Series Of Alicyclic Secondary Amines Research Articles

Kinetic study on aminolysis of aryl X-substituted-cinnamates in acetonitrile: differential medium effect determines reactivity and reaction mechanism

A kinetic study on nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted-cinnamates (1a–1f) and Y-substituted-phenyl cinnamates (2a–2g) with a series of alicyclic secondary amines in MeCN at 25.0 ± 0.1 °C is reported. The Brønsted-type plots for the reactions of 1a–1f are linear with βnuc = 0.47∼0.50, indicating that the bond formation between the amine nucleophile and the electrophilic center is advanced slightly in the transition state. The Brønsted-type plot for the reactions of 2a–2g with piperidine is also linear with βlg = –0.66, which is a typical βlg value for reactions reported previously to proceed through a concerted mechanism. Furthermore, the Hammett plot correlated with σ– constants results in much better linearity than that correlated with σo constants, implying that expulsion of the leaving group is advanced in the rate-determining step (RDS). Thus, the reactions are concluded to proceed through a concerted mechanism. The Hammett plots for the reactions of 1a–1f consist of two intersecting straight lines, whereas the corresponding Yukawa–Tsuno plots exhibit excellent linear correlations with ρX = 0.62∼0.71 and r = 0.65∼0.68. Apparently, the nonlinear Hammett plots are not due to a change in the reaction mechanism (or the RDS) but are caused by stabilization of the substrate possessing an electron-donating group (EDG) in the cinnamoyl moiety through resonance interactions between the EDG and the C=O bond of the substrate. Medium effects on reactivity and reaction mechanism are also discussed.

Hydrogen Bond Contribution to Preferential Solvation in SNAr Reactions

Preferential solvation in aromatic nucleophilic substitution reactions is discussed using a kinetic study complemented with quantum chemical calculations. The model system is the reaction of a series of secondary alicyclic amines toward phenyl 2,4,6-trinitrophenyl ether in aqueous ethanol mixtures of different compositions. From solvent effect studies, it is found that only piperidine is sensitive to solvation effects, a result that may be traced to the polarity of the solvent composition in the ethanol/water mixture, which points to a specific electrophilic solvation in the aqueous phase.

Aminolysis of Benzyl 2-Pyridyl Thionocarbonate and t-Butyl 2-Pyridyl Thionocarbonate: Effects of Nonleaving Groups on Reactivity and Reaction Mechanism

A kinetic study is reported for nucleophilic substitution reactions of benzyl 2-pyridyl thionocarbonate (5b) and t-butyl 2-pyridyl thionocarbonate (6b) with a series of alicyclic secondary amines in at . General-base catalysis, which has often been reported to occur for aminolysis of esters possessing a C=S electrophilic center, is absent for the reactions of 5b and 6b. The Brnsted-type plots for the reactions of 5b and 6b are linear with = 0.29 and 0.43, respectively, indicating that the reactions of 5b proceed through a stepwise mechanism with formation of a zwitterionic tetrahedral intermediate () being the rate-determining step while those of 6b proceed through a concerted mechanism. The reactivity of 5b and 6b is similar to that of their oxygen analogues (i.e., benzyl 2-pyridyl carbonate 5a and t-butyl 2-pyridyl carbonate 6a, respectively), indicating that the effect of modification of the electrophilic center from C=O to C=S (i.e., from 5a to 5b and from 6a to 6b) on reactivity is insignificant. In contrast, 6b is much less reactive than 5b, indicating that the replacement of the in 5b by the t-Bu in 6b results in a significant decrease in reactivity as well as a change in the reaction mechanism (i.e., from a stepwise mechanism to a concerted pathway). It has been concluded that the contrasting reactivity and reaction mechanism for the reactions of 5b and 6b are not due to the electronic effects of and t-Bu but are caused by the large steric hindrance exerted by the bulky t-Bu in 6b.

