Aminolysis of Y-substituted phenyl diphenylphosphinates and benzoates: Effect of modification of electrophilic center from C=O to P=O

Article abstract of DOI:10.1021/jo061308x

(Chemical Equation Presented) The effect of modification of the electrophilic center from C=O to P=O on reactivity and reaction mechanism has been investigated for aminolysis of Y-substituted phenyl diphenylphosphinates (1a-j) and benzoates (2a-i). The phosphinates 1a-j are less reactive than the benzoates 2a-i. The reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with alicyclic secondary amines resulted in a linear Bronsted-type plot with a β_nuc value of 0.38, while the corresponding reactions of 2,4-dinitrophenyl benzoate (2a) yielded a curved Bronsted-type plot. Similarly, a linear Bronsted-type plot with a β_1g value of -0.66 was obtained for the reactions of 1a-j with piperidine, while the corresponding reactions of 2a-i gave a curved Bronsted-type plot. The linear Bronsted-type plots for the reactions of 1a-j have been taken as evidence for a concerted mechanism, while the curved Bronsted-type plots for the reactions of 2a-i have been suggested to indicate a change in the rate-determining step of a stepwise mechanism. The Hammett plot for the reactions of 1b-j exhibited a poor correlation with σ^- constants (R² = 0.962) but slightly better correlation with σ^o (R² = 0.986). However, the Yukawa-Tsuno plot for the same reactions resulted in an excellent correlation (R² = 0.9993) with an r value of 0.30. The aminolysis of 1a-j has been suggested to proceed through a concerted mechanism with an early transition state on the basis of the small β_nuc and small r values.

Full text of DOI:10.1021/jo061308x

Aminolysis of Y-Substituted Phenyl Diphenylphosphinates and
Benzoates: Effect of Modification of Electrophilic Center from
CdO to PdO
Ik-Hwan Um,*,‡ Young-Hee Shin,‡ Jeong-Yoon Han,‡ and Masaaki Mishima†
Department of Chemistry, Ewha Womans UniVersity, Seoul 120-750, Korea, and Institute for Materials
Chemistry and Engineering, Kyushu UniVersity, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
ihum@ewha.ac.kr
ReceiVed June 25, 2006
The effect of modification of the electrophilic center from CdO to PdO on reactivity and reaction
mechanism has been investigated for aminolysis of Y-substituted phenyl diphenylphosphinates (1a-j)
and benzoates (2a-i). The phosphinates 1a-j are less reactive than the benzoates 2a-i. The reactions
of 2,4-dinitrophenyl diphenylphosphinate (1a) with alicyclic secondary amines resulted in a linear Brønsted-
type plot with a ânuc value of 0.38, while the corresponding reactions of 2,4-dinitrophenyl benzoate (2a)
yielded a curved Brønsted-type plot. Similarly, a linear Brønsted-type plot with a âlg value of -0.66 was
obtained for the reactions of 1a-j with piperidine, while the corresponding reactions of 2a-i gave a
curved Brønsted-type plot. The linear Brønsted-type plots for the reactions of 1a-j have been taken as
evidence for a concerted mechanism, while the curved Brønsted-type plots for the reactions of 2a-i
have been suggested to indicate a change in the rate-determining step of a stepwise mechanism. The
Hammett plot for the reactions of 1b-j exhibited a poor correlation with σ- constants (R2 ) 0.962) but
slightly better correlation with σo (R2 ) 0.986). However, the Yukawa-Tsuno plot for the same reactions
resulted in an excellent correlation (R2 ) 0.9993) with an r value of 0.30. The aminolysis of 1a-j has
been suggested to proceed through a concerted mechanism with an early transition state on the basis of
the small ânuc and small r values.
Introduction
to destroy stockpiles of toxic organophosphorus compounds has
led a number of groups to investigate different approaches
toward enhancing decomposition of these compounds. Accord-
ingly, a number of methods have been developed. These include
the use of highly reactive R-effect nucleophiles in the presence
of cationic surfactants2-4 and various metal ions.5-7 The R-effect
nucleophiles such as HOO-, o-iodosobenzoate, and oximate
anions have shown abnormally enhanced nucleophilic reactivi-
ties than would be predicted from their basicity in dephosphoryl
reactions.2-4 Furthermore, the enhanced reactivity of these
anionic nucleophiles toward phosphorus compounds has been
reported to be more remarkable in the presence of a cationic
surfactant such as hexadecyltrimethylammonium ion.2-4 Alkali
There has been continuous interest in phosphoryl transfer and
related reactions due to environmental significance as well as
biological importance.1-10 The need to develop efficient means
* Address correspondence to this author. Phone: 82-2-3277-2349. Fax: 82-
2-3277-2844.
