Nucleophilic substitution analysis

This chapter has a mechanistic emphasis designed to achieve a practical result. By understanding the mechanisms by which alkyl halides undergo nucleophilic substitution, we can choose experimental conditions best suited to cariying out a particular- functional group transfonnation. The difference between a successful reaction that leads cleanly to a desired product and one that fails is often a subtle one. Mechanistic analysis helps us to appreciate these subtleties and use them to our advantage. 

We have intentionally selected example reactions (Figs. 29-33) that would not usually be immediately obvious to a chemist. The examples chosen have all been concerned with rearrangements of various types, since their courses are frequently difficult to predict. It remains to emphasize that the reactivity functions contained in EROS perform perfectly well with other types of reaction. This is true, for example, with reactions that a chemist could derive directly from an analysis of the functional groups in a molecule. Thus, EROS predicts addition reactions to carbonyl compounds, nucleophilic substitutions, and condensation reactions, to name just a few examples. In all these reaction types, the possibility of assigning a quantitative estimate to the reactivity at the various sites via the reactivity functions is of particular merit. It... 

Chiral sulfonium ylides have been known for some 30 years, and their stereochemistry and properties have been studied.15 Optically active selenonium ylides were obtained by reacting selenoxides with 1,3-cyclohexanedione under asymmetric conditions by Sakaki and Oae in 1976 for the first time,16 and also optically resolved by fractional recrystallization of the diastereomeric mixtures in the early 1990s.17 In 1995, optically active selenonium ylides 6 were obtained in over 99% de by nucleophilic substitution of optically active chloroselenurane or selenoxide with active methylene compounds with retention of configuration.18 The absolute configurations were determined by X-ray analysis of one... 

Thioetherification of PECH is feasibly performed in DA-solvents as already described in the patent (20J. For example, the highest substitution was obtained by the reaction of P(ECH-EO)(1 1 copolymer of epichloro-hydrin and ethylene oxide) and equimolar thiophenoxide in HMPA at 100°C for 10 h as DS 83% for sodium and 93% for potassium salts. The DS in our nucleophilic substitution was estimated by the elemental analysis as well as the titration of liberated chloride ion with mercuric nitrate (21). In the latter method, reacted medium was pretreated with hydrogen peroxide when the reductive nucleophiles which can react with mercuric ion were used. As described before for PVC, thiolation was also achieved conveniently with iso-thiuronium salt followed by alkaline hydrolysis without the direct use of ill-smelling thiolate. The thiolated PECH obtained are rubbery solids, soluble in toluene, methylene chloride, ethyl methyl ketone and DMF and insoluble in water, acetone, dioxane and methanol. 

Organic chemistry and instrumental analysis Synthesis 3 Mechanisms of nucleophilic substitution reactions... 

Trudell and co-workers reported the N-arylation with 2-chloro-3-nitropyridine of [l,2,3]triazolines fused onto [4,5-dpyridazine (Scheme 5) and [4,5-,yjpyrimidine (Scheme 6) <2000JHC1597>. Substitution at the 2-position of the pyridine ring was confirmed by X-ray crystallographic analysis of products 8 and 9. Similarly, [l,2,3]triazolo[4,5-,yjpyrimidine gave 10 in low yield, after nucleophilic substitution of the chloro substituent activated by the nitro group in 2-chloronitrobenzene (Scheme 6). 

Pedersen used reactions of nucleophilic substitution to synthesize most of the crown ethers he has obtained. On the other hand, Lehn and his coworkers [17] (Fig. 7.1.4) carried out cyclization reactions involving amide formation under high dilution conditions in their quest for cryptands such as 54. Pedersen analysis of the selective inclusion of alkali metal cations into the crown ethers cavity... 

A mathematical analysis of all four isomeric thiadiazoles by the simple molecular orbital method has provided molecular diagrams of the free base and conjugate acid of each thiadiazole, with electron densities, bond orders, and free valencies. On this basis, predictions have been made concerning the reactivities of the six non-equivalent carbon atoms, the basicities of the nitrogen atoms, and the delocalization energies in these molecules. The 5-position in free 1,2,4-thiadiazole should possess maximum reactivity in nucleophilic substitution reactions. The treatment also accounts for the order of the polarographic half-wave potentials and the position of the absorption maxima in the ultraviolet region of the spectra of 1,2,4- and 1,3,4-thiadiazoles.4... 

The high reactivity of di- and trinitrophenyl fluorides towards nucleophiles has been used for the arylation of various N-nucleophiles. A method was developed for the determination of N-terminal amino acids in peptides. Thus, nucleophilic attack of the amino acid nitrogen at Sanger s reagent (2,4-dinitrophenyl fluoride, 4), hydrolysis and subsequent analysis of the N-(2,4-dinitrophenyl)amino acid allows determination of the amino acid.162,163 Although this method has been replaced by more efficient procedures, it marked a milestone in the elucidation of peptide structures (Nobel Prize 1958). A variety of N-nuclcophilcs (no amino acids) which have been used in the nucleophilic substitution of 2,4-dinitrophcnyl fluoride is listed. 

In Section II,B we reported significant data concerning the influence of the solvation in the case of nucleophilic substitutions by alkoxides at Si—OMe, Si—F, and Si—SMe bonds (55). The most important fact that emerges from these data is that the stereochemistry changes from retention to inversion when the alcohol content of the medium is increased. We propose the following analysis ... 

Nucleophilic substitution of fluorine in perfluorinated sulfonium ions yields the corresponding aminosulfonium ions when reacted with Me3SiNMe2 [Eq. (4.66)]. Crystal structure analysis of CF3S(NMe2)2+, (CF3)2SNMe2+, and F2SNMe2+ hexa-fluoroarsenates gives similar S—N bond distances (1.605, 1.578, and 1.535 A, respectively) 215,244... 

Arasabenzene, with chromium, 5, 339 Arcyriacyanin A, via Heck couplings, 11, 320 Arduengo-type carbenes with titanium(IV), 4, 366 with vanadium, 5, 10 (Arene(chromium carbonyls analytical applications, 5, 261 benzyl cation stabilization, 5, 245 biomedical applications, 5, 260 chiral, as asymmetric catalysis ligands, 5, 241 chromatographic separation, 5, 239 cine and tele nucleophilic substitutions, 5, 236 kinetic and mechanistic studies, 5, 257 liquid crystalline behaviour, 5, 262 lithiations and electrophile reactions, 5, 236 as main polymer chain unit, 5, 251 mass spectroscopic studies, 5, 256 miscellaneous compounds, 5, 258 NMR studies, 5, 255 palladium coupling, 5, 239 polymer-bound complexes, 5, 250 spectroscopic studies, 5, 256 X-ray data analysis, 5, 257... 

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