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1111

Total Synthesis of
Ketamine
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Total Synthesis of Ketamine


While theres 11 steps in the synthesis, its longitude is explained by the fact that all the
precursors and even some reagents are made from scratch, employing user-friendly
techniques and equipment (in fact, a need for vacuum is mentioned only once, and even that is
for the removal of solvent); as well as only easy-to-get reactants.
Still the synth is obviously for the skilled only; for one thing, it involves making a Grignard.
There is a potential possibility to use zinc organic compounds instead (discussed in detail
below) which is much cheaper and easier technically.
Also there is added an alternate preparation of o-chlorobenzonitrile

Experimental

sodium nitrite
Sodium nitrate is also synthesized industrially by neutralizing nitric acid with soda
ash
2 HNO3 + Na2CO3 2 NaNO3 + H2O + CO2
nitric acid HNO3 Molar mass 63.01 g mol1 / Density 1.5129 g cm3
soda ash

Molar mass 105.9784 g/mol (anhydrous) 124.00 g/mol


(monohydrate) 286.14 g/mol (decahydrate)
Density 2.54 g/cm3 (anhydrous) 2.25 g/cm3 (monohydrate) 1.51 g/cm3
(heptahydrate)
1.46 g/cm3 (decahydrate)

756 GRAMS (498 ML,S) NITRIC ACID HNO3


636 GRAMS (246 ML,S) SODIUM CARBONATE (SODA ASH)

.
1. o-Chlorobenzoic acid

Anthranilic acid 13,7g


HCl (conc., d=1,19)
NaNO2 8g ( sodium nitrite)
CuCl 10g (Copper Chlorides)

13,7 grams anthranilic acid is stirred in a glass beaker in 40ml,s destiled water, 28ml,s
hydrochloric acid HCl and 20 grams ice. With constant stirring and cooling there's added 8
grams sodium nitrite NaNO2 in 40ml,ss water. Thus obtained clear solution of diazonium salt

is very slowly added with stirring into a soln. of 10 grams copper chloride CuCl in 25 grams
hydrochloric acid HCl conc. A vigorous evolution of nitrogen is observed.
When the rxn ends, the ppt is filtered, washed with cold water and reprecipitated from aq.
Sodium carbonate Na2CO3. The product represents fine crystals and melts at 140-141C.
o-Bromobenzoic acid can be obtained in an analogous manner, substituting copper chloride
CuCl for CuBr.
CuBr (ver)
Preparation of Copper Chlorides
I prepared cuprous chloride by mixing copper wire, CuCO3 and a excess of
commercial 20 % hydrochloric acid HCl and warming it near boiling point
until all copper was dissolved. It was the deposition of a white powder
(cuprous chloride). This product can't be dried because it oxydizes
quickly, it was washed with water.
Normal reaction is with copper wire or powder, cupric chloride CuCl2 and
hydrochloric acid HCl, but I had then CuCO3.
CuCO3 (ver)
Also cupric chloride was prepared by reacting a solution of CuCO3 with an
slightly excess of hydrochloric acid HCl, then evaporating water and
finally, when product starts to turn brown, air dried to give a hydrate
form.
copper wire
CuCO3
20 % hydrochloric acid HCl solution
---------------------------------------------------------------------------

2. o-Chlorobenzonitrile
Preparation A.
(RCOO)2Zn + Pb(SCN)2 = 2 RCN + ZnS + PbS + 2 CO2
The best results are obtained when a zinc salt is employed instead of free acid. This rxn is
unsuitable for amino-, nitro- and oxy- acids, but can bee used for bromo- and chlorobenzoic
acids.
To a hot soln of 50 grams sodium hydroxide NaOH in 400ml,s water there's added 195 grams
o-chlorobenzoic acid. Carefully neutralize with ammonium hydroxide NH3 or sodium
bicarbonate NaHCO3 and add with heating 105 grams (~5% excess) zinc sulphate ZnSO4 in
400 ml,s destiled water. The precipitated salt is dried for prolonged time at 200C and mixed
intimately with 205 grams (Lead(II) thiocyanate) Pb(SCN)2. The mixture is coffee ground and
dried at 120-140C for a prolonged time, then heated on open flame - the mixture melts and
gases are evolved.

Distilled nitrile is treated with hydroxide de ammonia NH4OH, steam-distilled and salted out.
Yield 137 grams (80%), mp 43-46C, bp 232C. The rxn usually takes place within 30-60
mins, but the duration of dryings makes the method quite time-consuming.
Preparation B.
This one doesn't require a prolonged drying. Sulfaminic acid is dirt cheap and can be acquired
without causing any suspicion.
..
Electrowinning processing leaches zinc from the ore concentrate by sulfuric acid:[81]
ZnO + H2SO4 ZnSO4 + H2O
.............................................................................................................................................
o-Bromobenzonitrile
50 grams o-Bromobenzamide and 35 grams (25 grams =theory) sulfaminic (sulfamic) acid is
thoroughly mixed and heated in a Wurtz flask. At 250-255C distillation begins, which is over
at 285-295C (takes approx. 1.5-2 hrs). The collected product is redistilled, yield 36 grams
(80% of theory). mp 53-57C, bp 251-253C
As I found recently, this can bee simplified yet more, by forming benzamides in situ from the
corresponding acid and urea..but since this is a very good route to substd benzaldehydes
from benzoic acids, Ill post it later separately.
..

ADIPIC ACID
Into a 3-litre three-necked flask, fitted with a dropping funnel, a mechanical
stirrer (1) and a long reflux condenser, place 1900 ml. (2700 g.) of concentrated
nitric acid, sp. gr. 1-42. Since oxides of nitrogen are evolved in the subsequent
oxidation, the reaction should be carried out in a fume cupboard, or the oxides of
nitrogen are led by a tube from the top of the condenser to a water trap (Fig.//, 8,
l,c). Heat the nitric acid to boiling, set the stirrer in motion, add a few drops of
ciclohexanol and make certain that these are acted upon by the acid before
adding more ; an explosion may result if cyclohexanol is allowed to accumulate
in the acid. Once the reaction has started, add 500 g. of cyclohexanol through
the dropping funnel at such a rate that all is introduced in 4-5 hours ; if the
addition of the secondary alcohol is too slow, the corks (2), which are attacked
by nitrous fumes, may have to be replaced before the operation is complete.
Keep the reaction mixture at the boiling point during the addition of the
cyclohexanol and for a further period of about 15 minutes in order to complete

the oxidation. Pour the warm reaction mixture into a beaker ; upon cooling, the
adipic acid crystallises.
Filter on a large sintered glass funnel, and wash with 200 ml. of cold
water. Recrystallise the crude acid from 700 ml. of concentrated nitric
acid ; filter and wash as above. The yield of recrystallised adipic acid,
m.p. 152, is 400 g. (3).
2700 grams
500 grams
200 ml,s
700 ml,s

concentrated nitric acid


cyclohexanol
destiled water.
concentrated nitric acid

..
3. Cyclopentanone
100 grams adipic acid and 10 grams barium hydroxide Ba(OH)2 is intimately mixed and
placed into a flask with a thermometer. The rxn is heated to 280 C, the mixture initially melts
and then the distillation takes place, which lasts about 1-2 hrs. The hot distillate is saturated
with sodium chloride NaCl, the upper layer is decanted and distilled, collecting the fraction
boiling at 128-130 C. Dry with magnesium sulphate MgSO4.
Yield: 51 grams (89% of theory).
Notes:

Ca(OH)2 may bee substituted for barium hydroxide Ba(OH)2 without much loss in the
yield.
if one is to use pre-made Calcium oxide Ca or Ba adipinate, no temp control is
necessary.
Ca(OH)2

(ver)

Ba adipinate (ver)
.........................................................................................................................................