‡ Ewha Womans University.
† Kyushu University.
(1) (a) Toy, A. D. F.; Walsh, E. N. Phosphorus Chemistry in EVeryday
LiVing, 2nd ed.; American Chemical Society: Washington, DC, 1987;
Chapters 18-20. (b) Quin, L. D. A Guide to Organophosphorus Chemistry;
Willey: New York, 2000. (c) Hengge, A. C. AdV. Phys. Org. Chem. 2005,
40, 49-108.
(2) (a) Morles-Rojas, H.; Moss, R. A. Chem. ReV. 2002, 102, 2497-
2521. (b) Yang, Y. C.; Baker, J. A.; Ward, J. R. Chem. ReV. 1992, 92,
1729-1743. (c) Yang, Y. C. Acc. Chem. Res. 1999, 32, 109-115.
metal ions5 and divalent metal ions (e.g., Mg2+, Ca2+, Zn2+
Cu2+, Co2+, Mn2+, Pt2+ 6
have also exhibited significant
,
)
10.1021/jo061308x CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/02/2006
J. Org. Chem. 2006, 71, 7715-7720
7715

Um et al.
TABLE 1. Summary of Second-Order Rate Constants (kN, M-1
catalytic effects in nucleophilic substitution reactions of aryl
diphenylphosphinate and its analogues. Besides, La3+ ion has
been recently shown to be extremely effective on alkaline
methanolysis of phosphate di- and triesters.7
s-1) for the Reactions of 2,4-Dinitrophenyl Diphenylphosphinate (1a)
and 2,4-Dinitrophenyl Benzoate (2a) with Alicyclic Secondary
Amines in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C
kN/M-1 s-1
Kinetic studies have also been performed intensively to
investigate the mechanism of biological processes.5,8-10 How-
ever, most studies have been focused on hydrolysis in alkaline
conditions. Williams et al. have performed reactions of 4-ni-
trophenyl diphenylphosphinate with aryloxides in aqueous
medium and concluded that the reactions proceed through a
concerted mechanism.8a The evidence suggested for a concerted
mechanism is a linear Brønsted-type plot for the reactions with
a series of aryloxides whose pKa values are greater than and
less than that of the leaving 4-nitrophenoxide.8a On the other
hand, alkaline hydrolysis of aryl diphenylphosphinates has been
suggested to proceed through a pentacoordinate intermediate
with its formation being the rate-determining step (RDS) on
the basis of good Hammett correlations with σo constants.8b,c
A similar conclusion has been drawn for imidazole catalyzed
hydrolysis of aryl diphenylphosphinates8d and alkaline etha-
nolysis of aryl dimethylphosphinates.5a
Only few reports are available on aminolysis of phosphoryl
and related esters.9,10 Accordingly, their mechanism has not been
completely understood. Cook et al. have concluded that ami-
nolysis of 4-nitrophenyl diphenylphosphinate in MeCN proceed
through a stepwise mechanism in which breakdown of a
zwitterionic pentacoordinate intermediate is the RDS.9 In the
reaction with n-butylamine, the breakdown of the zwitterionic
intermediate has been shown to be general base catalyzed since
the reaction follows a two-term rate law, i.e., one first order in
amine and the other second order in amine.9 On the contrary,
a
entry
amine
pKa
1a
2ab
174
167
82.1
1
2
3
4
5
6
7
piperidine
11.02
10.8
9.85
9.38
8.65
7.98
5.95
4.19
4.29
2.34
0.939
0.573
0.332
0.0709
3-methylpiperidine
piperazine
1-(2-hydroxyethyl)piperazine
morpholine
1-formylpiperazine
piperazinium ion
19.6
5.43
0.467
a The pKa data in 20 mol % DMSO. Data were taken from ref 11. b The
data for the reactions of 2a were taken from ref 11.
Lee et al. have suggested that reactions of phenyl-substituted
phenyl chlorophosphates with pyridines proceed through a
concerted mechanism in MeCN, since the Brønsted-type plots
obtained are linear with small ânuc values (0.16-0.18).10a
We have performed two series of kinetic studies to investigate
the reaction mechanism, i.e., reactions of 1a with seven different
alicyclic secondary amines and reactions of piperidine with nine
different Y-substituted phenyl diphenylphosphinates (1a-j) in
water containing 20 mol % dimethyl sulfoxide (DMSO) at 25.0
( 0.1 °C. The kinetic data obtained in this study have been
compared with those reported for the corresponding reactions
of Y-substituted phenyl benzoates (2a-i) since the reaction
mechanism for aminolysis of these benzoates has been fairly
well understood. We report the effect of modification of the
electrophilic center from CdO to PdO on the reactivity and
reaction mechanism. We also show that deduction of reaction
mechanism based just on Hammett correlations with σ- or σo
constants alone can be misleading.
