Anilinolysis of O-butyl phenyl phosphonochloridothioate in acetonitrile: Synthesis, characterization, kinetic study, and reaction mechanism

Article abstract of DOI:10.1002/poc.3679

This paper describes a simple optimized method for the synthesis of O-butyl phenyl phosphonochloridothioate (4) under mild conditions. The target compounds were characterized by ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, and ³¹P-NMR spectroscopy, as well as mass spectroscopy. The apparent structure of 4 was confirmed by optimization using the B3LYP/6-311?+?G(d,p) level in the Gaussian 09 program in acetonitrile. The nucleophilic substitution reactions of 4 with X-anilines (XC₆H₄NH₂) and deuterated X-anilines (XC₆H₄ND₂) were investigated kinetically in acetonitrile at 55.0°C. The free energy relationship with X in the anilines looked biphasic concave upwards with a break region between X?=?H and X?=?3-MeO, giving large negative ρ_X and small positive β_X values. The deuterium kinetic isotope effects were secondary inverse (k_H/k_D?H/k_D), increased when the nucleophiles were changed from weakly basic to strongly basic anilines. A concerted S_N2 mechanism is proposed on the basis of the selectivity parameters and the variation trend of the deuterium kinetic isotope effects with X.

Full text of DOI:10.1002/poc.3679

Received: 9 September 2016
DOI 10.1002/poc.3679
Revised: 18 November 2016
Accepted: 28 November 2016
R E S E A R C H A R T I C L E
Anilinolysis of O‐butyl phenyl phosphonochloridothioate in
acetonitrile: Synthesis, characterization, kinetic study, and
reaction mechanism
Hasi Rani Barai1 | Ji‐hoon Kim2 | Sang Woo Joo1
1 School of Mechanical Engineering, Yeungnam
Abstract
University, Gyeongsan, Korea
2 Department of Chemistry, Yeungnam University,
Gyeongsan, Korea
This paper describes a simple optimized method for the synthesis of O‐butyl phenyl
phosphonochloridothioate (4) under mild conditions. The target compounds were
characterized by 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, and 31P‐NMR
spectroscopy, as well as mass spectroscopy. The apparent structure of 4 was con-
firmed by optimization using the B3LYP/6‐311 + G(d,p) level in the Gaussian 09
program in acetonitrile. The nucleophilic substitution reactions of 4 with X‐anilines
(XC6H4NH2) and deuterated X‐anilines (XC6H4ND2) were investigated kinetically
in acetonitrile at 55.0°C. The free energy relationship with X in the anilines looked
biphasic concave upwards with a break region between X = H and X = 3‐MeO,
giving large negative ρX and small positive βX values. The deuterium kinetic isotope
effects were secondary inverse (kH/kD < 1: 0.789‐0.995) and the magnitudes,
(kH/kD), increased when the nucleophiles were changed from weakly basic to
strongly basic anilines. A concerted SN2 mechanism is proposed on the basis
of the selectivity parameters and the variation trend of the deuterium kinetic
isotope effects with X.
Correspondence
Hasi Rani Barai and Sang Woo Joo, School of
Mechanical Engineering, Yeungnam University,
Gyeongsan 712‐749, Korea.
