Direct nucleophilic displacement

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. 

Direct nucleophilic displacement of halo substituents proceeds via attack on the ring carbon atom (see Section 5.10.5.6). Nucleophilic attack on the halogen has not been reported. 

Direct nucleophilic displacements of the phosphate leaving group in inert organic solvents by nucleophiles of the... 

The other mechanisms to be considered are the direct nucleophilic displacement of an alkylated benzyl cation by protonic hydrogen [Eq. (16)] and homolytic displacement of an alkylated benzyl radical by atomic hydrogen [Eq. (17)]. However, it is recognized that reactions in Eqs. (16)... 

Nevertheless, the direct nucleophilic displacement of support-bound carboxylates to prepare hydroxamates presents some limitations. For example, O-tert-butyldimethylsilyl-protected hydroxylamine displaces common acids from oxime resin however, further treatment with trifluoroacetic acid (TFA) is necessary to remove completely the silyl... 

The same procedure failed to work with 2-bromopyrimidine due to direct nucleophilic displacement of the bromine by the amine component <2007TL2339>. 

The direct nucleophilic displacement of a thione at position 7 has been reported (Scheme 13), together with the further conversion of the resulting hydrazine to an azide or to a triazole <1998FA113>. Similarly, 7-amination has been carried out by displacement of methanesulfinyl and methanesulfonyl groups <2006BMCL4257>. 

The reaction of the chlorosulfite ester Xld with palladium(O) may take place by direct nucleophilic displacement of the chlorosulfite group at carbon by palladium or via an intermediate sulfite complex Xlld. The direct nucleophilic displacement would be expected to take place with inversion of configuration. The reaction of the chlorosulfite ester to afford... 

Exercise 14-20 In the hydrolysis of chlorobenzene-1-14C with AM aqueous sodium hydroxide at 340°, the products are 58% benzenol-1-14C and 42% benzenol-2-14C. Calculate the percentage of reaction proceeding (a) by an elimination-addition mechanism, and (b) by direct nucleophilic displacement. Would you expect the amount of direct displacement to increase, or decrease, if the reaction were carried out (a) at 240° and (b) with lower concentrations of sodium hydroxide Give your reasoning. 

Keller and Heidelberger131 reported the kinetics of solvolysis of 1, 30, 38, and benz[a,/i]anthracene 5,6-oxide (228). These studies were carried out mostly in the pH < 7 region where nucleophilic addition ordinarily does not take place with either K-region or non-K-region epoxides. These authors found evidence for the formation of a carbonium ion and consequently were led to believe that the cell macromolecules react with arene oxides through a carbonium ion-trapping mechanism and not by a direct nucleophilic displacement on the oxides. 

Reaction 3, Figure 2, illustrates another variant, the reactivity of >C=0"- as a Lewis base (e.g. nucleophile) via reaction with electrophilic species. In the specific case of >C=0"- reacting with an alkyl halide (R—X), a direct nucleophilic displacement (Sw2) process was initially envisioned. However, it is now evident that these alkylations take... 

This involves the direct nucleophilic displacement of halogen in an alkyl halide by an alkoxide ion (the Williamson synthesis) (Expt 5.72), and the method is particularly useful for the preparation of mixed ethers. For an unsymmetrical ether [e.g. t-butyl ethyl ether (7)], the disconnection approach suggests two feasible routes. 

Direct nucleophilic displacement of the halogen in an aryl halide is difficult and hydrolysis to phenols requires high temperatures and pressures the method is therefore only suitable on the large scale. The presence of a nitro group in the ortho or para position, however, makes the halogen more labile since electron withdrawal by the nitro group in these positions stabilises the intermediate anion by electron delocalisation. p-Chloronitrobenzene, for example, is hydrolysed to p-nitrophenol when heated with 15 per cent sodium hydroxide solution at about 150 °C. 

