..... 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 (https://www.thevespiary.org/talk/index.php?topic=11482.msg26966700#msg26966700)
(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)
Antoncho
Look at this wonderful find! 8)
Patent GB1377317 (http://l2.espacenet.com/dips/viewer?PN=GB1377317&CY=gb&LG=en&DB=EPD)
, 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:
IS IT POSSIBLE TO METHYLATE THE HYDROXYL ORTHO- TO ALDEHYDE WITH METHYL IODIDE 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 :)
Yours,
Antoncho
I've had a revelation :) .
First, take a look at this procedure, from Patent US3962345 (http://l2.espacenet.com/dips/viewer?PN=US3962345&CY=gb&LG=en&DB=EPD)
:
EXAMPLE 1
n-Amyl-(4-methyl-3-propylthio) phenyl ether
12g (0.066 mole) of 4-methyl-3-propylthiophenol (bp 136.degree.-138.degree.C/3mmHg, 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 90.degree.C 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 136.degree.C-139.degree.C was obtained.
EXAMPLE 5
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 114.degree.-115.2.degree.C/2mmHg, 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 ;)
Antoncho
FUCK.
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.
Wrong.
It dissolves readily in MeOH.
When dissolved in water and acidified there is very little oil floating. Far too little.
Fuck.
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.
SWiHKAL has past the 1/2 way mark Antoncho! I'm pleased and inspired by this.
Just one Q/idea:
Cold temps were maintained throughout SWiHKAL's procedure. In Post 320904 (https://www.thevespiary.org/talk/index.php?topic=8824.msg32090400#msg32090400)
(Rhodium: "2,5-Dimethoxynitrostyrene w/ NaOH catalyst", Methods Discourse) conditions were different, allowing the mixture to eventually reach 60°C. I haven't really studied this reaction yet so I'm not sure what the reason for low temps are, but is it possible it may have adversely affected your yield ?
see https://www.jatox.com/jat.mar02.pdf (https://www.jatox.com/jat.mar02.pdf)
p 61 contain info on metabolism of 2c-b and a reimer tielman on the benzyloxy derivative from benzyloxy phenol