Catalysts for nucleophilic displacement

Phase transfer catalysts were used for nucleophilic displacement reactions of activated leaving groups by hydroxyfurazanyl anions. For example, tetrachloro-pyrazine was found to react with hydroxyfurazans in benzene/Na2C03/tetraalkyl-ammonium salts giving products of mono- or disubstitution (Scheme 173) (94MI1). The course of the reaction depends on the ratio of the reactants and the nature of the ammonium salt. 

Direct nucleophilic displacement of halide and sulfonate groups from aromatic rings is difficult, although the reaction can be useful in specific cases. These reactions can occur by either addition-elimination (Section 11.2.2) or elimination-addition (Section 11.2.3). Recently, there has been rapid development of metal ion catalysis, and old methods involving copper salts have been greatly improved. Palladium catalysts for nucleophilic substitutions have been developed and have led to better procedures. These reactions are discussed in Section 11.3. 

The resulting catalyst was highly active for cyanide and acetate ion displacements on 1-bromobutane. As expected, soluble low molecular weight quaternary ammonium salts and a soluble quaternized linear poly(ethyleneimine) were even more active, presumably because they had no mass transfer and intraparticle diffusional limitations. These catalysts had a much higher density of charged sites (at least within the micro domains of the poly(ethyleneimine)) than any of the other active quaternary ammonium ion catalysts reported for nucleophilic displacement reactions. 

The tetracoordinate silicon cation is a rather common species in solution. It may be generated by heterolytic cleavage of a bond from silicon to a reactive ligand, as a result of interaction of the silicon center with an uncharged nucleophile like amine, imine, phosphine, phosphine oxide, and amide. Since these nucleophiles are also known to be effective catalysts for many displacements at silicon including important silylation processes (86,89,235-238), the cations of tetracoordinate silicon have received attention as possible intermediates in these reactions according to Eq. (40) (78,235,239-243). 

Frequently, Pd(PPh3)4 (or another Pd" complex) is used as a catalyst for the displacement of aUyUc acetates or halides by nucleophiles. A general catalytic cycle is depicted in Scheme 30. If chloride ions are present, no ( 7r-allyl)PdL2 forms. Instead, a ((( -allyl)PdL2Cl intermediate is formed. Thus, different precursors (such as aUylic chlorides or aUylic acetates) or different reaction conditions can lead to different reactivities, regioselectivities, and enantioselectivities. 

Taking into account the former discussion on the difficulties associated with the efficient use of polymer-supported PTC, it is easy to understand that an appropriate design of the overall process is essential for success. Several factors have been found to be critical for the performance of the catalyst. For onium salts, the use of a bulky R groups is preferred, in particular for nucleophilic displacement reactions. For the substitution of bromide by iodide in 1-bromooctane, reaction rates... 

Ref, 19, 20) are well worth describing here in some detail, as they focus on the choice of a phase transfer catalyst and on several other factors which are of importance in the chemical modification of soluble poly(chloromethy1 styrene). In a first series of experiments involving solid-liquid reactions with potassium acetate as a nucleophile, Nishikubo and coworkers observe that while reactions carried out without any added phase transfer catalyst do not work in apolar solvents, satisfactory results can be obtained in DMF (Table 1) this confirms previous observations (Ref. 7, 14, 23, 24) which suggest that DMF and DMSO are excellent solvents for nucleophilic displacements on poly(chloromethyl styrene). 

The economic promise of polystyrene-supported phase transfer catalysts depends on their reuse in industrial processes. Under some of the reaction conditions described for nucleophilic displacement reactions and for alkylation of active methylene compounds, the... 

A bifunctional autocatalytic effect of azinones in general is possible in certain nucleophilic reactions such as amination. Zollinger has found that 2-pyridone is the best catalyst for anilino-dechlorination of various chloroazines. It seems likely that examples of autocatalysis will be found when the substrate contains an azinone moiety. The azinone hy-products of displacement reactions may also function in this way as catalysts for the main reaction. 

Recently, the above mentioned model reaction has been extended to polycondensation reactions for synthesis of polyethers and polysulfides [7,81]. In recent reports crown ether catalysts have mostly been used in the reaction of a bifunctional nucleophile with a bifunctional electrophile, as well as in the monomer species carrying both types of functional groups [7]. Table 5 describes the syntheses of aromatic polyethers by the nucleophilic displacement polymerization using PTC. 

Trost and coworkers7 have reported the use of palladium(O) as a catalyst for displacement of the phenylsulfonyl group by soft nucleophiles. Thus, treatment of allyl sulfone 12 with the sodium salt of dimethyl malonate in the presence of 5 mol % of... 

