Kinetics and Mechanism of the Pyridinolysis of Alkyl Aryl Thionocarbonates

Article abstract of DOI:10.1021/jo961921o

The reactions of methyl 4-nitrophenyl, ethyl 4-nitrophenyl, and ethyl 2,4-dinitrophenyl thionocarbonates (MNPTOC, ENPTOC, and EDNPTOC, respectively) with a series of 3- and 4-substituted pyridines are subjected to a kinetic investigation in water, 25.0°C, ionic strength 0.2 M (maintained with KCl). Under amine excess, pseudo-first-order rate coefficients (k_obsd) are obtained, which are linearly proportional to the free-pyridine concentration. The second-order rate coefficients (k_N) are obtained as the slopes of these plots. The Broensted-type plots found for the two mononitro derivatives coincide in one straight line (same slope and intercept) of slope β=1.0. The EDNPTOC pyridinolysis shows a curved Broensted-type plot with slopes β₁= 0.1 (high pK_a], β₂ = 1.0 (low pK_a), and pK_a^o = 6.8 (pK_a value at the center of curvature). These plots are consistent with the existence of a zwitterionic tetrahedral intermediate (T^±) on the reaction pathway whereby expulsion of aryloxide anion from T^± is rate determining (k₂ step) at low pK_a for EDNPTOC (and in the whole pK_a range for MNPTOC and ENPTOC), and there is a change to rate-limiting formation of T^± (k₁ step) at high pK_a for EDNPTOC. Comparison of these Broensted plots among them and with similar ones permits the following conclusions: (i) There is no variation of k_N by substitution of methoxy by ethoxy as the nonleaving group of the substrate. (ii) The pK_a^o value is smaller for the less basic aryloxide nucleofuge due to a larger k₂₅ value. (iii) The change of C=S by C=O as the electrophilic center of the substrate results in larger values for both k₁ (amine expulsion rate) and k₂, and also a larger k_-1/k₂ ratio for the carbonyl derivative. There is also an increase of k₁ by the same change. The K₁k₂ (= k₁k₂/k_-1) values are larger for the pyridinolysis of methyl 2,4-dinitrophenyl and methyl 4-nitrophenyl carbonates compared to the corresponding thionocarbonates (EDNPTOC and MNPTOC, respectively). (iv) Pyridines are more reactive than isobasic secondary alicyclic amines toward ENPTOC when either the k₁ step or the k₂ step is rate limiting. This is explained by the softer nature of pyridines than alicyclic amines (k₁ step) and the greater nucleofugality (k_-1) of the latter amines than isobasic pyridines, leading to a larger k₂/k_-1 ratio for pyridines (k₂ is little affected by the amine nature), and therefore a larger K₁k₂ value when the k₂ step is rate determining.

Full text of DOI:10.1021/jo961921o

2512
J . Org. Chem. 1997, 62, 2512-2517
Kin etics a n d Mech a n ism of th e P yr id in olysis of Alk yl Ar yl
Th ion oca r bon a tes
Enrique A. Castro,* Mar´ıa Cubillos, J ose´ G. Santos,* and J imena Te´llez
Facultad de Quı´mica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
Received October 10, 1996X
The reactions of methyl 4-nitrophenyl, ethyl 4-nitrophenyl, and ethyl 2,4-dinitrophenyl thionocar-
bonates (MNPTOC, ENPTOC, and EDNPTOC, respectively) with a series of 3- and 4-substituted
pyridines are subjected to a kinetic investigation in water, 25.0 °C, ionic strength 0.2 M (maintained
with KCl). Under amine excess, pseudo-first-order rate coefficients (kobsd) are obtained, which are
linearly proportional to the free-pyridine concentration. The second-order rate coefficients (kN)
are obtained as the slopes of these plots. The Bro¨nsted-type plots found for the two mononitro
derivatives coincide in one straight line (same slope and intercept) of slope â ) 1.0. The EDNPTOC
pyridinolysis shows a curved Bro¨nsted-type plot with slopes â1 ) 0.1 (high pKa), â2 ) 1.0 (low pKa),
and pKao ) 6.8 (pKa value at the center of curvature). These plots are consistent with the existence
of a zwitterionic tetrahedral intermediate (T() on the reaction pathway whereby expulsion of
aryloxide anion from T( is rate determining (k2 step) at low pKa for EDNPTOC (and in the whole
pKa range for MNPTOC and ENPTOC), and there is a change to rate-limiting formation of T( (k1
step) at high pKa for EDNPTOC. Comparison of these Bro¨nsted plots among them and with similar
ones permits the following conclusions: (i) There is no variation of kN by substitution of methoxy
by ethoxy as the nonleaving group of the substrate. (ii) The pKao value is smaller for the less basic
aryloxide nucleofuge due to a larger k2 value. (iii) The change of CdS by CdO as the electrophilic
center of the substrate results in larger values for both k-1 (amine expulsion rate) and k2, and also
a larger k-1/k2 ratio for the carbonyl derivative. There is also an increase of k1 by the same change.
The K1k2 () k1k2/k-1) values are larger for the pyridinolysis of methyl 2,4-dinitrophenyl and methyl
4-nitrophenyl carbonates compared to the corresponding thionocarbonates (EDNPTOC and
MNPTOC, respectively). (iv) Pyridines are more reactive than isobasic secondary alicyclic amines
toward ENPTOC when either the k1 step or the k2 step is rate limiting. This is explained by the
softer nature of pyridines than alicyclic amines (k1 step) and the greater nucleofugality (k-1) of the
latter amines than isobasic pyridines, leading to a larger k2/k-1 ratio for pyridines (k2 is little affected
by the amine nature), and therefore a larger K1k2 value when the k2 step is rate determining.
