Rate and product studies in the solvolyses of two cyclic phosphorochloridate esters

Article abstract of DOI:10.1080/10426500903061525

Kinetic and product studies of the solvolyses of acyclic phosphorochloridates are extended to two cyclic diesters, 2-chloro-1,3,2- dioxaphospholane-2-oxide (1) and 2-chloro-5,5-dimethyl-1,3,2-dioxaphosphorinane- 2-oxide (2). Slightly faster solvolyses are observed for 1 than for the acyclic dimethyl phosphorochloridate (3), and 2 solvolyzes somewhat slower than 3. An extended Grunwald-Winstein equation treatment shows similar sensitivities to changes in solvent nucleophilicity and solvent ionizing power for 1, 2, and 3, and a concerted SN2 attack is proposed in each case. Product studies for the solvolyses of 2 in aqueous alcohols are presented. [image presented]. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903061525

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Phosphorus, Sulfur, and Silicon and the
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Rate and Product Studies in
the Solvolyses of Two Cyclic
Phosphorochloridate Esters
Han Joong Koh a , Suk Jin Kang a & Dennis N. Kevill b
a Department of Science Education , Chonju National University of
Education , Chonju, Korea
b Department of Chemistry and Biochemistry , Northern Illinois
University , DeKalb, Illinois, USA
Published online: 03 Jul 2010.
To cite this article: Han Joong Koh , Suk Jin Kang & Dennis N. Kevill (2010) Rate and Product Studies
in the Solvolyses of Two Cyclic Phosphorochloridate Esters, Phosphorus, Sulfur, and Silicon and the
Related Elements, 185:7, 1404-1415, DOI: 10.1080/10426500903061525
To link to this article: http://dx.doi.org/10.1080/10426500903061525
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Phosphorus, Sulfur, and Silicon, 185:1404–1415, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903061525
RATE AND PRODUCT STUDIES IN THE SOLVOLYSES
OF TWO CYCLIC PHOSPHOROCHLORIDATE ESTERS
Han Joong Koh,1 Suk Jin Kang,1 and Dennis N. Kevill2
1Department of Science Education, Chonju National University of Education,
Chonju, Korea
2Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb,
Illinois, USA
Kinetic and product studies of the solvolyses of acyclic phosphorochloridates are extended to
two cyclic diesters, 2-chloro-1,3,2-dioxaphospholane-2-oxide (1) and 2-chloro-5,5-dimethyl-
1,3,2-dioxaphosphorinane-2-oxide (2). Slightly faster solvolyses are observed for 1 than for
the acyclic dimethyl phosphorochloridate (3), and 2 solvolyzes somewhat slower than 3. An
extended Grunwald–Winstein equation treatment shows similar sensitivities to changes in
solvent nucleophilicity and solvent ionizing power for 1, 2, and 3, and a concerted SN2 attack
is proposed in each case. Product studies for the solvolyses of 2 in aqueous alcohols are
presented.
O
O
O
MeO
MeO
O
O
O
O
Me
Me
P
P
P
Cl
Cl
Cl
(1)
(2)
(3)
Keywords Cyclic phosphorochloridates; extended Grunwald–Winstein equation; solvolysis
INTRODUCTION
The extended Grunwald–Winstein equation1–3 is used to correlate the specific rates of
solvolysis reactions in terms of solvent ionizing power2,4,5 and solvent nucleophilicity.3,6,7
In Equation (1), k and ko represent the specific rates of solvolysis in a given solvent and
in the standard solvent (80% ethanol), respectively; l represents the sensitivity to changes
Received 13 March 2009; accepted 22 May 2009.
Presented, in part, at the 17th International Conference on Phosphorus Chemistry (ICPC-17), April 15–21,
2007, Xiamen, China, and briefly summarized in the proceedings of the conference: H. J. Koh, S. J. Kang,
and D. N. Kevill, Phosphorus, Sulfur, and Silicon, 183, 364 (2008). H.J.K. thanks Chonju National University
of Education for the granting of a sabbatical leave during the time that a portion of this research was carried
out. Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American
Chemical Society, for partial support of this research. D.N.K. thanks Professor H. Mayr (Universita¨t Mu¨nchen)
for hospitality during the time this manuscript was being prepared.
