synthetic cocaine q labgurl - 6-1-2005 at 02:16
What would be the simplest reactions to use here? Tropinone to 2-Carbomethoxytropinone to Methylecgonine to Cocaine runlabrun - 6-1-2005 at 02:39
like many natural plant alkaloids there is NO simple way to make them.... if any at all...
Although back at the hive there was a few threads about synthtic cocaine, dont have those on disk though.... dont think they were very viable and were therefore abandoned....
-rlr Ref. cocaine synthesis solo - 6-1-2005 at 06:22
Of course rhodium had this pdf's on the subject.....let me know which one is of your interest.....solo
cocaineanalogs.pdf
cocaine.piperidine-based.analogs.sar-2.pdf cocaine.biosynthetic.pathway.pdf cocaine.biosynth.n-methylputrescine.pdf cocaine.analogs.clarke.pdf cocaine.total.synthesis.html cocaine.synthesis.txt
[Edited on 6-1-2005 by solo] guaguanco - 6-1-2005 at 08:57
Quote:
Although back at the hive there was a few threads about synthtic c ocaine, dont have those on disk though.... dont think they were very viable and were therefore abandoned.... -rlr
I actually knew of someone who tried this synthesis. They synthesized the tropanone ring structure (glutaraldehyde/methylamine/dimethyl acetonedicarboxylate) but abandoned the project. I still have the small amount of the product, isolated as the picrate.
labgurl - 6-1-2005 at 09:53
Once again the question is which REACTIONS would be most feasable? guaguanco - 6-1-2005 at 10:07
Quote:
Originally posted by labgurl Once again the question is which REACTIONS would be most feasable?
The classic synthesis is reacting glutaraldehyde, methylamine and acetone dicarboxlic acid (I misspoke in a previous post; the ester is not used) You end up with 4 diastereoisomers that have to eventually seperated by chromatography (if you want to end up with pure cocaine). Then you esterify the acid (diazomethane would work well), reduce the ketone, react with benzoyl chloride and trimethylamine in chloroform.
[Edited on 6-1-2005 by guaguanco] JohnWW - 6-1-2005 at 13:03
Diazomethane, CH2N2, is very dangerous to work with for esterification of carboxylic acids to methyl esters, being both highly toxic and explosive, like azide. The usual method of esterification is reaction of alcohols with carboxylic acids with a trac e of a strong mineral acid as catalyst, heating under reflux (takes a few hours usually). This is an equilibrium reaction, the yield of which can be increased by removing water as it is formed. Anhydrides react similarly with alcohols in the absence of acid. Acyl chlorides similarly react with alcohols with evolution of HCl. A more powerful methyl esterification reagent is sodium methoxide.
[Edited on 6-1-2005 by JohnWW] guaguanco - 6-1-2005 at 13:15
Sure, I just picked that as an example. There are a variety of reagents that could be used, although I would look for one that operate d under mild conditions. I don't know what the ruggedness of the tropanone moiety is. labgurl - 6-1-2005 at 17:29
What role does dimethylcarbonate play in the sodium methoxide/tropinone/ toluene/dimethylcarbonate reflux? Mendeleev - 6-1-2005 at 20:05
In my opinion it would be better to synthesize the methyl ester of tropinone in one huge step instead of first tropinone and then 2-CMT. Reaction of succindialdehyde, methylamine, and the anhydride of acetonedicarboxylic acid yields 2-CMT. Acetone dicarboxylic acid anhydride is produced by reacting acetone dicarboxylic acid with acet ic anhydride.
2-CMT is then reduced to methyl ec ognine. This can be done by catalytic hydrogenation or sodium amalgam, both methods kind of suck in my opinion. Hydrogenation = assloads of equipment construction (welding together apressure vessel, hydrogen tanks and connections, shaker, catalyst, eeeek!). Sodium amalgam=expensive + hard.
