Cyrax (Newbee)
11-10-01 03:11
No 235158
      Synthesis of Cocaine  Bookmark   

If you want to read a good article before going to bed, check this out:
 Tufariello, Journal of the American Chemical Society, (1979), vol 101, p 2435

Starting for Pyrroline 1-oxide, they get (+/-) coke after a 7 step reaction.  It looks very promessing.  As soon as I get the synthetic details, I 'll post them.

Does someone know how much coke one needs for 1 dose?
(Chief Bee)
11-10-01 10:55
No 235225
      Re: Synthesis of Cocaine  Bookmark   

10mg pure (-)-cocaine is considered a normal line.

I believe this is the route you are talking about:

(Old P2P Cook)
11-10-01 15:46
No 235296
      Re: Synthesis of Cocaine  Bookmark   

It looks very promessing.
I think not. I haven't looked at the details since this paper was first published but as I remember one fly in the ointment is the extreme dilution of reactants required at some steps in the sequence.
11-11-01 13:15
No 235598
      Re: Synthesis of Cocaine  Bookmark   

Terbium, do you actually have the rxn details for that rxn?  please post them if you do.  not really interested in the cocaine just interested in the chemistry behind those steps and the practical apps thereof.  and what kind of dilution are you talking about?  stuff like mg/L dilution (ppm/ppb?)
11-14-01 03:52
No 236625
      Re: Synthesis of Cocaine
(Rated as: excellent)

The chemists that did this synthesis went through hell before they found this route.  You need a well equipped lab if you think about trying this (do not do this in your kitchen).  I think we 'd better stick to the synthesis of meth.  But for educational purposes, I will post it anyway (in different posts because the reaction path is long)

* Step 1: Synthesis of 2-carbomethoxymethylhexahydro[1,2-b]isoxazole [1]

A solution of 1-pyrroline 1-oxide in 20 ml of dry toluene was prepared from 251 mg (2.88 mol) N-hydroxypyrrolidine and 1.61 g (2.5 eq.) of yellow mercuric oxide in 20 ml of dry CH2Cl2, followed by solvent exchange with toluene.  A solution of 143 mg (1.30 mmol) of methyl 3-butenoate in 5 ml of dry toluene was added and the mixture was refluxed for 15 h.  Removal of the solvent in vacuo gave a dark oil which was chromatographed on silica gel using 90:10 benzene/acetone as eluant, from which 230 mg (96 %) of the adduct was obtained.  Bulb to bulb distillation at 100 C (0.09 mm) gave a colorless liquid.

* Step 2: Synthesis of 5-(gamma-carbomethoxy-beta-hydroxypropyl)-1-pyrroline 1-oxide [2]

m-Chloroperbenzoic acid (85 %, 130 mg, 1 eq) was added to a solution of 123 mg (0.66 mmol) of [2] in 25 ml of dry CH2Cl2.  The reaction mixture was warmed to room temperature and extracted with water (2x25 ml).  The aquous layer was  vacuum distilled to give a light yellow oil, which was chromatographed on silica gel, using 95:5 CH2Cl2/MeOH as eluant, to give 118 mg (89 %) of the product as a clear oil.

I 'll post the rest next time.
11-15-01 02:04
No 236951
      Re: Synthesis of Cocaine
(Rated as: excellent)

* Step 3: 2-Carbomethoxy-7-(gamma-carbomethoxy-beta-hydroxypropyl)hexahydropyrrolo[1,2-b]isoxazole [3]

To 235 mg (1.27 mmol) of adduct [2] in 70 ml of dry CH2Cl2, while stirring in an ice bath under nitrogen, was added 284 mg (1.1 eq.) of 85 % m-chlorobenzoic acid.  After 2 h, the solution was warmed to room temperature and extracted with wather.  The aqueous layer was concentrated in vacuo to give a clear oil which was taken up in CH2Cl2, dried over sodium sulfate, and filtered.  The solvent was removed and the residue was dissolved in 70 ml of dry benzene, to which was added 5 ml of methyl acrylate.  The resulting light yellow solution was refluxed for 20 h, cooled to room temperature, and extracted with 1 N hydrochloric acid.  The acid extract was basicified with sodium bicarbonate, then extracted with CH2Cl2 to give, after drying over sodium sulfate, 282 mg (77 %) of a mixture of adducts [3] as a light yellow oil.

Step 4: 2-carbomethoxy-7-(gamma-carbomethoxy-beta-methanesulfonylpropyl)hexahydropyrrolo[1,2-b]isoxazole [4]

Freshly distilled methanesulfonyl chloride (91 microliter, 2 eq.) was added dropwise via a syringe to a stirred solution of 170 mg (0.59 mmol) of hydroxy ester [3] in 25 ml of freshly distilled, dry pyridine under a nitrogen atmosphere in an ice bath.  After 1 h, the solution was warmed to room temperature, stirred for an additional 3 h, then poured onto ice.  Potassium carbonate was added and the aqueous solution was extracted with CH2Cl2.  The organic extract was dried over sodium sulfate, filtered, and concentrated to give 204 g (95 %) of [4] as a light yellow oil.

