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Panache
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Quote: Originally posted by crazyboy  | | Well I just got finished performing this reaction using the ratios Klute posted, but I doubled everything. The reaction went very smoothly however it
used a considerable amount of methanol, DCM and hydroquinone but gave very little 4-methoxyphenol. I plant to repeat this reaction on a larger scale
but I will try to recycle some of the methanol/DCM. I |
Perhaps you should try it on the 1/10th scale and get it right before doubling it again. I'm not being nit picky i just wondered if perhaps you did
not see the silliness in those sentences.
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schwabb
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i was recently given a small vacuum pump by a friend, http://www.millipore.com/userguides/tech1/p30152, it pulls 25inHg, and i think its primary purpose is vacuum filtering, does anyone know if it
would be suitable for this distillation?
I have an aspirator as well but i have no reasonable way of attaching it to my sink (previously used A LOT of electrical tape  ).
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turd
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The whole distillation setup is scary. The thermometer adapter, the tubing, missing clamps, no stirrer?
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crazyboy
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| Quote: Originally posted by Panache |
Perhaps you should try it on the 1/10th scale and get it right before doubling it again. I'm not being nit picky i just wondered if perhaps you did
not see the silliness in those sentences. |
Well 1/10 scale seems a bit too small, with equipment losses I would get almost no product. I agree modifications should be made and I will repeat
this reaction without doubling again perhaps even to Klute's original measurements but I will not go 1/10 scale, there is no reason.
| Quote: |
The whole distillation setup is scary. The thermometer adapter, the tubing, missing clamps, no stirrer? |
I don't follow... The thermometer adapter is solid PTFE, coated with silicone vacuum grease, the o-ring is an inert fluoropolymer and it is vacuum
tight. The tubing is regular vinyl tubing it isn't dangerous. There is a Keck clip securing the receiving flask to the vacuum adapter, the vacuum
adapter is held firmly in place with the clamp. I have more Keck clips but I removed them so they didn't melt when I heated them with a paint
stripper. I have a hotplate/stirrer but find I generally get better heat control with a heating mantle.
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Fleaker
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One thing I do not understand: why the DCM extraction?
Why not neutralize the sulfuric acid with carbonate, distill/rotavap off the solvent/water, and then flush with argon and vacuum distill the product?
I think this would improve yields on the reaction and would be less solvent intensive. The crude product could then be recrystallized a la Klute
solvent system.
Neither flask nor beaker.
"Kid, you don't even know just what you don't know. "
--The Dark Lord Sauron
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crazyboy
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| Quote: Originally posted by Fleaker | One thing I do not understand: why the DCM extraction?
Why not neutralize the sulfuric acid with carbonate, distill/rotavap off the solvent/water, and then flush with argon and vacuum distill the product?
I think this would improve yields on the reaction and would be less solvent intensive. The crude product could then be recrystallized a la Klute
solvent system. |
The DCM extraction followed by brine and water washes does help clean the product but now that you mention it I don't think they really do enough to
justify their use as the product was heavily contaminated with black tar. I think I might try your suggestion, if it fails I can just dissolve the
residue in DCM and continue as if nothing happened.
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Klute
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Well, you would have to filter the precipitated Na2SO4, I tried this way once using conc NaOH solution, but near the end of the neutralisation, the
pheno; gets basified locally and forms a slush of the phenolate which darkens immadiatly and gives a hell of a mess.. I abandoned trying to
selectively neutralize the sulfuric acid, because if you cut it too low and there even a little sulfuric acid left, you get a goop of polymerized junk
during distillation.
The whole neutralization scheme is proposed in one of the related patents, but to me it just doesnt seem feasible, except perhaps by sacrifying some
p-methoxxyphenol by over basifying just a bit...
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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DrNoiZeZ
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2,5-Dihydroxyacetophenone methylation
I would like to know if anyone has tried to monomethylate the 2,5-Dihydroxyacetophenone using the same aproach used with hydroquinone in
MeOH/H2SO4/Benzoquinone?
