SYNTHESIS OF PHENYL-2-PROPANONE

Phenylacetone (103-79-7)

PRODUCT NAME

Phenylacetone

Phenylacetone (known also as phenylpropan-2-one, benzyl methyl ketone, or methyl benzyl ketone), is an organic

compound. It is a clear oil with a refractive index of 1.5168. This substance is used in the manufacture of

methamphetamine and amphetamine as a starting material or intermediate, where it is commonly known as P2P. Due to

the illicit uses in clandestine chemistry, it was declared a schedule II controlled substance in the United States 11

February 1980.

Preparation

There are many methods in the scientific literature to prepare phenylacetone, and due to its status as a controlled

substance, there is crossover into popular literature such as works by Uncle Fester and Alexander Shulgin. Large

amounts of data are available on the Internet relating to the preparation of phenylacetone.

A conceptually simple example of phenylacetone organic synthesis is the Friedel-Crafts alkylation of benzene with

chloroacetone.

Phenylacetone can also be produced from many other compounds. For example:

phenylacetic acid is distilled with lead acetate or calcium acetate to yield phenylacetone.

benzaldehyde is reacted with nitroethane yielding phenyl-2-nitropropene, which is reduced, usually in the presence of

acid, to phenylacetone.

Phenyl acetone is used as an intermediate to produce pesticides and anticoagulants. Active ingredients as

anticoagulants include:

Brodifacoum

Chlorophacinone

Coumachlor

Difenacoum

Diphenadione

2-Pivaloyl-1,3-indandione

2-Isovaleryl-1,3-indandione

Warfarin

3,4-Methylenedioxyphenylpropan-2-one (MDP2P) is a chemical compound consisting of a phenylacetone moiety

substituted with a methylenedioxy functional group. It is commonly synthesized from either safrole ((which, for

comparison, is 3-[3,4-(methylenedioxy)phenyl]-1-propene) or its isomer isosafrole via oxidation using the Wacker

oxidation or peroxyacid oxidation methods.

MDP2P is a precursor in the chemical synthesis of the methylenedioxyphenethylamine (MDxx) class of compounds, the

classic example of which is 3,4-methylenedioxy-N-methylamphetamine (MDMA), and is also an intermediate between

the MDxx family and their slightly more distant precursor safrole or isosafrole. On account of its relation to the MDxx

chemical class, MDP2P, as well as safrole and isosafrole, are in the United States (U.S.) Drug Enforcement

Administration (DEA) List I of Chemicals of the Controlled Substances Act (CSA) via the Chemical Diversion and

Trafficking Act (CDTA).

Phenyl acetone, use Phenyl acetone, Phenyl acetone in india, best quality Phenyl acetone Phenyl acetone, use Phenyl acetone, Phenyl acetone in india, Phenyl acetone in bulk, best quality Phenyl acetone, Phenyl Acetone (1 Phenyl 2-Propanone), phenylacetone india, CAS NO.:103-79-7 - Phenyl Acetone p2p, P2P, benzyl methyl ketone, phenyl 2 propanone, phenyl acetone manufacturers, phenyl acetone suppliers, phenyl acetone exporters, phenylacetone

manufacturers, Manufacturers, Suppliers & Exporters, fine chemicals, MulBerry Chemicals Pvt. Ltd. Phenyl Acetone, 1 Phenyl 2-Propanone, manufacturers, CAS NO.:103-79-7, chemicals manufacturer India, supply, trade, export, manufacturing, fine chemicals, Intermediaries, phenylacetone, phenyl acetone, phenyl acetone chemicals, phenyl-2-propanone, benzyl methyl ketone, methyl benzyl ketone, buy, best quality, manufacturers, suppliers, exporters,

mumbai, india, chemical, chemicals, p2p, P2P, chlorohexanone, 6 chlorohexanone, benzyl methyl ketone, phenyl 2 propanone, phenyl acetone manufacturers, phenyl acetone suppliers, phenyl acetone exporters, chloro hexanone, dibutyl ether, 1,4 dioxane, 6 methyl quinoline, 2 isobutyl quinoline, 6(8)secondary butyl quinoline, manufacturers, exporters, suppliers, mumbai, india Phenyl Acetone, 1-Phenyl 2-Propanone CAS NO.:103-79-7 - MulBerry Chemicals

Pvt. Ltd high quality chemicals Phenyl Acetone, phenylacetone manufacturers, Di-n-butyl Ether, 1, 4 Dioxine, Quinoline and Substituted Quinoline and Grignard reagents etc. We are manufacturers, supplier, exporter of Phenyl Acetone chemicals in India, provides chemicals, p2p,benzyl methyl ketone, phenyl 2 propanone, phenyl acetone manufacturers, phenyl acetone suppliers, phenyl acetone exporters, chloro hexanone, dibutyl ether, 1,4 dioxane, 6 methyl

quinoline, 2 isobutyl quinoline, 6(8)secondary butyl quinoline, manufacturers, suppliers and exporters in India.phenylacetone, phenyl acetone, phenyl acetone chemicals, phenyl-2-propanone, benzyl methyl ketone, methyl benzyl ketone, buy, best quality, manufacturers, suppliers, exporters, mumbai, india, dialnsearch Phenyl Acetone - Manufacturers, Suppliers and Exporters phenylacetone, (or phenyl-2-propanone, benzyl methyl ketone or methyl benzyl

ketone. Often it's referred to as P2P) is an organic compound. It is a clear oil with a refractive index of 1.5168. This substance is used in the manufacture of methamphetamine and amphetamine as a starting material or intermediate. Due to the illicit uses in clandestine chemistry, it was declared a schedule II controlled substance in the United States

Synthesis of Phenyl-2-Propanone (P2P)

Table of Contents

Table of Contents

Introduction

P2P from Benzyl Cyanide

P2P from Phenylacetic Acid

Friedel-Crafts Alkylation of Benzene with 2-Nitropropane

Reduction of Phenyl-2-Nitropropene

Friedel-Crafts Alkylation of Benzene with Chloroacetone

Hydrolysis of Ephedrine Derivatives

Electrochemical Coupling of Benzyl Chloride and Acetic Anhydride

Nickel-mediated Coupling of Benzyl Chloride and Acetyl Chloride

Semipinacol Rearrangement of Phenyl-2-Propanal

P2P from Bromobenzene/Acetone Enolate

Radical Alkylation of Benzene with Acetone, catalyzed by Mn3+

Oxythallation of alpha-methylstyrene

Wittig reaction of Benzaldehyde

Cu(I)-catalyzed Arylation of Potassium Acetylacetonate

Pd-catalyzed Arylation of Isopropenyl Acetate

Alkylation of Benzyl cyanide with Trimethylaluminium

P2P from Phenylacetaldehyde and Dimethyl Cadmium

P2P from Phenylacetyl Chloride and Dimethyl Cadmium

P2P via Grignard Addition to Acetic Anhydride

P2P via Grignard Addition to Benzyl Cyanide

References

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

\

Introduction

Aside from the often amateurish reduction of (pseudo)ephedrine to methamphetamine, the most

popular precursor to amphetamine and methamphetamine is phenyl-2-propanone (also called

P2P, BMK, Benzyl Methyl Ketone or Phenylacetone). There is an astounding array of synthetic

routes to this compound, both due to the relative simple structure of the compound, and also

because of its popularity. Many of the earliest routes to the compound has been more or less

abandoned due to restrictions on the pre-precursors used to make it, but there has always sprung

up new methods of performing the feat of making this compound. Here is a collection of some of

the possible methods of synthesizing phenyl-2-propanone, ranging from simple one-step methods

to elaborate multi-step variants, and from the very easy to the very complicated. Welcome to the

world of P2P.

