12-03-03 18:59
No 474583
Wondered about all the waste and huge amounts of chemicals used in the reported bromate oxidation of THF so SWIM decided to cut through some of the smoke and see if there wasn't a more efficient way to accomplish it. Thus, SWIM says,
Dissolve 60 grams NaBrO3 in 200 mls H2O with stirring in 2000 ml flask (high walls act as a kind of reflux mechanism. Or just set it up for reflux). Add 200 mls of a 27% solution of potassium hydrogen sulfate. Precipitation will occur, not to worry. Place the flask in a dish containing a few cups of crushed ice. This helps control the initial exothermic reaction and saves on bromine or solvent loss. Set it on the stirrer and commence stirring. Add 70 mls THF and either set up for reflux, no heat, or place a watch glass over the top, stoppering is not recommended (do say! need I mention that this is a product of trial and error people?). The next morning (16 hours) extract with 4 x 50 mls DCM. Bromine will come over with the DCM, not to fret. My feeling is that as long as you are getting bromine in the DCM washes (yellow color) you are also getting product, although yield does tend to drop off significantly after the 3rd wash. Combine the washes and remove the bromine as follows. Add about 30 mls of a 10% sodium sulfite solution and extract (about 1/20th as reported in the literature! And no bisulfate! why the hell did they include all that in the first place?). The yellow color of the bromine disappears and you have a relatively clean DCM solution of GBL, some residual THF (maybe), and traces of water and salt. Place in a warm (70oC) water bath with gentle breeze to drive off all solvents but GBL and decant or pipette from the crystalized salts (if any). Yield, approximately 20 mls water-white GBL, a little less if distilled.
Questions for you all: outside of balancing the bisulfate/bromate ratio and monitoring the kinetics, I don't believe this reaction has been optimized in the literature. What do you think the rate limiting factor happens to be? Extra THF was added and it is probable that some remained at the end of the reaction, though that's not certain- some evaporated during reaction, some was evaporated during workup and not a whole hell of a lot was converted. To carry the reaction past 16 hours caused a reduction in the yield of product according to the lit, but they were limited to equimolar quantities of THF which was eventually consumed leaving the bromine mechanism to work on the GBL, further oxidizing it to succinates and other compounds after a time. By having the THF in excess, the additional reactant should compete with the side reactions, ultimately resulting in higher yeilds of product, besides having more precursor. It did not. Let the reaction as described above continue longer? 24 hours? More? Keep adding THF incrementally, just as the bromine mechanism begins to kick in, say at 12-14 hours? What is the theoretical upper limit to yield on this reaction? Again, what is the rate limiting factor, or is there one? Is it truly an autocatalytic system? (I'm thinking bromate as the rlf, but once bromine is produced can you keep the reaction going through addition of H2O2?). I think some fine tuning of this reaction might make it an effective one indeed. Will keep you informed. Feedback appreciated.
-Beeswax
(Synaptic Self-Mutilator)
12-03-03 21:43
No 474605
Nice work! It's good to hear someone reporting success on the oxidation of THF to GBL. What was the yield after distillation? (a very important purification step, IMHO)
I think the way that we should investigate is with using hydrogen peroxide as the oxidant (w/catalytic bromine). That way we hopefully can use less reaction volume.
(A Different Title)
12-03-03 23:28
No 474610
I once experimented using aqueous solution of KBr & THF, dripping in oxone solution (which contains potassium bisulfate, so I figured why add any to begin with? probably a mistake). Yield was very low and very dirty (I didn't bother distilling after noting I only had ~5mL of possibly-GBL to work with out of the expected 50mL).
My best "success" was with using Ca(OCl)2 and HCl as catalyst, ~30% yield after distilling as I recall, however that reaction also created something which had a bp similar to GBL but definitely wasn't GBL, when I took my water-white (supposedly pure) GBL and added it to NaOH solution, it turned coffee-brown and tasted horrible, completely unfit for human consumption. Efforts to clean it up failed, whatever it was carried through conversion back to GBL and then back to GHB. Probably some sort of chloro-GBL...
Edit: Oh, forgot to mention, whatever the mystery substance was, after treating with NaOH it wasn't very water soluble, over the course of a week it started to precipitate out of solution forming a fine layer of black dust at the bottom of the flask. Never completely cleared up though.
