### Benzyl Chloride (Method 1)

Method 1. Fit a 600-ml. three-necked flask with a thermometer, a reflux condenser and a gas inlet tube, extending almost to the bottom of the flask. Connect the top of the condenser through a calcium chloride (or cotton wool) guard tube to two wash bottles containing 10 percent. sodium hydroxide solution: the long lead-in tubes in the wash bottles should be just above the surface of the alkali solution in order to avoid "sucking back." Place 100 g. (115.5 ml) of dry toluene and a few chips of porous plate in the flask. Boil the toluene gently and pass in a stream of chlorine from a cylinder (or from a gas generator) *interpose an empty wash bottle between the flask and the gas source* until the thermometer registers 157-158° (1). The reaction time may be considerably shortened by exposing the mixture to bright sunlight or to a small mercury-vapour lamp or any other UV lamp; if neither of these is practicable, support a ordinary 200-watt lamp a few inches from the flask.

Transfer the reaction mixture to a Claisen flask and distil under atmospheric pressure until the temperature reaches 135-140° (2). Distill the residue under diminished pressure and collect the benzyl chloride at 64-69°C at 12 mmHg. The latter upon redistillation boils largely at 63-65°C at 12 mmHg. The yield of benzyl chloride is about 100 g.

(1) An alternative method of determining the completion of the reaction is to weigh the flask and toluene, and to stop the passage of chlorine when the increase in weight is 37 g.

(2) The benzyl chloride may also be isolated by distillation under atmospheric pressure. The material boiling between 175°C and 185°C is collected and redistilled, the final product is collected at 178-182°C (pure benzyl chloride has bp 179°C). The resulting benzyl chloride is, however, of lower purity unless a fractionating column is used.

### Benzyl chloride (Method 2)

In a 500ml round-bottomed flask, fitted with an efficient reflux condenser, place 92g (106 ml) of toluene, 68 g (41 ml) of redistilled sulfuryl chloride and 1 g of dibenzoyl peroxide. Reflux gently, when a vigorous reaction takes place: the reaction is complete in 30 minutes. Isolate the benzyl chloride as described in Method 1. The yield is 60 g.

#### Dibenzoyl peroxide

Immerse a 600 ml. beaker, containing 50 ml. of "40-volume" hydrogen peroxide (100-volume is 30%) and equipped with a mechanical stirrer, in an ice bath. Support two dropping funnels, containing respectively 30 ml. of 1N sodium hydroxide solution and 30 g (25 ml) of redistilled benzoyl chloride, with their stems inside the beaker. Add the two reagents alternately a few drops at a time, taking care that the temperature does not rise above 5-8°C and that the solution is maintained faintly alkaline throughout. When all the reagents have been added, stir the solution for a further half an hour; by this time the odour of the benzoyl chloride should have disappeared. Filter off the flocculent precipitate at the pump, wash it with a little cold water, and dry upon filter paper. The yield of dibenzoyl peroxide is 12 g. It may be purified by dissolving in chloroform at *room temperature* and adding twice the volume of methyl alcohol. It should not be recrystallized from hot chloroform as serious explosion may result. The compound melts at 106°C with decomposition. Like all organic peroxides, dibenzoyl peroxide should be handled with care.

### Benzyl chloride (Method 3)

Into a 1-litre three-necked flask, equipped with a reflux (double surface) condenser, a mechanical stirrer (preferably of the Hershberg type, and a gas lead-in tube extending to near the bottom of the flask, place 200 g (227 ml) of dry benzene, 20g of paraformaldehyde (1) and 20 g of finely powdered anhydrous zinc chloride. Support the flask on a water bath so arranged that the level of the water in it is about the same height as the reaction. Heat the bath to 60°C and pass in (through an intervening empty wash bottle) a rapid stream of hydrogen chloride until no more gas is absorbed (about 20 minutes): allow to cool. Transfer the reaction mixture to a separatory funnel, wash it successively with two 50 ml. portions of cold water, two 50 ml. portions of saturated sodium bicarbonate solution (2) and finally with 20 ml. of water. Dry with anhydrous calcium chloride or magnesium sulfate, and distill under normal pressure from a Claisen flask with fractionating side arm until the temperature rises to 100-110°C. After cooling somewhat, distill under reduced pressure and collect the benzyl chloride at 63-65°C at 12 mmHg. The yield is 70 g. Some (about 4 g.) p-xylylene dichloride, m.p. 100°, and a small amount of diphenylmethane are present in the residue in the flask.

