benzyl alcohol oxidation

Oh, no, it's ok... I certainly don't know everything, but I'm not as ignorant as I appear

If I were to try to make benzaldehyde, I'd probably go with manganese dioxide oxidation. There are lots of other ways to do it, but that method looks easy and doesn't involve harsh conditions or especially dangerous chemicals.

Quote: Originally posted by Chemi Pharma

Melgar, please, give it a try! I've never read at nowhere, this reaction isn't scalable. Don't blame the authors if they only did a small batch run and ommited about the scalability of the reaction.

Hello, i have lurked around on SM for a while now but finally decided to make an account and contribute

Quote: Originally posted by thermochromic

Hello, i have lurked around on SM for a while now but finally decided to make an account and contribute I have successfully completed several solvent-less partial oxidations of benzyl alcohol with KMnO4, using a slight excess of benzyl alcohol, usually a molar ratio of 1:1.5 (KMnO4:BnOH). No benzoic acid has ever been detected. Benzyl alcohol is one of a diverse group of organic molecules that can act as an inhibitor of benzaldehyde oxidation, hence using the slight excess. It can be removed by fractional distillation under vacuum if desired, but leaving it in acts as a very effective stabilizer. In fact, it is so effective that it protects the benzaldehyde in some cases at temperatures as high as 433 K in the presence of 10 bar O2 pressure with metal catalysts present. No need to worry too much about over-oxidation. It has been shown that benzyl alcohol quantities as low as 2% were sufficient to inhibit the appearance of benzoic acid crystals when benzaldehyde was left sitting out for 90 min so I would assume that even the residual BnOH left in benzaldehyde after a fractioinal distillation might offer decent pretection (depending on how good your fraction column is). Benzaldehyde is usually auto-oxidized by a free radical chain process. The benzyl alcohol selectively removes one of the radicals normally present during autoxidation, thereby inhibiting the chain reaction and preventing any significant amount of benzoic acid from forming.

Quote: Originally posted by Magpie

Please see: https://www.sciencemadness.org/whisper/viewthread.php?tid=26... This is my prep in Prepublication of benzaldehyde from benzyl alcohol using persulfate.

Quote: Originally posted by RadicallyStabilized

I wonder whether the method outlined by Chemi Pharma is really going to work. First, if using TBAB, wouldn't the hypochlorite oxidise the bromide to bromine which would probably brominate the substrate or cause problems with the aldehyde group? (also see https://chemistry.stackexchange.com/questions/70893/does-br2...) Maybe that's why the paper uses TBA hydrogen sulfate instead. Second, the paper seems a bit sloppily done. In the first paragraph, "cyclohexane" instead of "cyclohexanone". Then, they first specify sodium hydrogen sulfite to neutralize unreacted hypochlorite whereas further below they use "sodium hydrogen sulfate". @Chemi Pharma: Did you really follow this procedure to make benzaldehyde with calcium hypochlorite? Which PTC did you use? [Edited on 7-3-2020 by RadicallyStabilized] [Edited on 7-3-2020 by RadicallyStabilized]

OK, I tried this and got a spectacularly shitty yield.

Lab notes start:

32.8 g (0.15 mol) of solid calcium hypochlorite (pool chlorinating agent, 65% available chlorine) were placed in a 300 ml Erlenmeyer flask. 10.8 g (0.1 mol) of benzyl alcohol ("puriss. p. a." but giving off a very slight smell of benzaldehyde) were mixed with about 150 ml of DCM. This mixture was added to the solids. 1.7 g of commercial TBAB were added, followed by a few ml of water. The water floated on top, forming a layer of about 3 mm width; the solutions were clear and colorless with the solids sitting at the bottom.

When magnetic stirring was turned on the mixture instantly turned yellow. A reflux condenser was fitted and the reaction mix was refluxed for one hour. Towards the end of the reaction chlorine gas could be smelled at the open end of the condenser.

The milky, slightly yellow suspension was cooled with a water bath and allowed to settle. The precipitate looked very fine and difficult to filter. A separate aqueous layer could not be observed.

