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Klute
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Secondary and benzylic alcohols oxydations using various oxydants
According to S.E.Martin and A. Garrone (Tet. Lett.; 4 (2003) 549-552), secondary and benzylic alcohols are easily oxydized to their
corresponding carbonyl compounds using 30% H2O2 and FeBr3 as catalyst.
These kind of oxydations been very important in organic chemistry, and H2O2 being a available clean, cheap and versatil oxidant, I decided to try out
this reaction and test it's viability.
FeBr3 was made from FeCl3, see my post in the general chemistry forum on the subject. This salt was obtained a red solution of roughly 1mol/L,
contamined by little amounts of inorganic salts (K2SO4, NaBr, etc) which shouldn't interfere with the reaction.
From the paper:
General Procedure. Oxidation reactions with H2O2 catalyzed by FeBr3
A typical experiment was carried out in a open reaction tube fitted with a condenser. To the catalyst FeBr3 (0.20 mmol) in 5mL of CH3CN (or
solvant-free) menthol was added (1 mmol). Then hydrogen peroxide (5 mmol, 30%) was slowly incorporated. The reaction mixture was stirred at room
temperature for 24H. GC was used to follow the reaction. When the reaction was complete, CH2Cl2 was added and both phases were seperated. The aqueous
layer was extracted with CH2Cl2. The combined organic layers were washed with water, dried over MgSO4, and the solvant was removed in vacuo. The
residu was chromatographed on silica gel (70-270 mesh ASTM) column, and eluted with ethylacetate/hexanes using various ratios. All products identified
were found to be indentical to authentic samples.
First trial
The reaction was tried out with benzyl alcohol.
To 15mL of the FeBr3 solution (containing aprox. ~15mmol of FeBr3) in a 100mL erlenmeyer with a 29/32 grounded joint, was added 5.1 g (50mmol) of
benzyl alcohol with slow stirring. Then 29 g of 30% H2O2 (250mmol) were placed in a dropping funnel fitted over the erlenmeyer, and the H2O2 slowly
dripped in (1 drop/2sec) with vigorous stirring. Bubbles appeared from the lower aqueous layer after about 10min. After 20min, the organic layer was
starting to turn orange/red. After 30min, the aqueous was bubbling nicely, about 10 mL of the H2O2 had been added.
During that time, TLC of pur samples of benzyl alcohol and benzaldehyde was prepared, to follow the reaction. The flask had started to warm up
slightly (~35°C), so I went to fetch some ice to cool it down. By the time I came back, the TLC had eluted to the near top of the plate, so I decided
to take it out before applying the ice bath.
As soon as I had taken the plate out, I heard a sizzling noise, and I turned to see the reaction runaway: everything bubbled vigorously, and started
climbing up the flask, and the noise became much louder. Alot of vapors were comming out from the top of the equalized drippping funnel, and
everything in the funnel turned black. I immediatly stopped the addition, and started to duck away as I though the whole thing was going to squert out
the top of the funnel. Luckily, the bubbling quickly stopped before, and everything calmed down, all the H2O2 must have been consumed. Nothing had
came out of the top except vapors. I touched the flask, it was burning hot. There was a strong benzaldehdye smell. Some benzaldeyde had actually
condensed in the dropping funnel, and was floating over the H2O2 left. Most of the organics in the flask had turned to carbon.
Pissed off, I flooded everything with water, and left it to cool. I seperated the yellowish oil in the funnel, and did a TLC on it (using DCM), so
then I could at least keep myself busy. There was a large stain at the aldehdye's rf, a small one at the alcohol's rf, and a hardly eluted one surely
correpsonding to the acid (it did stand over 30% h2o2 for a few minutes).
So the reaction seems to work, when it doesn't burn the shit out of everything in there. So I guess the addition must be done even more slowly,
perhaps one equivalent per hour, and everything in a cold water bath, with ice at hand to cool down quickly if need be. The temperature must never be
allowed to climb up to the point where there's a runaway. That temperature doesn't see be very high.
It was a stupid mistake not to have the ice bath at hand already, and no to have fitted a thermometer. But the way it's put in the ref lead me to
think the reaction was very smooth, and the temperature didn't need to be tightly controlled. Yeah, right.
The reaction will be tried out again next week, with more precautions. A large flask, long condenser, and cold bath at least during the addition, over
5hours. Never underestimate the strengh of 30% H2O2, never. I was lucky this time.
(Edited title, meaningless now. FeBr3/H2O2 doesn't stop at the aldehyde after 12h)
[Edited on 29-10-2007 by Klute]
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chemrox
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Too bad-
looks like you were well prepared and got distracted. I hate that and it's happened to me twice in the last couple of months during the preparation
of intermediates. I also ended up with carbonized shit and some strange mixtures of product I'm keeping for a members GC/MS when I get some 20 ml
vials.
I think chemistry is half theory and half practice. The theory part is easy.. just think and read. Anway, I keep an ice bath and a bulb-srynge handy
when doing a new workup now.
