Aminolyses of aryl diphenylphosphinates and diphenylphosphinothioates: Effect of modification of electrophilic center from P=O to P=S

Article abstract of DOI:10.1021/jo070171n

(Chemical Equation Presented) A kinetic study is reported for aminolysis of aryl diphenylphosphinothioates (2a-i). The phosphinothioates 2a-i are less reactive than aryl diphenylphosphinates (1a-i), the oxygen analogues of 2a-i, regardless of the basicity

Full text of DOI:10.1021/jo070171n

Aminolyses of Aryl Diphenylphosphinates and
Diphenylphosphinothioates: Effect of Modification of Electrophilic
Center from PdO to PdS
Ik-Hwan Um,* Kalsoom Akhtar, Young-Hee Shin, and Jeong-Yoon Han
DiVision of Nano Sciences and Department of Chemistry, Ewha Womans UniVersity, Seoul 120-750, Korea
ihum@ewha.ac.kr
ReceiVed January 29, 2007
A kinetic study is reported for aminolysis of aryl diphenylphosphinothioates (2a-i). The phosphinothioates
2a-i are less reactive than aryl diphenylphosphinates (1a-i), the oxygen analogues of 2a-i, regardless
of the basicity of the leaving aryloxides or the attacking amines. The Yukawa-Tsuno plot for the reactions
of 2b-i with piperidine exhibits good linearity with a small r value (r ) 0.28), indicating that the leaving
group departs at the rate-determining step with a small degree of bond fission. Reactions of
2,4-dinitrophenyl diphenylphosphinothioate (2a) with alicyclic secondary amines result in a good linear
Brønsted-type plot with ânuc ) 0.52, implying that the reactions proceed through a concerted mechanism.
The ânuc value determined for the reactions of 2a is slightly larger than that reported for the corresponding
reactions of 2,4-dinitrophenyl diphenylphosphinate (1a, i.e., ânuc ) 0.38), suggesting that reactions of 2a
proceed through a tighter transition state (TS) than that of 1a. The reaction of 2a with piperidine exhibits
a ca. 0.4 kcal/mol more favorable enthalpy of activation (∆Hq) than that of 1a. On the contrary, the
entropy of activation at 25.0 °C (T∆Sq) is ca. 1.5 kcal/mol more unfavorable for the reaction of 2a than
for that of 1a. This result supports the proposal that the reaction of 2a proceeds through a tighter TS than
that of 1a and explains why 2a-i are less reactive than 1a-i.
Introduction
methods have been developed. These include the use of highly
reactive R-effect nucleophiles2-4 or the use of various metal
ions as Lewis acid catalysts.5-7 The R-effect nucleophiles (e.g.,
oximates, o-iodosylbenzoate, and HOO- anions) have been
reported to exhibit significantly enhanced nucleophilic reactivity
than would be predicted from their basicity, particularly in the
presence of a cationic surfactant such as hexadecyltrimethyl-
ammonium ion.2-4 Alkali metal ions5 and divalent metal ions
There is continuous interest in phosphoryl transfer and related
reactions due to their importance in the environment as well as
in biological processes.1-12 The need for improved methods of
environmental decontamination has provided the impetus for
numerous studies aimed at enhancing the rate of decomposition
of toxic organophosphorus compounds.2-7 Accordingly, various
* Corresponding author. Tel.: 82-2-3277-2349. Fax: 82-2-3277-2844.
(1) (a) Hengge, A. C.; Onyido, I. Curr. Org. Chem. 2005, 9, 61-74. (b)
Rawlings, I.; Cleland, W. W.; Hengge, A. C. J. Am. Chem. Soc. 2006, 128,
17120-17125. (c) Onyido, I.; Swierzek, K.; Purcell, J.; Hengge, A. C. J.
Am. Chem. Soc. 2005, 127, 7703-7711. (d) Sorensen-Stowell, K.; Hengge,
A. C. J. Org. Chem. 2006, 71, 7180-7184. (e) Purcell, J.; Hengge, A. C.
J. Org. Chem. 2005, 70, 8437-8442. (f) Sorensen-Stowell, K.; Hengge,
A. C. J. Org. Chem. 2005, 70, 8303-8308. (g) Sorensen-Stowell, K.;
Hengge, A. C. J. Org. Chem. 2005, 70, 4805-4809.
(2) (a) Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley:
New York, 2000. (b) Wu, T. G.; Qiu, J. U. EnViron. Sci. Technol. 2006,
40, 5428-5434. (c) Eyer, P. Toxicol. ReV. 2003, 22, 165-190. (d) Morles-
Rojas, H.; Moss, R. A. Chem. ReV. 2002, 102, 2497-2521. (e) Yang, Y.
