Piperonal from guiacol?

[Aperson444]

I'm not sure if this has been discussed. According to Wikipedia (bear with my shoddy source), one can synthesize vanillin from KOH/CHCl3 and guiacol. The paper cited was (Reimer, 1876). I'm not sure of yields or anything. From there, you could go to O-demethylate the vanillin using BeCl2 (which is not the most pleasant chemical, but there are worse salts and it's fairly unwatched) in toluene. This method was described by Zhang in Demethylating Reactions of Methyl Ethers. He described a 95% yield using toluene and BeCl2 at reflux for 5 hours. An alternative O-demthylation was described in the same paper using SnO2 in CHCl2. So after that you have the two ortho hydroxyl groups. Using Rhodium's method, one can form the methylenedioxy portion by distilling from the catechol mixed with CH2Cl2 in DMSO. I suppose one could use CH2I2 or CH2Br2 as well.

From piperonal, one can Shulgin the process to make the nitroalkene, which can either be reduced to MDA or reduced using iron and HCl to MDP2P. My worry is the final step (the methyleneation). I've heard it's a messy process. I'm also worried that the guiacol --> vanillin method might be of low yield. I can't find the particular yield from that reaction.

EDIT: I found out the reaction name. It's called the "Reimer-Tiemann Reaction". It involves deprotonation of the phenol in guiacol and the addition of an electron to CHCl3 to get rid of one chloride anion. In Rhodium Chapter 5, they say this reaction is not effective for catechols, but I wonder what it would be for either ortho-dimethoxybenzene or guiacol. They also state a reaction from vanillin to piperonal, but instead of BeCl2, they use AlBr3 and the such. One could probably just buy vanillin itself, but who knows what the feds are looking after now.

[BungHole]

Originally Posted by Aperson444

I'm not sure if this has been discussed. According to Wikipedia (bear with my shoddy source), one can synthesize vanillin from KOH/CHCl3 and guiacol. The paper cited was (Reimer, 1876). I'm not sure of yields or anything. From there, you could go to O-demethylate the vanillin using BeCl2 (which is not the most pleasant chemical, but there are worse salts and it's fairly unwatched) in toluene. This method was described by Zhang in Demethylating Reactions of Methyl Ethers. He described a 95% yield using toluene and BeCl2 at reflux for 5 hours. An alternative O-demthylation was described in the same paper using SnO2 in CHCl2. So after that you have the two ortho hydroxyl groups. Using Rhodium's method, one can form the methylenedioxy portion by distilling from the catechol mixed with CH2Cl2 in DMSO. I suppose one could use CH2I2 or CH2Br2 as well.

From piperonal, one can Shulgin the process to make the nitroalkene, which can either be reduced to MDA or reduced using iron and HCl to MDP2P. My worry is the final step (the methyleneation). I've heard it's a messy process. I'm also worried that the guiacol --> vanillin method might be of low yield. I can't find the particular yield from that reaction.

EDIT: I found out the reaction name. It's called the "Reimer-Tiemann Reaction". It involves deprotonation of the phenol in guiacol and the addition of an electron to CHCl3 to get rid of one chloride anion. In Rhodium Chapter 5, they say this reaction is not effective for catechols, but I wonder what it would be for either ortho-dimethoxybenzene or guiacol. They also state a reaction from vanillin to piperonal, but instead of BeCl2, they use AlBr3 and the such. One could probably just buy vanillin itself, but who knows what the feds are looking after now.

Expect a majority of the product of the Reimer-Tiemann to be formylated ortho to the phenol, not para. Should be kinetically favored. Want this?

[Aperson444]

Ah well Esposito (1997) used glyoxylic acid with guiacol to synthesize it. This condensation reaction is fairly documented, but I can't find yields. Of course, one could buy guiacol. I was more interested in the O-demethylation using BeCl2. I'm not an organic chemist, but that paper looks a bit sketchy. However, I was able to find another source for this procedure (http://www.sciencedirect.com/science...40402096008150). They used BeCl2 to demethylate polyaryl molecules, but I see no reason why it wouldn't work on guiacol, vanillin or eugenol. Can anyone dig up more information?