#### Notes.

(1) Formalin (40 percent.) may also be used; the proportions are then 200g of benzene, 38g of 40% formalin and 50 g of pulverized zinc chloride.

(2) It is essential to remove all the zinc salts in the washing process, otherwise the product largely resinifies during the distillation.

All above three methods are from Vogel, Practical Organic Chemistry, 3rd Ed.

### Benzyl chloride (Method 3)

I remember you guys talking about this awhile back, w/ speculation on chlorine generators and stuff...I ran across this today, while browsing a CA 12, 2573 (1918)

U.S. Pat.#1,280,612

Toluene and dry bleaching powder are heated together to 105 degrees in the abscence of other reagents.This avoids by-product formation. If equal amts are used, volume-wise, there is a high conversion. If more bleaching powder is used, the conversion is more robust, but contaminants such as benzal chloride and benzotrichloride are formed...

### Benzyl Cyanide (Org Syn Coll Vol 1, p 107-109)

In a 5000ml round-bottomed flask, fitted with a stopper holding a reflux condenser and separatory funnel, are placed 500 g. (10 moles) of powdered sodium cyanide (96-98 percent pure) and 450ml of water. The mixture is warmed on a water bath in order to dissolve most of the sodium cyanide, and then 1000g (8 moles) of benzyl chloride (bp 170-180°C) mixed with 1000g of 95 percent alcohol is run in through the separatory funnel in the course of 30-45 minutes. The mixture is then heated under a reflux condenser on the steam bath for four hours, cooled and filtered with suction to remove most of the sodium chloride. It is well to wash the filtered salt with a small portion of alcohol in order to remove any benzyl cyanide which may have been mechanically held.

The flask is now fitted with a condenser, and as much alcohol as possible is distilled off on the steam bath. The residual liquid is cooled, filtered if necessary, and the layer of benzyl cyanide separated. This crude benzyl cyanide is now placed in a Claisen distilling flask and distilled under reduced pressure, the water and alcohol coming over first, and finally the cyanide (it is preferable to distill the last part of the solvents and the benzyl cyanide under vacuum). It is advantageous to use a fractionating column. The material is collected at 135-140°C at 38 mmHg. (115-120°C at 10 mmHg.). The yield is 740-830g. (80-90 per cent of the theoretical amount). It is preferable to wash the final product in order to remove foul-smelling benzyl isocyaide, and to significantly lengthen the shelf-life of the product. The once-distilled benzyl cyanide is shaken vigorously for five minutes with an equal volume of warm (60°C) 50 percent sulfuric acid, prepared by adding 275ml of concentrated sulfuric acid to 500 ml of water. The benzyl cyanide is separated and washed with an equal volume of saturated sodium bicarbonate solution followed by an equal volume of half-saturated sodium chloride solution. It is then dried and distilled under reduced pressure. The loss in the washings is negligible.

### alpha-Phenylacetoacetonitrile (Org Syn Coll Vol 2, p 487-489)

A solution of sodium ethoxide is prepared from 60 g. (2.6 mol) clean sodium and 700 cc. 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 234 g. (2 moles) of pure benzyl cyanide (prepared as above) d 264 g. (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 -10°C, and kept at this temperature for two hours. The sodium salt is collected on a 6 in. Buchner funnel and washed four times on the funnel with 250-cc. portions of ether. The filter cake is practically colorless and corresponds 250-275 g. of dry sodium salt, or 69-76 per cent 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 0°C, and the nitrile precipitated by adding slowly, with vigorous shaking, 90 cc. of glacial acetic acid, while the temperature is kept below 10°C. The precipitate separated by suction filtration and washed four times on the funnel with 250 cc. portions of water. The moist cake weighing about 300 g. corresponds to 188-206 g. (59-64 per cent) of dry colorless phenylaceto- acetonitrile, m.p. 87-89°C, which is suitable for most purposes.

### Phenyl-2-Propanone (P2P) (Org Syn Coll Vol 2, p 391-392)

350 ml of concentrated sulfuric acid is placed in a 3000ml flask and cooled to -10°C. The total first crop of moist alpha-phenylacetoacetonitrile obtained according to the procedure above (corresponding to 188-206 g., or 1.2-1.3 moles of dry product) is added slowly, with shaking, the temp being kept below 20°C (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 0°C, 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 20 g. 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 110-112°C at 24 mmHg is collected; it weighs 125-150g (77-86% of the theoretical amount).