C.; Baker, J. A.; Ward, J. R. Chem. ReV. 1992, 92, 1729-1743. (f) Kevill,
D. N.; Carver, J. S. Org. Biomol. Chem. 2004, 2, 2040-2043. (g) Kevill,
D. N.; D’Souza, M. J. Can. J. Chem. 1999, 77, 1118. (h) Kevill, D. N.;
Bond, M. W.; D’Souza, M. J. J. Org. Chem., 1997, 62, 7869. (i) Kevill, D.
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10.1021/jo070171n CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/11/2007
J. Org. Chem. 2007, 72, 3823-3829
3823

Um et al.
(e.g., Mg2+, Ca2+, Zn2+, Cu2+, Co2+, and Mn2+)6 have also
exhibited significant catalytic effects in nucleophilic substitution
reactions of aryl diphenylphosphinates and their analogues.
Besides, the La3+ ion has been shown to be highly effective on
alkaline methanolysis of phosphate di- and triesters.7
SCHEME 1
Kinetic studies have also been performed intensively to under-
stand the reaction mechanisms of biological processes.1-6,8-12
Linear free-energy relationships such as Hammett and Brønsted
equations have most commonly been employed to investigate
reaction mechanisms.1-6,8-12 For example, alkaline ethanolysis
of aryl dimethylphosphinates has been concluded to proceed
through a pentacoordinate intermediate with its formation being
the rate-determining step (RDS) on the basis of the fact that σo
constants result in significantly better Hammett correlations than
σ- constants.5a A similar conclusion has been drawn for alkaline
hydrolysis of aryl diphenylphosphinates8a,8b and imidazole
catalyzed hydrolysis of aryl diphenylphosphinates.9a
On the contrary, nucleophilic substitution reactions of 4-ni-
trophenyl diphenylphosphinate with aryloxides have been
concluded to proceed through a concerted mechanism.9b The
evidence provided for a concerted mechanism is a linear
Brønsted-type plot for the reactions with a series of substituted
phenoxides whose pKa values straddle the basicity of the leaving
4-nitrophenoxide.9b A similar result has been obtained for
reactions of aryl dimethylphosphinothioates with aryloxides (i.e.,
a linear Brønsted-type plot for the reactions of 4-nitrophenyl
dimethylphosphinothioate with aryloxides having a wide pKa
range (i.e., pKa ) 5.53-10.2)).1c Besides, σ- constants have
resulted in much better Hammett correlations than σo constants
for reactions of aryl dimethylphosphinothioates with phenoxide.
Accordingly, Hengge and co-workers have concluded that the
reactions proceed through a concerted mechanism.1c This
conclusion has been further supported by the primary 18O and
secondary 15N kinetic isotope effects.1c
(3) (a) Stairs, R. A.; Buncel, E. Can. J. Chem. 2006, 84, 1580-1591.
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2006, 22, 9009-9017. (c) Churchill, D.; Cheung, J. C. F.; Park, Y. S.;
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Only a few reports are available for aminolysis of phosphoryl
and related compounds.10-12 Reactions with amines have been
suggested to proceed either through a concerted or through a
stepwise mechanism. From studies of leaving group effects,
solvent effects, and activation parameters, Cook et al. have
concluded that aminolysis of aryl diphenylphosphinates and
related compounds in MeCN proceeds through a zwitterionic
pentacoordinate intermediate with its breakdown being the
RDS.10 However, Lee et al. have proposed that pyridinolysis
of phenyl-substituted phenyl chlorophosphates proceeds through
a concerted mechanism on the basis of linear Brønsted-type plots
with small ânuc values (ânuc ) 0.16-0.18).11
We have recently performed aminolysis of aryl diphenylphos-
phinates (1a-i) and concluded that the reactions proceed
through a concerted mechanism although σo constants result in
a better Hammett correlation than σ- constants.12 This was
because the Yukawa-Tsuno plot for the same reactions exhibits
a significantly better linearity than the Hammett plot correlated
with σo constants.12 The concerted mechanism has been further
supported from the linear Brønsted-type plot with ânuc ) 0.38
for the reactions of 2,4-dinitrophenyl diphenylphosphinate (1a)
with a series of alicyclic secondary amines.12
(8) (a) Cook, R. D.; Rahhal-Arabi, L. Tetrahedron Lett. 1985, 26, 3147-
3150. (b) Haake, P.; McCoy, D. R.; Okamura, W.; Alpha, S. R.; Wong, S.
W.; Tyssee, D. A.; McNeal, J. P.; Cook, R. D. Tetrahedron Lett. 1968,
5243-5246. (c) Wallerberg, G.; Haake, P. J. Org. Chem. 1981, 46, 43-
46.
