Primary carbon centers, nucleophilic reactions

II. NUCLEOPHILIC REACTIONS AT ALIPHATIC CARBONS A. Primary Carbon Centers... 

There is evidence, both experimental and theoretical, that there are intermediates in at least some Sn2 reactions in the gas phase, in charge type I reactions, where a negative ion nucleophile attacks a neutral substrate. Two energy minima, one before and one after the transition state, appear in the reaction coordinate (Fig. 10.1). The energy surface for the Sn2 Menshutkin reaction (p. 499) has been examined and it was shown that charge separation was promoted by the solvent.An ab initio study of the Sn2 reaction at primary and secondary carbon centers has looked at the energy barrier (at the transition state) to the reaction. These minima correspond to unsymmetrical ion-dipole complexes. Theoretical calculations also show such minima in certain solvents, (e.g., DMF), but not in water. "... 

Perfluoromethylenecyclopropane is extremely reactive towards nucleophiles most alcohols, amines, and water undergo exothermal addition at 0°C with the exocyclic carbon acting as the electrophilic center.The reaction of water with perfluoromethylenecyclopropane gave 2,2,3,3-tetrafluorocyclopropanecarboxylic acid (5). The primary addition products of amines formed the respective amides 4 upon subsequent reaction with water. 

Reaction mechanisms for hydrolysis can be classified according to the type of reaction center involved. The primary distinction is made between reaction at saturated and unsaturated centers. With respect to carbon-centered functional groups, which will be the primary focus of this chapter, hydrolysis involves reactions at sp (saturated) or sp (unsaturated) hybridized carbons. Nucleophilic reactions at sp carbons are termed nucleophilic substitution (2.7). The reaction at sp carbons is termed nucleophilic addition-elimination or acyl substitution (2.8). 

Nucleophilic anions, i.e. halides, pseudohalides, alkoxides, phenoxides, and thio-phenoxides, are particularly suitable for these reactions. Even anions of lower reactivity in nucleophilic displacements, i.e. carboxylates, nitrates, nitrites and hydroperoxides, find practical application under PTC conditions. Reactions are rigorously Sf,2 in mechanism primary substrates are thus most suitable, since secondary substrates afford elimination products in high yields, especially when reacted at high temperatures, and tertiary substrates only give rise to elimination. This behaviour is consistent with the low polarity of the organic phase, preventing unimolecular mechanisms and favouring elimination over substitution when the reaction center is not a primary carbon atom. 

The reaction proceeds well with unhindered secondary amines as both nucleophiles and bases. The yield of allylic amine formed depends upon how easily palladium hydride elimination occurs from the intermediate. In cases such as the phenylation of 2,4-pentadienoic acid, elimination is very facile and no allylic amines are formed with secondary amine nucleophiles, while phenylation of isoprene in the presence of piperidine gives 29% phenylated diene and 69% phenylated allylic amine (equation 30).84 Arylation occurs at the least-substituted and least-hindered terminal diene carbon and the amine attacks the least-hindered terminal ir-allyl carbon. If one of the terminal ir-allyl carbons is substituted with two methyl groups, however, then amine substitution takes place at this carbon. The reasons for this unexpected result are not clear but perhaps the intermediate reacts in a a- rather than a ir-form and the tertiary center is more accessible to the nucleophile. Primary amines have been used in this reaction also, but yields are only low to moderate.85 A cyclic version occurs with o-iodoaniline and isoprene.85... 

In the case of nucleophiles with an NH2 group, however, an enamine is the primary product. The second nucleophilic center subsequently attacks the N=C carbon atom linked to the active fluorine atom, forming a five-membered benzoheterocycle. The reaction of hexafluoropro-pylene and perfluoroisobutylene with or /zo-phenylenediamine, 2-aminophe-nol, and 2-aminothiophenol occurs analogously and leads to the derivatives of benzimidazole, benzoxazole, and benzthiazole, respectively. 

As discussed in the preceding sections of this chapter, the key to living cationic polymerization is to reduce the effect of chain transfer reactions (Scheme 4) because termination is much less important in the cationic polymerization of vinyl monomers. The primary reason for frequent chain transfer reactions of the growing carbocation (1) is the acidity of the /3-H atoms, next to the carbocationic center, where a considerable part of the positive charge is localized. Because of their electron deficiency, the protons can readily be abstracted by monomers, the counteranion (B ), and other basic components of the systems, to induce chain transfer reactions. It is particularly important to note that cationically polymerizable monomers are, by definition, basic or nucleophilic. Namely, they have an electron-rich carbon-carbon double bond that can be effectively poly-... 

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