After half an hour it became obvious that waiting for the solids to settle would last too long. The mixture was filtered using a glass fritte and a layer of celite. Along with the fine precipitate some granules of unreacted hypochlorite could be seen. The filtrate was a greenish-yellow liquid smelling of DCM, chlorine and benzaldehyde. A spatula of sodium metabisulfite was added and shaken vigorously but nothing happened. As an experiment some sodium thiosulfate was added as well with no result. A few ml of water were then added, followed my more thiosulfate. On shaking the mixture turned brown. Adding more metabisulfite and heavy swirling eventually caused it to turn almost colorless.

The organic phase was isolated using a separatory funnel and dried using Na2SO4. The solvent was then rotovapped off, leaving behind about 10.5 g of a deep yellow oil that smelled of benzaldehyde.

The bisulfite adduct procedure was then prepared according to the instructions of Eleusis:
Assuming 0.1 mole of aldehyde the bisulfite solution should contain 0.2 moles of sodium bisulfite corresponding to 0.1 mole of sodium metabisulfite (19 g).
20 g of Na2S2O5 were dissolved in the minimum amount of water (about 30 ml). 25 ml of 96% EtOH were added. The turbidity was dissolved by adding more water. The total volume of the solution was about 80 ml. The crude product was slowly added to the bisulfite solution which became turbid. It was stirred for one hour. After filtration and washing with 2 x 10 ml of 99% EtOH the result was 8.35 g of a wet white mass that was left to dry in the air.

The next day the weight was determined to be about 4.5 g. This stuff wasn't even fully dry and still smelled a little of benzyl alcohol. Assuming that it's the pure adduct (189.2 g/mol) the total yield is 23.8 mmol or 23.8 % of the theoretical.

Lab notes end.

Recovery of the pure aldehyde will probably incur losses of about 10%, bringing the yield of benzaldehyde down to maybe 20% or so.

What did I do wrong?
- Used 1.7 g of TBAB without calculating the molar equivalent for TBAHS? Probably not that big of a deal.
- Used more than a few drops of water for the aqueous phase?
- Reaction temperature too low? The solution was boiling but not very strongly. Reflux seemed fine though.
- Didn't decant the solids but filtered them off? I doubt that the paper authors waited for the stuff to settle. They claim it can be done within three hours which doesn't seem feasible to me. And how should this affect the yield. I washed the solids with DCM of course.
- Problems with the thiosulfate? This is a reducing agent used to quench bromine. And it wasn't very much anyway. I'm not sure how this could affect the yield this much.
- Too much bisulfite to reduce chlorine? Maybe the adduct formed in the DCM and dissolved in the aqueous layer. Then again, adduct formation usually takes quite a long time. Still I don't like to use metabisulfite for this (that's why I tried the thiosulfate).
- 10.5 g of crude... first I thought, ok, not so bad. But my guess is that much of this was still unreacted benzyl alcohol.

Any idea where I might have f..ed up? As of now, I'm not convinced

@Chemi Pharma: Thanks. Unfortunately I don't have any Al2O3 right now. Still I don't get how TBAB is supposed to work with solid phases like in the case of calcium hypochlorite.

@Mr. StinkyGas: I don't have any experience making nano particles...

I found another paper (see attachment) and thought to give it one last try, even though that paper has its fair share of errors as well. They claim a yield of over 90%. I didn't have 5% bleach though (I used 2.8%), so maybe that was the cause for my failure. My experience with other reactions (brominations) is that the absolute bleach concentration is not critical, but that may not be the case here.

Lab notes start:

11 g (0.1 mol) of benzyl alcohol were mixed with 50 ml of ethyl acetate in a 300 ml beaker. 3.2 g (0.01 mol) of TBAB were added and dissolved with magnetic stirring. 100 ml of fresh supermarket bleach (2.8% sodium hypochlorite) were added. The mixture turned greenish-yellow. It was covered with a watch glass and vigorously stirred for one hour at room temperature (18.5 °C).

The upper organic phase was separated and the aqueous phase extracted with 2 x 50 ml of EtOAc. 11.45 g of NaHCO3 were dissolved in about 140 ml of water (pH = 8.3). The organic phase was once washed with 30 ml of this solution (which was probably unnecessary as the aqueous phase had a pH of 10.5, so any acid formed would have been in this solution anyway). The organic phase was then washed with brine and the EtOAc rotovapped off. The crude product, a yellow liquid, smelled like benzaldehyde and weighed 14.77 g.