Email: hrbarai@ynu.ac.kr; swjoo@yu.ac.kr
KEYWORDS
deuterium kinetic isotope effects, Hammett and Brønsted constants, O‐butyl phenyl
phosphonochloridothioate, thiophosphoryl transfer reactions
1
|
INTRODUCTION
are discussed on the basis of the selectivity parameters, the
steric effects of the 2 ligands on the rates, and deuterium
Phosphoryl and thiophosphoryl transfer reactions of
tetracoordinate phosphorus involving a leaving group of
chloride have been studied extensively because of their
importance in biochemistry and organometallic chemistry
as well as their usefulness in synthesis. The stepwise and
concerted mechanisms are well known in neutral phospho-
ryl and thiophosphoryl group transfer reactions having a
trigonal bipyramidal pentacoordinate intermediate and at
phosphorus through a single pentacoordinate transition
state (TS).[1–3] In this work, the thiophosphoryl transfer
reactions of O‐butyl phenyl phosphonochloridothioate (4)
with substituted anilines (XC6H4NH2) and deuterated
anilines (XC6H4ND2) were investigated kinetically in ace-
tonitrile (MeCN) at 55.0 0.1°C (Scheme 1). The kinetics
kinetic isotope effects (DKIEs). This study examined the
substituent effects, the attacking direction of the nucleo-
philes to the reaction center, DKIEs, and the mechanism
of the thiophosphoryl transfer reactions. The novelty of this
work is to synthesize the 4 in a mild condition and to deter-
mine the mechanism kinetically with respect to nucleo-
philic substitution reactions with substituted anilines
(XC6H4NH2) and deuterated substituted anilines
(XC6H4ND2) in MeCN. The kinetic results of the present
work are compared with those of methyl [1: Ph(MeO)
P(=S)Cl],[2] ethyl [2: Ph(EtO)P(=S)Cl],[4] propyl [3:
Ph(PrO)P(=S)Cl],[2] and Y‐aryl [5: Ph(YC6H4O)P(=S)
Cl][5] phenyl chlorothiophosphates. The numbering of the
substrates follows the sequence of the summations of the
J Phys Org Chem 2017; e3679;
wileyonlinelibrary.com/journal/poc
Copyright © 2017 John Wiley & Sons, Ltd.
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DOI 10.1002/poc.3679

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BARAI ET AL.
SCHEME 1 Studied reactions of O‐butyl phenyl
phosphonochloridothioate(4)withXC6H4NH2(D)2
in MeCN at 55.0°C. MeCN, acetonitrile
Taft steric constants [ΣES = ES(R1) + ES(R2)] of the 2
2.3 | Synthesis of substrate, O‐butyl phenyl
phosphonochloridothioate (4)
ligands, Ph and Ri.[6,7]
The substrate, O‐butyl phenyl phosphonochloridothioate (4),
was synthesized by reacting phenylthiophosphonic dichloride
(>98%) with excess butanol at –10°C for 8 hours and main-
tained this temperature with constant stirring at 24 hours.[8]
The reaction mixture was separated by filtration from the
insoluble part. The remaining mixture was treated with water
and diethyl ether for work up. The organic layer of diethyl
ether was dried over anhydrous MgSO4 for 1 to 2 hours.
The product mixture was separated by column chromatogra-
phy (silica gel, ethyl acetate/n‐hexane, 60%) and dried under
reduced pressure. The substrate was characterized by spectral
analysis, thin‐layer chromatography, 1H‐NMR, 13C‐NMR,
31P‐NMR, and gas chromatography–mass spectrometry, as
follows (see electronic supporting information):
2
| EXPERIMENTAL
2.1 | Materials and synthetic procedure of deuterated
anilines
Phenylthiophosphonic dichloride (>98%) was purchased
from TCI; high‐performance liquid chromatography (HPLC)
grade MeCN (water content < 0.005%), chloroform‐d
(99.8% D, contains 0.03% [v/v] tetramethylsilane [TMS]),
and anilines were purchased from Sigma Aldrich and used
without further purification. The 1‐Butanol (99.9%, HPLC
grade) was acquired from Fisher Scientific Chem Ltd; ethyl
acetate (extra pure grade, 99.0%), diethyl ether (extra pure
grade, 99%), and n‐hexane (99.5%, HPLC grade) were
obtained from DUKSAN and used as received. MgSO4 (extra
pure reagents, ≥97%) was supplied by YAKURI Pure
Chemicals Co Ltd (Osaka, Japan). Deuterium oxide (99.999
atom % D) was acquired from Sigma Aldrich and used as
received. Deuterated anilines were synthesized using the pro-
cedure reported elsewhere.[1–5] Deuterated anilines were syn-
thesized by refluxing anilines in deuterium oxide (99.999
atom % D) with a few drops of hydrochloric acid as a catalyst
at 90°C for 72 hours and collected after numerous attempts.
The anilines were more than 98% deuterated, as confirmed
by 1H‐NMR.