Address correspondence to Dennis N. Kevill, Department of Chemistry and Biochemistry, Northern Illinois
University, DeKalb, Illinois, 60115-2862, USA. E-mail: dkevill@niu.edu
1404

SOLVOLYSES OF TWO CYCLIC PHOSPHOROCHLORIDATE ESTERS
1405
in solvent nucleophilicity (NT); m represents the sensitivity to changes in solvent ionizing
power (YX for a leaving group X); c represents a constant (residual) term.
log (k/k0) = lNT + mYX + c
(1)
The scale was initially developed for nucleophilic attack at sp3-carbon, but it has
been successfully applied to attack at sp2-carbon8 and at phosphorus9,10 and sulfur.11 The
previous studies of attack at phosphorus have included rate and product studies of the
solvolytic attack on dialkyll0 and diaryl12 phosphorochloridates, and a direct displacement
(SN2) reaction was proposed as the pathway.
In the present article, these studies are extended to the solvolyses of two cyclic
phosphorochloridate esters, 2-chloro-1,3,2-dioxaphospholane-2-oxide (1) and 2-chloro-
5,5-dimethyl-1,3,2-dioxaphosphorinane-2-oxide (2), and the specific rates (first-order rate
coefficients) and product studies are compared to those previously recorded for the open
chain analog, dimethyl phosphorochloridate (3).
O
O
O
MeO
MeO
O
O
O
O
Me
Me
P
P
P
Cl
Cl
Cl
(1)
(2)
(3)
This study is of especial interest since there is a considerable amount of evidence
that nucleophilic attack at the phosphorus of a five-membered ring diester can show quite
different characteristics to attack at situations with other ring sizes or at open chain analogs.
Large13,14 (sometimes enormous13) accelerations have been observed, and, in contrast to
the usually observed inversion, several nucleophilic substitution reactions of 2-chloro-4,5-
dimethyl-1,3,2-dioxaphospholane-2-oxide (a dimethyl derivative of 1) have been shown15
to give predominantly retention of configuration. In this context, it will be of interest to
examine the relative rates of reaction of 1, 2, and 3 under solvolytic conditions and, where
possible, to compare the product partitioning behavior in binary water–alcohol solvents.
RESULTS
The specific rates of solvolysis of 1 and 2 have been measured in a wide range
of solvents, including binary mixtures of water with 2,2,2-trifluoroethanol (TFE) and
1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The values at 25.0◦C for 1 and the values at
50.0◦C for 2 are reported in Table I, together with the literature values for NT3,7 and YCl
2,16
used in the multiple regression correlations. Values determined at other temperatures and
the calculated activation parameters are reported in Table II for 1 and in Table III for 2.
The calculations include also the appropriate specific rate value from Table I, and are based
on four temperatures, except for 2 in 100% ethanol, where reaction at 30◦C was too slow
for convenient measurement. Table II also includes calculated specific rate values for 2 at
25.0◦C, obtained by extrapolation from the measurements at higher temperatures.
Attempts to obtain the product partitioning for 1 from infinity titers failed due to
the relatively rapid solvolyses leading to appreciable reaction before homogeneity was
achieved. The slower solvolyses of 2 did not have this problem, and infinity titers, at
50.0◦C, could be conveniently used to establish the product partitioning ratio. Product
formation via reaction with water produces two equivalents of strong acid, and reaction
with an alcohol produces only one equivalent of strong acid (titration in acetone against