We have extended our study to aminolysis of aryl diphe-
nylphosphinothioates (2a-i), the thio analogues of 1a-i, as
shown in Scheme 1. Replacement of O by a polarizable S atom
in the PdO bond of 1a-i would be expected to provide insights
into both the reactivity and the comparative reaction mechanism.
We report the effect of modification of the electrophilic center
from PdO to PdS on reactivity and reaction mechanisms. In
addition to our Brønsted analysis, we have analyzed the
substituent effects according to the dual-parameter Yukawa-
(9) (a) Williams, A.; Naylor, R. A. J. Chem. Soc. B 1971, 1967-1972.
(b) Bourne, N.; Chrystiuk, E.; Davis, A. M.; Williams, A. J. Am. Chem.
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Samaha, M.; Shayban, F.; Tanielian, O. V. Can. J. Chem. 1986, 64, 213-
219.
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15. (b) Guha, A. K.; Lee, H. W.; Lee, I. J. Chem. Soc., Perkin Trans. 1999,
2, 765-770.
(12) Um, I. H.; Shin, Y. H.; Han, J. Y.; Mishima, M. J. Org. Chem.
2006, 71, 7715-7720.
3824 J. Org. Chem., Vol. 72, No. 10, 2007

Aryl Diphenylphosphinates/Diphenylphosphinothioates
TABLE 1. Summary of Second-Order Rate Constants (kN, M-1
s-1) for Reactions of X-Substituted Phenyl Diphenylphosphinates (1)
and Diphenylphosphinothioates (2) with Piperidine in 80 mol %
H2O/20 mol % DMSO at 25.0 ( 0.1 °C
TABLE 2. Summary of Second-Order Rate Constants (kN, M-1
s-1) for Reactions of 2,4-Dinitrophenyl Diphenylphosphinate (1a)
and Diphenylphosphinothioate (2a) with Alicyclic Secondary Amines
in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C
102 kN (M-1 s-1
)
102 kN (M-1s-1
)
a
pKa
1b
419
66.4
3.06
0.720
1.57
0.587
0.245
0.211
0.149
2
kNPdO/kN
amines
pKa
1ab
2a
kNPdO/kN
PdS
a
PdS
X
(X-PhOH)
a
b
c
d
e
f
g
h
i
2,4-(NO2)2
3,4-(NO2)2
4-NO2
4-CHO
4-CN
4-COMe
3-Cl
3-COMe
4-Cl
4.11
5.42
7.14
7.66
7.95
8.05
9.02
9.19
9.38
74.7
6.63
0.230
0.0634
0.147
0.0615
0.0213
0.0194
0.0166
5.6
10.0
13.3
11.4
10.7
9.5
11.5
10.9
9.0
piperidine
11.02 419
10.80 429
9.85 234
9.38
8.65
7.98
5.95
74.7
72.9
39.6
9.64
5.50
2.38
0.262
5.6
5.9
5.9
3-methyl piperidine
piperazine
1-(2-hydroxyethyl)-piperazine
morpholine
1-formyl piperazine
piperazinium ion
93.9
57.3
33.2
9.7
10.4
13.9
27.1
7.09
a pKa data in 20 mol % DMSO were taken from ref 15. b Data for the
reactions of 1a were taken from ref 12.
a The pKa data were taken from ref 36. b Data for the reactions of 1a-i
were taken from ref 12.
Effect of Replacing PdO by PdS on Reactivity. Table 1
shows that the phosphinothioates 2a-i are ca. 5-13 times less
reactive than their oxygen analogues 1a-i. The current result
is consistent with the reports that replacing the O atom in the
PdO bond of phosphoryl compounds by an S atom causes a
decrease in reactivity.1,2,20,21 The thio effect, defined as the ratio
of rate constants kPdO/kPdS, has been reported to be 4-11 for
reactions of the methyl 2,4-dinitrophenyl phosphate/phosphoro-
thioate system with various nucleophiles1c,20 and 12.4 for
alkaline hydrolysis of the triethyl phosphate/phosphorothioate
system.21 Similar results have been reported for reactions that
have been suggested to proceed through a concerted mechanism
(i.e., kPdO/kPdS ) 2-5 for alkaline hydrolysis of the aryl
dimethylphosphinate/phosphinothioate system).1c Several pro-
posals have been advanced to account for the decreased
reactivity on replacing PdO by PdS (e.g., decreased electron
donating ability of P-O- as compared to P-S-,22,23 greater
electrophilicity of phosphorus in phosphoryl than in thiophos-
phoryl compounds,24,25 and enhanced polarizability of the PdS
bond).26
Tsuno equation (eq 1).13,14 This combined approach has previ-
ously proven to be highly effective to elucidate ambiguities in
reaction mechanisms of acyl transfer and related reactions.12,15-18
log kX/kH ) FX[σo + r(σ- - σo)]
Results and Discussion
(1)
All reactions in this study obeyed pseudo-first-order kinetics
in the presence of a large excess of amine. Diphenylpiperidi-
nophosphine sulfide was found quantitatively as one of the
reaction products, indicating that the amine behaves as a
nucleophile but not as a general base catalyst. Pseudo-first-order
rate constants (kobsd) were determined from the equation ln(A∞
- At) ) -kobsdt + c. The plots of kobsd versus the amine
concentration were linear, indicating that general base catalysis
by the second amine molecule is absent. The second-order rate
constants (kN) were determined from the slope of the linear plots
of kobsd versus the amine concentration. The uncertainty in the
kN values is estimated to be less than 3% from replicate runs.