In tr od u ction
etates and dithioacetates.8 Also, the reactions of the
above and other amines with aryl thiobenzoates have
been subjected to kinetic investigations.9 We have also
examined the reactions of secondary alicyclic amines with
aryl thiolcarbonates10 and thionocarbonates.11
In spite of the above works on the aminolysis (mainly
secondary alicyclic amines) of aryl thioesters and thio-
carbonates, little is known on the influence of the amine
nature and the nonleaving, leaving, and electrophilic
groups of the substrate on the kinetics and mechanism
of these reactions.
We perform in the present work a kinetic study on the
pyridinolysis of methyl 4-nitrophenyl thionocarbonate
(MNPTOC), ethyl 4-nitrophenyl thionocarbonate (ENP-
TOC), and ethyl 2,4-dinitrophenyl thionocarbonate (ED-
NPTOC). The aim is to analyze the effect of the following
groups on the kinetics and mechanism of these reac-
tions: (i) Nonleaving (or acyl) group, by comparison of
the pyridinolysis of MNPTOC and ENPTOC; (ii) leaving
group, by comparison of the pyridinolysis of EDNPTOC
Although the aminolysis reactions of aryl acetates,1,2
benzoates,3 and carbonates4-7 have been extensively
studied and their mechanisms have been clarified, less
is known on the mechanism of the aminolysis of their
thio derivatives.
We have recently studied the kinetics and mechanism
of the reactions of secondary amines with aryl thiolac-
X Abstract published in Advance ACS Abstracts, March 1, 1997.
(1) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96,
7018.
(2) Akiyama, M. ; Hara, Y.; Tanabe, M. J . Chem. Soc., Perkin Trans.
2 1978, 288. Deady, L. W.; Finlayson, W. L. Aust. J . Chem. 1980, 33,
2441. Cox, M. M.; J encks, W. P. J . Am. Chem. Soc. 1981, 103, 572. de
Rossi, R. H.; Nu´n˜ez, A. Int. J . Chem. Kinet. 1983, 15, 1099. Kovach, I.
M.; Belz, M.; Larson, M.; Rousy, S.; Schowen, R. L. J . Am. Chem. Soc.
1985, 107, 7360. Neuvonen, H. J . Chem. Soc., Perkin Trans. 2 1987,
159. Yoh, S.-D.; Kang, J .-K.; Kim, S.-H. Bull. Korean Chem. Soc. 1989,
10, 204. Neuvonen, H. J . Chem. Soc., Perkin Trans. 2 1995, 951. Lee,
J .-P.; Yoh, S.-D. Bull Korean Chem. Soc. 1996, 17, 211. Arcelli, A.;
Concilio, C. J . Org. Chem. 1996, 61, 1682.
(3) (a) Menger, F. M.; Smith, J . H. J . Am. Chem. Soc. 1972, 94, 3824.
(b) Ciuffarin, E.; Loi, A.; Isola, M.; Lupetti, A.; Sagramora, L.; Senatore,
L. J . Org. Chem. 1983, 48, 1047. (c) Khan, M. N. J . Org. Chem. 1983,
48, 2046. (d) Castro, E. A.; Valdivia, J . L. J . Org. Chem. 1986, 51, 1668.
(e) Koh, H. J .; Lee, H. C.; Lee, H. W.; Lee, I. Bull. Korean Chem. Soc.
1995, 16, 839.
(8) (a) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
63. (b) Castro, E. A.; Iba´n˜ez, F.; Santos, J . G.; Ureta, C. J . Org. Chem.
1992, 57, 7024.
(4) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
6970.
(5) Castro, E. A.; Gil, F. J . J . Am. Chem. Soc. 1977, 99, 7611.
(6) Bond, P. M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1976,
679.
(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. (c) Castro,
E. A.; Iba´n˜ez, F.; Lagos, S.; Schick, M.; Santos, J . G. J . Org. Chem.
1992, 57, 2691. (d) Castro, E. A.; Iba´n˜ez, F.; Saitua, A. M.; Santos, J .
G. J . Chem. Res. (S) 1993, 56.
(9) (a) Oh, H. K.; Shin, C. H.; Lee, I. J . Chem. Soc., Perkin Trans. 2
1995, 1169. (b) Um, I.-H.; Kwon, H.-J .; Kwon, D.-S.; Park, J .-Y. J .
Chem. Res. (S) 1995, 301, (M) 1801-1817. (c) Oh, H. K.; Shin, C. H.;
Lee, I. Bull Korean Chem. Soc. 1995, 16, 657.
(10) (a) Castro, E. A.; Iba´n˜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. (c) Castro, E. A.; Cubillos, M.; Santos, J . G.
J . Org. Chem. 1994, 59, 3572.
(11) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1996,
61, 3501.
S0022-3263(96)01921-4 CCC: $14.00 © 1997 American Chemical Society

Pyridinolysis of Alkyl Aryl Thionocarbonates
J . Org. Chem., Vol. 62, No. 8, 1997 2513
P r od u ct Stu d ies. 4-Nitrophenol and 2,4-dinitrophenol
(and/or their conjugate bases) were identified as one of the final
products of the corresponding reactions. This was carried out
by comparison of the UV-vis spectra after completion of the
reactions with those of authentic samples at the same experi-
mental conditions.