[Edited on 21-10-2007 by chemrox]
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not_important
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Looks like you scaled up from their reported runs. For the authors the reaction may have gone smoothly simply because the small amounts they used
didn't generate enough heat to overcome losses and get into a runaway situation.
Good mixing might help in avoiding buildup of unreacted H2O2, and in avoiding hot spots in the reaction vessel.
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Klute
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Yes, I guess the scale up is the major reason. I don't think this would be practical/safe for bigger reactions. But with good precautions it could be
safer. When they do the reaction with CH3CN as solvant (AcOEt works fine too), they use 5 ml for 1mmol, wich would correspond to 250 ml here! But at
the same time, using 1ml of solvant wouldn't have been practical at that scale I guess. Anyway, we will see what happens next week.
I've always thought that using such a small scale doesn't bring much information apart that the reaction proceeds. Those kind of results can't be
adapted to preperative use, even less to industrial use, without further research. Just another publication and a little more fame, I guess.
Butan-2-ol might be tried for a proof that the reaction works well for secondary alcohols, but not having much 2° alcohol at disposition, I won't
pursue that much in that direction. I don't want to go into the hassle of making some just to see if they oxydize well, if I don't have any other uses
for them.
On the other hand, I have a few substitued benzyl alcohols at hand, most are solid form, so they will need the solvant method.
Has somebody have the ref in pdf or something? I can scan the article if need be, but I'm pretty sure I've already stumbled on it online somewhere. I
thought it was avaible here, but i just can seem to find it although it's been discussed before.
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Boomer
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Maybe a stupid question, but if the chloride does not work, and the bromide does, doesn't it seem logical that iodide would work too, maybe even
better? Or would it be too easily oxidized to elemental I2, falling out of solution quantitatively?
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Klute
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I don't know how it would react, one could think the Br- ions are getting partially oxidized to Br2, seeing the change in color of the organic phase.
I've seen Br2 used to oxidize benzylic alcohols before. But I don't remeber any use of I2 in that case. I could be worth a try, once the FeBr3 is
found to work out, but making FeI3 will be more expensive, and I don't know how stable it could be, releasing I2 and Fe oxydes upon contact with O2
maybe.
But the TCCA/KBr will be tried out first.
Please tryt it out ourself if you have the possibility, on any seconday or benzylic alcohols. Materials are fairly accesible. Simply making FeI3 and
seeing how stable it is would be usefull.
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woelen
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FeI3 is not stable. If it is formed (which I doubt), then it would decompose to FeI2 and I2.
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Antwain
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It doesent exist. I read it somewhere in the last 2 weeks... the ferric ion oxidises iodide to iodine
Edit- somehow i missed woelen saying exactly the same thing 
[Edited on 26-10-2007 by Antwain]
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Nicodem
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Klute, why did you bother preparing FeBr3 when the reaction, as I understood it, does not requires it? It only requires Fe(III) cations (or Fe(II)
since you will be adding H2O2 anyway) and bromide anions. There is no such thing as aqueous solution of FeBr3. It dissociates to various Fe(III) ions
complexed with H2O molecules and bromide ions, also solvated. It can make practically no difference to the reaction if you would have dissolved
FeSO4+1/2H2SO4 and 3KBr in a minimum amount of water and then used it instead of FeBr3 (H2O2 would then oxidize Fe(II) to Fe(III)). Potassium and
sulfate ions have no influence on bromate(I) esters decomposition, the mechanism on which this reaction is apparently based. The only thing that
speeds up their decomposition is light and heath so make sure you do not allow the temperature rising during the addition of H2O2. The reaction is
analogous to the classical oxidation of alcohols with NaOCl/AcOH with the exception that the intermediate hypochlorite esters do not require anything
special for decomposition. Variants using TCCA instead of hypochlorites also exist.
…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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Klute
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I suspected this would be the case. I'm glad you seem convinced of it. For the first few trials I wanted to perform the reaction with a procedure as
close as possible as the paper, with only minor differences (FeBr3 aq solution instead of salt). Seeing that sulfate ions are there as a possible
contamination anyway, it's true it didn't seem like a huge difference. I still want to give it a try this way until I obtain a isolated yield, and
then compare with FeCl3 and KBr, saving me a lot of work. We will see if they really could be interchangeable. I guess the argentin laboratory, and in
alot of others, they just needed to open the "anhydrous FeBr3" vial. Opening a "KBr" vial and a "Fe salt" vial would have taken twice the effort 
I'm glad we shared the same thought, see the thread in the general chem forum.
I doubted FeI3 would be stable. It's pity, could have been another path of expolration though.
One thing I'm concerned of would be possible ether cleavage when using ether-substitued alcohols, such as 2-methoxybenzylalcohol. FeBr3 is a lewis
acid, I'm not sure if it would be powerfull enough in a aq. solution to cause problems on that side. This has just appeared to me, I haven't looked
into it yet. I remebered concerns with using AlCl3 and various rearrangements, but I don't recall if it was in aq. solutions.
EDIT: Nicodem, so you think the mechanism would be similar to the one proposed in the KBr/TCCA paper? Then why bother with Fe salts in the first
place? They hardly mention hypervalent Fe species in the ref. I'd be interested in your interpretation of this mechanism, as I can't acces the library
at the moment.