4. Aluminium isopropoxide
Al(i-PrO)3 - Bp 130-140C at 7mmHg; mp 118C.

Into a 250 ml,s RBF equipped with an efficient reflux condenser there's added 6 grams Al
foil, 70 ml,s (51 ml,s in theory) abs. isopropanol IPA (commercial reagent grade isopropanol
IPA was used without any drying) and 0,1 grams sulfuric acid HgSO4. The mixture is heated.
In the beginning of boiling 0,5 ml,s (Macrophage inflammatory protein-1 (MIP-1) is a CC
chemokine CCl4 (CAREFUL! Extremely toxic!) and heating continued until hydrogen gas
H2 evolution starts, when it is stopped, sometimes even cooling's needed. After the rxn
subsides, heating is continued until almost full dissolution of aluminium metal Al (5-7 hrs).
The obtained solution is immediately used as is in the following preparation.
..
5. Cyclopentanol
Into a 250 ml,s RBF equipped with a 15 cm Vigreux column and distilling condenser there's
added 53 ml,s (50 grams) cyclopentanone in 50ml,s isopropanol IPA and the solt from the
previous prep, which contains about 40 grams Al isopropoxide. The rxn is gently heated,
which causes acetone with some water to distill off. The distillation is ended when the temp of
the vapors rises to ~85C.
The ppt inside the flask is carefully decomposed with 50% sulfuric acid H2SO4 until acidic
and saturated with sodium chloride NaCl. The upper layer is decanted and distilled, collecting
the fraction boiling at 137-140C. Drying with magnesium sulphate MgSO4.
Yield: 47grams (94%)
..

Sodium sulfate synthesis


it can be made by the rxn of sulphuric acid H2SO4 with sodium hydroxide NaOH
acid+base----> salt +water
2 NaOH+ H2SO4-----> Na2SO4+ 2 H2O
so you can mix (2M NaOH) and (1M H2SO4)
NaOH Molar mass 39.9971 g mol-1 / Density 2.13 g/cm3
H2SO4 (100%)

(1,8356 gcm-3 ) ( 98.08 g/mol)

or same concentration of both, but you have to double the amount of NaOH
then heat the product to evaporate the water and ur left with Na2SO4 which is of course
sodium sulphate
530 ML,S SULfURIC ACID H2SO4 (975 GRAMS H2SO4)
367 ML,S SODIUM HYDROXIDE (781,58 GRAMS NAOH)


6. Cyclopentylbromide
In a flask theres mixed 47ml,s (45grams) cyclopentanol and 60ml,s (90 grams) 48% aq. HBr.
10 grams sodium sulphate Na2SO4 is added. The rxn is left for 24hrs with vigorous stirring.
After that its diluted with 200 ml,s water and the lower organic phase is separated and
washed with water twice. Distill, collecting the fraction between 137-138C. Dryed with
magnesium sulphate MgSO4.
Yield = 58 grams (74%)

Hydrobromic acid
H2SO4 + KBr --> KHSO4 + HBr
220 grams of KBr (potassium bromide) or 190 gams of NaBr (sodium bromide) is dissolved
in 200 ml,s of distilled water and chilled in an ice bath. 90 ml,s of concentrated sulphuric acid
H2SO4 is chilled in the ice bath and then slowly added to the chilled bromide solution being
sure not to allow the temperature to rise above 75C, in order not to form any free bromine.
The solution is cooled to room temperature and the K2SO4 ( by product) that was formed is
filtered out. The solution is then placed in a 1000 ml,s boiling flask in a simple distillation
apparatus. Add a few boiling chips. Start a flow of water through the condenser and heat with
flame through a wire gauze. Water will distill over first, but when the temperature reaches
125C replace the receiving flask with a clean flask. Monitor the temperature as it will
continue to rise to 126C and remain there steadily until the constant boiling solution has
distilled over. When the temperature begins to drop stop the distillation. [It is important to
know the correct temperature in order to collect the proper fraction. To calibrate the
thermometer first boil water in the apparatus and note the temparature. If it reads 100 C, then
the thermometer reads correctly. If it reads say 101C, you should substract one degree when
reading your thermometer. If it reads say 99 C, you should add one degree when reading
your thermometer.] Even purer HBr can be obtained by redistilling and collecting the portion
boiling at 126 C.
The acid obtained is approximately 47.5% HBr with a density of 1.49g/ml.
Hydrobromic acid
220 grams of KBr (potassium bromide)

or

200 ml,s of distilled water


90 ml,s of concentrated sulphuric acid H2SO4
K2SO4 by product
Iodine Crystals

190 grams of NaBr (sodium bromide)

You will need:


Bunsen burner and asbestos square (or a hot plate)
Tripod and tin lid
Beaker, 250 ml,s
Separating funnel 100 ml,s
Evaporating dish
Hydrogen peroxide 20 volume
Tetrachloromethane or dichloromethane
Distilled water
1M solution of Sulphuric acid
Supply of ribbon seaweed (Laminaria) - that you can obtain a a biological supply store or
from the sea shore
Procedure
(You must work at a fume cupboard)
1-Collect and dry about a dozen 50 cm lenghts of the seaweed and heat them strongly on a tin
recipient until they are reduced to ash; probably it will reduce a quite small quantity, about a
spoonful.
2- Add to the ash 20 ml,s of distilled water in a beaker, and heat the suspension until it boils.
3 - Filter the suspension
4 - Acidify the filtered with Sulphuric acid solution
5 - Add then the hydrogen peroxide solution
You will observe the formation of a brown color due the iodine liberation from the iodine
ions present
6- Transfer the mixture to a separating funnel
7 -Extract the Iodine with tetrachloro methane or other solvent. The result is an organic
solution of iodine.
8 - In order to obtain crystals , the solvent may be allowed to evaporate at room temperature,
by placing it in an evaporating dish in a fume cupboard.
It will result crystals of iodine or rather gray-black brilliant flakes.
Hope that satisfies you. If you need a more sophisticated method, with a purifying step, just
ask again.
..
7. Cyclopentyl magnesium bromide
Into a 250 ml,s three-necked flask equipped with a reflux condenser, addition funnel and inert
gas inlet theres placed 50 ml,s THF (kept over potassium hydroxide KOH, prior to the rxn
150 ml,s refluxed over 30 grams CaO for 6hrs and distilled). 9 grams of fine magnesium Mg
turnings is added followed by some iodine crystals. The apparatus is flushed with argon and a
gentle stream of gas is left flowing in. Magnetic stirring is commenced. The mixture instantly
becomes cloudy from magnesium iodine MgI. From the addition funnel theres dripped 55
grams (40 ml,s) cyclopentyl bromide in 100 ml,s tetrahydrofuran THF so that the solt boils
smoothly. The rxn is usually over in an hour, it is accompanied by precipitation of a white
jelly-like mass, and at the bottom there may bee left some unreacted magnesium Mg as a
dark-grey powder.

