Kinetics and mechanism of the aminolysis of aryl phenyl chlorothiophosphates with anilines

Article abstract of DOI:10.1021/jo0700934

(Chemical Equation Presented) Kinetic studies of the reactions of aryl phenyl chlorothiophosphates (1) and aryl 4-chlorophenyl chlorothiophosphates (2) with substituted anilines in acetonitrile at 55.0°C are reported. The negative values of the cross-interaction constant ρ_XY (ρ_XY = -0.22 and -0.50 for 1 and 2, respectively) between substituents in the nucleophile (X) and substrate (Y) indicate that the reactions proceed by concerted S_N2 mechanism. The primary kinetic isotope effects (k_H/k_D = 1.11-1.13 and 1.10-1.46 for 1 and 2, respectively) involving deuterated aniline nucleophiles are obtained. Front- and back-side nucleophilic attack on the substrates is proposed mainly on the basis of the primary kinetic isotope effects. A hydrogen-bonded, four-center-type transition state is suggested for a front-side attack, while the trigonal bipyramidal pentacoordinate transition state is suggested for a back-side attack. The MO theoretical calculations of the model reactions of dimethyl chlorothiophosphate (1′) and dimethyl chlorophosphate (3′) with ammonia are carried out. Considering the specific solvation effect, the front-side nucleophilic attack can occur competitively with the back-side attack in the reaction of 1′.

Full text of DOI:10.1021/jo0700934

Kinetics and Mechanism of the Aminolysis of Aryl Phenyl
Chlorothiophosphates with Anilines
Md. Ehtesham Ul Hoque, Shuchismita Dey,† Arun Kanti Guha,‡ Chan Kyung Kim,
Bon-Su Lee,* and Hai Whang Lee*
Department of Chemistry, Inha UniVersity, Incheon 402-751, Korea
hwlee@inha.ac.kr; bslee@inha.ac.kr
ReceiVed January 28, 2007
Kinetic studies of the reactions of aryl phenyl chlorothiophosphates (1) and aryl 4-chlorophenyl
chlorothiophosphates (2) with substituted anilines in acetonitrile at 55.0 °C are reported. The negative
values of the cross-interaction constant FXY (FXY ) -0.22 and -0.50 for 1 and 2, respectively) between
substituents in the nucleophile (X) and substrate (Y) indicate that the reactions proceed by concerted SN2
mechanism. The primary kinetic isotope effects (kH/kD ) 1.11-1.13 and 1.10-1.46 for 1 and 2,
respectively) involving deuterated aniline nucleophiles are obtained. Front- and back-side nucleophilic
attack on the substrates is proposed mainly on the basis of the primary kinetic isotope effects. A hydrogen-
bonded, four-center-type transition state is suggested for a front-side attack, while the trigonal bipyramidal
pentacoordinate transition state is suggested for a back-side attack. The MO theoretical calculations of
the model reactions of dimethyl chlorothiophosphate (1′) and dimethyl chlorophosphate (3′) with ammonia
are carried out. Considering the specific solvation effect, the front-side nucleophilic attack can occur
competitively with the back-side attack in the reaction of 1′.
Introduction
on phosphoryl transfer reactions;1i,2 however, much less is
known about thiophosphoryl transfer reactions. Because predict-
ing the effects of replacing the oxygen atom in the phosphoryl
group with sulfur is important, we investigated the kinetics and
mechanism of thiophosphoryl transfer reactions from aryl phenyl
Organothiophosphate compounds are useful as agricultural
chemicals such as insectides, herbicides, acaricides, fungicides,
and plant growth regulators.1 Hence, the chemistry of organ-
othiophosphate compounds is important to a broad range of
interests. A considerable amount of work has been completed
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† Present address: Department of Textile Engineering, Southeast University,
Banani, Dhaka-1213, Bangladesh.
‡ Present address: Department of Textile Engineering, City University, Banani,
Dhaka-1213, Bangladesh.
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10.1021/jo0700934 CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/20/2007
J. Org. Chem. 2007, 72, 5493-5499
5493

Hoque et al.
