Cross-interaction Constant Research Articles

Nucleophilic Substitution Reactions of O-Aryl N-phenyl Thioncarbamates with Benzylamines in Acetonitrile

Hyuck Keun OhDepartment of Chemistry, Research Institute of Physics and Chemistry, Chonbuk National University, Chonju 561-756, KoreaE-mail: ohkeun@jbnu.ac.krReceived March 7, 2012, Accepted April 8, 2012Key Words : Nucleophilic substitution, O-Aryl N-phenyl thioncarbamates, Cross-interaction constant, Kineticisotope effects, Stepwise mechanismAlthough there is abundant literature on the kinetics andmechanism of the aminolysis of aryl carbonates

Kinetics and Mechanism of the Benzylaminolysis of O,O-Dimethyl S-Aryl Phosphorothioates in Dimethyl Sulfoxide

= 0.91 with the strongly basic nucleophiles. Proposed reaction mechanism is a stepwise process with a rate-limiting leaving group expulsion from the intermediate involving a backside nucleophilic attack with thestrongly basic nucleophiles and a frontside attack with the weakly basic nucleophiles. The kinetic results arecompared with those of the benzylaminolysis of O,O-diphenyl Z-S-aryl phosphorothioates.Key Words : Phosphoryl transfer reaction, Benzylaminolysis, O,O-Diethyl Z- S-aryl phosphorothioate, Cross-interaction constant, Concave downward free energy correlationIntroductionThe various phosphoryl and thiophosphoryl transfer reac-tions have been studied kinetically by this lab: anilinolysis,

Kinetics and Mechanism of the Pyridinolysis of Aryl Ethyl Chlorothiophosphates in Acetonitrile

Kinetic studies for the reactions of Y-aryl phenyl chlorothiophosphates with X-pyridines have been carried out in acetonitrile at 35.0 oC. The Hammett and Bronsted plots for substituent X variations in the nucleophiles are biphasic concave upwards with a break point at X = 3-Ph, while the Hammett plots for substituent Y variations in the substrates are biphasic concave downwards (and partially upwards) with a break point at Y = H. The signs and magnitudes of the cross-interaction constant (ρ XY) are strongly dependent upon the nature of substituents, X and Y. The proposed mechanism is a stepwise process with a rate-limiting step change from bond breaking with the weaker electrophiles to bond formation with the stronger eletrophiles. The nonlinear free energy correlations of biphasic concave upward plots for substituent X variations in the nucleophiles are rationalized by a change in the attacking direction of the nucleophile from a backside with less basic pyridines to a frontside attack with more basic pyridines.

Kinetics and Mechanism of the Anilinolysis of Bis(aryl) Chlorophosphates in Acetonitrile

C. The kinetic results of 1 are comparedwith those of Y-aryl phenyl chlorophosphates (2). The substrate 1 has one more identical substituent Ycompared to substrate 2. The cross-interaction between Y and Y, due to additional substituent Y, is significantenough to result in the change of the sign of cross-interaction constant (CIC) from negative ρ

Kinetics and Mechanism of the Aminolysis of O-Methyl S-Aryl Thiocarbonates in Acetonitrile

The aminolysis of O-methyl S-aryl thiocarbonates with benzylamines are studied in acetonitrile at -45.0<TEX>$^{\circ}C$</TEX>. The <TEX>${\beta}_X$</TEX>(<TEX>${\beta}_{nuc}$</TEX>) values are in the range 0.62-0.80 with a negative cross-interaction constant, <TEX>${\rho}_{XZ}$</TEX> = -0.42, which are interpreted to indicate a concerted mechanism. The kinetic isotope effects involving deuterated benzylamine nucleophiles (<TEX>$XC_6H_4CH_2ND_2$</TEX>) are large, <TEX>$k_H/k_D$</TEX> = 1.29-1.75, suggesting that the N-H(D) bond is partially broken in the transition state by forming a hydrogen-bonded four-center cyclic structure. The concerted mechanism is enforced by the strong push provided by the MeO group which enhances the nucleofugalities of both benzylamine and arenethiolate from the putative zwitterionic tetrahedral intermediate.

