Kinetics and mechanism of the aminolysis of methyl 4-nitrophenyl, methyl 2,4-dinitrophenyl, and phenyl 2,4-dinitrophenyl carbonates

Article abstract of DOI:10.1021/jo026390k

The reactions of methyl 4-nitrophenyl carbonate (MNPC) with a series of secondary alicyclic amines (SAA) and quinuclidines (QUIN), methyl 2,4-dinitrophenyl carbonate (MDNPC) with QUIN and 1-(2-hydroxyethyl)piperazinium ion (HPA), and phenyl 2,4-dinitrophenyl carbonate (PDNPC) with SAA are subjected to a kinetic investigation in aqueous solution, at 25.0°C and an ionic strength of 0.2 M. By following spectrophotometrically the nucleofuge release (330-400 nm) under amine excess, pseudo-first-order rate coefficients (k_obsd) are obtained. Plots of k_obsd VS [amine] at constant pH are linear, with the slope (k_N) being pH independent. The Broensted-type plot (log k_N vs amine pK_a) for the reactions of SAA with MNPC is biphasic with slopes β₁ = 0.3 (high pK_a region) and β₂ = 1.0 (low pK_a region) and a curvature center at pK_a⁰ = 9.3. This plot is consistent with a stepwise mechanism through a zwitterionic tetrahedral intermediate (T^±) and a change in the rate-determining step with SAA basicity. The Broensted plot for the quinuclidinolysis of MNPC is linear with slope β_N = 0.86, in line with a stepwise process where breakdown of T^± to products is rate limiting. A previous work on the reactions of SAA with MDNPC was revised by including the reaction of HPA. The Broensted plots for the reactions of QUIN and SAA with MDNPC and SAA with PDNPC are linear with slopes β = 0.51, 0.48, and 0.39, respectively, consistent with concerted mechanisms. Since quinuclidines are better leaving groups from T^± than isobasic SAA, yielding a less stable T^±, it seems doubtful that the quinuclidinolysis of PDNPC is stepwise, as reported.

Full text of DOI:10.1021/jo026390k

Kin etics a n d Mech a n ism of th e Am in olysis of Meth yl
4-Nitr op h en yl, Meth yl 2,4-Din itr op h en yl, a n d P h en yl
2,4-Din itr op h en yl Ca r bon a tes
Enrique A. Castro,* Margarita Aliaga, Paola Campodo´nico, and J ose´ G. Santos*
Facultad de Quı´mica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
ecastro@puc.cl
Received September 3, 2002
The reactions of methyl 4-nitrophenyl carbonate (MNPC) with a series of secondary alicyclic amines
(SAA) and quinuclidines (QUIN), methyl 2,4-dinitrophenyl carbonate (MDNPC) with QUIN and
1-(2-hydroxyethyl)piperazinium ion (HPA), and phenyl 2,4-dinitrophenyl carbonate (PDNPC) with
SAA are subjected to a kinetic investigation in aqueous solution, at 25.0 °C and an ionic strength
of 0.2 M. By following spectrophotometrically the nucleofuge release (330-400 nm) under amine
excess, pseudo-first-order rate coefficients (kobsd) are obtained. Plots of kobsd vs [amine] at constant
pH are linear, with the slope (kN) being pH independent. The Bro¨nsted-type plot (log kN vs amine
pKa) for the reactions of SAA with MNPC is biphasic with slopes â1 ) 0.3 (high pKa region) and â2
0
) 1.0 (low pKa region) and a curvature center at pKa ) 9.3. This plot is consistent with a stepwise
mechanism through a zwitterionic tetrahedral intermediate (T() and a change in the rate-
determining step with SAA basicity. The Bro¨nsted plot for the quinuclidinolysis of MNPC is linear
with slope âN ) 0.86, in line with a stepwise process where breakdown of T( to products is rate
limiting. A previous work on the reactions of SAA with MDNPC was revised by including the reaction
of HPA. The Bro¨nsted plots for the reactions of QUIN and SAA with MDNPC and SAA with PDNPC
are linear with slopes â ) 0.51, 0.48, and 0.39, respectively, consistent with concerted mechanisms.
Since quinuclidines are better leaving groups from T( than isobasic SAA, yielding a less stable T(,
it seems doubtful that the quinuclidinolysis of PDNPC is stepwise, as reported.
In tr od u ction
carbonates with quinuclidines (QUIN)5 and SAA.6 Most
of these reactions were found to proceed through a
zwitterionic tetrahedral addition intermediate (stepwise
mechanism),2-5 and others were found to occur in a single
step with no intermediate (concerted mechanism).6 In all
these studies, the Bro¨nsted-type plot has been employed
as an important tool for the diagnosis of the reaction
mechanism.
