Concerted pyridinolysis of aryl 2,4,6-trinitrophenyl carbonates

Article abstract of DOI:10.1021/jo901137f

(Chemical Equation Presented) The Bronsted plots for the title reactions are linear with slopes of 0.53-0.56. The magnitude of the slopes and the fact that there are no breaks at the predicted pK_a for stepwise mechanisms indicate that these rea

Full text of DOI:10.1021/jo901137f

pubs.acs.org/joc
tetrahedral intermediate (T() on the reaction pathway. On
Concerted Pyridinolysis of Aryl 2,4,6-Trinitrophenyl
Carbonates
the other hand, those aminolysis reactions (except
pyridinolysis) involving very reactive carbonates are driven
by a concerted mechanism; namely, these reactions occur in a
single step with no T( intermediate.6 Among such very reactive
substrates are 2,4-dinitrophenyl and 2,4,6-trinitrophenyl meth-
yl carbonates (1 and 2, respectively) and 4-X-phenyl 2,4-
dinitrophenyl carbonates, with X=H, Me, and Cl (3-5).6
In contrast, the pyridinolysis reactions of all the above very
reactive carbonates (1-5) are stepwise.9,10 The change in
mechanism, from stepwise for pyridines to concerted for the
other amines, has been explained by the greater nucleofugality
fromT( of the other amines relative to isobasic pyridines.4,9-11
This destabilizes T(, and the mechanism changes to concerted.
To extend our investigations on the pyridinolysis of very
reactive carbonates and with the aim to find out whether the
pyridinolysis of some very reactive carbonates can be con-
certed, we decided to study the reactions of 4-X-phenyl 2,4,6-
trinitrophenyl carbonates (X=H, Me, and Cl, carbonates 6,
7, and 8) with a series of pyridines in aqueous ethanol. We
found that these reactions are concerted. To our knowledge,
this is the first time a concerted pyridinolysis of carbonates in
water or mixed aqueous solvents is reported.
ꢀ
Enrique A. Castro,* Mariela Ramos, and Jose G. Santos*
´
ꢀ
Facultad de Quımica, Pontificia Universidad Catolica de
Chile, Casilla 306, Santiago 6094411, Chile
ecastro@uc.cl
Received May 29, 2009
The Brønsted plots for the title reactions are linear with
slopes of 0.53-0.56. The magnitude of the slopes and the
fact that there are no breaks at the predicted pKa for
stepwise mechanisms indicate that these reactions are
concerted. This finding is in great contrast to the stepwise
mechanisms found for the pyridinolysis of other carbo-
nates. The concerted mechanism is attributed to the fact
that the title carbonates possess two O-aryl groups, one of
them being an exceptionally good nucleofuge.
The kinetics of the reactions of primary and secondary
amines and quinuclidines with reactive carbonates has been
investigated to some extent.1-6 On the other hand, the
pyridinolysis of these compounds has received little atten-
tion.7-10 Most of the above aminolysis reactions are gov-
erned by a stepwise mechanism, with a zwitterionic
The rate law obtained for the pyridinolysis of the title
carbonates (under excess amine) is shown in eq 1, where
TNP- and S represent 2,4,6-trinitrophenoxide anion and the
substrate, respectively, and kobsd is the pseudo-first-order rate
constant. For the reactions of these substrates with the series of
pyridines, linear plots of kobsd against concentration of free
amine ([N]) were found, as depicted by eq 2, where k0 and kN are
the rate constants for solvolysis and pyridinolysis of the sub-
strates, respectively. The k0 values were much smaller than those
of kN[N] ineq2. The slopes(kN) were independent of pH for the
reactions of all pyridines, with the exception of 4-oxypyridine.
(1) (a) Koh, H. J.; Lee, J.-W.; Lee, H. W.; Lee, I. Can. J. Chem. 1998, 76,
710. (b) Tundo, P.; Rossi, L.; Loris, A. J. Org. Chem. 2005, 70, 2219.
(2) (a) Um, I.-H.; Park, H.-R.; Kim, E.-Y. Bull. Korean Chem. Soc. 2003,
24, 1251. (b) Um, I.-H.; Kim, E.-Y.; Park, H.-R.; Jeon, S.-E. J. Org. Chem.
2006, 71, 2302. (c) Um, I.-H.; Yoon, S.; Park, H.-R.; Han, H.-J. Org. Biomol.
Chem. 2008, 6, 1618.
(3) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6963.
(4) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970.
(5) Castro, E. A.; Andujar, M.; Toro, A.; Santos, J. G. J. Org. Chem.
