Author Topic: 2-hydroxy-5-MeO-BA: the continuation of the saga.  (Read 4322 times)

0 Members and 1 Guest are viewing this topic.


  • Guest
2-hydroxy-5-MeO-BA: the continuation of the saga.
« on: March 30, 2002, 12:36:00 PM »
..... Once i saw a Devil in a flame of fire, who arose beefore an Angel that sat on a cloud, and the Devil utter'd these words:

Some dirty, dark-brown p-MeO-phenol was obtained by xtracting w/benzene a standard HQ/BQ/H2SO4/MeOH methylation, described in

Post 269667

(Antoncho: "Re: P-MeO-phenol from hydroquinone: part II", Novel Discourse)
, evaporating the C6H6 and drying the melted product on a waterbath under fumehood in an enameled saucer. The product then stood in open air for some days.

12,5 g of this disgustingly looking shit was dissolved in hot solution of 32g NaOH/36ml H2O. 4ml MeOH was added. All was placed into 100ml FBF (SWIM doesn't have a 100 ml RBF :) ).

The flask immediately upon addition of phenol was flushed w/butane, and so was the efficient air condenser which was placed upon it. The latter was loosely corked to prevent air from getting in.

So... The flask was immersed into a water bath held at 70 C - that was achieved by taking the largest pot SWIM could find in the house and placing it, full of water, on a electric hotplate switched to "II" mode (of the three modes available  :)  :)  :) ). Surprizingly, it held the rxn at precisely 70 C all the time ;D

Every 15 mins 1 ml of fract. distilled CHCl3 (well, i guess, distillation could bee omitted, but SWIM's chloroform boiled at 57 C, so he decided any other modus operandi would bee unwise) was injected in w/a syringe, and the rxn immediately energetically swirled by hand to allow for absorption of CHCl3 into the mixture (this way it doesn't boil much - but boiling progressively increases during the course of the rxn).

After 4 hrs, add'n was stopped and the temp was kept at 70 C for 1 more hour.

The rxn was then cooled, acidified w/~80ml 25% H2SO4 - some black oil floats on top - xtracted w/25x25x15x10 mls of CHCl3, xtracts stirred w/a little NaHCO3 (solid - can you xplain me why they use a NaHCO3 solution all the time??? Please?? It's messy, and tends to form emulsions, whereas solid NaHCO3 is very simple to decant from), decanted, NaHCO3 washed w/a little bit of CHCl3, all combined in a 500 ml RBF, CHCl3 evap'd. Some black oil remains.

The flask is filled w/water and steam-distilled for like fucken eternity (>7hrs), collecting 600 ml distillate - after the 1st 300 mls are distilled, ~60 gr NaCl + 300 ml H2O are added to the flask. A visible qtty of yellow oil is seen floating on top of the distillate. SWIMis rather certain there still remains quite a bit of the product in the water, but.....

The distillate is saturated w/170 g NaCl, xtracted w/50x50x25x20 mls CHCl3 (all the way SWIM used the same CHCl3 he distilled off bee4 (including previous runs) + adding some from the bottle as necessary), dried w/NaSO4, decanted, drying agent also washed w/a little CHCl3, and the solv't evaporated on a boiling waterbath in a 100 ml flask - after bubbling ceases, it's held for some time more, open - to remove any residual CHCl3. Some of it still remains in the product, as it seems, but not much at all (a sample tested).

Yield - 6,2 mls of a dark-yellow transparent liquid w/a funny, undescribable aromaceous odour, completely dissimilar to that of vanillin. Irritant to skin. Crystallizes in the freezer (ChemFinder says mp 4 C - is it true or a typo?)

The following notes should bee also in order:

1) Antoncho, on SWIM's beehalf, would like to thank very much Karl, who was the pioneer of this procedure. Thank you, Karl!

2) An pre-run w/a smaller qtty gave an identical result - ~1ml of product from 2g starting ... er... material.

3) The 'improved' procedure from the patent at Rhodium's - with semi-solid NaOH in chloroform - DOESN'T WORK (at least, with this dirty compound). Only 0,7 mls was isolated from 3 g starting material. The rest is tar... which would make a really cool window-pane hermetizer :)

The Angel hearing this beecame almost blue; but mastering himself he grew yellow, & at last white, pink and smiling and then replied:

"Thou Idolater! Is not God One?"

