Methyl- Ether

[Fertile]

lah

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ibb.co

I have run into a situation where I require a methyl ether BUT the reaction falls outside the scope of the Williamson Ether Synthesis. In fact, the route I am considering will actually perform 2 steps in parallel. In fact, it appears so good that their is almost BOUND to be some kind of problem... but I ask anyway.

 

[ions]

I checked on dimethylether. It's a gas at room temperature. Which is why it's not used as a solvent. But it's an aerosol propellant.

 

[Rectify]

LAH is great for reducing betaphenylnitrostyrenes to amphetamines and all sorts of other reactions, BUT is notoriously moisture sensitive and difficult, though not impossible, to use.

 

[Fertile]

I checked on dimethylether. It's a gas at room temperature. Which is why it's not used as a solvent. But it's an aerosol propellant.

I did not suggest that the product was dimethyl ether - I said the compound I sought contained a methyl ether - I even provided an example and a possible alternative route.

 

[ions]

K, forget I said anything.

 

[Fertile]

BTW you don't even have to use red-al. A metal reduction will work and NaBH4 is easy to handle.

Back in 2001, Dutch law controlled 2CB & 2CC but because of it's rarity and use in functional-MRI, 2CI was not controlled.... so we made a lot of it. We even paid all of the tax owing. I THINK it was being sold as 2CB which really annoyed us but I guess we were hardly acting in a moral manner. One of our friends just bought the powder (of the hydrochloride sale) and that wasit.

It took 2 days because it takes SO LONG to quench the red-al..

BTW for all of you venturers into the grey light, NONE the nitrostyrenes and nitropropenes are controlled under the UNODC, UK law or any EU law I have looked at. I guess they presume that controlling nitroethane would be enough. That is why, if you know who to ask, you can buy 2,5-dimethoxy nitrostyrenes & 2,5-dimethoxynitropropene in bulk. The same place will sell you 100Kg of the unsubstituted nitropropene. Last time I talked to the guy, he mentioned one group of guys who were buying 250Kg a week.

Now I'm guessing, but I do not believe that anyone working at the 250Kg scale are going to be using complex metal hydrides to produce their product. The cheapest is Fe + HCl (to nitroalkana) & Zn + NH4Cl which you can just leave running with an overhead stirrer going....

Or you can go for Raney-Nickel.

I'm only telling you this now because I last talked to him a decade ago and since HE never mentioned a product.... it would be hard to move.

FYI he used (substituted) benzealdehyde + nitroethane in a cold basic media (or as he put it - 'just dump in 55 gallon drum and use stirrer'. He's an unusual guy and he doesn't appear in many places you might expect.... so I suspect he was one of the funnies.

BTW of course you can produce the nitroalcohol. Reduce that and you are only KOCN away from 4MAR.

 

[4meSM]

I don’t know if it’s because I’m tired but I’m not sure what your question is. Seems like you want to convert an alcohol into a methyl ether without using something like a methyl halide (via SN2 reaction)?

 

[Fertile]

Well if you look at the diagram, you will see it's a tertiary ether and so MeI nor (CH3)2SO4 do not work.

Believe me - I wouldn't be asking if any of the usual routes worked. Even a superbase will not make it work.

But formic anhydride is commercially available and LiAl4H will readily reduce esters to ethers.... but I just haven't seen it. I'm presuming it's because people generally use one of the 2 general routes. This is a very unusual circumstance.
And without going into details, the LiAlH4 will also allow a second reaction to be carried out in parallel. That's a VERY handy detail. Since the product needs to be >98% pure, it's going to save time and money on the workup. While preparative chromatogrsaphy is excellent, it's bound to take some yield and it can be a bit of a pain.

For other steps I've found an excellent Russian patient. It's yield is actually about 0.5% lower than the previous routes, but the purity is 99.15% so that's a big saving on workup.

 

[4meSM]

Well if you look at the diagram, you will see it's a tertiary ether and so MeI nor (CH3)2SO4 do not work.

Believe me - I wouldn't be asking if any of the usual routes worked. Even a superbase will not make it work.

But formic anhydride is commercially available and LiAl4H will readily reduce esters to ethers.... but I just haven't seen it. I'm presuming it's because people generally use one of the 2 general routes. This is a very unusual circumstance.
And without going into details, the LiAlH4 will also allow a second reaction to be carried out in parallel. That's a VERY handy detail. Since the product needs to be >98% pure, it's going to save time and money on the workup. While preparative chromatogrsaphy is excellent, it's bound to take some yield and it can be a bit of a pain.

For other steps I've found an excellent Russian patient. It's yield is actually about 0.5% lower than the previous routes, but the purity is 99.15% so that's a big saving on workup.

Oh right, I missed the fact that you wanted to make a tertiary ether.

Well I’m not sure about the reduction with LiAlH4 here, I’d be concerned with ending up with the starting alcohol. You think this can be avoided in this case?

 

[Fertile]

The Development of a General and Tunable Method for Ester to Ether Reduction

The development of methods to easily synthesize chemical structures is of great importance in the field of organic chemistry. Ether, a well-known functional group, may appear to be simple to synthesize by known methods. Unfortunately, this is not always the case, especially in considering the...

aquila.usm.edu

Catalytic Reductive Alcohol Etherifications with Carbonyl‐Based Compounds or CO2 and Related Transformations for the Synthesis of Ether Derivatives

Ether derivatives have myriad applications in several areas of chemical industry and academia. Hence, the development of more effective and sustainable protocols for their production is highly desired. Among the different methodologies reported for ether ...

www.ncbi.nlm.nih.gov

Synthesis of ethers from esters via Fe-catalyzed hydrosilylation

Triiron dodecacarbonyl allows for the selective reduction of esters into the corresponding ethers. This protocol has a wide substrate scope. In addition, cholesteryl pelarogonate has been reduced under the reaction conditions with an excellent yield.

pubs.rsc.org

It seems like science is just catching up with me. The use of PhSiH3 is certainly novel but several pieces refer to it.
It seems that forming the tertiary ester is tricky enough. It's the fact that I seek to form a tertiary formate ester and reduce that to the methyl ether that has some unusual electronic characteristics. Because, as I'm sure you will have been reminded, formic acid is ALSO an aldehyde. Being so small, it DOES mean that steric hinderance will not prevent the proton transfer and so I suspect I'm going to have to pursue.

Hydrosilation.