FOREWORD

Ladies and gentlemen!

Let me proudly introduce to you another story from Zealots dream

collection.

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
zincorganic compounds instead (discussed in detail beelow) which is
much cheaper and easier technically.

Also there is added an alternate preparation of o-chlorobenzonitrile by

zealot.

With this said, lets get to business.

- Antoncho

EXPERIMENTAL

1. o-Chlorobenzoic acid

Anthranilic acid 13,7g

HCl (conc., d=1,19)

NaNO2 8g

CuCl 10g

13,7g anthranilic acid is stirred in a glass beaker in 40mls water, 28mls HCl and
20g ice. With constant stirring and cooling there's added 8g NaNO 2 in 40mls
water. Thus obtained clear solution of diazonium salt is very slowly added with
stirring into a soln. of 10g CuCl in 25g 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. Na2CO3. The product represents fine crystals and melts
at 140-141C.

o-Bromobenzoic acid can bee obtained in an analogous manner, substituting

CuCl for CuBr.

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 50g NaOH in 400mls water there's added 195g o-chlorobenzoic
acid. Carefully neutralize with NH3 or NaHCO3 and add with heating 105g (~5%
excess) ZnSO4 in 400mls water. The precipitated salt is dried for prolonged time
at 200C and mixed intimately with 205g Pb(SCN) 2. The mixture is
coffeeground 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 NH4OH, steam-distilled and salted out. Yield 137g
(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 bee acquired without causing any suspicion.

o-Bromobenzonitrile

50g o-Bromobenzamide and 35g (25g=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 36g (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.

3. Cyclopentanone

100g adipic acid and 10g Ba(OH)2 is intimately mixed and placed into a flask
with a thermometer. The rxn is heated to 280C, the mixture initially melts and
then the distillation takes place, which lasts about 1-2 hrs. The hot distillate is
saturated with NaCl, the upper layer is decanted and distilled, collecting the
fraction boiling at 128-130C. Dry with MgSO4.

Yield: 51g (89% of theory).

Notes:

Ca(OH)2 may bee substituted for Ba(OH)2 without much loss in the yield.

if one is to use pre-made Ca or Ba adipinate, no temp control is

necessary.

4. Aluminium isopropoxide

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

Into a 250ml RBF equipped with an efficient reflux condenser there's added 6g
Al foil, 70mls (51mls in theory) abs. IPA (commercial reagent grade IPA was
used without any drying) and 0,1g HgSO4. The mixture is heated.

In the beginning of boiling 0,5mls CCl4 (CAREFUL! Extremely toxic!) and

heating continued until H2evolution starts, when it is stopped, sometimes even
cooling's needed. After the rxn subsides, heating is continued until almost full
dissolution of Al (5-7 hrs). The obtained solution is immediately used as is in
the following preparation.

5. Cyclopentanol

Into a 250ml RBF equipped with a 15cm Vigreux column and distilling
condenser there's added 53mls (50g) cyclopentanone in 50mls IPA and the soln
from the previous prep'n, which contains about 40g 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% H2SO4 until acidic and
saturated with NaCl. The upper layer is decanted and distilled, collecting the
fraction boiling at 137-140C. Drying with MgSO4.

Yield: 47g (94%)

6. Cyclopentylbromide

In a flask theres mixed 47mls (45g) cyclopentanol and 60mls (90g) 48% aq.
HBr. 10g Na2SO4 is added. The rxn is left for 24hrs with vigorous stirring. After
that its diluted with 200mls water and the lower organic phase is separated and
washed with water twice. Distill, collecting the fraction between 137-138C.
Dryed with MgSO4.

Yield = 58g (74%)

7. Cyclopentyl magnesium bromide

Into a 250mls three-necked flask equipped with a reflux condenser, addition

funnel and inert gas inlet theres placed 50mls THF (kept over KOH, prior to the
rxn 150mls refluxed over 30g CaO for 6hrs and distilled). 9g of fine 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 beecomes cloudy from MgI. From the addition funnel
theres dripped 55g (40mls) cyclopentyl bromide in 100mls THF so that the soln
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 maybee left
some unreacted Mg as a dark-grey powder.

Usage of THF instead of ether is preferred since the rxn in it proceeds better
and faster (THF is a more specific solvent for Grignards) , the yield is better as
well. Beesides, THF can bee 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 ZnR2compounds, they would work
equally well here - esp. if the rxn conditions are made harsher
(gentle reflux instead of RT?).
 What one CAN say for sure-is that the rxn with ZnR 2 will go just
fine if one is to use o-chlorobenzoyl chloride instead of
benzonitrile. Haloanhydrides generally are the best species for
coupling with metalloorganics.

Bis-dicyclopentyl zinc is conveniently made from the

corresponding bromide, no need to make iodide here. And o-
chlorobenzoyl chloride can bee easily prepared from o-
chlorobenzoic acid (obtained in Step 1) and PCl5 or some such."

