Bromine-chlorine exchange reactions

The regioselectivity of bromine-lithium exchange reactions in dibromoindole substrates has been studied by Li [381, 382]. With both 4,7-dibromoindoles (e.g., 145) [382] and 5,7-dibromoindoles (e.g., 146) [381], bromine-lithium exchange occurs preferentially at C7 (Fig. 5) upon treatment with ferf-butyllithium. A similar result was reported recently by Lachance involving the selective chlorine-lithium exchange observed with 6-azaindole 147 [383]. 

The procedure can be extended to achieve selective a-bromination and iodination of carboxylic acids and the general mechanism of the a-halogenation is outlined in Chapter 5, p 170. The autocatalytic effects in the selective a-chlorination of propionic acid to the 2-chloro and 2,2-dichloro acids have been studied in a semibatch reaction at 90-130 °C. The reaction was performed in the presence of chlorosulfonic acid and dichloroacetic acid as catalysts and oxygen as the radical scavenger. Kinetic experiments indicated autocatalytic formation of both products and that the selectivity was independent of the chlorine concentration in the liquid phase. The results confirmed the validity of the proposed reaction scheme which involved formation of the reaction intermediate, propanoyl chloride from propionic acid and chlorosulfonic acid, the acid-catalysed enolization of the acid, and a hydroxyl-chlorine exchange reaction. The acid-catalysed enolization was the rate-determining step in the reaction sequence. ... 

Reaction of 1,4-dilithio-l,3-dienes 1 with 1.1 or 1.2 equiv of CeFe at room temperature afforded the multi-substituted partially fluorinated naphthalene derivatives 2/6 in good to high isolated yields (Scheme 12) [56]. The reaction is assumed to proceed via double nucleophilic substitution. The naphthalene derivatives with different substitution patterns could be prepared conveniently by this method. Instead of nucleophilic substitution, when di-lithio reagents 1 were treated with hexachlorobenzene, chloropentafluorobenzene, or bromopentafluorobenzene, chlorine-lithium or bromine-lithium exchange reactions took place to afford the 1,4-dichloro- or 1,4-dibromo-l,3-diene derivatives. Preliminary results demonstrate that these partially fluorinated multi-substituted naphthalene derivatives show unique stacking fashions. 

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

The direct bromination of 2-hydroxypyridine is regioselective at C-3 whereas chlorination is not. Qu6guiner has developed a halide exchange reaction. Heating 3-bromo-2-hydroxypyridine in pyridine hydrochloride at reflux gives 3-chloro-2-hydroxypyridine in good yield <96TL(37)6695>. The directed aminomethylation of 3-hydroxy-2(lH)-pyridones and 3-hydroxy-4(lfl)-pyridones has been studied <96T(52)1835>. 

Other anomeric-oxygen exchange reactions have been recently investigated quite extensively. Closely related to the Koenigs-Knorr method is the introduction offluorine as the leaving group (Scheme 1, path B) (6,9-13). Because of the difference in halophilicity of this element as compared with bromine and chlorine, additional promoter systems besides silver salts were found useful as activators for glycosylation reactions (14-16). However,... 

Rhenium(VI) nitride compounds can be generated by oxidation of rhenium(VI) complexes with chlorine or bromine. The products formed are often unstable and ligand exchange reactions with CP or Br lead to a complex mixture of Re compounds. Oxidation of the rhenium(V) complex [ReN(PPh3)Cl(cpCo PO(OR)2 3)] with Ag(BF4), however, yields [ReN(PPh3)Cl(cpCo- P0(0R)2)3)](BF4) (53) in good yields. ... 

Bromine trifluoride is used to selectively substitute fluorine for bromine in brominated alkanes and esters. The reactions are carried out by gradual addition of bromine trifluoride to a solution of the substrate in CFC-113 or CFC-112 at 10-20nC. The bromine-fluorine exchange in mono-bromohaloalkanes is nonstereoselective and accompanied, in some eases, by skeletal rearrangements, hydride shifts, and halogen migrations. All three fluorine atoms in bromine trifluoride are involved in the fluorination reaction. Chlorine atoms in the substrate molecules remain intact.109... 

Only a few exchange reactions of substituents directly bound to the heterocyclic ring have been reported. Gompper has studied the nucleophilic substitution of bromo- and chloro-l,2,3-triazines and observed replacement of bromine or chlorine with sodium ethoxide, sodium ethanethiolate and amines. In most cases yields are quantitative. With the trihalo compound, first the 4-mono- then the 4,6-di-substituted derivative is obtained (79CB1529). Reaction of 5-chloro-2-methyl-4,6-bis(dimethylamino)-l,2,3-triazinium iodide (61) with malononitrile affords compound (62). Compounds of the general structure (63) are hydrolyzed to l,2,3-triazin-5(2//)-ones (64) (79CB1535). 

For the cr-telluranes 94, one characteristic is the smooth exchange reaction at the tellurium center. 10,10-Dibromo(diiodo)phenoxatellurines convert to dichlorides when treated with chlorine or sulfuryl chloride 10,10-diiodo derivatives under the action of bromine readily afford 10,10-dibro-mides and 10,10-dichloro- and 10,10-dibromophenoxatellurines are easily transformed to 10,10-diiodo derivatives when potassium iodide is added to their methanolic solutions (70MI2). 

Other inorganic metathetical exchange reactions studied include the replacement of bromine by fluorine and chlorine in N3P3Br6 and the preparation of azido-, cyano-, and isothiocyanatocyclophospha-zenes (21, 22, 249). In the reactions of N3P3C16 with KF and KSCN, addition of [18-Crown-6]ether considerably enhances the yields of substituted cyclophosphazenes, N3P3R6 (R = F, NCS) (449). 

The rates of reaction of hypophosphorous acid with iodine bromine ", chlorine ", iodine chlorides , iodate , selenious and tel-lurous acids, silver nitrate , cupric chloride and mercuric chloride" (all forming phosphorous acid or phosphites) have been measured, and the results of the earlier work summarized clearly" . All the data are consistent with the hypothesis that there is prior transformation to some reactive form (I). This form (I) does not discriminate very effectively between different oxidants and thus the oxidation steps are presumed to have rates close to the diffusion-controlled limit. The rates of formation of I deduced in these studies are close enough to the rates of deuterium and tritium exchange for the residual difference to represent an isotope effect. Mitchell wrote the formula H5PO3 for I. Others have supposed it to be a tautomer e.g. HPO(OH)2. Both the isotopic exchange results and the oxidation studies require that its formation and decomposition be subject to acid catalysis. For the general mechanism... 

Halogen exchange reactions may be used to prepare tetrahalotellurates(IV) that are not accessible through reactions of aryl tellurium trihalides and onium halides. Treatment of tetrachloro- or bromotrichlorotellurates with dilute hydrobromic acid produces the tetrabromotellurates. The conversion of bromotellurates to tetrachlorotellurates requires concentrated hydrochloric acid. Chlorine and bromine are easily replaced by iodine when the tellurates are reacted with excess potassium iodide in dilute hydrochloric acid. The iodotellurates cannot be converted to the bromo- or chlorotellurates ... 

Diaminopyrazine (57) and its 5,6-dichloro derivative react with thionyl chloride to give thiadiazolopyrazines. Attempts to react 2,3-diamino-5,6-dibromopyrazine with thionyl chloride have resulted in partial or complete chlorine exchange. Thionyl bromide gave only tars on reaction with the dibromodiaminopyrazine. The 5,6-dibromo derivative 58 was obtained by treatment of the corresponding dichloro compound with bromine in chloroform. 

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