To shed more light on the mechanisms of the aminoly-
sis of carbonates, we describe in this work a kinetic study
of the reactions of SAA and QUIN with methyl 4-nitro-
phenyl carbonate (MNPC), QUIN with methyl 2,4-dini-
trophenyl carbonate (MDNPC), and SAA with phenyl 2,4-
dinitrophenyl carbonate (PDNPC). We compare our
results with those obtained for the same aminolysis of
similar carbonates3,5,6 to assess the effect of the nonleav-
ing and leaving groups and the amine nature on the
kinetics and mechanism of these reactions.
Although much attention has been drawn to the
kinetics and mechanism of the aminolysis of aryl esters,1
the aminolyses of alkyl aryl carbonates2-4 and diaryl
carbonates5,6 have been less studied. The latter investiga-
tions include reports on the reactions of alkyl aryl
carbonates with pyridines,2 secondary alicyclic amines
(SAA),3 and benzylamines4 and the reactions of diaryl
(1) (a) J ohnson, S. L. Adv. Phys. Org. Chem. 1967, 5, 237. (b) J encks,
W. P.; Gilchrist, M. J . Am. Chem. Soc. 1968, 90, 2622. (c) Satterthwait,
A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96, 7018, 7031. (d) Kirby,
A. J . In Organic Reaction Mechanisms; Knipe, A. C., Watts, W. E.,
Eds.; Wiley and Sons: New York, 1980; p 29. (e) J encks, W. P. Chem.
Soc. Rev. 1981, 10, 345. (f) Williams, A. Acc. Chem. Res. 1989, 22, 387.
(g) Williams, A. Adv. Phys. Org. Chem. 1992, 27, 2. (h) Williams, A.
Chem. Soc. Rev. 1994, 23, 93. (i) Bennet, A. J .; Brown, R. S. In Physical
Organic Chemistry of Acyl Transfer Reactions, Comprehensive Biologi-
cal Catalysis; Academic Press: New York, 1998; Vol. 1, p 293.
(2) (a) Bond, P. M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2
1976, 679. (b) Castro, E. A.; Gil, F. J . J . Am. Chem. Soc. 1977, 99,
7611. (c) Castro, E. A.; Freudenberg, M. J . Org. Chem. 1980, 45, 906.
(d) Castro, E. A.; Iban˜ez, F.; Lagos, S.; Schick, M.; Santos, J . G. J .
Org. Chem. 1992, 57, 2691.
(3) (a) Castro, E. A.; Iban˜ez, F.; Saitu´a, A. M.; Santos, J . G. J . Chem.
Res. (S) 1993, 56. (b) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org.
Chem. 2001, 66, 6000.
(4) Koh, H. J .; Lee, J . W.; Lee, H. W.; Lee, I. Can. J . Chem. 1998,
76, 710.
(5) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
6970.
(6) Castro, E. A.; Andu´jar, M.; Campodo´nico, P.; Santos, J . G. Int.
J . Chem. Kinet. 2002, 34, 309.
In view of our kinetic results, in this work we also
revise the kinetic data obtained for the reactions of SAA
10.1021/jo026390k CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/08/2002
J . Org. Chem. 2002, 67, 8911-8916
8911

Castro et al.
TABLE 1. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis (SAA a n d QUIN) of Meth yl 4-Nitr op h en yl
Ca r bon a te (MNP C)a
TABLE 2. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis (QUIN a n d HP A) of Meth yl
2,4-Din itr op h en yl Ca r bon a te (MDNP C)a
103 [N]tot
Mc
/
no. of
103 [N]tot
Mc
/
no. of
b
b
amine
piperidine
pH
FN
103 kobsd/s-1 runs
amine
pH
FN
103 kobsd/s-1 runs
10.93 0.33
11.24 0.50
11.55 0.67
9.63 0.33
9.94 0.50
10.25 0.67
1.06-10.6 13.7-83.7
1.06-10.6 28.0-118
1.06-10.6 44.2-191
2.51-25.1 4.80-54.5
2.51-25.1 10.7-79.2
2.51-25.1 13.7-112
0.49-4.94 3.90-26.4
0.49-4.94 6.00-41.2
0.49-4.94 12.3-58.2
1.14-11.4 0.72-6.42
1.14-11.4 1.64-9.33
1.14-6.86 2.25-8.05
1.07-9.60 0.12-0.784
1.07-10.7 0.20-1.38
1.07-9.60 0.31-1.66
9.92-99.2 0.013-0.073
11.9-83.0 0.019-0.126
25.0-100.2 0.031-0.210
10
9
10
9
10
10
10
10
10
10
9
6
8
9
9
6
5
6
4
4
7
6
7
7
6
6
7
7
6
6
7
quinuclidine
8.5d 0.00126 0.42-4.2 29.6-139
8.8d 0.00251 0.42-4.2 61.0-326
