Benzyl chloride, hydrolysis

Benzyl chloride hydrolysis proceeds via a third mechanism (Sj.1). Results of studies of benzyl chloride hydrolysis ( 1) in distilled water and EPA-13 and EPA-2 sediment/water systems are summarized in Table V. Results for this compound include only overall first-order disappearance rate constants, but the data clearly show that the hydrolysis rate is independent of the fraction sorbed to sediment. Thus, the conclusion is again made that neutral hydrolysis proceeds via similar rate constants in both the aqueous and sediment-sorbed phases. 

It is interesting to note that the hydrolysis of unhindered benzoyl chlorides is not catalyzed by acids, but benzoyl fluoride is acid catalyzed and follows Kq (Bevan and Hudson, 1953). Similarly, acid catalysis of benzyl fluoride hydrolysis which follows occurs (Swain and Spalding, 1960), but no acid catalysis of benzyl chloride hydrolysis is known. Furthermore, benzyl halide reactions show non-linear pa correlations (Hudson and Klopman, 1962 Hill and Fry, 1962 Swain and Langsdorf, 1951). Although much less work has been carried out on benzoyl halides, it would appear then that nucleophilic reactions with benzoyl halides resemble, in many respects, nucleophilic reactions with benzyl systems, including the considerable uncertainty as to the S l or bimolecular nature of these reactions (Thornton, 1964). 

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. 

Benzylic halides resemble allylic halides m the readiness with which they form carbocations On comparing the rate of S l hydrolysis m aqueous acetone of the fol lowing two tertiary chlorides we find that the benzylic chloride reacts over 600 times faster than does tert butyl chloride... 

Binary azeotropic systems are reported for all three derivatives (9). The solubiHties of benzyl chloride, benzal chloride, and ben zotricbl oride in water have been calculated by a method devised for compounds with significant hydrolysis rates (10). 

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). 

The side-chain chlorine contents of benzyl chloride, benzal chloride, and benzotrichlorides are determined by hydrolysis with methanolic sodium hydroxide followed by titration with silver nitrate. Total chlorine determination, including ring chlorine, is made by standard combustion methods (55). Several procedures for the gas chromatographic analysis of chlorotoluene mixtures have been described (56,57). Proton and nuclear magnetic resonance shifts, characteristic iafrared absorption bands, and principal mass spectral peaks have been summarized including sources of reference spectra (58). Procedures for measuring trace benzyl chloride ia air (59) and ia water (60) have been described. 

The 2,4,6-trimethylbenzyl ester has been prepared from an amino acid and the benzyl chloride (Et3N, DMF, 25°, 12 h, 60-80% yield) it is cleaved by acidic hydrolysis (CF COOH, 25°, 60 min, 60-90% yield 2 N HBr/HOAc, 25°, 60 min, 80-95% yield) and by hydrogenolysis. It is stable to methanolic hydrogen chloride used to remove A-o-nitrophenylsulfenyl groups or triphenylmethyl esters. ... 

Tribromobenzoic acid has been prepared by the deamination of 2,4,6-tribromo-3-aminobenzoic acid (reagents not specified), by hydrolysis of 2,4,6-tribromobenzonitrile, " and by oxidation of the tribromotoluene, the benzyl chloride, the aldehyde,and the glyoxylic acid.i The present method is a modification of that of Bunnett, Robison, and Pennington.i ... 

Benzyl chloride can produce henzyl alcohol hy hydrolysis ... 

Benzylacetophenone has been prepared by the reduction of benzalacetophenone with zinc and acetic acid1 and catalytic-ally with palladium and hydrogen 2 by the reduction of /3-duplo-benzylidene acetophenone monosulfide 3 by the oxidation of the corresponding car bind with chromic acid 4 by the hydrolysis of ethyl benzyl benzoylacetate 5 from acetophenone and benzyl chloride by the action of sodamide 6 and from benzoic and hydrocinnamic adds using as catalysts manganese oxide 7 and ferric oxide.8... 