...... damn it, i think God is fucken Zero. But he does smile at times - like this:  8)



  • Guest
Why NaHCO3 solution?
« Reply #1 on: March 30, 2002, 02:36:00 PM »
An aqueous solution has an infinitely larger surface area than the solid NaHCO3 powder, which makes for a better contact between the phases. If this is necessary, I don't know, but that is the rationale behind it.


  • Guest
« Reply #2 on: March 30, 2002, 10:43:00 PM »
Thank you for clarification on the NaHCO3 issue!

Rhodium, you probably shiver with disgust every time you read one of my write-ups! ;D  ;D  

I understand you very well - i am very anal when it comes to chemistry, too :)  - however unimaginable that would seem ;) ; it is just the fact that i had absolutely no means to purify this crap that i had to go with it.

Sure, vac. distillation, column chromatography, blah-blah...  I'd dearly like to do all that - if i only could :(  Otherwise i wouldn't have spent two weeks trying to rextallize the crap from everything i had in the house - with which i still had no luck :-[



  • Guest
write up
« Reply #3 on: March 30, 2002, 11:03:00 PM »
ya need to break those write-ups into sections with titles
It would bee more readable, as I can't bring myself to pick thru the one up there, and this is the third time i've opened this thread

Those who give up essential liberties for temporary safety deserve neither liberty nor safety


  • Guest
Good work!
« Reply #4 on: March 31, 2002, 07:37:00 AM »
Antoncho: Actually I like your writeups because you have some of the most important qualities there is when it comes to chemistry - dedication, curiousity and a desire to solve the mysteries of chemical reactions. It doesn't matter if you have a $1000 lab or a $100000 lab, it is how you work that is what makes it interesting. It is only a sad thing that people like you doesn't have inexhaustible financial resources, as you have nothing else that would halt your endeavours.


  • Guest
Um... Em...
« Reply #5 on: March 31, 2002, 11:06:00 AM »
Foxy: hmmm.... Actually, i don't know how to divide this particular write-up into sections. Anyway - it wasn't meant for a casual reader, my goal was to create as much detailed description as possible, so those who repeat it won't have to fill in any gaps.

What i, basically, did want you to appreciate is - it turns out that one can get a decent (that is, suitable for a small-scale production) yield of rather clean 5-MeO-salicyladehyde from hydroquinone without purification of intermediate p-MeO-phenol, which is very difficult w/out a vac. distilling facility.

Rhodium - thank you very much for your compliments, i really needed that :)

Actually, i think of myself as of a purposefully ghetto chemist. The reasoning behind this is - if one makes psychedelics for his own consuption, without intent to have monetary profit from it (as SWIM does), he needs only small scale techiques and equipment, but can spare no extra money. OTOH, you can't do it on a larger scale w/out a proper lab, hence 'financial resources', but then you usually have those resources :)

Once again, thank you everyone for the positive input, i really appreciate this.



  • Guest
Ok nevermind
« Reply #6 on: April 01, 2002, 12:06:00 AM »
I guess its fine.
Just when i scan it initially for some reason it doesn't draw me in, but it is a good write-up.  Lots of details.
Sorry about my earlier post, I think it was more my attitude than your write-up.  :o

Those who give up essential liberties for temporary safety deserve neither liberty nor safety


  • Guest
A patented improvement
« Reply #7 on: July 09, 2002, 09:32:00 PM »
Look at this wonderful find! 8)

Patent GB1377317

, 2-hydroxy-5-methoxy-benzaldehyde by Reimer-Tiemann formylation of p-MeO-phenol.

To summarize shortly the point of the patent:

a) Improved yield (well, they say 48 to 53% of theory - not all that great as compared to Karl's 76% results, but still good, - take a note that Karl's product contained an unspecified amt of unreacted phenol, which also (slowly) steam-distills and was always detected in SWIM's and SWIVitsh's experiments in quite substantial qtties)

b) The main one - an isolation of the pure aldehyde without steam-distillation and bisulfite treatment!