CaO (ver)
Usage of tetrahydrofuran THF instead of ether is preferred since the rxn in it proceeds better
and faster (tetrahydrofuran THF is a more specific solvent for Grignards) , the yield is better
as well. Besides, tetrahydrofuran THF can be dried with CaO, while for ether ,sodium metal is
usually employed.
Notes on the possible usage of Zn-organics:
".. Nitriles are not bad as electrophiles, so it is possible that despite smaller reactivity of ZnR2
compounds, they would work equally well here - esp. if the rxn conditions are made harsher
(gentle reflux instead of RT?).
ZnR2

(ver)

What one CAN say for sure-is that the rxn with ZnR2 will go just fine if one is to use ochlorobenzoyl chloride instead of benzonitrile. Haloanhydrides generally are the best species
for coupling with metalorganics.
Bis-dicyclopentyl zinc is conveniently made from the corresponding bromide, no need to
make iodide here. And o-chlorobenzoyl chloride can be easily prepared from o-chlorobenzoic
acid (obtained in Step 1) and PCl5 or some such."

Ammonium chloride crystals


add dil. Hydrochloric acid HCl acid to NH3 amoniaco (aq) or NH4OH. don't add
NH3OH(aq) to HCl because it can create a highly exothermic reaction which might damage
you.
NH4OH + HCl --> NH4Cl(aq) + H2O
so according to this balanced equation do the amount calculations and add them in 1 : 1. then
heat the solution until you get the white crystals. water will be vapourised and you'll be left
with the crystals.
PARA ?????????????? DE AMMONIUM CHLORIDE CRYSTALS
1 LITRO ACIDO CLORIDRICO
1 LITRO DE AMONIACO

8. o-Chlorophenyl cyclopentyl ketone

To the thus obtained Grignard solt theres added 48 grams o-chlorobenzonitrile and the
mixture is stirred for 3 days at RT. It is then poured into a mixture of ice / ammonium
chloride NH4Cl, with addition of some conc. aq. Ammonia hydroxide NH3 and left at ambient
temp until all ice melts. The ketone partially floats, partially goes to the bottom. Its extracted
with benzene.
The yields fluctuate, but rarely drop below 55%.
.
9. alpha-Bromo-(o-chlorophenyl)-cyclopentyl ketone
40 grams ketone is dissolved in 70 ml,s (Macrophage inflammatory protein-1 (MIP-1) is a
CC chemokine CCl4 and with cooling in snow it is added into a solt of 48 grams dioxane
dibromide in 50 ml,s dioxane, and stirred at RT for 30mins. Then 30ml,sdestiled water are
added and the solt is washed with sodium carbonate Na2CO3 aq. until neutral. This may lead
to some preciptation of the bromoketone, which stays in (Macrophage inflammatory protein1 (MIP-1) is a CC chemokine CCl4. The solvent is removed, giving 47 grams (85%) of the
bromoketone.

10. (1-hydroxy-cyclopentyl)-(o-chlorophenyl)-N-methylketimine
45 grams of the above bromoketone is dissolved in 50 ml,s benzene, add there 50 ml,s
triethylamine (17g/23mL is required for neutralization of potassium bromine HBr, but a 2x
excess is used). The solt is then saturated with 5 grams methylamine, obtained by dripping a
saturated solt of 15 grams methanolic solution of methylamine hydrochloride MeNH2HCl
onto 10 grams sodium hydroxide NaOH, dried thru sodium hydroxide NaOH. The rxn is left
for 1 day and the solvents are removed under aspirator vacuum, giving 30 grams (80%) of
methylketimine.
.

Manufacture Of Ethyl Iodide


This is usually prepared by the action of iodine on alcohol in the presence of red phosphorus,
much as described under "ethyl bromide." Various proportions of ingredients have been
recommended. Thus Wurtz indicates phosphorus 7 parts, alcohol 35, and iodine 23; whilst
Frankland used these in the ratio of 7: 35: 14. According to Beilstein,
1 part of red phosphorus is placed in a retort with 5 parts of 90 per cent. alcohol, and then 10
parts of iodine are added gradually, and the mixture allowed to stand for twenty-four hours.
At the end of that period the retort is warmed, and the ethyl iodide distilled off. The crude
product is purified by washing first with dilute solution of sodium hydroxide, and then with
water, after which treatment it is dried over fused calcium chloride, and redistilled if
necessary.

Walker1 recommends the use of both red and yellow phosphorus, in equal quantities, and
obtains about 570 grams of the iodide for 500 grains of iodine used, or 93 per cent. of the
theoretical yield. As the dissolving of the iodine in the alcohol is tedious, he has devised an
arrangement to shorten the time and labour. This consists essentially in an adaptation of the
principle of the Soxhlet extractor to the purpose. A wide-mouthed, round-bottomed flask, of
about 1 litre capacity, carries a two-holed cork into which are fitted an adapter, serving as
receptacle for the iodine and a wide side-tube, up which the alcohol vapour passes. These are
connected at the top with a tube which passes to a reflux condenser. The arrangement is such
that when alcohol placed in the flask is boiled, its vapour passes up the side tube, is condensed
in the reflux condenser, falls back on the iodine contained in the adapter, dissolves more or
less of this iodine, and carries it down into the flask, where the solution of iodine in alcohol
reacts with the phosphorus present.
To obtain about 550 grams of ethyl iodide the ingredients used are 500 grams of iodine, 250
of alcohol, 30 of yellow phosphorus, and 30 of red phosphorus. The alcohol and the two kinds
of phosphorus are placed in the flask, with a few fragments of porous tile to prevent bumping,
and 100 grams of the iodine are packed tightly in the adapter. The flask is then connected up,
and heated on a water-bath to boil the alcohol. Distillation should not be allowed to proceed
too rapidly, as much heat is disengaged during the reaction. When all the iodine has been
dissolved, the heating is continued until there is no longer any coloration in the liquid due to
iodine. The flask is then cooled, and a fresh charge of iodine placed in the adapter, after which
the heating is re-commenced, and the operations repeated until the whole 500 grams of iodine
have been worked up.
When the reaction is completed, a small quantity of water is poured down the condenser to
destroy any phosphonium compounds which may have been formed. The flask is then
detached, and the liquid distilled off by means of a water-bath. The distillate, after being
washed with water, separated from the aqueous layer, and dried, is practically pure ethyl
iodide.
The chief precaution to be taken is the proper regulation of the temperature when the final
charge of iodine is being dealt with. Too much heat should be avoided, and the last stages
conducted slowly until experience has been gained.
Methyl iodide can be prepared in a similar manner.
30 Grams red phosphorus
30 Grams yellow phosphorus
250 Grams alcohol
iodine

(optional)
(synthesis)
(super mercados)

500 grams iodine crystals

(synthesis)

..