(3) (a) Balakrishnan, V. K.; Buncel, E.; van Loon, G. W. EnViron. Sci.
Technol. 2005, 39, 5824-5830. (b) Balakrishnan, V. K.; Han, X.; van Loon,
G. W.; Dust, J. M.; Toullec, J.; Buncel, E. Langmuir 2004, 20, 6586-
6593. (c) Bunton, C. A.; Foroudian, H. J. Langmuir 1993, 9, 2832-2835.
(d) Yang, Y. C.; Berg, F. J.; Szafraniec, L. L.; Beaudry, W. T.; Bunton, C.
A.; Kumar, A. J. Chem. Soc., Perkin Trans. 2 1997, 607-613. (e) Toullec,
J.; Moukawin, M. Chem. Commun. 1996, 221-222. (f) Bhattacharya, S.;
Vemula, P. K. J. Org. Chem. 2005, 70, 9677-9685.
(4) (a) Terrier, F.; Le Guevel, E.; Chartrousse, A. P.; Moutiers, G.;
Buncel, E. Chem. Commun. 2003, 600-601. (b) Bunton, C. A.; Nelson, S.
E.; Quan, C. J. Org. Chem. 1982, 47, 1157-1160. (c) Couderc, S.; Toullec,
J. Langmuir 2001, 17, 3819-3828.
(5) (a) Buncel, E.; Albright, K. G.; Onyido, I. Org. Biomol. Chem. 2004,
2, 601-610. (b) Nagelkerke, R.; Thatcher, G. R. J.; Buncel, E. Org. Biomol.
Chem. 2003, 1, 163-167. (c) Buncel, E.; Nagelkerke, R.; Thatcher, G. R.
J. Can. J. Chem. 2003, 81, 53-63. (d) Um, I. H.; Jeon, S. E.; Baek, M. H.;
Park, H. R. Chem. Commun. 2003, 3016-3017. (e) Pregel. M. J.; Buncel,
E. J. Am. Chem. Soc. 1993, 115, 10-14.
(6) (a) Zalatan, J.; Herschlag, D. J. Am. Chem. Soc. 2006, 128, 1293-
1303. (b) O’Brien, P. J.; Herschlag, D. Biochemistry 2001, 40, 5691-5699.
(c) Catrina, I. E.; Hennge, A. C. J. Am. Chem. Soc. 1999, 121, 2156-
2163. (d) Herschlag, D.; Jencks, W. P. J. Am. Chem. Soc. 1987, 109, 4665-
4674.
(7) (a) Gibson, G. T. T.; Neverov, A. A.; Teng, A. C. T.; Brown, R. S.
Can. J. Chem. 2005, 83, 1268-1276. (b) Tsang, J. S.; Neverov, A. A.;
Brown, R. S. J. Am. Chem. Soc. 2003, 125, 1559-1566. (c) Tsang, A. A.;
Neverov, A. A.; Brown, R. S. J. Am. Chem. Soc. 2003, 125, 7602-7607.
(8) (a) Bourne, N.; Chrystiuk, E.; Davis, A. M.; Williams, A. J. Am.
Chem. Soc. 1988, 110, 1890-1895. (b) Cook, R. D.; Rahhal-Arabi, L.
Tetrahedron Lett. 1985, 26, 3147-3150. (c) 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. (d) Williams, A.; Naylor,
J. J. Chem. Soc. B 1971, 1967-1972.
(9) Cook, R. D.; Daouk, W. A.; Hajj, A. N.; Kabbani, A.; Kurku, A.;
Samaha, M.; Shayban, F.; Tanielian, O. V. Can. J. Chem. 1986, 64, 213-
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(10) (a) Guha, A. K.; Lee, H. W.; Lee, I. J. Org. Chem. 2000, 65, 12-
15. (b) Guha, A. K.; Lee, H. W.; Lee, I. J. Chem. Soc., Perkin Trans 2
1999, 765-770.
Results and Discussion
All reactions in this study obeyed pseudo-first-order kinetics
in the presence of a large excess of amine. From product studies,
it is clear that the one molecule of amine involved is the
attacking nucleophile, and it is not acting as a general base
toward solvent attack. Pseudo-first-order rate constants (kobsd
)
were determined from the equation ln(A∞ - At) ) -kobsdt + c.
