1. Hexafluorobenzene Synthesis by Potassium Fluoride Influence on Hexachlorobenzene in the Presence of Catalysts
Fluorodechlorinating chloroaromatic compounds process carrying out in a row of low-chlorinated aromatic compounds in the presence of inter-phase transfer catalysts and high-boiling organic solvents is an essential late achievement of this process intensification [32-37]. Here we do not describe in detail this process due to the fact, that there are plenty of reviews devoted to this topic. We only will give the examples of synthesis of 4-fluorobenzonitrile [38] and trifluoro-s-triazine [39, 40]. Thus, during reaction of 4-chlorobenzonitrile and KF in 1,3-dimethyl-2-imidazolidone at 280 oC, pressure of 0.4 bar. in 2 hours we obtained 4-fluorobenzonitrile with the yield of 89.5 % (product's purity is 99 %). The reaction of trichloro-s-triazine and CsF at 80 oC in the presence of hexafluorophosphonium salt of 1,3-methylbutylimidazolinium results in forming of 10% yield trifluor-s-triazine along with mono- and di-fluorosubstituted products.
In terms of practice the application of inter-phase transfer catalysts not using solvents is of most interest. In this case there is no need to isolate reaction products out of solvent and also to regenerate it. Used catalysts along with high effectiveness should possess a number of characteristics: high stability at synthesis conditions, availability and reasonable price. Usually they use quaternary phosphonium salts, hexaethylguanidium chloride, tetrakis(diethylamino)phosphonium bromide, dialkyl ethers of polyethylene glycol and crown-ethers. At that, originally these catalysts were used for chlorobenzenes, containing NO2 group. It is stated, that catalysts of phase transfer (crown ethers, tri(oxalkyl)amines, quaternary ammonium and phosphonium salts) are effective for the processes of dechlorination chlorocontaining nitroarenes in the absence of aprotic solvents [41]. The yield of final products is 55-95%. The 20% excess of KF and 0.5-2 mole % catalysts of KF is used. Reactions pass in 0.5-8 hours at 160-180 oC. Influence of catalysts is in its ability to carry the ion fluoride from solid potassium fluoride to liquid organic medium effectively. As effectively, such catalysts are high thermal resistant (up to 280oC), well-soluble in organic phase, their cost is also not high, that allows to them on a commercial scale.
Under such conditions only one chlorine atom in para-position to nitrogroup is being substituted. It is stated, that quaternary ammonium and phosphonium salts are most effective catalysts. However at temperature exceeding 150 oC the effectiveness of ammonium salts decreases , what can be caused by low thermal stability [41].
Using example of chlorine exchange for fluorine in 2,4-dichlornitrobenzene we demonstrated the effectiveness of using quaternary ammonium salts [cetyltrimethylammonium bromide [28] and tetramethylammonium chloride [38]] for increasing of yield of corresponding 2,4-difluoronitrobenzene.
The synthesis of compounds like YArFwCl(x-w)R ( where Y = F, Cl, Br, NO2, CN, CF3, CHO, COOX, SO2X; n = 1-10, Ar = Ph, pyridyl, naphthyl) is carried out by interaction of chlorine containing derivatives AxArClyRz and alkali metals' fluoride or mixture of alkali metals fluorides in organic solvent or without it in the presence of one or mixture of quaternary ammonium compounds with the formula R1R2R3R4N+ . X- as catalyst at 50-200 oC [42,43]. Compounds R5(OCaH2a)bOR6 (R5, R6 = C1-16-alkyl; a = 2-6; b = 0-20) or crown-ether are used as solvent. We should note, that for this process we can obtain both monofluorine derivatives and poly-fluorinated aromatic compounds.
Quaternary phosphonium salt - Ph4P+. Cl- is also effective in case of chlorine exchange for fluorine by KF acting on 2,4-dinitrochlorobenzene [44,45] and 5-nitro-2-chloropyridine [45] (see table 3). At that the role of solvent is also important.
Electron-seeking groups such as CF3 [46], COOR [21,22] (see tables 4 and 5) do not react with catalysts, the chlorine exchange for fluorine takes place, though the yield of substituted for fluorine products is not high. When chlorine atom in benzene ring is in orto- or para-positions towards such substituents, the effective chlorine exchange for fluorine takes place, though the temperature of such process is rather high. At meta-position of chlorine the reaction goes slowly. It has been shown for the first time [21], that in the presence of phosphonium salts the rate of exchange of chlorine for fluorine increases, regardless of a number of chlorine atoms in benzene ring. In table 4 you can find the information on fluorodechlorination of benzotrifluoride derivatives [21]. The further saponification (sulphric acid, 140 oC, 4 h) results in forming of corresponding acids of high yield (88-95 %). Catalysts: Ph4PBr, (n-Bu)4PBr and Ph4P . HF2 are effective in the temperature range within 180-200 oC. They are well-soluble in polar solvents and they are thermal resistant [47]. However due to their high cost they can't be applied for technical purposes.
Table 3. The Influence of Inter-phase Transfer Catalyst on Chlorine for Fluorine Exchange in Monochloroderivatives of Benzene and Pyridine [45].
We observe the same situation in case of chlorine containing benzoic acid esters (table 5) [21]. However, we would have to note, that full exchange of chlorine atoms in benzene ring is possible not always, and as a rule, mixtures that are hard to segregate are formed.
For these processes the activating role of chlorine exchange for fluorine belongs to crown-ethers [48].
The catalysts' application effectiveness for carrying out the Halex process made different quinquivalent phosphorus derivatives synthesis necessary, as a rule they contain several nitrogene containing substituents, for example like (R2N)4PX, which are used in temperature range of 200 - 240 oC (table 6) [48-51]. However all catalysts of this type are toxic it is better to use phosphorus compounds, containing cyclic amines [52-54].
Table 4. Fluorodechlorinating Chlorobenzotrifluorides by KF in Catalysts' Presence [46]
Such salts as 1,1,1,3,3,3-hexapyrrolidino-diphosphazenium chloride and 1,1,1,3,3,3-hexapiperidino- diphosphazenium chloride based on aminophosphazene are effective catalysts for chlorine exchange for fluorine under the alkali metals' fluorides influence or ammonium fluoride. Thus, the reaction of 2,5-dichloro-2,4,6-trifluoropyridine and KF in the system of solvents sulfolane - chlorobenzene at 215 oC in the presence of these salts produces 3-chloro-2,4,5,6-tetrafluoropyridine with the yield of 75% and pentafluoropyridine with the yield of 24% [56]. 2,6-Difluorobenzaldehyde, which yield counted to 88.7-88.5%, was obtained the same way out of 2-chloro-6-fluorobenzaldehyde by KF acting in chlorobenzene at 190 oC [56].
Table 5. Fluorodechlorinating Some Derivatives of Benzoic Acid [21]
Amidophosphonium salts [(R1R2)N]4P+ . Hal- are also active in this process and produce fluoroderivatives with high yield when electron-seeking substituents are presented in benzene ring [55].
Table 6. Fluorinating Catalysts According to Halex Process
to be continued in the next volume