Similarly, Pd/tppts was used by Hoechst (Kohlpainter and Beller, 1997) as the catalyst in the synthesis of phenylacetic acid by biphasic carbonylation of benzyl chloride (Fig. 2.29). The new process replaces a classical synthesis by reaction of benzyl chloride with sodium cyanide, followed by hydrolysis of the resulting benzyl cyanide. Although the new process produces one equivalent of sodium chloride, this is substantially less salt production than in the original process. Moreover, sodium cyanide is about seven times as expensive per kg as carbon monoxide. 

Supemucleophilic polymers containing the 4-(pyrro-lidino)pyridine group were synthesized from the corresponding maleic anhydride copolymers and also by cyclopolymerization of N-4-pyridyl bis(methacryl-imide). The resulting polymers were examined for their kinetics of quaternization with benzyl chloride and hydrolysis of pj-nitrophenylacetate. In both instances, the polymer bound 4-(dialkylamino)pyridine was found to be a superior catalyst than the corresponding low molecular weight analog. 

Thus for hydrolysis in 50% aqueous acetone, a mixed second and first order rate equation is observed for phenylchloromethane (benzyl chloride, 10)—moving over almost completely to the SV1 mode in water alone. Diphenylchloromethane (11) is found to follow a first order rate equation, with a very large increase in total rate, while with triphenylchloromethane (trityl chloride, 12) the ionisation is so pronounced that the compound exhibits electrical conductivity when dissolved in liquid S02. The main reason for the greater promotion of ionisation—with consequent earlier changeover to the SW1 pathway in this series—is the considerable stabilisation of the carbocation, by delocalisation of its positive charge, that is now possible ... 

Benzyl chloride undergoes all the transformations of the alkyl halides. Hydrolysis with hot aqueous alkalis yields the corresponding alcohol, benzyl alcohol C6H5.CH2OH, a colourless liquid which boils at 206°. (Chap. V. 4, p. 220.)... 

Analysis of the Benzyl Chloride.—The quantitative determination of halogen in substances containing halogen in aliphatic combination is not carried out in a sealed tube by the Carius method (cf. p. 69), but by hydrolysis with standard alcoholic potassium hydroxide solution. Since this method is very often used, a check on the purity of the present preparation may be combined with practice in this method of analysis. 

The pyrolysis temperature and the rate of addition are chosen such that about 50% of the acid chloride is recovered as 2-toluic acid after hydrolysis. Under these conditions only a small amount of benzyl chloride and polymeric material is formed in addition to benzocyclobutenone. The percentage of reactant conversion depends not only on the pyrolysis temperature, but also on the pressure in the reactor and on the rate of reactant addition. It is advisable, therefore, to optimize the pyrolysis temperature in trial runs keeping the other variables constant. 

Slowly hydrolyzes in water forming HCl and benzyl alcohol. The estimated hydrolysis half-life in water at 25 °C and pH 7 is 15 h (Mabey and Mill, 1978). The hydrolysis rate constant for benzyl chloride at pH 7 and 59.2 °C was determined to be 0.0204/min, resulting in a half-life of 34 min (Ellington et al, 1986). 

Neutral Hydrolysis Studies. Investigations of neutral (pH-independent) hydrolysis kinetics in sediment/water systems were conducted for three organophosphorothioate insecticides (chlorpyrifos, diazinon and Ronnel), 4-(p-chlorophenoxy)butyl bromide, benzyl chloride, and hexachlorocyclopentadiene. 

Table V. Hydrolysis of Benzyl Chloride in Sediment/Water Systems at 25°C...