Decomposition of Paraoxon and Parathion by Amines, HOO-and OH-Ions: Reaction Mechanism and Origin of the α-Effect

The second-order rate constants have been measured spectrophotometrically for the reactions of paraoxon 1 and parathion 2 with a series of alicyclic secondary amines, and ions in at . A linear Brnsted-type plot with = 0.40 was obtained for the reactions of 1 with amines and . The reaction has been concluded to proceed through a concerted mechanism. deviates positively from the linear Brnsted-type plot, implying that the -effect is operative. The magnitude of the -effect () was found to be ca. 55 for the reaction of 1 and 290 for that of parathion 2, indicating that is highly effective in decomposition of the toxic phosphorus compounds although it is over 4 units less basic than . Among the theories suggested as origins of the -effect (e.g., TS stabilization through an intramolecular Hbonding interaction, solvent effect, and polarizability effect), polarizability effect appears to be the most important factor for the -effect in this study, since the polarizable exhibits a larger -effect for the reaction of the more polarizable substrate 2.

Kinetics and Reaction Mechanism for Aminolysis of Benzyl 4-Pyridyl Carbonate in H2O: Effect of Modification of Nucleofuge from 2-Pyridyloxide to 4-Pyridyloxide on Reactivity and Reaction Mechanism

Pseudo-first-order rate constants <TEX>$k_{amine}$</TEX> have been measured spectrophotometrically for the reactions of benzyl 4-pyridyl carbonate 6 with a series of alicyclic secondary amines in <TEX>$H_2O$</TEX> at <TEX>$25.0^{\circ}C$</TEX>. The plots of <TEX>$k_{amine}$</TEX> vs. [amine] curve upward, indicating that the reactions proceed through a stepwise mechanism with two intermediates, a zwitterionic tetrahedral intermediate <TEX>$T^{\pm}$</TEX> and its deprotonated form <TEX>$T^-$</TEX>. This contrasts to the report that the corresponding reactions of benzyl 2-pyridyl carbonate 5 proceed through a forced concerted pathway. The <TEX>$k_{amine}$</TEX> values for the reactions of 6 have been dissected into the second-order rate constant <TEX>$Kk_2$</TEX> and the thirdorder rate constant <TEX>$Kk_3$</TEX>. The Br<TEX>${\o}$</TEX>nsted-type plots are linear with <TEX>${\beta}_{nuc}=0.94$</TEX> and 1.18 for <TEX>$Kk_2$</TEX> and <TEX>$Kk_3$</TEX>, respectively. The <TEX>$Kk_2$</TEX> for the reaction of 6 is smaller than the second-order rate constant <TEX>$k_N$</TEX> for the corresponding reaction of 5, although 4-pyridyloxide in 6 is less basic and a better nucleofuge than 2-pyridyloxide in 5.

Kinetic study of solvent effects on the aminolysis of O‐ethyl S‐aryl dithiocarbonates

The nucleophilic substitution reactions of a series of O‐ethyl S‐aryl dithiocarbonates with a series of secondary alicyclic amines have been investigated, all in water–ethanol mixtures and some of them in protic and dipolar aprotic solvents. The solvent effects on rate and mechanism are studied using a multiparametric approach with solvent parameters such as acidity, basicity and polarity/polarizability. These results show that in a concerted mechanism, rate constants are increased by the increase of the solvent dipolarity/polarizability. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Aminolysis of Y- Substituted Phenyl Benzenesulfonates in MeCN: Effect of Medium on Reactivity and Reaction Mechanism

Second-order rate constants for nucleophilic substitution reactions of 2,4-dinitrophenyl benzenesulfonate 1a with a series of alicyclic secondary amines in MeCN have been measured spectrophotometrically and compared with those reported previously for the corresponding reactions performed in aqueous medium to investigate the effect of medium on reactivity and reaction mechanism. The amines employed in this study are found to be more reactive in the aprotic solvent than in <TEX>$H_2O$</TEX>. The reactions of 1a in MeCN result in a linear Br<TEX>${\o}$</TEX>nsted-type plot with <TEX>${\beta}_{nuc}$</TEX> = 0.58, which contrasts to the curved Br<TEX>${\o}$</TEX>nsted-type plot reported previously for the corresponding reactions performed in the aqueous medium (i.e., <TEX>${\beta}_2$</TEX> = 0.86 and <TEX>${\beta}_1$</TEX> = 0.38). Accordingly, it has been concluded that the reaction mechanism changes from a stepwise mechanism to a concerted pathway upon changing the medium from <TEX>$H_2O$</TEX> to MeCN. Reactions of Y-substituted phenyl benzenesulfonates 1a-c with piperidine in MeCN result in a linear Br<TEX>${\o}$</TEX>nsted-type plot with <TEX>${\beta}_{lg}$</TEX> = -1.31, indicating that expulsion of the leaving group is significantly more advanced than bond formation in the transition state. The trigonal bipyramidal intermediate (<TEX>$TBPy^{\pm}$</TEX>) proposed previously for the reactions in <TEX>$H_2O$</TEX> would be highly unstable in MeCN due to strong repulsion between the negative charge in <TEX>$TBPy^{\pm}$</TEX> and the negative dipole end of MeCN. Thus, destabilization of <TEX>$TBPy^{\pm}$</TEX> in MeCN has been concluded to change the reaction mechanism from a stepwise mechanism to a concerted pathway.