[Edited on 26-10-2007 by Klute]
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Klute
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Second Trial
In a 250ml 4-neck RBF equipped with a condenser, a dropping funnel, magnetic stirring and a thermometer, were charged 10ml of a solution containing
aprox. 10mmol FeBr3, and 5.4g (50mmol) BzOH.
25ml (250mmol) of 30% H2O2 were charged in the addition funnel, and the flask immerged in a ice water bath with steady stirring (highest setting
without splashing accuring). A large flask was used keeping in mind how the first experiment ended.
Once the temp was under 5°c, the H2O2 was very slowly dripped in (1drop/3sec). After 1H, the top organic phase started to turn orangish, no O2
evolution. TLC indiqued a little BzO was formed, alot of BzOH left.
The whole portion of H2O2 was added over 2H30. The ice bath was left to melt entirely, and temp left to climb up slowly to 10°C (ambient: 10°c).
After 3 hours, some oil sarted to fall to the bottom. TLC indicated more BzO formation, aswell a possible impurity, more eluted than the BzO. After
4H, nearly all of the oil falls to the bottom when stirring is stopped. Very little O2 evolution. TLC indicates more BzO formation, still some BzOH,
and still a little impurity (brominated product?). No sign of BzOOH yet.
The reaction will be continued until 24H have past. One last TLC before going to bed, and one in the morning. I was hopping 3-6H would be sufficient
for the reaction, but it seems it isn't the case, at these temps anyway. Apparently, the reaction procceds very slowly under 10°C, which seems to be
the ideal temp for the first half of the reaction. I don't want the temp to climb over 20°C in case the reaction fires off again. Looks promising.
Rfs: (DCM, 254nm silica plates, Merck)
BzOH 0.33
BzO 0.73
Imp 0.82
Part 2
The last TLC before bet time seemed good. A largish BzO stain, still some BzOH, and at least 2 minor impurities. 20mL of H2O were added to diluted
the remaining H2O2, as 5eq must be alot. Not much O2 evolution was seem at these temp. After 15hours reaction time, the orangish oil has turned to a
thick black oil, standing under a dark brown/black aq layer. When one of the necks of the RBF was opened, the caracteristic odour of BzOOH was
present. A few drops of the oil were placed in a little vial, and DCM added, causing immediate precipitation of a decent amount of a white solide,
BzOOH. Failure.
The reaction doesn't seem to stop at the aldehyde, as the paper magically claimed. In these cases, 1mmol experiments are rarely meaningfull, if you
can't prepare more than 0.1g of BzO at a time... I'm pretty sure the reaction works well with secondary alcohols, but not benzylic ones. I'll fire up
a butan-2-ol oxidation latter on to confirm. But it isn't too surprising that with 5eq of H2O2 hanging around the aldehyde is oxidized further to the
acid. After 6 hours reaction time, the oxidation seems uncomplete. Maybe using 2eq at <10°c would help, but I don't want to waste more time with
this oxidation.
The TCCA/KBr seems more intriging, I have more hope of it stopping at the aldehyde. Nicodem's proposed mecanism on TCCA oxidation (without KBr) in a
unrelated thread seems very pertinent, and in the TCCA patent, they clearly suggest HOBr is responsible for the oxydation, and being present in little
amount, could avoid over oxidations. The numerous given examples of benzylic oxydations confort me in the idea that this could actually work. In the
argentin paper, it seems benzylic oxidation is a just a "plus" added to the paper. They must have tried it, found BzO with GC, and said "it works".
Perhaps they had a very good results on 1mmol scale, but I couldn't reproduce those results, so to my eyes they are useless. I agree, I'm pissed off
from unreproduceable refs. Always the same story.
I'm getting some TCCA latter on, and trying the reaction as soon as the butan-2-ol trial is finished. The shorter rreaction times make this reaction
much more attractive for multiple experimentation.
More news latter.
THe TCCA/KBr paper I'm referring too:TCCA/KBr oxidation
[Edited on 29-10-2007 by Klute]
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Klute
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Oxydation of benzylic alcohols with TCCA catalyzed by KBr and wet SiO2
M. A. Zolfigol et al. Syn., 12 (2006) 2043–2046
The reaction was performed on a 50mmol scale, with benzyl alcohol.
In a 250mL 4-neck RBF with condenser, thermometer and magnetic stirring, 5.41g (50mmol) of benzylalcohol were diluted in 75mL DCM, under slight
agitation. 0.72g (6mmol) of dry KBr were then added, wich evidently didn't dissolve.