Oh and I'm sure someone mentioned this, but as I was looking for efficient vanillin synthesis protocols I found this: "An Efficient Synthesis of 3,4,5-Trimethoxybenzaldehyde from Vanillin" Rao, Durvasula V.; Stuber, F. A.

I can't access it, as I did not buy it (nor do I wish to), but is this that one synthesis with the electrochemical cell?

[fcknut]

Originally Posted by Aperson444

Oh and I'm sure someone mentioned this, but as I was looking for efficient vanillin synthesis protocols I found this: "An Efficient Synthesis of 3,4,5-Trimethoxybenzaldehyde from Vanillin" Rao, Durvasula V.; Stuber, F. A.

I can't access it, as I did not buy it (nor do I wish to), but is this that one synthesis with the electrochemical cell?

http://www.erowid.org/archive/rhodiu....vanillin.html

[armorking]

yeah you could go that way, or just BUY vanillin outright (its available everywhere) and demethylate that ah la rhodium and close the mthylene dioxy bridge as well, a somewhat easier and more efficient path than messing around with guiacol. unless of course you have a lot of guiacol floating around .....

[Aperson444]

Yea, I was thinking that too. I thought that vanillin might be too suspicious, but that was just paranoia speaking.

[armorking]

suspicious? hell no brother! its used in fricken everything from vanilla icecream to vanilla flavoured condoms-not that I'd KNOW what they taste like. actually , I'v got a 3/4 full 500ml bottle of guiacol, its quite thick stuff, just one of those things thats sits around till the day comes when i can make use of it. But the vanillin thing is pretty sweet really, even if you cant get the 100 percent powder, its easy to get rid of the other crap its mixed with, you've got the chjoice of solvent seperation or you could even make use of the aldehyde group and make a bisulphite addition product, which are insoluble in saturated metabisulphite solutions, ketones also can be seperated/purified this way too.

[BungHole]

I just bought two 14 gram jars of food grade vanillin for less than 10 USD including shipping. It's packaged exactly the way any spice rack type food product would be packaged.

I am thinking about making some from maple wood though, just for fun.

[nshanin]

^How do you plan to do the demethylation? Aluminum trihalide?

[BungHole]

Originally Posted by nshanin

^How do you plan to do the demethylation? Aluminum trihalide?

Who, me? I'm not really sure what I'm even doing with it. I saw it for sale and decided to buy it just because I figured I'll need it some day.

If I did demethylate it though, I probably would try AlCl₃. I've heard so many bad things about cleaving ethers with hydrogen halides.

Is pyridine effective for this reaction? I'll have to go read around rhodium a bit.

[Aperson444]

Have you heard of the thiourea/AlCl3 reaction? I heard it worked pretty well via thread on Sciencemadness.

Here's the thread: http://www.sciencemadness.org/talk/v....php?tid=11607

Thiourea, while not OTC, is not watched like pyridine. Looks cheaper too, some Chinese suppliers sell multi-kilo sacks of it for pharmaceutical companies and the like. The ratios are a bit wack, you need 4x the concentration (relative to vanillin) for AlCl3 and 2x for thiourea, but the reported yield was not bad at all.

[baffler]

Thiourea can actually be found as like a coin cleaner in mix with sulfuric acid (separable easily?? Idk).

Now this reaction has really not gotten the attention it deserves, I believe so I am (and by I, I of course mean my imaginary friend) going to give this a similar scale whirl, hopefully in not too long (a couple weeks max I would say, still not home yet--and then the challenge begins... in a couple ways..). Anyhow, it sounds good in theory and in practice so why the fuck not?? And vanillin is certainly not watched as long as you're being reasonable in quantity with it (I'm getting a friend to buy a couple pounds off ebay). Also, I hit gold with the Visa gift card, in utilizing that--just saying (hoping noone of authority finds this out soon). I bought over a pound of AlCl3 no sweat to a PO box, using the pre-prescribed name "AVS Registered" as it says to do on some online youtube vid. Aperson444 and others: I would recommend this for discreet purchases (don't know if it works for Ebay but perhaps...).

[Aperson444]

The O-demethylation and following methyleneation to piperonal are probably the most difficult steps in the process. I think in such cases, it would be justified to buy several pounds of vanillin (and appropriate reagents) because the yields cannot be expected to be very high. From there however, condensation with nitroethane to yield the nitroalkene would allow a smooth conversion via SnCl2/HCl to the desired ketone. If one can efficiently perform those first two steps to piperonal, the outcome of the process might not be all that bad.