Kinetics and Mechanism of the Benzylaminolysis of O,O-Diphenyl S-Aryl Phosphorothioates in Dimethyl Sulfoxide

Kinetic studies of the reactions of O,O-diphenyl Z-S-aryl phosphorothioates with X-benzylamines have been carried out in dimethyl sulfoxide at 55.0 <TEX>$^{\circ}C$</TEX>. The Hammett (log <TEX>$k_2$</TEX> vs <TEX>${\sigma}_X$</TEX>) and Bronsted [log <TEX>$k_2$</TEX> vs <TEX>$pK_a(X)$</TEX>] plots for substituent X variations in the nucleophiles are biphasic concave downwards with a maximum point at X = H, and the unusual positive <TEX>${\rho}_X$</TEX> and negative <TEX>${\beta}_X$</TEX> values are obtained for the strongly basic benzylamines. The sign of the cross-interaction constant (<TEX>${\rho}_{XZ}$</TEX>) is negative for both the strongly and weakly basic nucleophiles. Greater magnitude of <TEX>${\rho}_{XZ}$</TEX> value is observed with the weakly basic nucleophiles (<TEX>${\rho}_{XZ}$</TEX> = -2.35) compared to with the strongly basic nucleophiles (<TEX>${\rho}_{XZ}$</TEX> = -0.03). The deuterium kinetic isotope effects (<TEX>$k_H/k_D$</TEX>) involving deuterated benzylamines [<TEX>$XC_6H_4CH_2ND_2$</TEX>] are primary normal (<TEX>$k_H/k_D$</TEX> > 1). The proposed mechanism is a concerted <TEX>$S_N2$</TEX> involving a frontside nucleophilic attack with a hydrogen bonded, four-center-type transition state for both the strongly and weakly basic nucleophiles. The unusual positive <TEX>${\rho}_X$</TEX> and negative <TEX>${\beta}_X$</TEX> values with the strongly basic benzylamines are rationalized by through-space interaction between the <TEX>${\pi}$</TEX>-clouds of the electron-rich phenyl ring of benzylamine and the phenyl ring of the leaving group thiophenoxide.

Pyridinolysis of O,O-Diphenyl S-Phenyl Phosphorothiolates in Acetonitrile

are biphasic concave downwards with breaks at Z = H. The large magnitudes of ρ X (ρ nuc), β X (ρ nuc), and the cross-interaction constant, ρ XZ, suggest frontside nucleophilic attack toward the leaving group. The sign reversal of ρ Z from positive in σ Z ≤ 0 to negative in σ Z ≥ 0 is interpreted as the change in mechanism from concerted to stepwise with rate-limiting expulsion of the leaving group. The anomalous negative sign of ρ Z for leaving groups with electron-withdrawing substituents is interpreted as the intramolecular ligand exchange process of the leaving group from the equatorial position in the intermediate to the apical position in the TS.

Kinetics and Mechanism of Triethylamine Catalysed Michael Addition of Benzenethiol to 1-(2-Nitrovinyl)benzene in Acetonitrile

Nucleophilic addition reaction of benzenethiols (PhSH) to 1-(2-nitrovinyl) benzenes (<TEX>$\beta$</TEX> NS) in the presence of triethylamine (TEA) has been studied in acetonitrile at 25 <TEX>${^{\circ}C}$</TEX>. The rate is first order with respect to [PhSH], [TEA] and [<TEX>$\beta$</TEX> NS]. The reaction is found to proceed with the formation of ion-pair between benzenethiol and TEA. A suitable mechanism with the formation of an adduct between ion-pair and substrate in a slow step followed by its rearrangement to 1,2-addition product in a fast step has been proposed and corresponding rate law derived. From the rate law, the rate constants for the interaction between ion-pair and <TEX>$\beta$</TEX>NS have been evaluated. Interestingly, in both para-substituted substrates and benzenethiols the rate increases with the electron-withdrawing power of the substituents. The positive sign of <TEX>$\rho_x$</TEX> in benzenethiols has been explained. The magnitude of cross-interaction constant, <TEX>$\rho_{xy}$</TEX> is small (0.08). The magnitude of the Hammett <TEX>$\rho_x$</TEX> values is higher than that of the Bronsted, <TEX>$\beta_x$</TEX> values for benzenethiols. The kinetic isotope effect, <TEX>$k_H/k_D$</TEX>, is found to be greater than unity. A suitable transition state with simultaneous formation of <TEX>$C_\beta$</TEX> -H and <TEX>$B_\alpha$</TEX> -S bonds involving the ion-pair and <TEX>$\beta$</TEX>NS in a single concerted step has been proposed to account for these observations.