Step 5: 2-carbomethoxy-7-(3'-carbomethoxy-2'-trans-propenyl)hexahydropyrrolo[1,2-b]isoxazole [5]

Under nitrogen, 204 mg (0.56 mmol) of methanesulfonate ester [4] was dissolved in 25 ml of dry benzene, to which was added 138 mg (2 eq.) of freshly distilled 1,5-diazabicyclo[4.3.0]non-5-ene via a syringe.  The resulting suspension was stirred for 4h, washed with 25 ml of saturated sodium bicarbonate solution and twice with 25 ml of water, then dried over sodium sulfate.  The solvent was removed in vacuo to give 130 mg (86 %) of trans olefin [5] as a light yellow oil.

Step 6: 2-carbomethoxy-(1S*,2R*,3R*,6S*)-7-aza-8-oxotricyclo[]nonane [6]

A solution of 78 mg (0.29 mmol) of the crude trans olefin [5] in 50 ml of dry, distilled xylene was refluxed for 3h.  The solution was extracted with 1 N HCl.  The acid extracted was basicified with sodium bicarbonate, then backextracted with CH2Cl2.  The CH2Cl2 extract was dried over sodium sulfate, filtered, and concentrated to give a light yellow oil.  Sublimation at 70 C (0.08 mm) gave a mixture of 9 mg of [5] and 31 mg (66 %) of [6].  Crystallization from pentane gave an analytical sample of [6] as white plates.

Step 7: Methiodide of methyl (1S*,2R*,3R*,6S*)-7-aza-8-oxatricyclo[,7]nonane-2-carboxylate [7]

To a solution of 140 mg (0.77 mmol) of cycloadduct [6] in 10 ml of anhydrous ether and 3 ml of CH2Cl2 was added 2 ml of methyl iodide (32 mmol) and this mixture was stirred under nitrogen at room temperature for 12 h.  The resulting mixture was refluxed for an additional 24 h.  Concentration gave a yellow solid residue that was recrystallized form MeOH/Et20 giving 145 mg (58 %) of a white solid.

Step 8: Ecgonine methyl ester [8]

To a solution of 140 mg (0.77 mmol) of the methiodide [7] in 4 ml of 50 % aqueous acetic acid was added 0.6 g of activated zinc dust under a nitrogen atmosphere.  The resulting mixture was warmed to 70 C for 3.5.  The remaining solids were filtered and washed with 8 ml of hot water (ca 70 C)  The filtrate was saturated with solid sodium carbonateand continuously extracted with CH2Cl2 for 18 h.  The CH2Cl2 solution was dried (MgSO4), concentrated, and bulb to bulb distilled in a Kugelrohr apparatus giving 43 mg (47 %) of a colorless oil.

Step 9: dl-Cocaine [9]

Following the method of de Jong, 23 mg (0.12 mmol) of compound [8] in 1 ml of dry benzene was added to a mixture of 1 g (9.4 mmol) of anhydrous sodium carbonate, 0.5 ml (4.3 mmol) of benzoyl chloride, and 19 ml of dry benzene.  The resulting mixture was worked up as reported [ref.: Recl. Trav. Chim. Pays-bas (1940), vol 59, p 27-30] to give 9.8 mg (37 %) of a colorless oil that solidified on standing.

So, fellow bees, this is the synthesis of cocaine.  In retrospect, this synthesis is not very promessing because it is too difficult in comparison with a meth synthesis.  But, as a chemist, I have to say that Tufariello and coworkers did some great work (whow)
(Hive Bee)
12-11-01 23:01
No 246743
      Re: Synthesis of Cocaine  Bookmark   

Is this synthetic cocaine close to the reall thing?  I know it's made to be the same , but there's got to be some differences in the final product.??

How come phenethylamine free base doesn't go to solid upon cooling like cocaine free base does? I always wondered about that.

May The Source Bee With Yous
(Chief Bee)
12-12-01 07:37
No 246801
      Re: Synthesis of Cocaine  Bookmark   

This synthetic cocaine is racemic, while it is only one of the isomers that's really active, so it would have about half the potency of 100% pure cocaine from natural sources.

Phenethylamine freebase is a liquid, while cocaine freebase is a solid.
(Hive Bee)
01-02-02 11:08
No 252001
      Re: Synthesis of Cocaine  Bookmark   

Ahhh Yes,  cocaine free base is a liquid when heated though, or maybe an oil would be a better description (for phenethylamines as well) only phenethylamine free base doesn't solidify upon Thanks Cyrax/Rhodium

May The Source Bee With You....Always.
(Hive Bee)
01-05-02 22:20
No 253128
      Re: Synthesis of Cocaine  Bookmark   

at -60C it will freeze/solidify. Everything freezes.

No One's Jurisdiction