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mr_bovinejony
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Vilsmeier reagent/POCl3 formation
I have plans to try out the Vilsmeier Haack reaction, but only have PCl5 for it. I found a paper here that describes the formation of the reagent with
PCl5 in dmf
https://europepmc.org/article/pat/cn101490070
Seems like it would be easy enough, but I'd like to make some POCl3 just in case. Wikipedia suggests the reaction of water with PCl5 will create the
oxychloride, but all other information I've seen suggests the oxychloride will further react with water to give some acid product. The other option is
to react PCl5 with some acid and make the acid chloride plus POCl3 as a side product.
Is there a way to stop the reaction of POCl3 and water to where I'm only getting POCl3? Or am I better off going the second route and keeping it all
water free?
Has anyone tried the vilsmeier reaction with just plain PCl5? If it works like described in the paper I won't even need POCl3
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Texium
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The reaction with water should work as long as you add only one equivalent of water. Any POCl3 that overreacts will form phosphoric acid,
which should hypothetically react with excess PCl5 to re-form POCl3. Eventually it should all equilibrate to POCl3.
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clearly_not_atara
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I'd be shocked if V-H didn't work with PCl5 -- that defies all mechanistic rationale and "common sense", etc. Maybe PCl5 isn't a great Lewis acid? But
that doesn't make any sense either.
Save time and do a small-scale test run instead. The downside would be that PCl5 might also chlorinate other parts of the molecule.
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zed
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POCl3 can be synthesized by the reaction between P2O5 and NaCl. There is a procedure on this site. The yield is high.
P2O5 can be purchased fairly easily. PCl5 cannot be purchased easily. On this basis, I suggest you make the POCl3 from P2O5. Save that PCl5 for
something else.
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njl
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Where can P2O5 be easily purchased?
Reflux condenser?? I barely know her!
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mr_bovinejony
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I have the opposite problem, I have pcl5 easily but not p2o5. I have seen that procedure though, and that would be my last option if I had to order
the p2o5 from firefox-fx
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clearly_not_atara
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Quote: Originally posted by zed  | | POCl3 can be synthesized by the reaction between P2O5 and NaCl. There is a procedure on this site. The yield is high. |
The procedure is here:
https://www.sciencemadness.org/whisper/viewthread.php?tid=9&...
However, since the rxn temperature is so high (250 C), I wonder what would happen with other chlorides. The more nucleophilic chloride would be KCl;
the more Lewis acidic chloride would be CuCl2; neither is too hard to make.
Alternatively, we might look at bromides, since Br- is a stronger nucleophile.
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zed
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Yup! You are correct. In years past, we could just buy Phosphorus and its Chlorides outright. Weren't very expensive either.
Tarbutton's work, was a curiosity. Why bother?
With current restrictions on sales, the picture has changed. Making POCl3 is perhaps the only easy way to get it. AND, it's not that easy.
Len1 sort of updated the procedure and published it in his book. There might be better modifications possible.
See Lerner, Leonid (2011). Small-Scale Synthesis of Laboratory Reagents with Reaction Modeling. Boca Raton, Florida: CRC Press. pp. 169–177. ISBN
9781439813126. PDF available from libgen.
Quote:
19.3.1 Preparation from P2O5
The best reaction vessel for this preparation is a test tube with a quickfit joint, a capacity of at least 100 mL, and at least 22 mm in diameter. If
this is not available, a 100-mL, single-neck flask can be used instead with a slight loss of yield. Scaling the reaction requires proportionally
larger vessels.
First, 35.1 g (0.25 mol) of phosphorus pentoxide is rapidly introduced into the reaction vessel, ensuring that as little atmospheric moisture as
possible reacts with the P2O5, as it subsequently generates HCl and HPO3, which attacks the glass. The transfer is best done by inverting a powder
funnel inserted into the reaction vessel, over the mouth of the reagent bottle, and tilting until approximately the right amount of reagent is
transferred into the flask. Next, 34 g (0.58 mol) of finely ground and thoroughly desiccated (1 h at 250°C) NaCl is added, and the reagents
thoroughly mixed. The approximately twofold excess of NaCl improves the yield by about 10%. Finally, about 10 g NaCl is poured in a layer on top of
the mixture, which serves to convert unreacted P2O5 subliming from the reaction zone (bp 360°C). The reaction vessel is placed in an air oven and
connected to a bend leading through a Liebig condenser to a receiver flask immersed in cold water. The outlet from the flask is vented through a CaCl2
protection tube with a bubbler optionally attached for observation of reaction progress.