The appearance and later disappearance of an intermediate
was spectrophotometrically detected during the reactions. For
example, the intermediate found in the reaction of MNPTOC
with 4-aminopyridine has a λmax ) 315 nm. We identified this
intermediate as 1-(methoxythiocarbonyl)-4-aminopyridinium
ion.
with those of ENPTOC and O-ethyl 2,4-dinitrophenyl
dithiocarbonate;12 (iii) electrophilic group (CdO or CdS),
by comparison of the pyridinolysis of MNPTOC and
methyl 4-nitrophenyl carbonate;6 (iv) nucleophilic group,
by comparison of the pyridinolysis of ENPTOC with the
reactions of secondary alicyclic amines with the same
substrate.11
Exp er im en ta l Section
Ma ter ia ls. The pyridines were purified as reported.13
Ethyl 4-nitrophenyl thionocarbonate (ENPTOC) was synthe-
sized as described previously.11,14 Methyl 4-nitrophenyl thion-
ocarbonate (MNPTOC) and ethyl 2,4-dinitrophenyl thionocar-
bonate (EDNPTOC) have not been synthesized before, to our
knowledge. EDNPTOC was prepared by a general method,
using O-ethyl chlorothioformate and 2,4-dinitrophenol in py-
ridine.14 MNPTOC could not be prepared in satisfactory yield
by the general method14 employed for ENPTOC and EDNP-
TOC. MNPTOC was synthesized from potassium methoxide
and bis(4-nitrophenyl) thionocarbonate. The latter was pre-
pared by a modification of a reported procedure.14
Resu lts a n d Discu ssion
The reactions subjected to the present investigation
can be kinetically described by eqs 1 and 2, where Ar is
4-nitrophenyl or 2,4-dinitrophenyl, S represents the
d[ArO-]
dt
kobsd ) ko + kN[N]
) kobsd[S]
(1)
(2)
The synthesis of MNPTOC was carried out as follows: To
methanol (20 mL) in a Schlend round-bottomed flask was
added potassium (0.024 g) slowly under N2 atmosphere. After
all potassium was reacted, the excess of methanol was
evaporated off at room temperature. The product, potassium
methoxide, was dissolved in anhydrous THF (20 mL) and
rapidly transferred to a compensation funnel, under N2. In
another Schlend round-bottomed flask bis(4-nitrophenyl) thion-
ocarbonate (0.2 g) was dissolved in anhydrous THF under N2
and the flask placed in an ethanol-liquid N2 bath. The
compensation funnel was attached to the flask and the
potassium methoxide solution added dropwise with stirring
during 2 h. The mixture was left overnight with stirring under
N2 at ambient temperature. The final mixture was dissolved
in chloroform and 4-nitrophenoxide anion extracted with
water. The organic layer was dried with MgSO4 and filtered
under vacuum and the solvent evaporated off. The product
was purified by column chromatography on GF-254 Merck
silica gel, eluent ether-chloroform 3:1 (v/v); mp 109-110 °C.
MNPTOC and EDNPTOC were characterized as follows:
MNPTOC: 1H NMR (200 MHz, CDCl3) δ 4.20 (s, 3H), 7.30
(sd, 2H, J ) 9.1 Hz), 8.30 (sd, 2H, J ) 9.1 Hz); 13C NMR (50
MHz, CDCl3) δ 60.80 (CH3), 123.28 (C-2/6), 125.37 (C-3/5),
145.96 (C-4), 157.56 (C-1), 194.69 (CdS); IR (KBr) 1593 (CdC),
1520 and 1346 (C-NO2), 1295 (CdS), 1159 (C-0), 865 (CH,
arom) cm-1. Anal. Calcd for C8H7O4NS: C, 45.08; H, 3.31;
N, 6.57; S, 15.01. Found: C, 45.34; H, 3.24; N, 6.27; S, 15.54.
EDNPTOC: 1H NMR (200 MHz, CDCl3) δ 1.51 (t, 3H, J )
7.1 Hz), 4.66 (q, 2H, J ) 7.1 Hz), 7.52 (d, 1 H, J ) 8.9 Hz),
8.56 (dd, 1H, J ) 2.7, 8.9 Hz), 9.02 (d, 1H, J ) 2.7 Hz); 13C
NMR (50 MHz, CDCl3) δ 15.59 (CH3), 72.13 (CH2), 121.94 (C-
3), 127.43 (C-5), 129.28 (C-1), 141.50 (C-6), 145.49 (C-4), 150.12
(C-2), 195.94 (CdS); IR (KBr) 1611 (CdC), 1542 and 1380 (C-
NO2), 1308 (CdS) cm-1. Anal. Calcd for C9H8O6N2S: C, 39.72;
H, 2.96; N, 10.29; S, 11.78. Found: C, 39.94; H, 2.92; N, 10.38;
S, 11.49.
substrate, kobsd is the pseudo-first-order rate coefficient,
ko and kN are the rate coefficients for hydrolysis and
pyridinolysis of the substrate, respectively, and N rep-
resents the substituted pyridine free base.
The values of kobsd and the experimental conditions of
the reactions are shown in Table 1.
The values of ko and kN were obtained as the intercept
and slope, respectively, of plots of kobsd against [N] at
constant pH, using at least three pH values. The values
of kN were found to be pH independent over the pH range
employed.
The ko values were in general negligible compared to
those of kN [N] in eq 2, except in the slow aminolysis of
the substrates with the two less basic pyridines (3-
carbamoyl and unsubstituted pyridines).
The Bro¨nsted-type plots of Figure 1 were obtained from
the kN values and the pKa values of the pyridines shown
in Table 2.
