Sevoflurane

[ArnoldFan]

Hi all. I haven't found anything about this argument on the forum. Sevoflurane, (2,2,2-trifluoro-1-[trifluoromethyl]ethyl fluoromethyl ether), is a sweet-smelling, non-flammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. It is a liquid at room temperature with a boiling point of 58.6 °C at 101.325 kPa. Does anyone have any idea about how to synthetize this substance?

[megalomania]

Well, google is a nice place to start. Some patents on its synthesis come up as the top resulys if you search for (2,2,2-trifluoro-1-[trifluoromethyl]ethyl fluoromethyl ether).

United States Patent 6469219: An improved process for preparing fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether(sevoflurane) by reacting 1,1,1,3,3,3-hexafluoro-2-propanol with formaldahyde and hydrogen fluoride either A) under distillation conditions or B) in the presence of or with the subsequent addition of a solvent capable of selectively extracting sevoflurane.

I would have thought trifluoroethanol would be a good place to start, but hexafluoroisopropanol is recommended. Obtaining hexafluoroisopropanol will be the tricky part. Something like this you might want to just buy and save yourself the hassle, but I know full well how those words ring hollow to all but well funded chemists.

You can make hexafluoroisopropanol by hydrogenating hexafluoroacetone, and might I tentatively suggest a catalytic transfer hydrogenation using a microwave instead of the traditional high pressure hydrogen gas method. Hexafluoroacetone is so electronegative that it must tear those hydrogens to shreds to steal the electrons :) so I imagine the reaction proceeds under mild conditions.

There is actually a synthesis for hexafluoroacetone in Organic Synthesis: http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV7P0251

As for the hexafluoropropene, or hexafluoropropylene if you prefer has several patents concerning its synthesis. Check out US Patents 5068472; 5057634; and 5043491. These use hexachloropropylene as the starting material. That's all the farther I am going to track this beast.

Ahh, I can't resist. A mixture of chloroform and trichloroethylene in the presence of aluminum chloride, heated to 20 C, should form heptachloropropane, which when treated with alcoholic potassium hydroxide at room temp will form hexachloropropylene.

[ArnoldFan]

Thanks mega... I'll look for those patents. Have you ever thought about producing a little quantity of this substance? I think it could be regarded as the safest compound with which one can knock-out someone without fear of killing him...:D

P.S. I think that for this synth a well equipped laboratory is required... Am I right? Unless I'd try your last suggestion...

"A mixture of chloroform and trichloroethylene in the presence of aluminum chloride, heated to 20 C, should form heptachloropropane, which when treated with alcoholic potassium hydroxide at room temp will form hexachloropropylene."

:D

[megalomania]

You like that eh? I didn't know yesterday what reference that information came from, I just found it in a pdf. I got curious today because I like those old practical syntheses, vague as they are on specific details of time, yield, and purity, but it's not like they had an NMR to assist them, or column chromatography, or an accurate scale...

I found the original source today after a little legwork. It is from J. Chem. Soc., Abstr., 1913, 104, i1037 - i1122 which is available for free on the rsc.org website here:
http://www.rsc.org/publishing/journals/article.asp?doi=CA9130401037

Indeed it looks like all of the Journal of the Chemical Society, Abstracts issues are free:
http://www.rsc.org/Publishing/Journals/ca/Article.asp?Type=CurrentIssue

It is always thrilling to get a free journal, even what should be public domain material. The reason I tracked down the source is because I was hoping there would be more free articles like this. I have a particularly hard time getting journals from the Royal Society of Chemistry for some reason.

[FUTI]

I noticed also that some journals previously unavailable to me suddenly go public. UK journals were notorious in its pricing for an article that I didn't want to call them as I had the insane fear that Hello would cost 29,99GBP.

But Mega your link redirector doesn't work. It doesn't matter anyway as I have been able to find the way through RCS site based on your info. Thanks for spreading the word Mega.

I see that they changed also the site. I find it funny that they on previous site version had search that emphasized the long line of science in UK as it asked you to first select the year of the issue you want to see from a drop-down menu that started by default with for example 1732 and you had to scroll down to 200x you wanted to see current research.

This info is pure gold for me as it is close to some of my ideas...if I only could find a good neat way to convert those chlorine to fluorine that would be excellent.

[megalomania]

I apologize, link redirecting does not work for url's that have special symbols like question marks because of the possibility of abuse, but my status as admin also doesn't have the software yelling at me for errors like that...

The actual link is http://www.rsc.org/publishing/journals/article.asp and add this after the .asp ?doi=CA9130401037