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Nicodem
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Threads Merged
10-9-2011 at 07:51 |
peach
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Right, I'm off to drink wine and talk about weird stuff guys don't understand on a super saver coupon spa break, but here's what I've got thus far.
Two other people I chat to have been giving this a go and asked me to as well.
Synthesis of highly deuterium-labeled (R)-K-13675, PPAR a agonist, for use as an internal standard for low-level quantification of drugs in plasma -
Bioorganic & Medicinal Chemistry, Yukiyoshi Yamazaki, Shin-ichiro Ogawa, Kimiyuki Shibuya
| Quote: | 4.6. Synthesis of 4-methoxyphenol-d7
To a solution of 1,4-hydroquinone-d6 (9) (98 atom% D, 4.48 g,
38.6 mmol) and benzoquinone-d4 (98 atom% D, 325 mg,
2.90 mmol) in methanol-d4 (99.8 atom % D, 25 mL) was added sul-
furic acid (4.80 g) over 5 min at room temperature. The reaction
mixture was stirred for 14 h, poured into ice-water and neutralized
with 4 M aqueous NaOH. The aqueous solution was extracted with
Et2O. The organic layer was washed with brine, dried over Na2SO4
and concentrated in vacuo. The residue was purified by silica gel
column chromatography (n-hexane/EtOAc = 5:1) to give 3 as a pale
yellow solid (4.83 g, 95%): 1H NMR (400 MHz, CDCl3) d 3.72–3.76
(m, 0.06H), 4.87 (s, 1H), 6.76 (s, 0.10H), 6.79 (s, 0.10H); 13C NMR
(100 MHz, CDCl3) d 55.06*, 114.59*, 115.80*, 149.41, 153.48; IR
(solid sample): 3381, 2521, 2262, 2069, 1419, 1141, 1112 cmÀ1;
HRMS (EI): m/z [M+] calcd for C7HD7O2: 131.09564; found:
131.09642; mp 56–57 °C. |
From what they have already found, the neutralisation in large amounts of water and subsequent solvent extraction didn't seem to be working well, so
they modified it to instead use sodium bicarbonate directly into the methanol - which does appear to work, although I have not tried the referenced
method yet or looked at the solubility of my product in water; I will do some more when I get back perhaps.
I stick a 250ml beaker with a stir bar in it on the balance and tare it
<a href="http://img402.imageshack.us/i/img0423vl.jpg/" target="_blank"><img width="800"
src="http://img402.imageshack.us/img402/744/img0423vl.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a>
I add hydroquinone and retare
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src="http://img829.imageshack.us/img829/2643/img0424mr.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Benzoquinone had been prepared the day before and sublimated in the morning. You can see the preparation of that in this link. The interface is
going uber dark green / black, rapidly
<a href="http://img17.imageshack.us/i/img0425ev.jpg/" target="_blank"><img width="800"
src="http://img17.imageshack.us/img17/5874/img0425ev.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img90.imageshack.us/img90/9093/img0426oa.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
I measure out 125ml of methanol and add that
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src="http://img641.imageshack.us/img641/8507/img0427i.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Within the five minutes I spent measuring it out and adding the methanol, it has clumped from a free powder into annoying lumpy bits. I have to poke
around in there with a glass rod to break it up again, then leave it to spin for ten minutes to get it all free flowing again
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src="http://img40.imageshack.us/img40/5796/img0431zm.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
In the meantime, I weigh a cute, tiny beaker and pipette.
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src="http://img819.imageshack.us/img819/7360/img0432qz.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
I measure concentrated sulphuric into this
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src="http://img21.imageshack.us/img21/5111/img0433jr.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
The beaker after a spin
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src="http://img833.imageshack.us/img833/5078/img0437sq.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img694.imageshack.us/img694/3240/img0438eg.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
I film over both beakers and put them in the freezer for a while
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src="http://img834.imageshack.us/img834/6066/img0444cs.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img69.imageshack.us/img69/4740/img0446ot.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img191.imageshack.us/img191/1187/img0447es.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
They come out around -8C and, with it spinning quickly, I drip the cold, concentrated sulphuric directly into the vortex over ten minutes.
