaline solution. I'd have expected any AC yield from hydrolysis to also change the solution color to red, but there was no color change in previous attempts.
I carefully measured the crystal mp (72 C) before becoming aware of the dibenzoyl derivative (so no possible confirmation bias there), it was measured when heating to melting point, not when crystallising. Now there is also a waxy crystalline product measuring higher, closer to low 80's C. No obvious reaction with acid/alkali. Its a mixture. No TLC yet.


I've now redistilled the eugenol I've been using (using vigreux column), I was concerned there could be some eugenol acetate contamination but didn't see any sign of this. In fact it came over at a slightly lower temperature than expected, whereas eugenol acetate would come over higher. Its now water clear and has lost some of its viscosity, will soon find out if this has made any apparent change to how the demethylation reaction performs.

[Edited on 26-11-2018 by CycloKnight]
View user's profile View All Posts By User
Melgar
Anti-Spam Agent
*******




Posts: 2004
Registered: 23-2-2010
Location: Connecticut
Member Is Offline

Mood: Estrified

[*] posted on 26-11-2018 at 22:35


I posted a paper a while back where demethylation was performed with lithium iodide. Although it seemed like an unorthodox reagent to use, it's actually pretty straightforward to prepare, as long as you remember that lithium will react vigorously with nitrogen gas if it gets too hot. IIRC, it works better if the I2 is molten, and Li metal is added in very small portions. The reaction between lithium metal and elemental iodine is the least vigorous reaction between an alkali metal and a halogen, but it's still reasonably energetic. I guess it forms LiI3 first, then LiI.

Now I can't remember if I was successful in the workup or not, so attempt this at your own risk. All the sources I've found say LiH should be reacted with elemental iodine in ether, incidentally.




The first step in the process of learning something is admitting that you don't know it already.

I'm givin' the spam shields max power at full warp, but they just dinna have the power! We're gonna have to evacuate to new forum software!
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 28-11-2018 at 17:24


Update on the latest demethylation experiment, interesting results this evening!

Completed another eugenol demethylation run. Reagents used were 26 g eugenol (in 50 g toluene), 100 g bromine, 12 g Al in 110 ml bromotoluene/toluene.
Reaction and workup were carried out differently this time, but more on that later.



After hydrolysis, vacuum distilled the organic phase and toluene extracts. No steam distillation for this run.

Collected the fraction from 150 to 185 C.
Crystallized in isopropanol.

First vac filtration.
(Sample in FeCl3 hasn't been stirred, so the green granules are visible. When stirred the solution turns very dark green.)


First two.


Small sample in 5% aq NaOH.


Third is still crystallizing. The camera isn't too good, but the first crop is almost fluorescent white. It appears to melt in water at 50 C (forming a light brown oil) and solidifies rapidly when cooled below that temperature. I measured using an old thermometer, not the most accurate, so give or take a degree or so.
Intense dark green in alcoholic FeCl3 solution.
Don't have the final yield yet, still drying under vacuum. The damp weight of the two filter cakes is just over 13 g.

This may well be the product that's been contaminating the samples from previous runs, yielding a (false) green FeCl3 indication.

It has a rather unique (and useful!!) solubility characteristic in isopropanol; its solubility drops off very rapidly when cooled.

The crystals, in very fine needles drop out of solution and the discoloration remains in solution, yielding a snow white precipitate. No assay on purity yet.


[Edited on 29-11-2018 by CycloKnight]
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1713
Registered: 3-11-2013
Member Is Offline

Mood: No Mood

[*] posted on 28-11-2018 at 18:57


Quote: Originally posted by Melgar  
I posted a paper a while back where demethylation was performed with lithium iodide. Although it seemed like an unorthodox reagent to use, it's actually pretty straightforward to prepare, as long as you remember that lithium will react vigorously with nitrogen gas if it gets too hot. IIRC, it works better if the I2 is molten, and Li metal is added in very small portions. The reaction between lithium metal and elemental iodine is the least vigorous reaction between an alkali metal and a halogen, but it's still reasonably energetic. I guess it forms LiI3 first, then LiI.

