Antoncho (Official Hive Translator)
11-25-01 19:32
No 240358
      OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Antoncho continues to discover for himself the wonderful world of organic chemistry…smile

This time he found something that really blew his mind. Please, read on  - especially if you have access to Beilstein and other scientific literature –  some investigation is still needed to complete the proposed synthetic routes.

It is a scientific fact smile that phenols react with aqueous formaldehyde to give compounds called methylols – which is another name for a benzylic alcohol, a –CH2-OH group.  Now, this reaction proceeds pretty fast and usually more than one methylol groups are added. That’s why it’s not widely used for preparative purposes. In fact, in case of phenol, 2,4,6-trimethylolphenol can bee obtained.

These methylols can bee oxidized to the corresponding aldehydes by any known means.

And, eventually, these (poly)aldehydes can bee subjected to Dakin rxn (H2O2 in aq. alkali) to exchange –CHO groups to hydroxyls, most mportantly, if a –OH group is situated meta- to the formyl – it won’t split off and will remain essentially intact. More than that, this rxn, under certain conditions, will not oxidize polyphenilyc compounds to quinones – thus giving polyhydroxybenzaldehydes! And even more – these can (and should) bee then alkylated in the same pot!

Practically, this means that:

Phenol ---> tricarbinolylphenol ---> triformylphenol ---> 3,4,5-trimethoxybenzaldehyde.

Not to mention all sorts of (substituted) polyphenols that can bee made via this route - see the patent if you're interested in that.

Some will undoubtedly saywink that it’s still longer than the ‘classic’ routes  - but think of it, it is SO OTC and SO cheap! One can produce a huge amt of 3,4,5-TMBA from household ingredients and it won’t cost him more than 10$ (at least where I livesmilesmile) Antoncho’s private little imaginary friend is a low-income kitchen chemist – so he likes to fancy about things like that very much…

The only “narrow” place in this synth is that in the patent that describes these rxns the oxidation of methylols to BA’s is done w/O2 on platinum/palladium catalyst. But there are some obvious alternatives, the simplest being bichromate/H2SO4, found in Beilstein – see the ref. below.

And here are the proc’s:




US Patent #4,435,601
Stage 1: Preparation of 2,4,6-trimethylolphenol

100 g of a 30% strength solution of formaldehyde in water (1.0 mol) and 23.5 g of phenol were mixed in a 250 ml glass conical flask fitted with a magnetic stirrer. The volume was adjusted to 125 ml with about 10 ml of water, and 10.2 g of sodium hydroxide pellets (0.25 mol) were then added, under stirring. The mixture was cooled with an ice bath such as not to exceed 30.degree. to 40.degree. C. When the temperature had dropped to 25.degree. C., the flask was purged with argon, the stirring was terminated and the homogeneous solution was left to stand for 24 hours at ambient temperature (22.degree. to 23.degree. C.).

After this period, no more than 315 millimols of free formaldehyde were determined. The reaction mixture was then introduced into 800 ml of cold isopropanol, under stirring. The heterogeneous mixture was stirred for an additional 10 minutes and the copious pinkish-white precipitate was then filtered off on Buchner apparatus. The precipitate was rinsed with isopropanol and then with ether. It was dried in an oven at 40.degree. C. under a pressure of 1 mm of mercury, and this provided 40 g of a powder in which the following were determined by NMR:

11.5 mol % of a sodium dimethylolphenate;

83 mol % of sodium, 2,4,6-trimethylolphenate;

5.5 mol % of the disodium salt of a tetramethylolbis-hydroxydiphenylmethane.

Stage 2. Oxidation of the methylols

23.4 g of freshly prepared, crude sodium trimethylolphenate, containing 0.10 mol of substrate, and 400 ml of water were introduced into a 500 ml five-necked round-bottomed flask fitted with a central stirrer, a glass double electrode for measuring the pH, a thermometer, a dropping funnel and a gas inlet. The apparatus was purged with argon.