The oven is rapidly heated to 270°C, from where the temperature is raised more slowly to 450°C at about 65°C/h. A distillation conducted more
rapidly than this will serve both to reduce yield by excessive sublimation of P2O5, and increase the possibility of the reagent vessel bursting due to
excessive buildup of HCl and POCl3 pressure inside the reactor, as these do not have sufficient time to percolate through the viscous sodium
metaphosphate medium (the reagents liquefy during the reaction). About 8.2 g (0.053 mol) POCl3 collects in the receiver at the end of the reaction
while the reactor tube loses 9.3 g (the difference is due to losses in the distillation setup), corresponding to a yield of 76% (86% with respect to
reactor weight loss) based on P2O5.
[Edited on 18-5-2021 by zed]
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mr_bovinejony
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I'm not sure where you buy your reagents but the place I get mine from pocl3 is readily available, although it is more expensive than pcl5. They don't
even sell pentoxide for whatever reason, but I guess if you have access to pocl3 you wouldn't need it in the first place 
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karlos³
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"Hard to buy"?
I'll have to contact that one of my friends though, who offered to ampoule me some up freshly distilled....(dude I know you're fresh on here too, so I
might not even need to ask you personally ).
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Opylation
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In interesting alternative to the Vilsmeier–Haack reaction, at least for indoles, involves using iodine, activated carbon, and hexamine and
refluxing in DMF. The first paper is specific to indoles and I found another paper that performs the reaction on benzene and benzene analogs
Attachment: wang2017.pdf (668kB)
This file has been downloaded 618 times
Attachment: 10.24820@ark.5550190.0001.307.pdf (152kB)
This file has been downloaded 344 times
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clearly_not_atara
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Indole is about as reactive as phenol. Reactions that work on indoles do not generally generalize.
The second paper doesn't seem to say anything about HMTA/I2, but does mention the Duff on p-diethoxybenzene in a disappointing 34% yield.
I don't think either provides a useful alternative to V-H, although alternatives do exist.
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Opylation
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The indole paper is a pretty good alternative, for indoles. You don't have to work with POCl3 which is not the easiest reagent to come by, with it's
use in G-series nerve agents. I mean, it can be prepared easily but then you have to acquire the red phosphorus or PCl5/PCl3 which are equally as
difficult. Idk, as far as the other paper goes I would take low yields and easily reproduceable over having to use difficult to obtain or expensive
reagents. Unless you're working at a university or a professional/industrial lab I doubt you're gonna have an easy time acquiring phosphoryl chloride
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mr_bovinejony
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All experiments with the formation of the vh reagent in dmf and pcl5 have failed, I guess there is some thing I'm missing. The paper mentions the
reagent crashes out as white crystals which it never does, the addition to ice cold dmf generates some heat and then goes a nice pinkish red color.
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mr_bovinejony
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Some interesting thing happens now, 5 grams of pcl5 are added to 5 ml of ice cold dmf. After this is stirred for a bit and allowed to cool, 1 gram of
indole in ice cold dmf is added to the clear read solution. No change is seen, although sometimes hcl gas is given off. It was stirred for 8 hours and
eventually solidified into one chalky yellow lump. This was scraped off and poured into some dilute naoh which released a lot of hcl. Everything is
dissolved now in the light yellow water.
I'm doing this reaction based on shulgins notes, hopefully something will rystallize in another few hours. But the new formation of the yellow solid
is hopeful
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mr_bovinejony
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One last update until I get some real results, this first picture here is what I'm thinking is the final product. Everything I've found about indole
aldehyde says it's yellow, but we'll do a mp tests and an indole test if I can find it.
https://imgur.com/n873ZIR
The second picture is the vh reagent in dmf, about 2 minutes after it was stirred and all added. The paper says it's a white solid but I imagine the
red comes from the dmf. If I was with ether it might turn out white. The pcl5 dissolves all in dmf with no problem, but after the initial stirring it
forms these solids. The paper also says that a second crop of vh reagent dissolves in the dmf which would lead to a double yield of product.
https://imgur.com/7ZafHrq
The trick here was to use an equal weight of dmf and pcl5 like the paper suggests. I don't know why I didn't follow it in the first place, my first
tests being something like 1 g of pcl5 in 10 g dmf. At least this part of the reaction is reproducible now
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karlos³
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But you haven't just judged that this could be the product because its yellow, right?