I also posted a paper where demethylation was performed with LiCl, but it required a long reflux in DMF. Lithium-based reagents may be the key to this reaction because they will not catalyze Friedel-Crafts reactions, unlike Al.




[Edited on 04-20-1969 by clearly_not_atara]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 29-11-2018 at 06:08


Total dried yield is 12 g. The alcohol solution is still showing a strong green FeCl3 indication, perhaps removing solvent under vacuum and chilling would crash out more yield but time to move on I think.

As for the total yield, it's worth bearing in mind that no inert atmosphere was used. I had initially hoped that the Al Br complex would shield against oxidation/degradation but that doesn't seem to be the case. With each demethylation reaction, the reactants on the edge of the flask most exposed to air turn dark very quickly, particularly during the heating cycle. It creates a lot of tar, which causes problems with the workup later.
Anyhow, it would seem it is indeed necessary to heat to 100 C after the eugenol addition is complete, and hold for an hour. I've got the argon supply sorted now and will run the next reaction under argon, and I suspect it will make a significant improvement.
If there isn't too much tar, then after hydrolysis I'll try simply removing the solvent (bromotoluene & toluene) under full vacuum then add to isopropyl alcohol to try to precipitate the product. If that works then that will make life a lot easier.

That last vac distillation was a pain, too hot and slow. Everything solidified in the condenser, and the tar in the distilling flask will take some days to dissolve. That's the tar from the heating cycle during the demethylation, carried over in the solvent.

As an aside, the last bromine distillation run I did took 2.5 hours to complete (before drying). That was using the 3L RBF and overhead stirring. After drying with H2SO4, total bromine yield was exactly 625 g. Or enough to demethylate 163 g eugenol with the current procedure.


Water 350 ml (minimum quantity to dissolve NaBr)
NaBr 308g (3 mol)
KMno4 94g

After the above are mixed, 500g H2SO4 is slowly dripped into solution to distill the bromine. Expected yield is 228 g bromine or 95% of theoretical.

Last run used 3x scale as above, except I only used 750g H2SO4 instead of 1500 g (hence why my yield was less than 684 g).


[Edited on 29-11-2018 by CycloKnight]
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1713
Registered: 3-11-2013
Member Is Offline

Mood: No Mood

[*] posted on 29-11-2018 at 18:06


Very nice work! Store the product carefully, it oxidizes.



[Edited on 04-20-1969 by clearly_not_atara]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 29-11-2018 at 18:40


Thanks! Its all sealed, under argon and in a freezer now.
Just completed another eugenol run with continuous argon purge, same scale as previously. Haven't completed the workup yet but there is virtually no tar. The organic phase after hydrolysis had the appearance of off white toothpaste. Quite a difference to the usual dark brown and tar everywhere. It emulsified heavily, but after a little heating the phases have separated fine. If the FeCl3 indication is anything to go by, this looks to have gone very well so far. Will see what tomorrow brings.
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1713
Registered: 3-11-2013
Member Is Offline

Mood: No Mood

[*] posted on 29-11-2018 at 18:59


Oxygen is a jerk. It always climbs into the flask, helps itself to some electrons, and doesn't give a crap what else happens.



[Edited on 04-20-1969 by clearly_not_atara]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 30-11-2018 at 05:31


After hydrolysis step.
(Previous demethylation step also involved the heating to 100 C. Without inert atmosphere this normally creates a lot of tar.)


It whipped up into a vicious emulsion with the overhead mixer. Not HCl nor adding more toluene made much difference. Heating up to about 55 or 60 C did the trick, and separated into a clear bottom layer and honey/amber organic top layer of about 700 ml of (mostly) toluene. It was left to cool overnight to ambient temperature.