Kinetic Study on Aminolysis of 4-Pyridyl X-Substituted Benzoates: Effect of Substituent X on Reactivity and Reaction Mechanism

A kinetic study is reported for nucleophilic substitution reactions of 4-pyridyl X-substituted benzoates 7a-e with a series of alicyclic secondary amines in H2O. The Br<TEX>${\o}$</TEX>nsted-type plot for the reactions of 4-pyridyl benzoate 7c is linear with <TEX>${\beta}_{nuc}$</TEX> = 0.71. The corresponding reactions of 2-pyridyl benzoate 6, which is less reactive than 7c, resulted in also a linear Br<TEX>${\o}$</TEX>nsted-type plot with <TEX>${\beta}_{nuc}$</TEX> = 0.77. The fact that the more reactive 7c results in a smaller <TEX>${\beta}_{nuc}$</TEX> value appears to be in accord with the reactivity-selectivity principle. The aminolysis of 7c has been suggested to proceed through a stepwise mechanism in which breakdown of the intermediate is the rate-determining step (RDS). The Hammett plot for the reactions of 7a-e with piperidine consists of two intersecting straight lines, i.e., <TEX>${\rho}_X$</TEX> = 1.47 for substrates possessing an electron-donating group (EDG) and <TEX>${\rho}_X$</TEX> = 0.91 for those possessing an electron-withdrawing group (EWG). In contrast, the corresponding Yukawa-Tsuno plot exhibits excellent linear correlation with <TEX>${\rho}_X$</TEX> = 0.79 and r = 0.56. Thus, it has been concluded that the nonlinear Hammett plot is not due to a change in the RDS but is caused by stabilization of the ground state of the substrates possessing an EDG through resonance interaction between the EDG and the C=O bond of the substrates.

A Kinetic Study on Aminolysis of 2-Pyridyl X-Substituted Benzoates: Effect of Changing Leaving Group from 4-Nitrophenolate to 2-Pyridinolate on Reactivity and Mechanism

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for nucleophilic substitution reactions of 2-pyridyl X-substituted benzoates 8a-e with a series of alicyclic secondary amines in <TEX>$H_2O$</TEX> at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The <TEX>$k_N$</TEX> values for the reactions of 8a-e are slightly smaller than the corresponding reactions of 4-nitrophenyl X-substituted benzoates 1a-e (e.g., <TEX>$kN^{1a-e}/k_N^{8a-e}$</TEX> = 1.1 ~ 3.1), although 2-pyridinolate in 8a-e is ca. 4.5 <TEX>$pK_a$</TEX> units more basic than 4-nitrophenolate in 1a-e. The Br<TEX>$\o$</TEX>nsted-type plot for the aminolysis of 8c (X = H) is linear with <TEX>$\beta_{nuc}$</TEX> = 0.77 and <TEX>$R^2$</TEX> = 0.991 (Figure 1), which is typical for reactions reported previously to proceed through a stepwise mechanism with breakdown of a zwitterionic tetrahedral intermediate <TEX>$T^{\pm}$</TEX> being the rate-determining step (RDS), e.g., aminolysis of 4-nitrophenyl benzoate 1c. The Hammett plot for the reactions of 8a-e with piperidine consists of two intersecting straight lines (Figure 2), i.e., <TEX>$\rho$</TEX> = 1.71 for substrates possessing an electron-donating group (EDG) while <TEX>$\rho$</TEX> = 0.86 for those bearing an electron-withdrawing group (EWG). Traditionally, such a nonlinear Hammett plot has been interpreted as a change in RDS upon changing substituent X in the benzoyl moiety. However, it has been proposed that the nonlinear Hammett is not due to a change in RDS since the corresponding Yukawa-Tsuno plot exhibits excellent linear correlation with <TEX>$\rho$</TEX> = 0.85 and r = 0.62 (<TEX>$R^2$</TEX> = 0.995, Figure 3). Stabilization of substrates 8a-e in the ground state has been concluded to be responsible for the nonlinear Hammett plot.