8. o-Chlorophenyl cyclopentyl ketone

To the thus obtained Grignard soln theres added 48g o-chlorobenzonitrile and
the mixture is stirred for 3 days at RT. It is then poured into a mixture of
ice/NH4Cl, with addition of some conc. aq. 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 beelow 55%.

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

40g ketone is dissolved in 70mls CCl4 and with cooling in snow it is added into a
soln of 48g dioxane dibromide in 50mls dioxane, and stirred at RT for 30mins.
Then 30mls water are added and the soln is washed with Na 2CO3 aq. until
neutral. This may lead to some preciptation of the bromoketone, which stays in
CCl4. The solvent is removed, giving 47g (85%) of the bromoketone.

10. (1-hydroxy-cyclopentyl)-(o-chlorophenyl)-N-methylketimine

45g of the above bromoketone is dissolved in 50mls benzene, add therein

50mls triethylamine (17g/23mL is required for neutralization of HBr, but a 2x
excess is used). The soln is then saturated with 5g methylamine, obtained by
dripping a saturated soln of 15g MeNH2HCl onto 10g NaOH, dried thru NaOH.
The rxn is left for 1 day and the solvents are removed under aspirator vacuum,
giving 30g (80%) of methylketimine.

11. Ketamine

10g of methylketimine is dissolved in 100mls undecane and boiled at 195C for

3-4hrs. Ketamine is extracted with 20% HCl. Acidic extract is basified and
extracted with 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.

Synthesis of Ketamine :
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-(o-chlorophenyl)-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

119.0 g of cyclopentyl bromide and 19.4 g of magnesium are reacted in ether

or THF to give a cyclopentyl Grignard reagent. 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 g 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 g of the above ketone is added 10.0 g of bromine in 80 ml 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%).

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

29.0g of above bromoketone is dissolved in 50 ml 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 1-hydroxy-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 g of the preceeding N-methylimine is dissolved in 15 ml 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-(o-chlorophenyl)-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 HCl salt in order to be consumed in this manner.

Next Section: Structure Activity Relationships of PCP Analogs

Back to Contents

Ketamine's hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. The chemical
structure bears absolutely no resemblance to common salts.

Though I don't think home-based ketamine synthesis is realistic (usually, ketamine is

obtained from vet suppliers), here are the instructions, just for kicks:

Step 1: (o-chlorophenyl)-cyclopentyl ketone

119.0 g of cyclopentyl bromide and 19.4 g of magnesium are reacted in ether or THF to give
a cyclopentyl Grignard reagent. 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 g 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 g of the above ketone is added 10.0 g of bromine in 80 ml 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%).

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

29.0g of above bromoketone is dissolved in 50 ml 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 1-hydroxy-
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 g of the preceeding N-methylimine is dissolved in 15 ml 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-(o-chlorophenyl)-
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 HCl
salt in order to be consumed in this manner.

And here's a supposedly more "user-friendly" ketamine synthesis:

1. o-chlorobenzoic acid.

Anthranilic acid 13,7g

HClconc. (d=1,19)

NaNO2 8g

CuCl 10g

13,7g anthranilic acid is stirred in a glass beaker in 40mls water, 28mls HCl and 20g ice. With
constant stirring and cooling there's added 8g NaNO2 in 40mls water. Thus obtained clear
solution of diazonium salt is very slowly added with stirring into a soln. of 10g CuCl in 25g
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.
Na2CO3. The product represents fine crystals and melts at 140-141 C.

O-bromobenzoic acid can bee obtained in an analogous manner, substituting CuCl for CuBr.
2. o-chlorobenzonitrile.

Preparation A

(RCOO)2Zn + Pb(CNS)2 = 2RCN + ZnS + PbS + 2CO2

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 50g NaOH in 400mls water there's added 195g o-chlorobenzoic acid.
Carefully neutralize with NH3 or NaHCO3 and add with heating 105g (~5% excess) ZnSO4 in
400mls water. The precipitated salt is dried for prolonged time at 200 C and mixed intimately
with 205g Pb(SCN)2. The mixture is coffeeground and dried at 120-140 C for a prolonged
time, then heated on open flame - the mixture melts and gases are evolved.

Distilled nitrile is treated with NH4OH, steam-distilled and salted out. Yield 137g (80%),
mp=43-46 C, bp=232 C. The rxn usually takes place within 30-60 mins, but the duration of
dryings makes the method quite time-consuming.
Preparation B.

This one doesnt require a prolonged drying. Sulfaminic acid is dirt cheap and can
bee acquired without causing any suspicion.

o-bromo-benzonitrile.

50g o-Br-benzamide and 35g (25g=theory) sulfaminic(sulfamic) acid is thoroughly mixed

and heated in a Wurtz flask. At 250-255 C distillation begins, which is over at 285-295 C
(takes approx. 1,5-2 hrs). The collected product is redistilled, yield 36g (80% of theory).

mp = 53-57o, bp = 251-253o

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.

3.Cyclopentanone.

