Puzzling Reaction of Imidazole with Methyl Parathion: P=S versus P=O Mechanistic Shift Dilemma in Organophosphates

Abstract

Organophosphates (OPs) constitute many toxic agrochemicals and warfare and can undergo a wide spectrum of mechanisms, some which are fairly unexplored. In this sense, concise mechanistic elucidation stands out as a strategic tool for achieving efficient detoxification and for monitoring processes. Particularly intriguing is the effect of substituting the oxygen atom of the phosphoryl moiety (P=O) in OPs with a sulfur atom to give the thio‐derived OPs (i.e., OTPs, P=S). In general, imidazole (IMZ) reacts very efficiently with OPs by targeting the phosphorus atom, although herein we evidence a thio‐driven shift with OTPs: IMZ undergoes unusual nucleophilic attack at the aliphatic carbon atom of methyl parathion. Alkylation of IMZ under mild conditions (aqueous weakly basic medium) is also novel and should be applicable to other novel IMZ‐based architectures, and thereby, it can be a great ally for organic synthesis. Overall, a broader understanding of the mechanistic trend involved in such highly toxic agents is provided.

Are Imidazoles Versatile or Promiscuous in Reactions With Organophosphates? Insights From the Case of Parathion

“…It is interesting to note the small absorbance variation in the profiles of parathion and DEPT, which is significantly higher for PNP, that can be attributed to the greater molar absorptivity of PNP in contrast to parathion and DEPT. 21 As mentioned, previously we showed that in the reaction of imidazole with the similar OPs methyl parathion, only one path was confirmed at the aliphatic carbon. 21 Here, with parathion, we observe two concomitant reactions with imidazole.…”

“…This odd attack that forms alkylated imidazole under such mild conditions (aqueous, weakly basic) is peculiar and had been evidenced for the first time to occur exclusively by this means in the reaction of imidazole with methyl parathion, in a previous study. 21 Aside from the extraordinary impact that the facile alkylation of imidazole can bring to the field of organic synthesis, this pathway has important consequences when targeting chemical detoxification of OPs, since products of different nature are produced. Methyl parathion is very similar to parathion (contains ethyl groups instead of methyl), so one would expect that the same mechanism drives the reaction.…”

“…Finally, the last pathway that can occur herein is the attack of imidazole at the aromatic carbon of parathion, giving DNEPT and the derivative 1-NIMZ (path C, Figure 2). This path should be the least favorable one with imidazole (no reports to date) 19,21 and occurs predominantly with alpha-nucleophiles. 25 In order to infer how the reactions occur, a thorough kinetic study was carried out as well as it was followed by 1 H and 31 P NMR, to confirm possible intermediates and products.…”

“…Our research group has been studying some reactions with imidazole and the OPs compounds DEDNPP, 19 paraoxon, 20 and methyl parathion, shown in Figure 1. 21 Interestingly, with the P=O containing phosphates (DEDNPP and paraoxon), the imidazole attacks only the phosphorus center leading to an unstable imidazole phosphoryl intermediate and subsequently to diethyl phosphate and the nitrophenolate product. In this case, imidazole acts as an authentic catalyst generating less toxic products.…”

“…The kinetic profiles of absorbance vs. time were fitted according to pseudo-first order equations using iterative least-squares software. 21…”