Halex

Halex reaction Halfan [36167-63-2] Half-life data Half-lives Halftones Halide glasses Halide ions Halides... 

Halex rates can also be increased by phase-transfer catalysts (PTC) with widely varying stmctures quaternary ammonium salts (51—53) 18-crown-6-ether (54) pytidinium salts (55) quaternary phosphonium salts (56) and poly(ethylene glycol)s (57). Catalytic quantities of cesium duoride also enhance Halex reactions (58). 

The inertness of chlorine in the meta position in Halex reactions is of commercial value. For example, 3,4-dichloronitroben2ene [99-54-7] forms 3-chloro-4-duoronitroben2ene [350-30-1/, which is then reduced to 3-chloro-4-duoroaniline [367-21-5] for incorporation in the herbicide damprop—isopropyl or the duoroquinolone antibacterials, nordoxacin and pedoxacin. 

Explosions have been reported during preparation of duoronitroaromatics by the Halex reaction on a laboratory or industrial scale (9-duoronitroben2ene (65) 2,4-dinitroduoroben2ene (66) 2,4-diduoronitroben2ene (67) and l,5-diduoro-2,4-dinitroben2ene (68). 

Fluorodenitration of nitroaromatics represents an exchange duorination technique with commercial potential. For example, y -duoronittoben2ene [402-67-5] from y -dinitroben2ene [99-65-0] and KF in the presence of various promoters can be reali2ed (69—72). This is not feasible under Halex conditions with y -chlotonittoben2ene [121 -73-3]. 

Halex technology has also been employed to prepare l,2,3,4-tetrafluoroben2ene derivatives, eg, tetrachlorophthahc anhydride [117-08-8] was converted to 2,3,4,5-tetrafluoroben2oic acid [1201 -31 -6] for use ia fluoroquiaoloae antibacterials (219,220). 

For this reason, industrial fluorinations of aromatics are performed by other routes, mostly via the Schiemann or Halex reaction [54, 55]. As these processes are multi-step syntheses, they suffer from low total selectivity and waste production and demand high technical expenditure, i.e. a need for several pieces of apparatus. 

The selection of the solvent can affect a reaction drastically. In the Halex process for the conversion of 2,4-dichloronitrobenzene with KF to 2,4-difluoronitrobenzene, no reaction occurs in toluene as a solvent, presumably because KF has negligible solubility in toluene. In water, in which KF is highly soluble, no reaction occurs either, due to poor solubility of 2,4-dichloronitrobenzene in water and heavy solvation of fluoride rendering it ineffective. Dimethylformamide is suitable as the solvent KF has some solubility, while the product KCl precipitates (Atherton and Jones, 1995). 

Halex [Halogen exchange] A process for making fluoro-aromatic compounds by reacting the corresponding chloro- or bromo-aromatic comounds with an inorganic fluoride, usually potassium fluoride. Widely used for the manufacture of fluoro-intermediates. 

Number in parentheses refer to product brands (1) B. Braun, (2) Fresenius, (3) Baxter, (4) Halex Istar, (5) JP, (6) Merck, (7) EMS, (8) Elkins Sinn, (9)Ariston, (10) Geyer, (11) Hipolabor. RSD, relative standard deviation n.d., not detected (below LOD). 

Suppliers Abbott, Ariston, Aster, Baxter, Behring, B.Braun, Darrow, Fresenius, Fujisawa, Gayer, Halex Istar, Hypofarma, Santisa, Roche, Zenalb. 

There are two basic industrial approaches to the introduction of fluorine into an aromatic ring (1) diazotization procedures and (2) halogen exchange (Halex). A third - and the most promising - approach is aromatic electrophilic fluorination. 

Halogen exchange (halex). This procedure involves the displacement of an activated aromatic halogen with a fluorine anion [140,141]. It has been extensively used for the synthesis of fluorinated aromatic intermediates, such as 2,6-difluorobenzonitrile (Fig. 33) [142],... 

Halex Salt Lost or decomposed solvent Corrosion Decomposition of (toxic) solvent High temperature Activated aromatics expensive solvents, catalyst One step (omitting Ar-X manufacture) <86% (omitting Ar-X manufacture)... 

Another potential application of perfluorocarbons is their use as bulking agents where the volume of conventional solvent is reduced by replacement with a perfluorocarbon. Although the halex reaction is a successful industrial process, there are problems recovering the toxic dipolar aprotic solvents. Chambers [80] has shown that, on a preparative scale, up to 75% of the sulfolane can be replaced in the halex reaction by an equivalent volume of perfluorohydrophenanthrene (b. pt. = 215°C). On cooling the reaction mixture, it is a simple matter to separate off the fluorous solvent at the end of the reaction for recycling. 

Figure 9.22b Perfluorinated heterocyclic systems obtained by Halex procedures [53]...

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