Michael-type Reactions of 1-(X-substituted phenyl)-2-propyn-1-ones with Alicyclic Secondary Amines in MeCN and H2O: Effect of Medium on Reactivity and Transition-State Structure

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for Michael-type reactions of 1-(X-substituted phenyl)-2-propyn-1-ones (2a-f) with a series of alicyclic secondary amines in MeCN at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The <TEX>$k_N$</TEX> value increases as the incoming amine becomes more basic and the substituent X changes form an electron-donating group (EDG) to an electron-withdrawing group (EWG). The Br<TEX>${\o}$</TEX>nsted-type plots are linear with <TEX>${\beta}_{nuc}$</TEX> = 0.48 - 0.51. The Hammett plots for the reactions of 2a-f exhibit poor correlations but the corresponding Yukawa-Tsuno plots result in much better linear correlations with <TEX>${\rho}$</TEX> = 1.57 and r = 0.46 for the reactions with piperidine while <TEX>${\rho}$</TEX> = 1.72 and r = 0.39 for those with morpholine. The amines employed in this study are less reactive in MeCN than in water for reactions with substrates possessing an EDG, although they are ca. 8 pKa units more basic in the aprotic solvent. This indicates that the transition state (TS) is significantly more destabilized than the ground state (GS) in the aprotic solvent. It has been concluded that the reactions proceed through a stepwise mechanism with a partially charged TS, since such TS would be destabilized in the aprotic solvent due to the electronic repulsion between the negative-dipole end of MeCN and the negative charge of the TS. The fact that primary deuterium kinetic effect is absent supports a stepwise mechanism in which proton transfer occurs after the rate-determining step.

A Kinetic Study on Aminolysis of S-4-Nitrophenyl Thiobenzoate in H2O Containing 20 mol % DMSO and 44 wt % EtOH: Effect of Medium on Reactivity and Mechanism

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured for nucleophilic substitution reactions of S-4-nitrophenyl thiobenzoate with a series of alicyclic secondary amines in <TEX>$H_2O$</TEX> containing 20 mol % DMSO at 25.0 <TEX>${\pm}$</TEX> 0.1 <TEX>${^{\circ}C}$</TEX>. The Br<TEX>$\phi$</TEX>nsted-type plot exhibits a downward curvature, i.e., <TEX>$\beta_{nuc}$</TEX> decreases from 0.94 to 0.34 as the amine basicity increases. The reactions in the aqueous DMSO have also been suggested to proceed through a zwitterionic tetrahedral intermediate (T<TEX>${\pm}$</TEX>) with change in the RDS on the basis of the curved Br<TEX>$\phi$</TEX>nsted-type plot. The reactions in the aqueous DMSO exhibit larger <TEX>$k_N$</TEX> values than those in the aqueous EtOH. The macroscopic rate constants (<TEX>$k_N$</TEX>) for the reactions in the two solvent systems have been dissected into the microscopic rate constants (<TEX>$k_1\;and\;k_2/k_{-1}$</TEX> ratio) to investigate effect of medium on reactivity in the microscopic level. It has been found that the <TEX>$k_2/k_{-1}$</TEX> ratios are similar for the reactions in the two solvent systems, while <TEX>$k_1$</TEX> values are larger for the reactions in 20 mol % DMSO than for those in 44 wt % EtOH, indicating that the larger <TEX>$k_1$</TEX> is mainly responsible for the larger <TEX>$k_N$</TEX>. It has been suggested that the transition state is more stabilized in 20 mol % DMSO through mutual polarizability interaction than in 44 wt % EtOH through H-bonding interaction.