1 g of 4.3% strength by weight platinum-on-charcoal and 60 mg of bismuth (III) sulfate were added. The apparatus, connected to an oxygen supply at atmospheric pressure, was then purged with pure oxygen; the stirring rate was adjusted to 1,050 rpm.

The temperature was raised to 45.degree. C. and at the same time the pH was raised to 11.0 by introducing 30% strength by weight sodium hydroxide solution (12 g, i.e., 0.09 mol).

After 1 hour, 15 minutes, 3.8 liters of oxygen had been absorbed and no additional oxygen was consumed during the next 25 minutes (3.83 liters). The catalyst was filtered off hot on a glass frit of porosity 4, the solid was washed with water and the filtrate was cooled to about 10.degree. C. The latter was cautiously acidified with sulfuric acid; a precipitate began to appear at about pH 8. The addition of acid was terminated when the pH reached 4 (17 ml of 25% strength by weight H.sub.2 SO.sub.4 had been used). The yellow solid obtained was filtered off on a glass frit of porosity 3, washed with 10 ml of water, drained and dried at 30.degree. C. under a pressure of 1 mm of mercury. This yielded 14.7 g of yellow powder. The yield of weight of crude material, essentially containing triformylphenol and oligomers, was 82%.

The desired purified compound was isolated from this crude product by preparative liquid chromatography in a yield of 18%, relative to the starging 2,4,6-trimethylolphenol, namely, 3.2 g.

This compound, which is not described in the literature, possessed the following characteristics:

Melting point under a pressure of 760 mm of mercury: 206.degree. C.

2,4,6-Triformylphenol is insoluble in water at 25.degree. C. and has the following solubilities in organic solvents at 25.degree. C.
    ______________________________________
    ethanol             0.5    g/liter
    diethyl ether       0.25   g/liter
    benzene             3      g/liter
    ______________________________________


Stage 3. Oxidation of the triformylphenol with hydrogen peroxide at pH<7

450 mg of triformylphenol (2.5 mmols) were introduced into a 500 ml five-necked glass reactor fitted with a thermometer, an electrode, a condenser and two dropping funnels. 12.5 ml of deaerated water were added, the magnetic stirrer was started and the temperature was raised to 45.degree. C., everything being carried out under nitrogen.

The pH was raised to 4.5 with 10% strength by weight sodium hydroxide solution contained in the first funnel, and 1.96 g of 10% strength by weight hydrogen peroxide (5.8 mmols) were then dropwise introduced, over the course of 10 minutes, from the second funnel.

The solution, which was heterogeneous at the beginning, gradually became homogeneous. The reaction mixture was maintained at 45.degree. C. for:

50 minutes at pH 4.5, and

45 minutes at pH 5-5.5.

4.16 mmols of sodium hydroxide had been added in total.

Stage 4. Methylation of the 3,4,5-trihydroxybenzaldehyde

In order to more easily measure the yield of gallic aldehyde obtained during the previous step, all products obtained were methylated in the following manner:

In the apparatus described above, the dropping funnel containing 10% strength by weight sodium hydroxide solution was replaced by a funnel containing degassed 30% strength by weight sodium hydroxide solution. The funnel containing hydrogen peroxide was replaced by a funnel containing dimethyl sulfate (DMS).

The pH of the mixture was raised to 8, while maintaining a temperature of 45.degree. C. and a nitrogen atmosphere. 4.75 g of DMS (37.5 mmols) were then introduced over a period of 40 minutes, while maintaining the pH at 8-8.5. The experiment was terminated when the pH stabilized, which was after 1 hour, the amount of 30% strength sodium hydroxide solution used then being 4.2 g (31.5 mmols).

After cooling to 20.degree. C., the reaction mixture was acidified to pH 3.5 with 0.25 ml of 50% strength by weight H.sub.2 SO.sub.4 and extracted three times with 20 ml of dichloroethane. The organic extracts were washed with 10 ml of water, dried over sodium sulfate and analyzed by gas phase chromatography.