2003, 68, 3608.
(6) (a) Castro, E. A.; Cubillos, M.; Santos, J. G. J. Org. Chem. 2001, 66,
6000. (b) Castro, E. A.; Aliaga, M.; Campodonico, P.; Santos, J. G. J. Org.
Chem. 2002, 67, 8911. (c) Castro, E. A.; Campodonico, P.; Toro, A.; Santos,
J. G. J. Org. Chem. 2003, 68, 5930. (d) Castro, E. A.; Gazitua, M.; Santos, J.
G. J. Org. Chem. 2005, 70, 8088.
d½TNP-ꢀ
¼ kobsd½Sꢀ
ð1Þ
ð2Þ
dt
kobsd ¼ k0þkN½Nꢀ
(7) (a) Fife, T. H.; Hutchins, J. E. C. J. Am. Chem. Soc. 1981, 103, 4194.
(b) Brunelle, D. J. Tetrahedron Lett. 1982, 23, 1739.
(8) Bond, P. M.; Moodie, R. B. J. Chem. Soc., Perkin Trans. 2 1976, 679.
(9) (a) Castro, E. A.; Gil, F. J. J. Am. Chem. Soc. 1977, 99, 7611.
~
(b) Castro, E. A.; Ibanez, F.; Lagos, S.; Schick, M.; Santos, J. G. J. Org.
For the reactions with 4-oxypyridine, the values of kN were
pH-dependent. We attribute this to the fact that pH values
Chem. 1992, 57, 2691.
(10) Castro, E. A.; Acuna, M.; Soto, C.; Trujillo, C.; Vasquez, B.; Santos,
~
J. G. J. Phys. Org. Chem. 2008, 21, 816.
(11) Baidya, M.; Kobayashi, S.; Brotzel, F.; Schmidhammer, U.; Riedle,
E.; Mayr, H. Angew. Chem., Int. Ed. 2007, 46, 6176.
6374 J. Org. Chem. 2009, 74, 6374–6377
Published on Web 07/17/2009
DOI: 10.1021/jo901137f
r
2009 American Chemical Society

Castro et al.
JOCNote
SCHEME 1
much lower than the pKa of its conjugate acid had to be used,
due to the high reactivity of this pyridine. At these low
pH values, there is a competition between 4-oxypyridine
(species 9) and 4-hydroxypyridine (species 10) to attack the
substrate by their pyridinic nitrogen atoms (see Scheme 1).12
The values of K1 and K2 were determined experimentally in
44 wt % ethanol-water; the corresponding pKa values are
11.5 and 3.2, respectively.13 We have estimated the pK3 value
as follows: The pKa of a phenol is given by pKa=9.92 -
2.23σ, where σ is the Hammett substituent constant.14 Since
the σP value for a ring N is 0.83,14 this equation gives a pKa
(pK3) value of 8.07 for species 10. The pK4 value can be
deduced from pK4=pK1 þ pK2 - pK3, which yields pK4=
6.6. According to these pKa values, the main competition for
attack to a carbonate is between species 9 and 10, by their N
atoms.
FIGURE 1. Plots of kN,obsd/F10 against F9/F10 for the pyridinolysis
of carbonates 6-8 in 44 wt % ethanol-water, at 25.0 °C, and an
ionic strength of 0.2 M (KCl).
the same as that of the Hammett p-substituent constants in
the nonleaving group of the substrates: σP values in water for
Cl, H, and Me are þ0.23, 0.0, and -0.17, respectively.17
A
Hammett plot (log kN vs σP, not shown) for the reactions of
carbonates 6-8 with different pyridines shows a reaction
constant F of ca. 1.0. The positive value of this parameter is in
accordance with the fact that the greater the electron-with-
drawing effect from the nonleaving group of the carbonate,
the more positive the carbonyl carbon and, therefore, the
more prone it becomes to nucleophilic attack.
Therefore, these reactions can be depicted by eq 3, where
k9 and k10 are the nucleophilic rate constants (kN) of species 9
and 10; F9 and F10 are their corresponding amine fractions,
and [N]tot is the concentration of total amine.
The Brønsted plots for the pyridinolysis of carbonates 6-
8, obtained with the data in Table 1, are shown in Figure 2.