The linear and single Bro¨nsted-type plot found for the
pyridinolysis of ENPTOC and MNPTOC with slope â )
1.0 is consistent with a stepwise mechanism where a
zwitterionic tetrahedral intermediate (T() is formed on
the reaction pathway and its breakdown to products is
rate determining. Similar slope values have been found
in the aminolysis of phenyl and 4-nitrophenyl acetates,1
phenyl and 4-nitrophenyl methyl carbonates,6,16 4-nitro-
phenyl benzoate,9b,17 2,4-dinitrophenyl 4-chlorobenzoate,3d
and other reactive carbonyl compounds,1,4,5,13,16,18 where
a stepwise mechanism has been invoked with the break-
down of T( to products being the rate-determining step.
The value of â ) 1.0 for the above Bro¨nsted plot is also
similar to those obtained in the aminolysis of thioesters
and thiocarbonates when the breakdown of the tetrahe-
dral intermediate is rate limiting.8,9a,b,10c,11,15,17
Kin etic Mea su r em en ts. These were performed spectro-
photometrically by following the release of 4-nitrophenol or
2,4-dinitrophenol (and/or their conjugate bases) at 400 nm, by
the method and instrument previously described.15 The reac-
tions were studied under the following conditions: aqueous
solutions, 25.0 ( 0.1 °C, ionic strength 0.2 M (maintained with
KCl), and a 10-fold excess (at least) of total amine over the
substrate.
The nonlinear Bro¨nsted type plot found in the pyridi-
nolysis of EDNPTOC (Figure 1), with slopes â1 ) 0.1 and
â2 ) 1.0 at high and low pKa values, respectively, is
(12) Castro, E. A.; Araneda, C. A.; Santos, J . G., J . Org. Chem. 1997,
62, 126.
(13) Bond, P. M.; Castro, E. A.; Moodie, R. B. J . Chem. Soc., Perkin
(16) Castro, E. A.; Freudenberg, M. J . Org. Chem 1980, 45, 906.
(17) Campbell, P.; Lapinskas, B. A. J . Am. Chem. Soc. 1977, 99,
5378.
Trans. 2 1976, 68.
(14) Al-Kazimi, N.; Tarbell, D. S.; Plant, D. J . Am. Chem. Soc. 1955,
77, 2479.
(15) Castro, E. A.; Iba´n˜ez, F.; Santos, J . G.; Ureta, C. J . Org. Chem
1993, 58, 4908.
(18) (a) J ohnson, S. L. Adv. Phys. Org. Chem. 1967, 5, 237. (b)
Palling, D. J .; J encks, W. P. J . Am. Chem. Soc. 1984, 106, 4869. (c)
Fersht, A. R.; J encks, W. P. J . Am. Chem. Soc. 1970, 92, 5442. (d) Hall,
W. E.; Higuchi, T.; Pitman, I. H.; Uekama, K. J . Am. Chem. Soc. 1972,
94, 8153.

2514 J . Org. Chem., Vol. 62, No. 8, 1997
Castro et al.
Ta ble 1. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e P yr id in olysis of Alk yl Ar yl Th ion oca r bon a tesa
pyridine
substituent
no. of
runs
pH
103[N]tot/M
103kobsd/s-1
Methyl 4-Nitrophenyl Thionocarbonate (MNPTOC)
4-(dimethylamino)b
8.2
8.5
9.0
8.2
8.5
9.0
8.0
8.2
8.5
8.2
8.5
8.8
8.5
8.8
9.0
1.0-6.0
0.4-1.0
0.3-1.0
1.0-4.3
1.0-2.5
0.2-1.0
10-90
10-180
50-150
60-150
50-135
40-130
70-170
60-190
100-180
4.0-5.8
8
6
7
7
6
8
7
7
7
5
6
6
6
5
5
0.71-1.9
1.4-4.0
4-aminob
1.4-6.0
2.4-6.2
1.4-6.3
3,4-dimethyl
3-methylc
0.22-0.89
0.22-2.6
1.0-2.3
0.11-0.25
0.10-0.23
0.091-0.23
0.032-0.083
0.033-0.10
0.085-0.13
nonec
Ethyl 4-Nitrophenyl Thionocarbonate (ENPTOC)
4-(dimethylamino)
9.6
9.9
10.2
9.1
9.4
9.7
8.0
8.2
8.5
8.2
8.5
8.8
8.5
8.8
9.0
0.4-4.0
0.2-2.0
0.2-2.0
0.7-8.5
0.7-7.0
0.5-5.0
8.5-70
10-110
10-100
11-120
8.0-130
25-140
70-150
60-180
80-190
2.4-28
7
7
7
7
7
7
6
7
7
6
7
7
5
5
6
2.3-19
3.1-28
4-amino
3.5-44
5.3-57
4.5-49
3,4-dimethylc
3-methylc
0.24-1.2
0.24-1.8
0.18-1.7
0.045-0.23
0.045-0.24
0.052-0.27
0.029-0.077
0.034-0.10
0.045-0.10
F igu r e 1. Bro¨nsted-type plots obtained in the pyridinolysis
of MNPTOC (4), ENPTOC (b), and EDNPTOC (9), in aqueous
solution, at 25.0 °C, ionic strength 0.2 M (this work). Also
shown for comparison is the Bro¨nsted-type plot found in the
pyridinolysis of methyl 2,4-dinitrophenyl carbonate (O, ref 5)
under the same conditions.