BTW, they say that the originally published procedure gives a much worse result.

So, here goes:

200g of p-MeO-phenol were dissolved in a soln of 190g of NaOH in 550mls water and the resulting soln was heated to 50 C on a waterbath. to this soln maintained at 50-60 C there were added dropwise 420g of chloroform and a solution of 560g of NaOH in 500mls water from two separate dropping funnels and the rxn was heated for 1 hr at the same temp and atm pressure. after cooling the precipitated salt of 2-hydroxy-5-methoxybenzaldehyde was filtered and washed with 100mls EtOH.The sodium salt was dissolved in 800mls water and slightly acidified (1200 cm3 of 3N H2SO4 at RT) and xtracted w/200mls toluene. The solvent was dried w/CaCl2 and evap'ed and the residue distilled at reduced pressure to give 132g of the itle product, bp 110 C / 5 mmHg.

Cool, i really like that. Too bad SWIM has no time and money for dreaming during this summer :(  :(  :( .

A side question of an utter importance that i haven't ben able to get/find an answer to:

WITHOUT A PTC (the way Shulgin does).

It appears that that hydroxyl is too deactivated - at least in all examples i've seen DMS is used; also numerous failures/bad yields were reported in attempts to carry out that methylation the 'straight way'.
Please, bees, help if you can :)




  • Guest
Good stuff
« Reply #8 on: July 09, 2002, 11:04:00 PM »
Great find Antoncho!

In the coming weeks it is very likely that swim will dream this one (currently messing about with purification of p-meo-phenol).

Unfortunately I cannot help with your question of MeI methylation. In my dream I have some (not a lot) of DMS which will be used to make 2,5-DMBA. If this can get me to 2-CX at least once, I would then go back and investigate a more OTC method of methylation (the DMS won't last forever).
Hope other bees can give some input on this issue.


  • Guest
otc dms
« Reply #9 on: July 10, 2002, 07:21:00 AM »

reducing DMSO in Al/Hg should work, i think


  • Guest
DMS = dimethylsulfAte
« Reply #10 on: July 10, 2002, 08:09:00 AM »
DMS = dimethylsulfAte

I'm not fat just horizontally disproportionate.


  • Guest
« Reply #11 on: July 10, 2002, 08:39:00 AM »
Yes, dimethylsulfite is a methylating agent, but not a really good one. I've one patent on HD where it's used to methylate vanillin and such - but the yields are never good :-[

Beesides, it can't bee made from DMSO , much less so by reduction of it - in DMSO there's only one oxygen, and DMSite has three; more importantly, in DMSO methyls are attached to sulfur directly, while in DMSite - via oxygen bridges.

Currently an investigation is being carried out at HyperLab to make DMSulfate by CuCl2/MeOH/SO2 route to confirm Half-A-Pint's findings, but there are still no conclusive results - at least purification w/out vac distillat'n seems difficult....



  • Guest
A very (IMHO) curious idea
« Reply #12 on: July 10, 2002, 09:31:00 AM »
I've had a revelation :) .

First, take a look at this procedure, from

Patent US3962345


n-Amyl-(4-methyl-3-propylthio) phenyl ether

12g (0.066 mole) of 4-methyl-3-propylthiophenol (bp, n.sub.D.sup.25 1.5762), 3.6g (0.066 mole) of potassium hydroxide and 30 ml of dimethylformamide were mixed and the mixture was heated to a temperature above to obtain a complete solution thereof. Then, the resultant solution was cooled down to room temperature and, while further cooling the solution in an ice bath, 9.5g (0.063 mole) of n-amyl bromide was added thereto. After the addition of amyl bromide, the ice bath was removed and then the solution was stirred for 5 hours at room temperature. After completion of reaction, the reaction mixture was poured into 200 ml of water. A brown oily layer formed on an aqueous layer was extracted with benzene. The extract was washed successively with 5 % (by weight) hydrochloric acid solution, 5 % (by weight) sodium hydroxide solution and water. After the extract thus washed was dried by sodium sulfate, benzene was removed by distillation to obtain 16.6 g (99.6 % of theoretical) of n-amyl-(4-methyl-3-propylthio)phenyl ether. After purification by distillation, colorless and transparent oil having a boiling point of was obtained.