Reaction Mechanism and Structure of Transition State Determined from Analysis of Bronsted βnucfor Aminolysis of 4-Nitrophenyl Diphenylphosphinate

Useful information on reaction mechanism can be obtained from analysis of Bronsted-type plots. Curved Bronstedtype plots often found for reactions of esters possessing a good leaving group (e.g., 2,4-dinitrophenoxide) have been taken as evidence for a change in the rate-determining step (RDS) of a stepwise mechanism. In fact, a curved Bronsted-type plot has been reported for reactions of 2,4dinitrophenyl benzoate (1) with a series of alicyclic secondary amines, i.e., the βnuc value decreases from 0.74 to 0.34 as the amine basicity increases. In contrast, the corresponding reactions of 4-nitrophenyl benzoate (2) resulted in a linear Bronsted-type plot with βnuc = 0.88 in the pKa range 5.9511.02. Thus, it has been concluded that the aminolyses of 1 and 2 proceed through a stepwise mechanism and the RDS changes in the reactions of 1 but not in the reactions of 2 in that pKa range. 4a,b

Kinetic Study on Michael-type Reactions of 1-Phenyl-2-propyn-1-one with Alicyclic Secondary Amines: Effect of Medium on Reactivity and Mechanism

Second-order rate constants (kN) have been measured for Michael-type addition reactions of a series of alicyclic secondary amines to 1-phenyl-2-propyn-1-one (2) in MeCN at 25.0 <TEX>${\pm}$</TEX> 0.1 <TEX>${^{\circ}C}$</TEX>. All the amines studied are less reactive in MeCN than in <TEX>$H_2O$</TEX> although they are more basic in the aprotic solvent by 7-9 p<TEX>$K_a$</TEX> units. The Bronsted-type plot is linear with <TEX>$\beta_{nuc}$</TEX> = 0.40, which is slightly larger than that reported previously for the corresponding reactions in <TEX>$H_2O$</TEX> (<TEX>$\beta_{nuc}$</TEX> = 0.27). Product analysis has shown that only E-isomer is produced. Kinetic isotope effect is absent for the reactions of 2 with morpholine and deuterated morpholine (i.e., <TEX>$k^H/k^D$</TEX> = 1.0). Thus, the reaction has been concluded to proceed through a stepwise mechanism, in which proton transfer occurs after the rate-determining step. The reaction has been suggested to proceed through a tighter transition state in MeCN than in H2O on the basis of the larger <TEX>$\beta_{nuc}$</TEX> in the aprotic solvent. The nature of the transition state has been proposed to be responsible for the decreased reactivity in the aprotic solvent.

Aminolysis of 2,4-Dinitrophenyl and 3,4-Dinitrophenyl Benzoates: Effect of ortho-Nitro Group on Reactivity and Mechanism

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for reactions of 3,4-dinitrophenyl benzoates (5b) with a series of alicyclic secondary amines in 80 mol % <TEX>$H_2O$</TEX>/20 mol % DMSO at 25.0 <TEX>${\pm}$</TEX> 0.1 <TEX>${^{\circ}C}$</TEX>. The kinetic data have been compared with the data reported previously for the corresponding reactions of 2,4- dinitrophenyl benzoates (5a) to investigate the effect of changing the nucleofuge from 2,4-dinitrophenoxide to 3,4-dinitrophenoxide on reactivity and mechanism. The kinetic results show that aminolyses of 5a and 5b proceed through the same mechanism, i.e., a zwitterionic tetrahedral intermediate (<TEX>$T^{\pm}$</TEX>) with a change in the rate-determining step (RDS). Substrate 5a is more reactive than 5b when breakdown of <TEX>$T^{\pm}$</TEX> is the RDS but less reactive when formation of <TEX>$T^{\pm}$</TEX> is the RDS. Dissection of kN values into the microscopic rate constants (e.g., <TEX>$k_1$</TEX> and <TEX>$k_2/k_{-1 }$</TEX> ratio) has revealed that 5a results in larger <TEX>$k_2/k_{-1}$</TEX> ratios but smaller k1 values than 5b for all the amines studied. Since 2,4-dinitrophenoxide is less basic and a better nucleofuge than 3,4-dinitrophenoxide, the larger <TEX>$k_2/k_{-1}$</TEX> ratios determined for the reactions of 5a than for those of 5b are as expected. The steric hindrance exerted by the ortho-nitro group on 5a contributes to the smaller k1 values found for the reactions of 5a than for those of 5b.