5g of granular, amorphous silica gel (made from sodium silicate solution and aq. HCl, washed, dried and activated months ago) were grounded into a
fine powder with mortar and pestle. 5g (278mmol) of water were than added dropwise and left to absorb in the silica. The mixture was than grounded to
a fluid paste with the pestle. Another ~1g of silica was added and grounded until the paste turned to a powdery solid, easily "aired" with the spatula
(1). This solid was then added to the reaction mixture with steady stirring, and formed a snowflake-like suspension, looked like those little
decoration objects you shake to make some snow (who hasn't seen one of those?). Once all the hydrated silica was added, 5.05 g (20mmol) of 92% TCCA
powder(2), previously grounded, was added in 1/2g portions over 30 min. The first portion made the clear solution turn yellowish. This color
darkened to an light orange over the addition, and cleared up to a very light green at the end of the addition. A solid started to stick to the bootom
of the flask, even with the vigorous stirring, and was broken down with a glass rod regulary. It often agglomerated into lumps that were broken down
with the rod. The rod smelled nicely of benzaldehyde when smelled, with a chlorine-like smell. The temp increased very gently from 14°c to 18°c over
the 30min, the TCCA could have been added more quickly.
All in all, it sounds very promising, much cleaner reaction, shorter, and more gentle. A pleasure to work on.
According to another paper on secondary alcohols oxydations with TCCA in acetone that Sauron posted IIRC, I might give a try at addding the TCCA as a
solution acetone, with a base to catch the formed HCL, such as sodium acetate (cf US5821374) or triethylamine. Would be much more pratical and avoid
the clumping of the cyanuric acid formed (possibly trapping the unreacted TCCA).
Rest of the reaction later on!
(1) Getting the right consistency is essential, as otherwise the silica will stay in lumps even with stirring, which is surely detrimental to
the reagent's contact. When it turned from a paste to a powdery solid, it was easily broken down to fine, light flakes with the mag stirring. The
suspension is very easily stirred, even with 75ml DCM. Solvant amount could perhaps be cut to 50mL for 50mmol of substrate. On the other hand I'm
scarred the silica might damadge the inside of the flask, scrapping it. (Edit: it doesn't, the flask was as new after 12H in the base bath)
(2) Powdered "long-lasting" pool tablets were used, as they contained 92% TCCA, and 100% TCCA was much (twice) more expensive. No reaction
with dilute H2SO4, so no carbonates,possibly some cyanuric acid to stabilise or inert materials from production.
EDIT:
After 2h30 reaction time, TLC indicated presenc eof BzOH.. Another 0.5g of TCCA was added in 2 portions, care taken to crash the lumps that formed.
After another hour, BzOH was still present in fair quantites, so another 0.5g TCCA was added, as previously. After 4 h total reaction time, the piss
yellow DCM was decanted (strong smell of chlorine present), the white solids vacuum filtered (some solids appeared in the filteration flask, dissolved
cyanuric acid? BzOOH?), extracted with 2x20mL DCM followed by vac. filteration. The yellow organic phase was washed with 2x100mL sat. Na2CO3, no
bubbling (were did that HCl go? All turned to Cl2?)), the washes cleared to color greatly to a faint green/yellow, washed with 3x50ml dH2O until
neutral/nearly acidic (BzOOH), dried over Na2So4, and placed in the fridge for dist. of the solvant tomorow. Decided on removing solvant before
bisulfite extraction.
A variation with acetone as cosolvant, or solvant entirely, and a base to capture the HCl, which seems to quantitatively turn to chlorine, possibly
chlorinating and/or oxidizing the product, seems to be better approach, although this system appears to be much more efficient and clean thatn the
Fe3+/H2O2.
The TCCA clumping up, and the HCl turning to Cl2 are the major drawbacks. A base seems necessay when using acetone as solvant or chloriantion of the
solvant to lachrymatory chloroacetones could happen from what I've read in related threads. We will see how effective this system is tomorow, with the
isolated yields.
And now the deserved and awaited bedtime
[Edited on 29-10-2007 by Klute]
[Edited on 31-10-2007 by Klute]
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Klute
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BzOOH crystals were present in the erlenmeyer containing the solution, although it was kept under Argon. It was decanted from the Na2SO4 in a 250mL
flask, and the dessicant washed with a little fresh DCM. The DCM was removed on a 50°c water bath, under argon, to leave a clear oil, very slightly
yellow, smelling nicely of benzaldehyde, still containg a little DCM. It was transfered to a 100mL beaker, and a fresh sat solution of metabisulfite
added (~15mL), and everything stirred after the addition of 20mL denat EtOH. A beautiful white precipitate formed after a few minutes, making a thick
slurry. More EtOH was added to thine up the slurry, and everything left to stir for 15min, then filtered, washed with water, EtOH, and ether. After
being left to dry by suction of the buchner for 20min, and dried in a 40°c stove, the crystals weighed 4.28g (20.38mmol), 40.75% yield.
Some yellow oil droplets remained at the bottom of the aq./EtOH filtrate, surely unreacted BzOH contamined with impurities.
Not too bad for a first try. Leaving the solution over night caused aerial oxidation, and not trapping the formed HCl must have formed BzOOH by
oxidation, aswell as soom BzOCl, wich of course turned to more BzOOH upon aq. workup.
A trial with acetone as solvant and using a weak base will be tried tomorow, hopefully a workable yield will be obtained.