Methyl-(4-methyl-3-propylthio) phenyl ether

18.2 g (0.1 mole) of 4-methyl-3-propylthiophenol, 5.7 g (0.1 mole) of potassium hydroxide and 50 ml of dimethylacetamide and 17.0 g (0.12 mole) of methyl iodide were mixed and the resultant mixture was reacted at the room temperature for 5 hours. After completion of reaction, the reaction mixture was poured into 200 ml of water. A brown oily layer formed on an aqueous layer was extracted with benzene. Extract was washed with 5 % solution of sodium hydroxide and water, and dried with sodium sulfate. Then benzene was removed by distillation and 17.1 g (87.2 % of theoretical) methyl-(4-methyl-3-propylthio)phenyl ether, which was colorless and transparent oil having a boiling point of, was obtained.

There are other examples where they use DMF instead of diMe-acetamide, while the alkylating agents are propyl bromide and such. For what reason they use acetamide in case of MeI, what do you think? I'm personally puzzled. I'd think that they were afraid of MeI somehow forming a qurternary amide (is this possible at all?) with DMF, but AcO-NMe2 should bee even more susceptible to this (more electronegative nitrogen atom), shouldn't it? Well, anyhow.

Certainly, the phenol being methylated in this case is much more easily alkylated than our target aldehyde :) . But. Note that the amt of alkali used is equimolar - hence there's no free KOH to hydrolyse our MeI.

Now, in all patented methyl halide methylations i've personally seen they are always carried at a controlled pH, the reason for that being specified as to prevent hydrolytic destruction of the Me halide. That leads me to suggest that a procedure similar to the stated above would bee especially good - it's not basic, and the conditions may bee easily made harder - like the rxn could bee carried for 24 hrs instead of 5, and the temperature can bee increased all the way to, say, 100 C - like in methylenations with DCM, the large amt of DMF brings the boiling point way above that of DCM. Which is a big advantage comparing to doing it in acetone.

Did i begin to sound like FMAN yet? :)  

An important detail - do you think the small amt of water formed by interaction of KOH with the phenol should bee somehow removed? Like, simply by some drying agent like CaSO4?

Dear Hest, i know you've had some experience doing methylations in DMF - did you ever used MeI instead of DMF? What were the results?

Personally i have a feeling that methyl iodide in DMF at 100 C for 12-24 hours will methylate anything :)  - at least, dichloromethane methylenates protocatechualdehyde in even shorter time. Please, let me hear what you think, bees. Any input is highly appreciated ;)



  • Guest
R-T result
« Reply #13 on: July 24, 2002, 12:19:00 AM »

Some dirty, dark-brown p-MeO-phenol was obtained by xtracting w/benzene a standard HQ/BQ/H2SO4/MeOH methylation, described in Post No 269667, evaporating the C6H6

So I took some of that dirty dark-brown p-MeO-phenol (using DCM instead of C6H6) & tried the R-T:

I used more NaOH than the procedure at Rhod's (~ 3.5 vs 2.6 g NaOH/g phenol).
Had trouble maintaining temp, so a major part of the time it was probably as high as 80°C.
Afterwards there was a large amount of very dark-brown ppte which was filtered off.
I was pleased cos I thought that it must be the phenolate.
It dissolves readily in MeOH.
When dissolved in water and acidified there is very little oil floating. Far too little.
Is it possible to over-acidify, can it decompose the product ?
Too much NaOH used? (don't think so)
Was the temp too high maybe ? (probably)
Should I have used an inert atmosphere ?

Excuse the tone of the post - there's a lot of work in these words and it's frustrating to finally fail.


  • Guest
« Reply #14 on: July 24, 2002, 09:55:00 AM »
Tried it as well. SWiM had alot of tar, made the product useless. He is rather sure he should have controled the temperature much better than he did...