Many of the syntheses can also be tweaked to produce substituted phenyl-2-propanones, such as

the ever popular MDMA precursor MDP2P (3,4-methylenedioxyphenyl-2-propanone) by using

starting materials with the desirable aromatic substituents.

Appearance: Clear oil, flowery odor

Boiling Point: 214-216C/760mmHg, 86-87C/6mmHg

Melting Point: -15C

Molecular Weight: 134.19 g/mol

Density: 1.0057 g/ml (20C)

Refractive Index: 1.5168

Phenyl acetone, use Phenyl acetone, Phenyl acetone in india, best quality Phenyl acetone Phenyl acetone, use Phenyl acetone, Phenyl acetone in india, Phenyl acetone in bulk, best quality Phenyl acetone, Phenyl Acetone (1 Phenyl 2-Propanone), phenylacetone india, CAS NO.:103-79-7 - Phenyl Acetone p2p,

P2P, benzyl methyl ketone, phenyl 2 propanone, phenyl acetone manufacturers, phenyl acetone suppliers, phenyl acetone exporters, phenylacetone manufacturers, Manufacturers, Suppliers & Exporters, fine chemicals, MulBerry Chemicals Pvt. Ltd. Phenyl Acetone, 1 Phenyl 2-Propanone, manufacturers, CAS

NO.:103-79-7, chemicals manufacturer India, supply, trade, export, manufacturing, fine chemicals, Intermediaries, phenylacetone, phenyl acetone, phenyl acetone chemicals, phenyl-2-propanone, benzyl methyl ketone, methyl benzyl ketone, buy, best quality, manufacturers, suppliers, exporters, mumbai, india,

chemical, chemicals, p2p, P2P, chlorohexanone, 6 chlorohexanone, benzyl methyl ketone, phenyl 2 propanone, phenyl acetone manufacturers, phenyl acetone suppliers, phenyl acetone exporters, chloro hexanone, dibutyl ether, 1,4 dioxane, 6 methyl quinoline, 2 isobutyl quinoline, 6(8)secondary butyl quinoline,

manufacturers, exporters, suppliers, mumbai, india Phenyl Acetone, 1-Phenyl 2-Propanone CAS NO.:103-79-7 - MulBerry Chemicals Pvt. Ltd high quality chemicals Phenyl Acetone, phenylacetone manufacturers, Di-n-butyl Ether, 1, 4 Dioxine, Quinoline and Substituted Quinoline and Grignard reagents etc. We are

manufacturers, supplier, exporter of Phenyl Acetone chemicals in India, provides chemicals, p2p,benzyl methyl ketone, phenyl 2 propanone, phenyl acetone manufacturers, phenyl acetone suppliers, phenyl acetone exporters, chloro hexanone, dibutyl ether, 1,4 dioxane, 6 methyl quinoline, 2 isobutyl quinoline,

6(8)secondary butyl quinoline, manufacturers, suppliers and exporters in India.phenylacetone, phenyl acetone, phenyl acetone chemicals, phenyl-2-propanone, benzyl methyl ketone, methyl benzyl ketone, buy, best quality, manufacturers, suppliers, exporters, mumbai, india, dialnsearch Phenyl Acetone -

Manufacturers, Suppliers and Exporters phenylacetone, (or phenyl-2-propanone, benzyl methyl ketone or methyl benzyl ketone. Often it's referred to as P2P) is an organic compound. It is a clear oil with a refractive index of 1.5168. This substance is used in the manufacture of methamphetamine and amphetamine as

a starting material or intermediate. Due to the illicit uses in clandestine chemistry, it was declared a schedule II controlled substance in the United States

Phenyl-2-Propanone from Benzyl Cyanide

alpha-Phenylacetoacetonitrile1

A solution of sodium ethoxide is prepared from 60 g. (2.6 mol) clean sodium and 700 ml of

absolute alcohol (dried over calcium oxide or sodium) in a 2000 ml round-bottomed flask equipped

with a reflux condenser. To the hot solution added a mixture of 234g (2 moles) of pure benzyl

cyanide 264g (3 moles) of dry ethyl acetate (dried by refluxing over P2O5 for 30min followed by

distillation). The mixture is thoroughly shaken, the condenser closed with a calcium chloride tube,

and the solution heated on the steam bath for two hours before standing overnight. The next

morning the mixture is stirred with a wooden rod to break lumps, cooled in a freezing mixture to -

10C, and kept at this temperature for two hours. The sodium salt is collected on a 6 inch Buchner

funnel and washed four times on the funnel with 250 ml portions of ether. The filter cake is

practically colorless and corresponds 250-275g of dry sodium salt, or 69-76% of the calculated

mount. The combined filtrates are placed in the freezing mixture until they can be worked up as

indicated below.

The sodium salt still wet with ether is dissolved in 1.3 liters of distilled water at room temperature,

the solution cooled to 0C, and the nitrile precipitated by adding slowly, with vigorous shaking, 90

ml of glacial acetic acid, while the temperature is kept below 10C. The precipitate separated by

suction filtration and washed four times on the funnel with 250 ml portions of water. The moist

cake weighing about 300g corresponds to 188-206g (59-64%) of dry colorless alpha-

phenylacetoacetonitrile, mp 87-89C.

Phenyl-2-Propanone2

350 ml of concentrated sulfuric acid is placed in a 3000ml flask and cooled to -10C. The total first

crop of moist alpha-phenylacetoacetonitrile obtained according to the procedure above

(corresponding to 188-206g or 1.2-1.3 moles of dry product) is added slowly, with shaking, the

temp being kept below 20C (If pure dry alpha-phenylacetoacetonitrile is used, half its weight of

water should be added to the sulfuric acid or charring will take place on the steam bath). After all is

added the flask is warmed on the steam bath until solution is complete and then for five minutes

longer. The solution is cooled to 0C, 1750ml of water added rapidly, and the flask placed on a

vigorously boiling water bath and heated for two hours, with occasional shaking. The ketone forms

a layer and, after cooling, is separated and the acid layer extracted with 600ml of ether. The oil

and ether layers are washed successively with 100ml of water, the ether combined with the oil and

dried over 20g of anhydrous sodium sulfate. The sodium sulfate is collected on a filter, washed

with ether, and discarded. The ether is removed from the filtrates, and the residue distilled from a

modified Claisen flask with a 25 cm fractionating side arm. The fraction boiling at 110-112C at 24

mmHg is collected; it weighs 125-150g (77-86% of the theoretical amount).

A somewhat higher yield has been obtained by a different variation of this synthesis, originating

from Russia.

Phenyl-2-Propanone from Phenylacetic Acid

In this reaction, it is important that acetic anhydride is present in the reaction mixture in a large molar excess over the

phenylacetic acid. If the ratio is too small, the phenylacetone will condense with itself to form useless Dibenzyl Ketone.

Sodium Acetate Method (alternative)3b

The Phenylacetic Acid (PAA), Acetic Anhydride (AA) and Sodium Acetate (NaOAc) is put in to a large round-bottomed

flask equipped with a reflux condenser fitted with a drying tube. Heating of the reaction mixture to 145-150C on an oil

bath provides sufficiently energetic evolution of carbon dioxide. Formation of the ketone is controlled by mixing an

aliquot of the reaction mixture with excess of water and ammonium hydroxide until weakly alkaline upon heating to

boiling the oily layer must not disappear.

The reflux setup is rearranged for distillation and excess solvent is removed (acetic acid and acetic anhydride, purify

and reuse). To the residue there is added 400ml water and the mixture is extracted with 3x100mL dichloromethane (or

chloroform). The solvent is stripped off under vacuum and by vacuum distilling at 125-135C/30-32 mmHg the crude

product is obtained. A second distillation gives 50-55% yield of product boiling at 210-215C at atmospherical

pressure. Phenyl-2-Propanone Ketoxime was obtained in 88-90% yield, which was distilled at 154-156C/30mmHg.