BTW, FeBr3/H2O2 gave 79% yield of butanone, as a bisulfite adduct. Works well with secondary alcohol. Cyclohexanol must work out well, although I do
not have some on hand, only cyclohexanone. And I'm not good to reduce it just to try oxydizing it back again
The TCCA/acetone/pyridine paper I mentionned, thanks to Sauron for posting this.
TCCA in acetone in presence of pyrindine oxydation of secondary alcohol
[Edited on 31-10-2007 by Klute]
[Edited on 31-10-2007 by Klute]
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Klute
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TCCA/acetone/Na acetate oxydation
modifies from Syn. Comm., 22(11), 1589-1595 (1992)
In a 250mL 4-neck RBF with condenser, dropping funnel, thermometer and mag. stirring, 50mmol of BzOH were dissolved in 40mL dry acetone.
Roughly 6g (~23mmol) of 92% TCCA were dissolved in 50mL dry acetone, leaving some insoluble white powder (binders, the 8% crap) that were filtered
to give a milky solution (fine particules).
5.85g (71.32 mmol) of freshly fused sodium acetate were weighed and kept sealed.
The TCCA solution was charged in the adddtion funnel, and 1g of Na Acetate added to the benzyl alcohol solution. The TCCA was dripped in (1drop/sec),
with steady stirring. After 5 min, the suspension became milky, and started to thicken. The acetate was gradually added as the addition continued. The
suspension quickly turned to a thick slurry, still stireable, but very thick. Dry acetone was added to thin it up regularly. At then end of the
addition, more than 100mL of acetone had to be added for the thick white slurry te be stireable. TLC showed little BzOH left, and only another BzO
stain.
After 1h30 total reaction time, the white slurry was filtered twice on the same paper to clear the acetone filtrate up. The cake was washed with a
little fresh acetone. The filtrate (definate benzaldehyde smell) was transfered to a 250mL flask, purged with argon, to strip the solvant. By the time
the hot water bath had heated, the initially clear solution had turned milky. I thought it must have been some dissolved cyanuric acid crashing out.
The acetone was distilled off at 60-65°C bath temp, more and more solids were appearing, given a white suspension. The first 30mL of acetone had a
strong chlorine smell, but no lachrymatory effect (1). Once most the acetone ahd been stripped off, vacuum was applied to get the remains
out.
Then 20mL of water were added to the residue, a yellow oil crashed out, aswell as some white solid. All this was transfered to a 150mL seperating
funnel, 15mL DCM added to the flask and then transfered to the funnel, the aq. extracted, organic seperated, and the aq./solids extracted with another
15mL DCM. The combined organics were then washed with 2x50mL sat. Na2CO3 solution, 2x25mL water, and 2x25mL brine, dried, and solvant stipped off,
leaving 2.4g of yellow oil, smelling nicely of benzaldehyde (with a little acrid benzoic acid smell).
The oil was transfered to a 100mL beaker, diluted with some EtOH, and 15mL of sat. bisulfite solution added. After a few minutes, the adduct formed.
More EtOH was added to thin up the slurry, which was then vac. filtered, and washed generously with EtOH, and dried by suction, to recover, after 12H
drying, 3.84g (18.28 mmol) of beautifull white powder, 36.56%.
This time, there wasn't any oil in the filtrate.
(1) Not performing a KI/starch test was a mistake, there must have been more TCCA left in solution, cyanuric acid crashing out as it was
consumed (Cl2 in the distillate), without any base to capture the HCl. Heating the solution up to 60°c must have cooked alot of benzaldehyde into
benzoic acid. But considering that in the ref they leave the reaction to proceed for only 20 additional minutes, I didn't expect any TCCA to be left
after nearly h additional time... Apparently the highly dilute solution, and stirring difficulties must have slowered the recation down considerably.
Comments
Using sodium acetate as a base was a bad idea, as it made a unstirreable mass, and involved huge amounts of solvant.
Triethylamine will be stried today, hopefully with good results. Then a combination a this paper and the KBr one, using acetone, KBr, triethylamine
possibly SiO2. I don't knwo how it will work out in basic conditions, i guess OBr- will be formed rather than HOBr; basicly, I want the raection to
proceed with hyopobromite/ous, but capture the formed HCl to avoid Cl2 formation and consumption of the TCCA. I still don't understand why there isn't
any haloform reaction of acetone with TCCA in basic conditions though.....
We will see..
Please feel free to post any comments or suggestions towards these procedures.
EDIT: Found a reason for low yields
When cleaning up the glassware, I emptied the filtrate from the bisulfite adduct formation, all the filtrates had been combined as they were
refiltered to gather some crystals that had formed in the night. I emptied this clear solution in a washing bassin where was soaking the glassware
freshly taken out of the base bath, in other words, the water was very basic. This clear solution immediatly turned milky, some oil appeared, and a
strong smell of benzaldehyde emmited from the bassin. Apparently, the bisulfite adduct of benzaldehyde is somewhat soluble in 96% EtOH, enough for the
washes to retain a certain amount of it. I have no means of guessing the amount of benzaldehyde produce in there, but there was a fair amout visible.
Not just tiny droplets. So it seems the real yields of the reactions were higher than what I isolated. I will not use the bisulfite adduct to isolate
the futur products, or only wash sparingly with EtOh, and generously with Et2O.