Kinetics and Mechanism of the Addition of Benzylamines to Benzylidenedimethylmalonates in Acetonitrile

In most cases in aqueous solution the acid-base equilibria, TA ± TA , is rapidly established subsequently and hence nucleophilic addition, ka, is rate limiting. 2 In this mechanism, the development of resonance into the activating (electronacceptor) group (Z,Z') lags behind charge transfer or bond formation and hence the transition state (TS) becomes imbalanced. Thus the ease of the initial attack by amines on Cα and hence the polar electron-withdrawing effect of Z,Z', is the rate determining factor for the reaction in aqueous solution. This means that the greater the electron-withdrawing power (Σσ) of the activating group (Z,Z'), the faster becomes the rate. In contrast the rate in acetonitrile (eq. 1) increases with the sum of exalted substituent constants Σ , since the addition step, k2, involves π-orbitals through an sp carbon center, Cα. Another point of interest is the sign and magnitude of the cross-interaction constant, ρXY in eq. (3) where X an Y are substituents in the nucleophile, benzylamine (BA), and

Kinetics and Mechanism of the Addition of Benzylamines to α-Cyano-β-phenylacrylamides in Acetonitrile

Nucleophilic addition reactions of benzylamines (BA; XC 6 H 4 CH 2 NH 2 ) to α-cyano-β-phenylacrylamides (CPA; YC 6 H 4 CH=C(CN)CONH 2 ) have been investigated in acetonitrile at 25.0 °C. The rate is first order with respect to BA and CPA and no base catalysis is observed. The addition of BA to CPA occurs in a single step in which the addition of BA to C β of CPA and proton transfer from BA to C α of CPA take place concurrently with a four-membered cyclic transition state structure. The magnitude of the Hammett (px) and Bronsted (β x ) coefficients are rather small suggesting an early tansition state (TS). The sign and magnitude of the cross-interaction constant, ρXY(= -0.26), is comparable to those found in the normal bond formation processes in the S N 2 and addition reactions. The normal kinetic isotope effect (k H /k D > 1.0) and relatively low ΔH # and large negative ΔS ≠ values are also consistent with the mechanism proposed.

Aminolysis of Aryl N-Ethyl Thionocarbamates: Cooperative Effects of Atom Pairs O and S on the Reactivity and Mechanism

[reaction: see text] The aminolysis reactions of aryl N-ethyl thionocarbamates (ETNC/EtHN-C(=S)-OC6H4Z) with benzylamines (XC6H4CH2NH2) in acetonitrile are investigated at 30.0 degrees C. The rate of ETNC is slower by a factor of ca. 3 than the corresponding aminolysis of aryl N-ethyl thiocarbamate (AETC/EtHN-(C=O)-SC6H4Z), which has been interpreted in terms of cooperative effects of atom pairs O and S on the reactivity and mechanism. For concerted processes, these effects predict a rate sequence, -C(=S)-S- < -C(=S)-O- < -C-(=O)-S- < -C-(=O)-O-, and the present results are consistent with this order. The negative cross-interaction constant, rho(XZ) = -0.87, the magnitude of betaZ (= 0.36-0.50) and failure of the RSP are in accord with the concerted mechanism. The normal kinetic isotope effects, kH/kD = 1.52-1.78, involving deuterated benzylamines suggest a hydrogen-bonded cyclic transition state. Other factors influencing the mechanism are also discussed.