[C10H14OP(=S)Cl]: Colorless liquid; 1H‐NMR/ppm
(600 MHz, CDCl3 & TMS): δ 0.89 to 0.92 (m, 3H), 1.37
to 1.41 (m, 2H), 1.63 to 1.67 (m, 2H), 4.01 to 4.09 (m,
2H), 7.43 to 7.47 (m, 2H), 7.51 to 7.52 (m, 1H), 7.88 to
7.91 (m, 2H) (m, multiple). 13C‐NMR/ppm (150 MHz,
CDCl3, and TMS): δ 13.6, 18.8, 32.2, 66.5, 128.2, 130.9,
132.1, 133.7, 135.1. 31P‐NMR/ppm (243 MHz, CDCl3 &
TMS): δ 86.9 (1P, s, P = S) (s, singlet). Gas chromatogra-
phy–mass spectrometry (EI): m/z 248 [M+].
2.3.1
| Product analysis
O‐butyl phenyl phosphonochloridothioate (4) was reacted
with excess aniline for more than 15 half‐lives at 55.0°C in
MeCN. The solvent was evaporated under reduced pressure.
The product mixture was treated with diethyl ether by a
work‐up process with dilute hydrochloric acid and dried over
anhydrous MgSO4. The product was then isolated by column
chromatography (30% ethyl acetate/n‐hexane) and then dried
under reduced pressure. The analytical and spectroscopic
data of the product gave the following results (see electronic
supporting information):
2.2 | Kinetic measurements
The rates and selectivity parameters were calculated as
described previously.[1] The rates were measured
conductometrically using the conductivity bridge, which
was a self‐made computer‐automated analog‐to‐digital con-
verter conductivity bridge. The pseudo‐first‐order rate con-
stants (kobsd) were calculated by curve fitting analysis of the
decay profiles in the origin program 8.5. The concentrations
used in this study were [substrate] = 5 × 10‐3 M and [X‐ani-
lines] = (0.10‐0.30) M. The kobsd values were an average of at
least 3 runs, which were reproducible within 3%. The sec-
ond‐order rate constants, kH(D), were calculated from the
slope of a plot of kobsd vs [X‐anilines]. The selectivity param-
eters, ρX(H/D), were obtained from the slope of the plot of log
kH(D) vs σX and βX(H/D) from the slope of the log kH(D) vs
pKa(X) plot.
1
[C10H14OP(=S)NHC6H5]: Colorless liquid. H‐NMR/
ppm (300 MHz, CDCl3, and TMS): δ 0.89 to 0.94 (m,
3H), 1.40 to 1.47 (m, 2H), 1.67 to 1.74 (m, 2H), 4.00 to
4.38 (m, 2H), 5.53 (s, 1H), 6.77 to 7.87 (m, 10H) (m, mul-
tiple). 13C‐NMR/ppm (75 MHz, CDCl3, and TMS): δ 13.6,
18.9, 32.1, 64.8, 117.7, 121.9, 128.5, 129.5, 130.6, 131.8,
132.9, 134.8, 140.0. 31P‐NMR/ppm (243 MHz, CDCl3,

BARAI ET AL.
3 of 7
and TMS): δ 86.7 (1P, s, P = S) (s, singlet). Gas chromatog-
raphy–mass spectrometry (EI): m/z 305 [M+].
TABLE 1 Second‐order rate constants (kH(D) × 104/M–1 s–1) and DKIEs
(kH/kD) of the reactions of O‐butyl phenyl phosphonochloridothioate (4) with
XC6H4NH2(D2) in MeCN at 55.0°C
X
kH × 104
kD × 104
kH/kD
4‐MeO
4‐Me
3‐Me
H
799 1a
803
305
108
3
4
2
0.995 0.001b
0.984 0.001
0.935 0.001
0.858 0.001
0.854 0.001
0.821 0.001
0.789 0.001
2.4 | Theoretical studies of O‐butyl phenyl
phosphonochloridothioate (4)
300
101
2
2
The B3LYP/6‐311 + G(d,p) geometry, bond angles, and nat-
ural bond order charges of 4 in the gas phase[9] were calcu-
lated using the B3LYP/6‐311 + G(d,p) level in the
Gaussian 09 program and are shown on the optimized struc-
ture of 4 (Figure 1). The ground state structure of 4 does not
have a symmetry plane because it has 2 different ligands,
phenyl and butoxy. The molecular orbital theoretical struc-
ture shows that the 1 oxygen, 1 sulphur, 1 carbon attached
to the phenyl group, and 1 chlorine atom have a distorted tet-
rahedral geometry with the phosphorus atom at the reaction
center. The details of the optimized structure of 4 are given in
Table S1 and Figure S9.