The morning after.....







Isopropyl alcohol & FeCl3 solution.


Looks just like fiberglass, and there's quite a lot of it. The toluene hasn't even been fridge/freezer chilled and its saturated. Will be removing toluene under vacuum and then crystallizing straight from the toluene. Can't get much easier than that. So no vacuum distillation of the product, thank goodness.
Will find out the total yield maybe later today or tomorrow.
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 30-11-2018 at 06:49


Quote: Originally posted by clearly_not_atara  
Oxygen is a jerk. It always climbs into the flask, helps itself to some electrons, and doesn't give a crap what else happens.


Haha!
That oxygen chap does sound quite lazy with all that climbing into flasks and hanging around, not much of an aerobic I assume.

(anaerobic)

[Edited on 1-12-2018 by CycloKnight]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 30-11-2018 at 10:45


Its looking like a final synthesis and workup procedure isn't far off now, with provisions for refinements of course.
There is a lot that needs to be said regarding the complex formation step (bromine addition), by far the most hazardous step. There are some serious issues that need addressing (other than bromine handling). Particularly with reference to thermal runaway, and catastrophic gaseous HBr release due to over zealous bromine addition rate. The reaction can be deceptive, in that it can appear to have started when it hasn't and if bromine addition is continued anyway it can take off and go out of control very quickly. I've worked out how it's done safely so as long as some simple rules are followed then all should be fine. I'll include all this in more detail when I post the final write up.
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 1-12-2018 at 09:58


Total yield for the last experimental run looks to be close to 20 g, just removing the last traces of solvent still.

The exact bromine mass used for the last run was 105 g, and eugenol was 30 g.

The toluene solution was Guinness black by the time it was distilled down to 500 ml, so there has been a fair bit of degradation in the workup. I added a good few hundred ml trying to break the emulsion after the hydrolysis and probably about 100 ml 35% HCl.

For the next trial, will keep it all under argon even for the hydrolysis & phase separation steps and won't be adding solvent nor extra aq HCl to break the emulsion, just heating under argon.

Reagent ratios.
It's worth noting that the demethylating complex reagent to eugenol ratio being used so far is about 2.63 to 1, or very close.

The prototcatechualdehyde demethylation patent (US patent 2975214) claims a vanillin demethylation efficiency of 62% when using a complex to vanillin molar ratio of just 1:1. Compared with 91% when using a ratio of 2.5:1.

For this eugenol variation, if we consider the bromine being the limiting reagent (rather than eugenol), then that would scale to 67 g eugenol per 100 g bromine, 12 g Al + solvent.

Therefore, for the next trial - will be keeping the other reagent ratios the same except for eugenol which will be increased to 60 g (per 100 g bromine) to see how this performs.



View user's profile View All Posts By User
Loptr
International Hazard
*****




Posts: 1291
Registered: 20-5-2014
Location: USA
Member Is Offline

Mood: Grateful

[*] posted on 17-12-2018 at 15:30


Has anyone seen this paper about demethylation of methyl vallinate, and eugenol, using AlI3, ethyl acetate, and DIC in acetonitrile with yields up to 98%?

There is also an IBX/sodium hyposulfite method. There are a couple of others that I have not seen referenced before.

Attachment: tian2017.pdf (530kB)
This file has been downloaded 204 times

Screenshot_20181217-183243_Adobe Acrobat.jpg - 523kB

[Edited on 17-12-2018 by Loptr]




"Question everything generally thought to be obvious." - Dieter Rams
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1713
Registered: 3-11-2013
Member Is Offline

Mood: No Mood

[*] posted on 17-12-2018 at 21:16


DIC in that article stands for what I expected, diisopropylcarbodiimide.

https://www.sciencedirect.com/science/article/pii/S004040391...

For reasons I should not have to explain, there is no need to wonder about whether any amateur is ever going to perform this reaction; the answer is no.