9.0d 0.00397 0.42-4.2 106-539
7
6
7
6
6
7
7
6
7
7
6
6
3
3
6
piperazine
3-hydroxy-
quinuclidine
9.4 0.285
9.7 0.443
10.0 0.613
8.4 0.20
8.7 0.33
9.0 0.50
7.5 0.50
7.8 0.67
8.0 0.76
0.49-4.89 14.3-138
0.49-4.19 17.7-195
0.49-4.89 26.7-245
1.53-15.3 17.0-126
1.53-15.3 23.0-221
1.53-15.3 32.0-312
0.95-9.54 1.50-13.8
0.95-9.54 3.20-22.2
0.95-9.54 2.30-20.0
1-(2-hydroxyethyl)- 9.07 0.33
piperazine
3-chloro-
quinuclidine
9.38 0.50
9.69 0.67
8.41 0.33
8.78 0.50
9.09 0.67
morpholine
3-quinuclidinone
1-formylpiperazine 7.67 0.33
7.98 0.50
1-(2-hydroxyethyl)-
4.16 0.0128 10-40
0.07-0.35
0.11-0.71
0.21-2.2
piperazinium ion 4.36 0.0174 10-45
8.29 0.67
(HPA) 4.60 0.0233 10-100
piperazinium ion
5.51 0.33
5.81 0.50
6.12 0.67
a
b
In water, at 25.0 °C, ionic strength 0.2 M (KCl). Free amine
fraction. c Concentration of total amine (free base plus protonated
d
forms). In the presence of borate buffer 0.01M.
1-(2-hydroxyethyl)- 4.60 0.0233 40.0-126 0.0055-0.0343
piperazinium ion 4.90 0.0304 43.0-97.0 0.0154-0.0503
quinuclidine
8.5d 0.00126 0.80-8.0
8.8d 0.00251 0.80-8.0
9.0d 0.00397 0.80-8.0
0.67-2.78
1.15-4.51
2.20-7.26
Pseudo-first-order rate coefficients (kobsd) were found for all
the reactions; these were determined by means of the spec-
trophotometer kinetic software for first-order reactions.
Three pH values were employed in the reactions with each
amine. These pH values were maintained by the amine as its
own buffer (pH near the pKa of its conjugate acid), except in
the reactions of MNPC and MDNPC with quinuclidine and
that of PDNPC with piperidine, where external buffer was
used. For the reactions of the three substrates with HPA, the
pH was maintained by partial ionization of 1-(2-hydroxyethyl)-
piperazinium dication, whose pKa is 4.56 under the kinetic
conditions.10 Under these conditions, the pKa value of the
conjugate acid of HPA is 5.9.10
3-hydroxy-
quinuclidine
9.4
9.7
0.285
0.443
10.0 0.613
0.82-8.22 4.70-17.1
0.82-8.22 4.30-20.9
0.82-8.22 7.50-34.1
1.50-15.0 1.10-4.40
1.50-15.0 1.70-7.70
1.50-15.0 2.60-13.8
3.27-13.1 0.302-0.797
1.31-13.1 0.361-1.04
1.31-13.1 0.429-1.29
3-chloroqui-
nuclidine
8.4
8.7
9.0
7.5
7.8
8.0
0.20
0.33
0.50
0.50
0.67
0.76
3-quinuclidinone
7
a
b
In water, at 25.0 °C, ionic strength 0.2 M (KCl). Free amine
fraction. c Concentration of total amine (free base plus protonated
forms). In the presence of borate buffer 0.01M.
d
The kobsd values and the experimental conditions for the
reactions of MNPC with SAA and QUIN are shown in Table
1. Those for the reactions of MDNPC with QUIN and HPA
are exhibited in Table 2, and those for the reactions of PDNPC
with SAA can be seen in Table 3.
with MDNPC3a and discuss the mechanism proposed by
J encks for the reactions of quinuclidines with PDNPC.5
P r od u ct Stu d ies. 4-Nitrophenoxide anion and 2,4-dinitro-
phenoxide anion were identified as one of the products of the
aminolysis of MNPC and PDNPC, respectively. This was
achieved by comparison of the UV-vis spectra after completion
of these reactions with those of authentic samples of sodium
4-nitrophenoxide or sodium 2,4-dinitrophenoxide, under the
experimental kinetic conditions. The other product of the
reactions of MNPC and PDNPC with piperidine was identified
as the methyl carbamate of piperidine and the phenyl car-
bamate of piperidine, respectively. The identification was
carried out by HPLC through a comparison of the retention
times of authentic samples with those after completion of the
reactions. HPLC conditions: column, Supelcosil LC-18-DB (25
cm, 5 µm); eluant, acetonitrile/water ) 50/50; isocratic mode,
0.4 mL/min.