Sodium Acetate Method (alternative)3b

50 g phenylacetic acid, 25 g anhydrous sodium acetate and 850 ml acetic anhydride are refluxed with stirring under

moisture protection for 40 h. 500 ml acetic anhydride and acetic acid are distilled off, the rest is mixed with 1000 ml

water after cooling down, the crude product is extracted with 2x250ml dichloromethane and the pooled organic layers

are washed with cold diluted sodium hydroxide solution (any formed P2P enol ester must be hydrolyzed) until no more

acids are present in the organic layer. The solution is dried over Na2SO4 and the dichloromethane is distilled off under

ordinary pressure (and is saved for reuse) the rest of the volatiles are evaporated in vacuo, and the crude phenyl-2-

propanone is vacuum distilled at 25 mmHg, bp 120-140C. The yield about 30ml (70%).

Potassium Acetate/Copper Sulfate3c

To a mixture of 136 g (1.0 mol) phenylacetic acid, 70 g sodium or potassium acetate, and 16 g (0.1 mol) anhydrous

cupric sulphate is introduced 2000 ml anhydrous acetic anhydride in 4000 ml flask. The mixture is refluxed 24 h. After

cooling 500 ml of solvent (CCl4, CHCl3, CH2Cl2) is added and the mixture is poured to a flask containing 2000 ml ice-

water. After separation of layers upper layer is removed and lower layer is three times decanted with water, separated,

dried (Na2SO4, CaCl2), and distilled. The solvent is distilled off and fractionation column is placed on the top of the

flask. Remaining acetic acid and acetic anhydride is then removed, pure product is collected at 100C/15mmHg. Yield

70-90 g (52-67%).

Pyridine Method5

A mixture of phenylacetic acid (13.6 g, 0.1 mol), acetic anhydride (50 ml) and pyridine (50 ml) was refluxed six hours

(in the beginning carbon dioxide evolution was vigorous. After removal of the solvent the residue was taken up in

toluene and washed with 10% sodium hydroxide. Removal of the solvent left a residue witging 12g, which on fractional

vacuum distillation gave 7.5 g (56%) phenyl-2-propanone, bp 30-64C/0.1mmHg.

Lead Acetate Method6

Place 1000g phenylacetic acid and 3000g anhydrous (or trihydrate) lead acetate in a distillation apparatus and heat.

First an amount of water will distill, and next phenyl-2-propanone in this destructive distillation, which requires liberal

application of heat. The distillate will separate into two layers. The organic layer is separated and redistilled to give

pure phenyl-2-propanone, bp 105C/10 mmHg or 216C at atmospherical pressure.

A considerable improvement to this method has been made by Xtaldoc on a large scale.

The Lead(II)Acetate can be substituted with Calcium(II)Acetate, making the synthesis more environmentally friendly.

Methyllithium addition to Phenylacetic Acid27

In a 100ml rb flask equipped with a side tube for a gas inlet capillary, a reflux condenser protected by a sodium

hydroxide drying tube and magnetic stirring was placed 0.026 mole (3.5 g) of phenylacetic acid dissolved in 50 ml of

ether, and the air was then expelled with a rapid stream of dry nitrogen. After 2-3 minutes the gas stream was slowed

down, just to create sufficient bubbles for stirring the solution during the experiment.

When all air had been expelled 0.055 mole of an ethereal solution of methyllithium was added through the condenser.

A vivid reaction took place, the ether refluxed, and a white precipitate was formed (lithium salt of the acid). After the

addition of all the methyllithium the precipitate partly dissolved and a weakly opalescent solution was obtained. If

necessary, the solution was then refluxed for 10-30 minutes to complete the reaction. After the solution had reached

room temperature, water was slowly added. The excess of methyllithium was thus destroyed and lithium hydroxide

was formed from the intermediate dilithium salt.

The alkaline water layer, which contained the lithium salt of unreacted acid, was removed in a separatory funnel, and

the ethereal layer washed three times with half its volume of water. The ether solution was then dried over magnesium

sulphate, filtered and the ether driven off, first at ordinary pressure and then at aspirator vacuum to give 2.65g (76%)

of phenylacetone, usually pure enough for most purposes.

Phenyl-2-propanone by nitroalkylation of benzene

Titanium Tetrachloride Method7

To a stirred solution of 2-nitropropene (0.1 mol, 8.7g) in dry CH2Cl2 (300ml) was added benzene (0.5 mol, 39g) at

room temperature. Titanium tetrachloride (0.1 mol, 19g) was then added dropwise into the mixture with stirring at the

same temperature. After being stirred for 60 min (or when the starting material completely disappears on TLC), water

(150 ml) was added and the resultant heterogenous mixture was stirred at reflux for 2h. The organic phase was

separated, the aqueous phase extracted with CH2Cl2, and the pooled organic extracts washed with 1 M Na2CO3

solution and dried over MgSO4. Evaporation of the solvent followed by vacuum distillation (bp 100-101C at 14mmHg)

afforded Phenyl-2-propanone (ca 9g, 70% of theory).

Triflic Acid Method14

A solution of 2-nitropropene (300 mg) in benzene (30 equivalents) was added to a well-stirred solution of CF3SO3H

(10 equivalents with respect to 2-nitropropene) and benzene with the co-solvent of methylene chloride cooled to -40C

in a dry ice-acetone bath. The reaction mixture was immediately (after 1 minute) poured into large excess dry

methanol (100 mL) cooled to -78C with vigorous stirring. After being warmed to ambient temperature (10-15 min), the

yellow solution was diluted with water (150 mL), neutralized with powdered NaHCO3 and saturated with NaCl. The

solution was extracted with CH2Cl2, dried over Na2SO4, and concentrated, and the residue was flash

chromatographed (on SiO2, eluting with CH2Cl2:n-hexane 12:7) to give pure phenyl-2-propanone, 392 mg (85%), as

a colorless oil. The 2,4 dinitrophenylhydrazone derivative, recrystallized from methanol, had mp 152.5-153.5C.

Phenyl-2-Propanone from Phenyl-2-Nitropropene8

Sodium Borohydride/Nef Reaction

In this preparation, phenyl-2-nitropropene is reduced to phenyl-2-nitropropane with NaBH4 in methanol, followed by

hydrolysis of the nitro group with hydrogen peroxide and potassium carbonate, a variety of the Nef reaction. The

preparation is a one-pot synthesis, without isolation of the intermediate. This synthesis is not suitable for ring-

substituted phenyl-2-nitropropenes, as the side chain tends to be oxidized when electron-donating substituents are

present on the ring.

16.3g (0.1 mole) phenyl-2-nitropropene was dissolved in 200ml methanol in a 250ml Erlenmeyer flask situated on a

magnetic stirrer, and chilled to 0C with an ice/salt bath. Then, with good stirring, 7.6g (0.2 mole) of NaBH4 was added

a little at the time, and the temperature was not allowed to to rise above 15C. When the generation of heat had

subsided, the ice/salt- bath was removed and the solution was stirred at room temperature for two hours. At the end of

this period, the flask was once again placed in an ice/salt bath and the solution was allowed to cool to 0C again. 100

ml of 30% H2O2 was then added, together with 30 grams of anhydrous potassium carbonate, and the solution was left

to stir for 18-24 hours at room temp. During the addition of H2O2/K2CO3 a white, sticky precipitate forms, which can

be a bit too thick for a weak magnetic stirrer to handle, so the mass can be stirred with a glass rod now and then

during the first two hours, after which the precipitate will be much looser and no match for any mag-stirrer.