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mr_bovinejony
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Of course not, I'm looking for some indole identification right now
The stuff decomposed once it hit 190c. Indole aldehyde melts at 198 so I can assume this isn't it, I brought the temp to 210 and it just turned dark
brown
[Edited on 24-5-2021 by mr_bovinejony]
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mr_bovinejony
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The end of the vilsmeier saga: part one
5 grams of pcl5 is added to 5 ml of dmf. This heats up a bit and is stirred for a while. The mixture goes very thick, but with more stirring it gets
liquid again. 2 grams of indole dissolved in 5 ml of dmf are added kinda slow, some gas is given off but there isn't a crazy exotherm. This is stirred
again until it's too thick to stir. More dmf is added to get the bar going. The slurry is stirred for an hour until it cools to room temp
The slurry is poured onto ice and the beaker washed with water. The melted ice and water turns the solution a nice cherry red and all things are
dissolved now. 75 mls of 1 m naoh is added which precipitates the yellow aldehyde. 75 mls of cold water is added and it is all stirred for a while
Once the ice melts, this is all filtered. A weight wasn't taken, but the yellow stuff is now a dark tan for some reason. A mix of 50% aqueous dmf is
made and heated. The indole is recrystallized from this mix. In the fridge it goes, and it's all filtered again.
Once dry, a melting point is taken. On the hoptplate, a spatula full is added to the test tube and hot plate turned up to 250. Once the thermometer
reads 196, it starts turning black. Once it hits 197, it is all black and melted. I guess in this case the literature melting point also means
decomposition point? Unless I am wrong and some product I made has the same decomposition point as the melting point of indole 3 aldehyde.
Here is a picture of all combined product made during these trials. The whole mass was recrystallized from the aqueous dmf mix. The stuff looks dark
orange, although it's been reported that it is supposed to be yellow. I don't know how else to test this stuff without making tollens reagent, but I'm
too lazy for that.
https://imgur.com/V8DI7q6
So for now I'll call this method satisfactory, until the product can be further analyzed. The main discovery I made was to keep stirring the dmf and
pcl5 until it goes liquid again. Since I've done that, I've gotten consistently the same product from the workup. On part two of the saga, this will
be tried on some 1,4 dimethoxybenzene.
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Boffis
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@ mr_bovinejony; Very interesting work, I don't think I've seen an actual V-H synthesis reported on SM before and it is particularly interesting to
see an amateur trying a new slant on this reaction with PCl5 instead of the more usual POCl3 etc. Well done.
To test that you have an aldehyde could you prepare another derivative such as an oxime etc with a better defined melting point?
PS please could you embed the imagine before the links expire. Its better to embed the images then they are always there for the future.
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mr_bovinejony
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Not sure why I can't edit the posts, but I have the images saved for if they do disappear. I don't think imagur deletes pictures though
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clearly_not_atara
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Nice work! I applaud your persistence. Indole-3-aldehyde decomposing at 197 C doesn't sound like a surprise to me. Indoles are reactive, after all.
I think sometimes the dividing line between orange and yellow can be subjective. The crystals remind me of brown sugar, which seems fine.
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karlos³
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I wonder if you could prepare POCl3 in-situ from P2O5 in DMF, readily preparing the VH-reagent? But probably not.
Guess I'm going with oxalyl chloride then instead.
[Edited on 29-5-2021 by karlos³]
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mr_bovinejony
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This method also works no problem with 1,4 dimethoxybenzene. And the product is even more pure based on color, still haven't done an mp on it but it
looks the same as Commercially bought 2,5 dimethoxy benzaldehyde. That's the last I want to try with this pcl5 thing, if anyone wants something tested
just let me know. I love working with pcl5 and this has been a very fun experiment 
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zed
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Long ago my buddy Dr. Death, performed this reaction with POCl3 and Indole. Said it was easy, excepting the fuming of the POCl3.
Condensed the aldehyde with Nitro-ethane. The product....Not Yellow. As I recall, it was either a bright Chrome Orange... Or a bright Cherry Red.
Very interesting. So many Nitro-Styrenes and Nitro-Propenes. All a little different in color.
Back in those days of course, reagents were easy to get. And, many of the end product Phenethylamines, were completely legal. I didn't make very
many, but I saw many that were made.
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