TABLE 1. Second-Order Rate Constants (k2 × 104/M-1 s-1) and Selectivity Parametersa of the Aminolysis of Y-Aryl Phenyl
Chlorothiophosphates (1) with X-Anilines in Acetonitrile at 55.0 °C
d
X\Y
4-OMe
4-Me
11.0
H
3-Cl
26.2
6.81
1.80
0.198
0.0670
3.98
4-CN
FY
4-OMe
4-Me
H
9.20
2.10
0.802
0.0790
0.0289
3.81
12.6
2.50
1.01
0.0951
0.0343
3.88
43.1
12.6
3.70
0.314
0.117
4.01
1.41
0.73
0.89
0.70
0.67
0.67
2.20
0.873
0.0861
0.0309
3.85
4-Cl
3-Cl
b
-FX
FXYe ) -0.22
c
âX
1.34
1.35
1.36
1.40
a σ values were taken from Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165. The pKa values were taken from Streitwieser, A., Jr.; Heathcock,
C. H. Introduction to Organic Chemistry, 3rd ed.; Macmillan: New York, 1996; p 693. b Correlation coefficients, r, were better than 0.993. c r g 0.990.
d r g 0.984. e r ) 0.990.
chlorothiophosphates (1) and 4-chlorophenyl aryl chlorothio-
phosphates (2) as the PdS counterparts of PdO substrates. Two
main types of displacement processes are well known in neutral
phosphoryl and thiophosphoryl group transfer reactions: the
stepwise mechanism involving a trigonal bipyramidal pentaco-
ordinate (TBP-5C) intermediate2k,3 and the concerted displace-
ment at phosphorus through a single pentacoordinate transition
state (TS).2h,i,4,5 Another additional type is given by the reaction
of chlorophosphates with strong organic bases.6 The base itself
acts as a nucleophilic catalyst, and the leaving group is
substituted by base leading to a very reactive zwitterionic
intermediate. The nucleophile then reacts with this intermediate,
giving the product.
In previous work, we reported several phosphoryl transfer
reactions.7 Anilinolysis of aryl phenyl chlorophosphates (3)7a
and 4-chlorophenyl aryl chlorophosphates (4)7c in acetonitrile
at 55.0 °C was proceeded by a concerted mechanism with the
nucleophile (aniline) and leaving group (Cl) occupying apical
sites in the TS. For both reactions, the cross-interaction
constants,8 FXY in eqs 1a and 1b where X and Y are substituents
in the nucleophiles and substrates, respectively, have negative
values (FXY values are -1.31 and -0.31 for 3 and 4,
respectively), in agreement with our proposed mechanistic
criteria for the sign of FXY.
log(kXY/kHH) ) FXσX + FYσY + FXYσXσY
FXY ) ∂FX/∂σY ) ∂FY/∂σX
(1a)
(1b)
To further our understanding of the mechanism of thiophos-
phoryl transfer, as well as to compare the reactivity when the
oxygen atom in the phosphoryl group is replaced with sulfur,
here we examine the aminolyses of aryl phenyl chlorothiophos-
phates (1) and 4-chlorophenyl aryl chlorothiophosphates (2) with
anilines in acetonitrile at 55.0 °C as PdS counterparts of
PdO, 3 and 4.
(3) (a) Cook, R. D.; Rahhal-Arabi, L. Tetrahedron Lett. 1985, 26, 3147.
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Tilk, H.; Gajl, M. Int. J. Chem. Kinet. 1980, 12, 979. (b) Istomin, B. I.;
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Kumara Swamy, K. C. J. Chem. Sci. 2004, 116, 311. (b) Vijjulatha, M.;
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Leclercq, D. Tetrahedron 1989, 45, 1959. (e) Corriu, R. J. P.; Lanneau, G.
F.; Leclercq, D. Tetrahedron 1986, 42, 5591.
Results and Discussion
The pseudo-first-order rate constants observed (kobsd) for all
reactions obeyed eq 3 with negligible k0 (≈0) in acetonitrile.