47.2 0.1
35.8 1.35
13.8 0.1
3.77 0.1
55.0 0.1
41.9 0.4
16.8 0.1
4.78 0.1
3‐MeO
4‐Cl
3‐Cl
Abbreviations: DKIE, deuterium kinetic isotope effects; MeCN, acetonitrile.
aStandard deviation.
bStandard error {=1/kD[(ΔkH)2 + (kH/kD)2 × (ΔkD)2]1/2} from Crumpler and
Yoh.[10]
variations in the nucleophiles, respectively. The stronger
nucleophile leads to a faster rate, as observed in a typical
nucleophilic substitution reaction with positive charge devel-
opment at the nucleophilic N atom (ρX < 0) in the TS. On
the other hand, both the Hammett and the Brønsted plots
exhibit biphasic free energy correlations for substituent X var-
iations in the nucleophiles with a break region between at
X = H and X = 3‐MeO having 2 discrete regions: (1)
4‐MeO, 4‐Me, 3‐Me, and H and (2) 3‐MeO, 4‐Cl, and 3‐Cl
shown in Figures 2 and 3. The magnitudes of the ρX(H and D)
(ρX(H) = –4.57 and ρX(D) = –4.34) and βX(H and D) (βX(H) = 1.57
and βX(D) = 1.49) values with more basic anilines (X = 4‐MeO,
4‐Me, and 3‐Me, H) are much greater than those (ρX(H) = –
3.92, ρX(D) = –3.78, βX(H) = 1.36, and βX(D) = 1.31) with less
basic anilines (X = 3‐MeO, 4‐Cl, and 3‐Cl). The magnitudes of
the ρX and the βX values with the anilines are greater than those
3
| RESULTS AND DISCUSSION
The pseudo‐first‐order rate constants, kobsd, were observed
following Equation 1 for all reactions under the pseudo‐
first‐order conditions with a large excess of aniline as a nucle-
ophile. The k0 values in MeCN were negligible (k0 ≈ 0). The
second‐order rate constants (kH(D)) were determined from at
least 5 concentrations of anilines. The linear plots of Equa-
tion 1 suggest that there are no base catalysis or noticeable
adverse reactions and that the whole reaction can be
described by Scheme 1.
kobsd¼ k0þkHðDÞ½XC6H4NH2ðD2Þꢀ:
(1)
TABLE 2 Selectivity parameters (ρX and βX)a of the reactions of O‐butyl
phenyl phosphonochloridothioate (4) with XC6H4NH2(D2) in MeCN at
55.0°C
Table 1 summarizes the second‐order rate constants, kH
with X‐anilines, kD with deuterated X‐anilines, and the
DKIEs (kH/kD), and Table 2 summarizes the selectivity
parameters for Hammett ρX(H and D) and Brønsted βX(H and D)
Figures 2 (log kH(D) vs σX) and 3 (log kH(D) vs pKa[X]) show
ρX(βX)/X
4‐MeO to Hb
3‐MeO to 3‐Clh
–ρX(H)
βX(H)
4.57 0.08c,d
1.57 0.13c,e
4.34 0.04c,f
1.49 0.11c,g
3.92 0.07c,i
1.36 0.11c,j
3.78 0.08c,k
1.31 0.10c,l
.
–ρX(D)
βX(D)
the Hammett plots and the Brønsted plots for the substituent
Abbreviation: MeCN, acetonitrile.
aThe σ values were taken from Hansch, Leo, and Taft.[11] The pKa values of X‐
[12]
anilines in water were taken from ref.
bFor X = 4‐MeO, 4‐Me, 3‐Me, H.
cStandard deviation.
dCorrelation coefficient, r = .999.
er = .980.
fr = .999.
gr = .982.
hFor X = 3‐MeO, 4‐Cl, 3‐Cl.
ir = .999.
jr = .987.
kr = .999.
lr = .988.
