Benzyl chloride with magnesium

In their early publications on the synthesis of organosilicon derivatives. Kipping and coworkers reacted benzyl chloride with magnesium in the presence of silicon chlorides [93] ... 

Add 2-chloromethyl-2-propenyl benzyl ether3,42 (0.49 g, 2.5 mmol) and 1,2-dibromoethane (0.094 g, 0.5 mmol), and regulate the reaction temperature so as to induce and maintain a smooth reaction of the chloride with magnesium producing the desired Grignard reagent (about 90% yield). 

Prepare a solution of benzyl magnesium chloride in a 2-litre three-necked flask from 24-3 g. of magnesium turnings, 600 ml. of sodium-dried ether and 126-5 g. (115 ml.) of redistilled benzyl chloride follow the experimental details given under n-Propylbenzene (Section IV,7). Cool the flask in running water or in ice water. Place a solution of 456 g. of n-butyl-p-toluenesulphonate (Section IV,198) in about twice its volume of anhydrous ether in the dropping funnel, and add it slowly with stirring, at such a rate that the ether just boils a white solid soon forms. The addition is complete after about 2 hours. Pour the reaction product... 

Phenylacetic acid. Use 5 0 g. of magnesium, 25 g, (23 ml.) of redistilled benzyl chloride (Section IV,22) and 75 ml. of sodium-dried ether. Allow the reaction mixture to warm to 15° and then decompose it with dilute hydrochloric or sulphuric acid. Filter off the crude acid and recrystallize it from water. The yield of pure phenylacetic acid, m.p. 76-77°, is 11 g. 

Preparation of benzyl cyanide. Place 100 g. of powdered, technical sodium cyanide (97-98 per cent. NaCN) (CAUTION) and 90 ml. of water in a 1 litre round-bottomed flask provided with a reflux condenser. Warm on a water bath until the sodium cyanide dissolves. Add, by means of a separatory funnel fitted into the top of the condenser with a grooved cork, a solution of 200 g. (181-5 ml.) of benzyl chloride (Section IV.22) in 200 g. of rectified spirit during 30-45 minutes. Heat the mixture in a water bath for 4 hours, cool, and filter off the precipitated sodium chloride with suction wash with a little alcohol. Distil off as much as possible of the alcohol on a water bath (wrap the flask in a cloth) (Fig. II, 13, 3). Cool the residual liquid, filter if necessary, and separate the layer of crude benzyl cyanide. (Sometimes it is advantageous to extract the nitrile with ether or benzene.) Dry over a little anhydrous magnesium sulphate, and distil under diminished pressure from a Claisen flask, preferably with a fractionating side arm (Figs. II, 24, 2-5). Collect the benzyl cyanide at 102-103°/10 mm. The yield is 160 g. 

Benzyl chloride readily forms a Grignard compound by reaction with magnesium in ether with the concomitant formation of substantial coupling product, 1,2-diphenylethane [103-29-7]. Benzyl chloride is oxidized first to benzaldehyde [100-52-7] and then to benzoic acid. Nitric acid oxidizes directly to benzoic acid [65-85-0]. Reaction with ethylene oxide produces the benzyl chlorohydrin ether, CgH CH20CH2CH2Cl (18). Benzylphosphonic acid [10542-07-1] is formed from the reaction of benzyl chloride and triethyl phosphite followed by hydrolysis (19). 

In a 3-I. three-necked flask, fitted with a mechanical stirrer, a reflux condenser, and a separatory funnel, are placed 24.3 g. (i gram atom) of magnesium turnings, 500 cc. of absolute ether, a crystal of iodine, and a 5- to lo-cc. portion of 126.5 g- cc., I mole) of freshly distilled benzyl chloride (b.p. 177-179°). In a few minutes the reaction starts (Note 1) and is controlled if necessary by cooling with a wet towel. The stirrer is started and the balance of the benzyl chloride is run in as fast as the refluxing will permit. The addition requires from one to two hours, and when completed the mixture is refluxed ofi the steam bath with stirring for three hours. With the stirrer stUl running, 182 g. (r mole) of benzophenone (Org. Syn. Coll. Vol. i, 89) dissolved in 500 cc. of absolute ether is added at such a rate that the mixture refluxes rapidly. This requires about twenty minutes and then the reaction mixture is allowed to stand for two hours (Note 2). 