Once you have your methyl ecognine, it is reacting with either the chloride or the anhydride of benzoic acid. This last step doesn't seem too difficult, just react benzoic anhydride with methyl ecognine in benzene, nothing too fancy. I t hink the difficulty of this synthesis lies in the resolution of racemic mixtures over and over.
[Edited on 7-1-2005 by Mendeleev] labgurl - 6-1-2005 at 21:57
Darn, was hoping there was another r eduction method besides those 2. Hmmm wonder how one could obtain cocoa seeds within the u.s.? lol JohnWW - 7-1-2005 at 17:17
You have confused cocoa (cacao) seeds with coca seeds. They are two quite different species, the active principles in cocoa being t heobromine and caffeine. It is coca, from elevate d forest areas in northwestern South America, that contains cocaine and some related alkaloid
compounds. Coca should grow well in subtropical and warm temperate areas that do not have heavy frosts. (Cocoa, however, is strictly tropical; most commercial c ocoa plantations are within 10º of the equator, e.g. west Africa, and almost all are within 20º of the equator. This has to do with why cocoa butter is the vegetable oil with the highest melting point). labgurl - 8-1-2005 at 01:26
Thanks for clearing that up, I shall re try my search. jimwig - 8-1-2005 at 12:54
was looking into the same line of react ions and their viability OTC. it sounds something like this (if I remember correctly)
lactose > mucic acid > pyromucic acid > pyrrole > succinaldehyde > &
at which point i concluded my study
further along tropinone et al would have been realized but my masochistic/curious side got tired and quit on me.
as has been said it seems cheaper down on the corner. Nuke_Dukem - 12-1-2005 at 19:28
that shit is to involved. Go with the analog N-methyl,4-para-chloro-Phenyl, 3 -carboxy methyl ester staring with Arecoline. or you could make tropacocaine by hydrolysis of atropine to tropine and then esterfication with benzoic acid. warfox - 17-1-2005 at 14:46
Quote: Originally posted by solo cocaine.piperidine-based.analogs.sar-2.pdf
Can you send me the file to
[email protected] Thanks analog clareify yogi - 17-1-2005 at 15:48
Quote: Originally posted by Nuke_Dukem that shit is to involved. Go with the analog N-methyl,4-para-chloro-Phenyl, 3 -carboxy methyl ester staring with Arecoline.
Hi. Ive looked into this compound and cant find it in t he documents. Can u provide ref for this one? Chemdraw wont draw its structure either. Can u please clarify Nuke_Dukem?
[Edited on 17-1-2005 by yogi]
[Edited on 17-1-2005 by yogi] Nuke_Dukem - 17-1-2005 at 17:39
hey sorry that name I gave is just the name of arecoline. Heres one write up from rhodium, the authors calls the analog Coke-lite.
http://web.archive.org/web/20040210013016/www.rhodium.ws/che...
[Edited on 18-1-2005 by Nuke_Dukem] Reference for Worfox solo - 17-1-2005 at 18:05
Attachment: cocaine.piperidine-based.analogs.sar-2 copy.pdf (256kB) This file has been downloaded 699 times
Ref: synthetic cocaine solo - 18-1-2005 at 16:54
The work on Piperidine analogs of Phenyltropanes was done by Kozikowski...that should give you a start for looking in chem abstracts or med line.....solo labgurl - 19-1-2005 at 04:46
Can someone explain why benzocaine wouldn't be a viable starting material? sparkgap - 19-1-2005 at 07:04
Maybe that's because benzocaine is a derivative of PABA, not any of them two-ring heterocyclics that comprise cocaine. Same goes for most of the other "-caines" (check ChemFinder or the Merck Index if you want to verify my claims). Cocaine is quite unique among them.
Stick with the route from atropine. It isn't too hard to obtain, especially if nightshade/belladonna, bittersweet or henbane are common plants in your area.
