Reactions of 2-Propanol Radical with Halogenated Organics in Aqueous Solution: Theoretical Evidence for Proton-Coupled Electron Transfer and Competing Mechanisms

Abstract

The reactions of α-hydroxyalkyl radicals in aqueous medium are of interest because they exhibit a rich variety of fundamentally important competing mechanisms, such as proton-coupled electron transfer (PCET), hydrogen atom transfer, free radical substitutions, abstractions and additions, etc. We present a theoretical study of the mechanism and kinetics of the aqueous reactions of α-hydroxyisopropyl (2-propanol) radical with four halogenated organic substrates: iodoacetate (IAc), iodoacetamide (IAm), 5-bromouracil (5-BrU), and carbon tetrachloride (CCl). The reactions are studied using density functional theory (DFT) (M06-2X), and the solvent is modeled as a polarizable continuum, either without the explicit solvent molecules or with one added water molecule. For an additional refinement, the double hybrid DFT B2PLYP energies were calculated at the M06-2X stationary points. Within this framework, for each substrate, we determine the most favorable radical-induced decomposition pathway among the several found and compare the thermochemical predictions against the experimental kinetics. The following dominant decomposition mechanisms are inferred: PCET for IAc, PCET-HO and the I-atom abstraction for IAm, the ortho-addition to the double bond for 5-BrU, and the Cl-atom abstraction for CCl. These pathways are invariably characterized by the negative apparent activation energies. Whereas for 5-BrU and CCl the transition state theory rate constants are in good agreement with the experiment, the rate constants for IAc and IAm-the two substrates reacting preferably via the PCET-are difficult to predict correctly. Consequently, the corresponding reaction barriers necessitate lowering by 1-3 kcal mol to bring them in accord with experiment. The B2PLYP method provides a worthwhile improvement over the M06-2X energetics although the largest errors remain for the two PCET processes.

Reactions of a hydrogen atom with haloacetates in aqueous solutions: Computational evidence for proton‐coupled electron transfer and competing mechanisms

“…In the PCET transition state in presence of basic buffer anion the proton‐acceptor can be buffer as in PCET2 mechanism (Figure 2a) or carboxyl group of the haloacetate like in the PCET1 (Figure 2b). As seen in Table 1, the presence of has a limited effect on the rate of PCET, which can be attributed to the hydrophobicity of hydrogen atom and consequently hindered the formation of hydrogen bonds that in our previously studied systems played a key role in proton transfer 15,47,48 . Comparing the PCET activation Gibbs energies in Table 1 can be seen that iodoacetate reacts faster than bromo‐ and chloroacetate due to relatively weaker carbon‐iodine bond.…”

“…There are evidence of water potentially acting as an intermediate in the sense of the water‐assisted proton transfer, viz. the accepting the proton from the radical and concurrently yielding it to (Figure 3) The so‐ called PCET‐ was previously observed in reactions of α‐hydroxyisopropyl radical with iodoacetamide 47 where was shown the capability of water to act as the proton acceptor and donor to incite the PCET. Specifically, water receives the proton from the radical and transfers it further to the final product, much like the proton relay 14,47 .…”

“…the accepting the proton from the radical and concurrently yielding it to (Figure 3) The so‐ called PCET‐ was previously observed in reactions of α‐hydroxyisopropyl radical with iodoacetamide 47 where was shown the capability of water to act as the proton acceptor and donor to incite the PCET. Specifically, water receives the proton from the radical and transfers it further to the final product, much like the proton relay 14,47 . The final result is a complex of the water molecule and a carboxymethyl radical with the elimination of the anion.…”

“…Rather than the prelude to forming the single HO bond, the markedly increased density between the H atom and can be thought of as an “electron avenue” via which the transfer of the single electron takes place. Similarly, enhanced density between the electron‐donating and accepting atoms is regularly seen in the transition states of the related systems 15,47 . In the course of the PCET the carboxyl group accepts the proton and the α‐C atom of accepts the electron, which brings about the immediate scission of the CX bond.…”

“…In the course of the PCET the carboxyl group accepts the proton and the α‐C atom of accepts the electron, which brings about the immediate scission of the CX bond. The analogous route of PT, which consequently eliminates the need for an external base, was also demonstrated for the reaction of the α‐hydroxyisopropyl radical with in non‐buffered solution 47 . Populating LUMO orbital of the haloacetate with an electron causes the dehalogenation due to the presence of anti‐binding (C–X) interaction (ESI, Figure S5).…”