Diethylamine and triethylamine

The reaction which produces diethylamine also yields as byproducts


ethylamine and triethylamine The relative amounts of each compound
produced depends upon the molar ratio of the two starting materials.
Use of only a little ethyl iodide favors the formation of mostly ethylamine Use
of a lot of the ethyl iodide favors the formation of triethylamine Somewhere in
the middle, a roughly even split occurs.
This will be done here.
A section of clean steel pipe 2 or 3 inches in diameter is obtained, and fine
threads are cut into each end so that a cap may be screwed onto each end. A
really nice touch would be to have all the pieces
plated with a half-thousandths-inch of electroless nickel, but the plater may
think you are constructing a pipe bomb when he sees the pipe and caps.
The bottom of the pipe is secured by screwing the cap on over threads coated
with Teflon tape. Welding may also be used. The pipe is then nestled into a
Styrofoam cooler, and is then filled about 1/2 full of rubbing alcohol, and then
to this solvent dry ice is added, slowly at first to prevent it from boiling over,
then more rapidly. The top of the pipe should be covered to prevent frost
from forming inside the pipe as it cools down.
Next, add 175 ml,s of ethyl iodide to the pipe, and let it cool down. It will not
freeze, as its melting point is about 100 C below 0 C. Then liquid ammonia
is added to the pipe. This is best done by
inverting a cylinder of liquid ammonia, attaching plastic tubing to the valve,
and cracking open the valve to feed the liquid into the pipe. About 525 ml,s of
liquid ammonia is called for. In a 3-inch diameter pipe, that plus the ethyl
iodide will fill it half full. This is not an operation to be done in a residential
neighborhood, as the fumes are tremendous. A rural setting with beaucoup
ventilation is
more proper.
Now secure the top of the pipe by screwing on the cap tightly over Teflon
tape. The pipe is now moved into a tub of ice water, and allowed to sit in this
ice water for 45 minutes to an hour to warm up to 0 C.
When the pipe has warmed to 0 C, it should be shaken to mix the two
reactants, and returned to the ice water. This shaking should be repeated a
few times at 5-minute intervals. When 30 minutes have
passed from the first shaking, the pipe should be returned to the dry ice bath
and allowed to cool.
When the pipe has cooled, the cap on the top of the pipe is loosened.
Then the pipe is returned to the tub of ice water, and the ammonia is allowed
to slowly evaporate away. This will take overnight, and raise great plumes of
stink.
After most of the ammonia has evaporated, the contents of the pipe should
be emptied into a beaker. The foul substance is a mixture of ammonia,
ethlyamine, diethylamine, triethylamine, and the
hydriodides thereof. The best route to follow is to cool this mixture in, and
slowly add with stirring 90 grams of sodium hydroxide dissolved in 100 ml,s of
destiled water. This neutralizes the HI (ver) in the mix, yielding the freebases
of all.
This mixture should be extracted several times with toluene.
Toluene is chosen because it is available at the hardware store, and its
boiling point is higher than any of the amines. The extracts should be
filtered, and dried over sodium hydroxide pellets.

The toluene extracts should then be transferred to a flask, and the mixture
fractionally distilled through an efficient column Ethylamine distills at
16 C, diethylamine distills at 55 C, and triethlyamine distills at
89 C. The diethylamine fraction should be collected over a
20-degree range centered on 55 C, and this fraction then redistilled to get
the pure product. The yield of diethylamine is about 40 ml,s.
Absolute freedom from water in the product can be assured by letting the
crude distillate sit over a few chips of potassium hydroxide KOH for a few
hours prior to the final distillation.
10500 ml,s ethyl iodide
31500 ml,s liquid ammonia hydroxide
5400

grams sodium hydroxide

6000

ml,s

destiled water

Toluene
2

(for extraction)

kilos potassium hydroxide KOH

Bomb nickel coted


.
11. Ketamine
10 grams of methylketimine is dissolved in 100ml,s undecane and boiled at 195C for 3-4hrs.
Ketamine is extracted with 20% hydrochloric acid HCl. Acidic extract is basified and
extracted with dichloromethane DCM. Solvent is removed giving the product as an oil that
quickly crystallizes. It can bee purified by recrystallization from pentane/ether or
hexane/ether.
The yields are close to quantitative.
.
Preparation of Copper Chlorides
I prepared cuprous chloride by mixing copper wire, CuCO3 and a excess of
commercial 20 % hydrochloric acid HCl and warming it near boiling point
until all copper was
dissolved. It was the deposition of a white powder (cuprous chloride). This
product can't be dried because it oxydizes quickly, it was washed with
water.
Normal reaction is with copper wire or powder, CuCl2 and hydrochloric acid
HCl, but I had then CuCO3.
Also cupric chloride was prepared by reacting a solution of CuCO3 with an
slightly excess of hydrochloric acid HCl, then evaporating water and
finally, when product starts to turn brown, air dried to give a hydrate
form.

---------------------------------------------------------------------------

Total synthesis ( 100 grams )


o-Chlorobenzoic acid
274 grams Anthranilic acid

(synthesis)

200 ml,s

5% hypochlorite solution

400 ml,s

destiled water

40

phthalimide

(anthranilic acid synthesis)(lojas de piscinas)


(anthranilic acid synthesis)
(anthranilic acid synthesis) (ebay ver)

Hydrochloric acid HCl (conc., d=1,19)


160 grams NaNO2 (sodium nitrite)

(chines)
(synthesis)

756 GRAMS (498 ML,S) NITRIC ACID HNO3


(NaNO2 sodium nitrite)
636 GRAMS (246 ML,S) SODIUM CARBONATE (SODA ASH) (NaNO2 sodium nitrite)

200 grams CuCl (Copper Chlorides)

(synthesis)
(Copper Chlorides

300 grams copper wire

synthesis)
CuCO3
20 % hydrochloric acid HCl solution

(Copper Chlorides synthesis)


(Copper Chlorides synthesis)

o-Chlorobenzonitrile

1000 grams sodium hydroxide NaOH


16000 ml,s

destiled water

3900 grams o-chlorobenzoic acid


NH3 or NaHCO3 (sodium bicarbonate)

(chines)
(synthesis)
(synthesis)
(super market)

2100 grams (~5% excess) ZnSO4 (ZINC SULFATE)

(ver synthesis)

4100 grams Pb(SCN)2 (Lead(II) thiocyanate)

(ver synthesis)

NH4OH

( Hidrxido de amnio)

(ver)

Sulfaminic acid

( ver synthesis)

o-Bromobenzonitrile

1000 grams o-Bromobenzamide

(synthesis)

700 grams (500 grams sulfaminic (sulfamic) acid

( ver synthesis)

Cyclopentanone
2000 grams adipic acid

2700 grams
500 grams
200 ml,s
700 ml,s

( synthesis)

concentrated nitric acid


cyclohexanol
destiled water
concentrated nitric acid

(adipic acid synthesis)


