Sciencemadness Discussion Board - Cubane; Dimethyl Cubane-1,4-dicarboxylate synthesis

Cubane; Dimethyl Cubane-1,4-dicarboxylate synthesis

Tsjerk - 15-2-2020 at 04:23

I'm far from the full synthesis of dimethyl cubane-1,4-dicarboxylate, but I'm getting somewhere.

Based on this publication: Attachment: falkiner2013.pdf (1.4MB)
This file has been downloaded 750 times

The first step I took was making cyclopentanone ethylene diketal. presuming the product is pure, I did it with a yield of 69%. I'm planning to do a vacuum distillation before proceeding, so that will go down a bit.

What I did:

To make compound 8 from scheme 5 I bought cyclopentanone and ethylene glycol. As a catalyst for the ketalization I refluxed 25 ml of 96% sulfuric acid with 100 ml of toluene in a Dean Stark apparatus. I don't know if it is normal for this reaction to turn black, but after one hour of reflux at least the sulfuric acid layer seems to take up all the black tar (I guess it is tar) and the toluene layer on top becomes quite colorless, it has a bit of a green color. I stopped the reaction after I separated 2 ml of water in the Dean Stark trap.

I screwed up the above preparation once, I tried to separate the two layers (toluene/sulfuric acid) in clean, but not dry glassware. This will make the p-toluenesulfonic acid (TsOH) precipitate and clog the separation funnel. The TsOH hydrate is pretty insoluble in my pretended solvent (toluene) so I didn't try to get it back in solution or to do a laborious isolation of TsOH, which would also introduce a water molecule as it forms a monohydrate. With dry glassware, everything worked out fine. I just separated the two layers.

50 ml of the above prepared solution of TsOH was diluted with 150 ml of toluene and to this cyclopentanone (30.0 ml, 28.5 gr, 0.34 mol) and ethylene glycol (19.0 ml, 21.1 gr, 1.05 eq.) was added. This was refluxed for one hour at high heat in a Dean Stark apparatus, after which the calculated 6 ml of water was trapped by the Dean Stark. When heating was continued droplets of ethylene glycol were captured by the trap (ethylene glycol forms an azeotrope at 110, against the water azeotrope at 84) which was visually determined as the droplets sank into the water layer.

To be sure the reaction was finished (as I didn't know how much glycol came over with the first 6 ml) the water and ethylene glycol captured were returned into the boiling flask and the procedure was repeated but with lower heating. This time there was a clear difference in viscosity of the droplets captured before and after the 6 ml mark.

The reaction was cooled and washed with bicarbonate and brine. The toluene was evaporated under vacuum and the remaining organic layer was dried over magnesium sulfate. The crude yield was determined to be 30 gr. 69%.

I did screw up during the work-up, I had a suck back of (clean) water during the vacuum evaporation of the toluene, stupid mistake which made me dry the organics again, so the yield probably could have been higher. Also next time I will consider using worked up TsOH ( the hydrate will be captured by the Dean Stark anyway...) or something like acidic exchange resin as a catalyst (from a Brita cartridge?). But for a first attempt, not too bad I would say.

[Edited on 15-2-2020 by Tsjerk]

Tsjerk - 15-2-2020 at 04:35

The next step is the bromination of the diketal with 1,4-dioxane.Br2. I'm looking forward to receive my sodium bromide and sodium bromate, as I wasn't looking forward too much to distilling bromine. With the bromine/bromate and a bit of acid I can make bromine as a separate layer which will be dried with sulfuric acid.

Apparently this step only works with the dioxane-Br2 intermediate. The solvent doesn't seem very relevant to me... the reaction runs at room temperature. Only the dioxane/bromine complex seems to be important. I'm thinking about using a co-solvent instead of pure dioxane as the solvent.

