?'s about demethylation / methylation of eugenol

[nitrous351]

I have a few questions regarding this procedure:

1. Given the difficulty in obtaining / synthing pyridine, is there any substitute for this reagent?
2. Is there a substitute for the DMF in the methylation part?
3. Is there a substitute for the ether in the methylation part?
Thanks in advance for replies. peace

[Rhodium]

Please link to the procedures you are referring to. We are not mind-readers, despite having used psychedelics for several years...

[nitrous351]

Sorry, Rhodium... I gotta quit reading your site after talking to that sweet cannabis sativa.
The link is on your page, Rhodium:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.html

The procedure is the 4th one down (by Startinout).
I have a few more questions... I want to start experimenting with some of these procedures (all of them on that page, namely the 3rd and 4th one). Is there a way I can do inert gas shielding without fancy lab equipment? I have a lot of basic glassware, but I couldn't find any instructions on inert gas shielding.
I guess you do that in a glovebox?
Is the shielding to prevent side reactions? Is there a way I can hack around the inert gas shielding in the 3rd procedure? thanks for the help... peace

[Rhodium]

1) I don't think anything but pyridine hydrochloride would work as good in the microwave procedure, with the possible exception of triethylamine hydrochloride, but it will surely be lower yielding. I'd suggest that you use another method if you cannot get pyridine.

2 & 3) Did you read the whole document before asking? Check out

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.html#methylenation

and you'll find a lot of different procedures for the methylenation step, many of which uses neither DMF or ether.

[nitrous351]

So, will someone answer my questions about the inert gas shielding, please? Is there a way I can hack around it in the demethylation step? Please see my second post in this thread to read the questions. Thanks in advance! peace

[Rhodium]

When dealing with 3,4-dihydroxyallylbenzene in solution (especially in basic solution) you really should use an inert gas blanket, as to prevent oxidation of it to the corresponding deeply colored and polymerization-prone quinone.

It is not as hard as you think, and you don't need a glove box in this instance, just allow a very slow stream of nitrogen or argon (from a welding gas supplier) seep in through a side-arm of the reaction flask, and let it escape through the condenser (preferably with a septum with a needle stuck through it placed in the top joint). The ever so slight overpressure inside the flask (1.05 atmospheres?) prevents any atmospheric oxygen from entering and oxidize the 3,4-dihydroxyallylbenzene.

[nitrous351]

Ok, Rhodium (or anyone else that can answer this), will this work (this idea is using glassware/equipment that I already have....)
Take a multi-necked flask (1 more neck on the flask than is needed in the reaction). Plug the extra neck with an inlet adapter.
Attach a scuba tank filled with argon to the inlet adapter via a latex hose.
Take a rubber solid rubber stopper and drill a smal hole through the center. Place this stopper on top of the condenser.
Turn on the argon, and feel over the hole in the stopper for pressure.

Will the above plans work for inert gas shielding? Do I need to accurately measure the pressure of the argon, or is it ok as long as I can feel pressure coming from the hole in the stopper? Sorry for such newbee questions, but this will be my first try at gas shielding.... I want to make sure I get it correct! Thanks peace

PS- is argon expensive in the US? Will they fill up a tank for anyone, or do you have to have a welding job code or something?

[Rhodium]

Yes, that setup will work. You don't need a more rapid gas flow than you just being able to feel the gas exiting through the bore hole.

Argon is significantly more expensive than nitrogen, and there is no need to not use nitrogen here. Also, don't use any SCUBA gear here, use a gas tank which is designed to hold exactly the gas you are intending to use, as well as any appropriate pressure valves.

[nitrous351]

I have just a few more questions about the 3rd reaction (AlI_{3) on Rhodium's demethylation/methylation page. OK, this is a direct quote from the page: 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!).
It says, "note the excess of aluminum," but shouldn't it say, "note the excess of iodine?"
Next question: It says that I can exchange the cyclohexane solvent as needed.... what would bee some other choices that I could use? Could I use a dihalomethane?
Also it says to add the eugenol via a slow drip. Any recommendations on time here? Am I trying to keep a certain temp? Is there a rate I should be trying to match? Or do I just go slowly enough that the apparatus doesn't explode?
Lastly, is ethyl acetate suspicious at all to buy in the US? thanks for help. peace}

[Rhodium]

As the reaction goes like this:

2 Al + 3 I₂ -> 2 AlI₃

The ratio of Al to aluminum you theoretically whould use is 2:3, which is equal to the 1:1.5 molar ratio in the text (I dunno about the "excess" it talks about, as it is no excess used).

You can not use a dihalomethane as solvent, only hexane/cyclohexane/heptane, or petroleum ether with a bp of 60-90°C.

I don't know if toluene would be stable against halogenation under these conditions, but if it is, it might be a viable substitute.

[nitrous351]

In the methylenation step, all procedures say to steam distill the product for purity. Is it OK for swim to do a regular distillation here (i.e., simple distillation to remove dihalomethane and solvent, then switch to a vacuum distillation to isolate the safrole)?
Also, SWIM has one last question about the demethylation procedure (the 3rd procedure on Rhod's page, by Startinout using AlI3)... this is a direct quote from Rhod's page:

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...

So, is the solid that SWIN immerses in the ethyl acetate the one he wants to keep? Or, when I remove the ethyl acetate will a new precipitate form? What exactly is meant by "remove the ethyl acetate?" SWIN thinks someone is going to have to spell it out for him. He thanks everybee in advance for help! peace

[Rhodium]

all procedures say to steam distill the product for purity. Is it OK for swim to do a regular distillation here

If steam distilling the safrole from a basic aqueous solution, no phenolic products will be carried over, but with regular distillation that may still happen. A slow fractional vacuum distillation using high vacuum might work, as excessive heating of phenols with allylic compounds might result in polymerization.

So, is the solid that SWIN immerses in the ethyl acetate the one he wants to keep? Or, when I remove the ethyl acetate will a new precipitate form? What exactly is meant by "remove the ethyl acetate?"

Some of the immersed solid will dissolve, and some will not. The insolubles are undesired and they are filtered off. The filtrate consists of crude allylcatechol in ethyl acetate. Removal of the ethyl acetate by vacuum distillation (as to not heat it too much and to keep oxygen out) will result in a new precipitate (alternatively an oil, which slowly crystallizes), which is the crude allylcatechol.