FIGURE
1
B3LYP/6‐311+G(d,p) geometry of O‐butyl phenyl
posphonochloridothioate (4) in the gas phase

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BARAI ET AL.
anilinolysis rate should be 4 > 3 > 2 > 1 > 5 but the observed
sequence of the rate, 1 > 2 > 3 > 4 > 5, does not follow the
expected sequence regarding the electronic influence of the 2
ligands. Therefore, the positive charge at the reaction center P
atom does not play a major role in determining the reactivity
and mechanism of the thiophosphate chloride systems.
The second‐order rate constants for the anilinolyses of the
mentioned thiophosphate chlorides are kH = 7.53 × 10−3
M–1 s–1 for 1, kH = 6.93 × 10−3 M–1 s–1 for 2,
kH = 5.02 × 10−3 M–1 s–1 for 3, kH = 4.72 × 10−3 M–1 s–1
for 4, and kH = 1.50 × 10−3 M–1 s–1 for 5, giving relative rate
ratios of 5.02(1): 4.62 (2): 3.35 (3): 3.15 (4): 1.00 (5) in
MeCN at 55.0°C. From the observed rate ratio, the
anilinolysis rate, 1 > 2 > 3 > 4 > 5, follows the sequence
according to the sizes of the 2 ligands of the thiophosphate
chloride system: (MeO, Ph) 1 > (EtO, Ph) 2 > (PrO, Ph)
3 > (BuO, Ph) 4 > (PhO, Ph) 5. The sequence of the
anilinolysis rates of 1 > 2 > 3 > 4 > 5 is proportional to
the size of the 2 ligands; the greater the size of the 2 ligands,
the rate becomes slower. These results indicate that the steric
effects of the 2 ligands play an important role to determine the
anilinolysis rates of the phosphonochloridothioates.
FIGURE 2 Hammett plots (log kH(D) vs σX) with X of the reactions of O‐
butyl phenyl phosphonochloridothioate (4) with XC6H4NH2(D2) in MeCN
at 55.0°C
The Taft equation of “log kH = δΣES + C” may be used to
rationalize the steric effects of the 2 ligands on the reaction
rate, where kH is the second‐order rate constant with
unsubstituted aniline in MeCN at 55.0°C, ES is the Taft steric
constant [ES = 0(Me), –0.07(Et), –0.36(Pr), and –2.48(Ph)],
ΣES is the summation of the steric constants of the 2 ligands,
and δ is the sensitivity coefficient.[6,7] It should be noted that
the value of ΣES is not “ES(Ph) + ES(RiO)” but
“ES(Ph) + ES(Ri)” because the data of the Taft steric constant
of RiO are not available. Figure 4 shows the Taft plot of log
kH with unsubstituted aniline (C6H5NH2) against the summa-
tion of Taft steric constants of the 2 ligands for the
anilinolyses of 5 phosphonochloridothioates (1‐5) in MeCN
at 55.0°C, giving the sensitivity coefficients of
FIGURE 3 Brønsted plots (log kH(D) vs pKa[X]) with X of the reactions of
O‐butyl phenyl phosphonochloridothioate (4) with XC6H4NH2(D2) in MeCN
at 55.0°C
δ = 0.51
0.01 (r = .997) with 4 substrates 1 to 4. The
anilinolysis rate of 5 with phenoxy ligand shows positive
deviation from the Taft plot. The dependences of δ upon
with the deuterated anilines, suggesting greater sensitivity to
the substituent effects of the anilines compared to the deuter-
ated anilines and a change in the reaction mechanism from
the strongly basic to weakly basic anilines. The DKIEs inves-
tigated are secondary inverse (kH/kD < 1) and the magnitudes
of the DKIEs decrease constantly as the nucleophile is changed
from a more electron‐donating to a more electron‐withdrawing
substituent X: eg, X = 4‐MeO (kH/kD = 0.995) to X = 3‐Cl (kH/
kD = 0.789).
