Cocaine Synthesis

[tomjuan]

I have several questions about the synthesis of cocaine from pyrrole that I found on erowid’s site.
(

http://www.erowid.org/archive/hyperreal/drugs/stimulants/cocaine.synth

)

The basic route looks like this:

pyrrole -> succinaldoxime
succinaldoxime -> succinaldehyde
succinaldehyde -> tropinone
tropinone -> 2-carbomethoxytropinone
2-carbomethoxytropinone -> methylecgonine
methylecgonine -> cocaine

1. I realize it isn’t the easiest synthesis – it requires a lot of steps and affords plenty of opportunities for screw-ups – but if I get all the steps right, will it work and provide the right isomer?

2. The literature claims that pyrrole is distilled from bone oil, which is extracted from crushed, heated bones. Bones I can get. Does anyone know where I can find a more detailed description of extracting pyrrole from bones?

3. What is succinaldoxime? I don’t have Merck’s Index, but I can’t even find anything at all about it on the net. A search of the hive didn’t turn anything up either. It isn’t listed by any chemical supply places. Does it go by any other names? Does anyone know its physical properties, or have Merck entry for it?

4. Acetonedicarboxylic acid is on the watched list, and I would rather expend extra time and effort than take unecessary risks in trying to obtain it. Is there a synthesis for it that uses more readily available compounds?

5. In the conversion from succinaldehyde to tropinone, it says the reaction mixture should be allowed to set for six days. That’s a long time to sit and stare at a flask. Is there anyway around this?

6. The conversion from tropinone to 2-carbomethoxytropinone does not state the yield, and I am having some difficulty trying to come up with a balanced equation to even get the theoretical yield. Does anyone know of a detailed abstract that includes the yield?

7. No yield is given in the conversion from carbomethoxytropinone to methylecgonine, either, so I am wondering about a more detailed abtract for that reaction as well. Also, it says the methylecgonine needs to be tested for activity and further processed if it isn’t active. I have no idea what the author is talking about. What is the difference between “active” and “inactive” methylecgonine, and I how do I test it for activity?

8. The final step – methylecgonine to cocaine – calls for benzene as a solvent in the reaction:
Methylecgonine + benzoic anhydride in benzene --> cocaine.
Benzene is dangerous for a lot of reasons and it is not easy to come by. Can I used a different solvent, like dichloromethane or chloroform, or will they screw up the reaction? Also, once again no yield is given in this step.

[terbium]

1. I realize it isn’t the easiest synthesis – it requires a lot of steps and affords plenty of opportunities for screw-ups – but if I get all the steps right, will it work and provide the right isomer?

I am not familiar with the procedure at Erowid but there is a procedure published in the scientific literature for producing carbomethoxytropinone by the condensation of succindialdehyde, acetonedicarboxylic acid ester and methylamine; this works well and in good yield.

Reduction of the keto group to produce ecgonine is more problematic, I don't know of any published procedures for this other than the 100+ year old German procedure using Na/Hg amalgam where no yields were given. There are a number of isomers that can be produced by the reduction of the keto group and only one is the desired isomer.

If you can't even purchase pyrrole then this is going to be a very long and arduous task. Maybee an amusing hobby but much easier and cheaper to buy the Columbian product.

[tomjuan]

Thanks for your reply.

I am sure it would cheaper to buy cocaine then to try to make it (especially the first time), but buying isn't nearly as challenging.

The ketone reduction method in the synthesis I was referring to was a Raney Nickel reduction. I am thinking that it can possibly reduce to the wrong isomer, or to several isomers all mixed together. I can't find much on the stereochemistry of methylecgonine, so I am not sure how I would determine which isomer I even had . . . maybe someone else has some ideas?

[slappy]

I hate to seem like a downer, but if you cannot answer these questions for yourself, you probably don't have the skill to pull off the synthesis. Cociane from Tropinone is hard enough, but you want to start from pyrrole? And you want to try and get that from ground bones? Are you crazy? This is not an Amphetamine synth we're talking here.

Besides all that, this is a half century old synth that is far from being optimized for practicality. There are much better ways to get to cocain now a'days. I figure most chemists would try to find a starting material that already contains the tropane ring, instead of trying a percyclic reaction with dismal yields.

The optical enantiomers can be resolved with NMR, GC/MS, or even TLC on a chiralplate.

Think about what Terbium said. You can get quite pure cocain from the columbians at a fraction of what it would cost if you made it.

[terbium]

instead of trying a percyclic reaction with dismal yields

What reaction with dismal yields? The condensation of succindialdehyde, acetonedicarboxylic acid ester and methylamine to carbomethoxytropinone or dicarbomethoxytropinone proceeds in very good yield, this molecule really wants to be formed.

[tomjuan]

Of course you are right- I'm nowhere near ready to attempt synthing coke yet. But I'm not in any kind of rush. I'm not gonna so much as raise a test tube until I have all the equipment, chemicals and a thorough understanding of the processes involved.

That said, your comments about synthesis are true for ANY drug. It would definitely be *easier* for me to go buy a hit of ecstasy or a ball of speed than it would be to make either one of them myself. I'm not in this to save time or effort or even money. I just want to learn how to do it. I hope that my desire to learn is a good enough reason to be asking these questions . . .

[hobbie]

HEy dont know if this is any different than what you have...But

http://www.totse.com/en/drugs/speedy_drugs/cokemak.html

thought it may help you even just a little
GL...let me know if you get it to work...thanks
I dont know....something about lab rats........

[PoohBear4Ever]

Yea tomjuan, I'll take a kilo. You can mail it to:

Agent Smith
1234 Your Going Down St. NW
Washington D.C., 12345

Please use the appropriate return address, or else we migh not receive your package.

Thanks alot,

AS

* Is your brother's name Don?