Aminolysis of 2,4-Dinitrophenyl and 3,4-Dinitrophenyl 2-Thiophenecarboxylates: Effect of ortho-Nitro Group on Reactivity and Mechanism

Second-order rate constants (kN) have been measured spectrophotometrically for reactions of 3,4-dinitrophenyl 2-thiophenecarboxylate (2) with a series of alicyclic secondary amines in 80 mol % <TEX>$H_2O$</TEX>/20 mol % dimethyl sulfoxide at 25.0 <TEX>${^{\circ}C}$</TEX>. The Br&#x00F8;nsted-type plot exhibits a downward curvature for the aminolysis of 2. The curved Brønsted-type plot is similar to that reported for the corresponding reactions of 2,4-dinitrophenyl 2- thiophenecarboxylate (1). The reactions of 1 and 2 have been suggested to proceed through the same mechanism, i.e., through a zwitterionic tetrahedral intermediate (<TEX>$T^{\pm}$</TEX>) with a change in the rate-determining step. Substrate 2 is less reactive than 1 toward weakly basic amines (e.g., <TEX>$pK_a$</TEX> < 10.4) but becomes more reactive as the basicity of amines increases further. Dissection of kN into the microscopic rate constants has revealed that the reaction of 2 results in a smaller <TEX>$k_2/k_{-1}$</TEX> ratio but larger <TEX>$k_1$</TEX> than the corresponding reaction of 1. Steric hindrance exerted by the ortho-nitro group has been suggested to be responsible for the smaller <TEX>$k_1$</TEX> value found for the reactions of 1.

Aminolysis of 2,4-Dinitrophenyl 2-Furoate and 2-Thiophenecarboxylate: Effect of Modification of Nonleaving Group from Furoyl to Thiophenecarbonyl on Reactivity and Mechanism

Second-order rate constants have been determined spectrophotometrically for reactions of 2,4-dinitrophenyl 2thiophenecarboxylate (2) with a series of alicyclic secondary amines in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 o C. The Bronsted-type plot exhibits a downward curvature, i.e., the slope decreases from 0.74 to 0.34 as the amine basicity increases. The pKa at the center of the Bronsted curvature, defined as pKa o , has been determined to be 9.1. Comparison of the Bronsted-type plot for the reactions of 2 with that for the corresponding reactions of 2,4-dinitrophenyl 2-furoate (1) suggests that reactions of 1 and 2 proceed through a common mechanism, although 2 is less reactive than 1. The curved Bronsted-type plot has been interpreted as a change in RDS of a stepwise mechanism. The replacement of the O atom in the furoyl ring by an S atom (1 → 2) does not alter the reaction mechanism but causes a decrease in reactivity. Dissection of the apparent second-order rate constants into the microscopic rate constants has revealed that the k2/k–1 ratio is not influenced upon changing the nonleaving group from furoyl to thiophenecarbonyl. However, k1 has been calculated to be smaller for the reactions of 2 than for the corresponding reactions of 1, indicating that the C=O bond in the thiophenecarboxylate 2 is less electrophilic than that in the furoate 1. The smaller k1 for the reactions of 2 is fully responsible for the fact that 2 is less reactive than 1.

Aminolyses of 2,4-Dinitrophenyl and 3,4-Dinitrophenyl 2-Furoates: Effect of ortho-Substituent on Reactivity and Mechanism

Second-order rate constants (kN) have been measured spectrophotometrically for reactions of 3,4-dintrophenyl 2-furoate (2) with a series of secondary alicyclic amines in 80 mol % H2O/20 mol % dimethyl sulfoxide (DMSO) at 25.0 o C. The Bronsted-type plot exhibits a downward curvature for the aminolysis of 2, which is similar to that reported for the corresponding reactions of 2,4-dintrophenyl 2-furoate (1). Substrate 2 is less reactive than 1 toward all the amines studied but the reactivity difference becomes smaller as the amine basicity increases. Dissection of the second-order rate constants into the microscopic rate constants has revealed that the reaction of 2 results in a smaller k2/k–1 ratio but slightly larger k1 value than that of 1. Steric hindrance has been suggested to be responsible for the smaller k1 value found for the reactions of 1, since the ortho-substituent of 1 would inhibit the attack of amines (i.e., the k1 process).

