Kinetics and mechanism of the aminolysis of diaryl carbonates

The reactions of secondary alicyclic (SA) amines with 4-nitrophenyl 2,4-dinitrophenyl carbonate ( 4 ) and bis(2,4-dinitrophenyl) carbonate ( 5 ) are subjected to a kinetic investigation in 44 wt% ethanol-water, at 25.0ºC, ionic strength 0.2 M. The reactions are examined by monitoring spectrophotometrically the appearance of 2,4-dinitrophenoxide. Under conditions of excess amine, pseudo-first-order rate coefficients ( k obsd ) are found. Plots of kobsd against free amine concentration at constant pH are linear with k N as slope. The Brønsted-type plots (log k N vs amine p K a ) obtained are also linear with slopes 0.51 and 0.48 for the aminolysis of 4 and 5 , respectively. These slope values are in accordance with concerted (one step) mechanisms. The absence of a Brønsted break at the predicted p K a for hypothetical stepwise mechanisms confirms the concerted nature of these reactions.

With the aim of extending our kinetic investigation on the aminolysis of diaryl carbonates, we have now studied the mechanism of the reactions of SA amines with 4-nitrophenyl 2,4dinitrophenyl carbonate (4) and bis(2,4-dinitrophenyl) carbonate (5).Specific goals are to evaluate the effect of two good leaving groups in the carbonate and also the nature of the amine on the kinetics and mechanism.This will be achieved by comparison of the title reaction with the aminolyses (quinuclidines and anilines) of the same and similar carbonates.

Results and Discussion
The reactions investigated in this work are governed by the rate law given by Eqs 1 and 2, where P, S and NH represent a product, the substrate and the free amine, respectively, and k 0 and k N are the rate coefficients for hydrolysis and aminolysis of the substrates, respectively.f Free piperazine and piperazinium ion fractions are 0.001077 and 0.9383, respectively.g Free piperazine and piperazinium ion fractions are 0.002214 and 0.9796, respectively.h Free piperazine and piperazinium ion fractions are 0.004478 and 0.9796, respectively.i Free piperazine and piperazinium ion fractions are 0.008965 and 0.9830, respectively.j Free piperazine and piperazinium ion fractions are 0.01780 and 0.9782, respectively.f Free piperazine and piperazinium ion fractions are 0.002804 and 0.9722, respectively.g Free piperazine and piperazinium ion fractions are 0.004478 and 0.9796, respectively.h Free piperazine and piperazinium ion fractions are 0.007120 and 0.9828, respectively.
Due to the fact that the reactions with piperazine were too fast at pH = pK a , these reactions were studied at pH 6.7-8.2,where a mixture of piperazine (6) and piperazinium ion (7) are present.In these cases the k N values were obtained through Eqs 3 and 4, where k Nobsd is a global nucleophilic rate constant (corresponding to the mixture of nucleophiles), [N] tot is the total piperazine (species 6 and 7) concentration, F 6 and F 7 are their molar fractions, respectively, and k 6 and k 7 are their corresponding nucleophilic rate constants. 8The values of k Nobsd were obtained as the slopes of linear k obsd vs [N] tot plots at constant pH, according to eq 3. The k N values for the reactions of both carbonates with species 6 and 7 (k 6 and k 7 , respectively) were determined through Eq 4, as described. 8 N H H N N H