### Phenylacetic acid from benzyl chloride

10 pct. of a solution of 125 g benzyl chloride in 250 ml of sodium-distilled diethyl ether is added to 24 g magnesium turnings under 100 ml ether, and a small iodine crystal is added. after start of the grignard reaction the rest of the benzyl chlorideiis added with stirring to maintain gentle boiling (if the reaction becomes too vigorous, useless 1,2-diphenylethane is formed) and the mixture is heated and stirred until most magnesium is dissolved. The grignard reagent solution is poured on 1 kg water-free, crushed dry ice (solid CO2) and stirred for 2 hrs. 200 ml warm ether is added and the mixture is heated in a water-bath until the internal temperaturerreaches 25°C. 200 ml hydrochloric acid 32 pct. is added, and the heterogenous mixture stirred until any inorganic precipate is dissolved. after filtering, the organic layer is separated, washed with cold water, and dried over 20 g anhydr. sodium sulfate. the ether is distilled off, and the rest is recrystallized from water, to yield 75 pct - about 100 g - phenylacetic acid.

### P2P from phenylacetic acid, Sodium acetate method 1

50 g phenylacetic acid, 25 g anhydr. sodium acetate and 850 ml acetic anhydride are refluxed with stirring under moisture protection for 40 hrs. 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 two 250 ml portions of dichloromethane and the pooled organic layer is washed with cold diluted sodium hydroxide solution - any enol ester must be saponificated - until no more acids are present in the organic layer. The solution is dried over Na2SO4 and the dichloromethane is distilled of, the rest in a vacuum, and the crude phenylacetone is vacuum-distilled at 25 torr, b.range 120 - 140 degree celsius. yield about 30 ml - 70 pct. of theory.

### P2P from phenylacetic acid, Sodium acetate method 2

1000g anhydrous phenylacetic acid, 6000g acetic anhydride and 500g fused sodium acetate was loaded in a flask with vertical reflux condenser with attached CaCl2 tube. This mixture was refluxed at 145-150°C (bath temp) during 18 hrs. Then excess of solvent was distilled off, and after cooling the residue was partitioned between water and dichloroethane. The dichloroethane layer was separated, dried, and the solvent removed. The residue was vacuum distilled, the fraction 125-135°C (30-32 mmHg) was collected. After redistilling twice, the fraction had a bp of 210-215°C Yield 50-55% from theory. Ref: Magidson and Garkusha, Zh. Obsh. Khimii, 11(4) 339. CA 5868 (1941).

### P2P from phenylacetic acid, Pyridine method

A mixture of phenylacetic acid (13.6 g, 0.10 mole), acetic anhydride (50 ml) and pyridine (50 ml) was refluxed six hours, during the first part of which time carbon dioxide evolution was vigorous. After removal of the solvent the residue was taken up in benzene and shaken out with 10% sodium hydroxide. Removal of the benzene left 12 g of non-acidic material which on fractional distillation was separated into 7.5 g (56% yield) phenylacetone, bp 30-64°C (0.1 mm)

### Phenyl-2-Propanone from phenylacetic acid, Lead(IV)acetate method

Place 1000 gms of crude phenylacetic acid and 3000 gms of anhydrous (or monohydrate) lead acetate in a distillation apparatus and heat. Distill the water off first. Keep heating the flask and p-2-p will distill off next. Apply alot of heat (destructive distillation). The distillate will separate into two layers. Distill the organic layer and you will have pure P-2-P, boiling point 105°C at 10 mmHg or 216°C at STP. Osmium said: Ba or Ca acetate work, too. Just wanted to add this for the environmentalists among us.

### Phenylacetic acid from mandelic acid [Helv Chem Acta 22, 601 (1939)]

15 grams mandelic acid (0.1 mol), 2.07g KI (6.25% of theory), and 6g Red Phosphorous is dissolved in a solution of 70ml phosphoric acid and 10 ml of water, and this solution is refluxed for six hours (bp of soln 144°C). After the reaction mixture has cooled down, a little water is added to dissolve precipitated inorganic salts. The solution is extracted with ether, and the pooled extracts washed with a little dilute NaHSO3, followed by water, and is then dried over Na2SO4. The ether is removed under diminished pressureand the residue is distilled (bp 138-139 @13mmHg). The yield is 12.5 grams (90%) of phenylacetic acid melting at 76°C. 3.2 grams of phosphorous could be recovered from the aqueous solution.

