The Halobenzenes

Halobenzenes undergo nucleophilic aromatic substitution through either of two mechanisms. If the halobenzene has a strongly electron-withdrawing substituent in the ortho or para position, substitution occurs by addition of a nucleophile to the ring, followed by elimination of halide from the intermediate anion. If the halobenzene is not activated by an electron-withdrawing substituent, substitution can occur by elimination of HX to give a benzyne, followed by addition of a nucleophile. 

The halobenzenes also have an atom adjacent to the nucleus that carries an electron-pair thus specific stabilisation of the a complexes for o- and p-attack, (51c - 51d) and (52c++52d) respectively, can... 

That the steric factor is not the sole determinant is, however, seen in the figures for the nitration of the halobenzenes, which are o-/p-directing but on which overall attack is slightly slower than on benzene (p. 155) ... 

The reactivities of aryl halides, such as the halobenzenes, are exceedingly low toward nucleophilic reagents that normally effect displacements with alkyl halides and activated aryl halides. Substitutions do occur under forcing conditions of either high temperatures or very strong bases. For example, chlorobenzene reacts with sodium hydroxide solution at temperatures around 340° and this reaction was once an important commercial process for the production of benzenol (phenol) ... 

Very few examples of vinyl substitution with polynuclear aromatic halides have been reported but indications are that they generally react like the halobenzenes. 

The first adequate examination of the applicability of the Hammett equation to aromatic substitution was made by Roberts and his associates (1954). New data on the nitration of the halobenzenes together with the results for other substituted benzenes (Ingold, 1953) revealed that the rates for nitration in the meta position were, indeed, correlated satisfactorily by the Hammett rr-constants. Para substituents, in particular groups directing to the ortho and para positions, exhibit important deviations from the line defined by the meta reactivities (Fig. 3). It was suggested that these deviations were the consequence of significant resonance interactions in the transition state. At the same time, de la Mare (1954) examined the application of the Hammett parameters for the correlation of the relative rate data for non-catalytic chlorination. The poor agreement achieved (Fig. 4) prompted his conclusion that variable resonance interactions in the... 

The results for direct substitution of the halobenzenes are generally reliable. It should be noted, however, that the results for the selective bromination reaction are derived through the polymethylbenzene approach and subject to the limitations of that procedure. The mt values for chlorination were calculated from kinetic data. 

Unfortunately, the several investigators who have examined the nitration of the halobenzenes did not adopt similar conditions. Ingold and his associates (1931) nitrated benzene and toluene by the addition of nitric acid to acetic anhydride and nitromethane. In acetic anhydride, nitric acid is slowly converted to acetyl nitrate (Bordwell and Garbisch, 1960). The relative rates, kT/kB, observed were 23 and 21 for reaction in acetic anhydride and nitromethane respectively. Bird and Ingold (1938) adopted different conditions. In a study of the halobenzenes, these workers added pre-formed acetyl nitrate to the halobenzene in acetic anhydride, acetonitrile, and nitromethane. The results for fluoro-, chloro-, and bromobenzene are summarized in Table 17 (p. 78). 

Roberts and his associates (1954) re-examined the nitration of the halobenzenes using fuming nitric acid as the reagent in both acetic anhydride and nitromethane. These workers detected a significant solvent effect on the relative rate. Iodobenzene was nitrated by nitric acid in acetic anhydride at a rate 0.13 times that of benzene, in nitromethane this reagent provided a rate ratio of 0.22. 

The curious behavior of the halobenzenes has prompted considerable discussion of the influence of the halogen substituents on reactivity... 

K.E. Riley, K.M. Merz Jr., Insights into the strengths and origins of halogen bonding The halobenzene-formaldehyde dimer. J. Phys. Chem. A 111, 1688-1694 (2007)... 

Admitting the elsewhere enunciated problems with the enthalpy of formation of isopropyl fluoride, we conclude that the resonance energies of the halobenzenes decrease in the order F, 7.1 2.2 Cl, -12.3 2.1 Br, -20.2 4.9 I, - 20.6 6.1 kJ mol"1. The resonance energies of halobenzenes roughly track the earlier order with maximum stabilization for fluorine, although we must admit our surprise that only fluorobenzene is stabilized by this definition. Alternatively, since isopropylmethane and methylbenzene (i.e. isobutane and toluene) are common to all of the above reactions, it suffices to look merely at the differences of the enthalpies of formation of the correspondingly substituted benzene and propane (equation 31). 

In the absence of direct calorimetric data for the enthalpy of formation of tert-butyl fluoride, what happens if we use the value of-351.1 kJ mol"1 derived elsewhere in this study. So doing, we conclude the resonance energies of the halobenzenes are all negative and near-... 

Hydrogen replacement with benzene and the halobenzenes has been studied. The isomer distribution has been found to be very close to the statistical one and interpreted as the result of high-energy reactions. Halogen replacement yields increase in the series F-, C1-, Br- and iodobenzene showing dependence on the C—X bond energy both in liquid and in gas phase. 

Aryl halides may be carbonylated using several different palladium complexes and several different hydrogen donors839,840,842,843. In most synthetically useful reactions the conditions are reasonably low pressure (up to 6 bar) and reasonably low temperatures (below 100 °C). Halobenzenes have also been successfully carbonylated at 30 bar using a carbon monoxide/hydrogen mixture in the presence of a palladium catalyst and triethy-lamine. In this case the halobenzene must first be complexed with chromium tricarbonyl844. 

The dechlorinations of 4-chlorobiphenyl400,401 and of chlorobenzene402,403, ortho-, meta-and / ara-dichlorobenzene and 3,4-dichlorotoluene402 can be photosensitized by N,N-dimethylaniline. As with alkylamines, the reaction involves electron transfer but in this case it is not the halobenzene but the dimethylaniline (DMA) that is brought into an excited state. The reaction, supposed to proceed via a exciplex (Y), follows the steps indicated by equations 104-106. 

The halobenzenes are exceptions to the general rules. Halogens are deactivating groups, yet they are ortho, para-directors. We can explain this unusual combination of properties by considering that... 

In summary, the benzyne mechanism operates when the halobenzene is unactivated toward nucleophilic aromatic substitution, and forcing conditions are used with a strong base. A two-step elimination forms a reactive benzyne intermediate. Nucleophilic attack, followed by protonation, gives the substituted product. 

The rates at which several substituted benzenes quench triplet benzophenone have been measured 17 8). No single linear free energy relationship can be derived. For alkoxybenzenes, alkylbenzenes, benzene itself, and benzotrifluoride as quenchers, one finds a linear plot of log vs. IP with a slope similar to that found for the plot of all substituted benzenes and triplet a-trifluoroacetophenone. A given aromatic such as benzene quenches the fluorinated ketone triplet, which has an E - -E(A /A) value of only 16 kcal, some 50 times faster than it quenches triplet acetophenone or benzophenone 132>. This rate difference reflects only 20% of the full 12 kcal difference in thermodynamic redox potentials. However, the halobenzenes and benzonitrile quench triplet benzophenone faster than does benzene 178>. It seems likely that with these electron poor benzene derivatives, some alternate chemical reaction becomes dominant. Although a reverse CT process has been suggested, with the triplet ketone as donor, it is perhaps more likely that some sort of radical addition occurs with conjugating substituents on... 

Other possible reactions include (a) abstraction of a hydrogen atom from the solvent by the phenyl radical, (b) homogeneous reduction of a solvent radical by the halobenzene radical anion, and (c) heterogeneous reduction of a solvent radical at the electrode surface. 

---