7
H + H The values of k N for the reactions of both substrates are shown in Table 3.These values, as well as those of the pK a of the conjugate acids of the amines, were statistically corrected with q = 2 for piperazine and p = 2 for the conjugate acids of the amines, except that for piperazinium ion with p = 4. 8,9 With these corrected values, the Brønsted-type plots (shown in Figure 1) were obtained.Figure 1 shows the Brønsted-type plot for the reactions studied.These are linear with slopes β = 0.51 and 0.48 for the reactions of 4 and 5, respectively.These β values suggest a concerted mechanism (Scheme 1), since these slope values are in accordance with those found for the concerted aminolysis of similar compounds.Examples of these are the aminolyses (anilines and quinuclidines) of carbonates 1-3, with β values in the range 0.4 -0.7, some of them in water 5 and others in aqueous ethanol. 6,7 Another reason to conclude that the mechanisms for both reactions are concerted is the following: the reactions of SA amines with 4-methylphenyl and 4-chlorophenyl 2,4dinitrophenyl carbonates (2 and 3, respectively) have been described as concerted. 6,7This means that the putative zwitterionic tetrahedral intermediate (T ± ) formed is extremely unstable.Therefore, since 4-nitrophenoxy and 2,4-dinitrophenoxy are even more destabilizing nonleaving groups than 4-methylphenoxy and 4-chlorophenoxy, it is reasonable that the putative T ± intermediates formed in the title reactions would be even more destabilized, leading to a concerted mechanism.
It is known that the β value alone is not enough to conclude that a mechanism is concerted.It is also necessary to make sure that the expected pK a value at the center of the Brønsted curvature (pK a 0 ) for a hypothetical stepwise mechanism is within the pK a range used. 10,11The expected pK a 0 value for the title reactions if they were stepwise can be estimated as follows.
For the pyridinolysis of 4-methylphenyl and 4-chlorophenyl 4-nitrophenyl carbonates biphasic nonlinear (two linear regions and a curvature in between) downward Brønsted plots with pK a 0 values of ca.9.5 were found (unpublished work).For the SA aminolysis of the same substrates biphasic plots were also obtained, with pK a 0 values of ca.10.5. 6,12Therefore, the change from pyridines to SA amines increases the pK a 0 value by ca.one pK a unit.This has been explained by the superior leaving ability from the intermediate T ± of SA amines compared with isobasic pyridines.8b For the pyridinolysis of carbonates 2 and 3, nonlinear biphasic Brønsted plots were found, with pK a 0 = 7.5 and 7.2, respectively (unpublished data).Therefore, if the SA aminolysis of these substrates were stepwise, pK a 0 values of ca.8.2-8.5 would be expected.The absence of a break at these expected values (see Figure 1) confirm the concerted mechanisms (Scheme 1) for the reactions under investigation.
In order to evaluate the influence of the non-leaving group on the kinetics of the aminolysis reactions of aryl 2,4-dinitrophenyl carbonates, a multiparametric study was carried out.With the experimental k N values obtained in this work and those for the SA aminolysis of carbonates 2 and 3, 6,7 and the corresponding pK a values, Eq 5 was obtained (n = 24, R 2 = 0.958).In this equation pK N and pK nlg are the pK a of the conjugated acids of the nucleophiles and non-leaving groups, respectively.log k N = ( -0.22 ± 0.26) + ( 0.45 ± 0.03) pK N -(0.20 ± 0.01) pK nlg (5)   Figure 2 shows a logarithmic plot of the experimental k N values vs those calculated using Eq 5.The sensitivities of the pKa of the amine (β N ), leaving group (β lg ) and non-leaving group (β nlg ) can be related through Eq 6, 13 from which a value of β lg = -0.25 can be deduced.
The similar sensitivities of the coefficients for the leaving and non-leaving groups should be due to the fact that probably both groups belong to the same family (phenoxy).A similar result was found for the phenolysis reactions of a series of diaryl carbonates. 13perimental Section General Procedures.The SA amines were purified as reported.8a Carbonate 4 was synthesized by the reaction of 2,4-dinitrophenol with 4-nitrophenyl chloroformate, following the general method. 3,6,12Carbonate 5 was synthesized by the reaction of phosgene with 2,4-dinitrophenol, in accordance with the method described. 14Kinetic measurements.The reactions were followed spectrophotometrically (210-500 nm) by means of a diode array instrument.The rate constants were measured following the absorbance change due to the appearance of the 2,4-dinitrophenoxide ion at 360 nm.The reactions were investigated in 44 wt% ethanol-water solutions, at 25.0 ± 0.1 °C, and an ionic strength of 0.2 M (maintained with KCl).In all reactions the concentration of total amine (free amine plus its protonated form) was much greater (at least 10-fold) than that of the substrate.In all cases, pseudo-first-order rate coefficients (k obsd ) were obtained by means of the kinetic software of the spectrophotometer.All reactions were carried out in duplicate and the values of kobsd agreed within 5 %.
Product studies.One of the products in the aminolysis of both substrates was identified as 2,4dinitrophenoxide.The identification was carried out by comparison of the UV-vis spectra at the end of these reactions with that of an authentic sample 2,4-dinitrophenol, under the same reaction conditions.

k
obsd = k 0 + N [NH] (2) re determined as the slope of linear plots of k obsd vs [NH] r the reactions of SA amines with carbonates 4 and 5 are shown in Tables 1 nd 2, respectively.kThe values of k N for all the reactions we and were found to be pH independent.The values of k obsd fo a

Amine pH F N b 103[N] tot /M c 103 k obsd / s -1 No.of runs
cConcentration of total amine (free base plus protonated forms).d Carbonate buffer 0.01M.e Free piperazine and piperazinium ion fractions are 0.00051 and 0.88543, respectively.

Table 3 .
Values of pK a for the conjugate acids of secondary alicyclic (SA) amines and k