Effect of changing electrophilic center C=O to C=S on rates and mechanism: Pyridinolyses of O-2,4-dinitrophenyl thionobenzoate and its oxygen analogue

Article abstract of DOI:10.1021/jo0492160

Second-order rate constants have been measured spectrophotometrically for the reactions of O-2,4-dinitrophenyl thionobenzoate (1) and 2,4-dinitrophenyl benzoate (2) with a series of substituted pyridines in 80 mol % H ₂O/20 mol % DMSO at 25.0 ± 0.1 °C. The Bronsted-type plots obtained are nonlinear with β₁ = 0.26, β₂ = 1.07, and pK_a° = 7.5 for the reactions of 1 and β₂ = 0.40, β₂ = 0.90, and pK_a° = 9.5 for the reactions of 2, suggesting that the pyridinolyses of 1 and 2 proceed through a zwiterionic tetrahedral intermediate T^± with a change in the rate-determining step at pK_a° = 7.5 and 9.5, respectively. The thiono ester 1 is more reactive than its oxygen analogue 2 except for the reaction with the strongest basic pyridine studied (pK _a = 11.30). The k₁ value is larger for the reactions of 1 than for those of 2 in the low pK_a region, but the difference in the k₁ value becomes negligible with increasing the basicity of pyridines. On the other hand, 1 exhibits slightly larger k₂/k _-1 ratio than 2 in the low pK_a region but the difference in the K₂/k_-1 ratio becomes more significant with increasing the basicity of pyridines. Pyridines are more reactive than alicyclic secondary amines of similar basicity toward 2 in the pK_a above ca. 7.2 but less reactive in the pK_a below ca. 7.2. The k₁ value is slightly larger, but the k₂/k_-1 ratio is much smaller for the reactions of 2 with pyridines than with isobasic secondary amines in the low pK_a region, which is responsible for the fact that the weakly basic pyridines are less reactive than isobasic secondary amines.

Full text of DOI:10.1021/jo0492160

Effect of Ch a n gin g Electr op h ilic Cen ter fr om CdO to CdS on
Ra tes a n d Mech a n ism : P yr id in olyses of O-2,4-Din itr op h en yl
Th ion oben zoa te a n d Its Oxygen An a logu e
Ik-Hwan Um,* Hyun-J oo Han, Mi-Hwa Baek, and Sun-Young Bae
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
ihum@mm.ewha.ac.kr
Received May 10, 2004
Second-order rate constants have been measured spectrophotometrically for the reactions of O-2,4-
dinitrophenyl thionobenzoate (1) and 2,4-dinitrophenyl benzoate (2) with a series of substituted
pyridines in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The Brønsted-type plots obtained are
nonlinear with â1 ) 0.26, â2 ) 1.07, and pKa° ) 7.5 for the reactions of 1 and â1 ) 0.40, â2 ) 0.90,
and pKa° ) 9.5 for the reactions of 2, suggesting that the pyridinolyses of 1 and 2 proceed through
a zwiterionic tetrahedral intermediate T( with a change in the rate-determining step at pKa° )
7.5 and 9.5, respectively. The thiono ester 1 is more reactive than its oxygen analogue 2 except for
the reaction with the strongest basic pyridine studied (pKa ) 11.30). The k1 value is larger for the
reactions of 1 than for those of 2 in the low pKa region, but the difference in the k1 value becomes
negligible with increasing the basicity of pyridines. On the other hand, 1 exhibits slightly larger
k2/k-1 ratio than 2 in the low pKa region but the difference in the k2/k-1 ratio becomes more significant
with increasing the basicity of pyridines. Pyridines are more reactive than alicyclic secondary amines
of similar basicity toward 2 in the pKa above ca. 7.2 but less reactive in the pKa below ca. 7.2. The
k1 value is slightly larger, but the k2/k-1 ratio is much smaller for the reactions of 2 with pyridines
than with isobasic secondary amines in the low pKa region, which is responsible for the fact that
the weakly basic pyridines are less reactive than isobasic secondary amines.
In tr od u ction
terionic tetrahedral intermediate T(, in which the rate-
determining step (RDS) is dependent on the basicity of
the attacking amine and the leaving group.1-5
However, reactions of thiocarbonyl derivatives have
been much less investigated, and their reaction mecha-
nisms are not completely understood.6-12 Castro et al.
have shown that aminolysis of thiono esters such as
Nucleophilic substitution reactions of carbonyl deriva-
tives have recently received intensive attention due to
the importance in chemical and biological processes.1-5
The reactions of carboxylic esters with amines have
generally been understood to proceed through a zwit-
(1) (a) Page, M. I.; Williams, A. Organic & Bio-organic Mechanisms;
Longman: Harlow, 1997; Chapter 7. (b) Williams, A. Concerted Organic
and Bio-organic Mechanisms; CRC Press: Boca Raton, 2000; Chapter
4. (c) Carroll, F. A. Perspectives on Structure and Mechanism in Organic
Chemistry; Brooks/Cole Publishing Co: Pacific Grove, 1998; pp 434-
448. (d) Williams, A. Adv. Phys. Org. Chem. 1992, 27, 2-55.