The clean second-order rate constants, k2, obtained as the slope
of the plot of kobsd against aniline concentration are summarized
in Tables 1 and 2.
kobsd ) k0 + k2[An]
(3)
PdS substrates (1, 2) are less reactive than their PdO
counterparts (3,7a 47c) by ca. 1 order of magnitude. This order
of reactivity has been ascribed to the so-called “thio effect”.2d,h,5c,9
The rates are faster with a stronger nucleophile (δσX < 0) and
a stronger electron acceptor substituent in the substrate (δσY >
0) which are compatible with typical nucleophilic substitution
reactions where the reaction center, P, of the substrate becomes
more negatively charged in the TS. The rates of 2 are faster
(1.3-3.6 times) than those for the corresponding reactions of 1
(7) (a) Guha, A. K.; Lee, H. W.; Lee, I. J. Chem. Soc., Perkin Trans. 2
1999, 765. (b) Guha, A. K.; Lee, H. W.; Lee, I. J. Org. Chem. 2000, 65,
12. (c) Lee, H. W.; Guha, A. K.; Lee, I. Int. J. Chem. Kinet. 2002, 34, 632.
(d) Lee, H. W.; Guha, A. K.; Kim, C. K.; Lee, I. J. Org. Chem. 2002, 67,
2215. (e) Adhikary, K. K.; Lee, H. W.; Lee, I. Bull. Korean Chem. Soc.
2003, 24, 1135.
(8) (a) Lee, I. Chem. Soc. ReV. 1990, 19, 317. (b) Lee, I. AdV. Phys.
Org. Chem. 1992, 27, 57. (c) Lee, I.; Lee, H. W. Collect. Czech. Chem.
Commun. 1999, 64, 1529.
(9) (a) Oivanen, M.; Ora, M.; Lonnberg, H. Collect. Czech. Chem.
Commun. 1996, 61, S-1. (b) Hondal, R. J.; Bruzik, K. S.; Zhao, Z.; Tsai,
M. D. J. Am. Chem. Soc. 1997, 119, 5477. (c) Gregersen, B. A.; Lopez,
X.; York, D. M. J. Am. Chem. Soc. 2003, 125, 7178. (d) Liu, Y.; Gregersen,
B. A.; Hengge, A. C.; York, D. M. Biochemistry 2006, 45, 10043.
5494 J. Org. Chem., Vol. 72, No. 15, 2007

Aminolysis of Aryl Phenyl Chlorothiophosphates
TABLE 2. Second-Order Rate Constants (k2 × 104/M-1 s-1) and Selectivity Parametersa of the Aminolysis of Y-Aryl 4-Chlorophenyl
Chlorothiophosphates (2) with X-Anilines in Acetonitrile at 55.0 °C
d
X\Y
4-OMe
4-Me
14.6
4.40
1.40
0.234
0.0657
3.53
H
4-Cl
41.8
13.4
3.00
0.706
0.0954
3.86
4-CN
FY
4-OMe
4-Me
H
13.2
4.00
1.39
0.222
0.0628
3.49
16.2
6.11
1.48
0.274
0.0659
3.63
87.6
23.4
6.80
1.11
0.192
3.92
1.38
0.94
0.88
0.79
0.83
0.54
4-Cl
3-Cl
b
-FX
FXYe ) -0.50
c
âX
1.23
1.24
1.28
1.36
a Same as in Table 1. b r g 0.992. c r g 0.994. d r g 0.965. e r ) 0.990.
TABLE 3. Second-Order Rate Constants (k2 × 104/M-1 s-1) and
Kinetic Isotope Effects, kH/kD, for the Reactions of 1 and 2 with
Deuterated X-Anilines in Acetonitrile at 55.0 °C
and N-H(D) moiety. This result is supported by the primary
KIE (kH/kD ) 1.79) involving deuterated aniline nucleophile
with diphenyl chlorophosphinate ((C6H5)2P(dO)Cl; 6) in ac-
etonitrile at 55.0 °C: kH ) 1.73 × 10-3 M-1 s-1(approximately
two times faster than 3) and kD ) 9.69 × 10-4 M-1 s-1. The
kH/kD value for 6, kH/kD ) 1.79 (greater than unity), despite the
absence of the phenoxy oxygen, strongly suggests that there is
no hydrogen bonding between the phenoxy oxygen and hydro-
gen in N-H(D). Comparing again the charge of S (-0.450) in
PdS (1) and that of O (-1.021) in PdO (3), we find that the
hydrogen bonding between S and N-H(D) moiety is also not
possible.