Arecoline? Are areca/betel common plants there? cyclohexane - 19-7-2009 at 20:48
benzylmethylecgonine can be achived via a nitrone synthesis.
look on rhodium....its a picture.
in littile letters is refrences.
get those. yeild is lower slightly.......but seems less involved...more like a short series of brutal grignards lol :)
but what about benzoylecgonine.....can this be selectivly remethylated? setback - 19-7-2009 at 21:54
If it was practical to do this the Colombian drug lords wouldn't still be doing it the old fashion way. cyclohexane - 19-7-2009 at 23:11
its not as profitable to do it if you happen to live where there is millions of coca plants and can make peons pick em in order to not get shot........
but this is about chemistry, not profit. any fool can make tweek, make ecgonine takes real skill.
and the nitrone route benafits from uncommon reagents..... not hard to get anhydride,methylamine, sodium metal, ect. Sandmeyer - 20-7-2009 at 03:24
I don't know about the pharmacology of conformationally restricted analogues, but going from 1 to 2 gives 2 regioselectivly in 36% yield. Compund 2 can be elaborated further with c onventional chemistry to potentially strong analogues.
EDIT: I forgot to put methyl g roup on para pos. of phenyl ring in structure 1 . :D
[Edited on 20-7-2009 by Sandmeyer] Nicodem - 20-7-2009 at 04:07
That is a very ingenuous polar cycloaddition. What is the re ference? A dipolar addition with a plain alkene as dipolarophile is a bit unusual. I could only find two papers on 2-like structures (attached), both using this same synthetic strategy. In the attached papers they used vinyl sulfones as dienophiles, but the pericyclic reactions were intermolecular. I don't think LiClO4 or any other Lewis acid would catalyse the reaction. LiC lO4 helps to activate either the dienophile or diene in the Diels-Alder reactions, but I doubt it could find any role in a dipolar reaction of this type. The Li(+) might just sit on the -O(-) group and thus reduce the speed of resonance interchange betwee n the carbaoanion (required for the addition) and oxyanion.
Attachment: Tuning the Selectivity of Monoamine Transporter Inhibitors by the Stereochemistry of the Nitrogen Lone Pair.pdf (68kB) This file has been downloaded 151 times
Attachment: The synthesis of tricyclic cocaine analogs via the 1,3-dipolar cycloaddition of oxidopyridinium betaines.pdf (249kB) This file has been downloaded 176 times
Sandmeyer - 20-7-2009 at 04:18
Quote: Originally posted by Nicodem
I don't think LiClO4 or any other Lewis acid would catalyse the reaction. LiClO4 helps to activate either the dienophile or diene in the Diels-Alder reactions, but I doubt it could find any role in a dipolar reaction of this type. The Li(+) might just sit on the -O(-) group and thus reduce the speed of resonance interchange between the carbaoanion (required for the addition) and oxyanion.
I realised that too on a closer look... Sandmeyer - 20-7-2009 at 04:30
Quote: Originally posted by Nicodem That is a very ingenuous polar cycloaddition. What is the re ference? A dipolar addition with a plain alkene as dipolarophile is a bit unusual. I could only find two papers on 2 -like structures (attached), both using this same synthetic strategy. In the attached papers they used vinyl sulfones as dienophiles, but the pericyclic reactions were intermolecular.
The reference is in your own post, scroll down in the Kozikowski's tet. lett. paper and you'll see the intramolecuar cycloaddition...
[Edited on 20-7-2009 by Sandmeyer] Nicodem - 20-7-2009 at 05:58
Quote: Originally posted by Sandmeyer
The reference is in your own post, scroll down in the Kozikowski's tet. lett. paper and you'll see the intramolecuar cycloaddition...
Don't know how I managed to m iss that page on an only 4 page paper. :o They point to J. Chem. Soc., Chem. Commun., 1976, 367-368 as their reference, but at the moment I can't access the digital version. Sounds like a nice cyclisation reaction for building complex polycyclic systems - I never considered N-alkylated 3-hydroxypyridines as potential 1,3dipoles. It is interesting that the re acting 1,3-dipole is the resonance structure that one would least likely draw: cationic and anionic charges on carbons. Kind of logical and simple, but only after you see the reaction scheme. Otherwise, I would not have thought of it in a hundred years.