The correlation coefficient for the linear regression was usually
higher than 0.999. The plots of kobsd vs amine concentration
were linear passing through the origin, indicating that general
base catalysis by the second amine molecule is absent and the
contribution of H2O and/or OH- ion from amine equilibration
with water present to kobsd is negligible. The second-order rate
constants (kN) were determined from the slope of the linear plots
of kobsd vs 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 and 2.
Effect of Amine Basicity on Reactivity and Mechanism.
As shown in Table 1, the kN value for the reactions of 1a
decreases as the amine basicity decreases, i.e., it decreases from
4.19 M-1 s-1 to 0.939 and 0.0709 M-1 s-1 as the pKa of the
conjugate acid of the amine decreases from 11.02 to 9.38 and
5.95, respectively. A similar result can be seen for the
corresponding reactions of 2a. However, the phosphinate 1a is
much less reactive than the benzoate 2a regardless of the amine
basicity.
The effect of amine basicity on reactivity is illustrated in
Figure 1. The Brønsted-type plot for the reactions of 1a is linear
7716 J. Org. Chem., Vol. 71, No. 20, 2006

Phenyl Diphenylphosphinates and Benzoates
TABLE 2. Summary of Apparent Second-Order Rate Constants
(kN, M-1 s-1) for the Reactions of Y-Substitued Phenyl
Diphenylphosphinates (1a-j) and Y-Substitued Phenyl Benzoates
(2a-i) with Piperidine in 80 mol % H2O/20 mol % DMSO at 25.0 (
0.1 °C
SCHEME 1
kN/M-1 s-1
pKa
(Y-PhOH)
entry
Y
1
2b
a
b
c
2,4-(NO2)2
3,4-(NO2)2
2-NO2,4-Cl
4-NO2
4.11
5.42
6.46
7.14
4.19
0.664
174
191
6.18
5.94
d
0.0306
(0.000332)a
0.00720
0.0157
0.00587
0.00245
0.00211
0.00149
e
f
g
h
i
4-CHO
4-CN
4-COMe
3-Cl
3-COMe
4-Cl
7.66
7.95
8.05
9.02
9.19
9.38
0.852
0.236
0.0159
0.00650
shown in Scheme 1, since reactions of phosphinate esters have
been reported to result in smaller ânuc values than the corre-
sponding reactions of carbonyl or sulfonyl esters.14
j
a The kN value determined in MeCN. Reference 9. b The data for the
reactions of 2a-i were taken from ref 15 except the kN value of 2c. The kN
value for the reactions of 2c was determined in this study.
On the other hand, the ânuc value of the Brønsted-type plot
shown in Figure 1 for the reactions of 2a decreases from 0.74
to 0.34 as the amine basicity increases. On the basis of such a
nonlinear Brønsted-type plot, we reported that the aminolysis
of 2a proceeds through a stepwise mechanism with a change
in the RDS.11 However, Castro et al. have recently suggested
that the curved Brønsted-type plot for the aminolysis of 2a is
not due to a change in the RDS.13 It is because the slopes of
the nonlinear Brønsted-type plot are not in accordance with those
reported for the reactions which have been suggested to proceed
through a stepwise mechanism, i.e., â2 ) 0.74 at the low pKa
region is not large enough (e.g., â2 ) 0.8-1.1) while â1 ) 0.34
at the high pKa region is not small enough for a stepwise
mechanism (e.g., â2 ) 0.1-0.3).13 Accordingly, the aminolysis
of 2a has been suggested to proceed very likely through a
concerted mechanism.13 The same conclusion has been drawn
for the reactions of S-2,4-dinitrophenyl X-substituted thioben-
zoates with a series of alicyclic secondary amines.13a Although
Castro et al. have obtained curved Brønsted-type plots (i.e., â1
) 0.1-0.4 and â2 ) 0.7 at high and low pKa region,
respectively), the reactions have been concluded to proceed
through a concerted mechanism.13a
Thus, the curved Brønsted-type plot shown in Figure 1 for
the aminolysis of 2a appears to be insufficient to conclude
whether the reaction proceeds through a concerted mechanism
or through a stepwise pathway. To get more conclusive
information about the reaction mechanism, the effect of the
leaving group basicity on reactivity and mechanism has been
investigated in the following section.
FIGURE 1. Brønsted-type plots for the reactions of 2,4-dinitrophenyl
diphenylphosphinate (1a, b) and 2,4-dinitrophenyl benzoate (2a, O)
with alicyclic secondary amines in 80 mol % H2O/20 mol % DMSO
at 25.0 ( 0.1 °C. The identity of the points is given in Table 1.
Effect of Leaving Group on Reactivity and Mechanism.
