Sciencemadness Discussion Board - Methylenation of catechol derivetives (Base cataylized)

Methylenation of catechol derivetives (Base cataylized)

greenimp - 6-2-2009 at 20:35

I recently got into somewhat of a pie fight with a co-worker over the nature of base catalyzed methlyation of catechol derivatives. For those that may not be familiar with these reactions, I recommend the paper, The Methylenation of Catechols by W. Bonthrone and J. W. Cornforth in J. Chem. Soc. (C), 1202-1204 (1969).

Basically, you have 2 sequential Sn2 reactions between the catechoxide dianion with the methyl halide (usually DCM is used), the result is a methylenedioxybenzene.

The reaction is well worked out for unsubstituted catechol, and there are many improvements in the literature to the Bonthrone and Cronforth method, mostly involving PTC's.

It has also been shown to work for susbtituted catechols with aldehyde and ketone containing R groups.

Our argument arose when she claimed the methylation of catechol substituted with a alkene containing moiety would progress just as it does for the unsubstituted catechol. I should say our specific argument was over 4-ally-catechol. She claimed that the reaction will work just as it does for catechol.

It is my belief that based catalyzed methlyation of this molecule will fail. I have the feeling you will get some sort of a addition to the double bond and the reaction will either produce intramolecular cyclization or polymerization. My guess is maybe from the 3 or 4 postion carbon.

I asked her to show me one example of a catechol containing a alkene moiety undergoing this methylation reaction. She came up with nothing from the literature. There are many claims that it is possible, on various web sites, but no data to back it up.

Anyway, I'm hoping someone here might be able to add some insight. Am I way off base?

<sub>Edit by Nicodem: Changed "Methylation" to "Methylenation" in the tittle.</sub>

[Edited on 10/2/2009 by Nicodem]

article

chemrox - 6-2-2009 at 20:49

First lets start with the article so everyone can read it.

OK, "way off base." (?) hehehe .. anyway, she's right. There's no reason to think the reaction would be affected by a competing reaction in base or basic conditions.

By the way this could be of possible interest: http://www.erowid.org/archive/rhodium/chemistry/tcboe/chapte...

[Edited on 6-2-2009 by chemrox]

Attachment: methylation of catechols.pdf (362kB)
This file has been downloaded 2565 times

greenimp - 6-2-2009 at 20:50

Thanks, I forgot to attach it.

Ebao-lu - 7-2-2009 at 04:03

If you forgot to attach it, then you must have known, she was right, right?

[Edited on 7-2-2009 by Ebao-lu]

greenimp - 7-2-2009 at 08:54

Well, lets say there is more to the story, and that there is experimental data to show that the something is causing the base catalyzed methylation to fail.

Posting the experimental data here may get me into muddy waters, and I don't want to come up against the forum rules. I would post it on other forums, but to be honest the quality of the theoretical chemistry there is some what diminished. That said, the above argument is real. My coworker says "it theoretically possible" and I say, "Well, show me someone that has done it."

I have been trying to come up with ideas as to why it would fail. I though something like the electrophilic dichlorocarbene (monochlorcarbene?) addition to the alkene might be occuring during mehtlyation, but I feel that is reaching. Although, I don't think you could get that from DCM and strong base.

Of course there a number of other reasons the reaction would fail, but without posting the data it is really hard to diagnose the problem. I am fairly confident that it is not an experimental error, hence this post.

I'm still new around here and I have see that the moderators can have a trigger finger when discussing reactions that could lead listed precursors.

Anyway, I 'm sure one will come along soon and give me a thumbs up or down. If its an up, ill post the data and we can go from there.

[Edited on 7-2-2009 by greenimp]

greenimp - 7-2-2009 at 19:22

Ok so I've been told its ok to go in to experiential detail on this so here we go. (It is a very long post i apologize in advance)

So a little back story. Some of you may be familiar with my AlCl3/thiourea thread. It is a process that has been developed to demethyl, among other things, the methyl-ether of various catechol derivatives, I posted its successful use on vanillin.

Recently this reaction was adapted to eugenol. Now the product of this reaction should be 4-ally-catechol

some data on 4-ally-catechol, to easy the discussion.