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src="http://img198.imageshack.us/img198/7756/img0451zi.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
The addition is finished and the beaker has warmed to 34.5C. The room is at 17.5C.
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src="http://img221.imageshack.us/img221/985/img0454o.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Checking for a transfer error. The balance will refuse to sit still when weighing concentrated sulphuric. Like sodium / potassium hydroxide, roasted
drying agents and similar, the mass constantly goes up as they pick up things from the atmosphere. So long as measured soon after, the change isn't
too much of an issue since it's well below the mass of one drop
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src="http://img708.imageshack.us/img708/2848/img0455jg.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
The beaker is covered and left to spin overnight
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src="http://img850.imageshack.us/img850/6950/img0456k.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
14 and half hours later...
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src="http://img825.imageshack.us/img825/418/img0459n.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
The beaker is now at 24C. This is the temperature of the hotplate, which warms up a little when the motor is left going all night
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src="http://img827.imageshack.us/img827/7236/img0465bl.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
I measure out the sodium bicarbonate, I actually removed a little from this after checking the sulphuric numbers
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src="http://img713.imageshack.us/img713/4169/img0466m.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
14 hours and 50 minutes after completing the addition, I begin to neutralise.
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src="http://img32.imageshack.us/img32/5403/img0469bg.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
2NaHCO3 + H2SO4 -> Na2SO4 + 2H2CO3
Then,
2H2CO3 -> 2CO2 + 2H2O
Because the neutralisation has stage stages to pass through and the bicarbonate is going in as a powder, it takes a long time to fully react and needs
adding a bit at a time.
The novel thing here, as spotted by the guy who suggested the change, is that the neutralisation product is insoluble in the solvent and forms a
decahydrate, so it'll scavenge the water as well. One consequence of this is that you will get some lumps in the beaker as it clumps. Stir away
Toronto!
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src="http://img845.imageshack.us/img845/2366/img0475yf.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
As it gets going, it will thicken up to a gooy foam
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alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img42.imageshack.us/img42/4171/img0482as.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img268.imageshack.us/img268/2517/img0490x.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
After two hours the fizzing was showing signs of dying away. After another hour it was close to dead. I left it for an additional hour until there was
absolutely no sign of it. The temperature remained at 24C though out. Here's the sodium sulphate dropping out
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src="http://img90.imageshack.us/img90/5174/img0493l.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Having added what I'd calculated to be the precise mass of bicarbonate to neutralise the sulphuric, I tried dipping the pH probe in there
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src="http://img707.imageshack.us/img707/6440/img0494w.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Then a bit of paper
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src="http://img37.imageshack.us/img37/905/img0497gf.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Sodium sulphate begins releasing it's water of crystallisation at just 30C. Since this is now about that warm, I put it back in the freezer for a few
minutes
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src="http://img813.imageshack.us/img813/6884/img0498n.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Filtering isn't much of a problem
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src="http://img190.imageshack.us/img190/9582/img0501f.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
<a href="http://img84.imageshack.us/i/img0504g.jpg/" target="_blank"><img width="800"
src="http://img84.imageshack.us/img84/9420/img0504g.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
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src="http://img90.imageshack.us/img90/489/img0505ee.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
<a href="http://img684.imageshack.us/i/img0506ml.jpg/" target="_blank"><img width="800"
src="http://img684.imageshack.us/img684/5452/img0506ml.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Rinsing the last bits out
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src="http://img577.imageshack.us/img577/3006/img0507uz.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Rinsing the cake through with a bit more methanol
<a href="http://img710.imageshack.us/i/img0509ml.jpg/" target="_blank"><img width="800"
src="http://img710.imageshack.us/img710/7334/img0509ml.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Removing the methanol under vacuum
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src="http://img828.imageshack.us/img828/3710/img0513iu.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Done. As the last few bubbles appear, the contents of the flask immediately thicken to a chip shop style gravy. Once the flask it's self is back at
room temperature, around 17.5C, it solidifies. There appears to be a decent amount of some clean solid in there, coated in something brown. According
to an independent, triple blind peer review, it smells like 'plastic'. I'd say calamine cream as well. I put a tap on it, put it under vacuum and then
in the freezer, since I'm going to bed and don't know if this is going to go funny on me overnight.