(2) (a) Castro, E. A.; Bessolo, J .; Aguayo, R.; Santos, J . G. J . Org.
Chem. 2003, 68, 8157-8161. (b) Castro, E. A.; Campodonico, P.; Toro,
A.; Santos, J . G. J . Org. Chem. 2003, 68, 5930-5935. (c) Castro, E. A.;
Pavez, P.; Santos, J . G. J . Org. Chem. 2003, 68, 3640-3645. (d) Castro,
E. A.; Ruiz, M. G.; Santos, J . G. Int. J . Chem. Kinet. 2001, 33, 281-
287. (e) Castro, E. A.; Hormazabal, A.; Santos, J . G. Int. J . Chem. Kinet.
1998, 30, 267-272.
(3) (a) Oh, H. K.; Park, J . E.; Sung, D. D.; Lee, I. J . Org. Chem.
2004, 69, 3150-3153. (b) Lee, I.; Sung, D. D. Curr. Org. Chem. 2004,
8, 557-567. (c) Koh, H. J .; Kang, S. J .; Kim, C. J .; Lee, H. W.; Lee, I.
Bull. Korean Chem. Soc. 2003, 24, 925-930. (d) Oh, H. K.; Lee, J . Y.;
Lee, H. W.; Lee, I. New J . Chem. 2002, 26, 473-476. (e) Lee, H. W.;
Yun, Y. S.; Lee, B. S.; Koh, H. J .; Lee, I. J . Chem. Soc., Perkin Trans.
2 2000, 2302-2305. (f) Lee, I.; Kim, C. K.; Li, H. G.; Sohn, C. K.; Kim,
C. K.; Lee, H. W.; Lee, B. S. J . Am. Chem. Soc. 2000, 122, 11162-
11172.
(5) (a) Asaad, N.; Otter, M. J .; Engberts, J . B. F. N. Org. Biomol.
Chem. 2004, 2, 1404-1412. (b) Ahmed, N.; Tsang, W. Y.; Page, M. I.
Org. Lett. 2004, 6, 201-203. (c) Yang, W.; Drueckhammer, D. G. J .
Am. Chem. Soc. 2001, 123, 11004-11009. (d) Marlier, J . F. Acc. Chem.
Res. 2001, 34, 283-290.
(6) Castro, E. A. Chem. Rev. 1999, 99, 3505-3524.
(7) (a) Castro, E. A.; Ibanez, F.; Santos, J . G.; Ureta, C. J . Org. Chem.
1993, 58, 4908-4912. (b) Castro, E. A.; Galvez, A.; Leandro, L.; Santos,
J . G. J . Org. Chem. 2002, 67, 4309-4315. (c) Castro, E. A.; Cubillos,
M.; Santos, J . G. J . Org. Chem. 2001, 66, 6000-6003. (d) Castro, E.
A.; Garcia, P.; Leandro, L.; Quesieh, N.; Rebolledo, A.; Santos, J . G. J .
Org. Chem. 2000, 65, 9047-9053. (e) Castro, E. A.; Saavedra, C.;
Santos, J . G.; Umana, M. I. J . Org. Chem. 1999, 64, 5401-5407.
(8) (a) Oh, H. K.; Kim, S. K.; Lee, H. W.; Lee, I. J . Chem. Soc., Perkin
Trans. 2 2001, 1753-1757. (b) Oh, H. K.; Kim, S. K.; Lee, H. W.; Lee,
I. New J . Chem. 2001, 25, 313-317. (c) Oh, H. K.; Kim, S. K.; Cho, I.
H.; Lee, H. W.; Lee, I. J . Chem. Soc., Perkin Trans. 2 2000, 2306-
2310. (d) Oh, H. K.; Woo, S. Y.; Shin, C. H.; Park, Y. S.; Lee, I. J . Org.
Chem. 1997, 62, 5780-5784.
(9) Um, I. H.; Seok, J . A.; Kim, H. T.; Bae, S. K. J . Org. Chem. 2003,
68, 7742-7746.
(10) (a) Um, I. H.; Lee, S. E.; Kwon, H. J . J . Org. Chem. 2002, 67,
8999-9005. (b) Um, I. H.; Kwon, H. J .; Kwon, D. S. J . Chem. Res.
Synop. 1995, 301.
(11) Castro, E. A.; Arellano, D.; Pavez, P.; Santos, J . G. J . Org. Chem.