Table 3 lists the second‐order rate constants (kH) with
unsubstituted aniline, natural bond order charges at the reac-
tion center P atom [B3LYP/6‐311 + G(d,p) level of theory] in
the gas phase,[9] summations of the Taft steric constants
[∑ES = ES(R1) + ES(R2)] of the 2 ligands,[6,7] Brønsted coef-
ficients (βX(H)), and DKIEs (kH/kD) of the reactions of 1‐5
with XC6H4NH2(D2) in MeCN. Considering the magnitudes
of the positive charges at the reaction center P atom, the
the
2
ligands
of
both
chlorophosphate
and
chlorothiophosphate systems show quite similar trends, and
both substrates with phenoxy ligand(s) show positive devia-
tion from the Taft plots.[13–22] These results indicate that the
substrates with phenoxy ligand(s) of a group differ from those
without phenoxy ligand(s) of b group regarding the steric
effects of the 2 ligands on the anilinolysis rates. Groups a
and b are different reaction series regarding the steric effects
of the 2 ligands.
A concerted mechanism was proposed based on the neg-
ative ρXY = –0.38(5) value and positive Brønsted coefficients
βX(H) = 1.22 to 1.33 (5) for the anilinolysis of 5.[23–26] A con-
certed mechanism was also proposed for the anilinolyses of 1,
2, and 3 on the basis of the Brønsted coefficients βX(H) = 1.26
(1), 1.23 (2), and 1.04 (3).[1,2] In the present work, a con-
certed SN2 mechanism is proposed on the basis of the

BARAI ET AL.
5 of 7
TABLE 3 Summary of the second‐order rate constants (kH × 103/M–1 s–1) with C6H5NH2, NBO charges at the reaction center P atom, summations of the Taft
steric constants [∑ES = ES(R1) + ES(R2)] of the 2 ligands, Brønsted coefficients (βX(H)), and DKIEs (kH/kD) for the reactions of 1 to 5 with XC6H4NH2(D2) in
MeCN
b
c
Substrate
kH × 103a
Charge at P
−ΣES
βX(H)
1.26
kH/kD
Reference
1: (MeO, ph)P(=S)Cl
2: (EtO, ph)P(=S)Cl
3: (PrO, ph)P(=S)Cl
4. (BuO, ph)P(=S)Cl
5: (YC6H4O, ph)P(=S)Cl
7.53d
6.93d
5.02d
4.72d
1.50d,e
1.472
1.478
1.479
1.510
1.462e
2.48
2.55
2.84
2.87
4.96
1.08‐1.17d
0.93‐1.28d
1.02‐1.48d
0.789‐0.995d
0.44‐1.34d
Barai, Hoque, Lee, and Lee[2]
Hoque and Lee[4]
Barai, Hoque, Lee, and Lee[2]
1.23
1.04
1.57/1.36
This work
1.22‐1.33
Adhikary, Lumbiny, Dey, and Lee[5]
Abbreviations: DKIE, deuterium kinetic isotope effects; MeCN, acetonitrile; NBO, natural bond order.
aThe values with unsubstituted aniline at 55.0°C.
bNote that the value of ΣES is not “ES(Ph) + ES(RiO)” but “ES(Ph) + ES(Ri)” for 1 to 5 because the data of Taft steric constants of RiO are not available.
cStrongly/weakly basic anilines.
dExperimental kinetic value. See Barai et al[2], Hoque and Lee[4], Adhikary et al[5], and this work.
eValue with Y = H.
greater than unity, primary normal (kH/kD > 1.0), the partial
deprotonation of aniline occurs as the a rate‐limiting step by
hydrogen bonding[2,27–32] (eg, front side attack transition
state [TSf] in Scheme 2). On the other hand, the DKIEs are
only secondary inverse (kH/kD < 1.0) when an increase in the
steric congestion occurs in the bond‐making process[33–35]
(eg, backside attack transition state (TSb) in Scheme 2). This
is because the N–H(D) vibrational frequencies increase upon
going to the TS. Therefore, DKIEs provided a useful means
of determining the TS structures in nucleophilic substitution
reactions; in particular, changes in the substituents altered
the TS structures. The incorporation of deuterium in the
nucleophile has an advantage in that the α‐DKIEs resemble
only the degree of bond formation, especially for secondary
inverse DKIEs. Therefore, the greater the extent of bond
formation, the greater the steric congestion, and the kH/kD
values become smaller.