IBX is well-known. IBX is already not used because it's inaccessible; diisopropylcarbodiimide makes IBX look like toothpaste.

[Edited on 18-12-2018 by clearly_not_atara]




[Edited on 04-20-1969 by clearly_not_atara]
View user's profile View All Posts By User
Loptr
International Hazard
*****




Posts: 1291
Registered: 20-5-2014
Location: USA
Member Is Offline

Mood: Grateful

[*] posted on 18-12-2018 at 03:17


Quote: Originally posted by clearly_not_atara  
DIC in that article stands for what I expected, diisopropylcarbodiimide.

https://www.sciencedirect.com/science/article/pii/S004040391...

For reasons I should not have to explain, there is no need to wonder about whether any amateur is ever going to perform this reaction; the answer is no.

IBX is well-known. IBX is already not used because it's inaccessible; diisopropylcarbodiimide makes IBX look like toothpaste.

[Edited on 18-12-2018 by clearly_not_atara]


Yeah, I know what they are and for have a similar reagent on my shelf. It's a liquid similar to DCC.

The DIC is acting as a acid scavenger in this paper. Could another one with similar properties not be tried?

This was another paper that I hadn't seen before and thought I would share.




"Question everything generally thought to be obvious." - Dieter Rams
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1713
Registered: 3-11-2013
Member Is Offline

Mood: No Mood

[*] posted on 18-12-2018 at 11:26


You could probably do it with all sorts of things. Particularly, the rxn is known to work with no DIC, but in much worse yield.

DIC is a strange choice of "acid scavenger" (base?). I'd guess this was its purpose:

AlI4- + DIC >> iodo-DIC- (iPrN(-)C(I)=NiPr) + AlI3

i.e. it sequesters iodide from tetraiodoaluminate, reactivating it. That requires more than a typical "acid scavenger" like triethylamine. If you have a carbodiimide handy, it should be fine, but to me this seems like a waste compared to demethylations with LiX or PyHX etc.




[Edited on 04-20-1969 by clearly_not_atara]
View user's profile View All Posts By User
monolithic
Hazard to Others
***




Posts: 193
Registered: 5-3-2018
Member Is Offline

Mood: No Mood

[*] posted on 2-1-2019 at 19:33


Quote: Originally posted by Loptr  
Has anyone seen this paper about demethylation of methyl vallinate, and eugenol, using AlI3, ethyl acetate, and DIC in acetonitrile with yields up to 98%?

There is also an IBX/sodium hyposulfite method. There are a couple of others that I have not seen referenced before.





[Edited on 17-12-2018 by Loptr]


Check out 0.1055/s-0037-1610996 (attached) for a related paper. Still, I think one of their control experiments is a lot more interesting. 1 molar equiv. eugenol, 1.1 molar equiv. aluminum isopropoxide and 1.1 molar equiv. KI in acetonitrile. Heat for 18 hours at 80C to yield 52% 4-allylcatechol.

Yields are terrible compared to their AlI3 procedure, but aluminum isopropoxide is a hell of a lot cheaper to buy or prepare and KI is pretty much OTC.

[Edited on 3-1-2019 by monolithic]

[Edited on 3-1-2019 by monolithic]

Attachment: 10.1055_s-0037-1610996.pdf (479kB)
This file has been downloaded 224 times

View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 24-6-2019 at 05:42


Just a quick update.
I've abandoned the previous method I've used here for demethylating eugenol, this is why I haven't posted the procedure. Its incomplete.
Its a lot of work and rather low yielding (for the bromine used) to be of any interest other than strictly academic, and the product is contaminated with what I believe is likely to be 4-propyl catechol, mp 60 C, which is a nuisance to separate. There are also many side products, including various esters and some kind of vanilla analog(s) that I've yet to identify.

