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Author: Subject: Possible OTC, 'safe' methylating agents
itsafineday
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[*] posted on 14-2-2019 at 15:23


Doh! I am such and eeeeediot :) and good at wasting money in this hobby.
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[*] posted on 17-2-2019 at 21:55


I wonder if it would be possible to make dimethyl carbonate by dissolving magnesium in methanol, bubbling dry CO2 through it to make magnesium methyl carbonate, distilling to dryness, then cracking it with heat to dimethyl carbonate and magnesium carbonate.
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[*] posted on 21-2-2019 at 16:43


You know, I keep trying to think of a problem with that and I can't. It does seem like it would work better if you could obtain metallic calcium, just based on analogy to similar reactions, but Mg should be fine I guess.



[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 26-2-2019 at 11:13


I have a patent teaching how to produce (DMC) Dimeyhyl Carbonate without the use of Phosgen. They use just Dimethyl oxalate (easy to produce. See here at Doug's Lab You Tube vídeo: https://www.youtube.com/watch?v=imtSH3OAdKE) and Sodium Methoxide at 100ºC.

The Patent is attached:

Attachment: Dimethyl carbonate from dimethyl oxalate and sodium methoxide.pdf (269kB)
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[*] posted on 27-2-2019 at 12:08


That’s a very interesting post by Chemi Pharma on preparation of dimethyl carbonate.

Is an autoclave necessary to do this do you think, or could the DMC be distilled off as it is formed by heating up reactants in standard rbf? (Obviously CO would have to be vented or scrubbed).
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[*] posted on 27-2-2019 at 20:12


The Patent say that the temperature of the batch needs to stay between 50-150ºC. cause this I think an autoclave use is not mandatory. I'd rather heat the batch with a water bath (90-100ºC) at reflux. DMC has a boiling point of 90ºC, then it could be refluxed during the 1,25 hours needed, while CO escapes on the top of the column.
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[*] posted on 8-4-2019 at 17:16


I may have found a very OTC source of dimethyl carbonate: Savogran Heavy Duty SuperStrip (non-DCM). The MSDS shows the following, by weight:

45-50% dimethyl carbonate (MP 3C, BP 90C)
30-35% 1,3-dioxolane (MP -95C, BP 75C)
15-20% methanol (MP -98C, BP 65C)

It seems to sell for about $16/quart at the big orange hardware store.
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wakatutu
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[*] posted on 8-4-2019 at 22:54


https://images.homedepot-static.com/catalog/pdfImages/da/da1...
savogran super strip (dcm-free)


https://images.homedepot-static.com/catalog/pdfImages/b2/b29...
savogran super strip dcm-free (CA)

The second one has methyl acetate, and its warning section says "Inhalation of Vapor May Cause Death" whereas the warning on the first one simply says inhalation causes dizziness and stuff like that.

I'm not 100% whether it's canada or california that has the methyl acetate version.

Great find, monolithic!
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clearly_not_atara
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[*] posted on 17-4-2019 at 16:07


So I had a sudden realization.

Orthoesters are produced by reacting a nitrile with an alcohol in the presence of acid:

MeCN + 3 MeOH + H+ >> NH4+ + Et(OMe)3

Alkyl sulfonates are produced by reacting a sulfonic acid with an orthoester:

Et(OMe)3 + TsOH >> TsOMe + AcOMe + MeOH

Soooo... why can't these reactions happen in the same flask?

3 MeOH + 2 TsOH + MeCN >> TsOMe + NH4OTs + AcOMe + MeOH

The obvious objection is that ammonia will react with methyl tosylate. But with excess acid, there should be no ammonia present, only ammonium, which is not nucleophilic. Correspondingly, the rxn mixture cannot be neutralized; MeOTs must be distilled off directly. That should be fine, since MeOTs should be much more volatile than TsOH or ammonium tosylate but much less volatile than methanol or methyl acetate; i.e., no "azeotropes".




[Edited on 04-20-1969 by clearly_not_atara]
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AvBaeyer
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[*] posted on 17-4-2019 at 16:57


Where is the reference to converting nitriles to orthoesters? Without that the above is just pointless bs.