The hydroxyls had been totally methylated because neither gallic aldehyde, nor 5-hydroxy-p-vanillin, nor seringaldehyde (3,5-dimethoxy-4-hydroxybenzaldehyde) and/or its isomer, 3,4-dimethoxy-5-hydroxybenzaldehyde, were observed.
    ______________________________________
    Yield of 3,4,5-trimethoxybenzaldehyde,
                          216 mg = 44%
    relative to the triformylphenol introduced
    in step 3
    Yield of 1,3,4,5-tetramethoxybenzene
                           24 mg =  5%
    ______________________________________




Now please would someone really kind smile answer these questions that occupy Antoncho’s fictious friend’s head:

1.Someone with access to Beilstein, please post the procedure of methylol --- aldehyde oxidation with bichromate, found in “vol. 8, p. 31”.

2. Can anyone look up the Dutch patent #87,141 (I tried Espacenet – to no avail) – the same oxid’n with MnO2 in chloroform.

3. I guess that methylol oxidation w/Na2Cr2O7 will oxidize as well polyhydroxyBA’s to quinones. That shouldn’t appply to phenol or vanillin derivatives, right?

4. And – AFAIK, alcohols get oxidized to aldehydes pretty easily – is it possible that methylols can bee in situ oxidised to BA’s w/H2O2? At least, it is pretty evident that H2O2 won’t make acids of them under standart Dakin rxn conditions. That’d bee really cool!
Well, that’s finally it. Any input very appreciatedwink,

Antoncho
 
 
 
 
    Rhodium
(Chief Bee)
11-25-01 21:36
No 240394
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

I'm very interested in this methylol formation or "hydroxymethylation" as it is also called, but for a different reason - to make benzyl alcohols out of methylendioxybenzene and/or 1,4-dimethoxybenzene. This avoids the use of very noxious HCl gas in chloromethylation of the above compounds. The alcohols can be made into chlorides by aqueous HCl later.

Have you seen any references on this reaction for use with methoxybenzenes, and not just phenols?
 
 
 
 
    Antoncho
(Official Hive Translator)
11-25-01 22:11
No 240408
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   


Have you seen any references on this reaction for use with methoxybenzenes, and not just phenols?




No.... I was looking for that also - but there wasn't a single mention of it. Needless to say, that'd bee a #1 formylation method - if it workedtongue

Damn it, that doesn't mean it's impossible, of course! Just improbablewinklaugh... SWIM might check it, but not in the immediate future.

Antoncho

 
 
 
 
    Antoncho
(Official Hive Translator)
11-26-01 21:02
No 240875
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   


I'm very interested in this methylol formation or "hydroxymethylation" as it is also called, but for a different reason - to make benzyl alcohols out of methylendioxybenzene and/or 1,4-dimethoxybenzene




Hm... looks like we still might have smth. here. Here's an exerpt from US Pat. #5,811,587



Example 1 was reproduced using anisole in place of guaiacol.

0.75 g of H-mordenite zeolite with a Si/Al molar ratio of 18, 1 ml of anisole and 12 ml of an aqueous formaldehyde solution (37% by weight, 160 mmole) were used.

The reaction mixture was heated to 65.degree. C. with stirring.

After 4 hours of reaction, the following performances were obtained:

Conversion/anisole=89%

Selectivity/p-hydroxymethylanisole=45%

Selectivity/o-hydroxymethylanisole=5%.



With guaiacol they obtained similar results under similar cond's. Which leads me to think that at least phenol ethers are susceptible to this rxn.

I know nothing of these zeolites and what they're for and what would happen w/out them, so please, comment if you know.

Also there is always that danger of multiple substitution.

But it still sounds interesting.