The reaction scheme:

[Edited on 15-2-2020 by Tsjerk]

Dr.Bob - 15-2-2020 at 17:33

That looks pretty interesting. I have never seen this synthesis, but it looks good, practically a good organic test question. For most cases of the first step, you could simply start the reaction by mixing the ketone and glycol in toluene and then just add a little sulfuric acid as the catalyst, I believe. But pre-making toslic acid that way is a neat trick.

The bromination is interesting, it goes only 3/4 of the way, likely due to sterics. Then the dehydrobromination to the monobromo-cylcopentadiene, which does a Diels-Alder with itself. Good luck with the whole synthesis.

Tsjerk - 15-2-2020 at 22:08

Quote: Originally posted by Dr.Bob

For most cases of the first step, you could simply start the reaction by mixing the ketone and glycol in toluene and then just add a little sulfuric acid as the catalyst, I believe.

I was planning on doing that; but when I added the sulfuric acid to the toluene it turned black in minutes. I don't know if this happens to pure toluene or that it is due to an impurity that is polymerizing. It does look a lot like tar and the color is captured by the sulfuric acid layer after prolonged refluxing.

[Edited on 16-2-2020 by Tsjerk]

ninhydric1 - 16-2-2020 at 11:45

The polymerization is most likely due to (1) impurities, or (2) some sort of interesting polymerization with the ethylene glycol. Is the toluene/sulfuric acid fairly pure?

If they are, and the black tar still happens, I highly recommend making the tosylic acid first. Chances are EG polymerizes messily in the presence of sulfuric acid.

Tsjerk - 16-2-2020 at 12:16

Thank you for the reaction! Did you run the tosylic acid preparation yourself with pure toluene? I wonder whether it turns black with pure toluene.

What I did was running this preparation in two steps, first preparing the TsOH catalyst; see if I could capture some water in the trap, and than use the TsOH solution for the ketalizaition. I thought it would work as an one pot reaction, but it looked so dirty I separated the sulfuric acid (full of tar) from the toluene before using it. It forms a nice two layer system, and the final toluene layer was only slightly colored.

I guess my toluene contains something that polymerizes, It was dirt cheap...

ninhydric1 - 16-2-2020 at 15:33

I have, indeed, carried out the tosylic aicd preparation with pure toluene, and no such black tar had formed; the most discoloration was a slightly gray or a light orange-yellow. I suspect it has to be impurities and/or reaction with EG.

Tsjerk - 17-2-2020 at 04:26

The black tar was separated with the sulfuric acid layer before I added EG and cyclopentanone. After removing the tar and dilution of the TsOH with fresh toluene the solution was only slightly yellow, as is the diketal now.

Tdep - 24-6-2020 at 20:32

I'm really interested in doing this. The pilot scale synthesis paper is fantastic, and I found that before I found the thread, thinking "hey wonder if anyone from sciencemadness has tried this"... of course they have.

The difficult part of this experiment for me is the need for vacuum distillation. The boiling point of the ketal is what... 150 C? Distilling at standard pressure might "tar it up" at those temperatures I suppose... or break it apart and start distilling the two fragments... although there's no water left in the system?

An issue I've been thinking about is 1,4-dioxane production. You do have excess ethylene glycol and a hot, acidic environment. So maybe the vacuum dist. is to avoid the temperature needed to drive dioxane production?? But then you see in the Pilot-Scale paper, that they use dioxane as the solvent for the next step... so I guess who cares anyway?

If it's all about keeping the temperature low, could you run a Dean-Stark set-up with Benzene instead of toluene? Boiling point of azeotrope (91% benzene) is 69 C, and then after the reaction you can distil off the benzene at 80 C, leaving behind just your product, some small amounts of dioxane.... and you proceed to the bromination without further purification?

Tdep - 24-6-2020 at 20:36

On second thoughts, you'll have acid and excess ethylene glycol and potentially cyclopentanone and knowing me some tar... so it's probably worth distilling out the product before doing the bromination, right?