2003, 68, 6192-6196.
(12) Um, I. H.; Lee, J . Y.; Kim, H. T.; Bae, S. K. J . Org. Chem. 2004,
69, 2436-2441.
(4) (a) Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y. J .
Org. Chem. 2004, 69, 3937-3942. (b) Um, I. H.; Han, H. J .; Ahn, J . A.;
Kang, S.; Buncel, E. J . Org. Chem. 2002, 67, 8475-8480. (c) Um, I.
H.; Min, J . S.; Ahn, J . A.; Hahn, H. J . J . Org. Chem. 2000, 65, 5659-
5663. (d) Um, I. H.; Min, J . S.; Lee, H. W. Can. J . Chem. 1999, 77,
659-666. (e) Um, I. H.; Park, H. R.; Kim, E. Y. Bull. Korean Chem.
Soc. 2003, 24, 1251-1255.
10.1021/jo0492160 CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/19/2004
J . Org. Chem. 2004, 69, 6365-6370
6365

Um et al.
TABLE 1. Su m m a r y of Secon d -Or d er Ra te Con sta n ts
(kN) for th e Rea ction s of 1 a n d 2 w ith Z-Su bstitu ted
P yr id in es in 80 m ol % H2O/20 m ol % DMSO a t 25.0 (
0.1 °C
O-phenyl thionoacetate, O-aryl O-4-nitrophenyl thiono-
carbonates, and O-methyl O-4-nitrophenyl thionocarbon-
ates proceeds through T( and its deprotonated T- when
the attacking amines are weakly basic (e.g., piperazinium
ion and N-formylpiperazine) but without the deprotona-
tion process for the reaction with strongly basic pipera-
zine and piperidine.6,7 Thus, the basicity of amines has
been suggested to be an important factor to determine
the presence or absence of the deprotonation process from
the zwitterionic T(.6,7 Lee et al. have suggested that the
nature of the reaction medium is also an important factor
to determine the reaction mechanism, since the depro-
tonation process from T( to T-, which has often been
observed as the RDS for the reactions performed in H2O,
is absent for aminolyses of aryl dithioacetates and their
related esters in MeCN.8 On the contrary, we have
recently shown that the reaction of O-4-nitrophenyl
thionobenzoate (3) with a series of secondary amines
proceeds through the two intermediates (T( and T-)
regardless of amine basicity and the nature of reaction
medium.9 However, the corresponding reaction with
primary amines has been found to proceed without the
deprotonation process, indicating that the nature of
amine also influences the mechanism for aminolyses of
3.10
kN/M-1s-1
Z-pyridine, Z )
pKa
1
2
H
4.73a
5.09a
5.53a
5.78a
0.0537 ( 0.0004
0.106 ( 0.002
0.389 ( 0.001
0.727 ( 0.011
0.00861 ( 0.00005
0.0167 ( 0.0002
0.0469 ( 0.0007
0.0725 ( 0.0004
32.0 ( 0.5
3-Me
4-Me
3,4-Me2
4-NH2
4-NMe2
4-O-
8.93a 107 ( 2
9.12a 122 ( 2
11.30b 450 ( 8
43.0 ( 0.3
822 ( 7
a
The pKa data in 80 mol % H2O/20 mol % DMSO were taken
from ref 26. b Determined in this study by using the method shown
in ref 26.
reactions obeyed first-order kinetics over 90% of the
reaction. Pseudo-first-order rate constants (kobsd) were
determined from the slope of the linear plots of ln(A∞ -
At) vs time. The kinetic results obeyed the simple kinetic
law given by eqs 1 and 2.
d[ArO-]/dt ) kobsd[1 or 2]
kobsd ) kN[pyridine]
(1)
where
kN ) k1k2/(k-1 + k2)
(2)
Generally, five different pyridine concentrations were
used to determine the second-order rate constant (kN)
from the slope of the linear plots of kobsd vs pyridine
concentration. Correlation coefficients of the plots were
usually higher than 0.9995. It is estimated from replicate
runs that the uncertainty in the rate constants is less
than (3%. The second-order rate constants determined
in this way are summarized in Table 1.
The initial product (e.g., 1-thionobenzoyl-4-dimethyl-
aminopyridinium ion or its oxygen analogue) was de-
tected as explained in the Experimental Section but
hydrolyzed to yield thiobenzoate (or benzoate for the
reaction of 2) as shown in Scheme 1. Similar intermedi-
ates have been reported for the pyridinolyses of 5, 6, 7,14a
methyl chloroformate,14b-d and acetic anhydride.14e Since
the intermediate does not absorb at 420 nm where the
reactions were monitored, the kN values obtained are the
macroscopic rate constants for the formation of the
intermediate and 2,4-dinitrophenoxide ion.
