Benzyl chloride reactivity

Why is benzyl chloride reactive in both tests, whereas bromobenzene is unreactive ... 

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. 

Ingold and his co-workers used the competitive method in their experiments, in which nitration was brought about in acetic anhydride. Typically, the reaction solutions in these experiments contained o-8-I 4 mol of nitric acid, and the reaction time, depending on the reactivities of the compounds and the temperature, was 0-5-10 h. Results were obtained for the reactivities of toluene, > ethyl benzoate, the halogenobenzenes, ethyl phenyl acetate and benzyl chloride. Some of these and some later results are summarized in table 5.2. Results for the halogenobenzenes and nitrobiphenyls are discussed later ( 9.1.4, lo.i), and those for a series of benzylic compounds in 5,3.4. 

Carbocations derived from the alcohol are probably the reactive species, but data concerning by-products expected with carbocationic intermediates are lacking. Rearrangement of 2-alkylaminothiazoles to 2-amino-5-alkylthiazoles may also explain the observed products 2-aminothiazole with benzyl chloride yields first 2-benz Iaminothiazole (206). which then rearranges to 2-amino-5-benzvlthiazole (207) (Scheme 130) (163. 165. 198). 

According to Section 4.02.3.1.8 substituents removed from the pyrazole ring by two or more saturated carbon atoms and substituents on the benzene ring of indazoles are similar in reactivity to the corresponding aromatic derivatives. For instance, chloromethyl-pyrazoles are comparable to benzyl chlorides and 5-hydroxyindazoles to /3-naphthols in their reactivity. 

The second-order rate constants for the reaction of a number of amines with benzyl chloride are tabulated below. Calculate A// and A5 from the data. Offer an explanation for the relative reactivity order for the amines. What trends do you observe in A// with reactivity ... 

The thenyl chlorides appear to be more reactive in nucleophilic aliphatic substitution than the benzyl analogs. Thus, 2-thenyh chloride gives, in the reaction with sodium cyanide in ethanol, a mixture of ethyl 2-thenyl ether (25% yield) and 2-thenyl cyanide (32% yield), whereas benzyl chloride gives a high 3deld of benzyl cyanide uncontaminated with benzyl ether. When 2-thenyl chloride and benzyl chloride were allowed to compete for a deficiency of sodium amyloxide, 2-thenyl chloride reacted three times faster. In acetone solution 2-thenyl cyanide is obtained smoothl. ... 

The chloromethylation can be generally employed in aromatic chemistry benzene, naphthaline, anthracene, phenanthrene, biphenyls and many derivatives thereof are appropriate substrates. The benzylic chlorides thus obtained can be further transformed, for example to aromatic aldehydes. Ketones like benzophe-none are not reactive enough. In contrast phenols are so reactive that polymeric products are obtained. ... 

The alkylation of sodium 2-naphthoxide with benzyl bromide in tetrabutylam-monium and tetrabutylphosphonium halide salts was investigated by Brunet and Badri [50] (Scheme 5.1-21). The yields in this reaction were quantitative, and alkylation occurred predominantly on the oxygen atom of the naphthoxide ion (typically 93-97 %). The rate of the reaction was slower in the chloride salts, due to the benzyl bromide reacting with chloride ion to give the less reactive benzyl chloride. 

In order to determine the efficiency of the polymers as reagents in nucleophilic catalysis, it was decided to study the rate of quaternization with benzyl chloride. Table I shows the second-order-rate constants for the benzylation reaction in ethanol. Comparison with DMAP indicates that poly(butadiene-co-pyrrolidinopyridine) is the most reactive of all the polymers examined and is even more reactive than the monomeric model. This enhanced reactivity is probably due to the enhanced hydrophobicity of the polymer chain in the vicinity of the reactive sites. 

Wiberg has described the reactions of the silene Me2Si=C(SiMe3)2 with a wide variety of reagents and has reported on their relative rates of reaction (see Table VIII).98 174 Some silenes will add chlorogermanes and chlorostannanes174 as well as reactive organic halides such as chloroform, carbon tetrachloride, and benzyl chloride. 