The kN values determined are summarized in Tables 1-3. The
activation parameters (∆Hq and ∆Sq) were calculated from the
Arrhenius equation.19 The Arrhenius plots for the reactions of
1a and 2a with piperidine performed at five different temper-
atures resulted in good linear correlations (R2 ) 0.9930 and
0.9990 for the reactions of 1a and 2a, respectively; see Figure
S1 in the Supporting Information).
On the contrary, the 4-nitrophenyl phosphorothioate dianion
has been reported to be more reactive than its oxygen analogue,
4-nitrophenyl phosphate dianion, under alkaline hydrolysis
conditions (i.e., kPdO/kPdS ) 0.1-0.3).1e The enhanced reactivity
shown by the PdS compound has been attributed to the
difference in the reaction mechanism (i.e., a stepwise dissocia-
tive mechanism (i.e., DN + AN) for the phosphorothioate vs a
concerted mechanism for the phosphate).1e
Accordingly, the kPdO/kPdS ratio has been used to predict
mechanistic details of enzymatic phosphoryl transfer.27,28 How-
ever, the magnitude of the thio effect alone cannot differentiate
(13) (a) Tsuno, Y.; Fujio, M. AdV. Phys. Org. Chem. 1999, 32, 267-
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R.; Tsuno, Y. Bull. Chem. Soc. Jpn. 2006, 79, 1091-1099. (b) Fujio, M.;
Uchida, M.; Okada, A.; Alam, M. A.; Fujiyama, R.; Siehl, H. U.; Tsuno,
Y. Bull. Chem. Soc. Jpn. 2005, 78, 1834-1842. (c) Fujio, M.; Rappoport,
Z.; Uddin, H. J.; Kim, H. J.; Tsuno, Y. Bull. Chem. Soc. Jpn. 2003, 76,
163-169. (d) Nakata, K.; Fujio, M.; Nishimoto, K.; Tsuno, Y. J. Phys.
Org. Chem. 2003, 16, 323-335.
(20) Herschlag, D.; Piccirilli, J. A.; Cech, T. R. Biochemistry 1991, 30,
4844-4854.
(21) Fanni, T.; Taira, K.; Gorenstein, D. G.; Vaidyanathaswamy, R.;
Verkade, J. G. J. Am. Chem. Soc. 1986, 108, 6311-6314.
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1010-1016.
(23) Zhang, Y. L.; Hollfelder, F.; Gorden, S. J.; Chen, L.; Keng, Y. F.;
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(25) Neimysheva, A. A.; Savchikl, V. I.; Ermolaeva, W. V.; Knunyants,
I. L. Bull. Acad. Sci. USSR., DiV. Chem. Sci. (Engl. Transl.) 1968, 2104-
2108.
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Chem. 2004, 69, 3937-3942.
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J. Org. Chem, Vol. 72, No. 10, 2007 3825

Um et al.
TABLE 3. Summary of Kinetics Results for Reactions of 2,4-Dinitrophenyl Diphenylphosphinate (1a) and Diphenylphosphinothioate (2a) with
Piperidine in 80 mol % H2O/20 mol % DMSO at 15.0, 20.0, 25.0, 35.0, and 45.0 ( 0.1 °C
k
N (M-1 s-1
)
15.0 °C
20.0 °C
25.0 °C
35.0 °C
45.0 °C
∆Hq (kcal mol-1
)
∆Sq (eu)
1a
2a
3.09
0.489
3.85
0.584
4.19
0.747
7.71
1.16
12.0
1.79
7.73 ((0.56)
7.34 ((0.02)
-29.3 ((1.8)
-34.3 ((0.6)
a concerted mechanism from a stepwise associative mechanism
(i.e., AN + DN) since the kPdO/kPdS ratio has also been reported
to be ca. 10-25 for reactions that have been suggested to
proceed through a stepwise AN + DN mechanism (e.g., alkaline
hydrolysis of the alkyl dialkylphosphinate/phosphino-
thioate system29 and ethanolysis of the 4-nitrophenyl diethyl
phosphate/phosphorothioate system).5d Thus, the kPdO/kPdS ratio
of 5-13 observed in the current system cannot provide
conclusive information on the reaction mechanism. Clearly,
further analysis of the kinetic data is required to elucidate the
reaction mechanism.