Exp er im en ta l Section
Ma ter ia ls. The SAA were purified as described.7 The
substrates MNPC,2a MDNPC,2b,8 and PDNPC5 were synthe-
sized as described previously. One of the products of the
reactions of piperidine with MNPC and PDNPC, the methyl
carbamate and phenyl carbamate of piperidine, respectively,
were synthesized by the reactions of methyl and phenyl
chloroformates with piperidine, as described.9 Their NMR and
IR spectra were in accordance with their structures.
Kin etic Mea su r em en ts. These were carried out by means
of a diode array spectrophotometer in aqueous solution, at 25.0
( 0.1 °C, ionic strength 0.2 M (maintained with KCl). The
reactions of MNPC, except those with piperazinium and 1-(2-
(hydroxyethyl)piperazinium (HPA) ions, were followed at 400
nm (appearance of the 4-nitrophenoxide anion). The reactions
of MNPC with the above ions, carried out at low pH, were
followed at 330 nm (appearance of 4-nitrophenol). The quinu-
clidinolysis of MDNPC and the reactions of this substrate with
HPA, as well as the reactions of PDNPC with all the SAA were
studied at 360 nm (following the appearance of 2,4-dinitro-
phenoxide anion).
Resu lts a n d Discu ssion
The kinetic law obtained under the reaction conditions
is that described in eq 1,
d[P]
dt
) kobsd[S]
(1)
All reactions were investigated under an excess of the amine
over the substrate (13-fold at least). The initial substrate
concentration was 2.5 × 10-5 M.
where P is 4-nitrophenoxide anion (4-nitrophenol in the
reaction of MNPC with piperazinium ion and HPA) or
2,4-dinitrophenoxide anion, S is the substrate, and kobsd
(7) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54, 2153.
(8) Pianka, M. J . Sci. Food Agric. 1960, 17, 47.
(9) Castro, E. A.; Ruiz, M. G.; Santos, J . G. Int. J . Chem. Kinet. 2001,
33, 281.
(10) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2, 1991,
63.
8912 J . Org. Chem., Vol. 67, No. 25, 2002

Aminolysis of Methyl Aryl and Diaryl Carbonates
TABLE 3. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis (SAA) of P h en yl 2,4-Din itr op h en yl
Ca r bon a te (P DNP C)a
103 [N]tot
Mc
/
no. of
103 kobsd/s-1 runs
b
amine
piperidine
pH
FN
7.70d 0.00029 4.27-21.3 0.383-0.593
8.00d 0.00058 4.27-21.3 0.563-1.22
8.30d 0.00115 4.27-21.3 1.32-1.94
5
12
8
6
6
6
11
6
piperazine
9.64 0.333
9.94 0.500
10.24 0.667
4.21-25.3 55.8-27.5
4.21-25.3 101-367
4.07-24.4 111-260
6.85-41.1 26.4-139
5.80-34.8 42.8-161
5.30-26.5 33.8-154
4.02-24.1 15.8-86.5
4.02-24.1 17.6-113
4.02-24.1 43.0-151
3.23-11.3 11.8-39.9
4.68-29.1 14.4-44.0
3.24-22.6 20.0-68.9
4.03-24.2 1.09-3.78
4.18-25.1 1.29-5.70
4.32-26.0 1.21-1.08
1-(2-hydroxyethyl)- 9.08 0.333
piperazine
9.38 0.500
9.68 0.667
8.48 0.333
8.78 0.500
9.08 0.667
6
morpholine
11
11
6
5
5
7
6
6
10
7
1-formylpiperazine 7.68 0.333
7.98 0.500
8.28 0.667
piperazinium ion
5.51 0.333
5.81 0.500
6.11 0.667
F IGURE 1. Bronsted-type plots for the reactions of SAA with
MNPC (9), MDNPC (O), and PDNPC (b) in aqueous solution,
at 25.0 °C and an ionic strength of 0.2 M (KCl).
1-(2-hydroxyethyl)- 4.60 0.0233 4.38-30.7 0.365-0.681
piperazinium ion 4.80 0.0282 4.58-27.5 0.42-0.756
6
TABLE 5. Va lu es of p Ka for th e Con ju ga te Acid s of
Qu in u clid in es (QUIN) a n d kN Va lu es for th e Rea ction s of
QUIN w ith Meth yl 4-Nitr op h en yl Ca r bon a te (MNP C) a n d
Meth yl 2,4-Din itr op h en yl Ca r bon a te (MDNP C)a
a
b
In water, at 25.0 °C, ionic strength 0.2 M (KCl). Free amine
fraction. c Concentration of total amine (free base plus protonated
forms). In the presence of borate buffer 0.01M.