The next day, the solution is slowly acidified with 2M HCl with good stirring, care being taken for the evolution of heat

and CO2. About 300 ml of acid is needed. When the pH of the solution turned acid, the color became significantly

more yellow, but the acidity was confirmed with pH paper. All of the precipitate was also be gone at this point. The

solution was extracted with 3x100ml CH2Cl2, and the pooled organic extracts washed with 100ml 2M NaOH and

200ml H2O. The organic phase was dried over MgSO4, filtered with suction, and the solvent removed under vacuum

to give a clear yellow oil. After distillation of said oil at aspirator vacuum, the yield was around 60-70% of phenyl-2-

propanone (P2P) as a light yellow oil.

Reduction with Iron Powder13

If phenyl-2-nitropropene is reduced by iron powder in an acidic medium (such as acetic acid or aqueous hydrochloric

acid) the nitroalkene is reduced to the oxime, which is then hydrolyzed by the acid into the desired phenyl-2-

propanone.

Phenyl-2-nitropropene (10 g, 61 mmol) was dissolved in 75 ml HOAc and slowly dripped into a refluxing slurry of Fe

powder (32 g, 0.57 mol) in 140 ml HOAc. The mixture turned brownish and foamy, and the mixture was refluxed on

low heat for 1.5 h. The reaction mixture was poured into 2000ml water, and was extracted with 3x100 ml CH2Cl2. The

combined extracts was washed with 2x150 ml H2O and dried over MgSO4. The solvent was distilled off, and the

residue distilled under vacuum to give phenyl-2-propanone in 75% yield.

Reduction with Chromous Chloride18

Another method for reducing phenyl-2-nitropropene to phenyl-2-propanone in 80% yield is to use

Chromium(II)chloride as the reducing agent.

Phenyl-2-Propanone from Chloroacetone9

41 grams (0.31 mole) of anhydrous aluminum chloride and 100 ml of anhydrous benzene (free from thiophene) were

put in a 500ml three-necked flask which was equipped with a mercury-sealed stirrer, a reflux water condenser and a

small addition funnel. The top of the condenser was connected to a sulfuric acid trap and this trap was connected to a

gas absorption bottle. The mixture was stirred and heated to refluxing on a steam bath and 13.9 g (0.15 mole) of

chloroacetone was allowed drop in slowly during a period of 30 minutes. After refluxing for 5 hours, the solution was

practically black. After cooling to room temperature, the reaction mixture was decomposed by slowly adding water

through the condenser, stirring during the addition. When no more hydrogen chloride was evolved, 20 ml of water and

20 ml of concentrated hydrochloric acid was added. The benzene layer was separated and the aqueous layer

extracted with four 25 ml portions of benzene. All of the benzene solutions were combined and filtered. The benzene

was distilled off, and the remaining viscous oil was distilled under reduced pressure. Nine grams of liquid boiling below

123C/20-22mmHg was obtained. Approximately 10g of high-boiling material was left in the distilling flask. Phenyl-2-

Propanone was recovered from the distillate by making the bisulfite addition product, filtering, decomposing the

addition product with sodium carbonate solution, and steam distilled as long as any oil distilled over. The distillate was

extracted with ether, the ether dried over anhydrous MgSO4 and the ether distilled on a steam bath. The phenyl-2-

Propanone was distilled under reduced pressure, bp 108-114C/20-22mmHg. Yield 6.5 g (32%).

Phenyl-2-propanone from Ephedrine Derivatives10

When ephedrine and related compounds are heated in strong aqueous acid, they are dehydrated to the enamine,

which spontaneously can rearrange to the isomeric imine (Schiff Base), which then can be hydrolyzed into phenyl-2-

propanone and an amine salt. As all the steps are reversible processes, the reaction equilibrium is driven towards the

desired product by continuously removing the formed phenyl-2-propanone by the aid of steam distillation.

Ephedrine derivatives that can be used in this procedure include Ephedrine, Pseudoephedrine, Norephedrine and

Norpseudoephedrine (Phenylpropanolamine). Many other metal salts can be used instead of the zinc chloride, for

details, see the translation of the original patents.

1025g 75% sulfuric acid was mixed with 1g ZnCl2, and 192g (1.16 mol) Ephedrine or Pseudoephedrine freebase was

dissolved at a temperature of 50-100C, and the reaction mixture was heated further to 145-150C. At 125C steam is

passed through the solution to facilitate mixing of the contents. At 145C the stream of steam is increased, and during

2.5-3 hours the phenylacetone is steam distilled from the reaction mixture. The the crude phenyl-2-propanone, which

is free from propiophenone, is isolated by toluene extraction of the distillate. After distillation through a short vigreaux

column, 130g (82%) of phenyl-2-propanone is isolated in a purity of 99.8%.

Electrosynthesis of P2P from Benzyl Chloride4

Synthesis of phenyl-2-propanone from benzyl chloride (79 mmol) and acetic anhydride (686 mmol) by electrolysis of

the reaction mixture. The anode is made of magnesium or aluminium, the cathode of nickel, the solvent is DMF (110g)

and the supporting electrolyte is tetrabutylammonium fluoroborate (2 g, 6 mmol). After the electrolysis using a current

of 1A at a temperature of 0C (2.2 faradays per mole of benzyl chloride), the remaining benzyl chloride, the toluene

which is a byproduct of the reduction of benzyl chloride, and phenyl-2-propanone, both in free form and in the form of

its enol acetate, are present in the solution. After the DMF has been evaporated off and the residue has been

hydrolysed with hot dilute HCl, phenyl-2-propanone is isolated by extraction with ether in 64% yield.

Another procedure33, using a lead cathode and a carbon anode, DMF as the solvent and a tetrabutylammonium

tosylate electrolyte gives a 73% yield of phenyl-2-propanone after hydrolysis of the resulting enol ester.

Metallic Nickel-Mediated Synthesis of P2P from Benzyl Chloride and Acetyl Chloride28,29

Preparation of Metallic Nickel

A 50-mL two-neck flask was equipped with a magnetic stirrer, a rubber septum, and a condenser topped with argon

inlet and outlet to oil pump. Lithium metal was cut under mineral oil. One piece of lithium with a shining metal surface

was rinsed in hexane and transferred into a glass tube with a stopcock and a rubber septum which had been filled with

argon. The glass tube was evacuated to evaporate the hexane, filled with argon, and weighed. Nickel halide (1.0

equiv, 9-13 mmol), lithium (2.3 equiv, 21-30 mmol), and naphthalene (0.1 equiv, 0.9-1.3 mmol) were placed in the flask

through the side neck. The flask was evacuated and filled with argon two or three times. The use of a glovebox or -

bag is not required if contact of the lithium with air is kept to a minimum. Then, glyme (25-30 mL) was added through

the septum with a syringe, and the mixture was stirred for 12 h. During the reduction the surface of lithium became

pink. After the lithium metal was consumed completely, the stirring was stopped; metallic nickel which had adhered to

the walls of the flask was scraped off with the stirrer and a magnet. The nickel precipitated as a bulky black powder in

a clear colorless solution after standing. The septum on the side neck was replaced with an addition funnel, and a

mixture of appropriate reagents in glyme (10 mL) was then added to the nickel.