(adipic acid synthesis)
(adipic acid synthesis)
(adipic acid synthesis)

200 grams Ba(OH)2 (Barium hydroxide )

( ebay)

Sodium chloride NaCl (table salt)

(super market)

MgSO4 (magnesium sulphate)

(farmacias)

Aluminium isopropoxide

120 grams Al foil


1400 ml,s
2

isopropanol IPA (isopropanol)

grams HgSO4 (sulfuric acid)

100 ml,s CCl4 (carbon tetrachloride)

(super market)
(conservar e restaurar , farmacias)
(conservar e restaurar)
(ver)

Cyclopentanol

1060 ml,s (1000 grams ) cyclopentanone

(synthesis)

1000 ml,s IPA (isopropanol)

(famacias , conservar e restaurar)

800 grams Al isopropoxide

(synthesis)

Cyclopentylbromide

940 ml,s

(900 grams ) cyclopentanol

(synthesis)

1200 ml,s

(1800 grams) 48% aq. HBr (hydrobromic acid)

(synthesis)

220g KBr (potassium bromide) or 190g NaBr (sodium bromide)((hydrobromic acid synthesis)
200 ml,s distilled water )
90

(hydrobromic acid synthesis)

ml,s concentrated H2SO4 )

((hydrobromic acid synthesis)

K2SO4

( by product hydrobromic acid synthesis)

2000 grams Na2SO4 (sodium sulphate)

(synthesis)

1060 ML,S SULfURIC ACID H2SO4

(sodium sulphate synthesis)

734

(sodium sulphate synthesis)

ML,S SODIUM HYDROXIDE

4000 ml,s destiled water

(synthesis)

MgSO4 (magnesium sulphate)

(farmacias)

Cyclopentyl magnesium bromide

1000 ml,s

tetrahydrofuran Thf
KOH (Potassium hydroxide)

600 grams CaO (Calcium oxide)

(ver where to get)


(ebay)
(ebay)

180 grams Mg turnings

(ver where to get)

iodine crystals

(synthesis)

Hydrogen peroxide 20 volume

( iodine crystals synthesis)

Tetrachloromethane (ver) or dichloromethane

( iodine crystals synthesis)

Distilled water

( iodine crystals synthesis)

1M solution of Sulphuric acid

( iodine crystals synthesis)

Supply of ribbon seaweed(Laminaria) - that you can obtain a a biological supply store or from
the sea shore
( iodine crystals synthesis)
argon gas

(cylinder or generator (ver)

1100 grams ( 800 ml,s ) cyclopentyl bromide


2000 ml,s

tetrahydrofuran THF

(synthesis)
(solvent)

(ver where to get)

o-Chlorophenyl cyclopentyl ketone

960 grams o-chlorobenzonitrile


NH4Cl

(synthesis)

(ammonium chloride)

(synthesis)

1 LITRO ACIDO CLORIDRICO

(Ammonium chloride synthesis)

1 LITRO DE AMONIACO

(Ammonium chloride synthesis)

NH3 (ammonia hydroxide)

(chines farmacias)

alpha-Bromo-(o-chlorophenyl)-cyclopentyl ketone

800 grams o-Chlorophenyl cyclopentyl ketone


1400 ml,s

CCl4 (carbon tetrachloride)

960 grams dioxane dibromide

(synthesis)
(ver)
(ver)

1000 ml,s

dioxane (solvent)

600 ml,s

destiled water

(where to buy)
(synthesis)

Na2CO3 (sodium carbonate)

(super market)

1-hydroxy-cyclopentyl)-(o-chlorophenyl)-N-methylketimine

900 grams alpha-Bromo-(o-chlorophenyl)-cyclopentyl ketone


1000 ml,s

benzene

1000 ml,s

triethylamine

(synthesis)
(lojas de tintas)
(synthesis)

100 grams methylamine

(synthesis)

10500 ml,s ethyl iodide

(triethylamine and methylamine synthesis)

31500 ml,s

(triethylamine and methylamine synthesis)

liquid ammonia

5400

grams sodium hydroxide

(triethylamine and methylamine synthesis)

6000

ml,s

(triethylamine and methylamine synthesis)

destiled water

Toluene (for extraction)

(triethylamine and methylamine synthesis)

(triethylamine and methylamine synthesis)

kilos potassium hydroxide KOH

Bomb nickel coted


630 Grams red phosphorus

(triethylamine and methylamine synthesis)


(synthesis)

(ethyl iodide synthesis)

630 Grams yellow phosphorus (optional)

(ethyl iodide synthesis)

5250 Grams ethyl alcohol

(synthesis)

(ethyl iodide synthesis)

iodine

(super mercados)

(ethyl iodide synthesis)

10500 grams iodine crystals

(synthesis)

(ethyl iodide synthesis)

300

grams methanolic solution methylamine hydrochloride MeNH2HCl

600

grams sodium hydroxide NaOH

(solution)
(chines)

Ketamine
200 grams methylketimine

(synthesis)

2000 ml,s undecane

(ver )

20% hydrochloric acid HCl

(solution)

Dichloromethane DCM (solvent)

(lojas de tintas)

Pentane / ether or hexane / ether

(ver)

Synthesis of Ketamine

(2)

Ketamine is more difficult to synthesize than the previously considered PCP derivatives.
Although it is currently a popular and common drug on the illicit market, it is obtained
exclusively by diversion of commercial sources rather than synthesis. This route has an
overall yield of ~60%, with a difficulty rating of 2-3 out of 10 and a hazard rating of 1-2 out
of 10 (ref. 64). The general necessity of producing anhydrous methylamine in a clandestine
setting, rather than purchasing it, increases the difficulty. Use of propylamine rather than
methylamine would simplify this reaction, as its boiling point is above room temperature vs.
methylamine, which is a gas at room temperature.
The syntheis starts with the reaction of cyclopentyl Grignard and o-chlorobenzonitrile to give
o-chlorophenyl-cyclopentyl ketone, followed by alpha bromination of the ketone, and then
reaction with methylamine to form an alpha-hydroxy imine (1-Hydroxycyclopentyl-(ochlorophenyl)-ketone-N-methylimine). Heating this imine results in Ketamine via a novel
alpha-hydroxyimine rearangement (refs. 20, 21, 22, 23, 24 ). Overall yields are ~60%.
Tiletamine is synthesized by an analogous process in industry, substituting 2-thiophenyl
magnesium bromide for the phenyl grignard and ethylamine for methylamine. Two other
ketamine analogs have been found on the black market: the compound missing the 2-chloro
group on the phenyl ring, and its N-ethyl analog. Both of these compounds are most likely
more potent and longer lasting than ketamine.

Synthetic procedure for ketamine synthesis:


Step 1: (o-chlorophenyl)-cyclopentyl ketone
Cyclopentanone
100 grams adipic acid and 10 grams Ba(OH)2 is intimately mixed and placed into a flask with
a thermometer. The rxn is heated to 280 C, the mixture initially melts and then the
distillation takes place, which lasts about 1-2 hrs. The hot distillate is saturated with sodium
chloride NaCl, the upper layer is decanted and distilled, collecting the fraction boiling at 128130C. Dry with magnesium sulphate MgSO4.
Yield: 51 grams (89% of theory).

