Oxidation of 3,4,5-trimethoxy benzyl alcohol using household bleach and PTC

I have been experimenting with various methods to oxidize 3,4,5-trimethoxy benzyl alcohol to 3,4,5-trimethoxybenzaldehyde. I have had the most success with sodium hypochlorite solution and a phase transfer catalyst.

The method is based on US patent 4239702, with some modifications. That patent in turn references methods from "Phase Transfer Catalyzed Oxidation of Alcohols and amines by acqeous hypochlorite" (Lee, Freedman, 1967). I adapted according to the PTC I had on hand.

Dissolve 3.26g (16.4mmol) 3,4,5-TMB Alcohol in 40ml of chloroform. 10 mol-% = 0.5g of tetrabutyl ammonium bromide (TBAB) is added.

120ml of "household strength" bleach (42g/l sodium hypochlorite) is added, and the mixture is stirred magnetically at 60C (oil bath temperature). This is just under the BP of chloroform so a loosely stoppered conical flask is recommended.

After 1 hour, the chloroform layer is separated and dried with sodium sulfate. The chloroform is then evaporated, leaving a white pasty substance.
I did also do an extraction on the acqeous layer with ethyl acetate, but no product was apparent there.

The white material was recrystalized from boiling cyclohexane. An amount of dense insoluble dark orange oil is visible at the bottom of the boiling liquid. I decanted the liquid leaving the oil behind.

On cooling and filtering, a pure white powder is obtained. MP measured was 70 - 72C, lit 72 - 74C. (Note that the MP of 60 - 63C noted in the patent is completely wrong.)

With 1:1 hexane:EtOAc, the Rf of the aldehyde is 0.89, compared to the alcohol with 0.52. (Only a single spot on the TLC was noted for the aldehyde).

Yield was not excellent, with 1.77g = 55%; trying a different PTC may increase yield.

Oh, and when selecting household bleach from the supermarket, just make sure you don't get the bargain "lemon scented" variety accidently, or your aldehydes will smell of fresh laundry

Quote: Originally posted by DrDevice

I have been experimenting with various methods to oxidize 3,4,5-trimethoxy benzyl alcohol to 3,4,5-trimethoxybenzaldehyde. I have had the most success with sodium hypochlorite solution and a phase transfer catalyst. The method is based on US patent 4239702, with some modifications. That patent in turn references methods from "Phase Transfer Catalyzed Oxidation of Alcohols and amines by acqeous hypochlorite" (Lee, Freedman, 1967). I adapted according to the PTC I had on hand. Dissolve 3.26g (16.4mmol) 3,4,5-TMB Alcohol in 40ml of chloroform. 10 mol-% = 0.5g of tetrabutyl ammonium bromide (TBAB) is added. 120ml of "household strength" bleach (42g/l sodium hypochlorite) is added, and the mixture is stirred magnetically at 60C (oil bath temperature). This is just under the BP of chloroform so a loosely stoppered conical flask is recommended. After 1 hour, the chloroform layer is separated and dried with sodium sulfate. The chloroform is then evaporated, leaving a white pasty substance. I did also do an extraction on the acqeous layer with ethyl acetate, but no product was apparent there. The white material was recrystalized from boiling cyclohexane. An amount of dense insoluble dark orange oil is visible at the bottom of the boiling liquid. I decanted the liquid leaving the oil behind. On cooling and filtering, a pure white powder is obtained. MP measured was 70 - 72C, lit 72 - 74C. (Note that the MP of 60 - 63C noted in the patent is completely wrong.) With 1:1 hexane:EtOAc, the Rf of the aldehyde is 0.89, compared to the alcohol with 0.52. (Only a single spot on the TLC was noted for the aldehyde). Yield was not excellent, with 1.77g = 55%; trying a different PTC may increase yield. Oh, and when selecting household bleach from the supermarket, just make sure you don't get the bargain "lemon scented" variety accidently, or your aldehydes will smell of fresh laundry

Quote: Originally posted by LearnedAmateur

If it’s legal, you are free to discuss the syntheses and such, if it’s illegal then no but you can still talk about them and their precursors, just no sharing of or asking for ‘recipes’ regarding stuff that will land you in jail for making/possessing. Although to be fair, it’s quite unclear on whether you can do so providing a particular substance is legal in your country compared to those that other members reside in.. I’ll have to have a search but what can and cannot be discussed might make a good sticky thread.

Quote: Originally posted by JJay

It's not illegal to make 3,4,5-trimethyoxybenzaldehyde, and it's easy to purchase, so why wouldn't this be an acceptable topic of discussion?

Quote: Originally posted by JJay

We all know what the product could be used for, but as I understand it, those poopy criminal enterprises aren't really interested in it, so as long as the discussion is centered around the chemistry, there should be no problem. I don't see why the OP would use this particular route to oxidize such an expensive material except that bleach and PTC materials are readily available. Surely almost any other oxidizer would be less finicky and produce higher yields with less product lost in side reactions.