Reaction of Benzyl Chloride with Acetyl Chloride in the Presence of Metallic Nickel

Metallic nickel in glyme (25 mL), prepared from nickel iodide (2.97 mmol), lithium (0.152 g, 21.9 mmol), and

naphthalene (0.122 g, 0.95 mmol), was heated to reflux. A mixture of benzyl chloride (1.0 g, 7.9 mmol) and acetyl

chloride (0.65 g, 8.3 mmol) in glyme (10 mL) was added dropwise for 30 min. Additional heating was continued for 15

min, and the red-brown reaction mixture was cooled to room temperature, poured into a separatory funnel containing

hydrochloric acid solution (37%, 100 mL), and extracted with chloroform twice. The chloroform solution was washed

with water, and the aqueous phase was extracted with additional chloroform. The combined extracts were dried over

anhydrous sodium sulfate and concentrated. The crude oil was purified by silica gel chromatography. It was eluted

with hexane followed by chloroform to give phenyl-2-propanone (0.72 g, 68%), bp 95-96C (11 mmHg); IR (neat) 1710

cm-1 (C=O).

Phenyl-2-Propanone by Rearrangement of 2-Phenylpropanal11

2-Phenylpropanal can be rearranged with either mercuric chloride (HgCl2) or sulfuric acid (H2SO4) to form the

isomeric phenyl-2-Propanone (P2P). 2-Phenyl-propanal (hydratropic aldehyde) is an unwatched industrial chemical

which is used in the perfume industry. 2-phenylpropanal can also be made from alpha-methylstyrene.

The CAS number for 2-phenyl-propanal is [93-53-8], and synonyms for it include Hydratropic aldehyde; 2-

Phenylpropionaldehyde; Cumenealdehyde; alpha-methyl benzeneacetaldehyde and alpha-methyl

phenylacetaldehyde. Boiling point 92-94C/12mmHg, 222C/760mmHg.

There are other ways of performing this rearrangement, 2-phenylpropanal is isomerized to phenyl-2-propanone in up

to 87% yield by passing its vapor over an iron zeolite catalyst bed at 500C, followed by condensation of the vapors

and redistilling the P2P12.

Even if the method below which uses mercuric chloride is higher yielding than the one using cold sulfuric acid, I would

definitely reccommend the one with sulfuric acid, as it is much cheaper to use, and is not disastrous for your health or

the environment. 60g of mercuric chloride contains 45 grams of mercury, enough to poison a medium-sized lake if

released into the environment, and if you happen to ingest it yourself, it will accumulate in your body.

It is not possible to effectively separate 2-phenylpropanal (bp 222C/760mmHg) from phenyl-2-propanone (bp

214C/760mmHg) through simple distillation and certainly not via vacuum distillation as the boiling points are too

close. Fractional distillation could theoretically be used to separate them, but the size of the column that would have to

be used makes that option impractical. A good idea for separating a mixture of the two is to oxidize the mixture with a

mild oxidant which won't affect the P2P, but which will oxidize the aldehyde to 2-phenylpropionic acid. The acid can

then be separated from the ketone by dissolving the mixture in a non-polar solvent and washing the solution with

dilute sodium hydroxide. The P2P stays in the organic layer, which is then dried over MgSO4, the solvent removed

under vacuum and the residue vacuum distilled to give pure P2P.

Method A

30g of 2-phenylpropanal is heated together with a mixture of 60g mercuric chloride (HgCl2, 1 eq.) and 450ml 75%

ethanol in a pressure-safe sealed glass container for 4.5h at 100C in a boiling water bath, during which time a

precipitate forms. Water is added, and the solution is steam-distilled (during which operation the precipitate

redissolves). The distillate is extracted with ether, dried, and the solvent is evaporated. The oily residue is then

vacuum distilled with a fractionating column to collect the phenyl-2-propanone in a yield of 80% or more, bp 92-101C

at 14mmHg.

When 0.1 equivalents of HgCl2 was used, only 10% phenyl-2-propanone was formed, the rest consisted of

unchanged aldehyde.

Method B

9 g of 2-phenylpropanal is slowly added with good stirring during 35 minutes to 40ml concentrated sulfuric acid, while

the temperature of the reaction mixture is kept at -16C. After all the 2-phenylpropanal has been added, the mixture is

allowed to stand at the same temperature for another 15 minutes, and then the mixture is poured onto crushed ice

(100-150g is probably a suitable amount). When the ice has melted, the organics are extracted from the water phase

by 3x50ml diethyl ether, the pooled organic phases dried over MgSO4, the ether distilled off and finally the residue is

vacuum distilled (bp 91-96C at 11 mmHg) to give 5.6g (62%) of phenyl-2-propanone.

Phenyl-2-Propanone from Acetone Enolate

If acetone is reacted with a strong base, which is able to deprotonate one of the relatively acidic alpha protons of the

ketone, acetone enolate is formed in quantitative yield. Such strong bases include sodium amide, lithium

diisopropylamide and several alkoxides, for example potassium tert-butoxide.

If this enolate of acetone is allowed to react with a halobenzene (preferably iodobenzene, but bromobenzene should

also work) in DMSO under rigidly anhydrous conditions, the two species will combine to form phenyl- 2-propanone.

There has been no known actual attempts at this synthesis using the enolate of acetone and a halobenzene in DMSO

(but it has been done in liquid ammonia), but other ketone enolates, such as pinacolone has been extensively studied

in this medium. There are no theoretical obstacles at all to why it would not work in the production of phenyl-2-

propanone. The yields in the reactions range between 50 and 98%. The reaction can be catalyzed by iron salts,

oxygen or UV light.

For a more in-depth discussion of this synthesis, read Drone #342's Enolate Phenylacetone Synthesis FAQ 1.0

Free-Radical alkylation of Benzene with Acetone Catalyzed by Manganese(III)Acetate17

Phenyl-2-Propanone can be made in a single step by a free-radical reaction between benzene and acetone. The

reaction relies upon the special oxidative powers of manganese(III)acetate, a compound easily prepared from

potassium permanganate. The yield is relatively low, and requires high dilution of the reactants, but this can be

improved, and the reaction is also applicable for other substituted benzenes, as can be seen in the comprehensive

Manganese(III)acetate catalyzed aromatic acetonylation document on this site.

A mixture of Manganese(III)acetate dihydrate (13.4g, 50 mmol), benzene (150ml), acetone (150ml) and glacial acetic

acid (250ml) was refluxed under an inert atmosphere (argon, helium or nitrogen) until the dark brown color of

manganese(III)acetate changed to the pale pink of manganese(II)acetate (about 90 min). The reaction mixture was

partitioned between 400ml ether and 250ml water. The ether layer was separated and washed with 250ml water and

with 2x250ml 5% Na2CO3 to remove any remaining acetic acid. The ether was then dried over anhydrous Na2SO4

(or MgSO4), the solvent evaporated and the residue fractionately distilled to recover unreacted benzene, and to give

phenyl-2-propanone in 40% yield (1.34g) based on the reacted manganese(III)acetate, which is the limiting reagent in

this reaction.

Phenyl-2-Propanone by Oxythallation of alpha-methylstyrene with Thallium(III)Nitrate23

Warning: Thallium salts are exceedingly toxic, and may be lethal upon ingestion! Handle with gloves only!

A solution of Thallium(III)Nitrate (39g, 100 mmol) in 100ml methanol is added to a solution of alpha-methylstyrene

(11.82g, 100mmol) in 50ml methanol at room temperature with stirring, and there is an immediate precipitation of

Thallium(I)Nitrate, and after standing for 15 minutes, the precipitate is filtered off, washed with a little methanol, and

the filtrate is shaken for 5 min with 1M H2SO4 to hydrolyze the formed Phenyl-2-Propanone dimethyl acetal. The

solution is extracted with ether, dried over MgSO4 and the solvent distilled off, and the residue vacuum distilled to give

10.9g Phenyl-2-Propanone (81% yield).