Aluminium isopropoxide
Al(i-PrO)3 - Bp 130-140C at 7mmHg; mp 118C.
Into a 250 ml,s RBF equipped with an efficient reflux condenser there's added 6 gams Al foil,
70 ml,s (51ml,s in theory) abs. isopropanol IPA (commercial reagent grade IPA was used
without any drying) and 0,1 grams sulfuric acid HgSO4. The mixture is heated.

In the beginning of boiling 0,5 ,ml,s Macrophage inflammatory protein-1 (MIP-1) is a CC


chemokine CCl4 (CAREFUL! Extremely toxic!) and heating continued until hydrogen gas
H2 evolution starts, when it is stopped, sometimes even cooling's needed. After the rxn
subsides, heating is continued until almost full dissolution of aluminium metal Al (5-7 hrs).
The obtained solution is immediately used as is in the following preparation
.
Cyclopentanol
Into a 250 ml,s RBF equipped with a 15 cm Vigreux column and distilling condenser there's
added 53 ml,s (50 grams ) cyclopentanone in 50 ml,s isopropanol IPA and the solT from the
previous prep'n, which contains about 40 grams Al isopropoxide. The rxn is gently heated,
which causes acetone with some water to distill off. The distillation is ended when the temp of
the vapors rises to ~85C.
The ppt inside the flask is carefully decomposed with 50% sulfuric acid H2SO4 until acidic
and saturated with sodium chloride NaCl. The upper layer is decanted and distilled, collecting
the fraction boiling at 137-140C. Drying with magnesium sulphate MgSO4.
Yield: 47 grams (94%)

Cyclopentyl bromide
In a flask theres mixed 47 ml,s (45 grams) cyclopentanol and 60 ml,s (90 grams) 48% aq.
HBr. 10 grams sodium sulphate Na2SO4 is added. The rxn is left for 24hrs with vigorous
stirring. After that its diluted with 200 ml,s water and the lower organic phase is separated
and washed with water twice. Distill, collecting the fraction between 137-138C. Dryed with
mangnesium sulphate MgSO4.
Yield = 58 ramsg (74%)
cyclopentyl Grignard reagent
119.0 grams of cyclopentyl bromide and 19.4 grams of magnesium are reacted in ether or
tetrahydrofuran THF to give a cyclopentyl Grignard reagent.
...

Phthalimide to anthranilic acid


Go to the great big building supply house and pick up a couple of gallons of swimming pool
chlorination liquid. This stuff is 5% sodium hypochlorite. Yep, the same stuff as Clorox
bleach but twice as strong and several times less expensive. Now go to the chemicalsupply
and get a pound or so of phthalimide. This stuff costs about US$5.00 a pound and is
unwatched and uncontrolled. Quantities can be purchased also in 25 pound bags, but you have
to wait for it to come in.

In a 2 liter erlinmeyer flask put 200 ml,s of the hypochlorite solution and 400 ml,s of destiled
water. Mix well and cool to less than 30 C, 20 C is a perfect temperature. Now add 40
grams of phthalimide all at once. This is about 4 rounded tablespoons for the scale impared
out there. Stir this mess rapidly. The phthalimide will not dissolve, it will get wet and mix in
the solution. It'll also try to crawl up the sides of the flask a half inch or so. After a couple of
minutes of stirring (the warmer the solution, the less the time. Remember cooler is better) the
reaction will happen. The solution's temperature will rise and start to release gas. It will
appear to boil with the phthalimide changing into anthranilic acid and foaming on the top of
the now yellow colored liquid. Shake the flask and try to keep it all wet. Let the reaction
proceed for 3 minutes shaking often, add an equal volume of cold water, stir to cool down and
vacuum filter to collect the solids. One thing to note here is that you should use two coffee
filters to filter this. This is concentrated anthranilic acid and bleach, it will eat right through
the filter if you take too long filtering it. So filter quick and get the filter paper out and lay it
on a couple of paper towels to wick away more of the solution. Discard the filtered yellow
solution, there isn't enough product in there to bother with.
The anthranilic will try to cling to the sides of the flask and you'll have to rinse the flask a few
times to get it all into the filter paper, this is ok since it will also rinse away the rest of the
bleach solution leaving slightly yellow crystals.
You now have quite a pile of slightly impure anthranilic acid that needs to be recrystalized to
purify. Don't you just love it when people say, "recrystalize from water."? You try this and
either nothing happens and you lose your product or it comes out dirtier than when you
started. To clean this stuff dissolve it in boiling water, filter and let the water cool to
recrystalize the anthranilic. However, it is not very soluble in boiling water and almost not at
all in cold water, so it will take a heck of a lot of water to do the job.
Do it like this: put the anthranilic in a 1 liter flask, add 300 ml,s of destiled water and boil. Be
careful, watching it for boil over. The anthranillic acid forms long thin needle crystal that just
love to attach to bubbles forming in the boiling water and foam up. This foam will easily boil
out of the flack if you don't pay attention. Pour the boiling solution through 2 coffee filter
using only gravity. When the boiling solution starts to cool, it will immediately crystalize into
pretty white crystals. As it cools off, more will form until at around 25 C it's all out of
solution. The residual powder in the filter and flask needs another boiling water treatment to
get some more anthranilic acid. Keep this put-powder-in-flask, boil, filter operation going
until you don't get crystals in the filtered water. After all the solutions (you'll have multiple
containers) have cooled, vacuum filter and dry the powder. This operation will take as much
as 4 liters of water, so be patient and keep with it.
Possiblities of screw up. Heat is your enemy in the first part of the reaction, start off cool, be
sure to add the water to cool it off and filter it quickly to make sure the operation doesn't
proceed to far. If it gets too hot it'l turn dark and clean up is horrible. When recrystalizing
don't boil the solution too long or it will turn dark. Just bring it to a boil and filter, then do the
next boiling operation. DO NOT try to dissolve all of it in the water, you may be able to do it,
but it will certainly turn dark and ruin the batch. Some one may read how the solubility of the
anthranillic in water can be increased by adding sodium hydroxide NaOH to the water. This is
true, but it will also result in the anthranilic decomposing. Keep the sodium hydroxide NaOH
in the cupboard on the other side of the room. It would be best if you take it a half mile away
just to be sure.