Antoncho
 
 
 
 
    lugh
(Hive Bee)
11-27-01 01:29
No 240981
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

This reaction is prone to polymerization, since it is the route to Bakelites. It's known as the Lederer-Manasse reaction, see Synthesis 143 (1981) as an example smile
 
 
 
 
    bottleneck
(Stranger)
12-04-01 23:23
No 244182
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Zeolites are natural and as well as synthetic minerals which have been used for many years in various industries as catalysts. They're usually known as "molecular sieves".

I think boiling these minerals in nitric acid will produce a sort of solid "super acid".

Apparently, a certain kind of treatment called "pillaring" will mean vermiculite can be used in the same way as zeolites.
 
 
 
 
    megamole
(Hive Bee)
12-22-01 16:17
No 249803
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Antoncho,

Um, this method will give you trimethylphenol, not trimethoxy. I'm not sure what you'd do with this, but it doesn't sound all that useful.

Still, if you're looking for OTC 3,4,5-trimethoxybenzaldehyde, there is hope: this one's a classic.


vanillin -> 5-bromovanillin -> syringaldehyde -> 3,4,5-trimethoxybenzaldehyde

../rhodium/chemistry /345-tmb.html

Three steps, plus you can  substitute other alkoxyl groups in the 4- and 5- positions quite easily using this route (escaline and proscaline look pretty interesting.)

...a bracing colonic of Walt Disney magic, applied with a high-pressure firehose...
 
 
 
 
    yellium
(Hive Addict)
12-22-01 17:15
No 249816
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

I would go for meta-escaline (ME) instead of escaline. Lower bodyload.
 
 
 
 
    Antoncho
(Official Hive Translator)
12-22-01 18:43
No 249838
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   


Um, this method will give you trimethylphenol, not trimethoxy.




Megamole: hi, nice to hear from you - sorry for not answering your PM, but i'm very very busy (as usual), besides i'm really broke and have no money for experimentation ---> no newsfrown

But then, if carefully re-read my compilation, you'll notice that it is precisely 3,4,5-trihydroxy- (hence trimethoxy-) aldehyde that is produced this way. It is the way Dakin rxn works: splits off -CHO, replaces ot w/-OH.

As for the classic route, yes, it is surely more attractive, esp. small-scale, but more expensive too. And bromine... Yikes!
Actually, i was thinking that this rxn could bee used to produce smth. new some easy way - like maybee 1,2,4,5-tetrahydroxybenzene (for bis-methylenedioxy, recently discussed) - or some such, i think it has a great potential. Too bad noone seems to bee interestedfrown

But anyway - thanks for bringing it up!

As for subst'd analogues - that's very intriguing (Yellium, are you speaking from PiHKAL or from SWIY's experience?)

Do you guys think syringaldehyde can bee i-Pr'ted w/i-PrBr?

Thanks again,

Antoncho

 
 
 
 
    yellium
(Hive Addict)
12-22-01 22:28
No 249873
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

>Yellium, are you speaking from PiHKAL or from SWIY's experience?

Speaking from PiHKAL.
 
 
 
 
    megamole
(Hive Bee)
12-23-01 22:58
No 250108
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Antoncho,

As always, you come up with such clever ideas. Broke? By God, one of these days we really need to figure out a way to set up a Hive organic synthesis scholarship for young and talented organic chemistry students. Oh well; in the meantime you'll just have to spend more time in the library, and less time in the lab (trust me; if you go through with your degree and start working as a professional organic chemist, you'll have plenty of money for whatever projects you like.)


As for the classic route, yes, it is surely more attractive, esp. small-scale, but more expensive too.




More expensive? Heavens no! Now I must admit things may be different on the other side of the world, but at least here, vanillin is cheaper than dirt, and is avaiable at every Middle Eastern grocery store (its used as a flavoring in some traditional desserts.) The bromine can be generated in-situ from KBr, H2SO4, and H2O2, so you don't even have to handle the stuff. Very cheap, very OTC.