Thallium(III)Nitrate

50g Thallium(III)Oxide (Tl2O3) is dissolved in 150ml warm, concentrated nitric acid and cooling the pale yellow

solution to 0C. The colorless crystals of Thallium(III)Nitrate trihydrate are filtered, washed with a little dilute nitric acid

and dried in vacuo over phsphorus pentoxide. Thallium(III)Nitrate (mol wt 390) is stable indefinitely if stored in tightly

sealed bottles. The salt is readily soluble in methanol and dilute mineral acids.

alpha-Methylstyrene can also be treated with Bromine and Sulfuric Acid to yield P2P.

Phenyl-2-Propanone from Benzaldehyde and a Phosphonium Ylide (Wittig reaction)15

The phosphonium salt was prepared by dissolving triphenyl phosphine (76.4g, 0.29 mol) and alpha-chloroethyl methyl

ether16 (28.4g, 0.30 mol) in 125 mL benzene. After standing for 40 h the mixture was filtered and washed with ether

giving a white solid (112g, 88%) consisting of the crude phosphonium salt containing one molar equivalient of benzene

crystallization. This salt is slightly hygroscopic on exposure in air but can be stored indefinitely in a sealed container.

The ylid resulting from treatment of the phosphonium salt with base was found to be very unstable at room tempature,

the characteristic red color dissappearing within a few seconds. Accordingly, the preparation and reaction of this ylid

was best carried out at -40C.

The phosphonium salt (33 mmol) was suspended in 40 mL of glyme at -40C under nitrogen. Potassium tert-butoxide

(33 mmol) in 15 mL of glyme was added with stirring over 5 minutes. At this point a solution of benzaldehyde (30

mmol) in 5 mL of glyme was added over five minutes. The mixture was allowed to warm to room temp over 1h and

was then directly distilled, to give pure phenyl-2-propanone enol methyl ether).

Phenyl-2-propanone was conveniently prepared from the enol ether by mixing with one equivalent of water with 0.5%

HCl and enough methanol to effect solution. The solution was heated to boiling and the solvent was then evaporated

to give relatively pure phenyl-2-propanone in 88% overall yield.

Phenyl-2-Propanone by arylation of Potassium Acetylacetonate21

To a stirred solution of bromobenzene (31.4g, 200 mmol) in DMF (1 liter) was added cuprous iodide (32.4 g, 167

mmol) and potassium acetylacetonate hemihydrate (125g, 834 mmol; Aldrich). The mixture was stirred and heated at

100C for 24 hr, cooled, stirred with 2M sodium hydroxide (250 ml) for 1 hr and extracted with toluene (2x500 ml). The

combined extracts were washed with water, 1M hydrochloric acid and satd. aq. sodium bicarbonate, dried over

magnesium sulphate and concentrated in vacuo to leave a dark brown oil, which after purification gave phenyl-2-

propanone in 65% yield.

Phenyl-2-Propanone by Heck Arylation22

To a stirred solution of bromobenzene (60 mmol), isopropenyl acetate (9g, 90 mmol) and dichloro-bis-(tri-o-

tolylphosphine)palladium (0.47g, 0.67 mmol) in dry toluene (30 ml), under nitrogen, was added tributyltin methoxide

(25.9 ml, 90 mmol; Aldrich). The mixture was stirred and heated at 100C for 5 hr, cooled and the solvent evaporated

in vacuo. The residue was chromatographed on silica gel, to afford the phenyl-2-propanone in 67% yield.

Phenyl-2-Propanone from Benzyl cyanide and Trimethylaluminum25

Trimethylaluminium (30ml of a 2M solution in toluene) was added to a solution of benzyl cyanide (2.34g, 20 mmol) in

20ml of toluene at -78C and the mixture was under stirring allowed to slowly warm up to room temperature and

refluxed for 12h. After being cooled to 0C, the solution was poured over crushed ice and made acidic with 6M HCl.

Ethyl acetate was added and the mixture was vigorously stirred for one hour. The organic layer was washed with

aqueous NaHCO3, brine and dried over MgSO4. Removal of the solvent gave 2.75g of crude phenyl-2-propanone as

an oil, which can be purified by vacuum distillation or column chromatography.

Phenyl-2-Propanone from Phenylacetaldehyde and Dimethyl cadmium

Dimethyl Cadmium

2 MeMgI + CdCl2 => Me2Cd + 2 MgICl

To 500 ml. 3-neck rb. DRY FLASK attach a reflux condenser. Attach 125ml sep. funnel, add 31.3 ml. methyl iodide

either freshly prepared or dried overnight with calcium chloride. Add 60 ml. anhydrous diethyl ether to sep. funnel,

replace stopper.

Add 12.5 grams Magnesium turnings to flask. Add 75 ml anhydrous ether to flask. Allow aprox. 10 ml. of halide ether

solution to enter flask. If cloudiness does not become apparent in 1 or 2 min stop. Do not add more! Take a glass rod

about 12 inches in length and score with a 3 corner file 2 inches from one end using pliers and a rag to protect your

hands break away the 2 inch piece. using the remaing 10 inch piece gently poke at the magnesium turnings to expose

fresh metal.

If reaction starts, add halide dropwise as quickly as the reflux column can handle. Be prepared to stop and cool with

ice water bath if needed. When all the halide has been added and the reaction is no longer refluxing, add 31.2 grams

of anhydrous cadmium chloride in small portions through side neck restoppering after each addition.

After all the Cadmium chloride has been added, the flask will have a tannish brown solid mass inside. This is the

dimethyl cadmium, keep it covered and protected from air. Proceed immediately to next part if at all possible.

Notes: Avoid breathing the cadmium chloride dust (it needs to be finely ground after drying) avoid contact with the

methyl iodide or ether solution of methyl iodide avoid breathing any vapours of the metal conversion reaction (it smells

like garlic if you must know).

Phenyl-2-Propanone

To a clean dry sep. funnel add 64 ml. freshly distilled phenylacetaldehyde (Note 1) and 50 ml. anhydrous ether. Add

dropwise the aldehyde/ether solution to the dimethyl cadmium swirling occasionally to break up the clumps. Be

prepared to stop addition and cool if needed. When reflux has subsided do not heat. Quickly pour into a 1000 ml.

beaker containing 100 ml. distilled water 10 ml conc. HCl and 100 cc. of chipped ice. Neutralize with sat. sodium

bicarb untill fizzing stops. Separate, and extract water layer with 2x50 ml portions of technical grade ether. Distill under

reduced pressure to strip off excess ether. Test with bisulfite any product not forming addition is phenyl-2-propanol

(very small amount) can be saved for later oxidation. Hydrolyse addition product and distill if desired. bp. 100 at 13

mm. Yield 50-55 ml, ~85% of P2P.

Note 1: The phenylacetaldehyde will polymerise on standing. This polymer is degraded to the monomer on distillation.

For this preparation it also needs to be as dry as possible.

Phenyl-2-Propanone from Phenylacetyl Chloride and Dimethyl Cadmium32

A mixture of 40 ml. of anhydrous ether and 6.1 grams (0.25 mole) of magnesium was stirred under reflux while 35.5

grams (0.25 mole) of methyl iodide in 140 ml. of anhydrous ether was added over a 3-hour period; stirring under reflux

was continued for an additional hour. The reaction mixture was cooled with an ice bath and 22.4 grams (0.134 mole)

of powdered anhydrous cadmium chloride was added over a 5- to 10-minute period, warmed to room temperature,

and refluxed on a steam cone for 1 hour. Ether was removed by distillation on a steam bath. To theresidue was added

100 ml. of anhydrous benzene and the distillation was continued until about 50 ml. more of distillate was collected.

Again 100 ml of anhydrous benzene was added, the flask was cooled in an ice bath, and 30.9 grams (0.2 mole) of

phenylacetyl chloride in 75 ml of anhydrous benzene was added with stirring over a period of approximately 10

minutes. The reaction mixture was warmed to room temperature and refluxed with stirring on a steam cone for 1 hour.