At least this brings a little more hope back.
The TCCA ina cetone/triethylamine oxydation is currently taken place, and looks very promising. I will report the results later.
[Edited on 1-11-2007 by Klute]
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Klute
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TCCA in acetone in presence of triethylamine oxidation
To a 250mL 4-neck RBF with condenser, addition funnel, thermometer, and magnetic stirring, 5.41g (50 mmol) of benzyl alcohol were dissolved in 40
mL dry acetone, followed by 9.70mL (70mmol) of triethylamine.
5.93g (23.63 mmol) of TCCA were dissolved in 50mL acetone, and introduced in the addition funnel by filtering through a fluted paper to remove
insoluble binders.
The clear solution was dripped in (1d/sec) over 30 min. A white solid started forming quickly, giving a white suspension. A white fog apperaed
immediatly above the solution.
After 1h30 total reaction time, the suspension was filtered, and the clear filtrate transfered to a 250mL single neck RBF. The acetone was removed,
under Argon, over a 65°c water bath. THe initially totally clear solution started to turn yellow. The residu obtained was dark brown.
25mL H2O was added to it, and everything transfered to a seperating funnel. The very dark brown oil was seperated, and the orange/yellow aq.
extarcted with 2x10mL DCM. The combined oragnics were washed with 2x25mL 5% HCl, 2x25mL sat Na2CO3, 2x25mL H2O, dried, and the solvant removed. The
very dark, viscous oil remaining didn't smell at all of benzaldehyde. A TLC indicated very little benzaldehyde, alot of hardly eluted stains: crap.
I think heating the product with excess triethylamine in acetone caused severe crossed aldol condensations, which shouldn't have been a problem with
the products obtained in the refs (ketones), so I guess I obtain benzylideneacetone and dibenzylidene acetone. Sigh...
Tomorrow will be tried a combiantion of both papers: the susbtrate will be dissolved in DCM, with wet SiO2, KBr, and triethylamine gradually
incorporated, aswell as TCCA as a acetone solution: The formed HCl will be trapped, without having a strongly basic medium, the acetone will be
removed by washings with brine or water, while the product stays in the DCM. After washings and drying, it will hopefully be recovered as an oil, and
possibly treated by bisulfite if TLC indicates starting material. Wish me luck.
EDIT: actually, TCCA is even more soluble in EtOAc than in acetone (Cf TCCA review), so I will use that solvant to make the TCCA solution, no
condensation problems, and less alpha-chloriantion possible.
I'm also considering making some 4-oxo-TEMPO (TEMPON) as a catalyst for oxidations. Such catalyst are very documented in recent(ish) litterature, in
various applications. Oxidation of alcohols to carbonyl and/or acids is one of the most important one. The precursor 4-oxo-tetramethylpiperidine
(tiacetoneamine) can easily been made with acetone and ammonia (see related thread, patents mentionned herein), and then oxidized to the nitrosyl
compound with either oxone or basic H2O2 (cf thread and references mentionned herein). This TEMPO derivative is mentionned in numerous
tempo-derivatives-mediated alcohol oxidations, and could be fairly accesble to the home chemist. Reducing the carbonyl to an hydroxyl (TEMPOL) with
NaBH4, and possibly methylating it (4-MeO-TEMPO), or reductively aminating the carbonyl could open paths to other derivatives of this family. Alot of
work ahead.
[Edited on 1-11-2007 by Klute]
[Edited on 2-11-2007 by Klute]
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Nicodem
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Using acetone as reaction medium for TCCA in the presence of tertiary amines is useless as most TCCA will get consumed to oxidize acetone. You can use
ethyl acetate or acetonitrile instead.
What role is Et3N supposed to have?
[Edited on 2/11/2007 by Nicodem]
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Klute
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Strange you say that, as these are the conditons in Syn. Comm., 22(11), 1589-1595 (1992) : acetone, TCCA, pyridine, to trap the formed HCl.
They supposibly report a good yields of ketones (not applied to benzylic alcohols). But in any case I abandoned the idea of using acetone, as it is
too reactive towards the oxidant.
I use EtOAC to dissolve the TCCA, and added the solution to a DCM solution of the BzOH, KBr and SiO2, although the starting material wasn't consumed
even after 2 hours and 50% excess oxidant (from the paper, so 3x molar excess) after having been very gradually added, no impurites are present, the
filtrate only contains BzOH and BzO according to TLC. Unfortuanly, I added IPA to neutralise and remaing oxidant before filtration, and in a matter of
minutes, the solution started to turn yellow, and quickly came to a reflux : i guess it's the formed acetone reacting with TCCA, forming chloroacetone
(acidic media). I din't open the flask to see if this was the case. The flask was quickly cooled, the yellow color disappeared (??), and I thoroughly
washed the filtrate with sat. Na2CO3, water, and brine before drying. TLC indicated only BzOH and BzO, although I don't suppose chloroacetone would be
detectible with UV (254nm), but the basic washes should have go rid of any present.