The crystals when dry are mostly small needles, that fluff up and take a lot of space for the
weight. Needless to say there is substantial mechanical loss to this procedure, and it can be a
pain in the butt. The yield is only around 50%, but at US$5.00 for the phthalimide and almost
nothing for the sodium hypochlorite it is really cost effective and provides one with a good
source of this controlled substance.
200 ml,s

5% hypochlorite solution

400 ml,s

destiled water

40 grams phthalimide

o-Chlorobenzoic acid
Anthranilic acid 13,7 grams

(synthesis)

Hydrochloric acid HCl (conc., d=1,19)


8 grams NaNO2 (sodium nitrite)

(chines)
(synthesis)

10 grams CuCl (Copper Chlorides)

(ver where to get)

13,7 grams anthranilic acid is stirred in a glass beaker in 40 ml,s destiled water, 28 ml,s
hydrochloric acid HCl and 20 grams ice. With constant stirring and cooling there's added 8
grams sodium nitrite NaNO2 in 40 ml,s water. Thus obtained clear solution of diazonium salt
is very slowly added with stirring into a soln. of 10 grams copper chloride CuCl in 25 grams
hydrochloric acid HCl conc. A vigorous evolution of nitrogen is observed.
When the rxn ends, the ppt is filtered, washed with cold water and reprecipitated from aq.
Sodium bicarbonate Na2CO3. The product represents fine crystals and melts at 140-141C.
o-Bromobenzoic acid can bee obtained in an analogous manner, substituting copper chloride
CuCl for CuBr
CuBr
...
o-chlorobenzonitrile
Preparation A.
(RCOO)2Zn + Pb(SCN)2 = 2 RCN + ZnS + PbS + 2 CO2
The best results are obtained when a zinc salt is employed instead of free acid. This rxn is
unsuitable for amino-, nitro- and oxy- acids, but can bee used for bromo- and chlorobenzoic
acids.

To a hot soln of 50 grams sodium hydroxide NaOH in 400 ml,s water there's added 195 grams
o-chlorobenzoic acid. Carefully neutralize with ammonia hydride NH3 or sodium bicarbonate
NaHCO3 and add with heating 105 grams (~5% excess) zinc sulphate ZnSO4 in 400 ml,s
destiled water. The precipitated salt is dried for prolonged time at 200C and mixed intimately
with 205 grams Lead(II) thiocyanate Pb(SCN)2. The mixture is coffee ground and dried at
120-140C for a prolonged time, then heated on open flame - the mixture melts and gases are
evolved.
Distilled nitrile is treated with hydroxide ammonia NH4OH, steam-distilled and salted out.
Yield 137 grams (80%), mp 43-46C, bp 232C. The rxn usually takes place within 30-60
mins, but the duration of dryings makes the method quite time-consuming.
Preparation B.
This one doesn't require a prolonged drying. Sulfaminic acid is dirt cheap and can be acquired
without causing any suspicion.
..
The best yields are obtained if the ether solvent is distilled from the Grignard under vacuum
and replaced with hydrocarbon solvent, such as benzene.
55.2 grams of o-chlorobenzonitrile is then added to the reaction mixture and stirred for three
days. The reaction is then hydrolyzed by pouring it onto a mixture of crushed ice and
ammonium chloride, containing some ammonium hydroxide. Extracion of the mixture with
organic solvent gives o-chlorophenylcyclopentylketone, bp 96-97 C (0.3 mm Hg) (CAS#
6740-85-8).

Step 2: alpha-bromo (o-chlorophenyl)-cyclopentyl ketone


To 21.0 grams of the above ketone is added 10.0 grams of bromine in 80 ml,s of carbon
tetrachloride dropwise at 0 deg. C. After all of the Br2 has been added, an orange suspension
forms. This is washed with a dilute aqueous solution of sodium bisulfite and evaporated to
give 1-bromocyclopentyl-(o-chlorophenyl)-ketone, bp 111-114 C (0.1 mm Hg). Yield is
~66%. This bromoketone is unstable and must be used immediately. Also attempts to distill it
at 0.1 mm Hg lead to some decomposition, so it should be used without further purification.
The bromination may also be carried out with N-bromosuccinimide in somewhat higher
yields (~77%).
.

N-bromosuccinimide (NBS)

1.62 mol (160 grams) succinimide is dissolved in a mixture of 1.60mol (64 grams) sodium
hydroxide NaOH, 300 grams crushed ice and 400 ml,s destiled water. Cool the mixture in an
ice bath, and add 85 ml,s (1.65 mol, 264 grams) Br2 at once while stirring violently. Stir for
two more minutes, then filter the precipitated product and wash with ice water. Dry in a
desiccator. Yield 75-81%.
Don't clean up NBS too much, the stinky yellow stuff still containing a bit of Br2 works best.
1.62 mol (160 grams) succinimide
1.60mol (64 grams) sodium hydroxide NaOH,
300 grams crushed ice
400 ml,s destiled water
85 ml,s (1.65 mol, 264 grams) Br2

Methylamine from Ammonium Chloride and


Formaldehyde
Many bees are making methylamine out of hexamine and HCl acid. I think it's very time
consuming and HCl is pretty nasty. Thus I have found that one can easily make lots of good
quality methylamine from ammonium chloride and formaldehyde (formalin). Only drawback
with this method is that one must have good quality formaldehyde. It may have
paraformaldehyde sediment in the bottom, it doesn't hurt, not even a bit, but Formaldehyde
has to be strong and not some diluted shit, 35-40% is fine.
Now to the more-less foolproof method. If you do like said below, you get around 400-450
grams of pretty pure dimethylamine-free methylamine hydrochloride which is perfect for
Al/Hg reductive aminations.

Chemicals needed:

1100g of Ammonium Chloride


2 liters of 35-40% Formaldehyde
about half a litre of chloroform

The process

Pour your formaldehyde in a big round bottom flask (use at


least one of 5 liter capacity) along with ammonium chloride
and stir a bit. I used a 12 L RB flask. Start heating slowly,
and stir it every once in a while.
[ At 40C ] - [At 80C]
At about 90C, an exothermic reaction kicks in (it needs to
be cooled in a water bath once in a while at the beginning
in order to keep temperature below 104-106C).

Soon reaction slows down and cooling isn't needed anymore, reaction flask
must be heated carefully to keep temperature at 104-106C.

Keep that temperature 3-4 hours or so, then turn heat up and boil water away
until you see ammonium chloride coming out of solution. Cool to 20C and

vacuum filter it off on large Buchner funnel (I have one with 25 cm).
You should get a clear yellowish filtrate like in this picture.

Transfer it to a smaller flask and boil water away until you see
the internal temperature rise over 160C, then turn on the vacuum and continue,
first temperature falls a few tens of degrees and when it rises back to about
160C the methylamine is almost free of water. Turn off the vacuum and the heat.

Pour your crude methylamine hydrochloride in a beaker. At first it is still liquid


(in this picture it has started to solidify, you can still see some orange liquid
at the bottom of the beaker).

When it has cooled down, you'll have a big chunk of hard and dry methylamine.
Wash it a few times with chloroform and you'll end up with a fully white mush.
Vacuum filter to get pure and dry Methylamine.HCl which reeks of chloroform.
The smell can be removed by drying in a vacuum desiccator. Do not try to use
the oven to get rid of these traces of chloroform, the Methylamine.HCl picks up
water from air like nothing. You can only use vacuum for sucessful drying but
these CHCl3 traces don't hurt the methylamine at all and may be left in, but you
might perhaps be a perfectionist...