Names;

4-allyl Catechol, 1 - allyl-3 ,4-dihydroxyphenyl, 1,2-dihydroxy-4-allybenzene, dihydroxychavicol, DHAB

Properties from http://www.chemyq.com/En/xz/xz5/44248joggi.htm;

Miscellaneous phenol oil, slightly scented. Colorless acicular (needle like) crystals from petroleum ether recrystallization at 48 -> 49°C.

Boiling Point 139°C at 5.33 mBar / 3.99 torr; peach nomograph predicts an atmospheric BP of 302.2°C (eugenol 256°C)

Boiling point: 123-124°C/1mmHg, 141-144°C/7mmHg, 147-149°C/10mmHg, 155-157°C/13mmHg, 156-158°C/16mmHg.

Solubility (H2O): 25 g/l at 26°C.
Recrystallization solvents: Benzene, petroleum ether, diethyl ether.

Quickly turns red in alkaline solution, dark green in alcoholic ferric chloride. Will return to eugenol when reacted with methyl iodide.

Back to the story:

This is considered by some to be a tricky molecule to produce, and there has been alot of work put into obtaining it. The result of the demethyl reaction is a light brown oil that distilled under vacuum at 135-145 C, depending on how good my vacuum pump is feeling that day. For the record, eugenol distills at 101 C, with my pump. The oil turns rust-orange red in alkaline conditions, and gives a dark green color when reacted with alcoholic ferric chloride. One big problem is I have not been able to crystalize this product, so I can't say definitely this is 4-ally-catechol. This is variable one. If someone can give some advice on crystallization, be my guest. Everything I have read about obtaining a solid uses flash chromatography or sublimation.

So on to the methylation reactions. To date two have been attempted.

The first is the PTC Methylenation of Catechol (Using CTAB) from the Yugoslavian paper Tetrahedron 44(21) 6677-6680 (1988) (uploaded at end of post)

In sort:

11.0 grams (0.1 mol) catechol is dissolved in 1000ml of 20% NaOH, and 3.2 grams (0.1 mol) of cetyltrimethylammonium bromide (Cetrimonium Bromide, CTAB) is added. The mixture is heated to 60°C for 30 minutes and then allowed to cool to room temperature, whereupon 21.2 grams (0.25 mol) of dichloromethane is added with stirring. The mixture is then heated to 80°C with a good reflux condenser for 5 hours, the solution saturated with NaCl and filtered. The solution is then extracted with 3x50 ml CH2Cl2, the pooled extracts washed with 50ml 20% NaOH to remove any phenolic materials, and then with 50 ml brine. The solution is dried over MgSO4, and the solvent removed under vacuum. Yield 90% of 1,3-benzodioxole.

This procedure was followed to the letter, including the salt saturation step which made the DCM extractions a total pain. Wash the pooled DCM extract 20% NaOH made a vicious emulsion that took a little salt addition to break up. Upon vacuum distillation i got 6.8 grams of yellow oil that came over a 133-150 C (I am not set up to distill small volumes accuracy, so sorry for the big range)

This oil had distinctly different smell from that of the 4-ally-C and eugenol, almost a hint of ammonia. Thinking in the CTAB was not a good PTC, a second attempt was made with the original DMSO/NaOH method.

This attempt was based on example D of us patent 4082774

http://www.freepatentsonline.com/4082774.html

here is what they did

D. A solution of 110 g. of catechol, 120 ml. of 50 percent aqueous sodium hydroxide and 200 ml. of DMSO was heated to 98° C. and stirred at that temperature for 30 minutes. This solution at 98° C. was added over a 30 minute period to a refluxing solution of 120 ml. of methylene dichloride in 300 ml. of DMSO. Thereafter, the reaction mixture was stirred at reflux for 1.5 hours. Steam was then passed into the mixture to achieve steam distillation of the product. The distillate (600 ml.) was extracted with 100 ml. of methylene dichloride, which extract was washed once with 50 ml. of deionized water. The methylene dichloride solution was then concentrated in vacuo at 40° C. to yield 119.4 g. of a colorless oil. Gas chromatographic analysis showed 97.5 percent methylenedioxybenzene. Corrected yield--116.4 g. (95.4 percent).

worked nice for catechol, but as for everything eugenol based, it was not so straightforward.