The bisulfite adduct procedure was then done according to the instructions of Eleusis:
20 g (0.105 mol) of Na2S2O5 were dissolved in the minimum amount of water (about 30 ml). 25 ml of 96% EtOH were added. The turbidity was dissolved by adding a little more water. The total volume of the solution was about 80 ml. The crude benzaldehyde (without further drying) was slowly added to the bisulfite solution which became turbid. This time it was stirred for longer time. After two hours there was still not very much precipitate. A little (400 mg) of TBAB was added as recommended by https://www.sciencemadness.org/whisper/viewthread.php?tid=61... but there was no appreciable effect after a few minutes. The formed precipitate was filtered off and stirring was continued for six hours in total. No additional precipitate had formed. After standing for some time a separate layer formed on top, presumably benzyl alcohol/EtOAc (see image).

The filtered-off substance was washed with EtOAc and air-dried. The yield was 2.02 g of adduct (211.19 g/mol) = 9.6 mmol (9.6 % of the theoretical).

Lab notes end.

It seems that the hypochlorite oxidation doesn't work for me (as advertised, at least). Then again, I tried the persulfate method some time ago without getting too great of a yield either so perhaps it's just my bad luck with this reaction. Anyhow, I have enough adduct to make my experiments now. Should I find a way that works well (for me) I'll post it here.


Attachment: Selective Synthesis of Benzaldehydes.pdf (372kB)
This file has been downloaded 541 times

Below you'll find my notes on the oxidation of benzyl alcohol to benzaldehyde with 10 % H2O2 and a quaternary ammonium octamolybdate catalyst, as per Green Chem. 9 (5), 421–423. DOI: 10.1039/B700534B (see attachment). I opted to go with DDAC instead of making the butylpyridine bromide for the catalyst used in the paper, since it's cheap and readily available to the amateur.

Preparation of the catalyst (didecyldimethylammonium octamolybdate)
Bardac 22 (50 % DDAC, 14.50 g, 20 mmol, 1 eq.) and 75 mL water were place in a 250 mL Erlenmeyer flask and heated to 70–72 °C under stirring. A solution of sodium molybdate dihydrate (9.70 g, 40 mmol, 2 eq.) in 40 mL water, to which aq. HCl (37 %, 5.90 g, 60 mmol, 3 eq.) had been added, was poured into an addition funnel and dripped into the stirred DDAC solution at approx. 1 drop per 1–3 s, whereupon a colorless precipitate immediately formed. When the addition was complete the mixture was stirred for a further 20 min before cooling to room temperature. The resulting colorless solid was vacuum filtered and washed with a small amount of water. Filtration was difficult due to the product turning into a thick paste on the filter as water was removed.
Don't have a yield yet as it's still drying in the desiccator, but the wet catalyst can also be used, as below. In a previous attempt I was a bit sloppy, temperature was in the 60s °C, the molybdate solution was added via pipette at a much higher rate and I ended up with an extremely fine precipitate that was nearly impossible to filter. In that attempt I also used a great excess of DDAC as in the ref, which likely contributed to the difficulties and just seemed unnecessary. Also note that the molybdate solution will not mix with the DDAC unless the latter is sufficiently diluted. Fun fact: At 2490 g/mol the catalyst (DDAC)4Mo8O26 is the heaviest substance I've ever made!

Oxidation of benzyl alcohol to benzaldehyde
To wet didecyldimethylammonium octamolybdate (0.70 g, 0.3 mmol, 0.3 mol%) in a 100 mL round-bottom flask fitted with a condenser were added benzyl alcohol (10.80 g, 100 mmol, 1 eq.) and hydrogen peroxide (10 %, 35.40 g, 104 mmol, 1.04 eq.), and the mixture heated to reflux under stirring. The catalyst turned yellow, dissolved into the organic phase and darkened over the course of the reaction, while a change to green indicated the hydrogen peroxide had been consumed after 45 min. After cooling the apparatus was set up for distillation, and the product collected alongside water over a range of 96–98 °C, while the residue in the pot took on a deep blue color and was kept for a second run. The water was removed from the distillate via pipette, the crude product dried over MgSO4, gravity filtered through a pipette plugged with cotton and stored in the refrigerator under argon. Yield of crude benzaldehyde: 6.80 g (64 % of theoretical 10.61 g).
A significant amount of benzaldehyde likely remained in the sump and some was also lost during the removal of the cloudy water layer from the product in the final step. I'm currently performing a second run with the recycled catalyst and will combine the crude products before purification.