1406
H. J. KOH ET AL.
Table I Specific rates of solvolysis (k) of 2-chloro-1,3,2-dioxaphospholane-2-oxide (1)a at 25.0◦C and 2-chloro-
5,5-dimethyl-1,3,2-dioxaphosphorinane-2-oxide (2)a at 50.0◦C
102k(1), s−l c
104k(2), s−1 c
d
e
Solventb
25.0◦C
50.0◦C
NT
YC1
100% EtOH
90% EtOH
80% EtOH
70% EtOH
60% EtOH
50% EtOH
40% EtOH
20% EtOH
100% H2O
100% MeOH
90% MeOH
80% MeOH
70% MeOH
60% MeOH
40% MeOH
20% MeOH
90% Acetone
80% Acetone
70% Acetone
60% Acetone
50% Acetone
40% Acetone
20% Acetone
97% TFEf
0.378 0.003
1.86 0.03
3.28 0.04
5.32 0.11
10.7 0.1
15.9 0.1
20.8 0.4
44.5 1.7
0.458 0.005
1.23 0.01
2.02 0.01
2.78 0.01
3.38 0.03
4.32 0.08
5.62 0.05
8.66 0.04
14.3 0.7
0.964 0.008
1.95 0.05
3.01 0.04
3.97 0.01
4.82 0.06
7.06 0.04
10.1 0.1
0.37
0.16
0.00
−0.20
−0.38
−0.58
−0.74
−1.16
−1.38
0.17
−0.01
−0.06
−0.40
−0.54
−0.87
−1.23
−0.35
−0.37
−0.42
−0.52
−0.70
−0.83
−1.11
−3.30
−2.55
−2.19
−1.98
−1.73
−3.84
−2.94
−2.49
−2.52
−0.94
0.00
0.78
1.38
2.02
2.75
4.09
4.57
−1.17
−0.18
0.67
1.46
2.07
3.25
4.10
−2.39
−0.83
0.17
0.95
1.73
2.46
3.77
2.83
2.85
2.90
2.96
3.16
4.31
3.83
3.80
0.487 0.003
2.25 0.05
4.80 0.03
9.05 0.04
19.3 0.4
0.0977 0.0009
0.699 0.002
1.64 0.02
3.82 0.06
5.16 0.08
0.965 0.006
1.72 0.04
2.52 0.03
3.22 0.02
3.93 0.05
7.93 0.03
17.9 0.4
38.8 0.8
0.0113 0.0007
0.0641 0.0004
0.385 0.006
0.887 0.006
2.59 0.04
0.104 0.006
0.554 0.008
1.71 0.02
90% TFEf
80% TFEf
0.122 0.002
0.323 0.005
0.800 0.008
70% TFEf
50% TFEf
90% HFIPf
70% HFIPf
50% HFIPf
0.127 0.004
0.341 0.008
aSubstrate concentration of 0.0065 mol dm−3
.
bUnless otherwise indicated, on a vol/vol basis, at 25.0◦C, with the other component water.
cWith associated standard deviations.
dFrom refs. 3 and 7.
eFrom refs. 2 and 16.
fSolvent prepared on a weight/weight basis.
sodium methoxide in methanol, using resorcinol blue as an indicator). The situation is
summarized in Equation (2). If a water alcohol solvent is used, the equation, as presented,
O
O
O
O
2H2O
P
+
H3O+
+
Cl
H
O
O
O
2
( )
P
2ROH
Cl
O
O
+
P
+
ROH2
+
Cl
O
R
O

SOLVOLYSES OF TWO CYCLIC PHOSPHOROCHLORIDATE ESTERS
1407
Table II Specific rates and activation parameters for the solvolysis of 2-chloro-1,3,2-dioxaphospholane-2-oxide
(1) in pure and aqueous solvents
Solvent
Temp ◦C
102 k,s−1a
ꢀH= b (kcal/mol)
ꢀS= b (cal·mol−1 K−1
)
298
298
100% EtOH
35.0
45.0
55.0
35.0
45.0
55.0
35.0
45.0
55.0
35.0
45.0
55.0
35.0
45.0
55.0
35.0
45.0
55.0
0.545 0.007
0.840 0.003
1.28 0.02
4.17 0.06
5.56 0.01
7.70 0.03
0.701 0.002
1.22 0.01
7.3 0.1
4.9 0.1
9.1 0.2
9.7 0.1
11.3 0.1
6.3 0.1
−45.1 0.3
−49.0 0.3
−38.9 0.6
−39.8 0.4
−38.7 0.3
−51.1 0.3
80% EtOHc
100% MeOH
90% Acetonec
97% TFEd
2.14 0.01
0.155 0.002
0.272 0.003
0.478 0.008
0.0221 0.0004
0.0434 0.0003
0.0695 0.0008
0.144 0.003
0.204 0.003
0.305 0.003
90% HFIPd
aWith associated standard deviation.
bValues at 25.0◦C, from Table I, also used in the calculation; the activation parameters are accompanied by the
standard error.
cOn a volume/volume basis at 25.0◦C.
dOn a weight/weight basis.