Effect of Leaving Group on Reactivity. Table 1 shows that
the second-order rate constant kN increases as the basicity of
the leaving group decreases for the reactions of 1a-i and 2a-i
with piperidine. The effect of basicity of the leaving group on
reactivity is illustrated in Figure 1. The Brønsted-type plot for
the reactions of 2a-i is linear with many scattered points. A
similar Brønsted-type plot can be seen for the corresponding
reactions of 1a-i.
The linear Brønsted-type plots for the current system contrast
to the curved Brønsted-type plot reported for the corresponding
reactions of aryl benzoates. We have reported that the Brønsted
slope (âlg) changes from -1.50 to -0.36 as the basicity of the
leaving aryloxide decreases.30 Such a curved Brønsted-type plot
is typical for reactions that proceed through a stepwise mech-
anism with a change in the RDS (i.e., from breakdown of the
intermediate to its formation as the basicity of the leaving group
decreases).15-18 On the other hand, a linear Brønsted-type plot
with a moderate âlg value has often been reported for reactions
that proceed through a concerted mechanism.12,30-32 Although
the Brønsted-type plot for the reactions of 2a-i is linear with
a moderate âlg value, it exhibits many scattered points. Thus,
one cannot obtain reliable information on the reaction mecha-
nism from the current Brønsted plot.
Reaction Mechanism Determined from Hammett and
Yukawa-Tsuno Plots. Hammett correlations have most fre-
quently been used to investigate reaction mechanisms of aryl
phosphinates.1,5,8,33 It is generally accepted that σ- constants
result in a good correlation with rate constants for reactions in
which departure of the leaving group occurs at the RDS whether
the reaction proceeds through a concerted mechanism or through
a stepwise manner. On the other hand, σo constants give a good
correlation with rate constants for reactions that proceed through
a stepwise mechanism with departure of the leaving group
occurring after the RDS.
Hammett plots have been constructed for the reactions of
2b-i with piperidine with the use of the σ- and σo constants
obtained from the literature.34 As illustrated in Figure 2, the σ-
constants exhibit a poor correlation with rate constants (R2 )
0.956). However, as shown in the inset of Figure 2, the σo
constants result in a better correlation (R2 ) 0.987). The fact
that the σo constants give a better correlation than the σ-
constants implies that direct resonance interactions between the
substituent in the leaving group and the reaction center are not
occurring in the TS.35 Thus, one might conclude that the current
reactions proceed through a pentacoordinate intermediate in
which the departure of the leaving group is not advanced in the
RDS. A similar conclusion has been drawn for nucleophilic
substitution reactions of various phosphinates and phosphi-
nothioates on the basis of the result that σo constants result in
a better correlation than σ- constants (e.g., reactions of aryl
dimethylphosphinates with ethoxide,5a alkaline hydrolysis of aryl
diphenylphosphinothioates8a and diphenylphosphinates,8b and
imidazole catalyzed hydrolysis of aryl diphenylphosphinates).9a
We have recently reported that the determination of a reaction
mechanism based just on Hammett correlations with σ- or σo
constants as the only mechanistic evidence can be misleading.12
It has been shown that the dual-parameter Yukawa-Tsuno
equation (eq 1) is highly effective to elucidate ambiguities in
reaction mechanisms of phosphinyl transfer reactions.12 Ac-
cordingly, Yukawa-Tsuno plots have been constructed for the
current reactions. As shown in Figure 3, the Yukawa-Tsuno
plot for the reactions of 2b-i with piperidine results in a
significantly improved correlation (R2 ) 0.998) with FX ) 1.91
and r ) 0.28. A similar result is shown for the reactions of
1b-i (i.e., FX ) 1.91 and r ) 0.30). It is noted that the FX and
r values are practically identical for the reactions of 1b-i and
2b-i.
The magnitude of the r value in the Yukawa-Tsuno plot
represents the resonance demand of the reaction center or the
extent of resonance contribution.13,14 The fact that r ) 0.28 for
the aminolysis of 2b-i (or r ) 0.30 for the reactions of 1b-i)
indicates that a partial negative charge develops on the O atom
of the leaving aryloxides in the TS. Thus, one can conclude
that the departure of the leaving group occurs at the RDS,
although the degree of bond fission would not be significant
on the basis of the small r value. However, the current result
alone cannot discern whether the reactions proceed through a
concerted mechanism or through a stepwise manner with
departure of the leaving group being the RDS. To get further
information on the reaction mechanism, the reactions of 2a with
a series of alicylic secondary amines have been performed.