I also don't understand why the acetone wouldn't do a haloform in these conditons (Basic media, OCl-).
I will be doing a last try with the TCCA/KBr/SiO2 with triethylamine, in EtOAc today.
Details of the TCCA/KBr/SiO2 sans base to come.
The problem with not trapping the formed HCl, is that a lot of Cl2 is formed and most of the TCCA is consumed that way, that's why not all the BzOH
get's oxidized. This is pretty anoying. On the other hand, adding triethylamine might mess up the HOBr formation, and modify the catalysis cycle in
one way or another. But I can't use 10x molar excess of TCCA,a s the formed Cl2 will surely oxidize/chloriante the substarte and/or product. Any
suggestions?
Unfortuanly, I won't have time to isolate any tetramethylpyridine in the week to come, so I will let the NH3 and acetone together until I ahve a bit
more time to perform the oxidation to the nitrosyl and the alchols oxidations. I should have mixed both of them a week ago. I don't really have time
to gas the mixture with NH3 g and do a 15H reflux if I want to continu looking into the TCCA methods and give the substitued benzyl alcohols a go, so
the long contact method has to be used.
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Nicodem
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In the oxidation of acetone with TCCA the enolization step is the rate limiting step. Hence if you use pyridine, which is roughly 350,000-times less
basic than triethylamine, you can expect a so much slower oxidation of the solvent.
Catching the formed HCl with Et3N or pyridine does not really prevent the formation of Cl2 in the reaction mixture since the chloride anion is just as
easily oxidized to chlorine as is HCl. The result is the chlorine and amines forming Et3N*Cl2 or Py*Cl2 (which can also oxidize alcohols). It is
technically thus more correct to say that the amines serve to catch Cl2 instead. If the reaction media is anhydrous and aprotic, then what somewhat
inhibits the oxidation of benzaldehyde to benzoic acid (actually benzoyl chloride) is the absence of light and low temperature.
PS: The shorthand Bz- generally stands for benzoyl (PhCO-) and not for benzyl (for which the shorthand Bn- is generally used). Hence BzOH is benzoic
acid and not benzyl alcohol as you use it. BzO would thus be the radical PhCOO*.
…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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Klute
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So I guess adding Et3N isn't as efficient I supposed it to be. I will just stick to the TCCA/KBr protocole then. But having a certain amount of
unreacted BnOH (thank you for that reactification! ) is pretty annoying,
especially when using solid subsitued BnOH's, seperating the two aren(t that easy wihtout bisulfite adduct formation. A few recrystallizations might
do the trick.
During the oxidations, the temp rarely goes above 10°c, and I use only neon light to work, this might be less of of the problem if the
photodegradation is dependant on the spectrum of the light. I think I will cover the reaction flask with aluminium.
What do you suggest to avoid consumption of the TCCA by the HCl? I just can't understand how they supposbly get so high yields in the paper, while the
oxidation seems uncomplete even when using bigger excess and longer reaction time. At the same time, they simply evaporate the solvant and collect the
residu. It would seem pretty obvious that they used GC to determine the purity of the residu, and correct the yield, but it 's isn't explicitly
mentionned anywhere.
I'm thinking of trying the reaction on 2-MeOBnOH, and 5-bromo-2-MeOBnOH, aswell as either 4-BrBnOH or 4-NO2BnOH (although they have bad yeilds on this
one, can't imagine how bad it will be when I try it ) because I have then on
hand. If the reaction give correct yields without byproducts, even if uncomplete, I think we can safely say it's a valid protocole, necessitating some
recylcing in order to avoid waste of substrates. I will still send a few samples to GC/MS to see if any chlorinated product are present, as they could
possibly be hard to differentiate with TLC.
Again, any suggestions are welcome.
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not_important
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As an aside, when making chloro- or bromo- acetone, some used CaCO3 or NaHCO3 to neutralise the acid formed. You need good stirring to use those,
obviously.
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Klute
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I suppose the result would be the same as using Na acetate, ie a thick slurry, needing huge amounts of solvants. As there's already the silica and the
KBr in solid phase, having too much solids will surely prevent good contact between all the reagents...
The TCCA in EtOAC gave a little under 35% yield of the bisulfite (minium EtOH washes), and some chloroacetone was formed as I cried my eyes out when
the solvant was removed and I dismantled the distn setup... So some chloroacetone is present as an adduct in the white powder I guess...
I really don't know what else to do to get this working correctly. I will try adding Et3N anyway, to see if that really changes something or not. I
really feeling disapointed.
EDIT: I'm going to try solid Ca(OCl)2 with BnOH in DCM in presence of Bu4NBR... We will see what that gives... I might also try a ACOH/HOCl biphasic
oxidation... I'll finish by finding one procedure working if I try all of them, no?
[Edited on 3-11-2007 by Klute]
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Klute
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Benzyl alcohol oxidation by solid calcium hypochlorite in presence of TBAB
In a 250mL 4-neck RBF with condenser, thermometer and magnetic stirring, 5.41g (50mmol) of BnOH were dissolved in 75mL of DCM, followed by 0.65g (
2mmol) of TBAB (tetrabutylammonium bromide, PTC) (~5% molar to the hypochlorite).