Table III Specific rates of solvolysis of 2-chloro-5,5-dimethyl-1,3,2-dioxaphosphorinane-2-oxide (2) and the
calculated enthalpies (ꢀH=) and entropies (ꢀS=) of activation
ꢀH=b
ꢀS=b
323
Solvent
Temp.◦C
105 k,s−1 a
Kcal mol−1
cal mol−312K3 −1
100% EtOH
60.0
40.0
25.0
60.0
40.0
30.0
25.0
60.0
40.0
30.0
25.0
60.0
40.0
30.0
25.0
7.08 0.04
2.84 0.03
(1·34)c
8.8 0.1
−51.3 0.2
−29.7 0.2
80% EtOHd
100% H2O
100% MeOH
41.1 0.3
9.27 0.06
4.07 0.06
(2·69)c
14.8 0.1
16.7 0.1
15.3 0.1
293
4
−20.2 0.3
−29.8 0.2
57.1 0.4
22.5 0.1
(14·3)c
19.3 0.4
4.25 0.05
1.80 0.02
(1·18)c
aWith associated standard deviation.
bValues at 50.0◦C, from Table I, also used in the calculation; the activation parameters are accompanied by the
standard error.
cCalculated from the values at other temperatures, using the Arrhenius equation.
dOn a volume/volume basis at 25.0◦C (the other component is water).

1408
H. J. KOH ET AL.
Table IV Selectivity values (S)a for solvolyses at 50.0◦C of 2-chloro-5,5-dimethyl-1,3,2-dioxaphosphorinane-
2-oxide (2) in binary mixtures of water with ethanol, methanol, or 2,2,2-trifluoroethanol and a comparison with
the S values from solvolyses of dimethyl phosphorochloridate (3) at 25.0◦C
Solventb
%Esterc
S(2)
S(3)d
90% EtOH
80% EtOH
70% EtOH
60% EtOH
50% EtOH
40% EtOH
20% EtOH
90% MeOH
80% MeOH
70% MeOH
60% MeOH
40% MeOH
20% MeOH
80% TFE
84.6
61.8
50.7
40.3
29.7
24.5
13.4
89.8
79.8
66.4
50.8
28.2
15.6
15.1
3.8
2.0
1.3
1.4
1.5
1.4
1.6
2.0
2.2
2.3
1.9
1.6
1.3
1.7
0.23
0.09
0.07
0.36
0.46
0.56
0.85
0.84
e
e
e
70% TFE
50% TFE
1.3
aAs defined in Eq. (3).
bAqueous ethanol and methanol on a volume/volume basis at 25.0◦C and aqueous TFE on a weight/weight
basis.
cMolar percentage of ester formed in competition with the acid.
dValues from ref. 10.
eOnly very small amounts of ester formed, and the S value was too low to be determined by the titration
technique.
is simplified in that the second solvent molecule, used to extract the proton from the molecule
serving as the nucleophile, could be either water or alcohol. Further, the amounts of each
of the two shown protonated solvent species will be determined by a rapid equilibration
within the mixed solvent.
The partitioning ratio ([ester]/[acid]) is used in conjunction with the molar compo-
sition ratio for the solvent involved ([H2O]/[ROH]) to calculate the selectivity value (S),
defined as in Equation (3).
[ester in product]
[acid in product]
[H2O in solvent]
[ROH in solvent]
S =
·
(3)
Values for the percentages of reaction proceeding with ester formation (x%) for
solvolyses of 2, at 50.0◦C, in mixtures of water with ethanol, methanol, or TFE, are
reported in Table IV. The product ratios (x/100–x) are then used within Equation (3) to
give the S values, which are also present within Table IV.