Effect of Ch a n gin g CdO to CdS on Rea ction
Mech a n ism . As shown in Table 1, the second-order rate
constant (kN) increases as the basicity of pyridines
increases for the reactions of 1; i.e., kN increases from
0.0537 to 0.727 and 450 M-1 s-1 as the pKa of pyridines
increases from 4.73 to 5.78 and 11.30, respectively. A
similar result can be seen for the reactions of 2. The effect
of pyridine basicity on reactivity has been illustrated in
Another interesting argument is about the effect of
nonleaving group on the reaction mechanism. Castro
et al. have reported that the reactions of substituted
phenoxide anions with O-ethyl O-2,4-dinitrophenyl thion-
ocarbonate (6) proceed concertedly, while the correspond-
ing reactions with O-methyl and O-phenyl O-2,4-dinitro-
phenyl thionocarbonates (5 and 7, respectively) proceed
through an addition intermediate, indicating that the
nature of the nonleaving group affects the reaction
mechanism.11 However, we have recently shown that the
nature of the nonleaving group substituents does not
influence the reaction mechanism significantly for hy-
drolysis and aminolysis of thiocarbonyl12 as well as
carbonyl4a-d and sulfonyl esters.13a,b
We have extended our kinetic study to pyridinolyses
of O-2,4-dinitrophenyl thionobenzoate (1) and its oxygen
analogue, 2,4-dinitrophenyl benzoate (2). The aim is to
investigate (i) the effect of changing the electrophilic
center from a CdO to a CdS bond on the reaction rate
and mechanism and (ii) the effect of amine nature on the
reaction rate by comparing the kinetic data obtained in
this study with those reported for the reactions of 2 with
primary and secondary amines.4a,d
Resu lts a n d Discu ssion
(14) (a) Castro, E. A.; Cubillos, M.; Santos, J . G.; Tellez, J . J . Org.
Chem. 1997, 62, 2512-2517. (b) Bond, P. M.; Moodie, R. B. J . Chem.
Soc., Perkin Trans. 2 1976, 679-682. (c) Bond, P. M.; Castro, E. A.;
Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1976, 68-72. (d) Guillot-
Edelheit, G.; Laloi-Diard, M.; Guibe-J ampel, E.; Wakselman, M. J .
Chem. Soc., Perkin Trans. 2 1979, 1123-1127. Battye, P. J .; Ihsan, E.
M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1980, 741-785. (e)
Fersht, A. R.; J encks, W. P. J . Am. Chem. Soc. 1970, 92, 5432-5442.
Reactions of 1 and 2 with pyridines proceeded with
quantitative liberation of 2,4-dinitrophenoxide. All the
(13) (a) Um, I. H.; Hong, J . Y.; Kim, J . J .; Chae, O. M.; Bae, S. K. J .
Org. Chem. 2003, 68, 5180-5185. (b) Um, I. H.; Chun, S. M.; Chae, O.
M.; Fujio, M.; Tsuno, Y. J . Org. Chem. 2004, 69, 3166-3172.
6366 J . Org. Chem., Vol. 69, No. 19, 2004

Pyridinolysis of O-2,4-Dinitrophenyl Thionobenzoate
SCHEME 1
Figure 1. The Brønsted-type plot exhibits a downward
curvature for the reactions of 1. The corresponding plot
for the reaction of 2 is also nonlinear, although the
curvature is not significant. Such a nonlinear Brønsted-
type plot has often been observed for aminolyses of esters
with a good leaving group and interpreted as a change
in the RDS.1-6 Thus, one can suggest that the reactions
of 1 and 2 with pyridines proceed through T( with a
change in the RDS from the breakdown of T( to its
formation as the basicity of pyridines increases.
The nonlinear Brønsted-type plots shown in Figure 1
have been analyzed using a semiempirical equation (eq
3)2a,4a,15 in which â1 and â2 represent the slope of the
Brønsted-type plot at the high and the low pKa region,
respectively. The kN° refers to the kN value at pKa°, the
center of the curvature on the Brønsted-type plot, where
k-1 ) k2. The parameters determined from the fitting of
eq 3 to the experimental points are â1 ) 0.26, â2 ) 1.07,
and pKa° ) 7.5 for the reactions of 1 and â1 ) 0.40, â2 )
0.90, and pKa°) 9.5 for the reactions of 2.
of 1 and 2 proceed through a tetrahedral intermediate
T( with a change in the RDS on the basis of the
magnitude of â1 and â2 values.