substrate
X
Y
kH
kD
kH/kD
1
4-OMe
4-OMe
H
H
H
4-Cl
4-Cl
4-MeO
4-MeO
H
H
H
H
4-Cl
4-Cl
4-Cl
4-OMe
H
4-OMe
H
4-CN
H
4-CN
H
4-CN
4-MeO
H
4-Cl
4-CN
4-OMe
H
9.20
12.6
0.0802
1.10
3.70
0.0951
0.314
16.2
87.6
1.39
1.48
3.00
6.80
0.222
0.274
1.11
7.80
9.90
1.18
1.27
1.33
1.20
1.32
1.11
1.14
1.10
1.10
1.10
1.10
1.10
1.13
1.31
1.33
1.46
0.0603
0.839
2.80
0.0853
0.276
15.2
82.1
1.27
1.39
2.79
6.00
0.170
0.206
0.759
2
4-CN
because of the electron-withdrawing effect of the electron-
withdrawing ligand (4-ClC6H4O) in 2 which implies the
importance of bond making in the rate-determining step.
(2) The kH/kD value, which is greater than unity in the present
work, could be attributed to the base-catalyzed reaction in which
the second aniline acts as a base as shown in 7. If so, the reaction
rate constant should be third-order. However, no third-order or
higher-order terms were detected, and no complications were
found in the determination of kobsd or in the linear plots of eq
2 with a negligible intercept (k0 = 0.0) in the present studies.
This suggests that there is no base catalysis and the TS structure
7 can be neglected.
In our previous work7a,c on the anilinolyses of 3 and 4 in
acetonitrile, we proposed a concerted mechanism with a late,
product-like TS in which both bond making and leaving group
departure are extensive. In contrast to the back-side nucleophilic
attack on the substrates in the anilinolyses of 3 and 4, in the
present work, a front-side attack concerted mechanism through
a hydrogen-bonded four-center-type TS is proposed on the basis
of the following grounds:
(1) The kinetic isotope effects (KIEs), kH/kD, involving
deuterated aniline nucleophiles (XC6H4ND2) are determined as
shown in Table 3. The kH/kD values are all greater than unity,
kH/kD > 1, indicating that the rate-determining step is not a
simple bond-making process. In such cases, an inverse secondary
KIE, kH/kD < 1, would be expected because of an increase in
the N-H vibrational frequency as a result of steric congestion
of the N-H moiety in the bond-making step,10 as observed in
the anilinolyses of 3 (kH/kD ) 0.61-0.87) and 4 (kH/kD ) 0.64-
0.87). The kH/kD values (kH/kD > 1) in Table 3 suggest that
partial deprotonation of the aniline occurs in the rate-determining
step by hydrogen bonding.10 One plausible TS structure is shown
in 5. Comparing the nonbonding orbital (NBO) charges of the
phenoxy oxygens in 1 (-0.817, -0.824) and 3 (-0.806,
-0.814) as shown in Figure 1, we find that the magnitudes of
the phenoxy oxygen charges are similar and there is no
possibility of a hydrogen bond between the phenoxy oxygen
(3) The cross-interaction constants, FXY ) δFX/δσY ) δFY/
δσX, of 1 and 2 are -0.22 and -0.50, respectively. Figure 2
shows the good linearities (correlation coefficient r ) 0.990
for both reactions), which indicate that third-order
(σX σY, σXσY ) or self second-order (σX , σY ) term interactions
between the substituents of the substrate and/or nucleophiles
are not involved; rather, only the second-order term (σXσY)
interactions, represented in eq 1, between the substituents of
the substrate and nucleophile are involved. The sequence of the
2
2
2
2
(10) Lee, I. Chem. Soc. ReV. 1995, 24, 223.
(11) Hehre, W. J.; Random, L.; Schleyer, P. V. R.; Pople, J. A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986; Chapter 4.
FXY value magnitudes for 1 and 2 is reversed compared to that
of 3 and 4: |FXY(1)| ) 0.22 < |FXY(2)| ) 0.50, |FXY(3)| )
J. Org. Chem, Vol. 72, No. 15, 2007 5495

Hoque et al.
