Kinetics and mechanism of the aminolysis of aryl ethyl chloro and chlorothio phosphates with anilines

Abstract

The reactions of ethyl Y-phenyl chloro (1) and chlorothio (2) phosphates with X-anilines in acetonitrile at 55.0 degrees C are studied kinetically and theoretically. Kinetic results yield the primary kinetic isotope effects (k(H)/k(D) = 1.07-1.80 and 1.06-1.27 for 1 and 2, respectively) with deuterated aniline (XC(6)H(4)ND(2)) nucleophiles, and the cross-interaction constants rho(XY) = -0.60 and -0.28 for and , respectively. A concerted mechanism involving a partial frontside attack through a hydrogen-bonded, four-center-type transition state is proposed. The large rho(X) (rho(nuc) = -3.1 to -3.4) and beta(X) (beta(nuc) = 1.1-1.2) values seem to be characteristic of the anilinolysis of phosphates and thiophosphates with the Cl leaving group. Because of the relatively large size of the aniline nucleophile, the degree of steric hindrance could be the decisive factor that determines the direction of the nucleophilic attack to the phosphate and thiophosphate substrates with the relatively small-sized Cl leaving group.

Significant Substituent Effects on Pyridinolysis of Aryl Ethyl Chlorophosphates in Acetonitrile

“…Y-aryl ethyl chlorophosphates were prepared as previously described. 20 The physical constants of Y = (4-MeO, 4-Me, H, 3-MeO) were reported earlier 20 and those of ethyl 3-methylphenyl chlorophosphate were as follows (supporting information): Kinetic Measurements. The second-order rate constants and selectivity parameters were obtained as reported earlier.…”

Kinetics and Mechanism of the Anilinolysis of Aryl Ethyl Isothiocyanophosphates in Acetonitrile

“…The anilinolyses of tetracoordinate phosphorus with the Cl -leaving group have been studied extensively in this laboratory, and the data obtained for primary normal DKIEs involving deuterated anilines were rationalized by TSf-type, in which hydrogen bonding of an amine hydrogen atom occurs to the departing chloride. [32][33][34][35][36][37][38] The authors also suggested TSf-type in which hydrogen bonding of an amine hydrogen atom occurs to the departing phenoxy oxygen atom for the anilinolyses of aryl dimethyl, methyl and diphenyl phosphinates. Table 5 lists the activation parameters, enthalpies and entropies of activation, for the reactions of Y-aryl ethyl isothiocyanophosphates with unsubstituted aniline.…”

Theoretical Study of Phosphoryl Transfer Reactions

“…2,5,[6][7][8] The anilinolyses 5,6,7a-j and pyridinolyses 2,8a,c,e,f,g of R 1 R 2 P(=O or S)Cl-type substrates are extensively studied in MeCN. A backside and frontside nucleophilic attack were discussed on the basis of the deuterium kinetic isotope effects (DKIEs; k H /k D ), selectivity parameters (ρ X , ρ Y , β X , and ρ XY ) and free energy correlations (linear, biphasic concave upwards/downwards) for variation of substituent X and Y in the nucleophile and substrate, respectively.…”

“…2,[5][6][7]15 The real primary normal DKIE due to the hydrogen bond between the hydrogen of the N-H(D) moiety and the leaving group should be greater than the observed value, since the secondary inverse DKIE (k H /k D < 1) because of the steric hindrance that increases the out-of-plane bending vibrational The reaction mechanism of the anilinolyses of R 1 R 2 P (=O or S)Cl in MeCN in Table 1 were rationalized mainly based on the cross-interaction constants (CICs), 16 selectivity parameters (ρ X and β X ), and DKIEs. In O(PhO,PhO) and S(PhO,PhO), a concerted S N 2 mechanism was proposed on the basis of a negative ρ XY value (ρ XY = -1.31 and -0.22, respectively).…”