Experimental

A solution containing 105g of suspected 4-ally-catechol (all I had) 120 ml of 50% NaoH and 200 ml of DMSO where combined and brought to 95C, it had a red-brown color. A further 50 ml of H20 was used to rinse out the container holding the 4-ally-C, this was added to the solution, along with 25 G of NaOH pellets. (should have left good enough alone). This solution was added at 95C in 10 ml amounts to a refluxing solution of 120 ml DCM and 300 ml DMSO. The addition took 28 mins. During the addition a silt like precipitate formed in the flask, even with very good stirring. The flask was allowed to reflux for 1.5 hours. After which time the flask had a brown color, and a tan silt like precipitate mixing in it.

850 ml of steam was passed through the vessel and collected. This was extracted with 3x 50 ml DCM. The last to DCM extractions were clear. The reaming aq. layer was cloudy, i suspect from DMSO. The DCM was combined and removed via distillation, leaving 11 ml of a yellow oil. The oil reacted negatively with ferric chloride test (test stayed orange). It had a strange floral smell with sulfur overtone. This oil was then attempted to be vacuum fractionally distilled, resulting in 3-4 mls that came over a 80C and a large fraction that came over at 129.

Disappointed, the reaming reaction flask was distilled to dryness. A large ~800 ml fraction was obtained it was milky with a slight yellow oil on top. The was removed an proved to be 9 ml of a similar oil to that from the steam distillation. It too came over during distillation at around 127-9.

Feeling that someones vacuum pump is on the fritz, or that the small volume of oil was giving improper results a BP test was conducted at ATM. The yellow oil boiled at 229 C (corrected for altitude). While conducting the test, a very weak smell of root-beer was detected

Finally, as the reaction flask was being cleaned, as it had a large crusty precipitate (NaOH now, and the brown silt) as soon as water hit the inside of the flask a STRONG odor of root beer filled the room. As the precipitate broke up and came out the flask the experimenter crumbled it in his hands and was greater with even stronger root-beer smells.

Discussion:

The root-beer smell makes me think the reaction worked at a low level, and that a di-hydroxy compound was present in the starting oil. But the preciptate forming and nature of crunching remaing material makes me think a large side reaction is occuring....

Anyway, there it is. Like it is always said, experiment is always king. It should work, but something is weird is happening. Either a contaminate in the starting material, or a side reaction is occurring.

Attachment: Tetrahedron 44(21) 6677-6680 (1988) ctab methylation.pdf (393kB)
This file has been downloaded 1835 times

Tunnels - 8-2-2009 at 01:52

Quote:

Originally posted by greenimpAnyway, there it is. Like it is always said, experiment is always king. It should work, but something is weird is happening. Either a contaminate in the starting material, or a side reaction is occurring.

Bit o' both?

Or maybe not a contaminate, but a shortage? A full mole of 4-Ally isss closer to the 151 g mark now.

Also, perhaps add your catechol slower. Maybe ever under nitrogen. I imagine it'd be helpful to keep the dianion in a low concentration to prevent side reactions. And the inert atmosphere couldn't hurt.

greenimp - 8-2-2009 at 15:04

yup those were on my list....for other things to try...

apex of the vortex of the future

gritty_cryst - 8-2-2009 at 18:24

greenimp, you will go down in history bro.

After a long retirement, I think this will bring me back into the game. It won't be long before the kinks are worked out in this procedure. When we imagine demethylation (AlCl3 + thiourea) followed by methylenation of eugenol/vanillin as standard, we can see the rules changing before our eyes.

The writeup for methylenation of 4-allyl-catechol at http://www.erowid.org/archive/rhodium/chemistry/tcboe/chapte... uses anhydrous conditions under nitrogen, as in the original paper by Bonthrone and Conforth (http://www.erowid.org/archive/rhodium/chemistry/methylenatio...). The same writeup is also in this book: http://books.google.com/books?id=y5mZrW1KB_AC&pg=PA166&a...