FIGURE 1. B3LYP/6-311+G(d,p)11 geometries and NBO charges of 1 and 3 with Y ) H.
FIGURE 2. Plots of FX vs σY and FY vs σX for the reactions of substrates 1 and 2 with X-anilines in acetonitrile at 55.0 °C.
TABLE 4. Selectivity Parameters and Kinetic Isotope Effects of
F
XY value is obtained in stepwise mechanisms with rate-limiting
breakdown of the intermediate.8,12 The distinction between Pd
S and PdO systems is in the kinetic isotope effects, that is,
inverse secondary KIEs for PdO systems, kH/kD < 1, and
primary normal KIEs for PdS systems, kH/kD > 1 (Table 4).
The most plausible TS structure in the present work is the
hydrogen-bonded, four-center-type with a front-side nucleophile
attack; hydrogen bonding between the hydrogen atom of the
N-H(D) moiety and the negative charge developed the Cl
leaving group, as shown in 8 over the four-membered ring strain.
the Anilinolyses of Substrates 1, 2, 3, and 4 in Acetonitrile at 55.0
°C
substrate
-FX
âX
FY
-FXY
kH/kD
reference
1
2
3
4
3.8-4.0 1.3-1.4 0.7-0.9 0.22 1.1-1.3 this work
3.5-3.9 1.2-1.4 0.5-0.9 0.50 1.1-1.5 this work
3.4-4.6 1.2-1.7 0.2-0.9 1.31 0.6-0.9 7a
4.0-4.2 1.4-1.5 0.1-0.3 0.31 0.6-0.9 7c
1.31 > |FXY(4)| ) 0.31 (Table 4). The smaller magnitude of
|FXY(4)| compared to that of |FXY(3)| indicated partial electron
loss, or shunt, toward the electron acceptor equatorial ligand
(4-ClC6H4O) in the TBP-5C TS.7a,c The smaller magnitude of
FY(4) ) 0.1-0.3 compared to FY(3) ) 0.2-0.9 was also
explained in the same way (i.e., electron shunt; Table 4).7c If
there is no partial electron shunt due to the electron acceptor
ligand (4-ClC6H4O) and only the electron-withdrawing effect
of the ligand is considered, the larger magnitude of |FXY(2)| )
0.50 compared to that of |FXY(1)| ) 0.22 is taken for granted,
as the cross-interaction between the substituents of 2 is stronger
than that of 1. The different sequence of the FXY value
magnitudes between the PdS (1, 2) and PdO (3, 4) systems
strongly suggests that the TS structure of the PdS system differs
from that of the PdO system.
We have previously studied7d the reactions of Z-aryl bis(4-
methoxyphenyl) phosphates ((4-MeOC6H4O)2P(dO)OC6H4Z)
with pyridines (XC5H4N) in acetonitrile. In the case of more
basic phenolate groups (Z ) 4-Cl-3-CN) and less basic pyridines
(3-Cl-4-CN), we proposed the concerted mechanism with a
front-side nucleophile attack on the basis of the FX, âX, âZ, and
especially large negative FXZ () -1.98) values.
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1995, 16, 839. (j) Koh, H. J.; Lee, O. S.; Lee, H. W.; Lee, I. J. Phys. Org.
Chem. 1997, 10, 725. (k) Koh, H. J.; Han, K. L.; Lee, H. W.; Lee, I. J.
Org. Chem. 2000, 65, 4706. (l) Lee, K. S.; Adhikary, K. K.; Lee, H. W.;
Lee, B. S.; Lee, I. Org. Biomol. Chem. 2003, 1, 1989. (m) Lee, I.; Lee, H.
W.; Yu, Y. K. Bull. Korean Chem. Soc. 2003, 24, 993.
(4) The FX and âX values of the PdS (1, 2) and PdO (3, 4)
systems have similar magnitudes, and the FY values of 1, 2,
and 3 also have comparable magnitudes (Table 4). The sign of
FXY values obtained in the present work is negative, as it is in
PdO systems. The negative FXY value is characteristic of
concerted nucleophilic substitution reactions, while the positive
5496 J. Org. Chem., Vol. 72, No. 15, 2007

Aminolysis of Aryl Phenyl Chlorothiophosphates
show little difference within 1 kcal mol-1, respectively, in
acetonitrile and in aqueous solution. However, since the
experimental works are carried out in acetonitrile, we have
discussed the theoretical results obtained in aceonitrile, and the
results in aqueous solution are summarized in Supporting
Information. In this calculation, substitution reactions of methyl
chlorothiophosphate (1′) and methyl cholorophosphate (3′), in
which two phenyl groups in 1 and 3 are replaced by methyl
groups, with ammonia have been selected as model systems.