100g adipinic(adipic) acid and 10g 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 NaCl, the upper
layer is decanted and distilled, collecting the fraction boiling at 128-130 C. Dry with MgSO4.

Yield 51g (89% of theory).

Notes:

- Ca(OH)2 may bee substituted for Ba(OH)2 without much loss in the yield.

- if one is to use pre-made Ca or Ba adipinate, no temp control is necessary.

4. Aluminium isopropoxide.

Bp = 130-140C at 7mmHg; mp = 118C

Into a 250ml RBF equipped with an efficient reflux condenser there's added 6g Al foil, 70mls
(51mls in theory) abs. IPA (commercial reagent grade IPA was used without any drying) and
0,1g HgSO4. The mixture is heated.

In the beginning of boiling 0,5mls CCl4 (CAREFUL! Extremely toxic!) and heating continued
until H2 evolution starts, when it is stopped, sometimes even cooling's needed. After the rxn
subsides, heating is continued until almost full dissolution of Al (5-7 hrs). The obtained
solution is immediately used as is in the following preparation.
5. Cyclopentanol.

Into a 250ml RBF equipped with a 15cm Vigreux column and distilling condenser there's
added 53mls (50g) cyclopentanone in 50mls IPA and the soln from the previous prep'n,
which contains about 40g 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
~85 C.

The ppt inside the flask is carefully decomposed with 50% H2SO4 until acidic and saturated
with NaCl. The upper layer is decanted and distilled, collecting the fraction boiling at 137-140
C. Drying with MgSO4.
Yield 47g (94%)
6. Cyclopentylbromide.

In a flask theres mixed 47mls (45g) cyclopentanol and 60mls (90g) 48% aq. HBr.
10g NaSO4 is added. The rxn is left for 24hrs with vigorous stirring. After that its
diluted with 200mls water and the lower organic phase is separated and washed with water
twice. Distill, collecting the fraction between 137-138 C. Dryed with MgSO4.

Yield = 58g (74%)

7. Cyclopentyl magnesium bromide.

Into a 250mls three-necked flask equipped with a reflux condenser, addition funnel and inert
gas inlet theres placed 50mls THF (kept over KOH, prior to the rxn 150mls refluxed
over 30g CaO for 6hrs and distilled). 9g of fine 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 beecomes cloudy from MgI. From the
addition funnel theres dripped 55g (40mls) cyclopentyl bromide in 100mls THF so
that the soln 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 maybee left some unreacted
Mg as a dark-grey powder.

Usage of THF instead of ether is preferred since the rxn in it proceeds better and faster (THF
is a more specific solvent for Grignards) , the yield is better as well. Beesides, THF can bee
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?).

What one CAN say for sure-is that the rxn with ZnR2 will go just fine if one is to use o-
chlorobenzoyl chloride instead of benzonitrile. Haloanhydrides generally are the best species
for coupling with metalloorganics.

Bis-dicyclopentyl zinc is conveniently made from the corresponding bromide, no need to

make iodide here. And o-chlorobenzoyl chloride can bee easily prepared from o-
chlorobenzoic acid (obtained in Step 1) and PCl5 or some such."

8. (O-chlorophenyl)-cyclopentylketone.

To the thus obtained Grignard soln theres added 48g o-chlorobenzonitrile and the
mixture is stirred for 3 days at RT. It is then poured into a mixture of ice/NH4Cl, with
addition of some conc. aq. 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 beelow 55%.

9. alpha-bromo-(o-chlorophenyl)-cyclopentyl ketone.

40g ketone is dissolved in 70mls CCl4 and with cooling in snow it is added into a soln of 48g
dioxane dibromide in 50mls dioxane, and stirred at RT for 30mins. Then 30mls water are
added and the soln is washed with NaHCO3 aq. until neutral. This may lead to some
preciptation of the bromoketone, which stays in CCl4. The solvent is removed, giving 47g
(85%) of the bromoketone.
10. (1-hydroxy-cyclopentyl)-(o-chlorophenyl)-N-methylketimine.

45g of the above bromoketone is dissolved in 50mls benzene, add therein 50mls
(17g(=23mls) is required for neutralization of HBr, but a 2x excess is used). The soln is then
saturated with 5g methylamine, obtained by dripping a saturated soln of 15g MeNH2*HCl
onto 10g NaOH, dried thru NaOH. The rxn is left for 1 day and the solvents are removed
under aspirator vacuum, giving 30g (80%) of methylketimine.
11. Ketamine.

10g of methylketimine is dissolved in 100mls undecane and boiled at 195 C for 3-4hrs.
Ketamine is extracted with 20% HCl. Acidic extract is basified and extracted with 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.

Benzene is not a good organic solvent as it is carcinogenic, therefore I would suggest to use
diethyl ether instead. I understand that benzene is widely used solvent in the lab, however I
suspect the persons utilising this method are probably not highly skilled chemists nor have a
proper laboratory in order to carry out purification thechniques to a very high standard,
hence my suggestion.