Halogen exchanges

A related and useful process is the Wittig-Gilman reaction, in which an organolithium (R —Li) reacts with an alkyl halide to produce a new organolithium (R—Li) via metal-halogen exchange.222 Several mechanisms 

Chapter 8. Nucleophilic Species That Form Carbon-Carbon Bonds 

Although it is possible to start with perchloroethylene, HCFC-121, or HCFC-122 and convert these to HCFC-123 in the liquid phase using a TaXs [20] or SbCb [21] catalyst, it is only in the vapor phase over a heterogeneous catalyst that the conversion to the more highly fluorinated HCFC-124 or HFC-125 (eq 1) occurs to any appreciable extent. The rate of fluorination decreases as the fluorine substitution increases in the series HCFC-121 to HFC-125. The rate-determining step in the formation of HFC-125 is the fluorination of HCFC-124, and Coulson has shown that the fluorination of HCFC-123 to HFC-125 using Co/y-AbOs occurs sequentially on the catalyst surface [22]. Other metals on y-Ab03 have been claimed to fluorinate HCFC-123 to HFC-125, such as Zn and Cr [23] as well as a coextrudate 

The conversion of CHCI3 to HCFC-22 (eq 6) has been practiced for many years since HCFC-22 is a precursor to tetrafluoroethylene, a valued fluoromonomer. During the conversion a small amount of HFC-23 is formed. 

HCFC-22 can also be converted to HFC-23 by disproportionation (section 4.2.3) which has the advantage of lower temperature and no HF is used. However, HCFC-21, which is a product of the reaction will have to be recycled back to HCFC-22. For example, Guo and Cai reported the formation of HFC-23 in high yield ( 99%) using AIF3, Bi/La, and Co-activated AIF3 [33]. 

HFC-134a has been found to be especially useful as a substitute for CFC-12 in automobile air conditioners. A fairly direct preparation method is shown in eqs (7) and (8) TCE = trichloroethylene. The reactions shown are typically done separately in several reaction zones. HCFC-133a can be prepared using catalysts such as Cr/Mg [34], Cr203/A1F3 [35], AlCUF [36], Zn/fluorinated alumina [37], and Zn/Cr [38, 39]. 

As in the synthesis of HFC-134a from HCFC-133a, the conversion of CH2CI2 to HFC-32 (CH2F2) (eq 9) using HF is an equilibrium-limited reaction, and NaF has been used with Cr203 to remove HCl and drive the equilibrium to form more HFC-32 [51]. 

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Various halogenating agents have been used to replace hydroxyl with chlorine or bromine. Phosphoms trihaUdes, especially in the presence of pyridine, are particularly suitable (17,18). Propargyl iodide is easily prepared from propargyl bromide by halogen exchange (19). 

Halogen exchange with KF is not successful ia acetic acid (10). Hydrogen bonding of the acid hydrogen with the fluoride ion was postulated to cause acetate substitution for the haUde however, the products of dissolved KF ia acetic acid are potassium acetate and potassium bifluoride (11). Thus KF acts as a base rather than as a fluorinating agent ia acetic acid. 

Potassium fluoride [7789-23-3], KF, is the most frequently used of the alkaU metal fluorides, although reactivity of the alkaU fluorides is in the order CsF > RbF > KF > NaF > LiF (6). The preference for KF is based on cost and availabiUty traded off against relative reactivity. In its anhydrous form it can be used to convert alkyl haUdes and sulfonyl haUdes to the fluorides. The versatility makes it suitable for halogen exchange in various functional organic compounds like alcohols, acids and esters (7). For example, 2,2-difluoroethanol [359-13-7] can be made as shown in equation 9 and methyl difluoroacetate [433-53 ] as in equation 10. 

Another use of hydrogen fluoride, although not in halogen exchange, is the reaction with ethylenes or acetylenes to form the addition products, 1,1-difluoroethane [75-37-6] and vinyl fluoride [75-02-5]-. 

Ha.logen Fluorides. These include compounds such as IF, IF, GIF, etc, of which only a few, GIF, GIF, BrP, and IF, are used to some extent. They act both as halogen exchange agents and, in the case of the monofluorides, as addition agents to unsaturated bonds (17). 

Vlayl fluoride [75-02-5] (VF) (fluoroethene) is a colorless gas at ambient conditions. It was first prepared by reaction of l,l-difluoro-2-bromoethane [359-07-9] with ziac (1). Most approaches to vinyl fluoride synthesis have employed reactions of acetylene [74-86-2] with hydrogen fluoride (HF) either directly (2—5) or utilizing catalysts (3,6—10). Other routes have iavolved ethylene [74-85-1] and HF (11), pyrolysis of 1,1-difluoroethane [624-72-6] (12,13) and fluorochloroethanes (14—18), reaction of 1,1-difluoroethane with acetylene (19,20), and halogen exchange of vinyl chloride [75-01-4] with HF (21—23). Physical properties of vinyl fluoride are given ia Table 1. 