Bruce and Sutcliffe obtained l-acetyl-2-methyl-3-phenylindole (123) by the action of acetyl chloride on 2-methyl-3-pheiiylindole magnesium iodide in ether.These authors were able to obtain l-benzoyl-2-benzyl-3-phenylindole (124) but not l-acetyl-2-benzyl-3-phenylindole (125) from 2-benzyl-3-phenylindole magnesium iodide by analogous procedures.3-Acetyl-2-phenylindole (126) and 3-propionyl-2-pheny]indole (127) have recently been prepared in fair yield by the acylation of 2-phenylindole magnesium iodide with acetyl and propionyl chloride, respectively. Le ete obtained a mixture of l-acetyl-3-ethylindole (128) and 2-acetyl-3-ethylindole (129) by the interaction of acetyl chloride with 3-ethylindole magnesium iodide in ether. 

The stereospecific conversion of menthyl arenesulphinates into chiral aryl methyl sulphoxides may also be achieved by means of methyllithium . The reaction of methyllithium with diastereoisomerically or enantiomerically pure arenesulph-inamides 283 was found to give optically active aryl methyl sulphoxides 284 (equation 156). The preparation of optically active sulphoxides 285 and 286, which are chiral by virtue of isotopic substitution (H - D and - respectively), involves the reaction of the appropriate non-labelled menthyl sulphinates with fully deuteriated methyl magnesium iodide (equation 157) and with benzylmagnesium chloride prepared from benzyl chloride labelled with carbon (equation 158). 

One mole of benzylmagnesium chloride is prepared in a 2-1. three-neck round-bottom flask from 24.3 g. (1 mole) of magnesium turnings, 126.5 S- C1 m°le) of benzyl chloride and 500 cc. of anhydrous ether, according to the directions given in Org. Syn. 4,59. Stirring should be commenced with the first addition of the benzyl chloride. The time of addition of the benzyl chloride in this preparation is about two hours. When all has been added, the mixture is gently boiled for about fifteen minutes (Note 1). 

B. 1-Benzylindole. The slurry of indole sodium is cooled to 0° (ice bath), and 2.30 ml. (2.53 g., 0.02 mole) of benzyl chloride (Note 5) is added as rapidly as possible to the stirred mixture. The mixture is then stirred for 8-15 hours (overnight), during which time the ice in the ice bath melts and the temperature of the reaction flask gradually rises to room temperature. The mixture is then diluted with 15 ml. of water and extracted with three 25-ml. portions of ether. The combined ethereal extracts are washed with two 40-ml. portions of water and dried with anhydrous magnesium sulfate. After filtration the solvent is removed at reduced pressure, and 4.4 g. of crude 1-benzylindole is obtained as a liquid. After bulb-to-bulb distillation of this material in a Kiigelrohr oven [120-130° (0.0025 mm.)], crystallization of the distillate from 15 ml. of hot ethanol affords 3.46-3.61 g. (83-87%) of 1-benzylindole. A second crop amounting to 0.17-0.26 g. (4-6%) is obtained on concentration of the mother liquors to 6 ml. The total yield of 1-benzylindole, m.p. 43-44°, is 3.72-3.78 g. (90-91%) (Notes 6 and 7). 

Ethyl phenylacetate may be prepared by the treatment of benzyl cyanide with alcohol and hydrochloric acid gas.1 It is much more convenient in the laboratory, however, to use sulfuric acid in place of hydrochloric acid in fact, the yields obtained are better than those recorded in the literature. This ester may also be made by the esterification of phenylacetic acid with hydrochloric acid and alcohol 2 or with alcohol and sulfuric acid 3 the following less important methods of preparation may be mentioned the action of benzyl magnesium chloride upon ethyl chlorocarbonate,4 and the action of copper on a mixture of bromobenzene and ethyl chloroacetate at 1800.5... 

The method described is adapted from the procedures of Kym 3 and Engelhardt, Latschinoff, and Malyscheff.4 Thio-benzoic acid has been prepared by the reaction of benzoyl chloride with potassium sulfide,4 hydrogen sulfide in pyridine,6 6 and magnesium bromide hydrosulfide.7 It is formed from dibenzoyl disulfide with potassium hydrosulfide,4 potassium hydroxide,4 8 and ammonia.9 It is also formed from dibenzoyl sulfide, from phenyl benzoate, and from benzoic anhydride with alcoholic potassium hydrosulfide.4 It has been obtained from dibenzoyl sulfide and hydrogen sulfide,10 carbon oxysulfide and phenyl-magnesium bromide,11 12 dibenzyl disulfide and sodium ethoxide,13 benzyl chloride and sulfur in the presence of potassium hydroxide,14 and benzylthiosulfuric acid and alkali.18 16... 

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