Halobenzenes benzoylation

The key intermediates for the synthesis of mebendazole (14), flubendazole (15) and ciclobendazole (16) are 4-benzoyl-2-nitrohalobenzene (94a), 4-(4-fluoroben-zoyl)-2-nitrohalobenzene (94b) and 4-cyclopropylcarbonyl-2-nitrofluorobenzene (94c), respectively, which are prepared by Fridel-Crafts reaction of an acid chloride with the appropriate aromatic compounds. These substituted halobenzenes (94a-c) are converted into 14-16 as shown in scheme 4 [137-139]. 

On the basis of their earlier work with benzoyl nitrate and zeolites [16] Smith et al. [17,18] described a method for the nitration of simple aromatic compounds such as benzene, toluene, and halobenzenes. Using 90 % nitric acid, H-beta zeolite as catalyst, and acetic anhydride as water-trapping agent these aromatics are nitrated in quantitative yield with high para selectivity in a solvent-free process by use of a stoichiometric quantity of nitric acid and acetic anhydride at... 

Halobenzenes are selectively benzoylated at the para-position by a reaction with different BCs in the presence of anhydrous iron(III)sulfate (1% mol). Satisfactory to good yields are obtained by carrying out the reaction at 150°C under solventless conditions (Table 3.15). 

Table 3.15 Ferric-sulfate-catalyzed benzoylation of halobenzenes with BCs CO Cl...

Morley, J. O. 1977. Benzoylation of halobenzenes catalysed by iron(III) sulphate. Synthesis 54-55. 

---