Before giving up on this particular demethylating reagent approach, I tried using bromo eugenol instead of eugenol.
Much better results. No decomposition at all, I even let the temperature run to 115 C to push the limits somewhat, and for over 90 minutes, during the final demethylation heating stage. This would have turned eugenol to sludge.

The difficulty I've been having is the dehydrobromination step (necessary to form the 4-allylcatechol). So have been experimenting with bromo eugenol dehydrobromination to dial in the reaction parameters, before running it with the demethylated product (circa 7 grams from the last run).

The last dehydrobromination run was with 1g bromo eugenol, 20 ml anhydrous ethanol, and 4 g KOH (16:1 molar ratio, KOH:bromo eugenol), and refluxed for 5 hours. Still, little conversion to eugenol. Tested by checking for polymerisation in conc. sulfuric (sample diluted using 1 drop in a few ml methanol)
Suspecting the sec-alcohol has been formed instead, I tried heating a sample in a test tube with KHSO4 and then retesting as before, and there was a lot more polymerisation (strong red indication in conc sulfuric), and there was some moisture released indicating possibly that the alcohol has indeed been formed instead of the alkene.

It might be easier to just go down the aqueous alcohol KOH reflux to the sec-alcohol and take it from there, KHSO4 dehydration, etc. That's the next thing I'll be trying.

If I can't reproduce the allyl group in decent yields then there isn't much promise for this route, at least for 4-AC.
Anything else I could try?
View user's profile View All Posts By User
clearly_not_atara
International Hazard
*****




Posts: 1713
Registered: 3-11-2013
Member Is Offline

Mood: No Mood

[*] posted on 24-6-2019 at 08:36


When I had suggested using bromoeugenol previously, the next transformation was with acetate salts to form the acetate ester, 4-(2-acetoxypropyl)-catechol. This acetoxy group is easier to attach than dehydrohalogenation and it is quite stable. The acetoxy compound can be used directly in further transformations, eg methylenation.

Methanol or GAA are probably good solvents for this rxn (Sn2 Br >> AcO), but an aprotic solvent like propylene carbonate or DMF is ideal.




[Edited on 04-20-1969 by clearly_not_atara]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 25-6-2019 at 03:55


Thanks for the tip! I'll give it a try.
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 22-9-2019 at 08:45


Quote: Originally posted by clearly_not_atara  
When I had suggested using bromoeugenol previously, the next transformation was with acetate salts to form the acetate ester, 4-(2-acetoxypropyl)-catechol. This acetoxy group is easier to attach than dehydrohalogenation and it is quite stable. The acetoxy compound can be used directly in further transformations, eg methylenation.

Methanol or GAA are probably good solvents for this rxn (Sn2 Br >> AcO), but an aprotic solvent like propylene carbonate or DMF is ideal.


It works!
Yesterday's experiment went as follows:

Ester formation
5 g bromoeugenol (0.0204 mol)
3.8 g sodium acetate trihydrate (0.028 mol) (1 g excess)
50 ml methanol

Refluxed 90 minutes.
Water added, methanol distilled off.
Extracted with ethyl acetate

Hydrolysis
Ester + 2 g NaOH + 50 ml methanol
Refluxed for 4 hr 25 minutes
Water added, methanol distilled off.
Extracted with ethyl acetate

Ethyl acetate evaporated to yield 3.77 g amber oil

A small sample was placed in a test tube, along with a small amount of KHSO4, and heated to reflux using a hot air gun.
Water vapour came off immediately, condensing on the glass and droplets falling back into the hot oil and popping as water does in hot oil.

The remaining product contains eugenol, with a small amount of tar. No discernible alcohol remaining.
Normally this reaction would be carried out at lower temperature and under vacuum, so some tar is to be expected no doubt.

The alcohol (1-(4-Hydroxy-3-methoxyphenyl)-2-propanol) is quite distinctive as it's quite acrid, like pepper spray or capsaican. Much like its vanillyl methyl ketone sibling.