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clearly_not_atara
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[*] posted on 17-4-2019 at 22:09


It’s the Pinner reaction. But apparently HCl is required. However, the basic idea still has merit. If you perform the classic Pinner rxn to get the methyl acetimidate, you can use the anion metathesis here to convert it to the tosylate:

https://arca.unive.it/retrieve/handle/10278/38060/28512/c3gc...

Then adding methanol, heat, more TsOH should work. I guess this ultimately just replaces distilling the orthoester with solvent extraction of the alkyl imidate. But hey, it’s easier...

(Don’t use excess methanol in the imidate formation, it forms emulsions.)




[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 18-4-2019 at 18:04


This sort of reminds me of the synthesis of acetamidine starting from acetonitrile. The intermediate alkyl imitate reacts with excess ammonia form the imidine.

http://www.orgsyn.org/demo.aspx?prep=CV1P0005




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[*] posted on 20-4-2019 at 21:00


Quote: Originally posted by wakatutu  
https://images.homedepot-static.com/catalog/pdfImages/da/da1...
savogran super strip (dcm-free)


https://images.homedepot-static.com/catalog/pdfImages/b2/b29...
savogran super strip dcm-free (CA)

The second one has methyl acetate, and its warning section says "Inhalation of Vapor May Cause Death" whereas the warning on the first one simply says inhalation causes dizziness and stuff like that.

I'm not 100% whether it's canada or california that has the methyl acetate version.

Great find, monolithic!


I didn't realize that, but yes it appears the California compliant models do not contain DMC and instead contain methyl acetate. You can see the model numbers here: https://savogran.com/removers.html :)
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[*] posted on 10-2-2020 at 17:50


Slightly off topic, slightly on topic: any thoughts on whether dimethyl carbonate could be used to make diglyme from diethylene glycol? Apparently dimethyl carbonate can work under mild conditions, see http://www.sciencemadness.org/talk/viewthread.php?tid=22370 I wonder how it would fair with a slight excess of K2CO3 in a solventless environment of diethylene glycol. Reflux at 100-125 C and then fractionally distill the diglyme (BP 162 C) from unreacted diethylene glycol (BP 245 C) and 2-(2-Methoxyethoxy)ethanol (BP 194 C)?
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[*] posted on 10-2-2020 at 18:18


I think it could probably work, diglyme's protons are both relatively acidic by alcohol standards if methoxyethanol is any indication, and alkoxides are pretty strong nucleophiles. Carbonate is already known to make methoxide effectively.

That's a pretty clever idea ngl




[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 10-2-2020 at 18:57


Quote: Originally posted by clearly_not_atara  
I think it could probably work, diglyme's protons are both relatively acidic by alcohol standards if methoxyethanol is any indication, and alkoxides are pretty strong nucleophiles. Carbonate is already known to make methoxide effectively.

That's a pretty clever idea ngl


Diethylene glycol is the major constituent (>99%) of some sterno style fuels like https://blazeproducts.com/wp-content/themes/blaze-products/a... or https://www.webstaurantstore.com/choice-6-hour-wick-chafing-... . Might have to try the reaction. :)

[Edited on 2-11-2020 by monolithic]
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wakatutu
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[*] posted on 14-2-2020 at 10:28


I'd like to add to this discussion that I've put in the money and effort to buy a couple gallons of the new paint stripper, vacuum distill the dimethyl carbonate from it, and then run the vac distillation a couple more times to remove DMSO and a nasty smelling amine compound.

Overall I got a pretty decent amount of dimethyl carbonate from this.

I ran a couple experiments to determine the usefulness of such a compound. I am not impressed! Some literature claims that methylation won't take place at 900C and that you have to get the mixture up to around 130 degrees, and some literature claims good yields with some compounds at 90 degrees using TBAB and K2CO3.

I tried 8 hours at 90 degrees with huge excess of DMC, good amount (about .5 molar relative to substrate) of TBAB, and 3.3x molar amount of potassium carbonate. The result: I was able to get about 3-5% yield of the methylated compound, but mostly just got my initial compound back.