The optimized TS structures and calculated activation energy
barriers (∆Eq) are summarized in Figure 3 and Table 5,
respectively. Examination of Table 5 shows that the ∆Eq for
the back-side attack is more favorable by 0.98 kcal mol-1 for
3′ than for 1′. This fits well with the experimental results
discussed earlier (i.e., PdS substrates are less reactive than their
PdO analogues). On the other hand, the ∆Eq for the front-side
attack is more unfavorable by 1.59 kcal mol-1 for 3′ than that
for 1′. This strongly implies that the front-side attack mechanism
could occur competitively with the back-side attack mechanism
in the reaction of 1′ compared to that of 3′. Nevertheless, as
seen in Table 5, the ∆Eq for the back-side attack of 1′ is lower
than that for the front-side attack by 3.57 kcal mol-1; hence,
the contribution of the front-side attack mechanism could be
small. This seems inconsistent with the current proposed
mechanism. However, the SCRF method employed in this
theoretical approach considers only a bulk solvation effect
without a specific solvation effect. Therefore, if specific
solvation effects are included, the difference in ∆Eq between
the back- and front-side attacks could be decreased or reversed.
The TS structure for the front-side attack is a much more
product-like, that is, charge-separated, late TS relative compared
to that for the back-side attack (Figure 3), that is, the bond
making and breaking of P-N and P-Cl are advanced by 0.462
[2.360(a) - 1.898(b)] and 0.274 [2.440(b) - 2.166(a)] Å,
respectively, for the front-side attack TS structure compared to
the back-side attack. As a result, in the front-side attack TS,
the charge densities calculated by the natural population analysis
(NPA)18 are more negative for Cl fragments by -0.195e and
more positive for NH3 fragments by +0.239e, corresponding
to a leaving group and a nucleophile, respectively, than in the
back-side attack TS. This indicates that the degree of stabiliza-
tion by specific solvation effects could be larger in the TS
structure for the front-side attack. Indeed, when one acetonitrile
molecule is included to examine the specific solvation effect,
the difference between the activation energy barriers for the
back-side and the front-side attack (δ∆Eq) is decreased (i.e.,
the δ∆Eq is decreased as 1.63 kcal mol-1 when the specific
solvation effect of one acetonitrile molecule is considered).19
Therefore, a front-side attack concerted mechanism is a plausible
prediction in the reactions of 1 and 2, if the specific solvation
effects are fully considered. On the other hand, reaction
intermediates cannot locate as stable species on the hypothetical
potential energy surface. Therefore, the reactions are expected
to occur via the concerted mechanism; this is consistent with
the result obtained from the sign of FXY values (vide supra).
In the anilinolysis of 1-phenyl ethyl benzenesulfonates (1-
PEB),13 we proposed a hydrogen-bonded four-center TS with a
front-side nucleophile attack on the basis of the primary KIEs
with deuterated aniline nucleophile, kH/kD ) 1.70-2.35, in
acetonitrile at 30 °C. We also carried out optical rotation
measurements and found that ca. 55% of the original reactant
(1-PEB) stereochemistry was retained in the product because
of the front-side attack and that ca. 45% of the remaining
reactant was inverted because of the back-side attack.14
In the present work, we suggest that the nucleophile attacks
the substrate from both directions, front- and back-side, the same
as in the anilinolysis of 1-PEB.13 The observed primary KIE
seems relatively small because of (a) inverse secondary KIE
due to the partial participation of the back-side attack and (b)
heavy atom (N, Cl) participation in the reaction coordinate
motion. We also propose a four-center TS with a front- and
back-side attack for the anilinolysis of diphenyl chlorophos-
phinate (6) on the basis of the primary normal KIE, kH/kD
)
1.79.15
(5) To examine the activation energy barriers for front-side
and back-side nucleophilic attack of the substrate, MO theoreti-
cal calculations are carried out at the MP2/6-31+G(d) level16
of theory using the self-consistent reaction field (SCRF)
methodology of the CPCM17 polarizable conductor calculation
model in acetonitrile and in aqueous solution. All the trends in
acetonitrile medium are very similar to those in aqueous solution
(i.e., the TS structures and the relative energetics calculated by
the CPCM method are very similar in both acetonitrile and
aqueous solution). For example, bond lengths for bond making
of the nucleophile and breaking of the leaving group at TSs are
nearly the same within 0.01 Å, and the relative energetics also
(13) (a) Lee, I.; Kim, H. Y.; Kang, H. K.; Lee, H. W. J. Org. Chem.