nonec
Ethyl 2,4-Dinitrophenyl Thionocarbonate (EDNPTOC)
4-(dimethylamino)
9.6
9.9
10.2
9.1
9.4
9.7
8.0
8.2
8.5
8.2
8.5
8.8
5.1
5.4
5.7
8.5
8.8
9.0
0.40-4.0
0.20-2.0
0.20-2.0
0.70-8.5
0.70-7.0
0.50-5.0
1.0-12
1.8-27
2.7-21
3.3-27
5.0-65
7.7-71
5.4-78
4.0-61
10-123
16-120
1.6-25
1.8-34
1.1-20
3.4-20
3.6-39
3.6-31
0.16-0.68
0.20-0.69
0.18-0.74
7
7
7
7
7
7
7
6
6
7
7
7
7
7
7
7
7
6
nonlinear plot results from a change in the rate-
determining step, from that for k2 at low amine basicity
to that for k1 at high amine basicity.1,4,5,7c,d,8,9,13,15-19
Applying the steady state condition to T( in eq 3, the
equation kN ) k1k2/(k-1 + k2) is obtained, and this
accounts for the curvature of the Bro¨nsted plot. At high
pKa values k-1 , k2 and kN ) k1 (first step of eq 3 is rate
limiting). At low pKa values k-1 . k2 and kN ) k1k2/k-1
) K1k2 (second step limiting), where K1 is the equilibrium
constant for the first step of eq 3. Based on this, a
semiempirical equation has been deduced,4,12,13 which
satisfactorily accounts for the experimental points ob-
tained in the pyridinolysis of EDNPTOC (see Figure 1).
The parameters used in the semiempirical equation are:
4-amino
3,4-dimethylc
3-methylc
3.0-25
4.0-25
15-300
20-400
10-250
40-200
25-250
15-160
10-100
20-105
15-110
none
3-carbamoylc
a
In aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl).
In the presence of 0.05 M carbonate buffer. c In the presence of
o
â1 ) 0.1, â2 ) 1.0, and pKa ) 6.8; the latter is the pKa
b
value at the center of curvature, i.e., it represents the
pKa of an amine for which k-1 ) k2 in eq 3. In other
words, an amine of this basicity will leave T( as readily
as L-.4,5,8,13,19
0.005 M borate buffer.
similar to those obtained in the aminolysis of reactive
aryl esters1,7c,16 and carbonates,4,5,7c,d and in other carbo-
nyl derivatives,13,18 thioesters,8a,17 and thiocarbonates.12,19
All these reactions have been explained by the mecha-
nism described in eq 3, where R and L are the nonleaving
There are other explanations for curved Bro¨nsted-type
plots, based mainly on a structural variation of the
transition state as the reactivity of the amine changes
in a single step,20 as predicted by the Hammond postu-
late.21 Nevertheless, as in other reactions, we have had
no success in trying to fit equations based on the above
hypothesis20 to our experimental log kN vs pKa points.7d,19,22
(20) Marcus, R. A. J . Phys. Chem. 1968, 72, 891. Murdoch, J . R. J .
Am. Chem. Soc. 1972, 94, 4410. Albery, W. J .; Kreevoy, M. M. Adv.
Phys. Org. Chem. 1978, 16, 87. More O’Ferrall, R. A. J . Chem. Soc.,
Perkin Trans. 2 1981, 1084. Murdoch, J . R. J . Phys. Chem. 1983, 87,
1571.
and leaving groups, and N represents an amine. The
(19) Castro, E. A.; Iba´n˜ez, F.; Salas, M.; Santos, J . G.; Sepu´lveda,
P. J . Org. Chem. 1993, 58, 459.
(21) Hammond, G. S. J . Am. Chem. Soc. 1955, 77, 334.

Pyridinolysis of Alkyl Aryl Thionocarbonates
J . Org. Chem., Vol. 62, No. 8, 1997 2515
Ta ble 2. Va lu es of p Ka of P yr id in iu m Ion s a n d kN for th e P yr id in olysis of Alk yl Ar yl Th ion oca r bon a tesa
kN/s-1 M-1
pyridine
substitment
pKa
MNPTOC
ENPTOC
EDNPTOC
4-(dimethylamino)
4-amino
3,4-dimethyl
3-methyl
none
3-carbamoyl
9.87
9.42
6.77
5.80
5.37
3.43
32 ( 3
21 ( 1
20 ( 2
23 ( 1
16 ( 1
21 ( 2
0.015 ( 0.001
(1.5 ( 0.1) × 10-3
(5.2 ( 0.2) × 10-4
0.017 ( 0.001
(1.8 ( 0.2) × 10-3
(5.0 ( 0.1) × 10-4
5.0 ( 0.2
0.83 ( 0.03
0.31 ( 0.02
(6.0 ( 0.4) × 10-3
a
Both pKa and kN values were obtained in aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl). For abbreviations of the substrates
see Table 1.
A referee has pointed out that the nonlinear Bro¨nsted-
type plot for the pyridinolysis of EDNPTOC can be
explained by a requirement for structural reorganization
of the two aminopyridines upon bond order reorganiza-
tion in the transition state, which significantly decreases
the rate. Nevertheless, it can be seen in Figure 1 that
the two aminopyridines correlate well with the other less
basic amines in the pyridinolyses of both ENPTOC and
MNPTOC.
Moreover, good Bro¨nsted-type correlations (including
the two mentioned aminopyridines) are also shown in the
pyridinolyses of substrates with good leaving groups,
such as 2,4-dinitrophenyl 4-X-substituted benzoates (X
) NO2, CN, and Cl). These linear Bro¨nsted-type plots
exhibit a slope â ca.1, which indicates that a tetrahedral
intermediate is formed and its breakdown to products is
the rate-determining step.3d,23 Furthermore, in the py-
ridinolysis of methyl chloroformate there is a good linear
Bro¨nsted correlation between the above two aminopy-
ridines and other X-substituted pyridines (X ) H, 3-m-
ethyl and 4- methyl).13 Also, in the pyridinolysis of acetyl
chloride there is a good Bro¨nsted linearity between
4-(dimethylamino)pyridine and other pyridines (X ) H,
4-methyl and 3,4-dimethyl).18b
Moreover, Williams has recently found that 4-(dim-
ethylamino)- and 4-amino pyridines correlate well with
N-pyrid-4-ylmorpholine and 4-methoxy and 3,5-dimethyl
pyridines on the Bro¨nsted-type plot obtained in the
pyridinolysis of 1′-(4,6-diphenoxy-1,3,5-triazin-2-yl)pyri-
dinium chloride.24 Also the above two aminopyridines
correlate linearly with five other pyridines ranging from
pKa 6.7 down to 3.5 on the Bro¨nsted-type plot found in
the pyridinolysis of 4,6-diphenoxy-1,3,5-triazin-2-yl chlo-
ride.24
Another referee has suggested that the pyridinolysis
of EDNPTOC (Figure 1) could be concerted, as found by
J encks25,26 and Williams27,28 in related reactions. Nev-
ertheless, the Bro¨nsted curvature exhibited by the ED-
NPTOC reaction is far too sharp for a concerted process.