Probably conditions could be altered and more experiments should be done, but I was not impressed with all the effort and expense leading to such a crappy yield. The substance was protocatechualdehyde. The 3% yield was the fully methylated veratraldehyde. In the recovered starting material, there was no vanillin or isovanillin. I thought it was weird that the only material that was methylated at all was methylated twice.
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[*] posted on 14-2-2020 at 13:50


Quote: Originally posted by wakatutu  
I'd like to add to this discussion that I've put in the money and effort to buy a couple gallons of the new paint stripper, vacuum distill the dimethyl carbonate from it, and then run the vac distillation a couple more times to remove DMSO and a nasty smelling amine compound.

Overall I got a pretty decent amount of dimethyl carbonate from this.

I ran a couple experiments to determine the usefulness of such a compound. I am not impressed! Some literature claims that methylation won't take place at 900C and that you have to get the mixture up to around 130 degrees, and some literature claims good yields with some compounds at 90 degrees using TBAB and K2CO3.

I tried 8 hours at 90 degrees with huge excess of DMC, good amount (about .5 molar relative to substrate) of TBAB, and 3.3x molar amount of potassium carbonate. The result: I was able to get about 3-5% yield of the methylated compound, but mostly just got my initial compound back.

Probably conditions could be altered and more experiments should be done, but I was not impressed with all the effort and expense leading to such a crappy yield. The substance was protocatechualdehyde. The 3% yield was the fully methylated veratraldehyde. In the recovered starting material, there was no vanillin or isovanillin. I thought it was weird that the only material that was methylated at all was methylated twice.


Your temperature is too low and your reaction time is too short. You didn't mention what solvent you used. The solvent has to be a high boiling polar, aprotic solvent otherwise your DMC will boil off. See the below procedure -- DMF is proven to work. I imagine DMSO, NMP, and propylene carbonate would also work. An inert atmosphere may be required, or at least a protected atmosphere (flushed and sealed with an oil bubbler.) I've also heard that attempting o-methylation on two hydroxy groups is more difficult than a single hydroxy group, regardless of reaction time and excess of methylation agent. Once you improve temperature, solvent, reaction time, etc. you may consider recycling your unreacting starting material (separated from reaction mixture with dilute base wash) and give it another run.

Some supplemental reading on gentler methylation agents which might give some helpful information about reaction conditions:

US4453017 (TMP but discussion on solvent is relevant)
US6326501B1 (pay attention to the section on temperatures)
https://www.sciencemadness.org/whisper/viewthread.php?tid=22...

Quote:
20.15 g of syringaldehyde, 100 ml of dry DMF (technical grade, fractionally distilled once under vacuum and stored over 3 A molecular sieves), 11.71 g of anhydrous K2CO3 (anhydrous photography grade, ground by mortar and pestle and dried for 1 hour at 300 C), 6.10 g of TBAB, and 22 ml of dimethyl carbonate (technical grade, fractionally distilled once and stored over 3 A molecular sieves) were added to a 500 ml 3-neck round bottom flask equipped with a condenser, pressure equalizing addition funnel, thermometer, and magnetic stirring. The addition funnel was charged with an additional 22 ml of DMC. The apparatus was sealed from atmosphere by leading a hose adapter on the head of the condenser to a small beaker filled with mineral oil. A latex balloon septum was fitted to the head of the addition funnel and the apparatus was gently purged for 10 seconds with a nitrogen wine preserver, and then the septum was very quickly replaced with a stopper. Stirring was initiated and the reaction mixture was brought to a gentle reflux between 120 – 130 C. The DMC within the addition funnel was added in several small portions in the first 3 hours of reflux. From the initiation of reflux, the reaction was allowed to proceed for approximately 20 hours. A light brown/caramel reaction mixture was observed. The reaction mixture, while still hot, was poured into 200 ml of room temperature water. The solution turned a clear orange-red and no precipitation was observed. The mixture was allowed to cool to room temperature, accelerated by the use of a refrigerator. A milky precipitate was then observed, and so another 600 ml of water was added, the total volume now being approximately 1000 ml. Precipitation was observed immediately and the beaker was placed in a freezer for 1 hour. Large amounts of crystals were observed, which were vacuum filtered for approximately 5 minutes. The light beige colored filtrate was discarded and the delicate mass of crystals, off-white and slightly beige in appearance, were dissolved in 100 ml of ethyl acetate and transferred to a separatory funnel. The crude product was then washed with 2 x 50 ml of 5% w/w NaOH, 2 x 50 ml water, and 2 x 50 ml brine. At the conclusion of the washings, approximately 80 ml of a yellow liquid was collected, dried over MgSO4, and evaporated under gentle vacuum to yield 15.39 g (71% yield) of a crude 3,4,5-trimethoxybenzaldehyde as a light beige solid.