After I repeat this on a larger scale, I'll be able to work out the yield % but for now I'm pleased with the results!

[Edited on 22-9-2019 by CycloKnight]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 22-9-2019 at 09:49


Update on the bromoeugenol demethylation experiments.

The bromoeugenol preparation method I'm using is based on the Fester Method for bromo-saf. preparation, which I found somewhere on the internet. It'll come up with a quick internet search.
By volume, 1 part clove oil, 1 part GAA, 2 parts 48% HBr. Place in ice bath, maintain between 10 and 15 C, and gas with HCl until it turns dark purple blue. Mag stir for a few days, aroma changes from clove oil to fruity.
Quench, toluene extract, wash, and vac distill.
I lost a rotary pump due to HX release during the vac distillation(s), so an inline NaOH trap is a must (!!).

Workup is the same, except obviously the NaOH wash is omitted, since it will pull out the bromoeugenol. 120 g clove oil (just over 100 g eugenol) will yield about 100 g bromoeugenol.

For the demethylation experiments, I had a number of spectacular failures, couldn't quite figure out what the problem was. The toluene used for the AlBr2 demethylation complex solvent must be 100% dry, to achieve this I've been using chemically dried toluene and adding a small amount of mercurous chloride to the aluminium/toluene mixture, and allowing to stir an hour or two before beginning the Br2 addition.

If ANY moisture is present at all, then the final product will be heavily polymerised. On a small scale (~10 g bromoeugenol), it works fine. But when scaled up, the result was failure but I mistakenly assumed it to be moisture causing the problem.
It was actually poor mixing, mag stirring will not suffice on the >70 g bromoeugenol scale I had been using. I believe its down to a coating (either Al or Ar. AlBr2 complex?) that forms on the side of the RBF that accumulates, Overhead stirring is a must on that scale. The good news is that its all working now.

Additionally, I've found that it is necessary to perform an alkali hydrolysis (2 hr alkali reflux) with the demethylated product to yield the diol. As per S.C. Wack's suggestion earlier in the thread.
With the demethylated bromoeugenol, there is a lot of tar that's been forming in this step, about half the product being lost to tar. Argon atmosphere is used always.
Base hydrolysis is with KOH/methanol. So next step is to try with NaOH/methanol and reduce the molar excess.
So far I haven't made any 4-allyl catechol using the bromoeugenol variation yet, but shouldn't be too much longer before we find out whether this is a viable approach or not.

[Edited on 22-9-2019 by CycloKnight]
View user's profile View All Posts By User
CycloKnight
Hazard to Others
***




Posts: 127
Registered: 4-8-2003
Member Is Offline

Mood: Still waiting for the emulsion to settle.

[*] posted on 14-10-2019 at 12:37
Update


The bromoeugenol demethylation worked on the small scale (10 g), confirmed via methylenation, but the previous scaled up run (105 g) did produce a fair bit of polymerisation, I suspect due to insufficient Hg2Cl2 added, I only added a small amount as I'm running quite low. Haven't completed the workup on it yet, but I suspect the yield to be on the low'ish side.

As an aside, early in the summer I developed a method for isoeugenol synthesis from eugenol distilled from clove oil. Ethylene glycol is used as solvent (antifreeze, straight from the bottle without any refinement), and argon/inert atmosphere.
The ratios were eventually dialed in as follows:

120 ml ethylene glycol
150 g eugenol (vac distilled)
240 g potassium hydroxide

The potassium hydroxide is slowly added to warm ethylene glycol / eugenol in a 500 ml 3 neck flask with argon flow. This takes about 30 minutes, waiting for the KOH to dissolve and without it boiling over. Set up for reflux. The temperature is then brought to 155 - 160 C and held for 5-6 hours.

After which, its allowed to cool, neutralised, extracted with toluene, washed with distilled water and then vacuum distilled. Isoeugenol purity tested by buffered peracid oxidation and subsequent glycol hydrolysis to methyl vanillyl ketone, which it does though the ketone yield was consistently about 50%, somewhat lower than expected.