[baffler]

Ah agreed about the difficulty, but thankfully it's not the last few that are most likely to fuck up. However, have you checked out this??:

http://www.freepatentsonline.com/5936103.html

States yields in the 90s for methylenation so perhaps the yields won't be quite so low... I mean, it sounded like greenimp on SM saw some bitchin yields with just adding OTC tetrachloroethylene and probably furthing reflux for another hour or two. My imaginary friend has an idea of a setup and if all goes well will post his lab shit on my account (I'll let him use it I guess )

Also, I know it may not be advisable, but my imaginary friend is probably gonna rely on iron powder because of the forseeable future of Tin dichloride (dihydrate) getting harder to get. Iron powder ain't never gonna be hard to get though--at least not any time soon. Plus, it sounds like up to a couple hndred grams of Fe (~100 g nitropropene) and you can just use regular stirring equipment. It jst may be hard to work out the specifics of larger batches (blenders or some shit??) if those come along...

EDIT: the setup I was referring to was for the methylenation with DCM in N-methylpyrrolidone (patent). This sounds very viable as potassium carbonate would be a good base/deprotonator in the dipolar aprotic solvent which will dissolve ions well and thus promote SN2. The theory is there, so the yields will just have to be tested (sure as fuck sounds more optimistic than the dismal 61% on erowid/Rhodium's info page about dihydroxybenzaldehyde methylenation).

[Aperson444]

I swear there was a Rhodium article using CH2BrCl with high yields reported. Can't find it anymore however. Also, I believe that PTCs can boost yields very well. It might not be such a bad idea to throw together some dihalomethane, NaOH and a tetralkylammonium PTC just for teh lulz. I suppose the most uncertain step is the demethylation of vanillin however.

I plan on getting this: J. Org. Chem., 1962, 27 (6), pp 2037–2039 once I get back to the U and pirate me some ACS publications from the database. Fucking assholes charge premium for good literature

Iron powder/ketone should work fine. I think the advantage of this particular synthetic pathway is the fact that several of the reagants are cheap and OTC enough for bulk synthesis (100 kg of vanillin would be easy shit for most people), meaning moderately low yields are acceptable.

[baffler]

Cha bud no joke about fucking ACS... Well I'll be sure to post results. Shit's a little delayed though gettin started, but hopefully soon.

And hell ya about PTC's. It should be attempted at least

Also, you'd need a fucking cement truck for Shulgin's Fe and acetic acid method and 100 kg haha but large scale is large scale... Anyhow, that article has (on the first page at least) info that heating vanillin at 60 C with benzene and AlCl3 gives 67% yields and I figure that thiourea is even a better acceptor of (e-donator to) that electrophilic methyl group, so I'd be expecting better yields with that method... Though it's worth lookin into if ya can.

EDIT: Sorry, read that wrong. Actually a completely different reaction so disregard the heating vanillin part... Anyways if you got time try lookin up "J. Kamlet, U. S. Patent 2,975,214, March 14, 1961" into google and click on the SECOND site. I'm just reading through, but it may have some good info. Also, I'm reading through that article and it just talks about the pyridine/AlCl3 and nitrobenzene/AlBr3 methods, though it's mainly about the former... Basically says like CHCl3 or ethylene chloride or DCM or ethyl bromide (wtf) can be solvents instead of DCM and slightly lowers yields (from ~88 to ~75%)... Also it has a few things that could be switched out for pyridine but the best is triethylamine with still only a 61.5% yield... Anything else you wanna know and I can hook you up so you don't have tu wait to go back to the University. Pretty interesting though that this paper states that even once acidified, the protocatechualdehyde will be in the aqueous layer, with DCM as the solvent.

btw I hope nshanin and others weigh in on some o this shit.

[Stasis]

Originally Posted by Aperson444

I plan on getting this: J. Org. Chem., 1962, 27 (6), pp 2037–2039 once I get back to the U and pirate me some ACS publications from the database. Fucking assholes charge premium for good literature

http://www.4shared.com/office/8zkH7dBP/phenylethercleavage.html

DCM as solvent - one-pot reaction to MD ring anyone?