<a href="http://img339.imageshack.us/i/img0518d.jpg/" target="_blank"><img width="800"
src="http://img339.imageshack.us/img339/6082/img0518d.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
<a href="http://img684.imageshack.us/i/img0519yv.jpg/" target="_blank"><img width="800"
src="http://img684.imageshack.us/img684/1795/img0519yv.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
THE PROBLEMS BEGIN
The next day I set about transferring the contents of the 250ml flask to a 100ml, which went surprisingly well. When the flask was put into some warm
water, it'd go back to gravy consistency and pipette nicely. A few squirts of methanol and I had everything from one flask to the next, and out of the
pipette, and off the stir bars; so it's not as tarry as it may appear. The plan was, high vacuum fraction distillation.
<a href="http://img706.imageshack.us/i/img0539hy.jpg/" target="_blank"><img width="800"
src="http://img706.imageshack.us/img706/8202/img0539hy.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
I have all this sat on the desk and it's not going through
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src="http://img27.imageshack.us/img27/69/img0592cv.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
I tried this one first with hot water in the condenser
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src="http://img38.imageshack.us/img38/6193/img0594j.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Clogged at the point of the thermometer down, entirely
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src="http://img832.imageshack.us/img832/693/img0595wk.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Tried that one, same problem
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src="http://img842.imageshack.us/img842/7083/img0593xa.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Best off with something like this, where there is no long spout. The product solidifies so quickly it's going to block as soon as it leaves the water
jacket if not
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src="http://img15.imageshack.us/img15/83/img0558lf.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
And one of these to hand
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src="http://img824.imageshack.us/img824/2091/img0572za.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
'Bulb to bulb' style. The thing to be distilled also bumps a lot, meaning it's good to have some form of vigreux in the way if only to stop the
initial splattering from crossing over
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src="http://img651.imageshack.us/img651/1042/img0565ua.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
By the time I'd tried it in one, had it clog, transferred it to another, had that clog, I had obtained some yield, which immediately solidified to a
white crystalline mass. But by the time it'd been transferred into a third distillation setup, something must had happened along the way, because I
was now getting some kind of weird white plastic like, unmeltable material in the hot flask. So here it ends for now.
10g is not bad, but it's not great either, it should have been more like 20 or 25g. I think a lot of the blame, if not all of it, is the messing
around in the distillation. If I'd gone straight to the most simple, cheapest setup, I expect I'd have gotten close to that yield.
Also of note is that the pure white material was the first thing out the flask, the first drop solidified, and it was the dominant band, easily. The
temperature sat still around 94C under hard vacuum.
This adds more weight to the idea of simply using a bulb to bulb method, as there doesn't appear to be any gross contamination that needs to come off
first.
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src="http://img820.imageshack.us/img820/7310/img0559dm.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
There's what I've got.
What is there appears clean, as the stuff is near pure white, dry and crystallising all on it's lonesome.
You guys in the US have that shop 'Lush' right? That sells novelty soap.
You know that smell you get when you come within 100m of the door, before ever seeing it? That's what it smells like at the moment.
<a href="http://img705.imageshack.us/i/img0584vn.jpg/" target="_blank"><img width="800"
src="http://img705.imageshack.us/img705/7203/img0584vn.jpg" alt="Free Image Hosting at www.ImageShack.us" border="0"/></a><br>
Super quick summary because I am already late
I will have to give this a go on the TLC, check out the solubilities of what I've got and perhaps try some more basic distillation method.
The reference is likely using chromatography partly due to the difficulty of distilling this stuff.
Suggestions
Weigh the BQ and HQ separately and dissolve them in a bit of methanol alone, then mix them together. It'll be less prone to forming
clumps that way. It's not a major issue, since they break up easily enough, but it's an extra annoyance when they form.
USE A BEAKER! It benefits from a lot of hard stirring. Doing it in an RBF is not at all necessary and the bar won't stir it as well as a big
flat one in a beaker. Use a beaker that is twice the size of your solvent volume, in case it foams up and out. Mine didn't foam up more than an inch
or so, but it could if not constantly stirred or the bicarbonate is added in bulk.