Anyhow, this method produces a high boiling point fraction that I had assumed was likely to be cis isoeugenol. An isomerisation time of 5 hr 5 min was recorded.
From my notes, the vacuum distillation went as follows.
Fraction 1:
(19:00) 124 C, rapid heating to 132 C. Change to fraction 2.

Fraction 2 (isoeugenol)
(:03) 132.5 C. (:04) 134 C, ~ 4 ml. (:05) 136 C, 137 C. (:06) 138.5 C, 1.5 drips per second. (:07) 139 C, 140 C. (:08) 142 C. (:10) 144.5 C, water clear. (:12) 154 C, 155 C, ~ 30 ml. (:15) 155 C. Change to fraction 3.

Fraction 3
(:17) 160 C. (:19) 161 C, ~ 25 ml, water clear. (:22) 162 C, ~ 40 ml. (:25) 163 C, ~45 ml. (:28) 164 C, HEAT OFF.

Final yields:
F1 = 7 g, F2 = 54 g, F3 = 54 g.


Most of fraction 3 was used for other experiments, only several ml were left in a plastic container, back in June. Labelled as "High BP fraction" and hasn't been touched since.
Here it is now:



It was a water clear oil, now a very viscous semi-solid goop. The partial vacuum which has collapsed the container is likely from the oxygen being absorbed. All of my demethylation waste solutions (including bromide recycle bottles) containing leftover diols do the same, if the air isn't flushed out with argon before sealing.

Is there anything other than catechols, likely to be present, that will absorb oxygen under these circumstances?
Its probably nothing to get excited about, but no doubt worth following up!

[Edited on 15-10-2019 by CycloKnight]
View user's profile View All Posts By User
Mush
National Hazard
****




Posts: 468
Registered: 27-12-2008
Member Is Online

Mood: No Mood

[*] posted on 31-10-2019 at 14:16


http://williestop.tripod.com/orgysynpages/4allylcatechol.htm...
Quote:

4-allyl catechol

4-allyl catechol really only serves one purpose - as an intermediate to synthetic safrole. It is a white to tan powder with a characteristic smell of diesel/smoke. Quick or easy are two words that should never describe the synthesis of 4-allyl catechol. While it's not particularly hard, the reagents needed have to be made or bought from a special supplier. It is produced by reacting with an aluminum halide to form the phenol adduct, which is then hydrolyzed.

Aluminum Iodide demethylation

This route is perhaps the easiest, because I find it significantly easier to purchase iodine crystals than anything else. It is made by reacting aluminum with iodine in a solvent, then introducing the eugenol to this. I can't stress this enough: everything must be DRY! The only downside to this reaction is it takes an assload of iodine (which is expensive) to do any sizeable amounts.

2Al + 3I2 ----> 2AlI3

C10H12O2 + AlI3 ----> AlI2C9H9O2 + CH3I

AlI2C9H9O2 + 3H2O ----> C9H10O2 + 2HI + Al(OH)3


Materials
Eugenol
Aluminum metal (foil, powder, chips)
Iodine
Benzene or cyclohexane (NOTE A)
Inert Atmosphere (NOTE B)
Your favorite fabric softener

Equipment
Separatory funnel
Magnetic stirrer recomended
addition funnel (24/40 joints)
Vacuum filtration equipment
Reflux Column w/ 24/40 joints
Reflux Column w/ 24/40 joints
3 neck 1000ml RBF w/ 24/4joints

Prelab: After all of the glassware is washed, it should be dried in an oven to remove all traces of water. Set up the three neck flask with one stopper, one reflux column and the addition funnel. Once put together, attach a calcium chloride drying tube to the top of the condensor. Water elimination is extremely important as even 1ml of water can reduce the yeild to 0.