Nowhere are yields mentioned. But you used the aqueous, patented improvement described here (http://www.erowid.org/archive/rhodium/chemistry/methylenatio...), but that was reported to work with simple catechol, not the 4-allyl.

And you still smelled rootbeer. Bless you greenimp.

Can't wait to hear some more yield reports. Times are a changin'.

chemrox - 8-2-2009 at 22:46

a couple of recommendations: get a way to manage your vacuum system, "when my pump feels like it.." doesn't really cut it. I have a Cartesian manostat now but before that improvement I had a McLeod gauge and metering valve for a slow leak in the system to hold the vacuum at around 3-5 Torr. Now I can hold a vacuum at 0.1 torr if need be. Anyway, rig up some way to control it
2) while you're at it, rig up a way to evacuate your glass and replace the atmosphere with N2. A manifold is nice to have, they're expensive but a glassblower made me one for $50. Before that acquisition I used a pair of three-way stopcocks and a baloon. It's better collecting rootbeer than just smelling it.

greenimp - 8-2-2009 at 22:59

Thanks, I was going to try the nitrogen atmosphere on my next run. I have a argon welding tank that I think would be ok to use in place of nitrogen. Right?

Also, I have a automotive vaccum gauge on the pump, but it always reads at 23.8-24.2 inHg on the gauge. I don't think their too accurate.

I have used the distillation point of eugenol to baseline the gauge. Under vacuum eugenol comes over at 101. Maybe next time I prep some 4-ally-C i will spike the run with 20ml of eugenol, so I can verify the conditions of the system.

Nicodem - 9-2-2009 at 00:25

Greenimp, what is your question about? Are you asking about methylation or methylenation of catechols? You keep on talking about methylation, but the reference you posted is about methylenation, and a few times you even speak about "mehtlyation" (whatever that means). Neither in the case of methylation or methylenation is the allyl substituent of any concern since the basicity of the reaction medium and temperature required is not high enough to have affect it. Obviously you need an inert atmosphere since catechols just like hydroquinones are sensitive toward oxygen when in basic media, otherwise this reaction is just like any other alkylation (though in the case of methylenation the electrophile is quite weaker due to geminal halogens having inductive effect over each other).

PS: What is all that bullshit about an argument with a coworker? We don't need to read fiction here. Ask questions directly and coherently.

peach - 9-2-2009 at 01:57

Thanks gritty_cryst and nico

greenimp - 9-2-2009 at 02:20

Actually, there has been an argument. I keep saying the reaction won't work on 4-ally-C, based on my experiences. She, like a lot of you, seem to think it will. It's not BS, really.

[Edited on 9-2-2009 by greenimp]

Nicodem - 9-2-2009 at 04:07

I don't get it. Above you describe that the methylenation of your substrate worked and now again you say it does not. So does it or does it not?

Quote:

Originally posted by greenimp
This is variable one. If someone can give some advice on crystallization, be my guest. Everything I have read about obtaining a solid uses flash chromatography or sublimation.

If it does not crystallize it is not pure enough. You should try crystallizing by trituration in toluene/petroleum ether in cold. Alternatively, if you have access to analitical instrumentation, use it. At least check the TLC purity or, even better, ask a friend to make an 1H NMR of it. This way making experiments on such huge scale and writing sentences like "A solution containing 105g of suspected 4-ally-catechol (all I had)..." will not sound as dumb as they do now.

Quote:

So on to the methylation reactions. To date two have been attempted.

The first is the PTC Methylenation of Catechol (Using CTAB) from the Yugoslavian paper Tetrahedron 44(21) 6677-6680 (1988) (uploaded at end of post)

You got me confused again. Now you post a paper about alkylations that utmost could be useful for methylations, yet you talk about methylenation of your substrate.