Table 2 shows that the kN value for the reactions of the
phosphinates 1a-j with piperidine decreases as the basicity of
the leaving group increases, i.e., it decreases from 4.19 M-1
s-1 to 3.06 × 10-2 and 1.49 × 10-3 M-1 s-1 as the pKa of the
conjugate acid of the leaving aryloxide increases from 4.11 to
7.14 and 9.38, respectively. A similar result is obtained for the
corresponding reactions of the benzoates 2a-i.
The effect of the leaving group basicity on reactivity is illus-
trated in Figure 2. It is shown that the benzoates 2a-i are more
reactive than the phosphinates 1a-j. Besides, the Brønsted-
type plot for the reactions of 1a-j with piperidine is linear with
with a ânuc value of 0.38, while the one for the corresponding
reactions of 2a is curved with decreasing the ânuc value from
0.74 to 0.34 as the amine basicity increases.
The linear Brønsted-type plot found for the reaction of 1a
indicates that the basicity of amines does not affect the reaction
mechanism in the current reactions over 5 pKa units. The ânuc
of 0.38 determined for the reactions of 1a is slightly smaller
than the lower limit of ânuc reported for the reactions of
carboxylic esters which proceed through a concerted mechanism
(ânuc ) 0.4-0.7).12,13 However, one can suggest that the
aminolysis of 1a proceeds through a concerted mechanism as
(11) Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y. J. Org.
Chem. 2004, 69, 3937-3942.
(12) (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.
(13) (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.
(14) Um, I. H.; Hong, J. Y.; Buncel, E. Chem. Commun. 2001, 27-28.
J. Org. Chem, Vol. 71, No. 20, 2006 7717

Um et al.
As shown in Figure 2, the Brønsted-type plot for the reactions
of 2a-i is curved downwardly except 2a and 2c. The slope of
the curved Brønsted-type plot for the reactions of 2b and 2d-i
with piperidine decreases from -1.50 to -0.36 as the pKa of
the conjugate acid of the leaving aryloxide decreases. Since such
a curved Brønsted-type plot is typical for reactions which
proceed through a stepwise mechanism with a change in the
RDS, the reactions of 2b and 2d-i with piperidine have been
suggested to proceed through a stepwise mechanism.15
It is noted that 2a and 2c exhibit negative deviations from
the curved Brønsted-type plot. Furthermore, 2a is less reactive
than 2b although the former has a less basic leaving group than
the latter. Thus, one might insist that the reaction of 2a proceeds
through a different mechanism, e.g., through a concerted
mechanism. However, we propose that the negative deviation
shown by 2a and 2c is not due to the nature of the reaction
mechanism. Instead, steric hindrance is considered to be
responsible for the low reactivity shown by 2a and 2c. This is
because both 2a and 2c have a nitro group at the 2-position of
the leaving aryloxide, and the presence of the 2-NO2 group
would exert large steric hindrance. A similar conclusion has
been drawn for reactions of aryl phenyl carbonates with
quinuclidine. Gresser and Jencks have found that phenyl 2,4-
dinitrophenyl carbonate is less reactive than phenyl 3,4-
dinitrophenyl carbonate and concluded that steric hindrance
exerted by the 2-NO2 group is responsible for the lower
reactivity of the former carbonate.18
The steric hindrance appears to be insignificant for the
phosphinate system since 1a lies on the linear Brønsted-type
plot. Several factors can be suggested to account for the absence
of steric hindrance in the reactions of the phosphinate esters.
(1) Steric hindrance would be significant for reactions in which
bond formation between the electrophilic center and nucleophile
is advanced greatly in the TS. Since ânuc represents a relative
degree of bond formation in the TS, the small ânuc value
determined in the aminolysis of 1a (i.e., ânuc ) 0.38) suggests
that the bond formation is not much advanced. This argument
explains why the steric hindrance is unimportant for the reactions
of 1a. (2) The size of the electrophilic center is much larger in
the phosphinate ester than in the benzoate ester. Besides, the
electrophilic center of 1a is tetrahedral at the ground state but
becomes trigonal bipyramidal at the TS or the intermediate.9,10
The attacking and leaving groups have been suggested to occupy
the apical positions of the trigonal bipyramidal TS 4 or
intermediate 5.9,10 Thus, the 2-NO2 group in the leaving group
of 1a is too far away from the nucleophile to exert steric
hindrance.
FIGURE 2. Brønsted-type plots for the reactions of Y-substituted
phenyl diphenylphosphinates (1a-j, b) and Y-substituted phenyl
benzoates (2a-i, O) with piperidine in 80 mol % H2O/20 mol % DMSO
at 25.0 ( 0.1 °C. The identity of the points is given in Table 2.
