202 lines
11 KiB
Plaintext
202 lines
11 KiB
Plaintext
From: jmt0165@u.cc.utah.edu (Jon Taylor)
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Newsgroups: alt.drugs
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Subject: Cocaine Synthesis
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Date: 18 Apr 1994 18:30:40 -0600
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Message-ID: <2ov8ng$dg8@u.cc.utah.edu>
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Enjoy!
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-Jon
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CUT HERE
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/\/\/\/\/\/\/\/\/\/\/\/\
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Cocaine Synthesis
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Scanned From _Recreational Drugs: A Complete Guide to Manufacturing_
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COCAINE
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Although this drug is categorized as a local anesthetic, I have chosen
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to put it in with the hallucinogens because of the psycho- tomimetic
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effects that it produces. Cocaine is not a phenylethyl- amine, but it
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produces central nervous system arousal or stimulant effects which
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closely resemble those of the amphetamines, the
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methylenedioxyamphetamines in particular. This is due to the inhibition
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by cocaine of re-uptake of the norepinepherine released by the
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adrenergic nerve terminals, leading to an enhanced adrenergic
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stimulation of norepinephrine receptors. The increased sense of well
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being and intense, but short lived, euphoric state produced by cocaine
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requires frequent administration.
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Cocaine does not penetrate the intact skin, but is readily absorbed from
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the mucus membranes, creating the need to snort it. This accounts for
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the ulceration of the nasal septum after cocaine has been snorted for
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long periods.
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The basic formula for cocaine starts by purchasing or making tropinone,
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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, and
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changing that to cocaine. Sounds easy? It really is not very simple, but
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with Reagan's new drug policies, cracking down on all of the drug
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smuggling at the borders, this synthetic cocaine may be the source of
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the future. This synthesis is certainly worth performing with the high
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prices that cocaine is now commanding. As usual, I will start with the
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precursors and intermediates leading up to the product.
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Succindialdehyde. This can be purchased, too. 23.2 g of
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succinaldoxime powder in 410 ml of 1 N sulfuric acid and add dropwise
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with stirring at 0<> a solution of 27.6 g of sodium nitrite in 250 ml of
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water over 3 hours. After the addition, stir and let the mixture rise to
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room temp for about 2 hours, taking care not to let outside air into the
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reaction. Stir in 5 g of Ba carbonate and filter. Extract the filtrate
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with ether and dry, evaporate in vacuo to get the succindialdehyde. This
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was taken from JOC, 22, 1390 (1957). To make succinaldoxime, see JOC,
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21, 644 (1956).
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Complete Synthesis of Succindialdehyde. JACS, 68, 1608 (1946). In a 2
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liter 3 necked flask equipped with a stirrer, reflux condenser, and an
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addition funnel, is mixed 1 liter of ethanol, 67 g of freshly distilled
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pyrrole, and 141 g of hydroxylamine hydrochloride. Heat to reflux until
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dissolved, add 106 g of anhydrous sodium carbonate in small portions as
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fast as reaction will allow. Reflux for 24 hours and filter the mixture.
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Evaporate the filtrate to dryness under vacuo. Take up the residue in
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the minimum amount of boiling water, decolorize with carbon, filter and
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allow to recrystallize in refrigerator. Filter to get product and
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concentrate to get additional crop. Yield of succinaldoxime powder is a
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little over 40 g, mp is 171-172<37>.
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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
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portions of 7 g of sodium nitrite (if you add the nitrite too fast,
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nitrogen dioxide fumes will evolve). After the dioxime is completely
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dissolved, allow the solution to warm to 20<32> and effervescence to go to
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completion. Neutralize the yellow solution to litmus by adding small
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portions of barium carbonate. Filter off the barium sulfate that
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precipitates. The filtrate is 90% pure succindialdehyde and is not
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purified further for the reaction to create tropinone. Do this procedure
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3 more times to get the proper amount for the next step, or multiply the
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amounts given by four and proceed as described 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
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had better be 15.5 g of succindialdehyde) put into an Erlenmeyer flask
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of 4-5 liters capacity. Add 21.6 g of methylamine hydrochloride, 46.7 g
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of acetonedicarboxylic acid, and enough water to make a total volume of
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2 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<31> 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. Tropinone can also be obtained by
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oxidation of tropine with potassium dichromate, but I could not find the
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specifics for this operation.
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2-Carbomethoxytropinone. A mixture of 1.35 g of sodium methoxide (this
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is sodium in a minimum amount of methanol), 3.5 g of tropinone, 4 ml of
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dimethylcarbonate and 10 ml of toluene is refluxed for 30 min. Coo] to
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0<EFBFBD> and add 15 ml of water that contains 2.5 g of ammonium chloride.