Quote:

11.0 grams (0.1 mol) catechol is dissolved in 1000ml of 20% NaOH, and 3.2 grams (0.1 mol) of cetyltrimethylammonium bromide (Cetrimonium Bromide, CTAB) is added. The mixture is heated to 60°C for 30 minutes and then allowed to cool to room temperature, whereupon 21.2 grams (0.25 mol) of dichloromethane is added with stirring. The mixture is then heated to 80°C with a good reflux condenser for 5 hours, the solution saturated with NaCl and filtered. The solution is then extracted with 3x50 ml CH2Cl2, the pooled extracts washed with 50ml 20% NaOH to remove any phenolic materials, and then with 50 ml brine. The solution is dried over MgSO4, and the solvent removed under vacuum. Yield 90% of 1,3-benzodioxole.

This procedure was followed to the letter, including the salt saturation step which made the DCM extractions a total pain. Wash the pooled DCM extract 20% NaOH made a vicious emulsion that took a little salt addition to break up. Upon vacuum distillation i got 6.8 grams of yellow oil that came over a 133-150 C (I am not set up to distill small volumes accuracy, so sorry for the big range)

I can not find this experimental in that paper. Where did you got this from?

Quote:

Experimental

A solution containing 105g of suspected 4-ally-catechol (all I had) 120 ml of 50% NaoH and 200 ml of DMSO where combined and brought to 95C, it had a red-brown color. A further 50 ml of H20 was used to rinse out the container holding the 4-ally-C, this was added to the solution, along with 25 G of NaOH pellets. (should have left good enough alone). This solution was added at 95C in 10 ml amounts to a refluxing solution of 120 ml DCM and 300 ml DMSO. The addition took 28 mins. During the addition a silt like precipitate formed in the flask, even with very good stirring. The flask was allowed to reflux for 1.5 hours. After which time the flask had a brown color, and a tan silt like precipitate mixing in it.

Why didn't you use the stoichiometry from the patent example? Why the excess NaOH/H2O?
Also, it appears to me you did not perform the distillation with steam properly. It only works if you have a biphasic system while you used the steam from 850ml water only instead of first diluting the reaction mixture with at least four times as much volume water as DMSO used in order to reduce the solubility of the product. It looks to me like you barely used enough steam to get the product start to distil and then just stopped. You need to steam distil until the distillate is clear and no more turbidity forms upon condensation.

Good luck with your experiments. However, I strongly advise you to stick to one of the examples of this specific reaction as described in the literature (on this specific substrate). Particularly since you are not 100% sure your substrate is what you think it is (though I agree it most likely is) and how pure is it. You should have vacuum distilled it with a column. This way it would most likely crystallize spontaneously. Also, in your methylenation attempts, monitor the temperature of the reaction mixture (thermometer in the flask!) if you don't already. Unless you use a special apparatus to introduce the reflux underneath the reaction mixture, the CH2Cl2 will mostly just stick in the vapour phase if the reaction mixture is too hot, or the reaction will proceed to slowly if to cold. That's why the rate of addition of CH2Cl2 must be correlated to the temperature reading of the reaction mixture.

[Edited on 9/2/2009 by Nicodem]

greenimp - 9-2-2009 at 08:52

Quote:

I don't get it. Above you describe that the methylenation of your substrate worked and now again you say it does not. So does it or does it not?

I say it does in in that the yield is extremely low, from the DMSO method i got 1-2 mls. That and the NaOH cake that smelled of root-beer. I'm not saying that nothing is happening in the reaction, just not what I want to be.

Quote:

This is variable one. If someone can give some advice on crystallization, be my guest. Everything I have read about obtaining a solid uses flash chromatography or sublimation.

Quote:

Sorry if that sounds dumb to you, but it is the truth. It is a brown oil that I highly believe to be 4-ally-catechol. I have done everything I can with my current equipment to determine what the substance is. The next step if i can not get it to crystallize is to send it out for analysis. I know of a few places that will do a work up on it, but this can get expensive.

Can you expand on the crystallizing by trituration in toluene/petroleum ether process?

Quote:

You got me confused again. Now you post a paper about alkylations that utmost could be useful for methylations, yet you talk about methylenation of your substrate.