1988, 53, 2678. (b) Lee, I.; Koh, H. J.; Lee, B. S.; Lee, H. W. J. Chem.
Soc., Chem. Commun. 1990, 335.
(14) Lee, I.; Shim, C. S.; Lee, H. W.; Lee, B. S. Bull. Korean Chem.
Soc. 1991, 12, 255.
(15) One of the reviewers indicated the possible TS of 6 with hydrogen
bonding involving the strong acceptor PdO. The proposed TS cannot be
completely excluded, and further work on phosphinates will clarify the TS
structure.
(16) (a) Head-Gordon, M.; Pople, J. A.; Frisch, M. J. Chem. Phys. Lett.
1988, 153, 503. (b) Head-Gordon, M.; Pople, J. A. J. Chem. Phys. 1988,
89, 5777. (c) Frisch, M. J.; Head-Gordon, M.; Pople, J. A. Chem. Phys.
Lett. 1990, 166, 275. (d) Frisch, M. J.; Head-Gordon, M.; Pople, J. A. Chem.
Phys. Lett. 1990, 166, 281. (e) Head-Gordon, M.; Head-Gordon, T. Chem.
Phys. Lett. 1994, 220, 122.
(17) (a) Barone, V.; Cossi, M. J. Phys. Chem. A 1998, 102, 1995. (b)
Cossi, M.; Rega, N.; Scalmani, G.; Barone, V. J. Comput. Chem. 2003, 24,
669.
(18) (a) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. ReV. 1988, 88,
899. (b) Carpenter, J. E.; Weinhold, F. J. Mol. Struct.: THEOCHEM 1988,
169, 41. (c) Glendening, E. D.; Weinhold, F. J. Comput. Chem. 1998, 19,
593. (d) Glendening, E. D.; Weinhold, F. J. Comput. Chem. 1998, 19, 610.
(e) Glendening, E. D.; Badenhoop, J. K.; Weinhold, F. J. Comput. Chem.
1998, 19, 628.
(19) The specific solvation effects are calculated by a simple supermo-
lecular approach adding one acetonitrile molecule at the fixed TS geometries.
J. Org. Chem, Vol. 72, No. 15, 2007 5497

Hoque et al.
FIGURE 3. TS structures optimized at the CPCM-MP2/6-31+G(d) level of theory for the reactions of (a) 1′ (back-side attack), (b) 1′ (front-side
attack), (c) 3′ (back-side attack), and (d) 3′ (front-side attack) with ammonia in acetonitrile.
TABLE 5. Calculated Activation Energy Barriers (∆Eq in kcal
6-311+G(d,p) level and the calculated activation energy barriers
mol-1) at the CPCM-MP2/6-31+G(d) Level for the Reactions of 1′
(∆Eq) at the CPCM-MP2/6-31+G(d) level of theory.
and 3′ with Ammonia in Acetonitrile
∆Eq (back side)
∆Eq (front side)
δ∆Eq a
Experimental Section
1′
3′
6.11
5.13
9.68
11.27
3.57
6.14
Materials. Diphenylphosphinic chloride, 98% (substrate), and
HPLC-grade acetonitrile were used for kinetic studies without
further purification. Anilines were redistilled or recrystallized before
use as previously described.20 Deuterated anilines were prepared
by heating anilines with D2O at 85 °C for 72 h, and after numerous
attempts, anilines were deuterated more than 98%, as confirmed
by 1H NMR. The substrates were prepared by the two-step
synthesis.7a The starting materials, thiophosphoryl chloride, phenol,
4-chlorophenol, and triethylamine were G.R. grade and were used
without further purification.