DISCUSSION
The kinetic studies of the solvolyses of 1 and 2 over a wide range of hydroxylic
solvents, including the important water–fluoroalcohol systems,3 involved 28 solvents for
1, at 25.0◦C, and 27 solvents for 2, at 50.0◦C (Table I). Application of Equation (1)

SOLVOLYSES OF TWO CYCLIC PHOSPHOROCHLORIDATE ESTERS
1409
Figure 1 Plot of log (k/ko) for solvolyses of 1 at 25.0◦C against (1.16NT+0.60YC1).
to the data (Figures 1 and 2) led to the sensitivities (l) towards changes in solvent nu-
cleophilicity and to the sensitivities (m) towards changes in solvent ionizing power re-
ported in Table V. For both solvolyses, the correlation has a multiple correlation co-
efficient (R) of 0.974. The c values (residuals) were low at 0.04
0.05 for 1 and
0.09 0.06 for 2. The l/m ratios, considered to be a useful tool in assigning mecha-
nism,17 were at values of 1.93 and 2.40, respectively—within the range of values for
solvolyses believed to involve SN2 attack at phosphorus or sulfur (1.67 to 2.70 for the
examples in Table V). The other substrates included in the table for comparison are
N,N,N,ꢂNꢂ-tetramethyldiamidophosphorochloridate,9 dimethyl phosphorochloridate (3),10
diphenylphosphinyl chloride,18 p-methoxybenzenesulfonyl chloride,17 2-propanesulfonyl
chloride,11 and N,N-dimethylsulfamoyl chloride.11
The l and m values for solvolyses of 1 and 2 are similar to those for the other
solvolyses listed in Table V, they do not give any indication for special effects in either
of the solvolyses, and they, like the l/m ratio,18 are consistent with an SN2 pathway. In
particular, the l and m values are very similar for 1 and 3. In Table VI, the specific rate

1410
H. J. KOH ET AL.
Figure 2 Plot of log (k/ko) for solvolyses of 2 at 50.0◦C against (1.03NT+0.43YC1).
values for 1 and 2 are compared with those determined10 earlier for 3. For 2, values were
measured primarily at 50.0◦C, but for four of the solvolyses, values were calculated for
25.0◦C by extrapolation of data measured at higher temperatures (Table III), and for three
of these a corresponding specific rate value was available10 for solvolysis of 3.
The fastest solvolyses were those of 1, which reacted from twice as fast as 3 in 90%
acetone up to almost 80 times faster in 70% HFIP. Considering the wide variation in the type
of hydroxylic solvent involved, the extent of the variation in relative reactivities is rather
small, consistent with the similar l and m values for the two processes. The larger k(1)/k(3)
ratios in aqueous–fluoroalcohol solvents is due to the low nucleophilicity of these solvents,
coupled with a higher sensitivity to changes in solvent nucleophilicity for solvolyses of 3
(1.27) than for solvolyses of 1 (1.16).

SOLVOLYSES OF TWO CYCLIC PHOSPHOROCHLORIDATE ESTERS
1411
Table V Grunwald–Winstein correlations for solvolyses at phosphorus and sulfur
Substrate
na
T◦C
lb
mb
Rc
l/m
(Me2N)2POCld
3e
31
18
28
27
28
27
38
19
32
25.0
25.0
25.0
25.0
25.0
50.0
25.0
45.0
25.0
1.20 0.07
1.27 0.14
1.17 0.07
1.42 0.10
1.16 0.06
1.03 0.05
1.07 0.08
1.28 0.05
1.20 0.04
0.69 0.04
0.47 0.08
0.56 0.03
0.54 0.07
0.60 0.03
0.43 0.02
0.60 0.03
0.64 0.03
0.72 0.03
0.958
0.941
0.966
0.956
0.974
0.974
0.967
0.988
0.985
1.74
2.70
2.09
2.63
1.93
2.40
1.78
2.00
1.67
(MeO)2PSCle
Ph2POClf
1g
2g
p-MeOC6H4SO2Clh
i-PrSO2Cli
Me2NSO2Cli
aNumber of data points.
bFrom Eq. (1), and with associated standard error.
cMultiple correlation coefficient.
dFrom ref. 9.
eFrom ref. 10.
fFrom ref. 18.
gThis work.
hFrom ref. 17.
iFrom ref. 11.