Correct, the paper I posted does not have a specific example of a methylenation. The idea for the use of the CTAB/NaOH method comes from a long discussion about the subject on a board that no longer exists. (Hive) The rhodium archive contains a condensed version of this discussion, I was not totally surprised when it failed on the 4-ally-C. I do believe it is a suitable reaction for methylenation, when DCM is used. I have had success using it with protocatechaldehyde, admittedly with yields in the 40% range, but it worked.

Quote:

That is the interpenetration of the paper by psycokitty and others came up with about 10 years go at the hive. It was never tested to my knowledge until now. The procedure worked at about a 40% yield for protocatechaldehyde.

Quote:

Why didn't you use the stoichiometry from the patent example? Why the excess NaOH/H2O?

Pure researcher error. I had the DMSO/NaOH system setup and read to go, and when I went to add the catechol, there was less than I expected. In an attempt to get every lass drop of the catechol into the reaction the flask containing it was rinsed with h20. I added Naoh to keep the concentration right. Kind of stupid looking back on it, but sometimes one does not make the best decisions in the moment. Also, it was my first time running this reaction.

Quote:

Also, it appears to me you did not perform the distillation with steam properly. It only works if you have a biphasic system while you used the steam from 850ml water only instead of first diluting the reaction mixture with at least four times as much volume water as DMSO used in order to reduce the solubility of the product. It looks to me like you barely used enough steam to get the product start to distil and then just stopped. You need to steam distil until the distillate is clear and no more turbidity forms upon condensation.

That is all the paper said to use. It did not mention diluting to 4x the volume. In the paper they use 650 mls h20. I tested small samples of the distillate as it came over, by extracting with DCM. By 700 ml's the DCM layer was clear, leading me to believe I had gotten most of the product out.

Quote:

Good luck with your experiments. However, I strongly advise you to stick to one of the examples of this specific reaction as described in the literature (on this specific substrate). Particularly since you are not 100% sure your substrate is what you think it is (though I agree it most likely is) and how pure is it. You should have vacuum distilled it with a column. This way it would most likely crystallize spontaneously. Also, in your methylenation attempts, monitor the temperature of the reaction mixture (thermometer in the flask!) if you don't already. Unless you use a special apparatus to introduce the reflux underneath the reaction mixture, the CH2Cl2 will mostly just stick in the vapour phase if the reaction mixture is too hot, or the reaction will proceed to slowly if to cold. That's why the rate of addition of CH2Cl2 must be correlated to the temperature reading of the reaction mixture.

[Edited on 9/2/2009 by Nicodem]

Thanks for the input. The refluxing DCM is something I thought about alot. What kind of apparatus could deliver the condensating DCM to the bottom of the flask? I have been monitoring the reaction temperature. But I think when I go to the inert atmosphere I am going to run out of ports quickly. I might be able to rig something up. Maybe I can use a infra red thermometer.

The only column I have is a very large, 16 inch vigurex. Right now the runs are only producing about 50 grams of 4-ally-C. But I will combined 4-5 runs and fractional distill them. This might help alot. That or maybe I can get your trituration working. Trust me I hate working with a big unknown like this. But from reading all the various synthesis methods for 4-ally-c, a light brown oil that does not spontaneously crystallize is not a unheard of occurrence.

EDIT: after thinking about it for the better part of a day, I think I may not have dried the oil well enough before distillation. I could have a azetroph, and that would explain part of the wide range of temperatures that the oil comes over on. I need to re-prepare my drying agent, and will use an excess next time. That and fractional distillation.

[Edited on 9-2-2009 by greenimp]

Nicodem - 10-2-2009 at 02:21

Quote:

Originally posted by greenimp
Sorry if that sounds dumb to you, but it is the truth. It is a brown oil that I highly believe to be 4-ally-catechol. I have done everything I can with my current equipment to determine what the substance is. The next step if i can not get it to crystallize is to send it out for analysis. I know of a few places that will do a work up on it, but this can get expensive.