d
kN/s-1 M-1
TABLE 4. Va lu es of p Ka for th e Con ju ga te Acid s of
Secon d a r y Alicyclic Am in es (SAA) a n d kN Va lu es for th e
Rea ction s of SAA w ith Meth yl 4-Nitr op h en yl Ca r bon a te
(MNP C), Meth yl 2,4-Din itr op h en yl Ca r bon a te (MDNP C)
a n d P h en yl 2,4-Din itr op h en yl Ca r bon a te (P DNP C)a
amine
quinuclidine
3-hydroxyquinuclidine
3-chloroquinuclidine
3-quinuclidinone
pKa
MNPC
MDNPC
11.4
9.8
9.0
20 ( 1
305 ( 11
81 ( 5
0.58 ( 0.03
0.17 ( 0.01
41 ( 1
kN/s-1 M-1
7.5
0.009 ( 0.0004
3.0 ( 0,2
amine
piperidine
piperazine
1-(2-hydroxyethyl)-
piperazine
pKa
MNPC
MDNPCb
PDNPC
a
Both the pKa and kN values were determined in aqueous
solution, at 25.0 °C and an ionic strength of 0.2 M (KCl).
11.24 26 ( 1
9.94
9.38
280 ( 17
166 ( 17
73 ( 10
520 ( 24
318 ( 12
85 ( 3
6.4 ( 0.1
1.7 ( 0.1
the pKa of the conjugate acids of the amines, were
statistically corrected with q ) 2 for piperazine and p )
2 for all the conjugate acids of the amines, except that
for piperazinium ion with p ) 4.10,11 With these corrected
values the Bro¨nsted-type plots (shown in Figure 1) were
obtained.
The kN values found for the quinuclidinolysis of MNPC
and MDNPC are shown in Table 5; the corresponding
Bro¨nsted plots are exhibited in Figure 2.
morpholine
8.78
7.98
5.81
5.9
1.6 ( 0.1
41 ( 4
9 ( 1
83 ( 3
1-formylpiperazine
piperazinium ion
1-(2-hydroxyethyl)-
piperazinium ion
0.26 ( 0.01
31 ( 2
0.031 ( 0.002 1.4 ( 0.1
5.4 ( 0.4
0.067 ( 0.005 1.1 ( 0.1c 5.0 ( 0.2
a
Both the pKa and kN values were determined in aqueous
b
solution, at 25.0 °C, and an ionic strength of 0.2 M (KCl). Data
from ref 3a, except otherwise stated. c Datum obtained in this
work.
The nonlinear Bro¨nsted plot for the reactions of SAA
with MNPC (Figure 1) can be explained by the mecha-
nism described in Scheme 1, where NH represents a SAA.
The Bro¨nsted break results from a change in the rate-
determining step, from breakdown of the zwitterionic
tetrahedral intermediate (T() to products (k2 step) to T(
formation (k1 step) as the amine basicity increases.2,3a,5-7,10
The curved line for MNPC in Figure 1 was calculated
by means of a semiempirical equation based on the
existence of the intermediate T( in Scheme 1.2,5-7,10 This
equation contains four parameters: â1 and â2, which are
the Bro¨nsted slopes at high and low pKa, respectively,
is the pseudo-first-order rate coefficient (excess of amine
was used throughout).
Plots of kobsd against [amine] at constant pH were
linear, in accordance with eq 2,
kobsd ) k0 + kN[amine]
(2)
where k0 and kN are the rate coefficients for hydrolysis
and aminolysis of the substrates, respectively. In general,
k0 and kN were pH independent, except in the reaction
of MNPC with piperidine, where k0 was dependent on
pH. The values of k0 for the hydrolysis of MNPC are
102k0/s-1 ) 0.5, 1.5, and 2.4 at pH ) 10,93, 11.24, and
11.55, respectively.
0
and kN0 and pKa , which are the corresponding values at
the center of the curvature. The Bro¨nsted curve for
MNPC was calculated with the following parameters: log
0
0
kN ) 0.232, pKa ) 9.3, â1 ) 0.3 and â2 ) 1.0 (n ) 7, R
) 0.994). The errors of the slopes are (0.1, and those of
The values of kN (obtained as the slopes of plots of eq
2) for the reactions of SAA with MNPC, MDNPC, and
PDNPC are shown in Table 4. The data for MDNPC,
mostly taken from a previous study,3a include the datum
for HPA (this work). These values, as well as those of
0
0
pKa and log kN are (0.2 and (0.1, respectively.
(11) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959;
p 159.
J . Org. Chem, Vol. 67, No. 25, 2002 8913

Castro et al.
SCHEME 1
The k3 values for MNPC and the thiono derivatives
should be similar, since the proton transfers from the
intermediates 1, 2, and 3 (PN ) 4-nitrophenyl) to the
corresponding free amine are thermodynamically favor-
able.12,13 Therefore, these processes are diffusion-con-
trolled and a value of 1010 s-1 M-1 has been estimated
for k3.12-14
The faster 4-nitrophenoxide expulsion (larger k2 value)
from intermediate 1 relative to that from 2 or 3 is
reasonable in view of the greater ability of O- in 1
compared to S- in 2 or 3 to form a double bond with C
and expel the nucleofuge. This has been ascribed to the
stronger π-bonding energy of the carbonyl group than
that of thiocarbonyl.15
F IGURE 2. Bronsted-type plots for the quinuclidinolysis of
MNPC (O) and MDNPC (b) in aqueous solution, at 25.0 °C
and an ionic strength of 0.2 M (KCl).
