I'm planning in turn to try and synthesise lidocaine (apparently several people, Nile Red included, have had the same idea but I didn't see any report
showing up as yet). I think the easiest pathway (for me) is:
For 1a) I have found an article (Berg L. & AN-I Y. (1987): Separation of m-xylene from o-xylene by extractive distillation. Chemical Engineering
Communications, 54:1-6, 149-159, DOI: 10.1080/00986448708911904) which lists more than 100 possible extractive mixtures and their relative efficiency
at increasing the volatility of m-xylene w/r to o-xylene. The best (practical) combination I found is DMSO + methylsalicylate which increases the
volatililty from 1.15 (needing 75 plates to achieve 95% purity) to 1.39 (only 24 plates required, which would reasonably be achieved with my Vigreux
column). So I'll have to make wintergreen oil from aspirin as a preliminary step (I have DMSO). p-xylene can be extracted by fractional
crystallisation.
I haven't been much further into theoretical research right now, so I'm wondering if anyone got past this first step and proceeded with nitration. I
don't think there are many hurdles except maybe separating 2,6 xylidine from the other isomers produced during nitration. Has anyone experience with
this? Is it best to reduce the nitrobenzene after reducing it, or the other way round? Any input would be appreciated!
EDIT: found a nice paper about m-xylene nitration. Unfortunately, it seems the ratio of the 2,6-dimethylnitrobenzene to the 2,4 isomer is only 1:4. Might have
to tinker with the reaction conditions to get it slightly higher. Apparently the 3,5 isomer does not show up.
[Edited on 27-7-2019 by Keras]Pumukli - 27-7-2019 at 11:30
What would you like to do with lidocaine? Do you intend to actually use it as lidocaine is used, as an anaesthetic?
If yes, then I can't help, sorry.
But if you only want to be proud of some white powder in a nice, little sample bottle and show it to your beloved ones then here's my suggestion:
Forget the messy and tedious work with xylene isomers, the nitrated isomers, etc.
Start from say toluene!
It is true it is one methyl short, but who cares? It is still plenty of work (and fun) to do a synth starting from this compound! Toluene ->
o-nitro-toluene -> o-toluidine -> etc. etc.
Yepp, you can start even from benzoic acid -> benzamide -> aniline >>> whatever lidocain analog, which is two methyl short. Who knows,
it may still make your tongue numb.
Anyway, what I'd like to say is: chose a target what you can reasonably reach and you will gain confidence. A bad target is just frustration, wasted
money, time, resources.DraconicAcid - 27-7-2019 at 11:33
And just remember, don't chew on your fingernails or the end of your pencil during this experiment (a classmate had first-hand experience of this the
year I did this in third-year organic).Abromination - 27-7-2019 at 12:09
Why not extract it from anal lubricant like nile red? Or is avoiding that the reason for synthesis?Keras - 27-7-2019 at 12:10
Matter of fact, it was to give out as a birthday present to one of my friends who happens to be a dentist. So yeah, it's basically the real McCoy I'm
interested in. Though I imagine I could pack any powder into a ziploc bag and pretend it's lidocaine :p
That being said, I totally agree with what you say. Settling for smaller targets avoids big frustrations. I just happen to like challenges. I didn't
say I was about to do that right away (I don't even have xylene to start with). I can begin by synthesising wintergreen oil from aspirin. That would
be fun in the first place, then see if I'm able to successfully separate m-xylene from the other two isomers.
Besides, I have to finish a few things first, like successfully synthesise phenethyl alcohol from styrene via an anti-Markovnikov addition (probably
involving NaBH4 and iodine as a source of in situ diborane).
And just remember, don't chew on your fingernails or the end of your pencil during this experiment (a classmate had first-hand experience of this the
year I did this in third-year organic).
Why? It'll numb your tongue so you can bite it afterwards and not even feel pain? :p