The slopes (β) of the linear Brønsted plots are 0.53 ( 0.02,
0.53 ( 0.02, and 0.56 ( 0.02 for the reactions of carbonates 6,
7, and 8, respectively. The magnitude of the slopes is in
accordance with a concerted mechanism. In fact, the con-
certed reactions of secondary alicyclic amines, quinuclidines,
anilines, and other primary amines with very reactive carbo-
nates (such as 1-5) in aqueous solutions show linear
Brønsted plots with slopes in the range of 0.4-0.7.6 Never-
theless, the pyridinolysis of these very reactive carbonates
(1-5) either in water or in aqueous ethanol solution is
governed by a stepwise mechanism, as judged by the biphasic
(two linear portions and a curvature between) Brønsted plots
found.9,10
kobsd ¼ k0þðk9F9þk10F10Þ½Nꢀtot
ð3Þ
Plots of kobsd against [N]tot at constant pH were linear,
with the slopes (kN,obsd) pH-dependent. Equation 3 can be
rearranged to give eq 4. Plots of kN,obsd/F10 versus F9/F10
were linear, with intercept k10 and slope k9 (see Figure 1).
kN;obsdF10 ¼ k10þk9F9=F10
The values of F9 and F10 were calculated from eqs 5 and 6.15
ð4Þ
2
1=F9 ¼ 1þ½Hþꢀ=K1þ½Hþꢀ=K3þ½Hþꢀ =K1K2
ð5Þ
ð6Þ
F10 ¼ F9½Hþꢀ=K3
The kN values obtained for the reactions of all the pyr-
idines with the title carbonates, either through eq 2 or eq 4 (k9
for 4-oxypyridine),16 are shown in Table 1.
According to the kN values in Table 1, the order of
reactivities of these carbonates is 8>6>7. This sequence is
In order to confirm that the pyridinolyses of the title
carbonates are concerted, it is necessary to estimate the
0
pKa position at the center of the curvature (pKa ) of the
biphasic Brønsted plot for a hypothetical stepwise mechan-
ism.18,19 The stepwise pyridinolysis of carbonate 1 shows a
biphasic Brønsted plot with pKa0 =7.8, whereas the same
aminolysis of carbonate 2 shows pKa0=6.5. Namely, for
stepwise mechanisms, the change of 2,4-dinitrophenoxide by
2,4,6-trinitrophenoxide as the leaving group lowers the
Brønsted break by 1.3 pKa units. If this shift can be extended
(12) Although there is prototropy between species 10 and 4-pyridone, this
was not included in Scheme 1 for clarity reasons (see Perrin, D. D.; Dempsey,
B.; Serjeant, E. P. pKa Prediction for Organic Acids and Bases; Chapman and
Hall: London, 1981; p 55). The existence of this prototropy does not affect
the kinetic results.
(13) Castro, E. A.; Aguayo, R.; Bessolo, J.; Santos, J. G. J. Org. Chem.
2005, 70, 3530.
(14) Perrin, D. D.; Dempsey, B.; Serjeant, E. P. pKa Prediction for
Organic Acids and Bases; Chapman and Hall: London, 1981, p 56; p 139.
(15) Castro, E. A.; Ureta, C. J. Chem. Soc., Perkin Trans. 2 1991, 63.
(16) The kN value for 4-hydroxypyridine (k10) was not included in Table 1
due to the large error involved in its determination.
(17) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(18) (a) Chrystiuk, E.; Williams, A. J. Am. Chem. Soc. 1987, 109, 3040.
(b) Williams, A. Acc. Chem. Res. 1989, 22, 387.
(19) Williams, A. Free Energy Relationships in Organic and Bio-Organic
Chemistry; The Royal Society of Chemistry: Cambridge, 2003; p 171.
J. Org. Chem. Vol. 74, No. 16, 2009 6375

Castro et al.
JOCNote
TABLE 1. Values of pKa for the Conjugate Acids of Pyridines and kN Values for the Pyridinolysis of Carbonates 6, 7, and 8a
kN/s-1M-1
pyridine substituent
4-O-b
4-NH2
none
3-CONH2
pKa
6
7
8
11.5
8.98
4.63
2.67
0.80
(1.0 ( 0.2) ꢁ 105
5100 ( 100
51 ( 1
2.4 ( 0.1
0.15 ( 0.02
(6.1 ( 0.4) ꢁ 104
4340 ( 140
34 ( 1
1.5 ( 0.1
0.12 ( 0.01
(5.1 ( 0.3) ꢁ 105
10300 ( 300
90 ( 3
3.8 ( 0.2
0.40 ( 0.02
4-CN
aBoth the pKa and kN values were determined in 44 wt % ethanol-water, at 25.0 °C, and an ionic strength of 0.2 M (KCl).
bFor this pyridine, the kN values are those of k9 in eqs 3 and 4.
