Nucleophilic aliphatic substitution electronic effects

Nice examples of nucleophilic substitution on a thiophene ring are represented by nucleophilic substitutions of 5-acetyl-2-chloro-3-nitrothiophene (Scheme 103) [164], The acetyl group, as a second electron-withdrawing group, in addition to the nitro group, was necessary to support successful nucleophilic substitution. Various nucleophiles were effective, including aliphatic and aromatic V-nucleophiles, aliphatic 0-nucleophiles as well as aliphatic S-nucleophiles (Scheme 103) [164],... 

Thiols react more rapidly with nucleophilic radicals than with electrophilic radicals. They have very large Ctr with S and VAc, but near ideal transfer constants (C - 1.0) with acrylic monomers (Table 6.2). Aromatic thiols have higher C,r than aliphatic thiols but also give more retardation. This is a consequence of the poor reinitiation efficiency shown by the phenylthiyl radical. The substitution pattern of the alkanethiol appears to have only a small (<2-fokl) effect on the transfer constant. Studies on the reactions of small alkyl radicals with thiols indicate that the rate of the transfer reaction is accelerated in polar solvents and, in particular, water.5 Similar trends arc observed for transfer to 1 in S polymerization with Clr = 1.4 in benzene 3.6 in CUT and 6.1 in 5% aqueous CifiCN.1 In copolymerizations, the thiyl radicals react preferentially with electron-rich monomers (Section 3.4.3.2). 

The destabilization of sp -bound fluorine by p-jt repulsion activates fluorinated aromatic compounds totvard nucleophilic attack and subsequent substitution. The susceptibility of the carbon center toward nucleophiles is also enhanced by the negative inductive (—T) effect of fluorine. In particular, if the aromatic compound is also activated by —M electron-withdrawing substituents, for example a nitro or cyano group, in the ortho or para positions the fluorine is easily replaced by a variety of nucleophiles even under very mild conditions via a resonance stabilized Meisenheimer complex (Scheme 2.39). The ease of nucleophilic halogen replacement - F > Cl > Br > I - is in the opposite order to that for aliphatic nucleophilic substitution. 

The Skv I radical chain mechanism lor nucleophilic substitution [I70. as illustrated generally in eqs (2.64a-c), has been absent from our discussions. This mechanism has been shown to occur itt malty displacement reactions of leaving groups front both aromatic and aliphatic substrates. I low ever, in most of the aliphatic eases the substrates have a nitro or nilrophcnyl group (or other effective electron acceptor) in the a-position to the leaving group. The combination of I he nucleophile with the radical from the substrate must also lot m a relatively stable radical-anion in step 2.6lb. which is capable of propagating the chain... 

---