The flask was again cooled in an ice bath and the reaction mixture decomposed by the addition of a solution of 25

grams of ammonium chloride in 200 ml of cold water. The organic phase was separated, washed, and dried over

anhydrous sodium sulfate. The benzene was removed by flash distillation and the ketone distilled under reduced

pressure. There was thus obtained 15.5 grams (58%) of 1-phenyl-2-propanone, bp 74-76C/3 mmHg).

Phenyl-2-Propanone by Grignard Addition to Acetic Anhydride26

In a 500-mL three-necked flask, situated in a dry ice/acetone slush in a Dewar flask, there was added a solution of

acetic anhydride (40g, 2.55 mol) in diethyl ether (100ml), and the flask was equipped with a magnetic stirrer, a

thermometer and an addition funnel (modified so that the added liquid was cooled externally by dry ice/acetone). To

this was added an etheral solution of benzylmagnesium chloride, prepared from benzyl chloride (25.5g, 0.2 mol) and

magnesium shavings (4.9g, 0.2 mol). After the addition after one hour was finished, the reaction mixture was allowed

to stir at dry ice temperature for 2-3 hours, the cooling bath removed and the reaction quenched by the careful

addition of saturated aqueous ammonium chloride. The aqueous layer was separated, the organic phase washed with

10% sodium carbonate solution until the washes were no longer acidic to universal pH paper, followed by 50 ml brine.

The organic phase was dried over MgSO4, filtered, the ether evaporated on a water bath and the residue fractionately

distilled to yield phenyl-2-propanone (14g, 52%), bp 214-215C/760mmHg (100-101C/13mmHg).

Phenyl-2-Propanone by Grignard addition to Nitriles19,24

127g benzyl chloride was dissolved in 250mL Et2O, to this was added 27g Mg turnings in portions, an iodine crystal

being added after the first portion to initiate Grignard rxn. A thick white precipitate built up and clogged up some Mg,

but after all was added, there was excess unclogged Mg which would not react. [NOTE: This clogged-up material

didn't react fully w/the MeCN, and so was decomposed to toluene, so try to avoid it!].Submersion of the flask in cold

H2O was used as necessary during addition to prevent excessive boiling of the Et2O. After all Mg was added, and no

further reaction occurred, the rxn mixture was cooled in an ice-salt bath. A soln. of 62g acetonitrile in 100mL Et2O was

added slowly while stirring w/a thermometer. The reaction temperature rose to 30C. After completion of addition, the

mixture was refluxed gently, stirred thoroughly, then left to cool to room temp. 500mL 10% HCl was added slowly

under stirring. [NOTE: This seemed to cause the Et2O layer to take on a reddish tint. I think the purity of final product

would be higher if reaction mixture was first poured onto ice, then acidified.] After all effervescence had stopped, the

organic layer was separated. NaCl was added to the aqueous layer, which was then extracted w/Et2O [NOTE: I think

a lot of product was left behind in this aqueous layer; it was still very orange even after adding NaCl and extracting

with Et2O (which was a lighter shade of orange than the aq. layer!)]. The combined Et2O layers were washed with

H2O, dried over MgSO4. Et2O and a small amount of toluene were evaporated to give 42g crude phenyl-2-propanone

as a clear orange oil. Vacuum distillation of this oil afforded pure phenyl-2-propanone (bp 91-96C at 11 mmHg).

The intermediate phenyl-2-propanone imine magnesium salt can also be prepared from methylmagnesium iodide and

benzyl cyanide. Both are hydrolyzed to phenyl-2-propanone with dilute hydrochloric acid. The imine salt can also be

reduced directly to amphetamine by sodium borohydride in methanol in high yield.

Simplification of the above procedure, by Poodle:

In a dream, 0.2 mol benzylmagesiumchloride grignard reagent were prepared by standard methods in diethylether

(Total reaction volume: 200ml). Reaction initiated by heating the mixture to 60C for a short periode of time. About 2

moles of acetonitrile (100ml) was mixed with 100 ml of anhydrous diethylether and cooled in ice/water. The

benzylmagnesium chloride solution was added the acetonitrile over a periode of 10 minutes, using constant swirling of

the reaction mixture. A white percipitate was formed, corresponding to a intermediate complex, not soluble in ether or

acetonitrile. This complex was isolated by filtration through a buchner, and washed twice with water-free ether to

remove any unwanted remains of acetonitrile or benzyl chloride. The white complex was briefly dried, but as it began

to turn yellow, no chances was taken and 15 ml distilled water was added, then another 10 ml (The complex reacted

immediatly with the water, giving heat and causing remaining ether to boil, the solution turned yellow/orange with oily

orange bubbles.) The solution was exposed for a vacuum to remove any remaining ether in the solution. Upon using

the vaccum, ether was removed and the solution separated into two layers with an orange oil on top and a water layer

containing salts and undissolved salts. The oily layer was separated and gave 21 ml of possible P2P, about 75-80% of

the theoretical 26 ml. The ketone was frozen at -20, responding to that temperature by forming a solid, as theoretically

expected by a substance having a melting point at -16.

This method could be of interest for producing P2P from acetonitrile, as it greatly simplifies the procedure by

eliminating any need for extensive extraction of the ketone.

Phenyl-2-Propanone from Benzylchloride (via dibenzyl cadmium)20,30,31

2 PhCH2MgCl + CdCl2 (PhCH2)2Cd + 2 MgCl2

(PhCH2)2Cd + 2 CH3COCl 2 PhCH2COCH3 + CdO

Benzylmagnesium chloride was prepared from a solution of 0.2 mol benzyl chloride in 100ml anhydrous ether and 0.2

mol magnesium turnings (Org. Synth. Coll. Vol 1, p. 471). The clear dark solution was filtered under nitrogen through a

glass wool plug. The solution of the grignard reagent was diluted with ether so that the concentration was no greater

than 0.2 mol per 300ml and then cooled in an ice-bath. Anhydrous cadmium chloride (0.16 mol) was added with

vigorous stirring over 10-15 min. Stirring was continued with cooling for 2h.

A solution of 0.1 mol acetyl chloride in 3 volumes anhydrous ether was added to the cold benzyl cadmium reagent

over 5 min. It was necessary to use a 2:1 molar ratio of the cadmium reagent to acid chloride, if the ratio was less a

considerable amount of acid was found in the product. The mixture was stirred in an ice-bath for 8h, and hydrolyzed

with 20% H2SO4. The ether layer was separated and the aqueous phase extracted twice with ether. The combined

ether solutions were washed with water and 10% sodium bicarbonate, and was allowed to stand without drying

overight. The ether solution was then extracted with 4x25ml 10% sodium bicarbonate, and the combined aqueous

extracts were extracted twice with ether, and all the pooled ether extracts were washed with water and dried over

sodium sulfate. The ether was distilled off, and the residue vacuum distilled to give phenyl-2-propanone in 50-70%

yield (calculated on the acid chloride), (bp 91-96C at 11 mmHg).

The thermal stability of dibenzyl cadmium is low, so keep it on ice during handling. Using benzyl cadmium chloride or

dibenzyl cadmium gave little difference in yield.