(29) Cook, R. D.; Farah, S.; Ghawi, L.; Itani, A.; Rahil, J. Can. J. Chem.
1986, 64, 1630-1637.
(30) Um, I. H.; Lee, J. Y.; Ko, S. H.; Bae, S. K. J. Org. Chem. 2006,
71, 5800-5803.
(34) (a) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165-
195. (b) Taft, R. W. J. Phys. Chem. 1960, 64, 1805-1815.
(35) (a) Um, I. H.; Hwang, S. J.; Buncel, E. J. Org. Chem. 2006, 71,
915-920. (b) Um, I. H.; Lee, J. Y.; Kim, H. T.; Bae, S. K. J. Org. Chem.
2004, 69, 2436-2441. (c) Um, I. H.; Han, H. J.; Ahn, J. A.; Kang, S.;
Buncel, E. J. Org. Chem. 2002, 67, 8475-8480.
(36) Jencks, W. P.; Regenstein, J. In Handbook of Biochemistry, 2nd
ed.; Sober, H. A., Ed.; Chemical Rubber Publishing Co.: Cleveland, OH,
1970; p J-195.
(31) (a) Castro, E. A.; Gazitua, M.; Santos, J. J. Org. Chem. 2005, 70,
8088-8092. (b) Castro, E. A.; Aliaga, M.; Santos, J. J. Org. Chem. 2005,
70, 2679-2685.
(32) (a) Castro, E. A.; Aguayo, R.; Bessolo, J.; Santos, J. J. Org. Chem.
2005, 70, 7788-7791. (b) Castro, E. A.; Aguayo, R.; Bessolo, J.; Santos,
J. J. Org. Chem. 2005, 70, 3530-3536.
(33) Douglas, K. T.; Williams, A. J. Chem. Soc., Perkin Trans. 1976, 2,
515-521.
3826 J. Org. Chem., Vol. 72, No. 10, 2007

Aryl Diphenylphosphinates/Diphenylphosphinothioates
FIGURE 1. Brønsted-type plots for reactions of X-substituted phenyl
diphenylphosphinates (1a-i, O) and diphenylphosphinothioates (2a-
i, b) with piperidine in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1
°C. The identity of points is given in Table 1.
FIGURE 3. Yukawa-Tsuno plots for reactions of X-substituted phenyl
diphenylphosphinates (1b-i, O) and diphenylphosphinothioates (2b-
i, b) with piperidine in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1
°C. The identity of the points is given in Table 1.
FIGURE 2. Plots of log kN vs σ- (or σ°, inset) for reactions of
X-substituted phenyl diphenyl phosphinothioates (2b-i) with piperidine
in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The identity of
the points is given in Table 1.
FIGURE 4. Brønsted-type plots for reactions of 2,4-dinitrophenyl
diphenylphosphinate (1a, O) and diphenylphosphinothioate (2a, b) with
alicyclic secondary amines in 80 mol % H2O/20 mol % DMSO at 25.0
( 0.1 °C. The identity of points is given in Table 2.
Effect of Amine Basicity on Reactivity. Table 2 shows that
kN decreases as the basicity of amines decreases. It is also noted
that 2a is less reactive than 1a regardless of the amine basicity.
The effect of amine basicity on reactivity is illustrated in Figure
4. The Brønsted-type plots exhibit good linear correlations for
the reactions of 1a and 2a. These linear Brønsted-type plots
also contrast to the curved Brønsted-type plots reported for the
corresponding reactions of 2,4-dinitrophenyl benzoate and
related compounds that have been suggested to proceed through
a stepwise mechanism with a change in the RDS.16-18
J. Org. Chem, Vol. 72, No. 10, 2007 3827

Um et al.
odithioic acid (2.5 g, 10 mmol), N,N′-dicyclohexylcarbodiimide (1.5
equiv), and 4-(dimethylamino) pyridine (0.2 equiv) were dissolved
in methylene chloride (30 mL) and stirred for 3 h. X-Substituted
phenol (10 mmol) dissolved in methylene chloride (20 mL) was
added to the acid solution dropwise. The reaction mixture was
stirred under nitrogen at room temperature. The progress of the
reaction was monitored by TLC. When the reaction was completed,
the reaction mixture was worked up as follows: N,N′-dicyclohexy-
lthiourea was filtered off, and then the methylene chloride solution
was concentrated under a reduced pressure. The crude product was
purified by column chromatography (silica gel, methylene chloride/
n-hexane 50:50). The purity was checked by their melting points
for the known compounds, and the identity of unreported com-
pounds 2a, 2b, 2d, 2g, and 2h was checked by elemental analysis
and 1H NMR spectra (Supporting Information). All unreported
compounds gave good elemental analyses except 2a, which was
shown to contain a small amount of 2,4-dinitrophenol. However,
the phenol impurity was shown to have no effect on kinetic
determination.