Final yield of snow white non-sticky powder, (consisting of methylamine with a


few percent ammonium chloride, but and almost no dimethylamine hydrochloride),
easily exceeds 400g if everything done correctly, or even 500g if you used
40% formaldehyde.
......................................................................................................................................................
Step 3: 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine
29.0 grams of above bromoketone is dissolved in 50 ml,s of liquid methylamine freebase.
Benzene may also be used as solvent. After one hour, the excess liquid methylamine is
allowed to evaporate, although increasing the reaction time to 4-5 days may increase yield.
The residue is then dissolved in pentane and filtered. The solvent is evaporated to yield 1hydroxy-cyclopentyl-(o-chlorophenyl)-ketone N-methylimine, mp 62 C (yield ~84%).
Step 4: 2-Methylamino-2-(o-chlorophenyl)-cyclohexanone (Ketamine)
The final step is a thermal rearrangement, and gives almost quantitative yield after 180 C for
30 min. An alternative to the use of decalin as solvent in this step is to use a pressure bomb.
2.0 grams of the preceeding N-methylimine is dissolved in 15 ml,s of decalin and refluxed
for 2.5 h. After evaporation of the solvent under reduced pressure, the residue is extracted
with dilute hydrochloric acid, the solution treated with decolorizing charcoal, and the
resulting acidic solution is made basic. The liberated product, 2-methylamino-2-(ochlorophenyl)-cyclohexanone (Ketamine), after recrystallization from pentane-ether, has a mp
of 92-93C. The hydrochloride has a mp of 262-263 C.

As with PCE, the freebase is too caustic to be smoked, and must be converted into the
hydrochloric HCl salt in order to be consumed in this manner.

Total synthesis 100 grams


Step 1: (o-chlorophenyl)-cyclopentyl ketone
Cyclopentanone
17000 grams adipic acid

( ver)

1700 grams Ba(OH)2 (Barium hydroxide )

( ebay)

Sodium chloride NaCl (table salt)

(super market)

MgSO4 ( magnesium sulphate)

(farmacias)

Aluminium isopropoxide

7344 grams Al foil


85680 ml,s

(super market)

isopropanol IPA

123

grams HgSO4 (sulfuric acid)

620

ml,s

(conservar e restaurar , farmacias)


(conservar e restaurar)

CCl4(Macrophage inflammatory protein-1 (MIP-1) is a CC chemokine ) (ver)

Cyclopentanol

8109 ml,s (7650g) cyclopentanone

(synthesis)

7650 m,ls

IPA isopropanol

( conservar e restaurar , farmacias)

6120 grams

Al isopropoxide

(synthesis)

cyclopentyl bromide
5355

grams cyclopentanol

(synthesis)

10710 grams 48% aq. HBr (hydrobromic acid)

( synthesis)

220g KBr (potassium bromide) or 190g NaBr (sodium bromide)((hydrobromic acid synthesis)
200 ml,s distilled water

(hydrobromic acid synthesis)

90

(hydrobromic acid synthesis)

ml,s concentrated H2SO4

K2SO4
1190

( by product hydrobromic acid synthesis)


grams Na2SO4 sodium sulphate

23800 ml,s

(synthesis)

destiled water

(synthesis)

Sodium chloride NaCl (table salt )

(super market)

50% sulfuric acid H2SO4


MgSO4

(solution)

magnesium sulphate

(farmacias)

o-Chlorobenzoic acid

15228

grams Anthranilic acid

152400

ml,s

5% hypochlorite solution

304800

ml,s

destiled water

30480

grams

(synthesis)
(anthranilic acid synthesis)(lojas de piscinas)

phthalimide

Hydrochloric acid HCl (conc., d=1,19)


8736 grams NaNO2 ( sodium nitrite)

(anthranilic acid synthesis)


(anthranilic acid synthesis) (ebay ver)
(chines)
( synthesis)

6804 GRAMS
NITRIC ACID HNO3
(NaNO2 sodium nitrite)
6724 GRAMS SODIUM CARBONATE (SODA ASH)

10920 grams CuCl (Copper Chlorides)


12

kilos copper wire

(NaNO2 sodium nitrite)

(synthesis)
( Copper Chlorides synthesis)

(ver) CuCO3
20 % hydrochloric acid HCl solution

( Copper Chlorides synthesis)


( Copper Chlorides synthesis)

o-chlorobenzonitrile

1800

grams sodium hydroxide NaOH

44800 ml,s

(chines)

destiled water

(synthesis)

10920 grams o-chlorobenzoic acid

(synthesis)

NH3 ammonia hydroxide or NaHCO3 (sodium bicarbonate) (chines / super market)


5880 grams (~5% excess) ZnSO4 (zinc sulphate)

(ver)

11480 grams Pb(SCN)2 (Lead(II) thiocyanate)

(ver synthesis)

NH4OH (hydroxide de amonio)

cyclopentyl Grignard reagent (synthesis)

11900 grams cyclopentyl bromide

(synthesis)

1940 grams magnesium turnings

(where to get)

ether or thf
benzene (opitional)

(synthesis)
(lojas de tintas)

5520 grams o-chlorobenzonitrile

(synthesis)

ammonium chloride

(synthesis)

1 LITRO ACIDO CLORIDRICO

(Ammonium chloride synthesis)

1 LITRO DE AMONIACO

(Ammonium chloride synthesis)

ammonium hydroxide

(chines e farmacias)

Step 2: alpha-bromo (o-chlorophenyl)-cyclopentyl ketone

2100 grams o-chlorophenyl)-cyclopentyl ketone

(synthesis)

1000 grams bromine

(lojas de piscinas e ebay)

8000 ml,s carbon tetrachloride

(where to buy)

sodium bisulfite

(ebay)

N-bromosuccinimide (OPITIONAL)

(synthesis)

1.62 mol (160 grams) succinimide

(N-bromosuccinimide synthesis)

1.60mol (64 grams) sodium hydroxide NaOH

(N-bromosuccinimide synthesis)

300 grams crushed ice

(N-bromosuccinimide synthesis)

400 ml,s destiled water

(N-bromosuccinimide synthesis)

85 ml,s (1.65 mol, 264 grams) Br2

(N-bromosuccinimide synthesis)

Step 3: 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine

2900 grams alpha-bromo (o-chlorophenyl)-cyclopentyl ketone

(synthesis)

5000 ml,s

(synthesis)

methylamine

14300 grams Ammonium Chloride

(methylamine synthesis)

26

liters 35-40% Formaldehyde

(methylamine synthesis)

6500

ml,s

(methylamine synthesis)

chloroform

14300 LITRO ACIDO CLORIDRICO

(Ammonium chloride synthesis)

14300 LITRO DE AMONIACO

(Ammonium chloride synthesis)

Benzene (opitional)
pentane ?

(lojas de tintas)
(ver)

Step 4: 2-Methylamino-2-(o-chlorophenyl)-cyclohexanone (Ketamine)

1500 ml,s
200

decalin (solvent) (OPITIONAL)

grams 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine
hydrochloric acid

(ver)
(synthesis)
(chines)

decolorizing charcoal

(ver)

pentane-ether

(ver)