And now a word on chemoselectivity of oxidizing agents. While you can definately add plenty of methyl alcohols to benzene rings (the Blanc reaction), the selective oxidation to yield a formyl group (rather than oxidize the carbonyl all the way to yield a carboxylic acid) will mean you have to be careful with your choice of oxidizing agent; perhaps MnO2? Now, the Dakin reaction: how does one selectively oxidize only the two formyl groups ortho to the original hydroxyl group? As far as I know, all three formyl groups would be replaced with hydroxyls, yielding 1,2,3,5-tetrahydroxybenzene, like you said. Now this is all very nice and good, but what would you do with 1,2,3,5-tetrahydroxybenzene? I suppose 2,3,4,6-tetramethoxyPEA would be interesting, though I wonder how active it would be...


Do you guys think syringaldehyde can bee i-Pr'ted w/i-PrBr?




I do believe it can. There's a lot of precedence in the literature for SN2 alkylation of phenols, and 2-bromopropane would be the most obvious reagent of choice. Other alternatives of course include 2-iodopropane, as well as isopropyl tosylate, and maybe isopropyl mesylate. Conveniently, there aren't a lot of side-reaction possible in this situation, so it might just take longer than adding a primary alkyl group, but still give good yields.

Season's greetings,


-megamole


...a bracing colonic of Walt Disney magic, applied with a high-pressure firehose...
 
 
 
 
    Antoncho
(Official Hive Translator)
12-26-01 18:42
No 250568
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Megamole,



Broke? By God, one of these days we really need to figure out a way to set up a Hive organic synthesis scholarship for young and talented organic chemistry students.




laughlaugh I'm not a talented chemist, i'm afraidblush. Actually, i'm a psychology student - trying to work at the same time. And primarily, i'm a poet/musician - a talented one, i dare saycool. You can see now why i'm always so busy smile.
As for the scholarship - lol - i earn ~30$ per week, and that's considered a high wage! (i am a manager)- fuck, a fucking liter of THF costs 25$, fuck!mad
As for the chem degree...... That would bee probably surprizing to you, but in Russia it is a common practice to find a professor at a state university (subsided by government) making less money than a fucken janitor in the caffee next door. I'm not exagerrating, that's the way it is. So getting a degree is a purely abstract goal, not having anything to do with my (or SWIM's) income.

>Oh well; in the meantime you'll just have to spend more >time in the library

for me, there's no other library than the vast sea of Internet. I enjoy it a lot, though.


And now a word on chemoselectivity of oxidizing agents. While you can definately add plenty of methyl alcohols to benzene rings (the Blanc reaction),




yes, that's the main problem - one (presently) can't tell if there's any condidtions allowing for addition of one, two or three groups to the ring - and to which rings which... too bad - i'm certain this rxn has a great potential, but it needs such a lot of exploration bee4 it can bee effectively used!



the selective oxidation to yield a formyl group (rather than oxidize the carbonyl all the way to yield a carboxylic acid) will mean you have to be careful with your choice of oxidizing agent; perhaps MnO2?



re-read my original post: it's, maybee, as simple as Na2Cr2O7.


Now, the Dakin reaction: how does one selectively oxidize only the two formyl groups ortho to the original hydroxyl group?




Ok, re-read it again: the -CHO that has a -OH group meta- to it isn't subjected to Dakin's rxn!.




Happy New Year everyone!!!

- from Russia with love,

Antoncho
 
 
 
 
    megamole
(Hive Bee)
01-05-02 20:28
No 252963
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   


I'm not a talented chemist, i'm afraid.




Well, have you every considered changing your major area of studies? winkAs you can see, I'm not very good at hiding my feelings about the rewarding and exciting field of chemistry.


As for the chem degree...... That would bee probably surprizing to you, but in Russia it is a common practice to find a professor at a state university (subsided by government) making less money than a fucken janitor in the caffee next door. I'm not exagerrating, that's the way it is. So getting a degree is a purely abstract goal, not having anything to do with my (or SWIM's) income.