SCHEME 2
also produce such a change. For instance, the pyridinolysis
of carbonate 2 in water is stepwise.9b Substitution of MeO by
PhO as the nonleaving group (to yield carbonate 6) and
water to aqueous ethanol as solvent changes the mechanism
FIGURE 2. Brønsted plots obtained for the pyridinolysis of carbo-
nates 6-8 in 44 wt % ethanol-water, at 25.0 °C, and an ionic
strength of 0.2 M (KCl). For reasons of clarity, the points for 8 were
shifted one log unit upward and those for 7 were shifted one log unit
downward.
from stepwise to concerted. It is unlikely that this change in
mechanism is due to the change of solvent, in view of the
similar polarity of both solvents. On the other hand, sub-
stitution of Me by PhO also changes the mechanism, as
shown by the fact that the pyridinolysis of 2,4,6-trinitrophe-
nyl acetate in water is stepwise,9b in comparison with the
concerted pyridinolysis of carbonate 6. This is in agreement
with the fact that the aminolysis (secondary alicyclic amines)
of 2,4-dinitrophenyl acetate in water is stepwise,21 whereas
the same aminolysis of 2,4-dinitrophenyl phenyl carbonate
(3) in the same solvent is concerted.6b
The fact that the pyridinolyses of carbonates 1-5 are
governed by stepwise mechanisms, whereas the reactions of
the same carbonates with secondary alicyclic amines,6a,6b
anilines,6b,6c and quinuclidines22 are concerted, can be ex-
plained by the poorer nucleofugality of pyridines from the
intermediate T( compared with the other isobasic amines.4,15,23
This stabilizes the intermediate T( formed with pyridines, and
the stepwise pathway becomes of lower free energy relative to
the concerted mechanism for the other aminolyses.
to diaryl carbonates, and knowing that the Brønsted break for
0
the stepwise pyridinolysis of carbonate 3 is pKa =8.0,10 one
can predict a pKa0 value of 8.0 - 1.3 = 6.7 for the hypothetical
stepwise pyridinolysis of carbonate 6. Similarly, since the same
aminolyses of carbonates 4 and 5 show pKa0 values of 8.3,10
a
pKa0 value of 7.0 can be estimated for the hypothetical stepwise
pyridinolyses of carbonates 7 and 8. Perusal of the Brønsted
plots in Figure 2 shows that there are no breaks at pKa 6.7-7.0.
Therefore, the stepwise mechanism can be safely discarded for
the pyridinolysis of the title carbonates. Namely, the concerted
mechanism can be confirmed for these reactions (Scheme 2).
To our knowledge, this is the first time that a concerted
pyridinolysis of a carbonate in water or in its mixtures with
other solvents is reported. Even very reactive carbonates
such as 4-nitrophenyl 2,4-dinitrophenyl and bis(2,4-dinitro-
phenyl) carbonates exhibit stepwise pyridinolysis in aqueous
ethanol.10 The concerted mechanism for the title reactions
can be attributed to the great destabilization of the zwitter-
ionic tetrahedral intermediate (T() formed in the above
stepwise pyridinolyses by the change of the leaving group
to 2,4,6-trinitrophenoxide. This means that the intermediate
T( is so unstable that either it does not exist (enforced
concerted mechanism) or the intermediate still exists but
the concerted pathway has lower energy.20
In conclusion, we have found in this work that the
pyridinolysis reactions of carbonates 6-8 in aqueous etha-
nol are ruled by a concerted mechanism. To our knowledge,
this is the first report of a concerted pyridinolysis of any ester
or carbonate in water or mixed aqueous solvents. We
attribute this to the fact that the title carbonates are very
(21) Castro, E. A.; Ureta, C. J. Org. Chem. 1990, 55, 1676.
(22) Castro, E. A.; Campodonico, P. R.; Contreras, R.; Fuentealba, P.;
Santos, J. G.; Leis, J. R.; Garcia-Rio, L.; Saez, J. A.; Domingo, L. R.
Tetrahedron 2006, 62, 2555.
Not only the change of leaving group can cause a change in
mechanism. The substitution of the nonleaving group can
(20) (a) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161. (b) Jencks, W. P.
Chem. Soc Rev. 1981, 10, 345. (c) Williams, A. Chem. Soc. Rev. 1994, 23, 93.
(23) (a) Castro, E. A. Chem. Rev. 1999, 99, 3505. (b) Castro, E. A. J. Sulfur
Chem. 2007, 28, 401.
