Homolytic vs Heterolytic Paths in the Photochemistry of Haloanilines

Abstract

The photochemistry of 4-haloanilines and 4-halo-N,N-dimethylanilines has been studied in apolar, polar aprotic, and protic solvents. Photophysical and flash photolysis experiments show that the reaction proceeds in any case from the triplet state. It is rather unreactive in apolar media, the highest value being Phi = 0.05 for the iodoanilines in cyclohexane. Changing the solvent has little effect for iodoanilines and for the poorly reacting bromo analogue, while it leads to a variation of over 2 orders of magnitude in the quantum yield for the chloro and fluoro derivatives. The triplets have been characterized at the UB3LYP/6-31G(d) level of theory, evidencing a deformation and an elongation (except for C-F) of the C-X bond. Homolytic fragmentation is in every case endothermic, but calculations in acetonitrile solution show that heterolytic cleavage of C-Cl and C-Br is exothermic. Experimentally, the occurrence of heterolytic fragmentation has been monitored through selective trapping of the resulting phenyl cation by allyltrimethylsilane. Heterolytic dechlorination occurs efficiently in polar media (e.g., Phi = 0.77 in MeCN), while debromination remains ineffective due to the short lifetime of the triplet. Heterolytic defluorination is efficient only in protic solvents (Phi = 0.48 in MeOH), in accord with calculations showing that in the presence of an ancillary molecule of water fragmentation is exothermic due to the formation of the strong H-F bond. The energy profile for both homo- and heterolytic dissociation paths has been mapped along the reaction coordinates in the gas phase and in acetonitrile. The conditions determining the efficiency and mode of dehalogenation have been defined. This is significant for devising synthetic methods via photogenerated phenyl cations and for rationalizing the photodegradation of halogenated aromatic pollutants and the phototoxic effect of some fluorinated drugs.

Characterizing Ionic Liquids as Reaction Media through a Chemical Probe

“…The photoreactivity of 4-chloro-N,N-dimethylaniline (1), previously studied in organic solvents of different polarity, [10] was thus explored in some ILs. Specifically, we chose five methylalkylimidazolium salts (2 a-e) as a homogeneous series with similar polarity, polarizability, and hydrogenbond basicity and acidity by varying only the length of the alkyl chain (butyl or hexyl) and the counterion (at any rate, a non-nucleophilic anion, namely…”

Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester

“…[34] Such reactions would explain the oxygenindependent phototoxicity of this drug [Equation (2)]. Investigations aimed to document intermolecular reaction paths are ongoing.…”

“…Insertion into the CϪH bond would lead to a highly strained compound in this case, and thus hydrogen transfer takes place instead. Indeed, in the case of the 4-aminophenyl cation it has been demonstrated that alcohols and amines act as H donors, giving a radical cation that is then reduced to the final compound [34,40,47] (Scheme 7). In this case the second step would occur intramolecularly (overall a formal hydride transfer) to give cation 11.…”

“…Insertion into the CϪH bond would lead to a highly strained compound in this case, and thus hydrogen transfer takes place instead. Indeed, in the case of the 4-aminophenyl cation it has been demonstrated that alcohols and amines act as H donors, giving a radical cation that is then reduced to the final compound [34,40,47] transfer) to give cation 11. As one may expect, this is followed by deprotonation from the 2Ј-position to yield enediamines 3 and 4 (or the corresponding esters 9 and 10 from LOM-Me), a type of photoreaction not previously found among FQs, although degradation of the piperazine moiety, probably likewise initiated by intramolecular H abstraction, has been previously observed with structurally related orbifloxacin.…”

“…Apparently, the charge delocalization in the heteroaryl cation makes ionic cleavage possible, at least in a protic solvent. [34] The fluoroquinolones of this group, which is larger than the previous one, are modest oxygen sensitizers, [31] clearly due to the short lifetime of the excited states, which makes Equation (1) unimportant, although they are even more phototoxic than the previous group. As an example, lomefloxacin (LOM-H), a widely used drug of this family, is known to be photogenotoxic; indeed, it has been used as a model for determining the photogenotoxic potential of drugs.…”