Keep the distillation painfully simple. There's over a thousand dollars worth of glass on the desk there, yet it died on it's arse. It may be
possible to use a recovery bend or straight tube with two male adaptors on to go between two flasks. A frit, splash head or virgeux somewhere in
between is a good idea to avoid splattering.
[Edited on 10-30-2014 by Polverone]
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497
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I don't want to detract from you efforts peach, that is a very nice post.
Wouldn't it be potentially cleaner and easier to hydrolyze paracetamol, diazotize, and react that with methanol? If you could avoid the vacuum
distillation that way, it would be well worth it I think. And no need to buy hydroquinone. Has anyone brought this route up before? I really like the
sounds of it.
The reaction can also form the benzene derivative, but that tends to occur more with longer chain alcohols. Benzenediazonium chloride or sulfate and
methanol is said to give only methoxybenzene here: http://books.google.com/books?id=5eRYAAAAYAAJ&pg=PA226&a...
They say electron withdrawing substituents result in lower yields of the ether, but with methanol even a p-bromo or chloro yields mainly the ether.
Here they say m and p-aminotoluenes are converted to methyl ethers in 95% and 84% yield respectively. Not too bad.
http://books.google.com/books?id=FMziAAAAMAAJ&q=diazoniu...
If the reaction with methanol doesn't work, you could always methylate the paracetamol, then hydrolyze and diazotize. Not quite as elegant thought.
Edit:
Damn. According this paper paper p-hydroxybenzenediazonium salts react anomalously with methanol, forming phenol and tar only. That was fun while it lasted...
Still, what do you think of the potential for o-methylating and then diazotizing? I am certain those reaction will work.
[Edited on 2-10-2011 by 497]
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Nicodem
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Please provide proper references, like book/journal title, volume and page. Google-books links do not work for all (I know they are country specific,
but likely they are also cookie dependent). For example, if I click on your links I only get the book tittle instead of the page as you probably
intended. In general, please avoid using dynamic URL addresses, as it is futile doing so. When giving references, either write them out in a classical
sense or provide the DOI. Optionally, provide a quotation where possible, just like Peach does it.
| Quote: | | Damn. According this paper paper p-hydroxybenzenediazonium salts react anomalously with methanol, forming phenol and tar only. |
I guess you meant that it reacts normally with methanol to give a phenol as the main product, rather than giving the anomalous product (ether).
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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497
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Okay sorry, didn't realize they were country specific.
From the first link:
"Decomposition of Diazonium Salts by Alcohols
The reaction between diazonium salts and alcohols may proceed in two different ways:
RN2X + C2H5OH --> RH + C2H4O + N2 + HX
RN2X + C2H5OH --> ROC2H5 + N2 + HX
The former of these was originally regarded as a general reaction, but more recently researchers have shown that the second is the normal change. The
factors determining the course of the reaction are, however, numerous and complicated, involving (1) the nature of the alcohol; (2) the influence of
substituents in the diazonium salt; (3) the pressure and temperature at which the decomposition is affected.
The tendency to replace the diazo- group by hydrogen increases with the molecular weight of the alcohol. Benzenediazonium chloride or sulfate with
methyl alcohol give anisole exclusively. With ethyl alcohol these salts yield chiefly phenetole but benzene is produced. The diazonium salts of
p-chloro and p-bromo-aniline furnish only p-chloro and p-bromo-benzene with ethyl alcohol, but with methyl alcohol they give rise mainly to the methyl
ethers"
From the second link:
"Diazotized m- and p-aminotoluenes when thermally decomposed in methanol in the presence of air (to inhibit the radical process) gave the respective
ethers in yields of 95% and about 84%."
| Quote: | | I guess you meant that it reacts normally with methanol to give a phenol as the main product, rather than giving the anomalous product (ether).
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No, reread the first paragraph of the paper in the last link. It says:
"The anomalous effect of the phenolic hydroxyl, particularly with respect to methyl alcohol, is contrary to all other experience with it's reactivity,
since here it promotes the formation of the same product as would a nitro-group, and no longer behaves like other o,p directing groups which favor the
replacement of the diazo- group by the alkoxy-group."