24.20 g syringaldehyde, 120 ml DMF, 14.02 g K2CO3, 7.30 g TBAB, and 27 ml DMC was combined in the previously described apparatus. The addition funnel was charged with an additional 27 ml of DMC. The apparatus was protected from atmosphere and purged as before. The mixture was heated, with stirring, to a gentle reflux between 120 – 130 C. Additional DMC was added at the rate of one drop every 3-6 seconds once reflux was reached. Total reflux time was 14 hours. The reaction mixture, still hot, was quenched with 200 ml room temperature water. The mixture was allowed to cool to room temperature with aid of a refrigerator. Upon cooling, milky precipitate was noted. The mixture was then diluted with more water to the 1000 ml line, and the precipitate appeared more defined and crystalline, as in the previous trial. The mixture was placed into a freezer for 1 hour and the large volume of crystals was vacuum filtered for 5 minutes. The solids were dissolved in 100 ml of ethyl acetate and the workup was performed as before: 2 x 50 ml 5% w/w NaOH, 2 x 50 ml water, 2 x 50 ml brine. The yellow liquid was dried over MgSO4 and evaporated under gentle vacuum to yield 17.74 g (68% yield) of a crude 3,4,5-trimethoxybenzaldehyde as a light beige solid.

The outputs of both trials were combined, total mass of 33.09 g after accounting for some minor losses, and a short path vacuum distillation apparatus was set up. Because the product is a solid well above room temperature (lit. MP 73 C), it was a motherfucker to vacuum distill. The reaction flask and vertical section of the short path apparatus, except for small viewing ports, were wrapped in aluminum foil and the flask was heated over an oil bath with maximum stirring. The distillate rose up the vertical section of the still head but would repeatedly stall, and so the apparatus was brought up to temperature with a 750-watt heat gun. (Use metal keck clips so they don't melt.) The 3,4,5-trimethoxybenzaldehyde distilled at approximately 140 C, although it was hard to pinpoint an exact temperature due to the output of the heat gun. A small amount of dark brown/orange liquid which did not solidify at room temperature was left behind in the reaction flask. Total mass of recovered product was 29.75 g (90% recovery) as a snow-white amorphous mass which was stored in an air-tight container in a freezer, to protect against any potential degradation to 3,4,5-trimethoxybenzoic acid.



[Edited on 14-2-2020 by horribilis]
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[*] posted on 14-2-2020 at 15:05


Quote: Originally posted by horribilis  
Quote: Originally posted by wakatutu  
I'd like to add to this discussion that I've put in the money and effort to buy a couple gallons of the new paint stripper, vacuum distill the dimethyl carbonate from it, and then run the vac distillation a couple more times to remove DMSO and a nasty smelling amine compound.

Overall I got a pretty decent amount of dimethyl carbonate from this.

I ran a couple experiments to determine the usefulness of such a compound. I am not impressed! Some literature claims that methylation won't take place at 900C and that you have to get the mixture up to around 130 degrees, and some literature claims good yields with some compounds at 90 degrees using TBAB and K2CO3.

I tried 8 hours at 90 degrees with huge excess of DMC, good amount (about .5 molar relative to substrate) of TBAB, and 3.3x molar amount of potassium carbonate. The result: I was able to get about 3-5% yield of the methylated compound, but mostly just got my initial compound back.

Probably conditions could be altered and more experiments should be done, but I was not impressed with all the effort and expense leading to such a crappy yield. The substance was protocatechualdehyde. The 3% yield was the fully methylated veratraldehyde. In the recovered starting material, there was no vanillin or isovanillin. I thought it was weird that the only material that was methylated at all was methylated twice.


