Fluorides, Aryl Halides

No Name Boiling point, C Melting point c d Df Niiro derivative Sulfonamide Miscellaneous 

4-D jfluorobenzene 88 1 4423 1 I632( Boiling with NaOH — 4-fluorophenol, 48, 

No Name Boiling poinl, C Meiling point, C d DJ Nitro derivative Sulfonamide Miscellaneous 

8 1 Chloro 3-ethy Ibenzene 184 1 5199 1 053 Oxid - 3-chlorobenzoic acid, 158 

12 l Chloro-23-dimethyl 190 Oxid - 3-chloro-2-methylbenzoic acid. 

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The carbonylation of aryl halides under mild conditions in the presence of CsF afford.s the acid fluoride 490 in good yields. Unlike acyl chlorides, acyl fluorides are inert toward Pd(0) catalyst[345]. Benzenesulfonyl chloride (491) undergoes desulfonylation-carbonylation to give the benzoate 492 in the presence of titanium tetralkoxide at 160 °C[346]. 

Formation of aryl Grignard reagents (Section 14 4) Aryl halides react with magnesium to form the corresponding arylmagnesium halide Aryl iodides are the most reac tive aryl fluorides the least A similar reaction occurs with lithium to give aryllithium reagents (Section 14 3)... 

Palladium-catalyzed hydroarylation of sterically hindered PTAD adduct 157 with aryl halides in the presence of triphenylarsine, sodium acetate, and DMSO provides a 1 1 mixture of 170 and 171. The same reaction done with sodium fluoride and formic acid provides mixtures containing 171 as the major product. Apparently, the use of sodium fluoride as a base allows the selective formation of the opening products 171 in good yields (Equation 19). Similarly, the 2,3-phthalazine-l,4-dione adduct 172 provides the corresponding products 173 and 174 (Equation 20) <2002AGE3375>. 

The application of bases other than fluoride for activation of organosilicon compounds to crosscoupling is documented. NaOH can replace fluoride in the cross-coupling of aryl and alkenyldichloroalkylsilanes with aryl halides, including chlorides. Apart from providing milder reaction conditions, the reaction in the presence of NaOH is applicable to a wider range of substrates ((85) and (86)).294... 

Aryl halides can also be reduced by tin hydrides76,77, although these reactions always require initiators because the stronger C—X bonds in aryl halides are less reactive than the C—X bonds in alkyl halides. In fact, a series of meta- and para-substituted bromobenzenes, where X is either meta- or para-CH3O-, C=N, Cl, F, CF3, CH3, Bu-f or 2,6-dichloro, have been reduced by tributyltin deuteride (equation 60). It is worth noting that the more reactive bromide is reduced selectively in the presence of the less reactive chloride and fluoride groups (equation 61). 

Fluorosilylsubstituted aryl derivatives were found to be useful reagents for carbon-carbon bond formation via palladium-catalyzed cross-coupling with aryl halides in the presence of fluoride anions as Si—C bond activator in dimethylformamide (DMF), as well as rhodium-catalyzed 1,4-addition to a, 3-unsaturated ketones in the presence of a fluoride anion source (Equation 14.11) [66, 69, 70],... 

Mowery and DeShong reported on the use of siloxanes 72 (Figure 16) as versatile transmetallation agents for Pd(dba)3-catalyzed couplings with aryl halides and allylic alcohol derivates, in the presence of TBAF and at high temperature (95 They later used aryl silatrane 73 (Figure 16) as a suitable partner for the fluoride-promoted... 

The palladium catalyzed cross-coupling of organosilicon compounds and aryl halides found only limited application with azines compared to the Suzuki or Negishi coupling. In a recent paper DeShong reported the efficient coupling of bromopyridine derivatives with aryl siloxanes (7.44.) 62 The transmetalating ability of the siloxane was enhanced by the addition of tetrabutylammonium fluoride. 

Catalytic Carbonylation of Aryl Halides in the Presence of Potassium Fluoride General Procedure 33... 

Raney nickel, 265 Aryl halides Aryl fluorides... 

Until recently no satisfactory procedure for the direct conversion of a primary aliphatic amine into an alkyl halide was available. This contrasts sharply with the ready conversion of primary aromatic amines into aryl halides via the diazonium salt (Section 6.7, p.922). However a useful method has not been discovered which is not only applicable to the synthesis of simple alkyl and aralkyl chlorides, bromides, iodides and fluorides, but could clearly be of value when it is required to replace an amino group in a naturally occurring amine by a halogen.92... 

Reaction of a nitro-substituted aryl halide with a good nucleophile leads to nucleophilic aromatic substitution. Methoxide will displace fluoride from the ring, preferentially at the positions ortho and... 

Aryl halides are often susceptible to photochemical degradation. As described in Chapter 10 later in this book, cleavage of the C-X bond occurs with low quantum yield for aryl chlorides (132), higher quantum yields for aryl bromides and iodides (133), and high quantum yields for some aryl fluorides (e.g., fluoroquinolones) (134). Aryl chlorides are photolabile to homolytic and/or heterolytic dechlorination (43). For sertraline hydrochloride, decomposition of the aryl dichloride moiety occurs in solution when exposed to light (ultraviolet and fluorescent conditions). As shown in the following proposed mechanism, the major photochemical decomposition products include mono-chloro- and des-chloro-sertraline via homolytic cleavage (Fig. 91) (86). 

Aryl halides are excellent substrates for metal-halogen exchange by highly activated Rieke copper, affording aryl coppers at or below room temperature in fair to excellent yields. Functional groups such as nitriles, ketones and fluoride substituents are tolerated,... 

An improvement in this technique of sacrificial electrodes (Se and Mg) for the formation of the Z2-2 ions was achieved by using an undivided cell and by addition of fluoride ions to avoid the precipitation of the Se2Mg304. Thus, the reaction of 2-chloroquinoline with Se2-2 gave 79% yield of 248a. Following this methodology the diselenides 250 were prepared by reaction with aryl halides 249 (equation 162)303. 

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