I'm assuming this is because it is capable of forming a quinone, unlike other p-substituents?
[Edited on 2-10-2011 by 497]
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DrNoiZeZ
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Hi, I have a question concerning that reaction: does it will work with ethylhydroquinone? The result would be 4-methoxy 3-ethyl phenol or 4-methoxy
2-ethyl phenol? I think I will get 50/50 but I am asking that because I need the first one to formylate using Mg formylation. Thanks
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turd
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| Quote: Originally posted by peach | | From what they have already found, the neutralisation in large amounts of water and subsequent solvent extraction didn't seem to be working well, so
they modified it to instead use sodium bicarbonate directly into the methanol - which does appear to work, although I have not tried the referenced
method yet or looked at the solubility of my product in water; I will do some more when I get back perhaps. |
Did you (or your friends) try the workup that Klute posted above (extraction instead of neutralization)?
Someone who may be the worst synthetic chemist that ever walked this huge ball of fire dissolved 100 g hydroquinone and 10 g benzoquinone in 750 ml
MeOH and while stirring slowly poured in 100 ml H2SO4 (stupid - chemists with more than 2 brain cells would add first H2SO4, cool then add the rest).
The flask was stoppered and stirring continued for 24 h at RT (~20°C). ~200 ml MeOH were distilled of under weak vacuum (bp ~40-50°C) and 500 ml of
brine added. The dark oil was extracted thrice with DCM, the organic phase washed twice with water (good separation) and brine (catastrophe - emulsion
straight out of hell). To break the emulsion, the aqueous phase was diluted with water, organic layer taken off, diluted more, etc. The last bit of
emulsion was left standing over night and finally broken by vacuum filtration. The combined organic extracts were dried over Na2SO4 for 24 h, the DCM
distilled off at atmospheric pressure and weak vacuum applied to remove remaining solvent. Vacuum was removed when a white solid started to sublime.
The residue quickly crystallized and was distilled at reduced pressure (one of those ultra-cheap E-bay pumps) at 105°C until the distillate started
to become yellow (without temperature increase!). Yield of crude mequinol: 81 g (~72%) of nice crystals which are slightly yellow and therefore need
to be recrystallized. You probably would not even want catalytic amounts of benzoquinone in most reactions.
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peach
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Hi Turd,
I only just noticed this reply, months later, as the email hasn't been working for most of that time. But no, I didn't try the extraction, just what's
above.
The neutralisation suggested by the others works really well. It seems your extraction did too, but the neutralisation is good in terms of not having
to deal with the subsequent emulsion.
I am near certain the reason behind my yield being low was the distillation - it solidifying in the small passageways on the way out and needing
swapping around. Just needs doing in something that can have it's sides heated in case that begins to occur.
Thanks for taking the time to post up your results!
[Edited on 12-3-2012 by peach]
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lullu
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| Quote: Originally posted by Klute |
The patent suggets neutralizing the reaction mixture, and then directly distilling everything. But it can tricky to get the exact amount of base in
there, and so material is trapped in the formed Na2SO4, even after washing with fresh MeOH.
[Edited on 26-1-2008 by Klute] |
I followed peach's way and neutralized it with NaHCO3 to ph7.
It yielded a very light pink Na2SO4 (which I think trapped a lot of product) where washing the cake with more methanol does not seem to help, vacuum
filtration is nearly impossible even through celite.
Has anyone experience how I get the methoxyphenol out of this sludge?
[Edited on 30-10-2014 by lullu]
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DJF90
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I had no issue replicating Peach's work, and obtained granular solids on neutralisation. I suspect you have too much water present (wet solvent?) if
you're ending up with a sludge.
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lullu
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Thanks for your comment DJF90.
All solvents used where purum/synthesis quality, temperature was under 16°C the whole time.