Aminolysis of Aryl Chlorothionoformates with Anilines in Acetonitrile: Effects of Amine Nature and Solvent on the Mechanism

The aminolysis of aryl chlorothionoformates (7, YC(6)H(4)OC(=S)Cl) with anilines (XC(6)H(4)NH(2)) in acetonitrile at 5.0 degrees C has been investigated. The rates are slower than those for the corresponding reactions of aryl chloroformates (6, YC(6)H(4)OC(=O)Cl). This rate sequence is a reverse of that for alkyl chloroformates (1-4) in water, for which rate-limiting formation of a tetrahedral intermediate, T(+/-), is predicted. On the basis of the large negative cross-interaction constant, rho(XY) = -0.77, failure of the reactivity-selectivity principle, normal k(H)/k(D) values involving deuterated nucleophiles (XC(6)H(4)ND(2)), and low DeltaH(not equal) with large negative DeltaS(not equal) values, a concerted mechanism with a four-membered hydrogen bonded cyclic transition state (11) is proposed for the title reaction series. It has been shown that the solvent change from water to acetonitrile for the aminolysis of 6 and 7 causes a mechanistic change from stepwise to concerted.

Kinetics and mechanism of the addition of benzylamines to benzylidenediethylmalonates in acetonitrile.

Kinetic studies of the benzylamine additions to benzylidenediethylmalonates (BDM: YC(6)H(4)CH[double bond]C(COOEt)(2)) in acetonitrile at 20.0 degrees C are reported. The rates in acetonitrile are consistent with that expected from the through-conjugative electron-accepting power of the activating groups, (COOEt)(2). The sign and magnitude of the cross-interaction constant, rho(XY) = -0.45, are in general agreement with those for the single-step amine additions to activated olefins. The kinetic isotope effects (k(H)/k(D) > 1.0) measured with deuterated benzylamines (XC(6)H(4)CH(2)ND(2)) increase with a stronger electron-acceptor substituent in benzylamines (partial differential sigma(X) > 0) and a stronger electron donor in the substrate (partial differential sigma(Y) < 0). These trends are the same as those found for benzylidene-1,3-indandiones but are exactly opposite to those for other activated olefin series, e.g., beta-nitrostyrene. It has been shown that the former series are thermodynamically controlled, whereas the latter are intrinsically controlled with a relatively strong transition state imbalance. The activation parameters, Delta H(++) and Delta S(++), also support our proposed transition state involving concurrent C(alpha)-N and C(beta)-H bond formation with a four-membered cyclic structure.

Nucleophilic Substitution Reactions of Aryl Thiophene-2-carbodithioates with Pyridines in Acetonitrile

= 5.2 for R = thiophene ring in the present work is in agreement with those for the pyridinolysis of R = Meand 2-furyl, and attests to the insignificant effects of acyl group, R, on the breakpoint.Key Words : Nucleophilic substitution reaction, Pyridinolysis, Cross-interaction constant, Zwitterionic tetra-hedral intermediate, Stepwise mechanismIntroductionThe aminolysis of carbonyl and thiocarbonyl esters hasbeen a subject of considerable interest in mechanistic as wellas synthetic organic chemistry.

Kinetics and Mechanism of the Aminolysis of S-Aryl O-Ethyl Dithiocarbonates in Acetonitrile

The aminolysis of S-aryl O-ethyl dithiocarbonates with benzylamines are studied in acetonitrile at -25.0 °C. The βX (βnuc) values are in the range 0.67-0.77 with a negative cross-interaction constant, ρXZ = -0.24, which are interpreted to indicate a concerted mechanism. The kinetic isotope effects involving deuterated benzylamine nucleophiles (XC6H4CH2ND2) are large, kH/kD = 1.41-1.97, suggesting that the N-H(D) bond is partially broken in the transition state by forming a hydrogen-bonded four-center cyclic structure. The concerted mechanism is enforced by the strong push provided by the EtO group which enhances the nucleofugalities of both benzylamine and arenethiolate from the putative zwitterionic tetrahedral intermediate.

