DrDevice
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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 
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PhenethylamineMachine
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Hmmm...
Very interesting.
I actually had an incredibly long and detailed post written out, but erased most of it until I know if this conversation is appropriate for this site.
There is some miscellaneous nonsense below, but since I removed the discussion around it it probably will not be very helpful.
I actually know a good deal about related compounds and processes. However, I wanted to make sure the conversation here is appropriate. Personally I
do not care what you want 3,4,5-trimethoxybenzaldehyde for, but it might not entirely appropriate for the site.
MISCELLANEOUS
Conversation and details removed
gallic acid -----> 3,4,5-trimethoxybenzoic acid ----> 3,4,5-trimethoxybenzoyl chloride ------> 3,4,5-trimethoxybenzaldehyde.
MISCELLANEOUS
Conversation and details removed
3,4,5-trimethoxybenzyl alcohol in MeOH is stirred and chilled to 0°c. Then, bromine is slowly added with stirring at such a rate as to keep the
reaction temperature at 0°c. The reaction mixture is then allowed to return to room temperature and is then stirred for 2 additional hours. Next a
saturated sodium thiosulfate solution is added to destroy any remaining bromine, at which point the 3,4,5-Trimethoxybenzaldehyde would be filtered
off an re-crystallized from C6H6.
MISCELLANEOUS
Conversation and details removed
Another interesting reaction involving the compound involves producing 3,4,5-Trimethoxyphenylacetonitrile via the 3,4,5-Trimethoxybenzyl Alcohol to
3,4,5-Trimethoxybenzyl Chloride to 3,4,5-Trimethoxyphenylacetonitrile... ...Even though you were interested in 3,4,5-trimethoxybenzaldehyde I figured
3,4,5-Trimethoxyphenylacetonitrile would be equally of interest....
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Chemi Pharma
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Try calcium hypoclorite (HTH) and PTC, like the paper I attached say. The yield seems to be something better than with sodium hypochlorite.
(+- 78% yield).
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
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Attachment: Alcohols oxydation to aldehydes with Calcium hypochlorite and TBAB.pdf (712kB)
This file has been downloaded 474 times
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PhenethylamineMachine
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So I'm guessing I am ok to elaborate on this subject?
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JJay
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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?
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LearnedAmateur
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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.
In chemistry, sometimes the solution is the problem.
It’s been a while, but I’m not dead! Updated 7/1/2020. Shout out to Aga, we got along well.
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JJay
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From the site guidelines:
| Quote: |
Do not request spoonfeeding of information for clandestine drug manufacture. However, every sort of chemistry is a permissible topic of discussion if
you discuss it like a scientist. If someone is asking about obtaining chemicals used in drug manufacture and using the vocabulary of a SWIM—"someone
who isn't me"—-mer more than a chemist, report it and the thread will be dealt with after a moderator has confirmed your findings. Similarly, if
someone is asking for help with a synthetic "recipe" for a known street drug, report that too. Don't bother to berate the cooks in the thread itself
instead; that doesn't bring the mods any faster. In truth the mods and most members dislike any thread where someone is seeking or using a "recipe"
and doesn't show any deeper interest in chemistry, but this has been mostly a problem with drug synthesis because of the many people who want to
quickly get rich or high.
Certain topics are unwelcome no matter what section they are posted in. The discussion of criminal enterprises or weapons production is inappropriate.
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PhenethylamineMachine
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| 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. |
Ok, makes sense.
3,4,5-trimethoxybenzaldehyde is not scheduled as far as I know, and I can not see it as qualifying as an analogue, so I guess I am ok on this one.
Though honestly, it's not a precursor most would have any desire to obtain. Most would just preform an extraction from cactus material, which is
simply and legally obtained. But for conversations sake it's some interesting stuff.
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PhenethylamineMachine
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| 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?
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I suppose it wouldn't in that sense, though it's fairly obvious why most would want to obtain such a compound, so I figured I would check first before
I post any further.
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JJay
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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.
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PhenethylamineMachine
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| 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.
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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...
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JJay
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| 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...
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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.
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Tsjerk
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I think this quote is relevant:
| 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.
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http://www.sciencemadness.org/talk/viewthread.php?tid=66175#...
[Edited on 26-4-2018 by Tsjerk]
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Texium
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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.
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morganbw
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| 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. |
kudos to you sir. I have no interest in the chemestry in this thread but its allowance does have a certain importance to me.
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PhenethylamineMachine
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| 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...
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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. |
I suppose I hadn't thought about the "amateur friendly" aspect well enough...
You are completely correct though, pressurized reactions can present complications to the amateur chemist and dimethyl sulfate can be some nasty
stuff. Dimethyl-sulfate is highly toxic, a lung-full of vapours could be fatal, and the compound is fairly corrosive and will damage the skin.
Dimethyl sulfate can also react violently with certain substances such as concentrated aqueous ammonia, and while it acts as a highly effective
methylating agent, it was also used as a chemical weapon during the first world war, so as with any chemical compound, extreme care and caution should
be taken when working with this compound.
In all honesty 3,4,5-trimethoxybenzdehyde is not a compound that I have had much interest in, and I can say I really have not worked with it much
beyond the notebook, but the chemistry is damned interesting, and it's an area where I could use some further education.
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