Since k2 ) k-1 at pKa°, the basicity of the leaving group
and nucleophiles would be the most important factor to
determine the pKa° value. In fact, the pKa° value has
generally been reported to be ca. 4-5 pKa units higher
than the pKa of the conjugate acid of the leaving aryloxide
for aminolyses of various oxygen esters.1-5 The pKa of 2,4-
dinitrophenol was estimated to be ca. 5 in 80 mol % H2O/
20 mol % DMSO.17 Thus, one can expect that the pKa°
would be in a pKa range 9-10 for the reactions of 2, which
is consistent with the result that pKa° ) 9.5 for the
reaction of 2 in present study.
On the other hand, the pKa° value has often been
reported to be smaller for the reactions of thiocarbonyl
compounds compared to the corresponding carbonyl
compounds.10a,18-20 We have recently shown that pKa° )
8.8 for the reaction of 3 with a series of primary amines
in 80 mol % H2O/20 mol % DMSO, while pKa° > 11.2 for
the corresponding reaction of 4.10a A similar result has
been reported by Campbell et al. for the same reactions
run in 80% H2O/20% CH3CN; i.e., the Brønsted-type plot
has been found to be nonlinear with pKa° ) 9.2 for the
reactions of 3 but linear (pKa° > 11) for the reactions of
4 with primary amines.18 More significant decreases in
the pKa° value have been reported for pyridinolyses of
dithio compounds, i.e., pKa° ) 5.2 for reactions of aryl
furan 2-carbodithioates and aryl dithioacetates in MeCN19
and pKa° ) 6.9 for reactions of O-ethyl 2,4-dinitrophenyl
dithiocarbonate in H2O.20 Thus, the present result is
consistent with the report that replacing the CdO in a
carboxylic or carbonate ester by a CdS bond causes the
RDS change to occur at a lower pKa°.
log(kN/kN°) ) â2(pKa - pKa°) - log[(1 + a/2)]
log a ) (â2 - â1)(pKa - pKa°)
(3)
The â1 and â2 values for the reactions of 1 and 2 are
comparable to those obtained for the pyridinolyses of
various thionocarbonates, which have been suggested to
proceed in a stepwise manner (e.g., â1 ) 0.3 ( 0.1 and â2
) 0.9 ( 0.2 for reactions of O-phenyl O-2,4-dinitrophenyl
thionocarbonate (7),16a O-4-methylphenyl O-4-nitrophenyl
thionocarbonates,7d and bis (O-4-nitrophenyl) thionocar-
bonate16b). Thus, one can suggest that the pyridinolyses
Effect of Ch a n gin g CdO to CdS on Ra tes. Figure
1 demonstrates that the thiono ester 1 is more reactive
than its oxygen analogue 2 except for the reaction with
the strongest basic pyridine studied. However, a con-
trasting reactivity order has been reported; i.e., 3 is less
reactive than 4 toward anionic nucleophiles such as OH-
and EtO- ions.18,21 Similarily, Castro et al. have shown
(15) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963-
6970.
(16) (a) Castro, E. A.; Cubillos, M.; Aliaga, M.; Evangelisti, S.;
Santos, J . G. J . Org. Chem. 2004, 69, 2411-2416. (b) Castro, E. A.;
Santos, J . G.; Tellez, J .; Umana, M. I. J . Org. Chem. 1997, 62, 6568-
6574.
(17) Buncel, E.; Um, I. H.; Hoz, S. J . Am. Chem. Soc. 1989, 111,
971-975.
(18) Campbell, P.; Lapinskas, B. A. J . Am. Chem. Soc. 1977, 99,
5378-5382.
(19) (a) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J . Org. Chem. 2002,
67, 8995-8998. (b) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J . Org.
Chem. 2002, 67, 3874-3877.
(20) Castro, E. A.; Araneda, C. A.; Santos, J . G. J . Org. Chem. 1997,
62, 126-129.
F IGURE 1. Brønsted-type plots for the pyridinolyses of 1 (b)
and 2 (O) in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C.
J . Org. Chem, Vol. 69, No. 19, 2004 6367

Um et al.