Kostic et al. reported the use of various palladium(II) aqua complexes as catalysts for the hydration and alcoholysis of nitriles,435,456 decomposition of urea to carbon dioxide and ammonia, and alcoholysis of urea to ammonia and various carbamate esters.457 Labile aqua or other solvent ligands can be displaced by a substrate. In many cases, the coordinated substrate thus becomes activated toward nucleophilic addition of water or alcohols. 

Kostic et al. recently reported the use of various palladium(II) aqua complexes as catalysts for the hydration of nitriles.456 crossrefil. 34 Reactivity of coordination These complexes, some of which are shown in Figure 36, also catalyze hydrolytic cleavage of peptides, decomposition of urea to carbon dioxide and ammonia, and alcoholysis of urea to ammonia and various carbamate esters.420-424, 427,429,456,457 Qggj-jy palladium(II) aqua complexes are versatile catalysts for hydrolytic reactions. Their catalytic properties arise from the presence of labile water or other solvent ligands which can be displaced by a substrate. In many cases the coordinated substrate becomes activated toward nucleophilic additions of water/hydroxide or alcohols. New palladium(II) complexes cis-[Pd(dtod)Cl2] and c - Pd(dtod)(sol)2]2+ contain the bidentate ligand 3,6-dithiaoctane-l,8-diol (dtod) and unidentate ligands, chloride anions, or the solvent (sol) molecules. The latter complex is an efficient catalyst for the hydration and methanolysis of nitriles, reactions shown in Equation (3) 435... 

The most effective catalyst for the hydrolysis of p-nitrophenyl acetate was reported to be a cycloheptaamylose derivative containing approximately two imidazole groups per cycloheptaamylose molecule (Cramer and Mackensen, 1970). At pH 7.5 and 23°, this material accelerates the rate of release of phenol from p-nitrophenyl acetate by a factor of 300 when compared with the hydrolysis of this substrate in the absence of catalyst. However, when compared with an equivalent concentration of imidazole, which is an effective catalyst for ester hydrolysis at neutral pHs, the rate accelerations imposed by this cycloheptaamylose derivative are only two- to threefold. Cramer and Mackensen attributed this rate enhancement to nucleophilic displacement of phenol from the included ester by a cycloheptaamylose hydroxyl group, assisted internally by the attached imidazole group... 

An even simpler protocol for performing nucleophilic substitutions (aminations) and Suzuki reactions in one pot was reported by the Organ group for the generation of a 42-member library of styrene-based nicotinic acetylcholine receptor (nAChR) antagonists (Scheme 6.21) [49]. After considerable experimentation, the authors found that simultaneous nucleophilic displacement and Suzuki coupling could be carried out very effectively by charging the microwave process vessel with the palladium catalyst (0.5 mol% palladium-on-charcoal), the boronic acid [R1B(OH)2], the... 

In contrast, liquidiliquid phase-transfer catalysis is virtually ineffective for the conversion of a-bromoacetamides into aziridones (a-lactams). Maximum yields of only 17-23% have been reported [31, 32], using tetra-n-butylammonium hydrogen sulphate or benzyltriethylammonium bromide over a reaction time of 4-6 days. It is significant that a solidiliquid two-phase system, using solid potassium hydroxide in the presence of 18-crown-6 produces the aziridones in 50-94% yield [33], but there are no reports of the corresponding quaternary ammonium ion catalysed reaction. Under the liquidiliquid two-phase conditions, the major product of the reaction is the piperazine-2,5-dione, resulting from dimerization of the bromoacetamide [34, 38]. However, only moderate yields are isolated and a polymer-supported catalyst appears to provide the best results [34, 38], Significant side reactions result from nucleophilic displacement by the aqueous base to produce hydroxyamides and ethers. 

The simplest C-C bond formation reaction is the nucleophilic displacement of a halide ion from a haloalkane by the cyanide ion. This was one of the first reactions for which the kinetics under phase-transfer catalysed conditions was investigated and patented [l-3] and is widely used [e.g. 4-12], The reaction has been the subject of a large number of patents and it is frequently used as a standard reaction for the assessment of the effectiveness of the catalyst. Although the majority of reactions are conducted under liquiddiquid two-phase conditions, it has also been conducted under solidrliquid two-phase conditions [13] but, as with many other reactions carried out under such conditions, a trace of water is necessary for optimum success. Triphase catalysis [14] and use of the preformed quaternary ammonium cyanide [e.g. 15] have also been applied to the conversion of haloalkanes into the corresponding nitriles. Polymer-bound chloroalkanes react with sodium cyanide and cyanoalkanes under phase-transfer catalytic conditions [16],... 

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