Kinetic Procedure. Rates were measured conductometrically in
acetonitrile at 55.0 °C. A self-made computer connected automatic
A/D converter conductivity bridge was used in this work. Pseudo-
first-order rate constants, kobsd, were determined as previously
described7 with a large excess of anilines: [substrate] ) 3 × 10-3
M; [aniline] ) 0.1-0.5 M for 1, and [aniline] ) 0.1-0.3 M for 2.
The second-order rate constants, k2, were also obtained as previously
described.7 Product analysis is described in the Supporting Informa-
tion.
a δ∆Eq ) ∆Eq (front side) - ∆Eq (back side).
Summary
The aminolyses of aryl phenyl chlorothiophosphates (1) and
aryl 4-chlorophenyl chlorothiophosphates (2) with X-anilines
in acetonitrile at 55.0 °C are investigated. The cross-interaction
constants, FXY, are negative for both 1 and 2. The obtained
kinetic isotope effects (kH/kD) involving deuterated aniline
(XC6H4ND2) nucleophiles are greater than unity, kH/kD > 1,
suggesting that the rate-determining step involves partial depro-
tonation of the aniline by hydrogen bonding. This is consistent
with a front-side attack concerted mechanism through a
hydrogen-bonded four-center-type transition state. On the basis
of the cross-interaction constant and primary kinetic isotope
effects, we propose a concerted SN2 mechanism with front- and
back-side nucleophilic attack on substrate. A hydrogen-bonded,
four-center TS is suggested for a front-side attack, while the
TBP-5C TS is suggested for a back-side attack. The MO
theoretical calculations of the model reactions of 1′ and 3′ with
ammonia nucleophile are carried out. The charge densities
calculated by the NPA18 are more negative and more positive
for the leaving group (Cl) and the nucleophile, respectively, in
the front-side attack TS than in the back-side attack TS,
indicating that the degree of stabilization by specific solvation
effects could be larger in the front-side attack TS. This is
supported by the results of NBO analysis at the B3LYP/
Acknowledgment. This work was supported by a grant from
KOSEF of Korea (R01-2004-000-10279-0).
Supporting Information Available: Synthetic procedures,
product analysis, and analytical and spectroscopic data for all
compounds. The theoretical calculations containing the Cartesian
coordinates and absolute energies of optimized structures of the
compounds: (A) Reactant: aryl phenyl chlorothiophosphates (1)
(20) Lee, I.; Lee, H. W.; Sohn, S. C.; Kim, C. H. Tetrahedron 1985, 41,
2635.
5498 J. Org. Chem., Vol. 72, No. 15, 2007

Aminolysis of Aryl Phenyl Chlorothiophosphates
and aryl phenyl chlorophosphates (3); (B) modeling calculation (TS
structures in acetonitrile): (i) PdS back-side attacking TS for
dimethyl chlorothiophosphate (1′), (ii) PdS front-side attacking TS
for dimethyl chlorothiophosphate (1′), (iii) PdO back-side attacking
TS for dimethyl chlorophosphate (3′), (iv) PdO front-side attacking
TS for dimethyl chlorophosphate (3′) with NH3, (v) PdS back-
side attacking TS for dimethyl chlorothiophosphate (1′) with one
acetonitrile molecule, (vi) PdS front-side attacking TS for dimethyl
chlorothiophosphate (1′) with one acetonitrile molecule; and (C)
modeling calculation (TS structures in aqueous solution): (i) PdS
back-side attacking TS for dimethyl chlorothiophosphate (1′), (ii)
PdS front-side attacking TS for dimethyl chlorothiophosphate (1′),
(iii) PdO back-side attacking TS for dimethyl chlorophosphate (3′),
(iv) PdO front-side attacking TS for dimethyl chlorophosphate (3′)
with NH3, (v) PdS back-side attacking TS for dimethyl chlorothio-
phosphate (1′) with one water molecule, (vi) PdS front-side
attacking TS for dimethyl chlorothiophosphate (1′) with one water
molecule. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO0700934
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