The ânuc values are 0.38 and 0.52 for the reactions of 1a and
2a, respectively. The ânuc value of 0.38 or 0.52 is too small for
reactions that proceed through a stepwise mechanism with
breakdown of the intermediate being the RDS but is typical for
reactions that proceed through a concerted mechanism.30-32
Thus, one can suggest that the aminolysis of 1a and 2a proceeds
through a concerted mechanism. It is noted that the reactions
of 2a exhibit a larger ânuc value than those of 1a, indicating
that the degree of bond formation between the amine and the
electrophilic center at the RDS is slightly more advanced for
the reactions of 2a. On the other hand, the degree of the leaving
group departure would be the same for the reactions of 1a-i
and 2a-i on the basis of the fact that their FX and r values are
practically the same (Figure 3). Accordingly, one can propose
that the aminolysis of 2a-i proceeds through a tighter TS than
the corresponding reactions of 1a-i (i.e., the degree of bond
formation is more advanced for the reactions of 2a than for
those of 1a, while the leaving group departure is nearly identical
in the TS of the RDS).
TS Structures and Activation Parameters. The reactions
of 1a and 2a with piperidine have been performed at 15.0, 20.0,
25.0, 35.0, and 45.0 °C to determine the activation para-
meters (∆Hq and ∆Sq). As shown in Table 3, the enthal-
pies of activation (∆Hq) are 7.73 and 7.34 kcal/mol for the
reactions of 1a and 2a, respectively, indicating that the ∆Hq
term is ca. 0.4 kcal/mol more favorable for the reaction of 2a
than for that of 1a. On the contrary, the reaction of 2a is
accompanied by a more negative entropy of activation
(∆Sq) than that of 1a (i.e., -29.3 and -34.3 eu for the reactions
of 1a and 2a, respectively). This result implies that T∆Sq at
25.0 °C is ca. 1.5 kcal/mol more unfavorable for the reaction
of 2a than for that of 1a. Thus, one can suggest that the
difference in T∆Sq between the two systems is a possible origin
of the thio effect found in the current study. Furthermore, the
fact that 2a exhibits a more negative ∆Sq value than 1a indi-
cates that the TS is more ordered for the reaction of 2a than for
that of 1a. This argument clearly supports the preceding pro-
posal that the reactions of 2a proceed through a tighter TS than
those of 1a.
2,4-Dinitrophenyl Diphenylphosphinothioate (2a). mp 105-
108 °C; 1H NMR (250 MHz, CDCl3) δ 7.49-7.57 (m, 6H), 7.73-
7.77 (dd, J1 ) 1.3 Hz, J2 ) 10 Hz, 1H), 7.96-8.05 (m, 4H), 8.28-
8.33 (dd, J1 ) 2.8 Hz, J2 ) 10 Hz, 1H), 8.76-8.77 (d, J ) 2.3 Hz,
1H), Anal. Calcd for C18H13N2O5PS: C, 54.00; H, 3.27. Found:
C, 53.80; H, 3.37.
3,4-Dinitrophenyl Diphenylphosphinothioate (2b). mp 91-
1
93 °C; H NMR (250 MHz, CDCl3) δ 7.52-7.53 (d, J ) 2.5 Hz,
1H), 7.54-7.58 (m, 7H), 7.90-8.00 (m, 5H), Anal. Calcd for
C18H13N2O5PS: C, 54.00; H, 3.27. Found: C, 54.02; H, 3.29.
4-Formylphenyl Diphenylphosphinothioate (2d). mp 91-93
°C; 1H NMR (250 MHz, CDCl3) δ 6.92-7.25 (dd, J1 ) 2.5 Hz, J2
) 10 Hz, 2H), 7.50-7.55 (m, 6H), 7.78-7.82 (d, J ) 10 Hz, 2H),
7.94-8.03 (m, 4H), 10.27 (s, 1H), Anal. Calcd for C19H15O2PS:
C, 67.44; H, 4.47. Found: C, 67.53; H, 4.39.
3-Chlorophenyl Diphenylphosphinothioate (2g). mp 85-87
1
°C; H NMR (250 MHz, CDCl3) δ 7.08-7.12 (d, 10 Hz, 1H),
7.48-7.50 (m, 3H), 7.51-7.54 (m, 6H), 7.91-8.00 (m, 4H), Anal.
Calcd for C18H14ClOPS: C, 62.70; H, 4.09. Found: C, 62.71; H,
4.10.