J encks found a slight Bro¨nsted curvature in the ami-
nolysis of benzoyl fluorides, which together with the fact
that the curvature center does not shift with the change
of acyl substituents led him to the conclusion that the
mechanism is concerted.25 J encks also found that the
reactions of phenolate anions with acetate and formate
esters are concerted, but this conclusion was arrived at
from the linear Bro¨nsted-type plots obtained for structur-
ally homogeneous series of phenolate anions.26
Williams has found that acetyl and other groups
transfers between phenolate ions are concerted.27 He has
also found that methoxycarbonyl transfer between iso-
quinoline and pyridines is a concerted process.28 In all
these reactions a linear Bro¨nsted-type plot was ob-
tained.27,28 Williams has argued that acyl group transfers
between a given phenolate and pyridines (and other
amines) are stepwise, through a tetrahedral intermediate
which is stable enough to exist.27a Williams has agreed
with our claim that the pyridinolysis of acetic anhydride,27b
2,4,6-trinitrophenyl acetate,27c 2,4-dinitrophenyl methyl
carbonate (Bro¨nsted-type plot shown in Figure 1), and
other reactive carbonyl derivatives are all stepwise
reactions where a tetrahedral intermediate is formed.27a
On the other hand, Palling and J encks have claimed
that the pyridinolysis of acetyl chloride is stepwise.18b It
is noteworthy that this substrate possesses a better
leaving group than EDNPTOC, and therefore if a tetra-
hedral intermediate is formed in the former reaction, it
should be more likely to exist in the latter reaction (this
work) where it should be less unstable.
Therefore, according to what has been discussed above,
and in agreement with the kinetic law and the products
and intermediate studies, we believe that the reactions
under the present investigation can be depicted by the
mechanism shown in eq 4, where 1 is a tetrahedral
intermediate. In this equation, R is either methyl or
ethyl, Ar is either 4-nitrophenyl or 2,4-dinitrophenyl, and
-Nd represents a given pyridine.
Intermediate 2, 1-(alkoxythiocarbonyl)-substituted py-
ridinium ion, was detected as explained in the Experi-
mental Section, although its decomposition rate was not
measured. Compound 2 does not absorb at 400 nm where
the production of ArO- was followed and the kinetics of
the reactions were measured. Therefore, the kN values
obtained are the macroscopic rate coefficients for the
formation of 2 and ArO- from reactants.
(22) Castro, E. A.; Moodie, R. B. J . Chem. Soc., Chem. Commun.
1973, 828.
Similar intermediates to 2 have been found in the
reactions of pyridine and 3-carbamoylpyridine (nicotina-
mide) with O-ethyl 2,4-dinitrophenyl dithiocarbonate,12
and in the pyridinolysis of methyl chloroformate6,13,29 and
methyl 2,4-dinitrophenyl carbonate.5 Also 1-acetyl-
substituted pyridinium ions have been detected in the
pyridinolysis of acetic anhydride.30
(23) Castro, E. A.; Steinfort, G. B. J . Chem. Soc., Perkin Trans. 2
1983, 453. Castro, E. A.; Becerra, M. C. Bol. Soc. Chil. Quim. 1988,
33, 67.
(24) Cullum, N. R.; Renfrew, A. H. M.; Rettura, D.; Taylor, J . A.;
Whitmore, J . M. J .; Williams, A. J . Am. Chem. Soc. 1995, 117, 9200.
(25) Song, B. D.; J encks, W. P. J . Am. Chem. Soc. 1989, 111, 8479.
(26) Stefanidis, D.; Cho, S.; Dhe-Paganon, S.; J encks, W. P. J . Am.
Chem. Soc. 1993, 115, 1650.
(27) (a) Ba-Saif, S.; Luthra, A. K.; Williams, A. J . Am. Chem. Soc.
1987, 109, 6362. (b) Williams, A. Acc. Chem. Res. 1989, 22, 387. (c)
Williams, A. Chem. Soc. Rev. 1994, 23, 93. (d) Renfrew, A. H. M.;
Rettura, D.; Taylor, J . A.; Whitmore, J . M. J .; Williams, A. J . Am.
Chem. Soc. 1995, 117, 5484.
(29) Guillot-Edelheit, G.; Laloi-Diard, M.; Guibe´-J ampel, E.; Wak-
selman, M. J . Chem. Soc., Perkin Trans. 2 1979, 1123. Battye, P. J .;
Ihsan, E. M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1980, 741.
(28) Chrystiuk, E.; Williams, A. J . Am. Chem. Soc. 1987, 109, 3040.

2516 J . Org. Chem., Vol. 62, No. 8, 1997
Castro et al.
the nature of the leaving groups involved is different. In
fact, it has been reported that aryl oxide anions are better
nucleofuges from a tetrahedral intermediate than isoba-
sic arylthiolate anions.35 The higher basicity of DNPO-
relative to DNPS- should be partly counterbalanced by
the higher intrinsic nucleofugality of aryloxide anions.
