Professional Documents
Culture Documents
Total Synthesis of
Ketamine
[Type the document subtitle]
[Type the abstract of the document here. The abstract is typically a short summary of the
contents of the document. Type the abstract of the document here. The abstract is typically a
short summary of the contents of the document.]
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
.
1. o-Chlorobenzoic acid
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
..
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%)
..
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
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."
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.
.
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)
(synthesis)
..
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
6000
ml,s
destiled water
Toluene
2
(for extraction)
---------------------------------------------------------------------------
(synthesis)
200 ml,s
5% hypochlorite solution
400 ml,s
destiled water
40
phthalimide
(chines)
(synthesis)
(synthesis)
(Copper Chlorides
synthesis)
CuCO3
20 % hydrochloric acid HCl solution
o-Chlorobenzonitrile
destiled water
(chines)
(synthesis)
(synthesis)
(super market)
(ver synthesis)
(ver synthesis)
NH4OH
( Hidrxido de amnio)
(ver)
Sulfaminic acid
( ver synthesis)
o-Bromobenzonitrile
(synthesis)
( ver synthesis)
Cyclopentanone
2000 grams adipic acid
2700 grams
500 grams
200 ml,s
700 ml,s
( synthesis)
( ebay)
(super market)
(farmacias)
Aluminium isopropoxide
(super market)
(conservar e restaurar , farmacias)
(conservar e restaurar)
(ver)
Cyclopentanol
(synthesis)
(synthesis)
Cyclopentylbromide
940 ml,s
(synthesis)
1200 ml,s
(synthesis)
220g KBr (potassium bromide) or 190g NaBr (sodium bromide)((hydrobromic acid synthesis)
200 ml,s distilled water )
90
K2SO4
(synthesis)
734
(synthesis)
(farmacias)
1000 ml,s
tetrahydrofuran Thf
KOH (Potassium hydroxide)
iodine crystals
(synthesis)
Distilled water
Supply of ribbon seaweed(Laminaria) - that you can obtain a a biological supply store or from
the sea shore
( iodine crystals synthesis)
argon gas
tetrahydrofuran THF
(synthesis)
(solvent)
(synthesis)
(ammonium chloride)
(synthesis)
1 LITRO DE AMONIACO
(chines farmacias)
alpha-Bromo-(o-chlorophenyl)-cyclopentyl ketone
(synthesis)
(ver)
(ver)
1000 ml,s
dioxane (solvent)
600 ml,s
destiled water
(where to buy)
(synthesis)
(super market)
1-hydroxy-cyclopentyl)-(o-chlorophenyl)-N-methylketimine
benzene
1000 ml,s
triethylamine
(synthesis)
(lojas de tintas)
(synthesis)
(synthesis)
31500 ml,s
liquid ammonia
5400
6000
ml,s
destiled water
(synthesis)
iodine
(super mercados)
(synthesis)
300
600
(solution)
(chines)
Ketamine
200 grams methylketimine
(synthesis)
(ver )
(solution)
(lojas de tintas)
(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.
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.
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.
...
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)
(chines)
(synthesis)
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).
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
Chemicals needed:
The process
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.
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...
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.
( ver)
( ebay)
(super market)
(farmacias)
Aluminium isopropoxide
(super market)
isopropanol IPA
123
620
ml,s
Cyclopentanol
(synthesis)
7650 m,ls
IPA isopropanol
6120 grams
Al isopropoxide
(synthesis)
cyclopentyl bromide
5355
grams cyclopentanol
(synthesis)
( synthesis)
220g KBr (potassium bromide) or 190g NaBr (sodium bromide)((hydrobromic acid synthesis)
200 ml,s distilled water
90
K2SO4
1190
23800 ml,s
(synthesis)
destiled water
(synthesis)
(super market)
(solution)
magnesium sulphate
(farmacias)
o-Chlorobenzoic acid
15228
152400
ml,s
5% hypochlorite solution
304800
ml,s
destiled water
30480
grams
(synthesis)
(anthranilic acid synthesis)(lojas de piscinas)
phthalimide
6804 GRAMS
NITRIC ACID HNO3
(NaNO2 sodium nitrite)
6724 GRAMS SODIUM CARBONATE (SODA ASH)
(synthesis)
( Copper Chlorides synthesis)
(ver) CuCO3
20 % hydrochloric acid HCl solution
o-chlorobenzonitrile
1800
44800 ml,s
(chines)
destiled water
(synthesis)
(synthesis)
(ver)
(ver synthesis)
(synthesis)
(where to get)
ether or thf
benzene (opitional)
(synthesis)
(lojas de tintas)
(synthesis)
ammonium chloride
(synthesis)
1 LITRO DE AMONIACO
ammonium hydroxide
(chines e farmacias)
(synthesis)
(where to buy)
sodium bisulfite
(ebay)
N-bromosuccinimide (OPITIONAL)
(synthesis)
(N-bromosuccinimide synthesis)
(N-bromosuccinimide synthesis)
(N-bromosuccinimide synthesis)
(N-bromosuccinimide synthesis)
(N-bromosuccinimide synthesis)
Step 3: 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine
(synthesis)
5000 ml,s
(synthesis)
methylamine
(methylamine synthesis)
26
(methylamine synthesis)
6500
ml,s
(methylamine synthesis)
chloroform
Benzene (opitional)
pentane ?
(lojas de tintas)
(ver)
1500 ml,s
200
grams 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine
hydrochloric acid
(ver)
(synthesis)
(chines)
decolorizing charcoal
(ver)
pentane-ether
(ver)