Heptylene - 24-6-2020 at 23:18

Sigma says the boiling point of the ketal is 55 °C at 35 mmHg. That vacuum level can be easily reached with an aspirator. This whole synthesis looks very doable! Any updates Tsjerk?

Tsjerk - 25-6-2020 at 01:02

I indeed vacuum distilled the ketal, of which I have plenty now. The bromination went fine as far as I could tell but I couldn't filter the product, it was so fine it went straight through my finest glass filter. Gravity filtration also didn't work as the filter was clogged within seconds.

I left the product in an open beaker, the solid at the bottom seems stable, it stays nice and beige, but as soon as the liquid evaporated everything turned black.

I'm producing a big batch of KBrO3 out of KBr by electrolysis as we speak, so I can make more bromine. I will brominate some more ketal soon and figure out a way to filter the product.

One problem I'm facing is the source of UV in the 300 - 350 nm range. I have a nice quartz tube I can stick through a Teflon stopper, but looking for a UV led only got me here. The have leds's in the right range but they are expensive... They have a price list somewhere on the website.

Does anyone know a cheaper source?

Edit: about the tar produced by the toluene/sulfuric acid: I later found that happens with technical toluene and can be prevented by stirring the toluene with sulfuric acid at room temperature and seperating the acid before doing the Dean Stark.

sulfur in toluene

The yellow ketal nicely cleaned up by vacuum distilling it, indeed leaving black crap behind.

Edit2: I'm thinking about extracting the brominated product with DCM... This would then be dried with MgSO4 and evaporated under vacuum. That way there is no need for filtration. Also the product seems to be oxygen sensitive, this way not too much air would be around.

[Edited on 25-6-2020 by Tsjerk]

Endo - 25-6-2020 at 05:02

I recently purchased some UV LEDs from these guys.

EBAY supplier

Tdep - 25-6-2020 at 18:32

The wavelength has to be shorter than 350nm, which is frustrating, as most common UV LEDs are 365 nm. There's some deep UV LEDs, but they're pretty expensive still.
Really the peak absorbance perfectly overlaps with the 254nm UV line from a low-pressure mercury lamp. As fancy, fun and fresh LEDs are, this really looks like a lamp job to me

Quieraña - 25-6-2020 at 22:20

I saw this thing on yt about YAG crystal filled cubane molecules wrapped in tellurium or equivalent mirror shiny coating of nuclear unstable isotope which, when beamed with xray became filled with infrared via YAG component which would , when injected say, to a cancer cell, be there knocking off carcinomas via neutron bombardment AND a laser punch have ypur cake and eat it too, 'be rainbowed', channel on yt.

DavidJR - 25-6-2020 at 22:35

Quote: Originally posted by Tsjerk

I think this is caused by the presence of methylthiophenes in petroleum-derived toluene, which cannot be separated by distillation. These compounds are more readily sulfonated than toluene.

Tsjerk - 26-6-2020 at 01:39

Quote: Originally posted by DavidJR

I think this is caused by the presence of methylthiophenes in petroleum-derived toluene, which cannot be separated by distillation. These compounds are more readily sulfonated than toluene.

Indeed, I found out via this video. The method for purification shown in the video works nicely. I do think some p-TsOH is already formed at RT, as white fluffy crystals crystallize when the toluene is added in a wet separatory funnel. Depending on the purpose of the toluene this can easily be removed with some (bi)carbonate solution.

Quote: Originally posted by Tdep

The wavelength has to be shorter than 350nm, which is frustrating, as most common UV LEDs are 365 nm. There's some deep UV LEDs, but they're pretty expensive still.
Really the peak absorbance perfectly overlaps with the 254nm UV line from a low-pressure mercury lamp. As fancy, fun and fresh LEDs are, this really looks like a lamp job to me

I think I will order some of the cheap UV LEDs mentioned by Endo and hope they bleed enough into the <350 nm range. Maybe I can even ask the supplier if he has an emission spectrum.

Housane - 26-6-2020 at 10:02

Why do you want this Tsjerk? What idea do you have for it?

