A kinetic study is reported for aminolysis of aryl diphenylphosphinothioates (2a-i). The phosphinothioates 2a-i are less reactive than aryl diphenylphosphinates (1a-i), the oxygen analogues of 2a-i, regardless of the basicity of the leaving aryloxides or the attacking amines. The Yukawa-Tsuno plot for the reactions of 2b-i with piperidine exhibits good linearity with a small r value (r=0.28), indicating that the leaving group departs at the rate-determining step with a small degree of bond fission. Reactions of 2,4-dinitrophenyl diphenylphosphinothioate (2a) with alicyclic secondary amines result in a good linear Bronsted-type plot with betanuc=0.52, implying that the reactions proceed through a concerted mechanism. The betanuc value determined for the reactions of 2a is slightly larger than that reported for the corresponding reactions of 2,4-dinitrophenyl diphenylphosphinate (1a, i.e., betanuc=0.38), suggesting that reactions of 2a proceed through a tighter transition state (TS) than that of 1a. The reaction of 2a with piperidine exhibits a ca. 0.4 kcal/mol more favorable enthalpy of activation (DeltaH) than that of 1a. On the contrary, the entropy of activation at 25.0 degrees C (TDeltaS) is ca. 1.5 kcal/mol more unfavorable for the reaction of 2a than for that of 1a. This result supports the proposal that the reaction of 2a proceeds through a tighter TS than that of 1a and explains why 2a-i are less reactive than 1a-i.

Aminolyses of aryl diphenylphosphinates and diphenylphosphinothioates: effect of modification of electrophilic center from P=O to P=S.

The effect of modification of the electrophilic center from C=O to P=O on reactivity and reaction mechanism has been investigated for aminolysis of Y-substituted phenyl diphenylphosphinates (1a-j) and benzoates (2a-i). The phosphinates 1a-j are less reactive than the benzoates 2a-i. The reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with alicyclic secondary amines resulted in a linear Bronsted-type plot with a beta(nuc) value of 0.38, while the corresponding reactions of 2,4-dinitrophenyl benzoate (2a) yielded a curved Bronsted-type plot. Similarly, a linear Bronsted-type plot with a beta(lg) value of -0.66 was obtained for the reactions of 1a-j with piperidine, while the corresponding reactions of 2a-i gave a curved Bronsted-type plot. The linear Bronsted-type plots for the reactions of 1a-j have been taken as evidence for a concerted mechanism, while the curved Bronsted-type plots for the reactions of 2a-i have been suggested to indicate a change in the rate-determining step of a stepwise mechanism. The Hammett plot for the reactions of 1b-j exhibited a poor correlation with sigma(-) constants (R(2) = 0.962) but slightly better correlation with sigma(o) (R(2) = 0.986). However, the Yukawa-Tsuno plot for the same reactions resulted in an excellent correlation (R(2) = 0.9993) with an r value of 0.30. The aminolysis of 1a-j has been suggested to proceed through a concerted mechanism with an early transition state on the basis of the small beta(nuc) and small r values.

Aminolysis of Y-substituted phenyl diphenylphosphinates and benzoates: effect of modification of electrophilic center from C=O to P=O.

A kinetic study is reported for aminolysis of X-substituted phenyl diphenylphosphinates (1a-i) in 80 mol % H(2)O/20 mol % dimethyl sulfoxide at 25.0 +/- 0.1 degrees C. The Bronsted-type plot for the reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with primary amines is linear with beta(nuc) = 0.53. The reactions of 1a-i with ethylamine also result in a linear Bronsted-type plot with beta(lg) = -0.81. These beta(nuc) and beta(lg) values are slightly larger than those reported previously for the reactions of 1a with secondary amines (beta(nuc) = 0.38) and for those of 1a-i with piperidine (beta(lg) = -0.66) but typical for reactions that proceed through a concerted mechanism. It has been concluded that aminolysis of 1a-i proceed through a concerted mechanism and the nature of amines does not affect the reaction mechanism. However, the reactions with primary amines have been suggested to proceed through a later transition state (i.e., more bond formation and bond rupture in the transition state) on the basis of the larger beta(nuc) and beta(lg) values. The concerted mechanism has been further supported from the fact that the Yukawa-Tsuno plot for the reactions of 1a-i with ethylamine exhibits an excellent linear correlation with rho = 2.24 and r = 0.22. Weakly basic primary amines are less reactive than secondary amines of similar basicity. However, strongly basic ethylamine is ca. 2-fold more reactive than piperidine toward 1a, although the former is 0.35 pK(a) units less basic than the latter.

Aminolysis of X-substituted phenyl diphenylphosphinates: effect of amine nature on reactivity and transition-state structure.

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.

