Quaternary ammonium with aryl halides

The palladium-catalysed arylation of olefins with aryl halides, the Heck reaction, is usually performed in polar solvents such as acetonitrile or dimethyl sulfoxide, in combination with a base and a Pd(ii) pre-catalyst that may or may not be associated with a phosphorus ligand. Given that quaternary ammonium or phosphonium salts are known to increase reaction rates, ILs emerged as promising solvents for this reaction.In the case of imidazolium-based ionic liquids, the solvent, beside providing an unusual coulombic environment. 

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

The direct arylation (Heck) of thiophene by means of aryl halides and substituted thiophenes has been extensively studied by Lemaire and co-workers <1997TL8867, 1998JOM(567)49,2002TL1829, 2004T3221>. EWGs facilitate the reaction. With a 3-substituted thiophene, the major product was the 2-aryl derivative with 2-substituted thiophenes, the only product was the 5-aryl derivative. Yields ranged from 40% to 95%. The reaction has been extended to the synthesis of 2-arylbenzo[3]thiophenes as well (Equations 22 to 25). The yield improved on replacing the quaternary ammonium bromide by dicyclohexyl-18-crown-6. 

For the glycosylation of phenols with glycosyl halides, phase-transfer conditions using aqueous sodium or potassium hydroxide and quaternary ammonium salts have also been reported [89-94]. By using phase-transfer catalysis, a method for solid-phase synthesis of aryl glycosides was developed [95]. 

Ammonolysis of halides is usually limited to the aliphatic series, because of the generally low reactivity of aryl halides toward nucleophilic substitution. (However, see Chap. 25.) Ammonolysis has the disadvantage of yielding a mixture of different classes of amines. It is important to us as one of the most general methods of introducing the amino ( NH2) group into molecules of all kinds it can be used, for example, to convert bromoacids into amino acids. The exactly analogous reaction of halides with amines permits the preparation of every class of amine (as well as quaternary ammonium salts, R4N X ). 

The synthesis of aromatic azides (Scheme 37) from aryl halides with azide ions (SxAr) is particularly successful with systems that carry an activating substituent, an electron-withdrawing group, either in the ortho or the para position relative to the potential leaving group." -" A table with numerous examples can be found in the literature." Fluoride ion as a leaving group is superior to the other halides. Dipolar aprotic solvents, such as DMF for instance, have their special merits in these transformations, too. The reaction of 2,4- or 2,6-dinitroaryl halides with azide ions was shown to be accelerated in micelles or in the presence of quaternary ammonium salts." ... 

Tanaka and his associates demonstrated for the first time how to use non-volatile ionic liquids (ILs) as solvents in palladium-catalyzed carbonylations [163], In the case of alkoxycarbonylation of bromobenzene, higher yields were obtained when 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4] was used as the reaction medium compared with standard conditions. And the selectivity for the monocarb-onylation of iodobenzene with t -PrOH or Et2NH was significantly enhanced by [bmim][BF4]. After separation of the products, the solvent-catalyst system was easily recycled and exhibited catalytic activity up to seven times. Since then the replacement of traditional solvents with quaternary ammonium halides, imidazoli-um- or pyridinium-derived ILs has gained increasing importance [164—173]. Recently, the phosphonium salt IL trihexyl(tetradecyl)phosphonium bromide has proven to be an effective reaction medium for various carbonylation reactions of aryl and vinyl bromides or iodides under mild conditions (Scheme 2.17) [174]. 

Lie and coworkers developed various quaternary ammonium salts 9 and phosphorus-based organic ionic bases 10 that promote the coupling of aryl halides with aliphatic amines, which are difficult to achieve with traditional alkaline bases (Fig. 20.4) [49]. In a set of screened promoters, TBAA, TBPE, and TBPM exhibited the best results (Scheme 20.22). 

Certain aryl and benzyl halides react with primary and secondary amines yielding the corresponding secondary and tertiary amines, in addition to hydrogen halide, much in the same shion as described in section II.B.4. However, by virtue of the electronegative nature of the reagents, the reaction does not proceed further up to quatemisa-tion as with the previous case, neither does it yield quaternary ammonium compounds with tertiary amines. 

It is interesting to note that the very widely used Makosza catalyst , benzyl triethyl ammonium chloride, does not show high efficiency in this study. 4) Phosphonium ions are somewhat more effective and thermally stable than the corresponding ammonium catalysts and both are better than arsonium systems. 5) Substitution of the quaternary ion by alkyl rather than aryl groups yields more effective catalysts. 6) Reaction rates are generally greater in orf/io-dichlorobenzene (and presumably in other chlorocarbon media) than in benzene, and botli are better than heptane. In connection with this latter point, Ugelstad and coworkers have studied the reactions of quaternary ammonium phenoxide ions with alkyl halides in a variety of media and concluded that the... 

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