Kinetic Study on Aminolysis of 4-Nitrophenyl 2-Pyridyl Carbonate in Acetonitrile: Kinetic Evidence for a Stepwise Mechanism with Two Intermediates

Experimental Section

As shown in Figure 1, the plot of kobsd vs. [amine] for the reaction with morpholine is nonlinear. Similarly curved plots are obtained for the reactions with all the amines studied in this work as shown in Figures S1(a)-S4(a) in the Supporting Information (SI) section. Such nonlinear plot has often been reported for aminolysis of C=S centered esters (e.g., O-4-nitrophenyl thionobenzoate), in which a second amine molecule behaves as a general-base catalyst,5 but is very rare for aminolysis of C=O centered esters.6

Figure 1.Plot of kobsd vs. [amine] for the reaction of 4-nitrophenyl 2-pyridyl carbonate with morpholine in MeCN at 25.0 ± 0.1 oC.

Scheme 1

If the reaction proceeds through an intermediate (or a transition state) as modeled by III, general-base catalysis by a second amine molecule would not be necessary. This is because the H+ transfer occurs from the aminium moiety of III to the N atom of the leaving 2-pyridyloxide. Thus, if the reaction proceeds through III, one might expect that plot of kobsd vs. [amine] should be linear. However, the plots are nonlinear (Figure 1 and Figures S1a-S4a in the SI section), indicating that the reaction does not proceed through III but proceeds via a stepwise mechanism with two intermediates (i.e., T± and its deprotonated form T–) as shown in Scheme 1.

One can derive Eq. (1) on the basis of the kinetic results and the mechanism proposed in Scheme 1. Eq. (1) can be simplified to Eq. (2) under the assumption k2 < < k3[amine]. Thus, one might expect the plot of [amine]/kobsd vs. 1/[amine] is linear if the above assumption is valid. As shown in Figure 2(a), the plot of [amine]/kobsd vs. 1/[amine] is linear only when the amine concentration is high but curves downward as the amine concentration decreases. This indicates that the above assumption is invalid when the amine concentration is low. However, this is not surprising because the k3[amine] term becomes smaller as the amine concentration decreases.

Since the first step in Scheme 1 is a preequilibrium, one can assume that k–1 >> k2 + k3[amine]. Then, Eq. (1) can be simplified to Eq. (3). Thus, if the above assumption is valid, one might expect that the plot of kobsd/[amine] vs. [amine] is linear. In fact, as shown in Figure 2(b), the plot exhibits an excellent linear correlation with a positive intercept. The plots for the reactions with all the other amines used in this study are also linear as shown in Figures S1(c)-S4(c) in the SI section, indicating that the proposed reaction mechanism and the assumption k–1 >> k2 + k3[amine] are correct in all cases.

Figure 2.Plots of [amine]/kobsd vs. 1/[amine] (a) and kobsd/[amine] vs. [amine] (b) for the reaction of 4-nitrophenyl 2-pyridyl carbonate with morpholine in MeCN at 25.0 ± 0.1 oC.

Thus, the k1k2/k–1 and k1k3/k–1 values were determined from the intercept and slope of the linear plot, respectively, while the k3/k2 ratios were calculated from the k1k2/k–1 and k1k3/k–1 values. As shown in Table 1, the k1k2/k–1 and k1k3/k–1 values increase as the amine basicity increases, e.g., k1k2/k–1 increases from 1.12 M–1s–1 to 7.87 and 173 M–1s–1 as the pKa of the conjugate acid of the amine increases from 16.6 to 17.6 and 18.8, in turn. The statistically corrected Brønsted-type plots7 shown in Figure S5 in the SI section exhibit excellent linear correlations, indicating that the k1k2/k–1 and k1k3/k–1 values calculated are highly reliable. It is noted that the k3/k2 ratio decreases as the amine basicity increases. Besides, the maximum k3/k2 ratio is only ca. 80 for the reaction with the least basic morpholine. This explains why the plot of [amine]/kobsd vs. 1/[amine] shown in Figure 2(a) curves downward in a low amine concentration region.

Table 1.aThe pKa values in MeCN were taken from refs. 3a and 9, and the units of k1k2/k–1, k1k3/k–1 and k3/k2 are M–1s–1, M–2s–1 and M–1, in turn.

It is well known that k3 is independent of the amine basicity.5,6 Because a more basic amine would deprotonate more rapidly from the aminium moiety of T±, while the aminium ion would tend to hold the proton more strongly as the amine becomes more basic. In contrast, the effect of amine basicity on k2 is not clearly understood.6,8 Gresser etal. reported that amine basicity does not affect k2 in aminolysis of diaryl carbonates, since there is little or no electron donation from the aminium moiety of T± to push out the nucleofuge.8 However, we have proposed that the amine basicity affects k2 through an inductive effect, although the “push” by the aminium moiety of T± is absent.6

Figure 3.T± structure and three different reaction routes.

It is apparent that the basicity of the amines used in this study is affected by the “Z” moiety of the cyclic amines (e.g., the pKa of the conjugate acid of amine decreases from 18.8 to 17.6 and 16.6 as the “Z” changes from CH2 to NCH2CH2OH and O, in turn). Furthermore, the electronic nature of the Z moiety in the aminium moiety of T± would affect the electron density of the reaction site (i.e. the central carbon atom) through an inductive effect, although the effect would not be significant because of the long distance between the Z moiety and the reaction site. Accordingly, k2 would decrease as the Z moiety changes from CH2 to an electron-withdrawing oxygen atom (i.e., from a strongly basic piperidine to a weakly basic morpholine). This idea is consistent with the fact that the k3/k2 ratio increases as the amine becomes less basic or vice versa (Table 1).

In summary, (1) aminolysis of 4-nitrophenyl 2-pyridylcarbonate proceeds through a stepwise mechanism with two intermediates T± and T–, (2) the assumption k–1 >> k2 + k3[amine] is valid in the experimental conditions, (3) the k3/ k2 ratio is dependent on the amine basicity.