Dual Nucleophilic Substitution Reactions of O,O‐Diethyl 2,4‐dinitrophenyl Phosphate and Thionophosphate Triesters

Abstract

The reactions of the title compounds with phenoxides, secondary alicyclic (SA) amines, and pyridines, in 44 wt% ethanol-water, at 25 • C and an ionic strength of 0.2 M, were subjected to kinetic and product studies. From analytical techniques (HPLC and NMR), two pathways were detected (nucleophilic attack at the phosphoryl center and at the C-1 aromatic carbon) for the reactions of all the nucleophiles with the phosphate (2) and for the pyridinolysis of the thionophosphate (1). Only aromatic nucleophilic substitution was found for the reactions of 1 with phenoxides and SA amines. For the dual reactions, the nucleophilic rate constants (k N ) were separated in two terms: k P N and k Ar N , which are the rate constants for the corresponding electrophilic centers. The absence of a break in the Brønsted-type plots for the attack at P is consistent with concerted mechanisms. The Brønsted slopes, β Ar 0.32-0.71, for the attack at the aromatic C-1, are in agreement with stepwise mechanisms where formation of a Meisenheimer complex is the rate-determining step.

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

“…Recently the "thio effect" (i.e., the effect caused by exchanging the P=O by a P=S bond in OPs) became a matter of interest in reactions with organophosphates, where the solvent effect and the nature of nucleophiles were evaluated. 16,17 In this sense, Aguayo et al 6 studied the reaction of several pyridine and phenol derivatives with diethyl 2,4-dinitrophenylphosphate (DEDNPP) and diethyl 2,4-dinitrophenylthiophosphate (DEDNPSP). The results showed nucleophilic attacks at the aromatic carbon and phosphorus in different proportions, for pyridine nucleophiles.…”

“…Moreover, the attack at phosphorus was always majority for DEDNPP in contrast to DEDNPSP. 6 Rougier et al 18 studied the reaction of fenitrothion (thiophosphate structurally related to parathion) with some α-nucleophiles and observed that nitrogenated nucleophiles attack the phosphorus and aliphatic carbons. Indeed, there is no straightforward mechanistic trend of OPs containing P=O or its analogue with P=S and this comprehensive understanding related to structure is essential since this is one of the most valuable tools for destroying these compounds, leading to knowingly less toxic substances.…”

“…Due to the low solubility of parathion in water (around 38 µmol L -1 ), 27 40% of acetonitrile-d 3 was added to improve this, as done in similar studies. 6,21 Figure 7 presents the typical consecutive 31 P NMR decoupled spectra obtained during the reactions for pD 7. at 62.7 ppm was attributed to the reagent parathion, 23 which decreases along the reaction. At the same time, two signals appeared, one at 52.3 ppm, attributed to DEPT.…”

“…For example, the phosphoryl (P=O) or analogous thiophosphoryl (P=S) can present different electrophilic centers or even the aliphatic / aromatic groups anchored to the phosphoryl moiety can tune the mechanism. 6 Besides the synthetic applications (and threats) of the OPs, they are the pillars of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and other biological molecules. In the biological systems, the phosphoryl transfers are always mediated by enzymatic process.…”

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

“…One study shows that the reactiono fs econdary amines with the OP simulant diethyl-2,4-dinitrophenylphosphate (DEDNPP) occurs exclusively at the phosphorusa tom ( Figure 1, path c), but for the thio analogue, that is, DEDNPSP, this nucleophilic attack can happena tb otht he phosphorus and aromatic carbona toms (Figure 1, paths aa nd b). [3] In contrast, with the pesticidef enitrothion, primarya minesn ot only react at the phosphorus atom but also at the aliphatic carbon atom (Figure 1, pathsd and e). [4] Moreover,t he pesticide paraoxon was evaluated with various secondary amines, and it underwenta ttack solely at the phosphorus center ( Figure 1, path f).…”