Aminolysis of 4-nitrophenyl phenyl carbonate and thionocarbonate: effects of amine nature and modification of electrophilic center from CO to CS on reactivity and mechanism

A kinetic study is reported for the reactions of 4-nitrophenyl phenyl carbonate (5) and thionocarbonate (6) with a series of alicyclic secondary amines in 80 mol% H(2)O-20 mol% DMSO at 25.0 +/- 0.1 degrees C. The plots of k(obsd) vs. amine concentration are linear for the reactions of 5. On the contrary, the plots for the corresponding reactions of 6 curve upward as a function of increasing amine concentration, indicating that the reactions proceed through two intermediates (i.e., a zwitterionic tetrahedral intermediate T(+/-) and its deprotonated form T(-)). The Brønsted-type plot for 5 the reactions of with secondary amines exhibits a downward curvature, i.e., the slope decreases from 0.98 to 0.26 as the pK(a) of the conjugate acid of amines increases, implying that the reactions proceed through T(+/-) with a change in the rate-determining step (RDS). The k(N) values are larger for the reactions of with secondary amines than for those with primary amines of similar basicity. Dissection of k(N) values for the reactions of 5 into the microscopic rate constants (i.e., k(1) and k(2)/k(-1) ratio) has revealed that k(1) is larger for the reactions with secondary amines than for those with isobasic primary amines, while the k(2)/k(-1) ratio is nearly identical. On the other hand, for reactions of 6, secondary amines exhibit larger k(1) values but smaller k(2)/k(-1) ratios than primary amines. The current study has shown that the reactivity and reaction mechanism are strongly influenced by the nature of amines (primary vs. secondary amines) and electrophilic centers (C[double bond]O vs. C[double bond]S).

Aminolysis of Y-Substituted Phenyl X-Substituted Cinnamates and Benzoates: Effect of Modification of the Nonleaving Group from Benzoyl to Cinnamoyl

A kinetic study is reported for reactions of Y-substituted phenyl X-substituted cinnamates (1a-e and 3a-g) and benzoates (2a-e and 4a-g) with a series of alicyclic secondary amines in 80 mol % H2O/20 mol % DMSO at 25.0 +/- 0.1 degrees C. Reactions of 2,4-dinitrophenyl X-substituted cinnamates (1a-e) and benzoates (2a-e) with amines result in linear Yukawa-Tsuno plots. The rho(X) values are much smaller for the reactions of 1a-e than for those of 2a-e. A distance effect and the nature of the reaction mechanism (i.e., a concerted mechanism for 1a-e) have been suggested to be responsible for the small rho(X) values. The Brønsted-type plots for the reactions of 2,4-dinitrophenyl X-substituted cinnamates (1a, 1c, and 1e) with amines are curved with a decreasing betanuc value from 0.65 to 0.3-0.4. The reactions of Y-substituted phenyl cinnamates (3a-g) with morpholine also result in a curved Brønsted plot, while the corresponding reactions of Y-substituted phenyl benzoates (4a-e) exhibit a linear Brønsted plot. It has been concluded that the curved Brønsted plots found for the reactions of the cinnamates (1a, 1c, 1e, and 3a-g) are not due to a change in the rate-determining step (RDS) but due to a normal Hammond effect for a concerted mechanism, that is, an earlier transition state (TS) for a more reactive amine or substrate.

Aminolyses of 2,4-Dinitrophenyl 2-Furoate and Benzoate: Effect of Nonleaving Group on Reactivity and Mechanism

Second-order rate constants (kN) have been determined spectrophotometrically for reactions of 2,4-dintrophenyl 2-furoate (2) with a series of alicyclic secondary amines in 80 mol % H2O/20 mol % dimethyl sulfoxide (DMSO) at 25.0 oC. The furoate 2 is more reactive than 2,4-dintrophenyl benzoate (1) toward all the amines studied. The higher acidity of 2-furoic acid (pKa = 3.16) compared with benzoic acid (pKa = 4.20) has been suggested to be responsible for the reactivity order, at least in part. The Brønsted-type plots for the reactions of 1 and 2 are curved downwardly, indicating that the aminolyses of both 1 and 2 proceed through a zwitterionic tetrahedral intermediate (T±) with a change in the rate-determining step on changing the amine basicity. Dissection of the kN values into their microscopic rate constants has revealed that the pKao and k2/k-1 ratios for the reactions of 1 and 2 are identical, indicating that the nature of the nonleaving group (i.e., benzoyl and 2-furoyl) does not affect the reaction mechanism. The k1 values have been found to be larger for the reactions of 2 than for those of 1, which is fully responsible for the fact that the former is more reactive than the latter.