Maybe it is of any interest or help anyone in the future:
I used 750ml pure methanol for 200g hydroquinone and 22g benzoquinone (quinhydrone/hydroquinone defiled) and a 1:1.81 mol acid ratio .
p-methoxy-phenol is very soluble in methanol and it yielded no solids after 24h stirring.
After neutralization there was no methanol left, only a very thick mush.
It was diluted with around 2 litres methanol and filtered/washed again with methanol.
The mentioned light pink Na2SO4 had still the distinct smell of the product after a lot of washing.
The filtrate needs destillation, I'll report on the yield if it is done.
Maybe a Water/DCM extraction on the sulfate sludge will work fine although if someone tried a steam destillation or direct destillation from it
succesfully I would appreciate a comment on that.
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lullu
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To draw a picture:
neutralization:
After neutralization, magnetic stirring was continued and it let to this sludge.
[Edited on 31-10-2014 by lullu]
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Wolfgangg
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Just wanted to share my experiences with this reaction, as it's given me some problems in the past. After discovering xylene was a useful
recrystallization solvent, I decided to try something a little unique in an effort to skip the vacuum distillation and recrystallize the product right
out of the extraction solvent.
4.15 g p-benzoquinone was added to a solution of 41.5 g hydroquinone in 300 mL MeOH. The beaker was submerged in an ice bath and treated with the
careful dropwise addition of 42 mL 96% H2SO4 over the course of ~15 minutes. With the addition complete, the beaker was covered and left to stir for
24 H at ~20 C. 150 mL MeOH was evaporated off and the mixture was allowed to cool before adding 200 mL saturated aqueous NaCl. The mixture was
extracted with 4 x 75 mL xylene, washed once with 50 mL H2O, and washed with 2 x 50 mL saturated aqueous NaCl.
*With the exception of the use of xylene as an extraction solvent, here's where the workup differs*
A test was done. 5 g crude 4-methoxyphenol was recrystallized in xylene. When cool, the product + mother liquor had a volume of 17 mL. Expecting
~35-40 g crude product, the expected volume would be ~136 mL. The 300 mL of xylene was evaporated down to 135 mL and allowed to cool overnight.
No dice. The beaker was placed under draught and further evaporated down to 90 mL. The next morning, a crop of huge, surprisingly clean crystals had
formed at the bottom of the beaker, under the nearly black solvent. There was one chunk the size of the palm of my hand (had to take a picture ).
The crystals still had a tan taint to them, but considering what you get from extracting with DCM and evaporating to dryness, they are very clean.
The mother liquor was returned to the beaker and evaporated further under draught, eventually collecting 2 more crops of crystals that became
progressively dirtier (but still rather clean in comparison) with repeated collections.
In the end, ~34 g of light tan 4-methoxyphenol was collected. I've never bothered recrystallizing with EtOAc (and am currently running low) as vacuum
distillation always resulted in adequate purity for my needs, and so I don't know what the returns are like. If the crude product is collected in this
way, it should be pure enough for recrystallization with EtOAc (or xylene) and vacuum distillation can be skipped altogether.
Extraction solvent
Crystals under solvent
Giant chunk
Filtered product
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DJF90
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It seems like a potentially easy way to bypass the vacuum distillation. Toluene has been mentioned to give small cleanish crystals, so I'm kind of
surprised you see such a significant deviation from that using xylenes.
What would be nice to see is the recrystallisation of the isolated product, and whether that can completely control colour/impurities. A melting point
before and after a recrystallisation ought to be indicative. You may find a little activated carbon is needed (followed by hot filtration).
| Quote: |
The mixture was extracted with 4 x 75 mL xylene, washed once with 50 mL H2O, and washed with 2 x 50 mL saturated aqueous NaCl |
Out of curiousity, why do you wash the combined extracts with (two portions of) brine? It seems unnecessary to me, seeing how the solubility of water
in xylenes is minimal. Concentration will remove any water present via azeotrope. I mention it because its odd how people sometimes follow a
"standard" workup routine without thinking what each wash is removing (and if its actually necessary).
[Edited on 25-2-2015 by DJF90]
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lullu
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I had problems getting it to deposit when vacuum distilling bulb to bulb.
Thanks for sharing your experience Wolfgangg.
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