Nucleophilic aliphatic substitution halogen

A considerable number of ring-fluorinated diazines undergoes various nucleophilic aromatic substitution reactions. Nucleophilic aromatic substitution reactions follow the well-established two-step addition-elimination mechanism via a Meisenheimer intermediate. The destabilization of sp -C bound fluorine by p-Jt repulsion activates fluorinated aromatic compounds toward nucleophilic attack and subsequent substitution. The susceptibility of the carbon center toward nucleophiles is also enhanced by the negative inductive (-la) effect of fluorine. Therefore the ease of nucleophilic halogen replacement - F>Cl>Br>I - is in the opposite order to that for aliphatic... 

The relative orders in which the halogens are displaced in nucleophilic aromatic substitution reactions has been advanced as an u-ment both for and against the intermediate complex mechanism. In particular Fierens and Halleux (91), who found the order, F < Cl < Br < I, for the reactions of the l-halo-2,4-dinitrobenzenes and the l-halo-2,4-dinitro-6-methylbenzenes with potassium iodide in dry acetone, and Hammond and Parks (92), who obtained the same order for the reactions of the l-halo-2,4-dinitrobenzenes with N-methylaniline in both nitrobenzene and 99.8% ethanol, have offered these results as support for a one-step mechanism, since this is the sequence observed in non-activated nucleophilic aromatic substitution reactions and in typical aliphatic displacements. Hammond has, however, pointed out that these experiments do not permit a distinction between a one-step mechanism and a two-step mechanism in which the second step is rate-determining (90). 

The possibility that substitution results from halogen-atom transfer to the nucleophile, thus generating an alkyl radical that could then couple with its reduced or oxidized form, has been mentioned earlier in the reaction of iron(i) and iron(o) porphyrins with aliphatic halides. This mechanism has been extensively investigated in two cases, namely the oxidative addition of various aliphatic and benzylic halides to cobalt(n) and chromiumfn) complexes. 

Substitution of scheme a forms a well-documented class of reactions (see Costentin et al. 1999,2000, Costentin and Saveant 2000, Corsico and Rossi 2000, 2002, 2004, Adcock et al. 2001, Vanelle and Crozet 2002, Medebielle et al. 2002, Galli and Rappoport 2003, Rossi et al. 2003, Vanelle et al. 2004, and Bnden et al. 2005 and references therein). In contrast to conventional nucleophilic substitution, the nncleophile, Nu-, reacts not with the substrate, RX, to give a product but with the radical R. The latter emerges as a result of R-X bond cleavage. Snbstitnent X is very often a halogen atom, bnt other leaving groups can also be used (see section 7.8.1). In the majority of aromatic Sr I reactions, the anion-radical RX- (R=Ar) is the observable intermediate. It is depicted in scheme a. With aliphatic snbstrates, snbstitntion takes place rather than 8 2 or S l substitutions, and the concerted mechanism depicted in scheme b is feasible. 

Tables IV through IX summarize the data that are currently available on the rates of bimolecular substitution and dehydrohalogenation reactions between sulfur nucleophiles and halogenated aliphatic substrates in aqueous solution (i.e., either measured in water or extrapolated to water from a non-aqueous or partially aqueous solvent). The sulfrir nucleophiles considered in these tables are HS-, S2-, S42-, S52- (Table IV), S2032 (Tables V and VIII), SO32-, HSO3 (Table VI), thiolate anions (Tables VII, VIII, and IX), thiols, thioethers, and thioadds (Table VII).

Table Vm. Competition Between Dehydrohalogenation and Substitution Pathways for Reactions Between Halogenated Aliphatic Substrates and Sulfur Nucleophiles (Rate Constants Expressed in Units of M V1.)...

Table IX. Second-order Rate Constants (M V1) for Dehydrohalogenation and Substitution Reactions of Halogenated Aliphatic Substrates with Sulfur Nucleophiles (ks>E and kS(SN> Respectively), Compared to the Corresponding Rate Constants for H20 (kn20,E d kH20,SN> Respectively)...

Nucleophilic halogen substitution in solutions of halobenzenes containing aliphatic amines has been used by Norseyev and coworkers24-27 to produce astatobenzene and its substituted derivatives. 

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