TABLE 2. Su m m a r y of th e Micr oscop ic Ra te Con sta n ts
(k1 a n d k2/k-1) for th e Rea ction s of 1 a n d 2 w ith
Z-Su bstitu ted P yr id in es in 80 m ol % H2O/20 m ol % DMSO
a t 25.0 ( 0.1 °C
k1/M-1s-1
k2/k-1
Z-pyridine, Z ) pKa
1
2
1
2
H
4.73
5.09
5.53
5.78
8.93 114
9.12 128
11.30 450
8.34
8.60
14.4
17.3
2.10
2.70
4.58
5.32
93.7
109
925
0.00648 0.00412
3-Me
4-Me
3,4-Me2
4-NH2
4-NMe2
4-O-
0.0125
0.0278
0.0438
0.00624
0.0104
0.0138
0.519
13.5
19.0
1120
0.646
7.94
that 4-nitrophenyl chlorothionoformate and bis(4-nitro-
phenyl) thionocarbonate are less reactive than their
oxygen analogues toward phenoxide anions22a and alicy-
clic secondary amines,22b,c respectively. The contrasting
reactivity order might be explained by the hard and soft
acids and bases (HSAB) principle;23 i.e., the soft thiocar-
bonyl group relative to carbonyl would exhibit higher
reactivity toward relatively soft pyridines of low basicity
(pKa e 9.12), while the harder nature of the carbonyl
group would prefer to bind hard oxyanionic nucleophiles
(e.g., OH-, EtO- and phenoxide anions) and relatively
hard alicyclic secondary amines.23 However, the qualita-
tive HSAB principle cannot explain the finding that 3 is
more reactive than 4 toward relatively hard primary
amines,10,18 while 6 is less reactive than its oxygen
analogue toward relatively soft pyridines.14a
Since a larger kN value can be obtained by increasing
k1 and/or the k2/k-1 ratio, dissection of the apparent
second-order rate constant (kN) to its microscopic rate
constants would allow one to understand the reactivity
order more quantitatively. Thus, we have determined the
microscopic rate constants associated with the pyridi-
nolyses of 1 and 2 as shown below.
F IGURE 2. Plots of log k1 vs pKa for the pyridinolyses of 1
(b) and 2 (O) in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1
°C.
kN values in Table 1. The k1 values determined are
summarized in Table 2.
kN ) k1/(k-1/k2 + 1)
(10)
As shown in Table 2, 1 exhibits larger k1 values than
2 except for the reaction with the strongest basic pyridine
studied. The effect of the pyridine basicity on the k1 value
has been illustrated in Figure 2. The Brønsted-type plots
exhibit that the k1 value increases linearly with increas-
ing the basicity of pyridines for both reactions of 1 and 2
although 1 exhibits smaller slope than 2. It is also noted
that the k1 and the apparent second-order rate constant
(kN) for the reactions of 1 and 2 are in the same order.
As shown in Table 2, the k2/k-1 ratio increases as the
basicity of pyridine increases for the reactions of 1 and
2. The effect of pyridine basicity on the k2/k-1 ratio has
been illustrated in Figure 3. The Brønsted-type plots are
linear with -â-1 values of 0.81 and 0.50 for the reactions
of 1 and 2, respectively. The k2/k-1 ratio is slightly larger
for the reactions of 1 than for those of 2 when the pyridine
is weakly basic, but 1 exhibits much larger k2/k-1 ratio
than 2 as the basicity of pyridines increases.
Equation 2 can be simplified to eqs 4 and 5 depending
on the RDS. Accordingly, â1 and â2 can be expressed as
eqs 6 and 7, respectively.
kN ) k1k2/k-1, when k2 , k-1
kN ) k1, when k2 . k-1
â1 ) d(log k1)/d(pKa)
(4)
(5)
(6)
Effect of Am in e Na tu r e on Ra te. Tertiary amines
have generally been reported to be more reactive than
secondary and primary amines of similar basicity for
ester aminolyses4a,7e,13,14a,24 as well as for deprotonations
of various carbon acids (e.g., phenylnitromethane,25a
â2 ) d(log k1k2/k-1)/d(pKa)
) â1 + d(log k2/k-1)/d(pKa)
(7)
Equation 7 can be rearranged as eq 8. The integral of
(21) Kwon, D. S.; Park, H. S.; Um, I. H. Bull. Korean Chem. Soc.
1991, 12, 93-97.
eq 8 from pKa° results in eq 9. Since k2 ) k-1 at pKa°, the
term (log k2/k-1)pKa° is zero. Therefore, one can calculate
(22) (a) Castro, E. A.; Angel, M.; Arellano, D.; Santos, J . G. J . Org.
Chem. 2001, 66, 6571-6575. (b) Castro, E. A.; Ruiz, M. G.; Salinas,
S.; Santos, J . G. J . Org. Chem. 1999, 64, 4817-4820. (c) Castro, E. A.;
Cubillos, M.; Santos, J . G. J . Org. Chem. 1997, 62, 4395-4397.
(23) Pearson, R. G. J . Chem. Educ. 1968, 45, 581-587.
(24) (a) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1999,
64, 6342-6349. (b) Castro, E. A.; Leandro, L.; Millan, P.; Santos, J . G.
J . Org. Chem. 1999, 64, 1953-1957.
the k2/k-1 ratio from eq 9 using â1 ) 0.26, â2 ) 1.07, and
pKa° ) 7.5 for the reactions of 1 and â1 ) 0.40, â2 ) 0.90
,and pKa° ) 9.5 for the reactions of 2. The k2/k-1 ratios
determined by this method are summarized in Table 2.