### P2P from Benzylchloride (via Dibenzyl zinc)

Tis is all quite interesting but the dibenzyl zinc or dibenzyl cadmium route is much better and much quicker with no dimerization and no catalysts needed Add a slight excess of Mg to freshly dried/distilled benzyl chloride (vapor phase thru anhydrous CaCl2 will do nicely) in about 3x mol. of dry Et2O or THF add 1/2 equiv of freshly dried Zinc chloride or Cadmium Chloride as quickly as possible while still keeping things halfway tame (don't overun the reflux) When reaction has subsided add one equiv. acetic anhydride dropwise until reaction is finished. Quench in dilute HCl/ice water - yield 80~90%

### P2P from 2-Phenylpropanal

    > 2-PHENYLPROPANAL can be rearranged under certain conditions into P2P.
    > Rearrangement occurs under strong acidic conditions (meaning H2SO4) at low
    > temperatures (-10 to -20 deg C). I don't remember the strengh of acid he used,
    > but I'm quite sure it was in the 20 to 70% range (sorry, don't know anymore).
    > So simply add the cooled aldehyde into that cool acid, stir for an hour (or
    > maybe 2). Workup was done the usual way, namely stirring that acid mixture
    > into huge amount of cold water, steam distill or extract with org. solvent
    > and distill. As the aldehyde smells rather strong, purity can easily be
    > ascertained by your nose. Distillation doesn't work, bp of the two are close.

Rearrangement of 2-phenyl-propanal with OTC-chemicals to produce phenylacetone. Here's what I found out about this reaction:

A) 30 g of 2-phenylpropanal are refluxed with a solution of 60 g HgCl2 in 450 ml 75% EtOH for 5 hrs. Precipitate forms. Water is added and steam- distilled. Precipitate redissolves. Oily layer is extracted and fractionated (distilled over effective column). Yield: >80%! bp(11) 99-101°C.

B) 9 g of 2-phenylpropanal are slowly (40 min) added into conc. H2SO4. Temp is kept at -16°C. Stirring might be a good idea. Let stand 15 min. (same temperature). Pour on ice. The product is collected (extracted) and distilled. Yield: 5.6g (60%).

Both procedures are from an old german journal, meaning they will *probably* really work: S. Danilov, E. Venus-Danilova, Ber. 60, 1050 (1927).

[93-53-8]; Benzeneacetaldehyde, alpha-methyl-; 2-Phenylpropionaldehyde; Alpha-methyl tolualdehyde; 2-Phenyl propanal; Alpha methyl phenylacetaldehyde; Hydratropic aldehyde; Cumenealdehyde.

### Phenylacetone from chloroacetone

#### Chloroacetone, Method A:

Good method of preperation 150 ml acetone 50 ml water 12 g Cupric chloride 6 g lithium chloride. Reflux till reaction completes. Literature (Journal of the American Chemical Society vol 77 pgs 5274-5278) states 24 hours but the reaction has a half-life of about 24 minutes at 20°C (same article half of marker in 24 minutes, the marker being oxygen consumption in a slightly different reaction), therefore 5 hours is probably sufficient at reflux.

After reacting, distill everything below 123°C. The still bottoms can be reprocessed to recover cuprous chloride and lithium chloride. Both can be recovered by disolving with minimum water. The mix is easily converted to cupric chloride-lithium chloride by boiling with 20-35% hydrochloric acid.

Redistill slowly through a packed column to remove acetone. This leaves two fractions one distilling at 89C which is water and chloroacetone and the second distilling at 121C which is ?pure? chloroacetone. The second fraction may contain unsymetrical dichloroacetone I haven't had a sample analysed. Calcium Chloride will crash the water-chloroacetone mix which tends to form a colloidal solution.

Chloroacetone must be stabalized with 1% calcium carbonate or 0.1% water if it is stored or it forms an explosive sludge. Distillation of a water- chloroacetone mix at 89°C is the most efficient way of separating unsym- dichloroacetone from commercial products.

#### Chloroacetone, Method B:

This produces a product absolutely free from polychlorinated acetone, which usually is formed in the chlorination of acetone, and is almost impossible to completely remove by distillation.