The synthesis of the basic skeleton of 1-benzylisoquinoline alkaloids has been reported by Uff et al. 15) starting from isoquinoline and benzyl chloride (Scheme 5). The preparation of Reissert compound iV-benzyl-l-cyano-l,2-di-hydroisoquinoline (4) was performed in a dichloromethane-water two-phase system with potassium cyanide and benzoyl chloride in about 64-69% yield. The deprotonation of 4 with sodium hydride in dimethylformamide solution, the subsequent alkylation with benzyl chloride, and the final alkaline hydrolysis could be performed as a one-pot reaction sequence to supply 1-benzylisoquinoline (25) in an overall yield of 75-84%. 

Although the standard amidocarbonylation reaction involves an aldehyde and an amide, benzyl chloride can be used as the reactant. The amidocarbonylation of benzyl chloride was first reported by Wakamatsu eta/, in 1976 using Co2(CO)8 as catalyst precursor. This process was revisited by de Vries et al. in 1996 and iV-acetylphenylalanine 8 was obtained in 82% yield under the optimized conditions (Scheme 2)." Since the Co-catalyzed amidocarbonylation is carried out in the presence of CO and H2, formylation of benzyl chloride takes place first to form phenylacetalde-hyde in situ. In this particular case, as Scheme 2 illustrates, A-acetylenamine 10 is formed as intermediate, followed by the chelation-controlled HCo(CO)4 addition to give alkyl-Co intermediate II. Insertion of CO to the carbon-Co bond of II, forming acyl-Co complex 12, followed by hydrolysis affords 8 and regenerates active Co catalyst species. 

The previous extension of solvent mixtures involved solvent interfaces. This organic-water interfacial technique has been successfully extended to the synthesis of phenylacetic and phenylenediacetic acids based on the use of surface-active palla-dium-(4-dimethylaminophenyl)diphenylphosphine complex in conjunction with dode-cyl sodium sulfate to effect the carbonylation of benzyl chloride and dichloro-p-xylene in a toluene-aqueous sodium hydroxide mixture. The product yields at 60°C and 1 atm are essentially quantitative based on the substrate conversions, although carbon monoxide also undergoes a slow hydrolysis reaction along with the carbonylation reactions. The side reaction produces formic acid and is catalyzed by aqueous base but not by palladium. The phosphine ligand is stable to the carbonylation reactions and the palladium can be recovered quantitatively as a compact emulsion between the organic and aqueous phases after the reaction, but the catalytic activity of the recovered palladium is about a third of its initial activity due to product inhibition (Zhong et al., 1996). 

The common route to phenylacetic acid is conversion of benzyl chloride into benzyl cyanide by reaction with sodium cyanide, followed by hydrolysis. 

Other syrupy, benzylated bromides bearing O-acetyl or O-p-nitro-benzoyl groups were also prepared and characterized,86-84 as well as a partially benzylated chloride.85 Acid hydrolysis of 22 gave crystalline 2-O-benzyl-a-L-fucose, which was acylated with p-nitrobenzoyl chloride-pyridine. Treatment84 of the resulting tris(p-nitrobenzoate) with hydrogen bromide-dichloromethane led to precipitation of p-nitrobenzoic acid and formation of syrupy 2-0-benzyl-3,4-di-0-(p-nitro-benzoyl)-a-L-fucopyranosyl bromide (33). 

When treating the overall transformation kinetics of an organic compound as we have done for the hydrolysis of benzyl chloride (Eq. 12-11), we assume that the reverse reaction (i.e., the formation of benzyl chloride from benzyl alcohol) can be neglected. For many of the reactions discussed in the following chapters we will make this assumption either because the reverse reaction has an extremely small rate constant (i.e., the reaction is practically irreversible), or because the concentration ) of the reactant(s) are very large as compared to the concentration(s) of the product(s). There are, however, situations in which the reverse reaction has to be taken into account. We have already encountered such a reaction in Illustrative Example 12.1. To demonstrate how to handle the reaction kinetics in such a case, we use the hydration of an aldehyde to yield a diol (Fig. 12.3). This example will also illustrate how the equilibrium reaction constant, Kn is related to the kinetic rate constants, kY and k2, of the forward and reverse reaction. 

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