The quinuclidinolysis of MNPC shows a linear Bro¨n-
sted plot (Figure 2) of slope â ) 0.86 ( 0.05. This slope
value is consistent with a pathway through a zwitterionic
tetrahedral intermediate (T() whose breakdown to prod-
ucts is rate determining. Namely, these reactions behave
according to Scheme 1, with the formation of T( as an
The values of â1 and â2 for the aminolysis of MNPC
are in accord with those reported for other reactions
governed by stepwise mechanisms: â1 ) 0.1-0.3 and â2
) 0.8-1.1.2,5-7,10
The simple mechanism shown by the reactions of SAA
with MNPC (Scheme 1) is in contrast with the more
complex one exhibited by the reactions of the same
amines with methyl 4-nitrophenyl thionocarbonate (MNP-
TOC)12 and ethyl 4-nitrophenyl thionocarbonate (ENP-
TOC).13 In these cases there is an additional path for the
intermediate T( in Scheme 1: its deprotonation by the
corresponding amine to yield an anionic tetrahedral
intermediate (k3 step). On the basis of the nonlinear
upward kobsd vs [SAA] plots obtained in these reactions,
it was concluded that the rate constant for proton
transfer (k3[SAA]) is similar to that for the nucleofuge
expulsion from T( (k2).12,13 Since the value of k3 and the
concentration range of SAA are similar for the reactions
of MNPC and the thiono derivatives (see below), it follows
that the simpler reaction scheme for the carbonate arises
from its larger k2 value compared to that for the thiono-
carbonates MNPTOC and ENPTOC.
equilibrium step and the k2 step as rate limiting (k-1
k2 in Scheme 1).
.
The linear Bro¨nsted plot for the reactions of MNPC
with QUIN, in contrast to the biphasic plot for the
reactions of this substrate with SAA, can be attributed
to the fact that QUIN are better nucleofuges from a
tetrahedral intermediate than isobasic SAA.16 The pKa
0
value at the Bro¨nsted curvature center (pKa ) is related
to the k-1/k2 ratio, as described in eq 3,17
0
log(k-1/k2) ) (â2 - â1) (pKa - pKa)
(3)
where â1 and â2 are the Bro¨nsted slopes for formation
and breakdown of the intermediate T(, respectively.
(14) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1.
(15) Hill, S. V.; Thea, S.; Williams, A. J . Chem. Soc., Perkin Trans.
2 1983, 437. Cottrell, T. L. The Strengths of Chemical Bonds, 2nd ed;
Butterworth: London, 1959; p 275. Kwon, D. S.; Park, H. S.; Um, I.
H. Bull. Korean Chem. Soc. 1991, 12, 93.
(12) Castro, E. A.; Saavedra, C.; Santos, J . G.; Uman˜a, M. I. J . Org.
Chem. 1999, 64, 5401.
(13) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1996,
61, 3501.
(16) Castro, E. A.; Mun˜oz, P.; Santos, J . G. J . Org. Chem. 1999, 64,
8298.
(17) Castro, E. A.; Araneda, C. A.; Santos, J . G. J . Org. Chem. 1997,
62, 126.
8914 J . Org. Chem., Vol. 67, No. 25, 2002

Aminolysis of Methyl Aryl and Diaryl Carbonates
Since â1 and â2 are little dependent on the amine
nature1b,c,2,5,7,10 and pKa0 is larger for the QUIN reactions
0
(its pKa value is larger than 11.4, according to Figure
2), it follows from eq 3 that the k-1/k2 ratio is larger for
a given QUIN compared to an isobasic SAA. Since the k2
value should be independent of the amine nature and
basicity,5 it follows that the value of k-1 is larger for a
QUIN than for an isobasic SAA. Therefore, the lack of
Bro¨nsted curvature within the pKa range 7.5-11.4 for
the reactions of MNPC with QUIN can be explained by
a larger nucleofugality from T( of QUIN compared to an
isobasic SAA. A similar result was found in the reactions
of QUIN and SAA with ethyl S-(4-nitrophenyl) thiolcar-
bonate.16
The Bro¨nsted plots (statistically corrected) for the
reactions of MDNPC and PDNPC with SAA are shown
in Figure 1. The Bro¨nsted plot for the quinuclidinolysis
of the former substrate is exhibited in Figure 2. The three
plots are linear with slope (â) values of 0.48 ( 0.05, 0.39
( 0.05, and 0.51 ( 0.08, respectively.18 The magnitude
of these â values suggests that these reactions are
concerted. Similar â values have been found in the
concerted aminolysis of related substrates. Linear Bro¨n-
sted plots with slopes â ) 0.56 and 0.48 are exhibited in
the reactions of SAA with S-(2,4-dinitrophenyl) and
S-(2,4,6-trinitrophenyl) ethyl thiolcarbonates.19 In the
reactions of the same amines with methyl 2,4,6-trinitro-
phenyl carbonate, a â value of 0.36 was found.3b Also,
the concerted methoxycarbonyl transfer from N-(meth-
oxycarbonyl)isoquinolinium to pyridines shows a linear
Bro¨nsted plot of slope â ) 0.58.20
F IGURE 3. Bronsted-type plots for the reactions of MDNPC
(this work) with QUIN (O) and SAA (b) and those of EDNPTC
with QUIN (0, ref 16) and SAA (9, ref 19a) in aqueous
solution, at 25.0 °C and an ionic strength of 0.2 M (KCl).
