Preparation of 3-halo-halobenzenes and 1-halo-3,5-dihalobenzenes
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to the field of haloaromatics. 
     2. Description of the Background Art 
     Haloaromatics, their production, and the reactions in which they are used, are of great interest in organic chemistry since haloaromatics are important in the production of industrial, pharmaceutical and agricultural chemicals. 
     While many methods for producing haloaromatics are known, because of their great commercial importance, there remains a need in the art for new and improved methods for producing haloaromatics which are more efficient and/or less expensive than prior art methods. 
     SUMMARY OF THE INVENTION 
     In accordance with the present invention, a process for producing a 3-halo-halobenzene or a 1-halo-3,5 dihalobenzene comprises forming a mixture of a deaminating agent and a first member selected from the group consisting of 2-halo-4-haloaniline and 2-halo-4,6-dihaloaniline, and deaminating said first member so as to form a corresponding second member selected from the group consisting of 3-halo-halobenzene and 1-halo-3,5-dihalobenzene. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Starting materials for the process of the present invention can be selected from the group consisting of 2-haloanilines (such as 2-fluoroaniline), 4-haloanilines (such as 4-fluoroaniline), 2,4-dihaloanilines (such as 2,4-difluoroaniline) as well as mixtures thereof. 
     The starting material is mixed with a halogenating agent, which can be represented by the formula X 2 , wherein X is a halogen such bromine, chlorine and the like. In preferred embodiments, X is bromine. Tetrabutylammonium trihalides (such as tetrabutylammonium tribromide) work well as halogenating agents. 
     The starting material is halogenated with the halogenating agent, under halogenating conditions, (e.g., at about 10° ) in a suitable aprotic solvent (e.g., CH 2  Cl 2 , 1,2-dichloroethane, toluene, fluorobenzene, and the like) so as to form a corresponding 2-halo-4-haloaniline or 2-halo-4,6-dihaloaniline, which usually is isolated as the hydrohalide salt. 
     In accordance with the present invention, the 2-halo-4-haloaniline or 2-halo-4,6-dihaloaniline thus formed is mixed with a deaminating agent, such as NaNO 2  and H 3  PO 2  (hypophosphorous acid). The 2-halo-4-haloaniline or 2-halo-4,6-dihaloaniline then is deaminated under deaminating conditions, so as to form a corresponding 3-halo-halobenzene or 1-halo-3,5-dihalo-halobenzene. The deamination is run in aqueous acid (e.g., HCl, HBr, H 2  SO 4 , or the like) by diazotizing the amine at about 0°-5° C. and then adding hypophosphorous acid before the decomposition. 
     In the above-described process wherein the 3-halo-halobenzene is formed, the 2-halo-4-haloaniline is provided as 2-halo-4-haloaniline.HX if the halogenating agent utilized is X 2 . 
     When the original starting material is selected from the group consisting of 2-fluoroaniline, 4-fluoroaniline, 2,4-difluoroaniline and mixtures thereof, and the halogenating agent is Br 2 , the corresponding 2-halo-4-aniline formed is selected from the group consisting of 2-bromo-4-fluoroaniline, 4-bromo-2-fluoroaniline, 2-bromo-4,6-difluoroaniline and mixtures thereof. Deamination of this product in accordance with the present invention, as described above, provides a desired end product, 3-bromofluorobenzene, and 1-bromo-3,5-difluorobenzene. 
     In a particularly preferred embodiment of the present invention, Br 2  is mixed with a starting material selected from the group consisting of 2-fluoroaniline, 4-fluoroaniline, 2,4-difluoroaniline or a mixture thereof. The Br 2  is reacted with the selected starting material to form a corresponding intermediate material selected from the group consisting of 2-bromo-4-fluoroaniline.HBr, 4-bromo-2-fluoroaniline.HBr, 2-bromo-4,6-difluoroaniline.HBr and mixtures thereof. The resulting intermediate material then is mixed with a deaminating agent comprising NaNO 2  and H 3  PO 2 . The intermediate material then is deaminated, under deaminating conditions, so as to form the desired end product, 3-bromofluorobenzene or 1-bromo-3,5-difluorobenzene. 
     The invention is further illustrated by the following examples, which are not intended to be limiting. 
     Since many modifications, variations and changes in detail may be made to the described embodiments, it is intended that all matter in the foregoing description be interpreted as illustrative and not in a limiting sense. 
     EXAMPLE I 
     Preparation of 3-Halo-Halobenzenes 
     In a suitable aprotic solvent (e.g., CH 2  Cl 2 , toluene, fluorobenzene, or the like) 1 mole of tetrabutylammonium bromide is dissolved and stirred as 1 mole of Br 2  (bromine) is added. This mixture of tetrabutylammonium trihalide and solvent is cooled to 10° before 1 mole of 2-fluoroaniline or 4-fluoroanilin, or a mixture of both, is added. The reaction takes place immediately to produce 4-bromo-2-fluoroaniline.HBr, or 2-bromo-4-fluoroaniline.HBr, or a mixture of the two. The salt is then collected and dried before carrying it up to the next step. Catalyst and solvent are recovered for recycle. 
     The deamination is run in aqueous acid (e.g., HCl, HBr, H 2  SO 4 , or the like) by diazotizing the amine at about 0°-5° C. and then adding hypophosphorous acid before the decomposition. One mole of the aniline salt is slurried in aqueous HCl as one mole of NaNO 2  dissolved in water is added at 0° to 5° C. The mixture goes into solution and 1.1 to 1.5 moles of 30 to 50% aqueous hypophosphorous acid then is added at 0° to 5° C. The reaction then is controlled to &lt;30° C. by cooling as nitrogen gas is evolved to give the desired 3-bromofluorobenzene in 80-85% yield. 
     Either bromine or chlorine can be used for the halogen source and any 2 or 4 substituted aniline will give the corresponding 3-halo-substituted halobenzene. Halogenation of aromatic amine compounds is described in commonly owned U.S. Pat. No. 5,053,542 and U.S. Ser. No. 07/641,396, filed Jan. 15, 1991. 
     EXAMPLE 11 
     Preparation of 1-Halo-3,5-Dihalobenzenes 
     In a suitable aprotic solvent (e.g., CH 2  Cl 2 , 1,2-dichloroethane, toluene, fluorobenzene, or the like), 1 mole of 2,4-dihaloaniline, such as 2,4-difluoroaniline is dissolved. The reaction mixture is cooled to about 10° C. and one mole of Bromine is added. There will be an immediate reaction with an exotherm, which can be held to 30° C. The slurry of 2-bromo-4,6-difluoroaniline hydrobromide then is filtered and the solvent recycled for the next run. The solid then is dried. 
     In accordance with the above process, I have achieved a yield of 2-bromo-4,6-difluoroaniline.HBr (95%) of 98%. Aqueous diazotization of 1 mole of 2-bromo-4,6-difluoroaniline hydrobromide in aqueous HCl using 1.1-1.10 moles of NaNO 2  at 0°-5° afforded a solution of diazonium salt. Hypophosphorous acid (1.5 moles) was added at less than 5° C. and the solution was allowed to warm to 15° C. with nitrogen evolution. After stirring for one hour, the mixture was decanted and extracted with an appropriate organic solvent to yield 75% (mole basis) of the desired 1-bromo-3,5-difluorobenzene, distilled yield of 99+% pure material. Other 1-bromo-3,5-dihalobenzenes were similarly prepared.