(1) synthesis of p-MeO-phenol; SWiM knows there is a certain amount of p-anisic acid present, but not more than 5% of the whole. He didn't make an effort to remove it.
(2) tried the British patent, which says to keep temperature between 50-60°C. As usual, SWiM forgot and when he saw the mixture boiling, he thought... ooo-ooooooo  ::) . Temperature was almost 80°C at that time. He noted some shiny yellow/white components in the heavily stirred mixture. When the mixture was cooled to room temperature, there was a problem... When emptying the reaction flask, it became clear there was alot of tar. The tar wasn't present during the reaction. Maybe the CHCl3 was evaporated (cooling took 3 hours) and tar settled down. When adding CHCl3, the tar dissolved. hmmm, "dissolved"... SWiM tried to filter it, but didn't work. The tar ruins all. Just threw everything away then.

- SWiM thinks he should have monitored his temperature much better than he did. His breath had an unusual EtOH odour that morning though.
- timing of adding the products: SWiM thinks he added the NaOH and the CHCl3 too quickly, hereby adding to the heat development of the reaction.

Note: SWiM used distilled CHCl3. Undistilled stuff contains too many phtalates.

Doped(TM) since 19.... euhm... a long time  :)


  • Guest
« Reply #15 on: July 24, 2002, 10:43:00 AM »
Guys and girls, don't bee afraid. SWIM definitely performed this synth. If he could, you can as well. I mean, i'm not making up anything. Keep trying.

One thing i'm positive about is FOLLOW the directions. ESPECIALLY the temp and alkali conc'n - SWIM did see masssive tar formations when the directions were not followed. The pH is of a major concern.

SWIM tried the british patent he dug up and found it of no use. At least on the unpurified p-MeO-phenol. Do Karl's proc. It has been found to bee the best thus far.

Another thought - that deep yellow coloration of all the products SWIM's seen w/that Reimer-Tiemann (passes thru the steam-dist'n as well!!). Probably, SWIM thinks, it's the quinone. Will try to get rid of it the next time w/ a prior bisulfite wash.

The only problem SWIM now has is trying to alkylate that aldehyde with MeI :(  :(  :(  Three diff. solv'ts were used, with not much success.

If you have any q's - always at your service. I've had some xperience w/this rxn by this time, more that i care to admit ;D  ;D  ;D


P.S. 80 C at some prolonged (like 30 mins) time even at the proper concentration of the alkali is a definite murdering of the rxn :)


  • Guest
« Reply #16 on: July 24, 2002, 11:54:00 AM »
>The only problem SWIM now has is trying to alkylate that aldehyde with MeI Three diff. solv'ts were used, with not much success.

some excess MeI/excess of finely divided K2CO3 in acetone and prolonged (~12h) reflux with stirring generally methylates phenols well. Not too convenient to perform without hotplate-stirrer (without stirring K2CO3 sinks to bottom and mixture does not boil properly)


  • Guest
« Reply #17 on: July 24, 2002, 12:52:00 PM »
SWiM knows the reaction is achievable Antoncho, at least in theory. He only tried the British patent under EtOH-induced mental problems  ::) . It's typically SWiM that he fucks up his first trial cum laude and that all following are more promissing. But really, that UK patent tar looked awfull  :P . Time for another procedure  ;D .

PS: SWiM thinks Villsmayer is easier...

Doped(TM) since 19.... euhm... a long time  :)


  • Guest
« Reply #18 on: July 24, 2002, 10:49:00 PM »
Thanks for the input guys.
I generally also mess up v.1 of a reaction.
Your response was encouraging Antoncho - it's not so bad failing when you've got a good idea why.
So back to begin (order more hydroquinone, distill more DCM from paint stripper, make more CHCl3... - my cold & deadly determination worries me sometimes..) ::)


  • Guest
Methyl iodide methylation of 2-OH-5-MeO-BA.
« Reply #19 on: August 24, 2002, 12:44:00 PM »
Due to a shortage of money :-[ , Antoncho has been lately unable to buy antipsychotic medication for his, young and temperamental, but unfortunately schizophrenic aunt. As a result, she re-developed some pretty unusual hallucinations, describing adventures of an imaginary character called  SWiHKAL. A truly notable person he is, albeit a hallucination :) . Here is one of her schizoid fantasies that touched Antoncho's heart so deeply that he couldn't resist the temptation of sharing it to his brethren bees :) .