Tsjerk - 26-6-2020 at 11:01

For the fun of it, it would be nice to have a NMR spectrum with that specific cubane hydrogen peak.

Heptylene - 27-6-2020 at 01:13

Philips makes some UV-B fluorescent tubes. Not cheap though. But maybe there's an affordable source near you, since Philips is a dutch company!

Otherwise, go with a mercury vapor lamp, high pressure if possible as it emits more UV-B.
I think almost any mercury vapor lamp is going to be better than any LED at those wavelength.
Mercury vapor lamp efficiencies are in the tens of percents, with multi-watts outputs, while deep UV-B and UV-C are less than a percent efficient, and only emit milliwatts per LED.

Tdep - 27-6-2020 at 20:52

Quote: Originally posted by Tsjerk

I think I will order some of the cheap UV LEDs mentioned by Endo and hope they bleed enough into the <350 nm range. Maybe I can even ask the supplier if he has an emission spectrum.

An emission spectrum is always nice to have, but I wouldn't expect them to bleed much at all into the 350nm range. The UV leds tend to peak rapidly and then bleed into longer wavelengths a lot. So it probably has hardly any emission even at 360nm, but still a whole lot at 380nm. They tend to be named after the shortest wavelength they produce in any meaningful way.

Also, as it heats up, it'll red shift some more, so if you plan to run them a long time, it'll get less efficient with time I believe.

Not meaning to rain on your parade on anything, I wish the absorbance spectrum at least showed some of the peak in at 360nm, then I'd be heaps more keen for LEDs.

I've been looking at lamps on Amazon, and holy shit, what's with these prices? Is this some kind of chinese scam, or do they legitimately produce UV-C radiation?? Crazy. Are they regulated? Link to product in picture: https://www.amazon.com/ultravioleta-germicida-esterilizador-...

Heptylene - 28-6-2020 at 01:09

Tsjerk: The emission spectrum is guaranteed to be in the datasheet of the LED. Have a look on digikey for some UV LEDs, for instance this one.

Tdep: These lamp really produce UV-C and in large quantities too! I bought a big 20W bulb for $15 a while ago and it produces a weird smell of burnt skin when skin is exposed to it. It can excite calcium tungstate phosphor, which doesn't glow with UV-A. It's the real deal, and will damage your eyesight without protection.

Tsjerk - 28-6-2020 at 09:31

I found the perfect lamp! UV-B from Philips, peak at 310nm, 28 mm diameter so it would fit through a NS 29/32 neck. Only it costs around 40 euro...

These lamps are cheaper, but have their maximum intensity around 254nm. I could get one of these for around 10 euro.

What do you guys think? Would 254nm do the job? I don't know too much about light catalyzed reactions...

[Edited on 28-6-2020 by Tsjerk]

Tdep - 28-6-2020 at 22:37

254nm is perfect, that's what you want. You want the emission to overlap with the absorption of the compound, and that spectrum is what I posted earlier in the thread, from the Supp info of the Pilot scale synthesis.

The absorbance peaks at ~245nm, so the emission of 254nm from the lamp is perfect.

Heptylene: That's amazing. I was wondering if they were some kind of fake product that's meant to capitalise on Corona fears... just strap a normal lamp with some blue glass together or something... but it's amazing that they are real! I'm really keen to get one and try this out, this sounds like a lot of fun. I'll want a big acrylic box or something for safety... hm

Tsjerk - 29-6-2020 at 00:21

Quote: Originally posted by Tdep

254nm is perfect, that's what you want. You want the emission to overlap with the absorption of the compound, and that spectrum is what I posted earlier in the thread, from the Supp info of the Pilot scale synthesis.

The absorbance peaks at ~245nm, so the emission of 254nm from the lamp is perfect.

Then I don't get this statement in the Falkiner article...