The synthetic method may be seen to be complementary to direct nucleophilic displacement. Whereas amines often react relatively sluggishly in metal-mediated nucleophilic displacements, they usually undergo facile reaction with carbonyls to form imines. The reduction of the imines (free or co-ordinated) may then be achieved by reduction with Na[BH4] or (less conveniently) by direct hydrogenation. This provides a very convenient method for the preparation of cyclic amines (Fig. 6-14). 

Direct nucleophilic displacement reactions constitute one of the most widespread classes of reactions with which chemists deal. The general reaction is described by equation (1) in which RY is regarded as the substrate. X as the... 

Neither L-alanine nor L-cysteine was incorporated into (113), but both L-serine (112) and glycine were. Good evidence was obtained that utilization of glycine is by way of L-serine. L-Serine was utilized without loss of the tritium that was sited at C-3, so the construction of the /Mactam ring occurs without change in the oxidation state at this carbon atom,97 in contrast to the parallel situation in the biosynthesis of penicillins.2 For nocardicin A (113), direct nucleophilic displacement of a (presumably activated) hydroxy-group of a seryl unit by amide nitrogen apparently occurs. 

The alternative modes of addition under equations (11) and (12) can be easily distinguished on the basis of the primary product distribution. However, bridged species other than open ions are frequently involved as intermediates and ring opening may occur by direct nucleophilic displacement processes (Poutsma and Ibarbia, 1971). 

An alternative view has been expressed by Birch et al., who formulate echitamine base as the carbinolamine ether LIX (86). This could be formed by direct nucleophilic displacement of the positively charged... 

Direct nucleophilic displacement of halide ion by a group R, not necessarily organic, attached to copper is considered 31) to be important only in the presence of ligands, L, which strongly coordinate with copper and aid the formation of the species (CuL4) + R . 

The complexes Co2(CO)e(RC2R ) are derived formally from Co2(CO)8 (I) through replacement of two bridging carbonyl groups by one alkyne unit. It has been suggested that formation of the complexes could proceed either by direct nucleophilic displacement (Su2 mechanism) or by a mechanism involving prior dissociation of the Co2(CO)b (SnI mechanism). 

Oxygen or, particularly, nitrogen adjacent to a carbon-fluorine bond greatly increases reactivity towards nucleophiles. Hydrolysis of a,a-difluoro ethers occurs under acid conditions [39] (Figure 5.19). Orthoesters are produced by reaction with aUcoxides such reactions may, however, occur via initial elimination of hydrogen fluoride, rather than by direct nucleophilic displacement of fluoride [40] (Figure 5.20). 

The presence of C—H bonds in a perfluoiinated system can, of course, have a profound effect, but the subsequent increase in reactivity usually stems from an elimination-addition rather than direct nucleophilic displacement of fluoride ion (see below). 

Intermediate VI, produced either by direct nucleophilic displacement or 1,4 addition depending on whether V is the actual substrate, may then be transformed into the final product. This may occur either by way of an acidic-type fragmentation via the bimolecular attack of the methoxide anion on the benzoyl... 

Reactions of the chloro compounds with lithium dimethylamide are complicated by the fact that nucleophilic displacement of hydrogen often precedes that of chlorine, giving complex mixtures of products. - The results obtained in reactions of potassium amide with chloro- and iodobenzo[ -]cin-nolines show that elimination-addition processes via arynes 93 and 94 are more important than direct nucleophilic displacement (addition-elimina-tion), Surprisingly, no l-aminobenzo[c]cinnoline is formed from the 1-and 2-halogeno compounds, while 4-chlorobenzo[c]dnnoline gives small amounts of 2-aminobenzo[c]cinnoline by a 1,3-displacement. 

An electron-transfer in the first step would give cationic intermediate 168. Formation of R3 SiX may then arise via a direct nucleophilic displacement of the silyl ligand, or through the neutral intermediate 169 by a reductive-elimination process. Cleavage reaction may also occur by competitive pathways. In the present state of knowledge, since few experiments have been done, it is difficult to pinpoint definitive mechanisms. 

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