âlg ) -0.66, while that for the corresponding reactions of 2a-i
is curved with decreasing âlg from -1.50 (âlg2) to -0.36 (âlg1).
The linear Brønsted-type plot for the reactions of 1a-j with
piperidine indicates that the mechanism (or the RDS) is not
varied on changing the leaving group basicity over 5 pKa units.
The âlg value of -0.66 is too small for a stepwise mechanism
in which collapse of the addition intermediate is the RDS or
too large for reactions which proceed through rate determining
formation of the intermediate. Accordingly, one can suggest that
the aminolysis of 1a-j in the current study proceeds through a
concerted mechanism. This is consistent with the preceding
argument that the aminolysis of 1a proceeds through a concerted
mechanism on the basis of the linear Brønsted-type plot with
ânuc ) 0.38.
However, Cook et al. have concluded that reactions of
4-nitrophenyl diphenylphosphinate (1d) with various types of
amines (including piperidine and morpholine) in MeCN proceed
through a zwitterionic pentacoordinate intermediate in which
collapse of the intermediate is the RDS.9 One can suggest that
the medium change from MeCN to aqueous DMSO is respon-
sible for the opposing reaction mechanism since the reactions
in the current study were performed in H2O containing 20 mol
% DMSO. This argument can be supported from the fact that
the effect of medium on the reactivity and amine basicity is
significant, e.g., as shown in Table 2, piperidine is ca. 2 orders
of power less reactive toward 1d in MeCN (kN ) 3.32 × 10-4
M-1 s-1) than in the aqueous DMSO (kN ) 3.06 × 10-2 M-1
s-1) although it has been reported to be ca. 7 pKa units more
basic in the former medium than in the latter.16 Furthermore,
we have recently shown that the medium change from aqueous
DMSO to MeCN causes a change in reaction mechanism for
aminolysis of aryl benzoates.17
Reaction Mechanism Determined from Hammett and
Yukawa-Tsuno Plots. To get further information on the
mechanism for the reactions of 1a-j with piperidine, Hammett
plots have been constructed with use of σo and σ- constants in
Figure 3. Correlations of rate constants with σo and σ- constants
(15) Um, I. H.; Lee, J. Y.; Ko, S. H.; Bae, S. K. J. Org. Chem. 2006,
71, 5800-5803.
(16) Spillane, W. J.; McGrath, P.; Brack, C.; O’Byne, A. B. J. Org. Chem.
2001, 66, 6313-6316.
(17) Um, I. H.; Jeon, S. E.; Seok, J. A. Chem. Eur. J. 2006, 12, 1237-
(18) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6963-
6970.
1243.
7718 J. Org. Chem., Vol. 71, No. 20, 2006

Phenyl Diphenylphosphinates and Benzoates
FIGURE 3. Plots of log kN vs σ- (or σï, inset) for the reactions of
Y-substituted phenyl diphenylphosphinates (1b-j) with piperidine in
80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The identity of the
points is given in Table 2.
have often been attempted to investigate whether the leaving
group departure occurs at the RDS or not.5a,8b,c,19 If the leaving
group departure occurs at the RDS either in a concerted or
stepwise mechanism, a partial negative charge would develop
at the oxygen atom of the leaving aryloxide. Since such a
negative charge can be delocalized on the substituent in the
leaving group, σ- constants should give a better linear correla-
tion than σo. On the contrary, σo constants should result in a
better linearity than σ- when the leaving group departure occurs
after the RDS. In fact, σo constants have been reported to exhibit
much better Hammett correlations than σ- constants for alkaline
hydrolysis of aryl diphenylphosphinates8c and diphenylphos-
phinothioates,8b imidazole catalyzed hydrolysis of aryl diphenyl-
phosphinates,8d and alkaline ethanolysis of aryl dimethylphosphin-
ates.5a Thus, these reactions have been concluded to proceed
through a stepwise mechanism in which the leaving group
departure occurs after the RDS.5a,8b-d
FIGURE 4. Yukawa-Tsuno plot for the reactions of Y-substituted
phenyl diphenylphosphinates (1b-j) with piperidine in 80 mol % H2O/
20 mol % DMSO at 25.0 ( 0.1 °C. The identity of the points is given
in Table 2.
plot decreases as the substituent X in the benzoyl moiety changes
from electron donating groups to electron withdrawing ones.11
Traditionally, such a nonlinear Hammett plot has been inter-
preted as a change in the RDS. However, we have shown that
the nonlinear Hammett plot is not due to a change in the RDS
on the basis of the fact that the Yukawa-Tsuno plot for the
same reaction exhibits excellent linearity.11
log(kX/kH) ) F[σo + r(σ- - σo)]
(1)
The Yukawa-Tsuno equation (eq 1)23,24 has been employed
in this study. The magnitude of the r value in the Yukawa-
Tsuno equation represents the resonance demand of the reaction
center or the extent of resonance contribution.23,24 As shown in
Figure 4, the Yukawa-Tsuno plot for the reactions of 1b-j
with piperidine results in an excellent linear correlation (R2 )
0.9993) with r ) 0.30. The best correlation would be obtained
with σ- constants when r ) 1 or with σo constants when r )
0. Since the r value determined in this study is neither 0 nor 1,
the Yukawa-Tsuno plot exhibits the best linear correlation.