The three available rate ratios for 2 relative to 3 are in the 0.01 to 0.05 range. Overall,
the data of Table VI show that there are no very large differences in rate when 1, 2, and 3 are
solvolyzed under conditions of identical solvent and temperature, with 1 reacting slightly
faster than 3, which in turn reacts somewhat faster than 2.
Table VI A comparison of the specific rates of solvolysis, at 25.0◦C, of dimethyl phosphorochloridate (3),
2-chloro-1,3,2-dioxaphospholane-2-oxide (1), and 2-chloro-5,5-dimethyl-1,3,2-dioxaphosphorinane-2-oxide (2)
Solventa
k(1)/k(3)b
k(2)/k(3)b
0.045
100% EtOH
90% EtOH
80% EtOH
70% EtOH
100% MeOH
90% MeOH
80% MeOH
90% Acetone
80% Acetone
70% Acetone
60% Acetone
97% TFE
90% TFE
80% TFE
70% TFE
50% TFE
70% HFIP
50% HFIP
12.8
11.6
11.5
12.8
4.3
7.3
9.7
2.0
4.1
0.0095
0.011
5.1
7.6
31.4
35.8
32.3
25.5
13.9
78.3
58.0
aOn volume/volume basis, except TFE-H2O mixtures on a weight/weight basis.
bThe k(1) values from Table I, the k(2) values from Table III, and the k(3) values from ref. 10.

1412
H. J. KOH ET AL.
Earlier studies19–24 of the rates of other nucleophilic substitution reactions of cyclic
esters of phosphoric acid found that rings with six or seven members reacted at about the
same rate as similar acyclic esters,22–24 consistent with the present study. However, it was
also found that reactions involving five-membered rings were enormously accelerated.
In particular, the rate measurements for the oxygen exchange of the corresponding
acids (in H2O18) and the hydrolysis of the methyl esters (the chlorine of 1, replaced by
a methoxy group) indicated a 107 rate difference for exchange and a 106 rate difference
for hydrolysis, favoring the reactions of the ethylene phosphate derivative.19–21 The ring-
opening reactions were also very fast, which was readily explained in terms of the relief of
strain within the five-membered ring, but a different approach was needed to explain the
competitive exocyclic hydrolyses with retention of the ring structure (Scheme 1).
O
O
O
O
O
O
O
+ OH
P
P
OMe
100% for pH > 12
Scheme 1
Westheimer20 proposed that the hydrolytic replacement of an exocyclic substituent
(OH by a labeled O18H group14 or OCH3 by an OH group19), under either acid or basic con-
ditions, involves an ionic pentacoordinate trigonal bipyramid intermediate. This undergoes
a favorable reduction in ring strain during the progress of the reaction through the involve-
ment of pseudorotations. The hydrolyses with ring opening do not require pseudorotations,
and they were proposed to proceed through an intermediate resembling an SN2 transition
state, situated along an alternative reaction channel.
The proposal of intermediates in these substitution pathways differs from our recent
suggestions that several acyclic phosphorochloridates undergo solvolysis by SN2 attack at
phosphorus with displacement of chloride ion, in a concerted process.9,10,18 The two view-
points are easily reconciled since concerted pathways would be much more favorable for a
relatively good leaving group, such as chloride, compared to a relatively poor leaving group,
such as hydroxide or methoxide. For the latter, a process involving addition (association) to
give an intermediate, eventually followed by loss of the leaving group (dissociation), could
well be the most favorable pathway. Indeed, in the extreme case, with only extremely poor
leaving groups available, one would expect to observe only an equilibrium addition as, for
example, in the hydration of aldehydes and ketones.