A dried ether solution (approximately 500ml) containing 0.5 mole of diazomethane was placed in a 1000ml three-necked flask and practical grade acetyl chloride (0.25 mole) was added slowly from a dropping funnel with constant stirring of the solution which was maintained at a temperature not greater than 5°C. The reaction mixture was allowed to stand for two hours after the addition of the acetyl chloride and was then saturated with anhydrous HCl over a period of two hours. The bulk of the ether was removed by distillation, and the residual solution fractionated through a small column. The product boiling at 118-119°C at weighed 15.8g (68%), d 1.126.

Ref: JACS 76, 1186 (1954)

#### Phenylacetone:

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 123°C (20-22 mm) was obtained. Approximately 10 grams of high-boiling material was left in the distilling flask. Phenylacetone 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 magnesium sulfate and the ether distilled on a steam bath. The phenylacetone was distilled under reduced pressure, bp 108-114°C at 20-22 mmHg. Yield 6.5 grams, or 32%.

Ref: JACS 62, 1622 (1940)

### Synthesis of P2P via Propiophenone:

#### Propionyl Chloride [1]

Propionyl chloride was prepared not only by the usual methods with phosphorus bichloride or phosphorus pentachloride, but also by the chlorination of propionic acid in the cold with sulfur monochloride present.

To 540 g of propionic acid, 245 g of sulfur monochloride was added and chlorine was passed through the mixture while it was stirred for 15 hours. The chlorination proved to be incomplete at this point, since 150 g of unchanged propionic acid was recovered. There was also considerable sulfur monochloride, which was removed from the propionyl chloride by treatment with hydrogen sulfide. The propionyl chloride obtained amounted to 250 g. This product functioned as satisfactorily in the subsequent preparation of propiophenone as that prepared by the phosphorus halide methods.

#### Propiophenone [1]

Propiophenone was made by Pampel and Schmidt in 1886 by application of the Friedel and Crafts reaction. These investigators state that their yields were good, but give no data. In our preparation it was found necessary to employ vigorous mechanical stirring, and to keep the temperature of the reaction mixture below 20°C until all reagents were added. Where occasional shaking was depended upon, the yields amounted on an average to 40% but, with the above precautions, yields were more than doubled. The following preparation is given as typical of the final procedure.

Two hundred grams of finely divided anhydrous aluminum chloride was suspended in 300 g of dry benzene in a flask equipped so that the mixture could be thoroughly stirred and cooled. A mixture of 126 g of propionyl chloride and 105 g of benzene was run in drop by drop, the entire time of addition being 3 hours. At the end of this time the reaction mixture was kept for 2 hours at 50°C. The contents of the flask were cooled and poured over crushed ice; and, after 50 ml of conc hydrochloric acid had been added, the propiophenone and benzene were removed by distillation with steam. Thus, 152 g of propiophenone was obtained, boiling point 200-220°C; yield 84%.

#### 2-Chloro-propiophenone [2]

55g (0.41 mol) of thionyl chloride was added dropwise to a stirred solution of 50g (0.37 mol) of propiophenone in 250ml of carbon tetrachloride. The temperature of the mixture should never exceed 40°C. The solution was washed several times with water and dried over MgSO4. The 2-chloro-propiophenone was purified by distillation under vacuum (bp 108-110°C 1 mmHg). The yield was 80% of theory.

### 2-Chloro-1-phenylpropanol [3]

Meerwein-Pondoff-Verley reduction with Aluminum Isopropoxide and isopropanol.

#### 1-Phenyl-1,2-epoxypropane (propenylbenzene epoxide) [2]

75 uL of distilled water, 4 ml of DMF and 0.330g (2.4 mmol) of potassium carbonate was added to 0.79 mmol of 2-chloro-1-phenylpropanol. The mixture was stirred at room temp for 24 hours, diluted with water and extracted with ether. The etheral solution was washed with a saturated solution of NaCl and dried over MgSO4. The ether was evaporated under vacuum, to yield ~70% of crude epoxide. It can be purified by elution on a silica gel column with pentane as eluent.

#### Phenyl-2-Propanone

12g of 1-Phenyl-1,2-epoxypropane (propenylbenzene epoxide) was dissolved in 18 ml of tetraglyme and treated with anhydrous LiI (0.130g, 0.97 mmol) at 130°C for 5h. After cooling, the products were distilled under vacuum, recovering P2P in good yield.

[1] JACS 44, 1751-1752 (1922)
[2] Tetrahedron: Asymmetry 5(7), 1249-1268 (1994)

[3] JACS 62, 1424 (1940)