0
the reactions of carbonates, a pKa value of 9.8 (7.8 + 2)
can be estimated for the hypothetical stepwise reactions
0
of SAA with MDNPC. Nevertheless, this pKa value
cannot be larger than that for the same aminolysis of
MNPC (9.3, this work), since 2,4-dinitrophenoxide is a
better leaving group than 4-nitrophenoxide.1b,c,5 There-
0
fore, it seems that the pKa increase (from pyridines to
SAA) of ca. 2 pKa units for acetates cannot be applied to
0
carbonates. We can only assume that the pKa value for
the hypothetical stepwise reactions of SAA with MDNPC
should be larger than 7.8 but smaller than 9.3.
As seen in Figure 1, there is no break within this pKa
range in the corresponding Bro¨nsted plot. Therefore, we
conclude that the reactions of SAA with MDNPC are
concerted. Since QUIN are better leaving groups from a
tetrahedral intermediate than isobasic SAA (see above),
it follows that the reactions of QUIN with MDNPC should
also be concerted, in view of the greater instability of the
hypothetical intermediate formed with QUIN than that
with SAA.
Another proof for concertedness of the above reactions
is the similar reactivity pattern of QUIN and SAA toward
MDNPC and its thiol derivative ethyl S-(2,4-dinitrophe-
nyl) thiolcarbonate (EDNPTC, see Figure 3).23,24 It is
known that the latter reactions are concerted.16,19a As
seen in this figure, these two amine series are equally
reactive toward a given substrate, and the Bro¨nsted slope
values for the aminolysis of these substrates are very
similar.
The value of the Bro¨nsted â alone is not sufficient for
the diagnosis of a concerted mechanism.21 It is also
0
important to calculate the hypothetical pKa value (pKa
at the center of the Bro¨nsted curvature) for a stepwise
mechanism; the lack of Bro¨nsted curvature within the
pKa range of the nucleophiles employed is a clear indica-
tion of a concerted mechanism.21
A biphasic Bro¨nsted plot was found in the stepwise
pyridinolysis of MDNPC in water, with pKa ) 7.8.2b It
0
is known that SAA are better nucleofuges from a tetra-
hedral intermediate than isobasic pyridines, as judged
0
by the larger pKa values found for the former amines.
0
For instance, the pKa values for the reactions of 2,4-
dinitrophenyl acetate with pyridines and SAA are 7.3 and
9.1, respectively.2c,22 Similarly, for the reactions of 2,4-
dinitrophenyl thiolacetate with pyridines and SAA, the
0
pKa values obtained are 6.6 and 8.9, respectively.10
0
Namely, there is a pKa increase of ca. 2 units in going
from pyridines to SAA. Assuming a similar increase for
The fact that the reactions of SAA with MNPC are
stepwise, whereas those of these amines with MDNPC
are concerted, means that the tetrahedral intermediate
T( is greatly destabilized by the introduction of a second
nitro group in the nucleofuge. This should be due to the
much greater nucleofugality of 2,4-dinitrophenoxide from
the hypothetical dinitro intermediate compared to that
of 4-nitrophenoxide from 1, which destabilizes it kineti-
cally. A similar situation was found in the reactions of
(18) The Bro¨nsted-type plot for the reactions of SAA with MDNPC
appeared as nonlinear in our original work (ref 3a) and the stepwise
mechanism was preferred to the concerted one. The reason for the
curved plot was that the point for the piperazinium ion was wrongly
located in the plot, although the kN value in the table was correct. In
this work we checked this kN value and obtained a similar one. With
this point rightly located, the Bro¨nsted plot becomes linear. To be sure
of the linearity, we also measured (in this work) the kN value for the
reaction of this substrate with 1-(2-hydroxyethyl)piperazinium ion (see
Table 2). As seen in Figure 1, with these two new points, the Bro¨nsted
plot for MDNPC looks linear.