What sounded dumb is that you were doing a trial reaction, of which you were sceptic in the first place, by using such a huge amount of starting material (of which you had no more). Experimenting on new reactions is done on a couple of mmol scale, not on almost molar scale.
That your putative 4-allylcatechol is a liquid is not unusual per se. Some compounds with a low mp can be relatively pure (>95%) and still refuse to crystallize at room temperature. Some are even diamorphous, meaning they can be both solid or liquid at the same temperature even if completely pure and will not crystallize unless seeded with a crystal or by mere coincidence. The problem is that your putative 4-allylcatechol, being a liquid, could also be a 1 : 1 mixture with eugenol, for example, as far as you know. That's why you would need to ascertain its purity. Checking its TLC purity is something every amateur can do with a minimum of effort (though I admit TLC plates are not exactly cheap, but one pack will last you forever).

Quote:

Can you expand on the crystallizing by trituration in toluene/petroleum ether process?

There is nothing to expand. Just pour some petroleum ether over some of your product and stir with a glass rod (also by scratching on the glass wall to produce some crystallization seeds). Keep cold by immersing in an ice bath. If it does not work, decant the petroluem ether, pour in some fresh one and continue. However, giving you use vacuum distillation to isolate this compound, I would rather suggest you to fractionate it. If you don't have a small enough Vigreux, then pack a 10-20cm adaptor with column packings (or glass shards) and use this instead. Improvise.

Quote:

You can't just follow patents without understanding what you do. DMSO is a cosolvent increasing the solubility of the reaction product. Unless you have a clear cut biphasic system where the desired product to be distilled is soluble in one phase only, you are very far from the ideality of steam distillation. It is quite likely you were deluded by the absence of turbidity in the distillate because you were actually only collecting the initial CH2Cl2/H2O mixture, while the desired product had not even begun to distil since the reaction mixture did not condense enough water to make this product insoluble. Read the theory before following experimental procedures, because they are written in such minimalistic manner as for other experts to understand. Not to mention the way patents are written...

Quote:

Thanks for the input. The refluxing DCM is something I thought about alot. What kind of apparatus could deliver the condensating DCM to the bottom of the flask?

A custom made apparatus, though improvising you could use a dropping funnel with the exit prolonged with a tube immersed in the reaction mixture. But it is not like this is going to help as much as just corresponding the addition rate with the reaction temperature. A good stirring with the reflux dropping inside the vortex might be just as efficient as a special apparatus.

Quote:

I have been monitoring the reaction temperature. But I think when I go to the inert atmosphere I am going to run out of ports quickly. I might be able to rig something up.

You can introduce inert atmosphere trough the same port where the thermometer is by using a septum with a hole for the thermometer and a needle for argon or nitrogen. Mind that once you purge the apparatus and start adding CH2Cl2 you must reduce the gas flow to a few ml/min or else most CH2Cl2 will simply be flushed away (just check the vapour pressure of CH2Cl2 at room temperature!). You only need to maintain a minimal overpressure to keep the air away.

PS: Please pay attention at the frameset of quotations in your posts and edit them when scrambled like the above one.

greenimp - 10-2-2009 at 02:55

Quote:

Originally posted by Nicodem

That your putative 4-allylcatechol is a liquid is not unusual per se. Some compounds with a low mp can be relatively pure (>95%) and still refuse to crystallize at room temperature. Some are even diamorphous, meaning they can be both solid or liquid at the same temperature even if completely pure and will not crystallize unless seeded with a crystal or by mere coincidence. The problem is that your putative 4-allylcatechol, being a liquid, could also be a 1 : 1 mixture with eugenol, for example, as far as you know. That's why you would need to ascertain its purity. Checking its TLC purity is something every amateur can do with a minimum of effort (though I admit TLC plates are not exactly cheap, but one pack will last you forever).

I have done alot of TLC, I should have some in the lab anyway. I really don't think there is any eugneol in my unknown. I know smell is not something you should depend on, but the product has almost no odor.

Quote:

I did another run tonight, my yields are up around 75%. And the reaction is become very routine at this point. I get 55-65 grams per run, which isn't too bad. Once I get more eugenol I plan to scale it up. Did a fractional vacuum distillation this time. At 23.5 inHg on my automotive vacuum gauge, it came over at 139-144, with the bulk at 140. I will try to re crystallize this time.

