Benzylation benzyl chloride

Thermolysis of 88 (R1 = PhCH2) with excess benzyl chloride to give 79 (87%) must be a related reaction, as must that between pyrazoles 89 (Scheme 22) and hydrochloric acid to yield 90 and 91.7 Labeling with UCH3 at C-4 showed ease of loss of R to be PhCH2 > CH2=CHCH2 Me for R = benzyl, benzyl chloride (91%) was also isolated.7... 

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

Thiourea, unlike urea, readily reacts in the tautomeric form (I) in the presence of suitable reagents, particularly alkyl halides thus benzyl chloride reacts with... 

Add in turn benzyl chloride (8 3 g., 8 o ml.) and powdered thiourea (5 gm.) to 10 ml. of 95% ethanol in a 100 ml. flask fitted with a reflux condenser. Warm the mixture on the water-bath with gentle shaking until the reaction occurs and the effervescence subsides then boil the mixture under reflux for 30 minutes. Cool the clear solution in ice-water, filter off the crystalline deposit of the benzylthiouronium chloride at the pump, wash it with ice-cold ethyl acetate, and dry in a desiccator. Yield, 11-12 g., m.p. 170-174°. The white product is sufficiently pure for use as a reagent. It is very soluble in cold water and ethanol, but can be recrystallised by adding ethanol dropwise to a boiling suspension in ethyl acetate or acetone until a clear solution is just obtained, and then rapidly cooling. 

Benzoic Acid, CeHgCOOH, from Benzyl Chloride, CeHaCH.Cl. 

In the following preparation, the oxidation of benzyl chloride instead of toluene is therefore given in order to reduce the time required. It should be borne in mind, however, that the procedure is othenvise independent of the nature of the side chain. 

Required Anhydrous sodium carbonate, 5 g. potassium permanganate, 10 g. benzyl chloride, 5 ml. sodium sulphite, ca. 20 g. 

In the example given below, phenylarsonic acid is reduced to dichlorophenyh arsine, Ccll jAsCl. This compound when added to aqueous sodium hydroxide and treated with benzyl chloride gives benzylphenylarsinic acid, which is readily isolated from solution. 

Methyl iodide, ethyl bromide and iodide, higher alpihatic halides chloroform, iodoform, carbon tetrachloride chlorobenzene, bromobenzene, iodobenzene benzyl chloride. 

Thiourea. Boil in ethanolic solution with benzyl chloride to prepare the crystalline benzylthiouronium chloride, m.p. lyo i 74" (P- 126). 

Alkaline permanganate. Heat under reflux i g. of i,2 naph thoquinone, 50 ml. of saturated aqueous KMn04 solution and 2 g. of anhydrous NajCO for 30 minutes. Then proceed as for oxidation of benzyl chloride (p. 393). 1,2-Naphthoquinone gives phthalic acid, m.p. 195°. Phenanthraquinone gives diphenic acid, HOOC CeH CeH COOH, m.p. 229°. 

Chlorobenzene, CjHjCl, bromobenzene, CgHgBr, and iodobenzene possess aromatic odours. Benzyl chloride, CgHjCHgCl, has a sharp irritating odour and is lachrymatory. 

Ethyl bromide and ethyl iodide behave similarly. Benzyl chloride gives a faint precipitate in the cold, but the precipitation is complete on gentle warming. 

Similar results are obtained with methyl iodide, ethyl bromide, ethyl iodide, iodoform, carbon tetrachloride, and benzyl chloride. 

Bromobenzene, iodobenzene and benzyl chloride behave somewhat similarly. The />-nitro-derivatives of the first two compounds frequently crystallise out even before pouring into water p-nitrobenzyl chloride usually remains as an oil for several minutes before solidifying. 

Formation of 2 naphthyl ethers. Alkyl halides and aryl-alkyl halides (e.g. benzyl chloride) are converted into 2-naphthyl ethers thus ... 

Heat together under reflux 1 g. of 2-naphthol, 3 ml. of 10% NaOH solution and 0 5 ml. of the halide (e.g. benzyl chloride) for 30 minutes. Cool, shake w ith about 10 ml, of water and filter off the solid ether. Recrystallise from ethanol m.p. 101 5 ... 

I. Oxidation to benzoic acid. Boil a mixture of i ml. of benzyl chloride, 50 ml. of saturated aqueous KMn04 solution and 2 g. of anhydrous Na.jCOj under reflux for 30 minutes. Acidify with cone. HCl and then add 25% Na SOj solution until the brown precipitate of MnOj has dissolved. On cooling, benzoic acid crystallises out. Filter through a small Buchner funnel, wash with water and identify (P 347) When recrystallised from water, benzoic acid has m.p. 121 . 

Oxidation, (a) Oxidise 1 g. of styrene with KMn04 and NajCOj (for details see oxidation of benzyl chloride, p. 391). Benzoic acid, m.p. 121 is obtained. Stilbene similarly gives benzoic acid, but requires longer heating—about 1 hour. 

Pungent odour. Formic acid, acetic acid, acetyl chloride, acetic anhydride, benzoyl chloride, benzyl chloride, pyridine. Benzoquinone (when warmed with water). 

By-products are formed in both preparations thus in the former, anthracene, and o- and p-dibenzylbenzenes are present in the fraction of high boiling point. Diphenylmethane is more conveniently obtained by the interaction of benzyl chloride and benzene in the presence of aluminium amalgam ... 

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... 

In the absence of catalysts, toluene when treated with chlorine (or bromine) at the boiling point, preferably with exposure to sunlight or other bright light source, undergoes halogenation in the side chain. The entrance of the first chlorine atom, for example, proceeds at a much faster rate than the entrance of the second chlorine atom so that in practice the major portion of the toluene is converted into benzyl chloride before appreciable chlorination of benzyl chloride occurs ... 

Transfer the reaction mixture to a Claisen flask and distil vmder atmospheric pressure imtil the temperature reaches 135-140° (3). Distil the residue under diminished pressure and coUeot the benzyl chloride at 64—69°/12 mm. The latter upon redistillation boils largely at 63- 65°/12 mm. The yield of benzyl chloride is about 100 g. 

The benzyl chloride may also be isolated by distillation under atmospheric pressure. The material boiling between 165° and 185° is collected and redistilled the final product is collected at 178-182° (pure benzyl chloride has b.p. 179°). The resulting benzyl chloride is, however, of lower purity unless an efficient fractionating column is used. 

Method 2. In a 500-ml. rovmd-bottomed flask, fitted with an efficient reflux condenser, place 92 g, (106 ml.) of toluene, 68 g. (41 ml.) of redistilled sulphuryl cldoride and 1 g, of dibenzoyl peroxide (Section IV,196). 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 50 g. 

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