(19) (a) Castro, E. A.; Iban˜ez, F.; Salas, M.; Santos, J . G J . Org.
Chem. 1991, 56, 4819. (b) Castro, E. A.; Salas, M.; Santos, J . G. J .
Org. Chem. 1994, 59, 30.
(20) Chrystiuk, E.; Williams, A. J . Am. Chem. Soc. 1987, 109, 3040.
(21) Williams, A. Acc. Chem. Res. 1989, 22, 387.
(23) The change of methoxy to ethoxy as the nonleaving group of
carbonates has very little effect on the rate constants involved in these
reactions.24
(24) Castro, E. A.; Cubillos, M.; Santos, J . G.; Tellez, J . J . Org. Chem.
1997, 62, 2512.
(22) Castro, E. A.; Ureta, C. J . Org. Chem. 1990, 55, 1676.
J . Org. Chem, Vol. 67, No. 25, 2002 8915

Castro et al.
SAA with the corresponding thiol derivatives: The reac-
tions of ethyl S-4-nitrophenyl thiolcarbonate are step-
wise,25 in contrast to those of EDNPTC, which are
concerted.19a
The reactions of SAA with 4-methylphenyl 4-nitrophe-
nyl carbonate in aqueous ethanol have been found to be
stepwise.6 It is known that a zwitterionic tetrahedral
intermediate (T() is more stabilized in the more polar
solvents.5 Therefore, these reactions should also be
stepwise in water. On the other hand, the change of Me
to H in the nonleaving group of the substrate should not
change the mechanism, as indicated by the similar
inductive effects26,27 of 4-MePhO and PhO.6 Therefore, it
is very likely that the reactions of SAA with PNPC in
water are stepwise.
Another indication that the above reactions are step-
wise is the fact that the quinuclidinolysis of PNPC is
stepwise, as evidenced by the linear Bro¨nsted plot of slope
1.0 obtained.5 If these reactions are stepwise, it is more
likely that the reactions of this substrate with SAA are
stepwise in view of the slower nucleofugality of SAA from
the intermediate T( than isobasic QUIN (see above),
which stabilizes this intermediate.16
The fact that the reactions of SAA with PDNPC in
water are concerted, whereas those of the same amines
with PNPC in the same solvent are stepwise, is another
example of the great destabilization caused to the T(
species by the addition of a second nitro group to the
nucleofuge of the substrate.
The greater reactivity of PDNPC than MDNPC toward
SAA (Table 4 and Figure 1) is in contrast to the larger
rate constant for SAA attack, to form the zwitterionic
tetrahedral intermediate (k1), on methyl 4-nitrophenyl
thionocarbonate compared to that on phenyl 4-nitrophe-
nyl thionocarbonate.12 The latter result was attributed
to the greater steric hindrance of phenyl relative to
methyl toward SAA attack, despite the greater electron-
withdrawing effect of PhO compared to MeO in the
corresponding thionocarbonates.12 These contradicting
results could be explained by assuming that steric
F IGURE 4. Bronsted-type plots for the reactions of PDNPC
with QUIN (O) and SAA (b) in aqueous solution, at 25.0 °C
and an ionic strength of 0.2 M (KCl). The data for QUIN was
replotted from ref 5.
hindrance is less important for a concerted mechanism
than a stepwise process through the tetrahedral species.
The quinuclidinolysis of PDNPC in water has been
described as stepwise, through a zwitterionic tetrahedral
intermediate.5 On the other hand, quinuclidines are
known to be better nucleofuges from a zwitterionic
intermediate than isobasic SAA (see above).16 This means
that quinuclidines destabilize the tetrahedral intermedi-
ate relative to isobasic SAA.16 Since we have found in
this work that the reactions of SAA with PDNPC are
concerted, it is doubtful that the reactions of quinuclid-
ines with the same substrate be stepwise. Careful
examination of the Bro¨nsted-type plot obtained for the
latter reactions shows that the points are better accom-
modated by a linear relation rather than a biphasic one
(see Figure 4). The linear plot shows a slope â ) 0.36 (
0.05 (R2 ) 0.98), which is very similar to that found by
us in the reactions of SAA with the same substrate
(Figure 4, â ) 0.39 ( 0.05).
(25) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1994,
59, 3572.
(26) The inductive effects exerted by a substituent in a tetrahedral
species are more important than the resonance effects.27
(27) Sayer, J . M.; J encks, W. P. J . Am. Chem. Soc. 1973, 95, 5637.
Fox, J . P.; J encks, W. P. J . Am. Chem. Soc. 1974, 96, 1436.
Ack n ow led gm en t. We thank FONDECYT of Chile
(project 1020538) for financial assistance.
J O026390K
8916 J . Org. Chem., Vol. 67, No. 25, 2002