Quote:

The long reaction time for this process can be attributed principally to the polychromatic nature of medium-pressure Hg vapor lamps, with only minor emissions in the critical region of 300 to 350 nm (see Supporting Information for UV spectrum of 6 under the conditions of the reaction). A better matched light source would be expected to significantly reduce irradiation time, and the concomitant waste of energy.

This is why I was looking for something between 300 and 350 nm.

Tdep - 29-6-2020 at 21:40

Oh that's because..... um...... hm I have no idea. Why did they use a medium pressure lamp? There's a small peak in the 300-350 range but its <1/10th the size of the main peak at 250nm.

Maybe you have to always target the first transition in a photochemical reaction? Ground/S0 -> S1 transition, not the S0 -> S2 or whatever? They must have used a medium pressure lamp for a reason, but I fail to see how the Supp Info figure shows that "300-350nm is a critical region"

Heptylene - 30-6-2020 at 11:08

I also fail to see why one peak should be favored and would love an explanation.

Tsjerk - 30-6-2020 at 12:23

In the article they state their lamp is inefficient for this process, and 300-350nm is the optimum... So I'm leaning towards the 310nm lamp...

Edit: screw it, I just bought the 310nm lamp. If it doesn't work I can always buy the 254nm one, those are only 10 euro and fit in the same socket.

[Edited on 30-6-2020 by Tsjerk]

Tsjerk - 1-7-2020 at 02:23

I just realized they use a pyrex reaction for the photocyclization, which absorps anything below 275 and most below 300nm anyway... not sure what to make of that. Would that mean lower wavelengths do work but are not considered as they are not transmitted by the pyrex anyway, coming to the conclusion 300-350nm is the optimum because that is the lowest that can pass. Or did they use the pyrex reactor because 300-350nm is the optimum anyway?

Edit: this is the spectrum of a medium pressure Hg lamp after pyrex filtering the light.

emission_Hg_medium_pressure_pyrex_filtered.png - 14kB

[Edited on 1-7-2020 by Tsjerk]

Tdep - 1-7-2020 at 04:24

What's also strange, is that the medium pressure lamp seems to originate from this reference, where they did the photo-reaction in... benzene?? A solvent that would completely absorb all <300 nm light in the first centimetre of the reaction vessel.. completely impenetrable.

So did they use a medium pressure lamp because they had to use benzene for the reaction, which forced them to use ~350nm light? Or did they chose benzene because the <350nm light doesn't matter? Or was the medium pressure lamp just what they had and everyone just did it too? Does everyone hate quartz glassware? Is this a conspiracy????

Tsjerk - 1-7-2020 at 04:57

Well, the 85:5 methanol/water solvent system used by Falkiner et al. also absorbs significant amounts of everything <300nm, just as the benzene does. So I don't think conspiracies theories are needed here as an explanation (bummer), and pyrex is just cheaper than quartz.

[Edited on 1-7-2020 by Tsjerk]

Tdep - 1-7-2020 at 06:01

That's a weird diagram, because I know methanol is transparent to UV down to about 215nm, I've used it as a solvent for UV-Vis. Methanol/water mix won't absorb the 250nm low pressure mercury emission peak at all. But yes, maybe the critical region really is just where the substance absorbs but normal glass transmits fine

Tsjerk - 1-7-2020 at 07:16

The scale on that last graph is logarithmic, so absorption would be around 10% max indeed.

Tsjerk - 1-7-2020 at 11:29

I contacted the corresponding author of the Falkiner article and he told me that 300-350nm is the target. They use Pyrex on purpose because shorter wavelengths would induce unwanted side reactions. He said the mercury lamp produces about ten percent at the correct wavelengths, so with about 200 watt they can transform 0.25 gram/minute.

[Edited on 1-7-2020 by Tsjerk]

Tdep - 1-7-2020 at 19:04

Alright, I guess that's the answer then, good choice on buying the UV-B bulb. Excited to see how you go with it!