FIGURE 4 Taft plot of log kH vs ΣES for the reactions of 1 to 5 with
C6H5NH2 in MeCN at 55.0°C. The number of the substrate and 2 ligands
of R1 and R2 are displayed next to the corresponding point
The DKIEs of 1 (kH/kD = 1.08‐1.17) and 3 (kH/kD =1.02‐
1.48) are primary normal while those of 4 (kH/kD =0.789‐
0.995) are secondary inverse. The DKIEs of 2 (kH/
kD =0.93‐1.28) and 5 (kH/kD = 0.44‐1.34) are both secondary
inverse and primary normal. The kH/kD values of 1 to 3 and 5
increase as the aniline becomes less basic, but those of 4
increase as the aniline becomes more basic. The authors can-
not find the consistent correlations between the βX values and
DKIEs, between the βX values and variation trends of DKIEs,
between the DKIEs and 2 ligands, or between the reaction
Brønsted coefficient [βX(H) = 1.57/1.36 (4): comparable with
βX(H) = 1.26 (1), 1.23 (2), 1.04 (3), and 1.22 to 1.33 (5)
although it has a break region between X = H and X = 3‐
MeO. The relatively large Brønsted coefficients (βX(H) = 1.57/
1.36) are typical for the anilinolyses of the
chlorothiophosphates even though the reactions go through
a concerted SN2 mechanism.
The DKIE (kH/kD) is a strong tool for clarifying the reac-
tion mechanism and TS structure. When the kH/kD values are
SCHEME 2 Backside attack involving in‐line‐
type TSb and front side attack involving a
hydrogen bonded, 4‐center‐type TSf. TSb,
backside attack transition state; TSf, front side
attack transition state

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BARAI ET AL.
TABLE 4 aActivation parameters for the reactions of O‐butyl phenyl
phosphonochloridothioate (4) with anilines in acetonitrile
basic to strongly basic anilines. A concerted SN2 mechanism
with predominant backside nucleophilic attack involving in‐
line‐type TSb was proposed based on the selectivity parame-
ters and variation trend of the DKIEs with X. The linear free
energy relationship in the present work suggests that the
attacking direction of the aniline changes gradually from a
backside with the strongly basic anilines to a front side involv-
ing a hydrogen‐bonded 4‐center‐type TSf with weakly basic
anilines.
t/oC
kH × 103/ M–1 s–1
ΔH‡/kcal.Mol‐1
─ΔS‡/cal.Mol‐1. K‐1
66
45
55
65
3.02 0.01
4.72 0.01
7.41 0.01
8.9 0.1
1
aEyring equation.
mechanism and variation trends of DKIEs. The attacking
direction of aniline nucleophile can be semiquantitatively
divided into 3 groups on the basis of the magnitudes of the
kH/kD values: (1) predominant backside attack inline‐type
TSb (Scheme 2) when kH/kD < 1; (2) the fraction of the front
side attack hydrogen bonded, 4‐center‐type TSf (Scheme 2)
is greater than that of backside attack TSb when 1.0 < kH/
kD < 1.1; and (3) predominant front side attack TSf when
kH/kD > 1.1. The secondary inverse DKIEs are strengthened
by backside nucleophilic attack involving in‐line‐type TSb
(Scheme 2). The intermediates TS are very rapidly changed
from the attacking direction of the nucleophiles. The magni-
tudes of the kH/kD values decrease constantly as a more elec-
tron‐withdrawing substituent X (4‐MeO → 3‐Cl) is present
in the nucleophiles. This means that steric congestion in
the TS invariably increases as the aniline becomes weakly
basic. The lower reactivity of the nucleophile results in a
greater degree of bond formation. Accordingly, the value
of kH/kD (0.789‐0.995) indicates very severe steric conges-
tion in the TS, suggesting a great extent of bond formation.
Activation parameters, enthalpies, and entropies of activa-
tion, are summarized in Table 4. The enthalpies of activation
are relatively low (8.9 kcal/mol) and entropies of activation
are relatively large negative value (‐66 cal/mol/K) as shown in
Table 4. The relatively low value of activation enthalpy and
large negative value of activation entropy are typical for the
aminolyses of P = S systems. Therefore, the clarification of
the reaction mechanism by means of the activation parameters
is wretched for the aminolyses of P = S systems.
ACKNOWLEDGEMENTS
This study was supported by Yeungnam University Research
Fund.
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4
| CONCLUSIONS
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Anilinolysis of O‐butyl phenyl phosphonochlori-
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