Halobenzenes

Some compounds gave abnormal results thus fluorobenzene with neat chlorosulfonic acid (40 C) only gave 4,4 -difluorodiphenyl sulfone. On the other hand, treatment of fluorobenzene with the reagent in chloroform solution afforded some /7-fluorobenzenesulfonyl chloride while m-difluorobenzene reacted with excess reagent (30-40 C, 3 hours) to give 2,4-difluorobenzenesulfonyl chloride (98.6% yield).  

Chlorobenzene reacts with an equimolar amount of chlorosulfonic acid to give mainly the p-sulfonic acid together with a little of the sulfonyl chloride and the sulfone. With an excess of the reagent good yields of p-chlorobenzenesulfonyl chloride are obtained. The kinetics of the sulfonation of chlorobenzene with chlorosulfonic acid have been studied, and the reaction has been reported in several patents. These involved various modifications such as the use of excess reagent in hydrocarbon solvents containing alkali metal or ammonium salts, or a mixture of the reagent with thionyl chloride in the presence of sulfamic acid, sodium sulfate or dimethylformamide. In the reaction, the yield of 4,4 -dichlorodiphenyl sulfone can be increased under a variety of conditions the 

Chlorobenzene, by prolonged heating with excess chlorosulfonic acid, gives the 2,4-disulfonyl chloride.  

In contrast, attempts to chlorosulfonate 1,2,4,5-tetrachlorobenzene 59 with chlorosulfonic acid were unsuccessful the reaction with excess reagent (150 °C, 18 hours) only afforded hexachlorobenzene 60 in agreement with previous studies.  

A mechanism was proposed for the conversion of 59— 60 involving initial formation of the sulfonyl chloride 61 which subsequently suffered thermal decomposition with loss of sulfur dioxide and formation of pentachlorobenzene 62. Finally repetition of these steps gave hexachlorobenzene 60, as indicated in Equation 17. The mechanism is in agreement with the observation that several arylsulfonyl chlorides undergo thermal decomposition with concomitant chlorination.  

---

Returning to Table 12 2 notice that halogen substituents direct an incoming electrophile to the ortho and para positions but deactivate the ring toward substitution Nitration of chlorobenzene is a typical example of electrophilic aromatic substitution m a halobenzene... 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

Potassium tert butoxide reacts with halobenzenes on heating in dimethyl sulfoxide to give ten butyl phenyl ether... 

N-Arylation of azoles is achieved either by using arynes, activated halobenzenes (e.g. dinitro) or under Ullmann conditions. Thus benzyne reacts with imidazoles to give N-arylimidazoles (70AHC(12)103), and these compounds have also been prepared under modified Ullmann conditions. 

Polarographic studies on haloisoxazoles in anhydrous DMF containing R4N" were performed and the magnitude of the half-wave potentials were recorded. Cleavage of the C—X bond was faster in phenylhaloisoxazoles than in halobenzenes. Substitution patterns affected the reduction (79ZOB1322). 

There are several methods for generation of benzyne in addition to base-catalyzed elimination of hydrogen halide from a halobenzene, and some of these are more generally applicable for preparative work. Probably the most convenient method is diazotization of o-aminobenzoic acid. Concerted loss of nitrogen and carbon dioxide follows diazotization and generates benzyne. Benzyne can be formed in this manner in the presence of a variety of compounds with which it reacts rapidly. 

Approximate Relative Rates of Halogen Displacement FROM 4-Substituted Halobenzenes and 4-Substituted 2-Nitrohalobenzenes... 

Halobenzenes without electron-withdrawing substituents don t react with nucleophiles under most conditions. At high temperature and pressure, however, even chlorobenzene can be forced to react. Chemists at the Dow Chemical Company discovered in 1928 that phenol could be prepared on a large industrial scale by treatment of chlorobenzene with dilute aqueous NaOH at 34U °C under 170 atm pressure. 

Many variations of the reaction can be carried out, including halogenation, nitration, and sulfonation. Friedel-Crafts alkylation and acylation reactions, which involve reaction of an aromatic ling with carbocation electrophiles, are particularly useful. They are limited, however, by the fact that the aromatic ring must be at least as reactive as a halobenzene. In addition, polyalkylation and carbocation rearrangements often occur in Friedel-Crafts alkylation. 

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. 

Pure samples are best prepd by the methylation of acetanilide or benzanilide to the N-methyl compds followed by acid hyd. It has been prepd commercially by the action of methyl ale on aniline in an autoclave under press and by the action of methyl amine on halobenzenes. For a summary of prepns see Refs 6 9. It may be separated from aniline and dime thy laniline by treatment of the mixt with benzenesulfonyl chloride. Dimethylamline fails to react and is extd out with dil acid. Aniline forms benzenesulfonanilide which is acidic and is removed by washing with dil base, leaving the N-methylbenzenesulfonanilide. Purified N-methylaniline is obtd by acid hyd (Ref 8). N-Methylaniline is used as an additive to raise the octane no of motor fuels (Ref 6), as a dyestuff intermediate (Ref 3), in the prepn of Tetryl (see below), and in the prepn of Methylcentralite (Encycl, Vol 2, C137-R)... 

The anion of DMSO undergoes a phenylation reaction with aryl halides under sunlight stimulation38. The presence of benzhydryl methyl sulfoxide (maximum yield 5%) in all runs, the sunlight activation, the order of reactivity of halobenzenes (I > Br > Cl), the inhibition of the reaction with oxygen, all hint at the SRN139-44 mechanism (Scheme 3). 

When arenesulfonyl radicals are generated in benzene the only reported products are those of disproportionation50,95 (vide supra). However, Camaggi and coworkers95 have found that arenesulfonyl radicals in halobenzene replace the halogen atom at 150-190 °C, the relative reactivities being for Cl Br I, 1 5.9 18.6. These authors95 proposed that the reaction proceeds via a reversible ip.vo-substitution,... 

Aromatic brominations have been mainly carried out using X, Y and L zeolites. Improved para/ortho ratios have been observed upon brominating halobenzenes, benzyl halides, and biphenyl. The side product HBr leads to decreased activity and selectivity. This problem has been addressed by adding scavengers, by working in the gas phase, and by applying oxidative bromination. 

Cu-exchanged zeolites have been examined in the nucleophilic substitution of halobenzenes towards aminated and oxygenated systems. Selectivities are dependent on the zeolite s pore sizes. 

Quite some papers and patents deal with zeolite-catalyzed aromatic bromination. Most work pertains to bromination of halobenzenes and of toluene, using X-, Y-and L-type zeolites. 

In an early paper by our group (ref. 19) halobenzenes are brominated at 298 K in the liquid phase over various Y-zeolites (Fig. 7). Improved p/o-ratios with respect to conventional (FeBr3) catalysis are observed. 

Figure 10. Reactions in Cu-zeolite catalyzed amination of halobenzenes.

---