Tsjerk - 9-8-2020 at 06:18

Update: I'm pretty sure I finally got compound 10 (the dibromdicyclopentadiene-1,8-dione ketal)... The bromination and dehydrobromination were straightforward, just put the reactants together and stir/reflux. After adding water a brownish precipitate forms which settle to the bottom after some time.

In a separatory funnel I got rid of most of the supernatant, but then trouble started...

The brown sludge is impossible to filter, the stuff is so fine it clogs any filter in minutes. I managed to pull of a large part of the water over many hours over a high vacuum on a large Buchner filter. I then evaporated much water under vacuum over a 50 degrees water bath. The sludge was then left to stand for a couple of weeks after which most of the water evaporated.

The last 100 ml of water was pulled of again on a Buchner filter. After an hour the brown (partly black) product was extracted with ethyl acetate by boiling and hot filtering the mixture. A little black crud was left, but probably only 5-10% of the amount of product.

The solution in ethyl acetate is now evaporating, as in the freezer only water froze out. The solution has an orange color, but I saw some nice white/colorless crystals in the brine I used pull out the water from the ethyl acetate before leaving it to evaporate.

JJay - 9-8-2020 at 13:57

I've been watching this very cool project with some interest. I'm tempted to buy some adipic acid and follow along.

Tsjerk - 9-8-2020 at 14:26

Cool! I can advice when making the ethylene diketal to run the Dean Stark as slow as you can. Ethylene glycol and toluene also form an azeotrope (110 degrees) which I'm sure screwed up my yield considerably by making me believe the reaction was done.

During the vacuum distillation of the ketal I'm pretty sure I also distilled some glycol as at the end a more viscous liquid came over. I wouldn't be surprised if my bromination/dehydrobromination would have been a lot less black if my ketal would have been cleaner.

I guesstimate I have about 30 gr of compound 10 now as really nice white crystals. They crystallize from the orange liquid, and there will probably be an orange crust when totally dry, but I won't try to clean that up as in the article they talk about a beige powder used without recrystallization.

Edit: I started with 40 gr of ketal.

[Edited on 9-8-2020 by Tsjerk]

Tdep - 9-8-2020 at 17:54

So I'm officially very invested in this project, here's my into video outlying the plan: https://youtu.be/ney-qTU3m4I
and my first attempt at making the ketal: https://youtu.be/sBA_UV15k0c

It'll be nothing new to you Tsjerk, or anyone following this thread closely. Looks like i've made a lot of mistakes too... aldol condensation... ethylene glycol-toluene azeotrope (I hadn't thought of that, that explains what I was seeing in the dean Stark I think!).... but isn't everything so much easier with hindsight! Hopefully the next attempt will be much more refined.

Tsjerk - 27-12-2020 at 07:46

Very nice video on YouTube Tdep! Good idea to not do the bromination and dehydrobromination in one pot. Your work-up looks a lot easier than my filtration did. Hopefully this won't happen after you do the dehydrobromination...

I do think the use of less than an equimolar amount of dioxane is what caused the off-gassing, not the use of DCM as a solvent. Bromine doesn't dissolve in DCM very well, while it forms a complex with dioxane. I think the combination of free bromine and HBr causes the gas to come off. I didn't notice any gas coming off.

Edit: I once dried sieves in a microwave/oven, thinking I turned on the oven part... Turned out I turned on the microwave part for 20 minutes which completely fused the sieves, the beaker and the glass plate in the microwave/oven combination. Apparently sieves happily absorb microwaves.

I was noticed by the smoke alarm things weren't going as I intended as the rubber lining below the glass plate was being turned to tar.

[Edited on 27-12-2020 by Tsjerk]

Tsjerk - 27-12-2020 at 07:55

Btw, I performed the de-ketalization. Straight forward process, I performed the reaction on a day the temperature in my lab was about 25 degrees during the day and didn't drop much at night. Good to know is that the reaction starts off quite exothermic, so cooling was necessary at the start.

Help with NMR spectra

Tdep - 7-3-2021 at 04:05

Hey everyone!