Kinetics and Mechanism of the Addition of Benzylamines to Benzylidene Meldrum's Acids in Acetonitrile

Nucleophilic addition reactions of benzylamines <TEX>$(XC_6H_4CH_2NH_2)$</TEX> to benzylidene Meldrum's acids (BMA; <TEX>$YC_6H_4CH=C(COO)_2C(CH_3)_2$</TEX>) have been investigated in acetonitrile at 20.0 ℃. The rates of addition are greatly enhanced due to the abnormally high acidity of Meldrum's acid. The magnitudes of the Hammett <TEX>$({\rho}_X\;and\;{\rho}_Y)$</TEX> and Bronsted <TEX>$({\rho}_X$)$</TEX> coefficients are rather small suggesting an early transition state. The sign and magnitude of the cross-interaction constant, <TEX>${\rho}_{XY}$</TEX> (= -0.33), and kinetic isotope effects <TEX>$(k_H/k_D\;{\stackrel}{~}{=}\;1.5-1.7)$</TEX> involving deuterated benzylamine nucleophilies <TEX>$(XC_6H_4CH_2ND_2)$</TEX> are indicative of hydrogen-bonded cyclic transition state. The activation parameters, <TEX>${\Delta}H^{\neq}\;{\stackrel}{~}{=}\;4\;kcal\;mol^{-1}\;and\;{\Delta}S^{\neq}\;{\stackrel}{~}{=}\;-37\;e.u.$</TEX>, are also in line with the proposed mechanism.

Kinetic Studies on the Nucleophilic Addition Reactons of Vinylic β-Diketones

The kinetics of the addition of X-substituted benzylamines (BA) to Y-substituted Benzylideneacetylacetones (BAA) have been investigated in acetonitrile at <TEX>$25.0^{\circ}C$</TEX>. The reaction is studied under pseudo-first-order conditions by keeping a large excess of BA over BAA. The addition of BA to BAA occurs in a single step in which the addition of BA to <TEX>$C_\alpha$</TEX> of BAA and proton transfer from BA to <TEX>$C_\beta$</TEX> of BAA take place concurrently with a four-membered cyclic transition state structure. The magnitude of the Hammett (<TEX>$p_X$</TEX>) and Bronsted (<TEX>$\beta_x$</TEX>) coefficients are rather small suggesting an early tansition state (TS). The sign and magnitude of the cross-interaction constant, <TEX>$p_{XY}$</TEX> (= -0.49), is comparatible to those found in the normal bond formation processes in the <TEX>$S_N2$</TEX> and addition reactions. The normal kinetic isotope effect (<TEX>$K_H/K_D$</TEX> > 1.0) and relatively low <TEX>$\Delta</TEX><TEX>$H^{</TEX>${\neq}$</TEX>}$</TEX> and large negative <TEX>$\Delta</TEX><TEX>$S^{<TEX>${\neq}$</TEX>}$</TEX> values are also consistent with the mechanism proposed.

Transition-state variation in the nucleophilic substitution reactions of aryl bis(4-methoxyphenyl) phosphates with pyridines in acetonitrile.

The kinetics and mechanism of the reactions of Z-aryl bis(4-methoxyphenyl) phosphates, (4-MeOC(6)H(4)O)(2)P(=O)OC(6)H(4)Z, with pyridines (XC(5)H(4)N) are investigated in acetonitrile at 55.0 degrees C. In the case of more basic phenolate leaving groups (Z = 4-Cl, 3-CN), the magnitudes of beta(X) (beta(nuc)) and beta(Z) (beta(lg)) indicate that mechanism changes from a concerted process (beta(X) = 0.22-0.36, beta(Z) = -0.42 to -0.56) for the weakly basic pyridines (X = 3-Cl, 4-CN) to a stepwise process with rate-limiting formation of a trigonal bipyramidal pentacoordinate (TBP-5C) intermediate (beta(X) = 0.09-0.14, beta(Z) = -0.08 to -0.28) for the more basic pyridines (X = 4-NH(2), 3-CH(3)). This proposal is supported by a large negative cross-interaction constant (rho(XZ) = -1.98) for the former and a positive rho(XZ) (+0.97) for the latter processes. In the case of less basic phenolate leaving groups (Z = 3-CN, 4-NO(2)), the unusually small magnitude of beta(Z) values is indicative of a direct backside attack TBP-5C TS in which the two apical sites are occupied by the nucleophile and leaving group, ap(NX)-ap(LZ). The instability of the putative TBP-5C intermediate leading to a concerted displacement is considered to result from relatively strong proximate charge transfer interactions between the pi-lone pairs on the directly bonded equatorial oxygen atoms and the apical bond (n(O)(eq) - sigma(ap)). These are supported by the results of natural bond orbital (NBO) analyses at the NBO-HF/6-311+G//B3LYP/6-311+G level of theory.