Attachment: Ming-Lin, Hui-Zhen 2007 - Selective oxidation of benzyl alcohol.pdf (280kB)
This file has been downloaded 486 times



Edit: So I performed the reaction again in the same RBF including the residue from the distillation and without adding fresh catalyst. However, I increased the amount of benzyl alcohol by 33 % (14.35 g, 133 mmol, 1 eq.) and used 1.2 eq. of H2O2 (10 %, 54.30 g, 160 mmol), leading to a reaction time of 4 h. After distillation the water was removed in a separatory funnel. Everything else was performed exactly as above, yielding 10.50 g (74 % of theoretical 14.11 g) of crude benzaldehyde.
A significant amount of dark green/blue oil remained in the sump after distillation, which solidified fairly quickly upon cooling. Guess this will mostly be benzoic acid.
I didn't bother with extracting the aqeous layer in the sep funnel, but I'll likely do that when I scale the reaction up.

So far I like this reaction. Aside from the messy filtration of the catalyst I can't think of a way to screw this up. All the reagents are easily accessible and cheap as well. I'll see if I can clean up the catalyst for future batches, but I might just save it as is.

[Edited on 2021-2-7 by dawt]

Quote: Originally posted by arkoma

lovely...................working on nitroethane ATM wink wink

Small update on the procedure I posted about on the previous page, using dilute H₂O₂ and an octamolybdate catalyst to oxidise benzyl alcohol:

Yield for the preparation of the catalyst was 93 %. I've also attempted to scale up the reaction 10x using 1.1 eq. of H₂O₂, and while heating up the mixture kicked off a violent reaction when the bath temperature was only approx. 85–90 °C. Luckily I had my eye on the mixture and was able to remove it from the oil bath the second it started acting up, and I had also used my longest condenser, but the bubbling nearly reached the top nonetheless. The picture below was taken 5-10 min after the erruption started, and you can see the reaction was still quite vigorous. For the workup I followed the same procedure as before and ended up with an 81 % yield, though I did have to abort the distillation with approx. 100 mL left in the pot since it started foaming.

I suspect there's still a significant amount of benzyl alcohol and some benzoic acid in my product, so I'll purify it via the bisulfite adduct next.

Here is another green path from benzyl alcohol to benzaldehyde. It is almost OTC, provided you can put your hands on Oxone (potassium peroxymonosulfate).

Source : Oxone/Sodium Chloride: A Simple and Efficient Catalytic System for the Oxidation of Alcohols to Symmetric Esters and Ketones. Synthetic Communications, 36: 1147–1156, 2006. DOI: 10.1080/00397910500514030

Oxone and sodium chloride can be used to either synthesise symmetric alkyl esters or aromatic aldehydes (non-enolisable).

EXPERIMENTAL:

31 g of Oxone (100 mmol) are dissolved into 150 mL of water in a 250 mL beaker using strong stirring. To this is added 6 g (100 mmol) of NaCl. WARNING: upon addition, chlorine gas in released, so this must be conducted in a well ventilated area. Immediately after the sodium chloride has dissolved, 10,8 mL of benzyl alcohol (d ~ 1, 100 mmol) is added to the mixture, which is left to stir at r.t. for 5 hours under a watch glass or similar loose capping, to avoid sur-oxidation to benzoic acid. After a few minutes, the emulsion becomes greenish in colour, probably due to the presence of dissolved chlorine gas.

After 5 hours of continuous stirring, the mixture is left to stand. The upper yellow layer containing benzaldehyde (strong aroma of almonds) and unreacted benzyl alcohol (total: 11 mL) separates from the bottom aqueous layer containing salt and Oxone. The organic phase is collected, washed with water twice. Pure benzaldehyde can be obtained using the bisulfate adduct method (with ~ 15 ml of a saturated solution of sodium bisulfate or metabisulfate).

Pictures: separated upper layer before purification ; Washing of the bisulfite adduct with ethanol



[Edited on 31-10-2021 by Keras]