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

A kinetic study is reported for nucleophilic substitution reactions of 4-nitrophenyl phenyl carbonate (5) and 4-nitrophenyl phenyl thionocarbonate (6) with a series of primary amines. The thiono compound 6 is less reactive than its oxygen analogue 5 toward strongly basic amines but is more reactive toward weakly basic CF3CH2NH2. The Bronsted-type plots obtained from the aminolyses of 5 and 6 are curved downwardly. The reactions are proposed to proceed through a stepwise mechanism with a change in the RDS on the basis of the curved Bronsted-type plots. The microscopic rate constants (k(1) and k(2)/k(-1) ratio) associated with the current aminolyses are consistent with the proposed reaction mechanism. The replacement of the C=O bond in 5 by a polarizable C=S group results in a decrease in the k(1) value but an increase in the k(2)/k(-1) ratio. Besides, such a modification of the electrophilic center causes a decrease in pKa degrees , defined as the pK(a) at the curvature center of curved Bronsted-type plots, but does not alter the reaction mechanism. The larger k(2)/k(-1) ratio for the reactions of 6 compared to those of 5 is proposed to be responsible for the decreased pK(a) degrees value.

Aminolyses of 4-nitrophenyl phenyl carbonate and thionocarbonate: effect of modification of electrophilic center from C=O to C=S on reactivity and mechanism.

We report on a spectrophotometric kinetic study of the effect of Li+ and K+ cations on the ethanolysis of 4-nitrophenyl dimethylphosphinate (4a) in ethanol at 25 °C. The nucleophilic displacement reaction of 4a with LiOEt and KOEt in the absence and presence of 18-crown-6 ether (18-C-6) furnished observed first-order rate constants which increase in the order EtO− δGip for Li+ and δGts
				∼
				δGip for K+. These results indicate moderate catalysis by Li+, with 4a manifesting lesser susceptibility to catalysis than other substrates previously studied. Second-order rate constants for the reaction of the aryl dimethylphosphinates 4a–f with free EtO− were obtained from plots of log kobsvs. [KOEt], measured in the presence of excess 18-C-6. Hammett plots with σ and σ° substituent constants give significantly better correlation of rates than σ− and yield a moderately large ρ(ρ°) value; this is interpreted in terms of a stepwise mechanism involving rate-limiting formation of a pentacoordinate intermediate. Comparison of the present results with those of Williams on the aqueous alkaline hydrolysis of Me2P(O)–OPhX and Ph2P(O)–OPhX esters, establishes the rationale for a change in mechanism in the more basic EtO−/EtOH nucleophile/solvent system by a stepwise mechanism instead of a concerted one in aqueous base. Structure–reactivity correlations following Jencks show that the change in mechanism is accounted for by cross interactions between the nucleophile and the leaving group in the transition state. The observed duality of mechanism is rationalized on the basis of the More O'Ferrall–Jencks diagram, as a spectrum of transition states covering a wide range of nucleophile and leaving group basicities.

Nucleophilic displacement on 4-nitrophenyl dimethyl phosphinate by ethoxide ion: alkali metal ion catalysis and mechanism.

This paper reports on a spectrophotometric kinetic study of the effects of the alkali metal ions Li+ and K+ on the ethanolysis of the aryl methyl phenyl phosphinate esters 3a–f in anhydrous ethanol at 25 °C. Rate data obtained in the absence and presence of complexing agents afford the second-order rate constants for the reaction of free ethoxide (kEtO−) and metal ion-ethoxide ion pairs (kMOEt). The sequence kEtO− δGip for Li+ and K+. Hammett plots show significantly better correlation of rates with σ and σo substituent constants than with σ−, yielding moderately large ρ(ρo) values that are consistent with a stepwise mechanism in which formation of a pentacoordinate (phosphorane) intermediate is the rate-limiting step. The range of the values of the selectivity parameter, ρn (= ρ/ρeq), 1.3–1.6, obtained for the uncatalyzed and alkali metal ion catalyzed reactions indicates that there is no significant perturbation of the transition state (TS) structure upon chelation of the metal ions. This finding is relevant to the mechanism of enzymatic phosphoryl transfer involving metal ion co-factors. The present results enable one to compare structural effects for nucleophilic reactions of several series of organophosphorus substrates. It is shown that the order of reactivity of the substrates: 4-nitrophenyl dimethyl phosphinate (2) > 3a > 4-nitrophenyl diphenyl phosphinate (1) is determined mainly by the steric effects of the alkyl/aryl substituents around the central P atom in the TS of the reaction.

Catalysis of the ethanolysis of aryl methyl phenyl phosphinate esters by alkali metal ions: transition state structures for uncatalyzed and metal ion-catalyzed reactions.

Kendall G. Albright

Papers

Nucleophilic displacement on 4-nitrophenyl dimethyl phosphinate by ethoxide ion: alkali metal ion catalysis and mechanism.

Catalysis of the ethanolysis of aryl methyl phenyl phosphinate esters by alkali metal ions: transition state structures for uncatalyzed and metal ion-catalyzed reactions.