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Extract the solution after shaking 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
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solution of aqueous ammonium chloride and extract with chloroform, dry,
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and evaporate in vacuo to get an oil. The oil is dissolved in hot
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acetone, cool, and 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
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hot methyl acetate and add 4 ml of cold water and 4 ml of acetone. Put
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in freezer for 2l/2 to 3 hours. Filter and wash the precipitate with
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cold 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
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not react with the reaction, like stainless steel or glass). 10 g of
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Raney Nickle is added with good agitation (stirring or shaking) followed
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by 2- 3 ml of 20% NaOH solution. Seal vessel, introduce 50 psi of
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hydrogen atmosphere (after flushing vessel with hydrogen) and heat to
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40-50<35>. After no more uptake of hydrogen (pressure gauge will hold
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steady after dropping to its lowest point) bleed off pressure and filter
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the nickle off, rinse out bottle with chloroform and use this rinse to
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rinse off the nickle while still on the filter paper. Make the filtrate
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basic with KOH after cooling to 10<31>. Extract with chloroform dry, and
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evaporate the chloroform in vacuo to get an oil. Mix the oil plus any
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precipitate with an equal volume of dry ether and filter. Add more dry
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ether to the filtrate until no more precipitate forms, filter and add to
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the rest of the precipitate. Recrystallize from isopropanol to get pure
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methylecgonine. Test for activity. If active, skip down to the step for
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cocaine. If not active, proceed as follows. Stir with activated carbon
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for 30 min, filter, evaporate in vacuo, dissolve the brown liquid in
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methanol, and neutralize with 10% HCI acid in dry ether. Evaporate the
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ether until the two layers disappear, and allow to stand for 2 hours at
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0<EFBFBD> to precipitate the title product. There are many ways to reduce
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2-carbomethoxytropinone to methylecgonine. I chose to design a Raney
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Nickle reduction because it is cheap and not as suspicious as LAH and it
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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
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ml of dry benzene are gently refluxed for 4 hours taking precaution
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against H20 in the air (drying tube). Cool in an ice bath, acidify
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carefully with hydrochloric acid, dry, and evaporate in a vacuum to get
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a red oil which is treated with a little portion of isopropanoi to
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precipitate cocaine.
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As you can see, this is quite a chore. The coca leaves give ecgonine,
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which as you can see, is only a Jump away from cocaine. If you can get
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egconine, then dissolve 8l/2 g of it in 100 ml of ethanol and pass
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(bubble) dry HC1 gas through this solution for 30 min. Let cool to room
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temp and let stand for another 11/2 hours. Gently reflux for 30 min and
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evaporate in vacuo. Basify the residue oil with NaOH and filter to get
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8.4 g of methylecgonine, which is converted to cocaine as in the cocaine
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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
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synthetic production of cocaine and several other alkaloids. After
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reviewing this method, I found it to be simpler than the above in many
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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
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160<EFBFBD>. During the reaction (which is complete in about 10 min) the temp
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should not exceed 172<37>. The resulting reaction product is dissolved in
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water, then saturated with potassium carbonate, and the oil, which
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separates, is boiled with dilute sulfuric acid. 2.9 g of tropinone
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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
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weight of 20% sulfuric acid are added 25 g of a 4% solution of potassium
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permanganate in 2 or 3 g portions over 45 min while keeping the temp at
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10-12<31>. The addition of permanganate will cause heat (keep the temp
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10-12<31>) and precipitation of manganese dioxide. The reaction mixture is
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complete in I hour. A large excess of NaOH is added and the reaction is
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steam distilled until I liter of distillate has been collected. The
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tropinone is isolated as the dibenzal compound by mixing the distillate
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with 40 g of benzaldehyde in 500 cc of alcohol and 40 g of 10% sodium
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hydroxide solution. Let stand several days to get dibenzaltropinone as
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yellow needles. Yield: 15.5 g, 28%. Recrystallize from ethanol to
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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
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stirring over a period of 4 hours to a solution of 25 g of tropine in
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500 cc of glacial acetic acid that has been warmed to 60-70<37> and is
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maintained at this temp during the addition. Heat the mixture for a
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short time on a steam bath until all the chromic acid has disappeared,
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cool and make strongly alkaline with NaOH. Extract with six 500 cc
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portions of ether and evaporate the ether in vacuo to get an oil that
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crystallizes readily. Purify by converting to the picrate or
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fractionally distill, collecting the fraction at 224-225<32> at 714 mm
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vacuo.
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The tropinones can be used in the above formula (or in a formula that
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you have found elsewhere) to be converted to cocaine. Remember to
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recrystallize the 2-carbomethoxytropinone before converting to
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methylecgonine.
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