I'd be very curious, how does your GBL respond when treated with NaOH? Tried distilling it yet? One fraction come over or more?
If I had a thermometer & thermometer adapter (dropped them a while back, can't afford to replace them, seriously
, things like food & bills must come first), I'd investigate KBr + H2O2 + KHSO4 + THF... maybe some day...
They call them fingers, but I never see them fing... oh, there they go.
(Stranger)
12-04-03 16:07
No 474718
Lost a ml or two upon distillation the first time I tried it, most likely mechanical loss. The line for the GC was kinda long, so I went for the bioassay. Smelled like GBL, sweet with a slight anise aroma (no ether-like THF), tasted right (terrible) and subjective effects were just like I remember, so I skipped the distillation altogether in subsequent batches.
Bromine and H2O2 eh? Got a rough protocol you might suggest? I think I can give that a shot next week if I get a chance.
(Hive Bee)
12-04-03 21:20
No 474752
I was going to give comments on Chromics proposed preliminary method posted in Post 473746 (Chromic: "Uhm", Methods Discourse) but never did. I think it sounds ok although a little low in bromide compared to literature, there is also no mention of the volume of water to be used.
Here is a method strictly based on the Soviet electrocatalytic and the US elemental halogen THF oxidation patents. This is theoretical, small scale, and has not been tested. It uses little water volume which of course might cause problems with THF evaporation in some circumstances (lack of a reflux condenser etc), but is a good thing considering scale-up. If the water volume is to be increased the amount of sulfuric acid should be scaled proportionally as the optimal pH is around 1. The amount of the bromide salt is quite conservative, molar 20% of the amount of THF.
Now, my main concern is that the THF gets salted out of the solution in these conditions or that there is a problem with salt solubility -- and even if that happened the reaction might still work well, who knows? Experiment is king. Comments appreciated.
90 mL H2O
0.15 mol bromide salt (17.8 g KBr or 15.4 g NaBr)
0.92 g 96% H2SO4
0.75 mol THF (60.8 mL)
To a well-stirred mixture described above is added 107 mL of 30% H2O2 (1.65 mol, 1.1 equivalents) at such a rate that the temperature does not rise past 40°C. Work-up as usual.
fear fear hate hate
(Stranger)
12-05-03 20:20
No 474939
(Rated as: good read)
The conversion of THF to GBL was recently tried in the two phase Br2 / H2O2 oxydation system described in: Organic Process Research & Development 2(4), 261-269 (1998) (../rhodium/pdf /br-cat.h2o2-
DOI:DOI:10.1021/op980028j
Post 468078 (moo: "Oxidations and brominations w/ H2O2/Br2/HBr", Methods Discourse)
Post 468126 (Rhodium: "THF to GBL in 75% yield in 4h using H2O2/Br2", Methods Discourse)
Unfortunately yealds were low.
The procedure:
0,12mol Br2 was generated in situ by dissolving 33g KBr (slight excess) in 150ml water, than carefully adding 24g of 50% H2SO4 (0,12mol) followed by 16ml of 30% H2O2. To this yellow solution 150ml DCM and 25ml (0,3mol) THF was added. The two phase system was refluxed for 1h w/ intensive stierring (efficent condenser is required!), than 18ml 30% H2O2 was added followed by another hour of reflux and another 18ml of 30% H2O2 and finally 2h of reflux.
The DCM phase was separeted and the aq. phase further extracted w/ 2x 50ml DCM. The combined organic extracts were washed with 200ml of 15% NaHSO3 sol. Followed by 2x 150 ml of water washes. Dried (MgSO4) and stored overnight over some anhydrous Fe2SO4 (this precaution is most likely non necessery since the bisulfite wash should remove possible peroxides. Note that the used Fe2SO4 did not turn red at all.)
After stripping off DCM, the dark brown residue was distilled yealding 2,5ml clear liquide
(~11% Yeld). Sucks!!!
Further trials are to be expected in order to improve the yield!
What do you think, could the bisulfite remove some of the GBL from the DCM phase through the adduct?