So I'm still working on this project, you might have seen my videos on Youtube already but I'll link the series: Cubane Youtube playlist
It's been a lot of fun so far, and I'm up to the deprotection/de-ketalization stage. Rather than removing both ketal groups in one step as per the reference at the start of this thread, I'm intending to deprotect only one side of the molecule. See the reaction scheme. This apparently makes the UV photochem step cleaner, which is looking like the biggest hurdle of this reaction scheme, so any help there is important. This comes from "CUBANE DERIVATIVES FOR PROPELLANT APPLICATIONS" (1989).

So I tried the step, ended up with some powder that looked like my starting material after 9 hours of reflux. Recently however, I got the opportunity to send some samples off for NMR analysis! I sent the diketal starting material (from the end of Episode 7) and some material from the deprotection reaction pot (End of Episode 8)
It's been a few years since I had to do NMR, and even then I wasn't very good at it.... so sorry for the multiple pictures, but is the following interpretation correct?

"Using the 1H peak integration, the monoketal reaction mix is 15% diketal and 85% monoketal, with no traces of the fully deprotected product?"

The first 3 images are NMR predictions of the NMR spectra of the diketal, monoketal and fully deprotected molecules. Thanks!

Tdep - 7-3-2021 at 04:09

Here's the reference that's been a really big help for me. Lots of tips in this about the synthesis of cubane, many of which are in the falkiner2013 paper, but there's a lot more detail. Such as them reporting different solvents they dried which didn't work, and ones that worked okay but not that well, not just reporting it being done in one solvent and not expanding on it. Cool stuff

Attachment: CUBANE DERIVATIVES FOR PROPELLANT APPLICATIONS 1989.pdf (2.7MB)
This file has been downloaded 352 times

Metacelsus - 7-3-2021 at 04:25

Yeah, so going by intergration it looks like the ratio of diketal : monoketal is roughly 0.15 : 1.03
Which is a molar percentage of 13% diketal. The mass percentage will be a bit higher because of the higher molecular weight.

I wouldn't be sure that there's "no trace" of the fully deprotected product; there are a few very small peaks that could be it. You should try to find a literature spectrum for the fully deprotected product so you can compare.

edit: also, as you can see, "ChemNMR estimation" is terrible for stuff like this. It's possible to make better estimations using QM software like Gaussian, but this can be a bit tricky.

edit edit: also I'm a huge fan of your channel and I'm very impressed by this project!

[Edited on 2021-3-7 by Metacelsus]

Tdep - 7-3-2021 at 05:43

Thanks mate!

Quote: Originally posted by Metacelsus

I wouldn't be sure that there's "no trace" of the fully deprotected product; there are a few very small peaks that could be it.

Because I'm not super familiar, what sort of statement could I make about the purity then? Just in a sort of handwave-y way. Less than 5% of other products? Or it's impossible to say?

Quote: Originally posted by Metacelsus

You should try to find a literature spectrum for the fully deprotected product so you can compare.

Yeah I haven't found one for the fully deprotected one. There's some reference stuff from the 1989 paper for the diketal and monoketal, although it's a scanned copy so the quality is pretty awful. But there's nothing in there that doesn't match to my spectrum

Metacelsus - 7-3-2021 at 08:29

Yeah it's certainly less than 5% fully deprotected product. It looks to me like less than 1%.

Assuming your product is free of inorganic salts, it's almost entirely monoketal and diketal. There is also a bit of water too, but sometimes that's from the NMR solvent not being dry and not from your product, and I can't tell in this case. I also think I see some DCM around 5.3 ppm.

Tdep - 9-3-2021 at 17:36

Thanks a lot. Yeah the reaction was water and DCM, so no surprise that they show up, good spot with the DCM! But very cool. I'm amazed the products have come out so clean honestly. I've sort of been fumbling along and for the products to be 99%, even with all the possible isomers and impurities is sensational to see!