Kinetics and Mechanism of the Pyridinolysis of O-Aryl Methyl Phosphonochloridothioates in Acetonitrile

Abstract

Continuing the experimental (anilinolyses 1 and pyridinolyses 2 ) and theoretical studies 3 on the phosphoryl transfer reactions, the reactions of Y-O-aryl methyl phosphonochloridothioates with X-pyridines in acetonitrile at 35.0 ± 0.1 o C (Scheme 1) have been carried out kinetically to gain further information into the phosphoryl transfer reactions and substituent effects of the nucleophiles and substrates on the reaction mechanism, as well as to compare with the relevant pyridinolyses of R 1 R 2 P(=S)Cl-type substrates in MeCN.The pseudo-first-order rate constants observed (k obsd ) for all reactions obey eq. (1) with negligible k 0 (≈ 0) in MeCN. The second-order rate constants were determined with at least five pyridine concentrations [XC 5 H 4 N]. No third-order or higher-order terms were detected, and no complications were found in the determination of k obsd or in the linear plot of eq. (1). This suggests that there is no base-catalysis or noticeable side reactions, and the overall reaction follows the path given by Scheme 1.The second-order rate constants [)] are summarized in Table 1, together with selectivity parameters, ρ X , β X , ρ Y , and ρ XY . The β X values were determined using pK a values in water; the slopes from the plots of log k 2 (MeCN) against pK a (H 2 O). Justification of this procedure has been experimentally and theoretically provided.6 The substituent effects in the nucleophiles and substrates on the rates are compatible with those for a typical nucleophilic substitution reaction with positive charge development at the nucleophilic N atom (ρ X < 0 and β X > 0) and negative charge development at the reaction center P atom (ρ Y > 0) in the transition state (TS). However, the Hammett (log k 2 vs σ X ) and Brönsted [log k 2 vs pK a (X)] plots for substituent X variations in the nucleophiles exhibit a break region between X = H and 3-Cl, resulting in discrete two parts with one part for the strongly basic pyridines (X = 4-MeO, 4-Me, 3-Me, H) and the other part for the weakly basic pyridines (X = 3-Cl, 3-Ac, 4-Ac), respectively (Fig. 1). The Hammett plots (log k 2 vs σ Y ) for substituent Y variations in the substrates are biphasic downwards with a break point at Y = H (Fig. 2).

Kinetics and Mechanism of the Pyridinolysis of Diethyl Isothiocyanophosphate in Acetonitrile

“…15 As observed in the present work, the discrete two slopes for substituent X variations in the nucleophiles with relatively large β X (= 0.66-1.04 and 2.13-2.14 with more basic and less basic pyridines, respectively) values were observed for the reactions of Y-O-aryl methyl phosphonochloridothioates [Me(YC 6 H 4 O)P(=S)Cl] with Xpyridines in MeCN. 16 The obtained CICs (ρ XY ) are −1.76, 0, 2.80, and ~0 with stronger nucleophiles and weaker electrophiles, weaker nucleophiles and weaker electrophiles, Scheme 2. Backside attack TSb and frontside attack TSf.…”

“…17 A concerted mechanism (or a stepwise mechanism with a rate-limiting bond formation) was proposed for stronger nucleophiles and weaker electrophiles, 18 while a stepwise mechanism with a rate-limiting bond breaking was proposed for weaker nucleophiles and weaker electrophiles, stronger nucleophiles and stronger electrophiles, and weaker nucleophiles and stronger electrophiles on the basis of the sign and magnitudes of CICs (ρ XY ). 16 In the present work, thus, the authors propose a concerted S N 2 mechanism for more basic pyridines and a stepwise mechanism with a rate-limiting leaving group departure from the TBP-5C intermediate for less basic pyridines on the basis of the pyridinolysis mechanism of Y-O-aryl methyl phosphonochloridothioates, showing same free energy relationship as the present work with X. The relatively large β X values with more basic and less basic pyridines imply much greater fraction of frontside nucleophilic attack TSf than that of backside attack TSb (Scheme 2).…”

Kinetics and Mechanism of the Pyridinolyses of O‐Methyl and O‐Ethyl Phenyl Phosphonochloridothioates in Acetonitrile

“…In 1, the free energy correlations with X exhibited two discrete slopes and those with Y exhibited biphasic downward with a break point. The authors pointed out that a subtle combination of small (Me) and large (YC 6 H 4 O) ligands in 1 leads to unexpected results for the pyridinolysis [1] and anilinolysis [16] …”

“…(i) in Y-O-aryl methyl phosphonochloridothioates [1; Me(YC 6 H 4 O)P(=S)Cl], the free energy correlations with X are discrete biphasic with a break region whereas those with Y are biphasic concave downward [1]; (ii) in Y-O-aryl phenyl phosphonochloridothioates [4; Ph(YC 6 H 4 O)P(=S)Cl], the free energy correlations for both substituent X and Y variations are linear [2]; and (iii) in Y-S-aryl phenyl phosphonochloridothioates [5; Ph(YC 6 H 4 S)P(=S)Cl], the free energy correlations with X are concave upward with a break point, whereas those with Y are biphasic concave upward with a break (minimum) point [3]. As part on going kinetic studies on the pyridinolyses of the phosphonochloridothioates, the nucleophilic substitution reactions of O-methyl (2) and O-ethyl (3) phenyl phosphonochloridothioates with X-pyridines have been carried out kinetically in acetonitrile (MeCN) at 35.0 ± 0.1…”