Bobo find this unlikely, since significant amounts of bisulfite adduct dont form from DCM phase without PTC. OTOH GBL is somewhat water soluable (10% w/v).
Next time Na2S2O3 might be used to remove Br2...
(Edit:) BTW bioessay of product was convincing...
(Chief Bee)
12-06-03 07:14
No 475018
GBL isn't supposed to give a bisulfite adduct.
(Synaptic Self-Mutilator)
12-06-03 09:42
No 475040
>OTOH GBL is somewhat water soluable (10% w/v).
No, GBL is miscible with water. You should try separating the DCM, then extracting 2x150ml DCM... then skipping the water and bicarbonate washes and heading straight to distillation after treatment with FeSO4 (if you're worried about peroxides, which under these strong oxidizing conditions, I wouldn't be too worried about). Also, don't bother drying the DCM. There's no point.. just separate off the water, and go straight to the distillation. The few drops of water will distill across without a problem.
Again, most of your GBL likely ended up in the bicarbonate and water washes. (and a fair amount never made it to the DCM, as your volumes were kind of low)
... OR ...
If you want to start trying to improve the method try to reduce the amount of water used... also reducing the amount of bromide salt might be nice too (to get the solvent volume down, but do that later). Try 50ml water, ~30g KBr.
i.e. .3 mol scale:
28.6g KBr, 50ml water, 14ml H2O2 slowly drip in 12g H2SO4. Then add 150ml DCM, 21.6g THF (25ml), then reflux 1 hr, 14ml H2O2, another 1hr, 14ml H2O2, another 2hr... then workup by separating the DCM, extract 3x100ml DCM... treat with FeSO4 (if you think it necessary), distill.
Since there's people working on this, I think I'll stay out of this. Using THF to get to GBL, for me, would be just as expensive as GABA.
(Stranger)
12-06-03 12:55
No 475063
>GBL isn't supposed to give a bisulfite adduct.
Heh, I failed to realize GBL was an ester.
Thanx, Rhodium!Chromic, indeed the amount of water used is to high, thanx for pointing that out.
>…then skipping the water and bicarbonate washes and heading straight to distillation after treatment with FeSO4…
The bisulfite (not bicarbonate) wash is required to remove the excess Br2 from the DCM phase (and of course also to reduce peroxydes). Water washes should be applied after the bisulfite to remove SO2 …
A good idea would be to use less bisulfite solution, and saturating the subsequent water washes w/ NaCl than back-extracting w/ some DCM.
Some drying shouldn’t hurt, besides it can be done at the same time as treating w/ FeSO4.
The 2 phase ox. system works best w/ 2:5 Br2 : THF (40%), according to table 13. in the paper.
OTOH I’m slightly skeptical wether the 2 phase system is really preferable to an aquaeus system in a large scale run. In an aquaeus mixture less Br2 should be sufficent, eg. 1:5 Br2 : THF as suggested by Moo above. BTW shouldn’t more H2SO4 be used there?
(Synaptic Self-Mutilator)
12-12-03 16:56
No 476510
I think it would be a good idea to use DCM as well, it's important for temp control. This oxidation runs hot. Btw, "work up as usual" means a workup like the one I've posted for getting the GBL from the GABA reaction--not like what is posted in these threads... I'm sure this is the reason why people are seeing such pitiful yields.
(Hive Bee)
12-18-03 08:13
No 477627
SWIM followed Beeswax' write up to the last bit with the only difference that he used BIsulfite to neutralize the bromine. In the final steps, instead of evap. the solvents, she choosed to distill of DCM, which it did, but only at 100ºC (?)
Now, after final destillation of DCM she's got:
(Numbers are aprox.)
170 ml DCM with a STRONG GBL smell
80 ml of some yellow (piss) coloured liquid with a very slight (just a faint) smell of burnt candy. As a side note, it has a very stingy taste (??)
110 ml of deep red bromine coloured liquid
and a lot of dirty white solids (salts?)
Now SWIM's questions are:
1) Is GBL mixed there in the DCM he distilled? (Seems so)Should she evap the solvent to recover it?
2) What the hell is the yellow thing??
3) Can bromine be recover and purify from the red liquid?
Comments welcomed
Chemically enhanced.