Quote: Originally posted by PhenethylamineMachine

Quote: Originally posted by JJay   We all know what the product could be used for, but as I understand it, those poopy criminal enterprises aren't really interested in it, so as long as the discussion is centered around the chemistry, there should be no problem. I don't see why the OP would use this particular route to oxidize such an expensive material except that bleach and PTC materials are readily available. Surely almost any other oxidizer would be less finicky and produce higher yields with less product lost in side reactions. Which route would you suggest? Honestly, if I wanted to synthesize 3,4,5-trimethoxybenzaldehyde I would start from para-cresol. Its fairly simple, and only requires two steps. para-cresol is treated with bromine in the presence of carbon tetrachloride. when the initial reaction has completed water is added and the reaction mixture is held at reflux, and is then chilled, at which point 3,5-dibromo-4-hydroxybenzaldehyde will precipitate out and is filtered-off and collected. Next the 3,5-dibromo-4-hydroxybenzaldehyde is reacted under heat and pressure with sodium methoxide and a cuprous chloride catalyst, next the reaction mixture is treated with dimethylsulfate and NaOH, at which point 3,4,5-trimethoxybenzaldehyde is precipitated out and collected by filtration. Seems far more simple to me... Though it's possible that the original poster just happened to have some 3,4,5-trimethoxy benzyl alcohol to experiment with...

Quote: Originally posted by Polverone

It's probably spitting into the wind but I would like to remind everyone that the legal restrictions (or lack thereof) on possessing/manufacturing a substance has never been a reason for me to shut down discussions here. Hence the large, flourishing Energetic Materials section. I would actually enjoy more discussion of novel psychoactive substances here, or novel routes to popular materials. Much how I enjoy new substances or synthetic routes to energetic materials when they're discussed in the EM section. The USA has some of the most overbearing synthetic drug laws but some of the most permissive free speech laws in the world, so there is no risk to the forum or myself from discussing any chemistry here no matter how great the legal penalties might be if you get caught trying to implement said chemistry in your own home. I don't like low-effort threads started by people who are apparently just looking for a quick way to get high or get rich. Nor do I like low-effort threads started by people who just want to make a big, impressive explosion without too much work. But I am never going to lock a thread just because it might be a felony to do the chemistry where I live, or where some other members live. Everything is fine to write about and some members may be more risk-tolerant or lucky enough to live in less legally uptight jurisdictions. The legal considerations, like the personal safety risks, are the responsibility and choice of the individual contemplating doing some chemistry. So please, feel free to discuss synthetic routes to this ketamine metabolite or any other interesting molecule that crosses your mind.

Yes, this thread is fine. It reports a procedure that the OP actually did, and the discussion has remained scientific and professional. Scientific discussions of making psychoactive compounds and precursors are tolerable. Alternatively if it was a thread where the OP was "how I make 3,4,5-trimethoxybenzdehyde plz help " it would already be in Detritus. Discussion of using psychoactive substances, especially those made in an amateur lab, is also discouraged, and if you ever want to talk about that subject I'd suggest finding another outlet.

Quote: Originally posted by Texium (zts16)

Yes, this thread is fine. It reports a procedure that the OP actually did, and the discussion has remained scientific and professional. Scientific discussions of making psychoactive compounds and precursors are tolerable. Alternatively if it was a thread where the OP was "how I make 3,4,5-trimethoxybenzdehyde plz help " it would already be in Detritus. Discussion of using psychoactive substances, especially those made in an amateur lab, is also discouraged, and if you ever want to talk about that subject I'd suggest finding another outlet.

Quote: Originally posted by JJay

Quote: Originally posted by PhenethylamineMachine   Quote: Originally posted by JJay   We all know what the product could be used for, but as I understand it, those poopy criminal enterprises aren't really interested in it, so as long as the discussion is centered around the chemistry, there should be no problem. I don't see why the OP would use this particular route to oxidize such an expensive material except that bleach and PTC materials are readily available. Surely almost any other oxidizer would be less finicky and produce higher yields with less product lost in side reactions. Which route would you suggest? Honestly, if I wanted to synthesize 3,4,5-trimethoxybenzaldehyde I would start from para-cresol. Its fairly simple, and only requires two steps. para-cresol is treated with bromine in the presence of carbon tetrachloride. when the initial reaction has completed water is added and the reaction mixture is held at reflux, and is then chilled, at which point 3,5-dibromo-4-hydroxybenzaldehyde will precipitate out and is filtered-off and collected. Next the 3,5-dibromo-4-hydroxybenzaldehyde is reacted under heat and pressure with sodium methoxide and a cuprous chloride catalyst, next the reaction mixture is treated with dimethylsulfate and NaOH, at which point 3,4,5-trimethoxybenzaldehyde is precipitated out and collected by filtration. Seems far more simple to me... Though it's possible that the original poster just happened to have some 3,4,5-trimethoxy benzyl alcohol to experiment with... I hadn't really thought about it, but manganese dioxide, PCC, nitric acid, and oxone come to mind. From an amateur point of view, the major problems with the synthesis you just gave are pressure and dimethyl sulfate. Pressurized reactions are not necessarily amateur-friendly, and dimethyl sulfate is nasty stuff.