Forgive me for my ignorance, but I've always been curious about these things. While doctors of chemistry hired by the Russian state make such pitiful wages, what about those working for private corporations? I have to say I've met a lot of brilliant students and scientists from the former Soviet Union, and I've never been able to understand how such tremendous human resources can be so underutilized. How do these guys live on such wages?

Considering the wages of these state chemists, I keep thinking to myself: the amount of money I spend on a weekly basis on drugs and alcohol could buy me a research team of Russian organic chemists. Goddammit, if only I knew how to go about buying such things! A team of Eastern European scientists, researching every chemical whim that interested me: that would be a whole new level of senseless, decadent debauchery! The very thought makes me nauseous with delight. Muhahahahaha.... Its enough to keep a person from sleeping...smile


yes, that's the main problem - one (presently) can't tell if there's any condidtions allowing for addition of one, two or three groups to the ring - and to which rings which... too bad - i'm certain this rxn has a great potential, but it needs such a lot of exploration bee4 it can bee effectively used!




There's a second problem, and I think this one would be bigger than the chemoselective oxidation. I knew this reaction looked familiar, but it wasn't until last week that I remembered where I've seen this before, and why this is going to be very messy to perform. Treating phenol with formaldehyde under either acidic or basic conditions will indeed give you you're desired alcohol, but this compound will further react with phenols with unsubstituted ortho- and para- positions, forming methylene bridges. This polymerization reaction yields a class of materials known as "novolacs", which are produced on the order of many, many  thousands of tons per year.

Now assuming you can keep polymerization down to a relative minemum, you run into some serious separations issues: your product will not be distillable, and so you'll have to separate your compound from mono- and di-methanolated phenolic compounds, as well as from a large variety of oligomers and polymers. Chromatography would seems a natural choice, but that's going to make scaling this procedure up economically and technically prohibitive.


re-read my original post: it's, maybee, as simple as Na2Cr2O7.




Re-read my responsesmile. Alkali dichromates are not going to be chemoselective, and will oxidize all the way to the corresponding benzoic acid. Pyridinyl chromyl chloride will work, but then again, its not OTC, and its considerably more expensive.


Ok, re-read it again: the -CHO that has a -OH group meta- to it isn't subjected to Dakin's rxn!.




Okay, but if that's true, then you care only replace one of the carbonyls. How would convert your phenol-2,4,6-tricarboxaldehyde into tetrahydroybenzene?

Merry Chrismas (in case your Orthodox),


...a bracing colonic of Walt Disney magic, applied with a high-pressure firehose...
 
 
 
 
    amalgum
(Hive Bee)
01-05-02 21:58
No 252986
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Hmmm.  I remember reading somewhere that propenylbenzenes can be oxdised with O3 to form a benzaldehyde.  Ozone can easily be generated.  So you could just find some calamus, dig it up, extract the oil, distill the asarone, and then maybe gas it with O3 and collect the benzaldehyde?
 
 
 
 
    lugh
(Hive Bee)
01-06-02 01:37
No 253016
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   


There's a second problem, and I think this one would be bigger than the chemoselective oxidation. I knew this reaction looked familiar, but it wasn't until last week that I remembered where I've seen this before, and why this is going to be very messy to perform. Treating phenol with formaldehyde under either acidic or basic conditions will indeed give you you're desired alcohol, but this compound will further react with phenols with unsubstituted ortho- and para- positions, forming methylene bridges. This polymerization reaction yields a class of materials known as "novolacs", which are produced on the order of many, many  thousands of tons per year.