6376 J. Org. Chem. Vol. 74, No. 16, 2009

Castro et al.
JOCNote
reactive due to their diaryl nature and the very large nucleo-
fugality of the leaving group. Therefore, the hypothetical
tetrahedral intermediate should be extremely unstable or
nonexistent. This makes the stepwise pathway highly ener-
getic, and the concerted mechanism takes over.
Kinetic Measurements. These were carried out by means of a
diode array spectrophotometer in 44 wt % ethanol aqueous
solution at 25.0 ( 0.1 °C and an ionic strength of 0.2 M (KCl).
The reactions were studied by monitoring the appearance of
2,4,6-trinitrophenoxide anion.
All of the reactions were examined under excess amine over
the substrate. The initial substrate concentration was about 5 ꢁ
10-5 M, and in most cases, the pH was maintained by using
external buffer (0.01 M phosphate or 0.01 M acetate buffer).
Experimental Section
Materials. Pyridines were distilled or crystallized before use.
To our knowledge, carbonates 6-8 have not been synthesized.
These were prepared by a modification of the general method
described.3 Equimolar quantities of anhydrous picric acid and
the corresponding chloroformate, both in dry dichloromethane
solution and in the presence of pyridine, were reacted under
nitrogen for 4 h at room temperature. The solid phase was
disregarded and the liquid phase washed three times with cold
water, dried with magnesium sulfate, and the solvent eliminated.
The products were obtained by crystallization of the solids in
hexane. These were identified by the following properties.
Phenyl 2,4,6-trinitrophenyl carbonate (6): 1H NMR(400 MHz,
CDCl3) δ 7.31-7.37 (m, 3H), 7.47 (t, 2H), 9.21 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 120.8, 125.4, 127.6, 130.2, 142.9, 143.9,
144.8, 149.0, 150.9; HRMS calcd for C13H7N3O8 349.01823,
found 349.01818.
Pseudo-first-order rate coefficients (kobsd
) were found
throughout and determined by means of the spectrophotometer
kinetics software for first-order reactions. The experimental
conditions of the reactions and the values of kobsd and amine
concentrations, together with their corresponding plots, are
shown in Tables S1-S3 in Supporting Information.
Determination of pKa. The pKa value for the conjugate acid
of 4-cyanopyridine was determined spectrophotometrically at
276 nm, by the reported method.24 The experimental conditions
usedwerethe sameas thosefor the kineticmeasurements(44wt%
ethanol-water, 25.0 ( 0.1 °C, ionic strength 0.2 M). Under these
conditions, the pKa obtained for the conjugate acid of 4-cyano-
pyridine was 0.8.
Product Studies. One of the products of the reactions under
scrutiny was identified as 2,4,6-trinitrophenoxide anion, as
shown by a comparison of the UV-vis spectra after completion
of the reactions with that of an authentic sample under the same
experimental conditions.
4-Methylphenyl 2,4,6-trinitrophenyl carbonate (7): 1H MNR
(400 MHz, acetone-d6) δ 7.23 (d, 2H), 7.34 (d, 2H), 9.35 (s, 2H),
2.37 (s, 3H); 13C MNR (100 MHz, acetone-d6) δ 19.9, 120.3,
125.8, 130.4, 137.2, 141.8, 143.4, 145.2, 148.8, 149.1; HRMS
calcd for C14H9N3O9 363.03388, found 363.0332.
Acknowledgment. We thank MECESUP of Chile (Project
UCH-0601) and FONDECYT of Chile (Project 1060593) for
financial support.
4-Chlorophenyl 2,4,6-trinitrophenyl carbonate (8): 1H MNR
(400 MHz, acetone-d6) δ 7.43 (d, 2H), 7.59 (d, 2H), 9.36 (s, 2H);
13C MNR (100 MHz, acetone-d6) δ 122.5, 125.9, 130.1, 132.3,
141.6, 143.4, 145.2, 148.8, 149.5; HRMS calcd for C13H6ClN3O9
382.97926, found 382.97911.
Supporting Information Available: Tables S1-S3 contain-
ing [amine], kobsd, and pH data for the title reactions, and H
1
NMR and 13C NMR spectra of carbonates 6-8. This material is
available free of charge via the Internet at http://pubs.acs.org.
(24) Albert, A.; Serjeant, E. P. The Determination of Ionization Constants,
2nd ed.; Champman and Hall: London, 1971; p 44.
J. Org. Chem. Vol. 74, No. 16, 2009 6377