â2 - â1 ) d(log k2/k-1)/d(pKa)
(log k2/k-1 pKa ) (â2 - â1)(pKa - pKa°)
(8)
(9)
(25) (a) Bernasconi, C. F.; Kliner, D. A. V.; Mullin, A. S.; Ni, J . X. J .
Org. Chem. 1988, 53, 3342-3351. (b) Bernasconi, C. F.; Hibdon, S. A.
J . Am. Chem. Soc. 1983, 105, 4343-4348. (c) Bernasconi, C. F.; Terrier,
F. J . Am. Chem. Soc. 1987, 109, 7115-7121. (d) Bernasconi, C. F.;
Murray, C. J . J . Am. Chem. Soc. 1986, 108, 5251-5257. (e) Bernasconi,
C. F.; Leyes, A. E.; Eventova, I.; Rappoport, Z. J . Am. Chem. Soc. 1995,
117, 1703-1711.
)
Since eq 2 can be rearranged to eq 10, one can calculate
the k1 values using the k2/k-1 ratios in Table 2 and the
6368 J . Org. Chem., Vol. 69, No. 19, 2004

Pyridinolysis of O-2,4-Dinitrophenyl Thionobenzoate
F IGURE 3. Plots of log k2/k-1 vs pKa for the pyridinolyses of
1 (b) and 2 (O) in 80 mol % H2O/20 mol % DMSO at 25.0 (
0.1 °C.
F IGURE 5. Plots of log k1 vs pKa for the reactions of 2 with
pyridines (4), alicyclic secondary amines (b), and primary
amines (O) in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1
°C. The data for the reactions of 2 with primary and secondary
amines were taken from ref 4a.
O-ethyl aryl dithiocarbonates,25a O-methyl O-4-nitro-
phenyl thionocarbonate,7e ethyl S-aryl carbonates,25b and
O-ethyl O-4-nitrophenyl thionocarbonate14a).
The reactivity of 2 toward pyridines and amines has
been compared in the microscopic rate constant level.
Figure 5 shows that log k1 increases linearly with
increasing the pKa of the conjugate acid of pyridines and
amines. Interestingly, all the pyridines studied exhibit
larger k1 values than primary and secondary amines of
similar basicity, although pyridines are less reactive than
isobasic secondary amines in the low pKa region (e.g., pKa
< ca. 7.2). This result clearly suggests that the reactivity
order shown in Figure 4 is not due to the k1 value.
Gresser and J encks have suggested that k-1 would be
smaller for the reactions with pyridines than for those
with other amines of similar basicity.15 The poor nucleo-
fugality of pyridines from the tetrahedral intermediate
T( has been attributed to a significant contribution of
resonance stabilization by electron donation from the
pyridine to the carbonyl group of the product and to the
oxygen leaving group in the transition-state for the
breakdown of the tetrahedral intermediate.15 Since k2 has
been suggested to be independent of the nature of
amines,2-4,8-12 one can expect that the k2/k-1 ratio would
be larger for the reactions with pyridines than for those
with primary and secondary amines of similar basicity.
However, the result shown in Figure 6 is contrary to the
expectation; i.e., the k2/k-1 ratio is smaller for the
reactions with pyridines (except for the reaction with the
strongest basic pyridine studied) than for those with
primary and secondary amines of similar basicity. The
difference in the k2/k-1 ratio is negligible for highly basic
pyridines but it becomes significant as the pKa decreases.
This result can account for the fact that pyridine becomes
less reactive than isobasic secondary amine as the
basicity of pyridines decreases, although the former
exhibits slightly larger k1 values than the latter in the
low pKa region.
F IGURE 4. Brønsted-type plots for the reactions of 2 with
pyridines (4), alicyclic secondary amines (b), and primary
amines (O) in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1
°C. The data for the reactions of 2 with primary and secondary
amines were taken from ref 4a.
4-nitrophenylacetonitrile,25b and 9-carbomethoxyfluorene25c
)
and additions to activated ethylenes (e.g., benzylidene
Meldrum’s acid25d and â-methoxy-R-nitrostylbene25e). Since
solvation energy has been reported to decrease in the
order RNH3+ > R2NH2+ > R3NH+, solvent effect has been
suggested to be responsible for the reactivity order.25
As shown in Figure 4, pyridines are more reactive than
isobasic secondary amines in the high pKa region (e.g.,
pKa > ca. 7.2) but less reactive in the low pKa region (e.g.,
pKa < ca. 7.2). This is an interesting result since
pyridines have often been reported to be more reactive
than isobasic secondary amines toward various esters
(e.g., 4-methylphenyl 4-nitrophenyl thionocarbonate,7d
(26) Um, I. H.; Baek, M. H.; Han, H. J . Bull. Korean Chem. Soc.