On the other hand the push exerted by DNPO in 1 to
expel the amine should be slightly stronger than that by
DNPS.8a,35a Taking into account the pull and push effects
of these two groups in the corresponding tetrahedral
intermediates, one concludes that the k-1/k2 value for a
given amine should be slightly larger for DNPO compared
The fact that the experimental points for the pyridi-
nolysis of both ENPTOC and MNPTOC fall on the same
straight line of the Bro¨nsted-type plot (Figure 1) means
that the value of k1k2/k-1 (eq 4) is the same for both
reactions (see above). It is known that electron with-
drawal from R in the tetrahedral intermediate T( (eq 3)
o
to DNPS, producing a little larger pKa value for the
pyridinolysis of EDNPTOC relative to EDNPDTC, ac-
cording to the tetrahedral intermediate hypothesis.4,8 The
fact that the pKao values for the two reactions concerned
are equal within experimental error indicates that the
nonleaving RO group in 1 must also play a significant
role by affecting the k-1/k2 ratio. This is evident by
comparison of the pKao values in the pyridinolysis of 2,4-
dinitrophenyl acetate (DNPA) and 2,4-dinitrophenyl thi-
o
increases the pKa value, and therefore the k-1/k2 ratio,
favoring amine expulsion from T( relative to L-.4 Since
the electronic effects from R in T( and RO in 1 (eq 4) are
mainly inductive, due to the fact that the central carbon
atom is tetrahedral,31 similar values for the k-1/k2 ratios
are expected for R ) Me and Et in eq 4, in view of the
similar σI values involved (0.29 and 0.26, respectively).32
Moreover, since the other groups attached to the central
carbon in 1 are the same, the similar σI values for R )
Me and Et in 1 should imply similar k-1 and k2 values
for both intermediates. The k1 values for the two
reactions concerned (eq 4) should be governed by both
resonance and inductive effects since there is a trigonal
central carbon involved in the substrates. The σR value
for MeO is -0.56, the absolute value of which is slightly
greater than that for EtO (σR ) -0.50);32 nevertheless,
the slightly stronger electron donation by resonance of
MeO relative to EtO is counterbalanced by a slightly
stronger electron-withdrawing inductive effect (see above)
of MeO. This suggests that the k1 values could also be
similar for the pyridinolysis of MNPTOC and ENPTOC.
Therefore, if the k1k2/k-1 ) K1k2 values are the same
(within experimental error) for both reactions, the con-
clusion from the above discussion is that both K1 and k2
should be similar for both reactions.
o
olacetate (DNPTA). There is a decrease in pKa of 0.6
unit by the change of DNPO by DNPS as the L group of
T( in eq 3 (R ) Me).8a,16 There is also a smaller decrease
of pKao (0.2 units) by the same change in the reactions of
secondary alicyclic amines with the same substrates.8a,36
A linear Bro¨nsted-type plot of slope â ) 1.0 can be
obtained in the pyridinolysis of methyl 4-nitrophenyl
carbonate,6,37 with the same slope as that found in the
same reactions of MNPTOC (this work), although, the
kN values are larger for the former reactions. Similarly
the kN values are larger in the reactions of secondary
alicyclic amines with 4-nitrophenyl benzoate compared
to the same aminolysis of 4-nitrophenyl thionobenzoate.9b
As seen in Figure 1, the change of R ) Me by Et in the
tetrahedral intermediate 1 of eq 4 does not alter the kN
values, nor is K1 or k2 changed significantly (see above).
Taking this into account a comparison between the
pyridinolysis of EDNPTOC and methyl 2,4-dinitrophenyl
carbonate (MDNPC) should be valid; the Bro¨nsted-type
plot for the latter reactions is included in Figure 1 for
this purpose.5 It can be seen in this figure that the
substitution of the thiocarbonyl group in EDNPTOC by
a carbonyl in MDNPC shifts the center of the Bro¨nsted
The pKa value for the center of the Bro¨nsted curvature
o
for the pyridinolysis of EDNPTOC is pKa ) 6.8, which
o
is lower than that for the pyridinolysis of ENPTOC (pKa
> 10, see Figure 1). This is in accordance with the results
found in the aminolysis of aryl acetates,33 diaryl carbon-
ates,4 aryl methyl carbonates,5,6,7c aryl thiolacetates,8a and
o
curvature to higher pKa values, that is from pKa ) 6.8
to 7.8.5 A similar effect has been found in the aminolysis
of 4-nitrophenyl thionobenzoate and benzoate: A non-
aryl O-ethyl dithiocarbonates,19 i.e. the pKa value de-
o
linear Bro¨nsted-type plot with pKao ) 9.2 was exhibited
creases as the basicity of the nucleofuge diminishes. This
fact is in agreement with the stepwise mechanism, since
the lower the leaving group basicity the larger the value
of k2 in eqs 3 and 4, and therefore the lower the amine
pKa for which k-1 ) k2.4-6,8,13
o
by the former reactions, whereas a linear plot (pKa
>
11) was obtained for the latter reactions.17 The larger
pKao value means a larger k-1/k2 ratio (for a given amine
and leaving group) for the carbonyl compound compared
to the thiocarbonyl derivative.4,8 It has been reported
that the change of S- by O- in 3 increases both k-1 and
k2, with k-1 bearing the larger increase.15 It seems that
the same situation holds for the reactions discussed
above.
