170 lines
10 KiB
Plaintext
170 lines
10 KiB
Plaintext
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H O W T O M A K E C O C A I N E
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BROUGHT TO YOU BY: CUBE 1994-05-04
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Welcome to the complete guide of how to make cocaine. If you do
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everything right you are going to be king of the world, either in your
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own world or in the real world. Please read the disclaimer at the end of
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this text.
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Now, let's get to action!
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The basic formula for cocaine starts by purchasing or making tropinine,
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converting the tropinone into 2-carbomethoxytropinone (also known as
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methyl-tropan-3-one-2-carboxylate), reducing this to ecgonine,
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and changing that to cocaine.
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Succindialdehyde. This can be purchased, too. 23.2 g of succinaldoxime
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powder in 410 ml of 1 N sulfuric acid and add dropwise with stirring at
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0* a solution of 27.6 g of sodium nitrite in 250 ml of water over
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3 hours. After the addition, stir and let the mixture rise to room temp
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for about 2 hours, taking care not to let outside air into the reaction.
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Stir in 5 g of Ba carbonate and filter. Extract the filtrate with ether
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and dry, evaporate in vacuo to get the succindialdehyde. This was t
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aken from JOC, 22, 1390 (1957). To make succinaldoxime, see JOC, 21,
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644 (1956).
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Complete Synthesis of Succindialdehyde. JACS, 68, 1608 (1946). In a 2 liter
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3 necked flask equipped with a stirrer, reflux condenser, and an addition
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funnel, is mixed 1 liter of ethanol, 67 g of freshly distilled pyrrole, and
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141 g of hydroxylamine hydrochloride. Heat to reflux until dissolved, add
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106 g of anhydrous sodium carbonate in small portions as fast as reaction
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will allow. Reflux for 24 hours and filter the mixture. Evaporate the
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filtrate to dryness under vacuo. Take up the residue in the minimum amount
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of boiling water, decolorize with carbon, filter and allow to recrystallize
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in refrigerator. Filter to get product and concentrate to get additional
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crop. Yield of succinaldoxime powder is a little over 40 g, mp is 171-172*.
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5.8 g of the above powder is placed in a beaker of 250 ml capacity and
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54 ml of 10% sulfuric acid is added. Cool to 0* and add in small portions
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of 7 g of sodium nitrite (if you add the nitrite too fast, nitrogen dioxide
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fumes will evolve). After the dioxime is completely dissolved, allow the
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solution to warm to 20* and effervescence to go to completion. Neutralize
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the yellow solution to litmus by adding small portions of barium carbonate.
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Filter off the barium sulfate that precipitates. The filtrate is 90% pure
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succindialdehyde and is not purified further for the reaction to create
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tropinone. Do this procedure 3 more times to get the proper amount for the
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next step, or multiply the amounts given by four and proceed as described
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above.
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Take the total amount of succinaldehyde (obtained from 4 of the above
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syntheses combined) and without further treatment or purification (this had
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better be 15.5 g of succindialdehyde) put into an Erlenmeyer flask of
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4-5 liters capacity. Add 21.6 g of methylamine hydrochloride, 46.7 g of
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acetonedicarboxylic acid, and enough water to make a total volume of 2
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liters. Adjust the pH to 8-10 by slowly adding a saturated solution of
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disodium phosphate. The condensate of this reaction (allow to set for
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about 6 days) is extracted with ether, the ethereal solution is dried
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over sodium sulphate and distilled, the product coming over at 113* at
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25 mm of pressure is collected. Upon cooling, 14 g of tropinone
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crystallizes in the pure state.
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2-Carbomethoxytropinone. A mixture of 1.35 g of sodium methoxide
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(this is sodium in a minimum amount of methanol), 3.5 g of tropinone,
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4 ml of dimethylcarbonate and 10 ml of toluene is refluxed for 30 min.
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Cool to 0* and add 15 ml of water that contains 2.5 g of ammonium chloride.
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Extract the solution after shaking with with four 50 ml portions of
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chloroform, dry, evaporate the chloroform in vacuo. Dissolve the oil
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residue in 100 ml of ether, wash twice with a mixture of 6 ml of
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saturated potassium carbonate and three ml of 3 N KOH. Dry and evaporate
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in vacuo to recover the unreacted tropinone. Take up the oil in a solution
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of aqueous ammonium chloride and extract with chloroform, dry, and evaporate
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in vacuo to get an oil. The oil is dissolved in hot acetone, cool, and
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scratch inside of flask with glass rod to precipitate
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2-carbomethoxytropinone. Recrystallize 16 g of this product in 30 ml of hot
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methyl acetate and add 4 ml of cold water and 4 ml of acetone. Put in
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freezer for 2 1/2 to 3 hours. Filter and wash the precipitate with cold
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methyl acetate to get pure product.
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Methylecgonine. 0.4 mole of tropinone is suspended in 80 ml of ethanol
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in a Parr hydrogenation flask (or something that can take 100 psi and not
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react with the reaction, like stainless steel or glass). 10 g of Raney
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Nickle is added with good agitation (stirring or shaking) followed by
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2-3 ml of 20% NaOH solution. Seal vessel, introduce 50 psi of hydrogen
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atmosphere (after flushing vessel with hydrogen) and heat to 40-50*.