3-Acetylphenyl Diphenylphosphinothioate (2h). mp 61-62 °C;
1H NMR (250 MHz, CDCl3) δ 2.50 (s, 3H), 7.25-7.49 (m, 2H),
7.50-7.53 (m, 7H), 7.54-7.57 (d, J ) 7.5 Hz, 1H), 7.94-8.03
(m, 4H), Anal. Calcd for C20H17O2PS: C, 68.17; H, 4.86. Found:
C, 68.20; H, 4.84.
Amines and other chemicals were of the highest quality available.
Doubly glass distilled water was further boiled and cooled under
nitrogen just before use. Because of a low solubility of 2a-i in
pure water, aqueous DMSO (80 mol % H2O/20 mol % DMSO)
was used as the reaction medium.
Kinetics. The kinetic study was performed with a UV-vis
spectrophotometer equipped with a constant temperature circulating
bath. The reactions were followed by monitoring the appear-
ance of the leaving aryloxide. All the reactions were carried out
under pseudo-first-order conditions in which amine concen-
trations were at least 100 times greater than the substrate concentra-
tion. The amine stock solution of ca. 0.2 M was prepared by
dissolving 2 equiv of free amine and 1 equiv of standardized HCl
solution to make a self-buffered solution in a 25.0 mL volumetric
flask.
Conclusion
The present study has allowed us to conclude the follow-
ing: (1) the phosphinothioates 2a-i are less reactive than
their oxygen analogues 1a-i, regardless of the basicity of the
leaving group or attacking amine. (2) The Yukawa-Tsuno
plots exhibit good linear correlations with a small r value for
the reactions of 1b-i and 2b-i, implying that departure
of the leaving group occurs at the RDS but that the de-
gree of bond fission is insignificant. (3) The Brønsted-type
plots are linear for the reactions of 1a and 2a with ânuc values
of 0.38 and 0.52, respectively, suggesting that these
reactions proceed through a concerted mechanism. (4) The
aminolysis of 2a exhibits ca. 0.4 kcal/mol more favorable
∆Hq but ca. 1.5 kcal/mol more unfavorable T∆Sq than that of
1a, indicating that the T∆Sq term is a possible origin of
the thio effect found in this study. (5) The fact that 2a
exhibits a larger ânuc and more negative T∆Sq suggests
that the reaction of 2a proceeds through a tighter TS than
that of 1a.
Typically, the reaction was initiated by adding 5 µL of a 0.02
solution of 2,4-dinitrophenyl diphenylphosphinothioate
M
(2a) in acetonitrile to a 10 mm quartz UV cell containing 2.50 mL
of the thermostated reaction mixture made up of solvent and an
aliquot of the amine stock solution. All the solutions were
transferred by gastight syringes. Generally, the amine concen-
tration was varied over the range (5-200) × 10-3 M, while the
substrate concentration was 2 × 10-5 M. Pseudo-first-order
Experimental Section
Materials. Aryl diphenylphosphinothioates 2a-i were prepared
rate constants (kobsd) were calculated from the equation, ln(A∞ -
by modification of literature procedures:10,22 Diphenylphosphin-
At) ) -kobsdt + C. The plots of ln(A∞ - At) versus time were
3828 J. Org. Chem., Vol. 72, No. 10, 2007

Aryl Diphenylphosphinates/Diphenylphosphinothioates
linear over ca. 90% of the total reaction. Usually, five dif-
ferent amine 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 versus amine
concentrations.
Product Analysis. X-Substituted phenoxide was liberated
quantitatively and identified as one of the products in the reaction
of 2a-i with piperidine by comparison of the UV-vis spectra
after completion of the reaction with the authentic sample under
the same reaction conditions. The other product from the reac-
tions of 2a-i with piperidine (i.e., diphenylpiperidinophos-
phine sulfide) was analyzed quantitatively by HPLC (Rt ) 10.4
min, a reversed phase 250 mm × 4.6 mm i.d. column, CH3CN/
H2O ) 70:30 as a mobile phase, flow rate ) 1.0 mL/min, detection
at 229 nm).
Acknowledgment. This work was supported by the Korea
Research Foundation (2005-015-C00256). The authors are also
grateful for a BK 21 Scholarship.
Supporting Information Available: 1H NMR spectra for
compounds 2a, 2b, 2d, 2g, and 2h; Tables S1-S9 of the kinetic
conditions and data for the reactions of 2a-i with piperidine; Tables
S10-S16 of the reactions of 2a with seven different alicyclic
secondary amines; and Tables S17-S20 of the reactions of 1a and
2a with piperidine at 15.0, 20.0, 35.0, and 45.0 °C. Figure S1 of
Arrhenius plots for the reactions of 1a and 2a with piperidine at
five different temperatures. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO070171N
J. Org. Chem, Vol. 72, No. 10, 2007 3829