Post 240981 (lugh: "Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!", Novel Discourse) Novolacs must be the same polymers as Bakelites smile

 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
01-06-02 09:54
No 253172
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Phenol-formaldehyde resins are evidently avoided in #4,435,601, possibly by keeping the temperature below 40o. Trying to view that patent, Adobe chose that moment to crap out on me. (Won't even display local .PDF files.) Guess I'm left with the mystery, of how a 2,4,6-triformyl phenol in step 3 becomes a 3,4,5-trihydroxy benzaldehyde in step 4. Wonderful reaction, this Dakin "oxidation" must bee.

turning science fact into <<science fiction>>
 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
01-06-02 23:26
No 253330
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Bear with me here. I must bee kind of slow to catch on. Phenol is activating, yes? And strongly ortho, para-directing? That would make the 2,4,6-trisubstituted phenol what we are basicly talking about here, or I must have missed another cue. Where does the 3,4,5 substitution pattern come out of, the thin air? Does everybody else catch on to this but me? Are we in the Twilight Zone now?

A 2,4,6 trimethoxy benzaldehyde is very exciting, because Shulgin expected this pattern to follow the very successful path set by the 2,4,5 phenethylamines. It would bee great not to have to deal with phloroglucinol in this. If we are indeed talking about a 3,4,5 pattern of substitution, well that's fine. It just adds another arrow to our quiver, so to speak. One more way into Nature's mescaline mine.

But for the life of me, I can't see the transition in this thread, from the one to the other. It's as though somebody had snipped and spliced the time lines. We'll talk about this, and we're still talking about this, and of course we're now talking about the other, and we always were talking about the other, don't you remember? Seems a little weird to me!

turning science fact into <<science fiction>>
 
 
 
 
    PrimoPyro
(Hive Prodigy)
01-06-02 23:44
No 253333
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

halfapint:

The reaction proceeds because of the selective oxidation of certain aldehyde groups, while leaving another alone.

I am not trying to insult your intelligence so please dont think that. You are one of the bees here whom I have a very deep respect for. But think of it on the simplest picture basis:

Reactant: benzene ring + CHO. There is a OH para to the CHO. There are two more CHO groups ortho to the OH, each thus being meta to the lone CHO.

There is a reaction known as the Dakin reaction, whereby an aromatic aldehyde with either an amide or hydroxide artho to the aldehyde, is oxidized to a phenol. Essentially, the CHO is transformed into an OH. But for the mechanism to proceed, the aldehyde CHO MUST have an amide or hydroxide ortho to itself. A lone CHO group with OH para to it will not be oxidized.

So, the two ortho CHO groups to the OH are subject to this Dakin oxidation, while the "lone" CHO para to the OH is not. This is how the compound is selectively oxidized (theoretically) to the 3,4,5-trihydroxy-benzaldehyde compound.

The entire theory is based on the assumption that the hydroxy will activate both ortho aldehydes.

                                                   PrimoPyro

Vivent Longtemps la Ruche!
 
 
 
 
    halfapint
(Ubiquitous Precursor Medal Winner)
01-07-02 12:59
No 253530
      Re: OTC 3,4,5-TMBA from _phenol_ in 3 steps!  Bookmark   

Thanks, PrimoPyro. I get it now. It was my failure to visualize what was happening that slowed my understanding. I had the fixed picture in my mind, that the original hydroxyl group was somehow getting changed into an aldehyde in the process, so I never grasped the possibility I should turn the molecule over! Now I see that the original hydroxyl just stays as is, while two new ones come into being ortho to it, and the aldehyde manifests para to it, as the overall result.

My imagination is overly visual and geometrical. That has slowed down my comprehension of the more abstract types of math as well. Wish there were a Hive molecule modeler program, that we could just pick out and emphasize particular parts of a chemical species we wished to discuss. That way we could show molecular imagery while preserving our anonymity. A benzene smiley, an indole smiley. No worries about whether a picture might show more than was intended.

Now that I belatedly see what's going on, congrats to Antoncho once again for bringing this really attractive route to mescaline to our attention. I have no phenol, but I can sure make some. What is the function of the bismuth salt in the catalytic oxidation? Think it may just bee a fancy frill, an inessential co-catalyst. Some of the alternative oxidations mentioned seem more useful.



turning science fact into <<science fiction>>