Kozikovski et al also have a patent on his work from the above papers: WO0007994 Polverone - 20-7-2009 at 09:02
Quote: Originally posted by Nicodem Quote: Originally posted by Sandmeyer
The reference is in your own post, scroll down in the Kozikowski's tet. lett. paper and you'll see the intramolecuar cycloaddition...
Don't know how I managed to miss that page on an only 4 page paper. :o They point to J. Chem. Soc., Chem. Commun., 1976, 367-368 as their reference, but at the moment I can't access the digital version.
http://www.sciencemadness.org/scipics/c39760000367.pdf Sandmeyer - 20-7-2009 at 15:04
Quote: Originally posted by Nicodem Kind of logical and simple, but only after you see the reaction scheme. Otherwise, I would not have thought of it in a hundred ye ars.
Yes, that reaction is very nice. Anyhow, solution I find truly amazing is the following one step reaction by Boger and his co-workers:
note how five contiguous stereocenters (not to me ntion all the rings) are neatly installed in agreement with the natural prod vindoline. Now that's a hell of a reaction, imagine running the NMR after it - pure euphoria. :D Such reactions should be made illegal, they release more monoamines than MDxA.
...and also the first link in my signature is not to forget :D
sorry for driving the thread off topic... ;)
[Edited on 20-7-2009 by Sandmeyer]
setback - 20-7-2009 at 15:23
That's a synth for a chemotherapy drug, r ight? benzylchloride1 - 21-7-2009 at 12:37
Make atropine, not cocaine. Same reactions, no illegal drug. Use acetone dicarboxylic acid instead of the monomethyl ester for the reaction to form tropinone. JohnWW - 21-7-2009 at 14:19
Atropine, the principal active substance in deadly nightshade, is used in small quantities as a muscle relaxant drug, but has no hallucinogenic or euphoric e ffects. For this purpose, it is used as an anti-diarrhetic, and may be use as an antidote for poisoning with other alkaloids which cause muscle spasms, such as strychnine/brucine. donlaszlow - 3-8-2009 at 12:30
If you are a Chemist you are faithful to your oath, you use your knowledge to help others. :D Cocaine is illegal for a reason. :( JohnWW - 3-8-2009 at 13:44
Quote: Originally posted by donlaszlow
Cocaine is illegal for a reason. For largely political and business reasons, pushed by the pharmaceuticals, alcohol, and tobacco lobbies, and religious reasons pushed by the so-called "temperance lobby", I am sor ry to have to say; - and propagandized in the phoney "War/Whore On Dr ugs". For many years, the stuff was a principal active ingredient of Coca-Cola; and until about the 1920s, one could buy any amount of it over-the-counter at any good drugstore, w ithout a prescription and no questions asked. S.C. Wack - 3-8-2009 at 17:15
It is always unwise to take a thread in a chemistry forum and turn it away from chemistry.
Quote: Originally posted by JohnWW
For largely political and business reasons, pushed by the pharmaceuticals, alcohol, and tobacco lobbies, and religious reasons pushed by the so-called "temperance lobby"
You seem not much of an authority on c ocaine. The early critics of cocaine were doctors who already knew of its morphine-deep addictiveness starting at least as early as 1886 in both the US and Germany, and in Britain in 1889, immediately after becoming widely used and available. And its proponents were drug companies such as Merck and Parke, Davis & Co. Many early addicts were members of the temperance lobby, who drank alcoholic preparations and became both alcoholics and coke addicts.
Anyone who doubts the addictiveness of cocaine and the problems that t hat causes is ignorant beyond belief. The_Davster - 3-8-2009 at 17:35
Beginning of thread was cookery, and got worse inserting a drug debate. closed.
Unfortunate as the organic chemistry in the middle was valid.
[Edited on 4-8-09 by The_Davster]