12.7g (40mmol) of 45% hypochlorite granules were powedred as fine as possible, and 2/3 of the powder was introduced slowly, in portions, to see if
any exothermic reactions setted in. The first portion turned the initially clear solution yellow, and at the end of the addition, the color of the
suspension was canary yellow, and then fainted away slightly after 5min. The suspension was very fluid, and easy to stir. The temp increased slowly
from 9°c to 12°c over 10min, so an ice bath was applied to take it down to 3-5°C.
2 drops of water were added, they stayed at the surface and quickly turned white at first, then disappeared slowly as the suspension was becomming
more and more milky (CaCl2 formation). Should have added wet silica.
At 30 min total reaction time, TLC indicated a large BnO stain, and still some BnOH left. A large portion of the remaining hypochlorite was added
in one portion (no apparent change in color), and the ice bath was removed. The temp increased slowly to 12°c over 10 min.
At 1H TRT, TLC indicated a large BnO stain, still some BnOH, and a tiny spot above the BnO stain, indicating some kind of impurity
(benzoylchloride?). The color was now lemon green, alot of very fine dust in suspension when stirring is stopped. The last portion of hypochlorite was
added, without the ice bath. The temp increased gradually to 15°c, so the ice bath was applied to get it back to 10°c.
3.10g (~10mmol) of hypochlorite were weighed and grinded, one gram was added. An washing bottle attached to a gas outlet on top of the condenser
indicated some gas evolution. Surely carbonates present reacting with formed HCl, or Cl2. No pungnent smell when a side arm is opened.
At 1H30 TRT, TLC indicated large BnO stain, BnOH (smaller), but larger impurity stain.
The reaction mixture was filtered twice over the same paper to clear it up completly, the cake being washed with 2x15mL DCM. The totally limpid
emeraude green combined filtrates were then washed with: 50mL water (turned slightly milky), 2x37.5mL 5% HCl (cleared up a bit), 50mL dH2O, 2x50mL
sat. Na2CO3 (cleared up totally, took a yellowish color), 3x50mL water (until neutral, stayed totally clear), and 75mL brine, before being dried over
Na2SO4. The workup was a breeze, no emulsions (as I thought there would be because of the PTC), very clean. The green-yellow solution was keeped over
Na2SO4, under argon, infridge over night. Currently performing TLC.
This oxidation looks much better then the TCCA ones. Very quick, easy and clean. I think at least 2x excess should be used right at the beggining,
and the temp kept under 10°C, so the impurity formation can be avoided. I think it's some benzoylchloride, fomed from the BnO and Cl2, than the
washes remove easily.
I used a solid/liquid system unlike a liquid/liquid dual phase systeme, becasue IIRC, aldehdye oxidation to acid or benzoylchloride transists
through a hydrate of the aldehdye. Please correct me if I am wrong, but if it's the case, have hardly any water in there could minimize over
oxidation. The calcium hypochlorite used was some granules for swimming pools. I guess htye contain a large amount of carbonates and CaCl2, aswell as
what thye call a "clarifiant" and a "tartre fixer". I'll try looking for an MSDS to see what these could be, but they don't seems to interfer with the
reaction. This method looks very promising.
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yan123
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i have used CrO3 /SiO2 about harf year before, is a good chioce. i am sorrry i forget the referrence. maybe on tetrahedron? i am not sure.
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Klute
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Thank you for sharing your experience. Unfortunaly, I can't acces CrO3, and I don't think I would use it if I could, I din't like working with Cr
salts.. Finding more available and less toxic oxidants is one of the main reasons I tried all these reactions, so we could put all these traditional
toxic ones aside.
Just out of curiousity, did you prepare the supported-oxidant yourself? Or was it a purchased reagent?
The Ca(OCl)2 reaction gave a much cleaner product, a slightly yellow oil, have a very pleasant small, without that stinging ting to it, as the
others had. But the impurity was still present after the washings, so it can't be the benzoylchloride. Maybe some kind of chlorinated product,
although I doubt chlorinating an aroamtic aldehdye could be done so easily, in the cold. But without further means of caracterisation, I can only
guess.
I will try the reaction with 2-MeO-5-BrBnOH today, and see what gives. Hopefully, I will be able to recycle the starting prodcut, as the price and
availability of the substarte isn't the same! So no bisulfite adduct this time. I hope a steam distillation will be able to effectivily speperate the
two. I will surely fractionnate the two once I've done a few reactions. Fractionnating 5g product (at best) in a 50mL distn. setup is asking for
mechnanical looses.
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Boomer
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"Please tryt it out ourself if you have the possibility, on any seconday or benzylic alcohols."
The only secondary alcohol I have is IPA, and making acetone is not exactly exiting, it being three times cheaper than the IPA over here.
That is unless it gets banned due to teenies and terrorists peroxidising it... 
The only benzylic alcohol I have is much less boring, and stands right next to the nitroethane and butylamine. But I would never break laws just to
verify a concept!
Oh btw it is 3,4-methylenedioxy-benzylalcohol.... 
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