Into the 1000ml RBF, pour 150ml of benzene or cyclohexane (NOTE A). To this, add 60g of iodine crystals, followed by 4.5g of aluminum (foil, chips, powder). Reflux this until the red/violet iodine color disappears and a grey-tan color is introduced. Once this is done, set up your inert atmosphere (NOTE B) by hooking it to the previously stoppered joint on the flask. Displace any air in the system with the inert atmosphere as you cool it in an ice bath to below 30C. Once below 30C (or roughly). Charge the addition funnel with 30g of eugenol, 3-5ml of your favorite fabric softener (I used snuggle), and a little (~20ml) benzene or cyclohexane to wash it all down. Begin slowly adding this to the mixture while maintaining the cool water through the condenser. If you do not have a 3-neck flask, or an addition funnel, you may drip it through the reflux column.

At this point, methyl iodide is being formed. It boils at 42C, so you can see why reducing the temp below 30C is important. Methyl iodide is quite poisonous and adequate ventilation is necessary. Continue slowly adding, while maintaining the inert atmosphere. It is recommended to include magnetic stirring at this point, but I did without it. Once it has all been added, reflux it for 1-2 hours with the inert atmosphere still running. After this time, you'll have a flask full of anything from dark brown to light tan solids. Let it cool to room temp and add 100-200ml of water. Continue the inert atmosphere the entire time. If there are clumps in there, you will have to break them up in some fashion to fully hydrolyze it. Once it is a fine suspension, transfer it to a beaker of adequate size. Use a wash bottle to get out any of the remaining solid. You may discontinue the inert atmosphere at this time. Let the precipitate settle to the bottom for a couple hours. Once settled, decant the water into a filter, and follow it by the precipiate. Use vacuum and get off as much liquid as possible in the filter. You must let it settle first, otherwise you will be waiting forever for it to filter, and atmospheric exposure to wet 4-allylcatechol can decompose it.

Place 100-150ml of diethyl ether in the 1000ml flask from before to get any residue, then pour it into a 600ml beaker. Add the solid material on the filter to the beaker of ether and stir it well. This will extract the 4-allyl catechol from the aluminum hydroxide and other salts. Cover the beaker and let it settle for a few hours again. Once again, decant the ether into a filter, followed by the solid. Run a small portion of ether through the solid before it clogs up the filter completely. You must let it settle and decant first, otherwise the superfine aluminum salts will clog up the filter and your ether will evaporate faster than it can go through the filter. If there is water in your ether, separate it with a separatory funnel, then just evaporate the ether off with a water bath or with vacuum. You should be left with a white to tan colored solid. This can be recrystallized from petroleum ether. Theoretical yeild is 23.67g but you should obtain about 20g.

NOTE A: Substitute the solvent as you like with a non-polar solvent. Do not use diethyl ether or ethyl acetate. Useable solvents include benzene, cyclohexane, toluene, xylene, chloroform (reduced yeild), nitrobenzene (poor yeild), chlorobenzene, etc.

NOTE B: For the inert atmosphere, nitrogen is recommended, but this requires a cylinder of nitrogen. Propane can be used without any problem. Use a torch and connect a rubber tube to it. Run it through a calcium chloride dryer first, then run it into the flask. At the top of the reflux condenser, place a stopper with a small peice of glass tubing extending from it. Since propane is very flammable and also contributes to global warming, it is best to burn it as it is used. Let propane flow through the flask/condenser for 30 seconds, then light the little glass tube. You only want a very small flame - similar to a cigarette lighter - to come from the tube. You can increase the size if it wont stay lit. A benefit of this, is it will burn off any methyl iodide that leaves the condenser, producing CO2, H2O and I2 in the gas phase. Iodine is toxic, so ventilation is required, but it's less dangerous than methyl iodide and gives an interesting purple smoke as it burns.




View user's profile View All Posts By User
 Pages:  1    3  

  Go To Top