The fact that r * 0 for the aminolysis of 1b-j indicates that
the leaving group cleavage occurs at the RDS. This is consistent
As shown in Figure 3, σ- constants exhibit a poor Hammett
correlation (R2 ) 0.962). A slightly better correlation with σo
is shown (R2 ) 0.986) in the inset of Figure 3, indicating that
the leaving group departure is not advanced at the RDS. Thus,
one might suggest that the aminolysis of 1b-j proceeds through
a stepwise mechanism in which the departure of the leaving
group occurs after the RDS. Clearly, this is inconsistent with
the preceding argument that the reactions of 1a-j proceed
through a concerted mechanism on the basis of the linear
Brønsted-type plots with ânuc ) 0.38 (Figure 1) and âlg ) -0.66
(Figure 2).
We have recently shown that determination of reaction
mechanism based just on a linear or nonlinear Hammett plot
can be misleading for nucleophilic substitution reactions of aryl
benzoates and related systems.11,20-22 For example, the Hammett
plot for aminolysis of 2,4-dinitrophenyl X-substituted benzoates
has been found to be nonlinear, i.e., the slope of the Hammett
(20) (a) Um, I. H.; Lee, J. Y.; Lee, H. W.; Nagano, Y.; Fujio, M.; Tsuno,
Y. J. Org. Chem. 2005, 70, 4980-4987. (b) Um, I. H.; Min, J. S.; Ahn, J.
A.; Hahn, H. J. J. Org. Chem. 2000, 65, 5659-5663.
(21) (a) Um, I. H.; Hong, J. Y.; Seok, J. A. J. Org. Chem. 2005, 70,
1438-1444. (b) Um, I. H.; Chun, S. M.; Chae, O. M.; Fujio, M.; Tsuno,
Y. J. Org. Chem. 2004, 69, 3166-3172.
(22) Um, I. H.; Lee, E. J.; Seok, J. A.; Kim, K. H. J. Org. Chem. 2005,
70, 7530-7536.
(23) (a) Tsuno, Y.; Fujio, M. AdV. Phys. Org. Chem. 1999, 32, 267-
385. (b) Tsuno, Y.; Fujio, M. Chem. Soc. ReV. 1996, 25, 129-139. (c)
Yukawa, Y.; Tsuno, Y. Bull. Chem. Soc. Jpn. 1959, 32, 965-970.
(24) (a) Fujio, M.; Rappoport, Z.; Uddin, H. J.; Kim, H. J.; Tsuno, Y.
Bull. Chem. Soc. Jpn. 2003, 76, 163-169. (b) Nakata, K.; Fujio, M.;
Nishimoto, K.; Tsuno, Y. J. Phys. Org. Chem. 2003, 16, 323-335.
(19) (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.
J. Org. Chem, Vol. 71, No. 20, 2006 7719

Um et al.
4-Chlorophenyl diphenylphosphinate (1j): mp 119-121 °C;
1H NMR (250 MHz, CDCl3) δ 7.16-7.19 (m, 4H), 7.46-7.53 (m,
6H), 7.83-7.91 (m, 4H). Anal. Calcd for C18H14ClO2P: C, 65.77;
H, 4.29. Found: C, 65.62; H, 4.26.
Amines and other chemicals were of the highest quality available.
Doubly glass distilled water was further boiled and cooled under
nitrogen just before use. Due to low solubility of 1a-j in pure
water, aqueous DMSO (80 mol % H2O/20 mol % DMSO) was
used as the reaction medium.
with the preceding argument that the current aminolysis of 1a-j
proceeds through a concerted mechanism. However, one can
suggest that only a small amount of negative charge would
develop on the oxygen atom of the leaving aryloxide on the
basis of the small r value. Thus, one can conclude that the
aminolysis of 1a-j proceeds through a concerted mechanism
in which nucleophilic attack and leaving group departure are
advanced only to a small extent at the TS on the basis of the
small ânuc ()0.38) and small r ()0.30) values, respectively.