Methyl a-D-glucopyranoside may be converted,271 in a remarkably selective reaction, into its 2,4,6-tribenzyl ether (in 62% yield) on treatment with three molar equivalents of sodium hydride in benzyl chloride at 110°, a substitution pattern that might have been predicted in view of the low, relative reactivity of HO-3 towards alkylation in the mechanistically related, Haworth procedure.268 Similar, selective benzylations have also been achieved on partially substituted derivatives of methyl a- and /3-D-galactopyranoside272 and on methyl 6-deoxy-a-L-galactopyranoside62 in all of these, an unexpectedly high relative-reactivity of HO-4 (ax) compared to that of HO-3 (eq) was noted, indicating that steric factors are not the sole influence on reactivity in these cases. Nevertheless, the primary hydroxyl... 

Functionalization of these reactive anionic chain ends can be achieved by a variety of methods all based on the general concepts of carbanion chemistry. For example, reaction with C02 or succinnic anhydride leads to the carboxy terminated derivatives [10], while hydroxy-terminated polymers can be easily obtained by reaction with ethylene oxide (Scheme 3) [11]. In select functionalization reactions, such as alkylation with p-vinyl benzyl chloride, the nucleophilicity of the carbanionic species may be necessary and this can be achieved by reaction of the chain end with 1,1-diphenylethene followed by functionalization [12,13]. 

How is the course of halogen substitution in the benzene nucleus to be explained It is not at all probable that direct replacement of hydrogen occurs, such as we must assume in the formation of benzyl chloride and in the reaction between methane and chlorine, since the hydrogen attached to the doubly bound carbon atom of olefines exhibits no special reactivity. However, various facts which will be considered later (p. 164) indicate that benzene reacts with halogen in fundamentally the same way as does ethylene. The behaviour of ethylene towards bromine is the subject of the next preparation. 

Knochel et al. (1977a) have studied the effect of the structure of the ligand on its ability to catalyse the reaction between solid metal acetates and benzyl chloride dissolved in acetonitrile. Approximate half-lives for the reactions are given in Table 29. For crown ethers, the reactivity sequence decreases in the... 

In some cases, the nature of the electrophile and the type of base used can determine the type of product isolated. For example, after treatment of bis(pyrazol-l-yl)methane (Scheme 34) with ri-BuLi at 25°C, reactive alkyl halides such as methyl iodide or benzyl chloride favor formation of the methylene substituted (kinetic) products, whereas with carbonyl... 

As a rule, the annular nitrogen atoms in 1,3,4-thiadiazoles are very reactive towards electrophiles as shown by facile alkylation reactions and quaternary salt formation. A thorough study on the quaternization of 2,5-disubstituted thiadiazoles, and its comparison with pyridazines has been published <84CHEC-i(4)545>. Electrophilic attack by benzyl chloride on 2-aminothiadiazole to give (44) in a regiospecific manner was utilized in the synthesis of an antiviral candidate <92MI 4io-oi>. 

The most important point about the alkyl halide reactivities in triphase catalysis is that the reactions which have the highest intrinsic rates are the most likely to be limited by intraparticle diffusion. The cyanide ion reactions which showed the greatest particle size and cross-linking dependence with 1-bromooctane had half-lives of 0.5 to 2 h and with benzyl bromide had half-lives of 0.13 to 0.75 h. The reactions of 1-bromooctane and of benzyl chloride which were insensitive to particle size and cross-linking had half-lives of 14 h and 3 h respectively. Practical triphase liquid/ liquid/solid catalysis with polystyrene-bound onium ions has intraparticle diffusional limitations. 

Spacer chain catalysts 3, 4, and 19 have been investigated under carefully controlled conditions in which mass transfer is unimportant (Table 5)80). Activity increased as chain length increased. Fig. 7 shows that catalysts 3 and 4 were more active with 17-19% RS than with 7-9% RS for cyanide reaction with 1-bromooctane (Eq. (3)) but not for the slower cyanide reaction with 1-chlorooctane (Eq. (1)). The unusual behavior in the 1-bromooctane reactions must have been due to intraparticle diffusional effects, not to intrinsic reactivity effects. The aliphatic spacer chains made the catalyst more lipophilic, and caused ion transport to become a limiting factor in the case of the 7-9 % RS catalysts. At > 30 % RS organic reactant transport was a rate limiting factor in the 1-bromooctane reations80), In contrast, the rate constants for the 1 -chlorooctane reactions were so small that they were likely limited only by intrinsic reactivity. (The rate constants were even smaller than those for the analogous reactions of 1-bromooctane and of benzyl chloride catalyzed by polystyrene-bound benzyl-... 

---