Anomalous Behavior of the Ethyl Group in the Aminolysis of S-Phenyl Acetate with Benzylamine in Acetonitrile

The rates of the aminolysis of S-phenyl substituted-acetate series <TEX>$(RC(=O)SC_6H_4Z$</TEX>, with R=Me, Et, i-Pr, t-Bu and Bn) with benzylamines <TEX>$(XC_6H_4CH_2NH_2)$</TEX> are not correlated simply with the Taft's polar <TEX>$({\sigma}^{\ast})$</TEX> and/or steric effect constants <TEX>$(E_s)$</TEX> of the substituents due to abnormally enhanced rate of the substrate with R=Et. Furthermore, the cross-interaction constant, <TEX>${\rho}x_z$</TEX> , is the largest with R=Et. These anomalous behaviors can only be explained by invoking the vicinal bond <TEX>$({\sigma})$</TEX>-antibond <TEX>$({\sigma}^{\ast})$</TEX> charge transfer interaction between C-<TEX>$C{\alpha}$</TEX> and C-S bonds. In the tetrahedral zwitterionic intermediate, <TEX>$T^{\pm}$</TEX> , formed with R=Et the vicinal <TEX>${\sigma}_{c-c}-{\sigma}^{\ast}_{c-s}$</TEX> delocalization is the strongest with an optimum antiperiplanar arrangement and a narrow energy gap, <TEX>${\Delta}{\varepsilon}={\varepsilon}_{{\sigma}^{\ast}}-{\varepsilon}_{\sigma}$</TEX>. Due to this charge transfer interaction, the stability of the intermediate increases (with the concomitant increase in the equilibrium constant K (= <TEX>$k_a/k_{-a}$</TEX>)) and also the leaving ability of the thiophenolate leaving group increases (and hence <TEX>$k_b$</TEX> increases) so that the overall rate, <TEX>$k_n\;=\;Kk_b$</TEX>, is strongly enhanced. Theoretical support is provided by the natural bond orbital (NBO) analyses at the B3LYP/6-31+<TEX>$G^{\ast}$</TEX> level. The anomaly exhibited by R=Et attests to the stepwise reaction mechanism in which the leaving group departure is rate limiting.

Kinetics and Mechanism of the Addition of Benzylamines to Ethyl-α-cyanocinnamates in Acetonitrile

Nucleophilic addition reactions of benzylamines (BA; <TEX>$XC_6H_4CH_2NH_2$</TEX>) to ethyl-<TEX>${\alpha}$</TEX>-cyanocinnamates (ECC;<TEX>$YC_6H_4CH$</TEX>=C(CN)COOEt) have been investigated in acetonitrile at <TEX>$30.0^{\circ}C$</TEX>. The rate is first order with respect to BA and ECC. The rate is slower than that expected from the additive effect of <TEX>${\sigma}^-$</TEX> or <TEX>$R^-$</TEX> for the activating groups (CN and COOEt). Natural. bond orbital <TEX>${\pi}^{\ast}_{c=c}$</TEX> calculations show that the contribution of COOEt group may not be fully effective despite the coplanar molecular structure. The selectivity parameters including the cross-interaction constant (<TEX>${\rho}_{xy}$</TEX> = -0.22) indicate that the addition occurs in a single step. The kinetic isotope effects (<TEX>$k_H/k_D$</TEX>=2.5-2.8) involving deuterated BA (<TEX>$XC_6H_4CH_2ND_2$</TEX>) nucleophiles and activation parameters (<TEX>${\Delta}H^{\neq}=4{\sim}6\;kcal\;mol^{-1};{\Delta}S^{\neq}=-45{\sim}-52\;e.u.$</TEX>) suggest a cyclic transition state in which N-<TEX>$C_{\alpha}$</TEX> and H-<TEX>$C_{\beta}$</TEX> bonds are formed concurrently.