The above value of pKao ) 6.8 ((0.1) is the same within
experimental error as that found in the pyridinolysis of
O-ethyl 2,4-dinitrophenyl dithiocarbonate (EDNPDTC,
pKao ) 6.9 ( 0.1).12 This is somewhat surprising in view
of the lower basicity of 2,4-dinitrobenzenethiolate anion
(DNPS-) compared to 2,4-dinitrophenoxide anion (DNPO-)
(pKa 3.4 and 4.0 at 25 °C, respectively).8a,34 Nevertheless,
The kN values for the pyridinolysis of EDNPTOC are
smaller than those for MDNPC (Figure 1) in the entire
pKa region. Namely, this is independent of the rate-
determining step. When expulsion of DNPO- is rate
limiting (linear portion of the Bronsted plot at low pKa)
(30) Fersht, A. R.; J encks, W. P. J . Am. Chem. Soc. 1970, 92. 5432.
Guibe-J ampel, E.; Le Corre, G.; Wakselman, M. Tetrahedron Lett.
1979, 1157.
(31) 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.
(32) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(33) J encks, W. P.; Gilchrist, M. J . Am. Chem. Soc. 1968, 90, 2622.
(34) Albert, A.; Serjeant, E. P. The Determination of Ionization
Constants; Chapman and Hall: London, 1971; p 87.
(35) (a) Hupe, D. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 451.
(b) Douglas, K. T.; Alborz, M. J . Chem. Soc. Chem. Commun. 1981,
551. (c) Douglas, K. T. Acc. Chem. Res. 1986, 19, 186.
(36) Castro, E. A.; Ureta, C. J . Org.Chem. 1990, 55, 1676.
(37) This plot can be obtained with the data in Table 1 of ref 6.

Pyridinolysis of Alkyl Aryl Thionocarbonates
J . Org. Chem., Vol. 62, No. 8, 1997 2517
kN ) k1k2/k-1. Since k2/k-1 is smaller for MDNPC, its
larger kN value must rise for a much larger k1 relative to
that for EDNPTOC. This is evident in Figure 1 at high
pKa values, where the formation of the tetrahedral
intermediate (k1 step) is the rate-determining step. The
k1 values are ca. 10-fold larger for the carbonate. Larger
k1 values for the aminolysis of phenyl acetate relative to
those for the same reactions of phenyl thionoacetate have
been reported.15 This has been ascribed to the hard
nature of a carbonyl center (compared to the softer
thiocarbonyl) which prefers to bind a relatively hard
alicyclic amine.15,38 Pyridines should be softer than
alicyclic amines,38 but still show higher nucleophilicity
toward the CdO electrophilic center of MDNPC com-
pared to the CdS in EDNPTOC.
The reactions of ENPTOC with secondary alicyclic
amines have been subjected to a kinetic investigation
whereby the rate microcoefficients k1, k-1, and k2 have
been measured.11 From these data it is possible to draw
a Bro¨nsted-type plot for kN ) k1k2/(k-1 + k2) with the
purpose of comparing it with that for the pyridinolysis
of the same substrate (this work). Figure 2 shows such
plots, together with a Bro¨nsted-type plot for k1 for the
former reactions. The plots for the reactions of secondary
amines are statistically corrected.39 Some conclusions
can be drawn from these plots:
F igu r e 2. Bro¨nsted-type plots found in the pyridinolysis of
ENPTOC (b, this work), and in the reactions of secondary
alicyclic amines with the same substrate (4, kN values; 9, k1
values, ref 11). The Bro¨nsted plots for the reactions of
secondary amines are statistically corrected (see text). Experi-
mental reaction conditions as in Figure 1.
(i) The kN ) K1k2 values for the two most basic
pyridines are larger than the k1 values for isobasic
secondary alicyclic amines. This means that for py-
ridines of higher pKa values (hypothetical) for which the
formation of the tetrahedral intermediate would be rate
determining (k1 step), the k1 values for these pyridines
would be larger than those of isobasic secondary alicyclic
amines. This is in agreement with what was discussed
above regarding hard and soft acids and bases. If
pyridines show larger k1 values than isobasic secondary
alicyclic amines toward carbonyl compounds, the k1
values should be even larger for pyridines toward a softer
thiocarbonyl center.38 The higher reactivity of pyridines
than isobasic secondary alicyclic amines is also reason-
able in terms of the lower steric hindrance of the former
amines.40
larger for pyridines relative to the other isobasic amines.
This can be explained as follows: It has been estimated
that the value of k2 should be independent of the amine
nature or basicity since the cationic amine cannot exert
a push to expel an aryloxide leaving group from the
zwitterionic tetrahedral intermediate due to the lack of
an electron pair on its nitrogen atom.4 On the other hand
it has been found that the value of k-1 is larger for
secondary alicyclic amines than isobasic pyridines.8,10,36
Therefore, it is reasonable that the K1k2 () k1k2/k-1
)
values be larger for pyridines since both k1 and the ratio
k2/k-1 are larger for the reactions of these amines
compared to isobasic alicyclic amines. In line with our
finding is the larger reactivity of pyridines toward 2,4-
dinitrophenyl and 2,4,6-trinitrophenyl O-ethyl dithiocar-
bonates relative to isobasic secondary alicyclic amines
when expulsion of the corresponding benzenthiolate
anion is rate limiting.12,19
(ii) The kN values for both reaction series at low pKa
(where kN ) K1k2 for both series of reactions) are also
(38) Pearson, R. G. J . Chem. Educ. 1968, 45, 581. Pearson, R. G. J .
Org.Chem. 1989, 54, 1423.
(39) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959;
p 159.
Ack n ow led gm en t. We thank FONDECYT of Chile
for financial support.
(40) We thank a referee for this comment.
J O961921O