Quote:

good advice. I read up on steam distillation last night, and sure enough you are right. The Kings chem guide also recommends the 4x dilution. Live and learn. Steam distillation was not really taught in my chem classes, or if it was we did one experiment with it, and I have no recollection of it. My O. chem lab manual had a very good description though, so I don't think I'll screw that up again.

Quote:

I'll give it a try. I was thinking of using a 3 neck flask with a stop cock on the bottom and maybe collecting the condensing DCM and introducing it through the bottom of the flask.

Quote:

The needle idea is fantastic. I have alot of experience blowing out O2 from fermentations in order to do mixing and oxygen uptake tests.

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PS: Please pay attention at the frameset of quotations in your posts and edit them when scrambled like the above one.

You don't know how many times I edited the post trying to fix them. I gave up.

Thanks so much for your input.

greenimp - 13-2-2009 at 19:55

Well she proved me wrong. Here is a paper documenting the actual methylenation of 4-ally-C. It can (and has) be done.

Some things of note, they use K2CO3 as their base, and use it at a higher concentration than any of the NaOH/DMSO papers I've seen.

The run the reaction for 3H, most others are 1-2. Although the temps are the same.

They too use N2.

They use the higher yielding CH2I2 than DCM.

Without a catalyst, their yields are 50%. 50%! With Ch2I2, 3H, and roughly twice the base. No wounder my yields have been so horrible.

Anyway, for the few people that are interested, here is the paper.

Oh, and I sent a sample off for NMR. 40$, not bad.

Attachment: methyleneation of allylebenzene.pdf (296kB)
This file has been downloaded 56532 times

Nicodem - 16-2-2009 at 00:33

Quote:

Originally posted by greenimp
Well she proved me wrong. Here is a paper documenting the actual methylenation of 4-ally-C. It can (and has) be done.

You never said that you never even saw a reference about 4-allylcatechol methylenation. You were told there exist in the replies above.

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Some things of note, they use K2CO3 as their base, and use it at a higher concentration than any of the NaOH/DMSO papers I've seen.

You are wrong about that. They use 12% excess of CH2I2 and K2CO3. The ratio between CH2I2 and K2CO3 is stoichiometric (1 : 2).

greenimp - 1-5-2009 at 21:20

I wanted to try to bring this thread to a happy ending. After a lot of work and trouble shooting, the problem I was having turned out not to be the reaction, but the starting reagent. I was finally able to determine that I DID NOT have 4AC when I posted this. Makes it kind of hard to get the methylenation to work with out it.

Unsurprisingly, the reaction works as described if a proper di-hydroxy substrate is used.

GI

Nicodem - 4-5-2009 at 23:53

Another example on why claiming anything without analytical data is useless.

Anyway, out of curiosity, what was that thing that you believed it to be 4-allylcatechol?

greenimp - 5-5-2009 at 06:54

Well, I was trying out a new method for converting eugenol to 4AC. Needless to say it wasn't working.

Basically I was just getting a a nice eugenol fraction back. But as you know I was using BP's under vacuum to try and determine the fraction's identity. Even with my gauge, which I now know to be inaccurate, it was a loss.

I switched back to a method I know worked, abit at low yields, and sure enough the methylenation worked.

I really think my next purchase will be a a box of TLC plates. Lesson learned.

[Edited on 5-5-2009 by greenimp]

zed - 16-5-2009 at 15:34

Seal up your vacuum system. And, buy a real vacuum gauge. It is an inexpensive necessity.

An accurate gauge might have made most of this discussion unnecessary, and it could have saved you that NMR fee.

Such gauges are available at way below retail on e-bay.

Simply vacuum distilling some of your starting material as a reference, and then vacuum distilling your product, (with an accurate gauge).......Might have revealed to you, that there was no change in BP......And, quite possibly, no reaction.

Of course, hindsight is always 20/20......And the purchase of equipment, that I personally, won't have to pay for, is easily recommended.

Arrhenius - 16-5-2009 at 22:49

I was told that it is possible to achieve the desired methylenedioxy product from a catechol by reaction with formaldehyde or its dimethyl acetal. This would be an acetalization.

Has anyone heard of this?