2003, 24, 1245-1250.
J . Org. Chem, Vol. 69, No. 19, 2004 6369

Um et al.
purity of 1 were checked by mp (113-113.5 °C), 1H NMR
spectroscopy, and elemental analysis: 1H NMR (CDCl3) δ 7.52
(m, 3H), 7.69 (t, J ) 8 Hz, 1H), 8.33 (d, J ) 8 Hz, 2H), 8.59
(m, 1H), 9.06 (s, 1H). The 1H NMR spectrum of 1 is also shown
in the Supporting Information. Anal. Calcd for C13N2O5S: C,
51.31; H, 2.65; N, 9.21; O, 26.29; S, 10.54. Found: C, 51.46;
H, 2.62; N, 9.18; S, 10.32.
Kin etics. The kinetic study was performed with a UV-vis
spectrophotometer for slow reactions (t1/2 g 10s) or with a
stopped-flow spectrophotometer for fast reactions (t1/2 < 10s)
equipped with a constant temperature circulating bath at 25.0
( 0.1 °C. All the solutions were transferred by gastight
syringes. The reactions were followed by monitoring the
appearance of the leaving 2,4-dinitrophenoxide ion at 420 nm.
All the reactions were carried out under pseudo-first-order
conditions in which pyridine concentrations were at least 50
times greater than the substrate concentration.
Typically, a reaction was initiated by adding 5 µL of a 0.01
M solution of O-2,4-dinitrophenyl thionobenzoate (1) in aceto-
nitrile by syringe to a 10-mm quartz UV cell containing 2.50
mL of the thermostated reaction mixture made up of solvent
and aliquot of the pyridine stock solution. The pyridine stock
solution of ca. 0.2 M was prepared by dissolving 2 equiv of
pyridine and 1 equiv of standardized HCl solution to keep the
pH constant by making a self-buffered solution. Generally, the
pyridine concentration was varied over the range (1-100) ×
10-3 M, while the substrate concentration was 2 × 10-5 M.
Pseudo-first-order rate constants (kobsd) were calculated from
F IGURE 6. Plots of log k2/k-1 vs pKa for the reactions of 2
with pyridines (4), alicyclic secondary amines (b), and primary
amines (O) in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1
°C. The data for the reactions of 2 with primary and secondary
amines were taken from ref 4a.
Con clu sion s
the equation, ln(A∞ - At) ) -kobsdt + c. The plots of ln(A∞
-
At) vs time were linear over ca. 90% reaction. Usually, five
different pyridine concentrations were employed and replicate
values of kobsd were determined to obtain the second-order rate
constants (kN) from the slope of linear plots of kobsd vs pyridine
concentrations. Detailed kinetic conditions and results for the
reactions of 1 and 2 with pyridines are summarized in the
Supporting Information.
P r od u cts An a lysis. 2,4-dinitrophenoxide was liberated
quantitatively and identified as one of the products in the
pyridinolyses of 1 and 2 by comparison of the UV-vis spectra
after completion of the reactions with those of authentic
samples under the same reaction conditions. The formation
and later decomposition of the initial product (e.g., 1-thiono-
benzoyl-4-dimethylaminopyridinium ion, λmax ) 360 nm) was
detected spectrophotometrically during the reactions.
The present study has allowed us to conclude the
following: (1) The pyridinolyses of 1 and 2 proceed
through an addition intermediate T( in which a change
in the RDS occurs at pKa° 7.5 and 9.5, respectively. (2)
The thiono ester 1 is more reactive than its oxygen
analogue 2 except for the reaction with the strongest
basic pyridine studied (pKa ) 11.30). The higher reactiv-
ity shown by 1 compared to 2 in the low pKa region has
been attributed to the fact that the former exhibits much
larger k1 for the reactions with weakly basic pyridines.
(3) Pyridines are more reactive than alicyclic secondary
amines of similar basicity toward 2 in the pKa above ca.
7.2 but become less reactive in the pKa below ca. 7.2.
Pyridines exhibit slightly larger k1 values but much
smaller k2/k-1 ratios than isobasic secondary amines in
the low pKa region, which accounts for the lower reactiv-
ity shown by the weakly basic pyridines toward 2.
Ack n ow led gm en t. This work was supported by a
grant from KOSEF of Korea (R01-1999-00047).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectrum
for 1 and detailed kinetic conditions and results (Tables S1-
S14). This material is available free of charge via the Internet
at http://pubs.acs.org.
Exp er im en ta l Section
Ma ter ia ls. Compound 1 was prepared by treating thiono-
benzoyl chloride and 2,4-dinitrophenol under the presence of
triethylamine in anhydrous ether.9,10,18 The structure and
J O0492160
6370 J . Org. Chem., Vol. 69, No. 19, 2004