Kinetics. The kinetic study was performed with a UV-vis
spectrophotometer equipped with a constant temperature circulating
bath to keep the reaction mixture at 25.0 ( 0.1 °C. The reactions
were followed by monitoring the appearance of the leaving
aryloxide. All the reactions were carried out under pseudo-first-
order conditions in which amine concentrations were at least 20
times greater than the substrate concentration. 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.
Typically, the reaction was initiated by adding 5 µL of a 0.02
M solution of 2,4-dinitrophenyl diphenylphosphinate (1a) in
acetonitrile to a 10 mm quartz UV cell containing 2.50 mL of the
thermostated reaction mixture made up of solvent and aliquot of
the amine stock solution. All the solutions were transferred by
gastight syringes. Generally, the amine concentration was varied
over the range (5-100) × 10-3 M, while the substrate concentration
was 4 × 10-5 M. Pseudo-first-order rate constants (kobsd) were
calculated from the equation ln(A∞ - At) ) - kobsdt + C. The plots
of ln(A∞ - At) vs time were linear over ca. 90% of the total reaction.
Usually, five different 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 vs amine
concentrations.
Conclusions
The present study has allowed us to conclude the following:
(1) The phophinates 1a-j are less reactive than the benzoates
2a-i. (2) The aminolysis of 1a-j proceeds through a concerted
mechanism, while the corresponding reaction of 2a-i proceeds
through a stepwise mechanism with a change in the RDS. (3)
The reactions of 1b-j result in a poor Hammett correlation with
σ- constants but slightly better correlation with σo. However,
this result does not indicate that the departure of the leaving
group occurs after the RDS, since the corresponding Yukawa-
Tsuno plot exhibits an excellent linear correlation with r ) 0.30.
(4) The aminolysis of 1a-j proceeds through an early TS, i.e.,
bond formation of nucleophiles and bond cleavage of the leaving
group are advanced only to a small extent at the TS.
Experimental Section
Materials. Aryl diphenylphosphinates 1a-j were prepared by
modification of literature procedures.5,8a,9 Diphenylphosphinyl
chloride (1.9 mL, 10 mmol) was dissolved in dry ether (20 mL).
Y-substituted phenol (10 mmol) and triethylamine (1.4 mL, 10
mmol) were dissolved in dry ether (20 mL) and added to the acid
chloride solution slowly. The reaction mixture was stirred under
nitrogen at room temperature. The progress of the reaction was
monitored by TLC. When the reaction was complete, the reaction
mixture was worked up as follows: Et3NH+Cl- was filtered off,
and then the ether solution was concentrated under reduced pressure.
The crude product was purified by column chromatography (silica
gel, methylene chloride/ethyl acetate 50/50). Their purity was
checked by their melting points for the known compounds and the
identity of unknown compounds 1h, 1i, and 1j was checked by
elemental analysis and 1H NMR spectra (Supporting Information).
3-Chlorophenyl diphenylphosphinate (1h): mp 108-110 °C;
1H NMR (250 MHz, CDCl3) δ 7.01-7.14 (m, 4H), 7.47-7.54 (m,
6H), 7.84-7.92 (m, 4H). Anal. Calcd for C18H14ClO2P: C, 65.77;
H, 4.29. Found: C, 65.77; H, 4.30.
Products Analysis. Y-substituted phenoxide was liberated
quantitatively and identified as one of the products in the reaction
of 1a-j with piperidine by comparison of the UV-vis spectra after
completion of the reactions with those of authentic samples under
the same reaction conditions. The other product, diphenylpiperi-
dinophosphine oxide, was analyzed quantitatively by HPLC (Rf )
3.60 min, eluent ) CH3CN, flow rate ) 1.0 mL/min, detection at
225 nm).
Acknowledgment. This work was supported by the Korea
Research Foundation (2005-015-C00256).
Supporting Information Available: 1H NMR spectra for
compounds 1h, 1i, and 1j; Tables S1-S7 for the kinetic conditions
and data for reactions of 1a with seven different alicyclic secondary
amines and Tables S8-S16 for the kinetic data for reactions of
1b-j and 2c with piperidine. This material is available free of
charge via the Internet at http://pubs.acs.org.
3-Acetylphenyl diphenylphosphinate (1i): mp 99-101 °C; 1H
NMR (250 MHz, CDCl3) δ 2.52 (s, 3H), 7.15-7.25 (m, 1H), 7.34-
7.48 (m, 7H), 7.50-7.54 (m, 2H), 7.86-7.94 (m, 4H). Anal. Calcd
for C20H17O3P: C, 71.42; H, 5.09. Found: C, 71.23; H, 5.11.
JO061308X
7720 J. Org. Chem., Vol. 71, No. 20, 2006