References

Org. Syn. Coll. Vol. 2, p 487-489

Org. Syn. Coll. Vol. 2, p 391-392

Magidson and Garkusha, Zh. Obsh. Khimii, 11(4) 339 (1941); Chem. Abs. 5868 (1941)

Chem. Ber. 68, 2112 (1935)

Juraj Kizlink, Chemicke Listy 84(9), 993-4 (1990)

US Pat 4,629,541

[ Reference Lost ]

A. I. Vogel, Practical Organic Chemistry, 5th Ed, p. 612-613.

Tet. Lett. 29(24), 2977-2978 (1988)

R. Ballini, Synthesis 723-726 (1994)

J. Amer. Chem. Soc. 62, 1622 (1940)

German Patents 3,026,698 and 3,200,232

Danilov and Danilova, Chem. Ber. 60, 1050 (1927)

US Patent 4,694,107

Alexander Shulgin, Pihkal #109

Okabe, K.; Ohwada, T.; Ohta, T.; Shudo, K. J. Org. Chem. 54, 733 (1989)

Okabe, K.; Ohwada, T.; Ohta, T.; Shudo, K. Tetrahedron 46, 7539-7555 (1990)

D. R. Coulsen, A new Synthesis of Methyl Ketones, Tet. Lett. 45, 3323-3326 (1964)

Ann. Chem. 225, 269 (1884)

J. Org. Chem. 49, 1603-1607 (1984)

Tet. Lett. 26, 3777 (1985)

Tet. Lett. 21, 155-158 (1980)

J. Am. Chem. Soc. 82, 1975 (1960)

Chem. Lett. 597-600 (1982)

Bull. Soc. Chem. Jap. 57, 242 (1984)

A. McKillop, Oxidative Rearrangement of Olefins with Thallium(III)nitrate, Tet. Lett. 60, 5275-5280 (1970),

A. H. Frye, Oxidation of Olefinic Compounds with Solutions of Thallium(III) Salts, US Pat 3,452,047

J. Org. Chem. 37, 3369-3370 (1972)

US Pat 5,639,780

J. Am. Chem. Soc. 67, 154 (1945)

Acta Chem. Scand. 6, 782-790 (1952)

J. Org. Chem. 50, 1373-1381 (1985)

Tet. Lett. 24, 2451-2452 (1983)

J. Amer. Chem. Soc. 61, 741 (1939)

H. Gilman., J. F. Nelson, Rec. Trav. Chim. 55, 518-530 (1936)

E.H. Sund and H.R. Henze, Alkyl Benzyl Ketones and Hydantoin Derivatives, J. Chem. Engineering Data 15(1),

200-201 (1970)

I. Nishiguchi, T. Oki, T. Hirashima and J. Shiokawa, Electroreductive Acylation of Benzyl Chlorides with Acid

Anhydrides, Chemistry Letters 2005-2008 (1991)

Phenyl acetone is used as an intermediate to produce sympathomimetic amines such as

phenbenzamine, phenyl isopropyl amine, amphetamine, prenylamine, pargyline and

estramustine. Phenylacetone is called MDP2P (3,4-methylenedioxy phenyl-2-propanone)

which is used in the clandestine synthesis of MDMA (3,4-

methylenedioxymethamphetamine), commonly known as ecstasy. Phenylacetone shipment

is available only to the importer who has import licence issued by Government.

We are leading Manufacturers and exporters of phenylacetone, phenylacetone is also called

phenyl-2-propanone, benzyl methyl ketone, methyl benzyl ketone, , 1-phenyl-(103-79-7)

Benzyl methyl ketone(103-79-7) C9H10O 1-PHENYLACETONE1-PHENYL-2-

PROPANONEBENZYL METHYL KETONEPHENYLACETONEPHENYL-2-PROPANONE1-

phenyl-2-propanon1-phenyl-propan-2-one2-Propanone. Often it's referred to as P2P) is an

organic compound.

Phenyl acetone family compounds are widely used as a parent compound to make drugs,

dyes, rubber chemicals, fungicides, biocides, alkaloids, and flavoring agents. We are one of

the leading manufacturers of fine chemicals, suppliers & exporters of phenylacetone,

phenylacetone is also called phenyl-2-propanone, benzyl methyl ketone or methyl benzyl

ketone (Phenyl-2-propanone / Benzyl methyl ketone). Often it's referred to as P2P (C9H10O)

is an organic compound. It is clear oil with a refractive index of 1.5168. This substance is

used in the manufacture of methamphetamine and amphetamine as a starting material or

intermediate. Due to the illicit uses in clandestine chemistry, it was declared a schedule II

controlled substance in the United States 11. February 1980. With prime focus on quality, we

have adopted high level of operational quality standards that are strict on both the domestic

as well as international market grounds. We accept the complete responsibility for the

process and quality aspects of each and every product we offer. This commitment to quality

and the obligation to our customers have been the foundation of our business since its

inception.

Technical Service:

Our team of scientists has experience in all areas of research including Life Science,

Material Science, Chemical Synthesis, Chromatography, Analytical and many others.

Bulk Ordering & Pricing:

Need larger quantities for your development, manufacturing or research applications?

Phenyl acetone is used as an intermediate to produce sympathomimetic amines such as

phenbenzamine, phenyl isopropyl amine, amphetamine, prenylamine, pargyline and

estramustine. Phenylacetone is called MDP2P (3,4-methylenedioxy phenyl-2-propanone)

which is used in the clandestine synthesis of MDMA (3,4-

methylenedioxymethamphetamine), commonly known as ecstasy. Phenylacetone shipment

is available only to the importer who has import licence issued by Government.

Phenyl acetone is structurally related to coumarine or cinnamic acid for the application of

rodenticide anticoagulant and to phenethylamine which is a main structure in the activity of

the sympathetic nervous system.

Phenyl acetone is used as an intermediate to produce pesticides and anticoagulants. Active

ingredients as anticoagulant include:

Brodifacoum

Chlorophacinone

Coumachlor

Difenacoum

Diphacinane

2-Pivaloyl-1,3-indandione

2-Isovaleryl-1,3-indandione

Warfarin

Note: Reproduction of any materials from the site is strictly forbidden without permission.

CAUTION : PHENYL ACETONE MAY BE A CONTROLLED COMMODITY IN YOUR

COUNTRY

Phenyl acetone is used as an intermediate to produce sympathomimetic amines such as

phenbenzamine, phenyl isopropyl amine, amphetamine, prenylamine, pargyline and

estramustine. Phenylacetone is called MDP2P (3,4-methylenedioxy phenyl-2-propanone)

which is used in the clandestine synthesis of MDMA (3,4-

methylenedioxymethamphetamine), commonly known as ecstasy. Phenylacetone shipment

is available only to the importer who has import licence issued by Government. Other use as

an intermediate in the manufacture of

Amphetamine

Prenylamine

Pargyline

Estramustine

Chlorophacinone & Diphacinone (rodenticides)

Phenylacetone

1-phenylpropan-2-one

Other names

benzyl methyl ketone; methyl benzyl ketone; phenyl-2-

propanone

Identifiers

CAS number 103-79-7

PubChem 7678

ChemSpider 21106366

UNII O7IZH10V9Y

KEGG C15512

ChEBI CHEBI:52052

Properties

Molecular formula C9H10O

Molar mass 134.18 g mol- 1

Density 1.006 g/mL

Melting point -15 C, 258 K, 5 F

Boiling point 214-216 C, 487-489 K, 417-421 F

Contact information for

MulBerry Chemicals Pvt. Ltd in India.

Plot No. - 1019, Vill. - Sarigam,

G.I.D.C. , Road No. 10,

Dist. - Valsad,

State of Gujrat.

Pin Code - 396142

*** Reproduction of any materials from the site is strictly forbidden without permission.

2009-2011. MulBerry Chemicals Pvt. Ltd . (India)All Rights Reserved. Chemicals Manufacturers In India

* Trademark of The MulBerry Chemicals Pvt. Ltd ("Mulberry Chemicals") or an affiliated company of MBC.

The above information is believed to be correct but does not purport to be all-inclusive and shall be used

only as a guide. Shall not be held liable for any damage resulting from handling or from contact

with the above product.