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After no more uptake of hydrogen (pressure gauge will hold steady after
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dropping to its lowest point) bleed off pressure and filter the nickle off,
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rinse out bottle with chloroform and use this rinse to rinse off the nickle
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while still on the filter paper. Make the filtrate basic with KOH after
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cooling to 10*. Extract with chloroform dry, and evaporate the chloroform
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in vacuo to get an oil. Mix the oil plus any precipitate with an equal
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volume of dry ether and filter. Add more dry ether to the filtrate until
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no more precipitate forms, filter and add to the rest of the precipetate.
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Recrystallize from isopropanol to get pure methylecgonine. Test for activity.
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If active, skip down to the step for cocaine. If not active, proceed as
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follows. Stir with activated carbon for 30 min, filter, evaporate in vacuo,
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dissolve the brown liquid in methanol, and neutralize with 10% HCl acid in
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dry ether. Evaporate the ether until the two layers disappear, and allow to
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stand for 2 hours at 0* to precipitate the title product. There are many
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ways to reduce 2-carbomethoxytropinone to methylecgonine. I chose to design
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a Raney Nickle reduction because it is cheap and not as suspicious as LAH
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and it is much easier than zinc or sodium amalgams.
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Cocaine. 4.15 g of methylecgonine and 5.7 g of benzoic anhydride in 150 ml
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of dry benzene are gently refluxed for 4 hours taking precaution against
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H20 (the 2 should be on a lower level) in the air (drying tube). Cool in an
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ice bath, acidify carefully with hydrochloric acid, dry, and evaporate in a
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vacuum to get a red oil which is treated with a little portion of isopropanol
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to precipitate cocaine.
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As you can see, this is quite a chore. The coca leaves give ecgonine, which
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as you can see, is only a jump away from cocaine. If you can get egconine,
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then dissolve 8 1/2 g of it in 100 ml of ethanol and pass (bubble) dry HC1
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gas through this solution for 30 min. Let cool to room temp and let stand
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for another 1 1/2 hours. Gently reflux for 30 min and evaporate in vacuo.
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Basify the residue oil with NaOH and filter to get 8.4 g of methylecgonine,
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which is converted to cocaine as in the cocain step above.
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Below is given a somewhat easier method of producing tropinone by the
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general methods of Willstatter, who was instrumental in the first synthetic
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production of cocaine and several other alkaloids. After reviewing this
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method, I found it to be simpler than the above in many respects.
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Tropinone. 10 g of pyrrolidinediethyl diacetate are heated with 10 g of
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cymene and 2 g of sodium powder, the reaction taking place at about 160*.
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During the reaction (which is complete in about 10 min) the temp should not
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exceed 172*. The resulting reaction product in dissolved in water, then
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saturated with potassium carbonate, and the oil, which separates, is boiled
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with dilute sulfuric acid. 2.9 g of tropinone picrate forms and is filtered.
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Here are two more formulas devised by Willstatter that produce tropinone
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from tropine. Take note of the yield differences.
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Tropinone. To a solution of 25 g tropine, dissolved in 10 times its weight
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of 20% sulfuric acid are added 25 g of a 4% solution of potassiumpermanganate
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in 2 or 3 g portions over 45 min while keeping the temp at 10-12*. The
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addition of permanganate will cause heat (keep the temp 10-12*) and
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precipitation of manganese dioxide. The reaction mixture is complete in
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1 hour. A large excess of NaOH is added and the reaction is steam distilled
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until 1 liter of distillate has been collected. The tropinone is
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isolated as the dibenzal compound by mixing the distillate with 40 g of
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benzaldehyde in 500 cc of alcohol and 40 of 10% sodium hydroxide solution.
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Let stand several days to get dibenzaltropinone as yellow needles.
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Yield: 15.5 g, 28%. Recrystallize from ethanol to purify.
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Tropinone. A solution of 12 g of chromic acid in the same amount of
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water (12 g) and 60 g of glacial acetic acid is added dropwise with stirring
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over a period of 4 hours to a solution of 25 g of tropine in 500 cc of
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glacial acetic acid that has been warmed to 60-70* and is maintained at this
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temp during the addition. Heat the mixture for a short time on a steam bath
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until all the chromic acid has disappeared, cool and make strongly alkaline
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with NaOH. Extract with six 500 cc portions of ether and evaporate the ether
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in vacuo to get an oil that crystallizes readily. Purify by convering to the
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picrate or fractionally distill, collecting the fraction at 224-225* at
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714 mm vacuo.
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The tropinones can be used in the above formula (or in a formula that you
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have found elsewhere) to be converted to cocaine. Remember to recrystallize
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the 2-carbomethoxytropinone before converting to methylecgonine.
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This text is spread for informational purpose only. I am not responsible
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if someone is injured while using this information. After all, information
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wants to be free.
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