The melting, boiling, and sublimation points of many of the phosphoms hahdes are well defined and therefore serve for identification. Distillation is the easiest method of purification. Phosphoms-31 nmr can be used to analy2e mixtures of hahdes that undergo halogen-exchange reactions. 

Qua.driva.Ient, Zirconium tetrafluoride is prepared by fluorination of zirconium metal, but this is hampered by the low volatility of the tetrafluoride which coats the surface of the metal. An effective method is the halogen exchange between flowing hydrogen fluoride gas and zirconium tetrachloride at 300°C. Large volumes are produced by the addition of concentrated hydrofluoric acid to a concentrated nitric acid solution of zirconium zirconium tetrafluoride monohydrate [14956-11-3] precipitates (69). The recovered crystals ate dried and treated with hydrogen fluoride gas at 450°C in a fluid-bed reactor. The thermal dissociation of fluorozirconates also yields zirconium tetrafluoride. 

Zirconium tetrabromide [13777-25-8] ZrBr, is prepared direcdy from the elements or by the reaction of bromine on a mixture of zirconium oxide and carbon. It may also be made by halogen exchange between the tetrachloride and aluminum bromide. The physical properties are given in Table 7. The chemical behavior is similar to that of the tetrachloride. 

Zirconium tetraiodide [13986-26-0], Zrl, is prepared directly from the elements, by the reaction of iodine on zirconium carbide, or by halogen exchange with aluminum triiodide. The reaction of iodine with zirconium oxide and carbon does not proceed. The physical properties are given in Table 7. 

Fluorinated and iodinated derivatives are usually prepared by halogen exchange reactions, although the Baltz-Schiemann reaction has been applied to the synthesis of 2-fluoroquin-oxaline (66JHC435>. 

Bromo-3-methyl-4-nitroisothiazole can be converted into the 5-iodo analogue by reaction with sodium iodide in acetone (65AHC(4)107). Halogen exchange also takes place when 4-bromo-3-methylisothiazole-5-diazonium chloride is treated with methyl methacrylate and hydrolyzed, giving the chloro compound (150) (72AHC(14)l). 

Claisen condensation, 6, 156 reactions, S, 92 IsothiazoIe-3-carboxyIic acids decarboxylation, 6, 156 Isothiazole-4-carboxylic acids decarboxylation, 6, 156 Isothiazole-5-carboxylic acids decarboxylation, S, 92 6, 156 IR spectroscopy, 6, 142 Isothiazole-3-diazonium borofluoride decomposition, 6, 158 IsothiazoIe-4-diazonium chloride, 3-methyl-reactions with thiourea, 6, 158 Isothiazole-5-diazonium chloride, 4-bromo-3-methyl-halogen exchange, 6, 163 Isothiazole-5-diazonium chloride, 3-methyl-reactions... 

S W A R T S Halogen exchange Substitution of chlonne atoms with Huorine atoms by means of SbFs... 

General acid and base Halogenation exchange racemization of ketones RCOCHj+X. =RCOCH.X + XH... 

Polymer-supported tetraphenylphosphonium bromide is a recyclable catalyst for halogen-exchange reactions. The reaction of 1 equivalent of chloro-2,4-dinitrobenzene with 1 5 equivalents of spray-dned potassium fluoride and 0.1 equivalent of this catalyst in acetonitnle at 80 C for 12 h gives 2,4-dinitro-fluorobenzene m 98% yield An 11% yield is obtained without the catalyst [3 /]. 

Table 8. Halogen Exchange with Silver Tetrafluoroborate [72]...

Acylhalogenation of haloolefins is most often carried out with aluminum chloride as the catalyst The yields are variable because of side reactions including halogen exehange Halogen exchange is avoided and yields are higher when ferric chloride is substituted for aluminum chloride in the reaction of fluoroethene with acid chlorides [3] (equation 3)... 

Vinyl and phenyl mfluoromethyl groups are reactive in the presence of aluminum chloride [10] Replacement of fluorine by chlorine often occurs Polyfluori-nated trifluoromethylbenzenes form reactive a,a-difluorobenzyl cations in antimony pentafluoride [11] 1 Phenylperfluoropropene cyclizes in aluminum chloride to afford 1,1,3-trichloro 2 fluoroindene [10] (equation 10) The reaction IS hypothesized to proceed via an allylic carbocation, whose fluoride atoms undergo halogen exchange... 

The metal-halogen exchange reaction is useful in the synthesis of numerous perfluoroalkylmagnesium halides, some of which are shown in Table 2... 

Although the metal-halogen exchange reaction is the preferred method of synthesis, the conventional Grignard synthesis through the reaction of a per-fluoroorgano halide and magnesium occasionally is still used [49, 50]... 

Table 2. Perfluoroalkylmagnesium Halides (RfMgX) Prepared by Metal-Halogen Exchange...

Novel polyfluoroethyl Gngnard reagents containmg fluonne, chlorine, and bromine are prepared through the metal-halogen exchange reaction [46] (equation 20)... 

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