4,7 g of crude dark-brown 2-hydroxy-5-MeO-benzaldehyde obtained by Reimer-Tiemann formylation (steam-distilled) was placed into a 150ml three-necked RBF. There was added 25mls dioxane (undried, but kept over FeSO4 to remove peroxides), 5g freshly fused potassium carbonate, 1ml MeOH (Note 1) and, at last, 2mls (4,6g = 25% molar xcess) methyl iodide. The central neck of the flask was fitted w/a condenser, one of the side-necks - w/a thermometer, and the 3rd one was plugged to bee later used for various tests and additions. The apparatus was flushed w/butane and all was brought to a very gentle reflux on a waterbath.

The temp, measured inside the boiling liquid, at first was ~77 C, increased to 85 C in ~30mins, and went up to 92 C over the next 3 hours. Boiling was cont'd overnight (Note 2)

An aliquot of the liquid was taken w/a syringe, acidified, evaporated under draught to remove carcinogenic dioxane and smelled. The specific smell of unreacted starting material was apparent, mixed w/a somewhat similar, but sweet, aroma of p-diMeO-benzene (Note 3).

So 0,7mls of MeI were added and reflux recommenced. After 4 hrs (internal  temp 92 C) another test was taken which again indicated the presence of the starting material. Another 0,7 mls MeI were added and refluxed for several more hours; the third test revealed the completion of the rxn.

The rxn was flooded w/60 mls of 20% KOH, saturated w/NaCl and xtracted w/30+15 mls of IPA. Alcohol was separated, some 10g of Na2SO4 were added in a faint attempt of drying :) , followed by 90mls of saturated aq. metabisulfite. The mixtr was subjected to vigorous mech stirring for 7mins and the precipitate (which ended up in the alcohol layer) was filtered, washed twice with a lil IPA to almost completely remove yellow coloration (Note 4), pressed between filter paper and somewhat dried under draught. Still containing some IPA, it weighed 8,7 g.

Thus obtained adduct was thrown into 50mls of pre-chilled in the freezer 20% KOH, stirred and left for 30 mins in warm water(Note 5). Precipitated aldehyde was filtered, washed with water 3 times, pressed between filters as dry as possible, chopped on a plate and left to air-dry. Still containing a little water, it looked like not-quite-white, but still pretty, fine vanillin-like powder w/out any noticeable smell and weighed 3,6 g (Note 6). After drying it was 2,7 g -  :) .


1. Dioxane was chosen for the following reasons: a) a much higher bp as compared to acetone; b) unreactivity towards the carbonyl group, which is a
possible disadvantage of using acetone and c) ability to dissolve both MeI and, to some xtent, alkali.

The rationale beehind addind MeOH was the following: K2CO3 reacts w/it to form KHCO3 and KOCH3. The latter, being more soluble than K2CO3, was supposed to act as sort of a PTC :) . Unfortunately, it later turned out that SWiHKAL's MeOH was VERY wet (not to mention water in dioxane ::) ), so the effectiveness of this additive remains to bee researched.

In any case, the two-fold amt of MeI that was required for the rxn, warrants further investigation. Probably, unhydrous conditions would bee better. Maybee, methanol shouldn't bee added at all - to minimize hydro/methanolysis of MeI, which is the major side rxn.

2. Probably, there is no need to reflux the mixtr more than 30-60 mins after the internal temp reached maximum. SWiHKAL just wanted to bee sure :) .

3. p-MeO-phenol is a major impurity contained in the hydroxyaldehyde isolated by steam-distillation from a RT formylation. It's hard to estimate, but there is quite a bit of it in there, probably not less than 20%.

4. This intensely colored yellow impurity is, probably, benzoquinone which survives all the transformations since its usage in methylation of hydroquinone. The next time SWiHKAL does that, he'll 1st try to remove it with bisulfite from the crude p-MeO-phenol.

5. SWiHKAL wanted to make sure all adduct decomposed. Since the appearance of the substance virtually doen't change, several tests were needed to confirm that. However, decomposition of the adduct seems to proceed fast even w/cold KOH.

6. The mp was measured and found to bee circa 45 C, whereas the lit value is 51 C. Could anyone suggest to what kind of (im)purity that corresponds?