Your temperature is too low and your reaction time is too short. You didn't mention what solvent you used. The solvent has to be a high boiling polar, aprotic solvent otherwise your DMC will boil off. See the below procedure -- DMF is proven to work. I imagine DMSO, NMP, and propylene carbonate would also work. An inert atmosphere may be required, or at least a protected atmosphere (flushed and sealed with an oil bubbler.) I've also heard that attempting o-methylation on two hydroxy groups is more difficult than a single hydroxy group, regardless of reaction time and excess of methylation agent. Once you improve temperature, solvent, reaction time, etc. you may consider recycling your unreacting starting material (separated from reaction mixture with dilute base wash) and give it another run.

Some supplemental reading on gentler methylation agents which might give some helpful information about reaction conditions:

US4453017 (TMP but discussion on solvent is relevant)
US6326501B1 (pay attention to the section on temperatures)
https://www.sciencemadness.org/whisper/viewthread.php?tid=22...


[Edited on 14-2-2020 by horribilis]


Any thoughts on dimethyl carbonate working in a solventless environment (diethylene glycol)?
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[*] posted on 15-2-2020 at 07:59


wakatutu: Do you mean that you started with 3,4-dihydroxybenzaldehyde? It's helpful to explain the precise conditions used.

Overall, solventless DMC is not very good. DMC itself is not very polar; its dipole moment is lower than ethyl acetate. For making diglyme it shouldn't be a problem because the alkoxide is a really strong nucleophile, but you do run a risk of transesterification instead of methylation. Ideally it is always used with a highly polar solvent which will promote SN2 reactions. DMSO or PC8 would seem ideal because their dipole moments are very high.

With DMC and a catechol I wonder if you might accidentally produce the cyclic carbonate. That would be a problem.

For high-yielding methylation of difficult substrates, transesterifying DMC with TsOH gives TsOMe, which methylates many otherwise weak nucleophiles.

[Edited on 15-2-2020 by clearly_not_atara]




[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 15-2-2020 at 12:35


***Never mind, misunderstood!

[Edited on 2-15-2020 by monolithic]
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[*] posted on 15-2-2020 at 15:10


I used 3,4-dihydroxybenzaldehyde and only used DMC as its own reaction solvent. I was working with information from a paper published around 2001 for the optimization of reaction conditions for methylating vanillin and eugenol. I have also tried the transesterification with DMC and p-toluenesulfonic acid, which resulted in a very poor yield of methyl tosylate. However, I have had some pretty hefty difficulties arriving at p-TsOH of decent purity, so I haven't put a lot of time into that route.
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[*] posted on 16-2-2020 at 07:55


Yeah, TsOH synthesis is conceptually simple but technically difficult. TsOH must be in excess for the reaction to proceed, as noted on the last page.

It would be nice to have a simpler route to sulfonic acids, but that doesn't seem to exist.




[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 16-2-2020 at 19:52


I suggest that dimethyl oxalate be explored as an easy to obtain methylation reagent in the home lab setting. It has been shown to alkylate phenols among other functionalities. It operates by a novel mechanism not available to dimethyl carbonate (DMC) in a manner which precludes the transesterification problem associated with DMC. Furthermore, dimethyl oxalate is easily accesssible.

I have posted some references for relating to dimethyl oxalate.

Also there is a review on DMC chemistry.

I apologize if I am going over plowed ground in this series of posts.

AvB

Attachment: DImethyl Oxalate OrgSyn cv2p0414.pdf (126kB)
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Attachment: Alkylation with Oxalic Esters. Scope and Mechanism..pdf (684kB)
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Attachment: 1799-Anomalous-ether-formation-in-attempts-to-transesterify-oxalate-esters-with-phenoxides807f.pdf (293kB)
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Attachment: The Chemistry of Dimethyl Carbonate Accts C Res 35_706_2002.pdf (229kB)
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[*] posted on 16-2-2020 at 21:35


Earlier byok3y tried the Orgsyn prep of Me2C2O4 using oxalic acid dihydrate, but it failed. It seems like you need to use anhydrous oxalic acid. So what is missing here is a way to prepare anhydrous oxalic acid.

As for the properties of Me2C2O4, I really don't know, but for salicylaldehyde and other resistant phenols I'd use a 2x molar excess.




[Edited on 04-20-1969 by clearly_not_atara]
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