An important observation in this regard was that by Mikolajczyk and coworkers25
for the basic solvolyses of 2-halogeno-4-methyl-2-thio-1,3,2-dioxaphosphorinans. They
observed inversion of configuration for the bromo and chloro compounds but retention for
the fluoro compound. This can be rationalized in terms of SN2 attack for the chloro and
bromo compounds but an addition–elimination pathway for the fluoro compound, due to the
much poorer fluoride leaving group. Similarly, Corriu and coworkers26 found that reactions
of cyclic halogenophosphorochloridates with aryloxide in tetrahydrofuran all showed an
excess of retention of configuration, in conjunction with the reaction of the fluoro compound
showing a greater degree of retention than either the chloro or bromo compound. Also,
for reactions with lithium or sodium p-methylphenoxide in acetonitrile-d3 or acetone-d6,
the fluoro compound reacted slightly faster than the chloro compound (kF/kCl values of

SOLVOLYSES OF TWO CYCLIC PHOSPHOROCHLORIDATE ESTERS
1413
1.1 to 2.5).27 This behavior is similar to that observed for several nucleophilic substitution
reactions of haloformates (ROCOX)28 or halobenzenes,29 where strong evidence exists
for an addition–elimination pathway. Mechanistic studies of nucleophilic displacement of
halide ion from tetracoordinate phosphorus, including a discussion of the work by Corriu
and Mikalajczyk, have recently been reviewed.9
Specific rates at temperatures other than the ones used to obtain the values in Table I,
together with the enthalpies and entropies of activation, are reported for six solvolyses of 1
in Table II and for four solvolyses of 2 in Table III. The enthalpies of activation are lower
for the solvolyses of 1, 4.9 to 11.3 kcal mol−1, than for the solvolyses of 2, 8.8 to 16.7 kcal
mol−1. The higher specific rates for 1 to be expected based on these values are, however,
moderated by generally less favorable (highly negative) entropies of activation of −38.9 to
−51.1 cal mol−1 K−1 for 1, compared to values of -20.2 to -51.3 cal mol−1 K−1 for 2 (with
three of the four values for 2 in the −20 to −30 cal mol−1 K−1 range). With this balancing
of effects, the solvolyses of 1, at 25.0◦C, proceed, relative to those of 2 and using the data of
Table VI, about 300 times faster in ethanol, about 400 times faster in methanol, and about
1200 times faster in 80% ethanol. These are appreciable values, but they are considerably
lower than the values of in excess of a million observed for catalyzed hydrolyses of related
acids and esters.20 The appreciably negative entropies of activation for 1 and 2 are consistent
with the proposed lack of ring opening. Reaction with ring opening would be expected to
have a less negative, possibly positive, entropy of activation, especially for opening of the
five-membered ring of 1. Further, such ring-opening reaction would be expected to favor
considerably faster reaction for 1 and 2 than for 3, as opposed to the only modestly higher
solvolysis rates for 1 relative to 3 and for 3 relative to 2 (Table VI).
The selectivity values [S, Equation (3)] for 2, at 50.0◦C, in mixtures of water with al-
cohol, were almost constant, with a range of 1.3 to 2.3, in ethanol/water and methanol/water,
containing from 90% to 20% (by volume) alcohol. For both mixed systems, a slight fall in
values as the alcohol content was decreased was reversed at about the 40% alcohol content
(Table IV). In all determinations, there was a slight preference for reaction with alcohol
rather than water. In contrast, the S values previously determined, at 25.0◦C, for solvolyses
of 3 have values somewhat below unity, 0.36 to 0.85, indicating a faster reaction with
the water component. The influence of the 25.0◦C difference in temperature is probably
slight,30 and it appears that in the balance between steric effects and nucleophilicity,3 both
higher for ethanol and methanol, the tying back of the two alkoxy substituents in a ring
leads to solvent nucleophilicity effects dominating for 2, whereas the reverse is true for 3,
with its two methoxy substituents.
In the TFE/water mixtures, as one would expect, there is a considerable preference
for reaction with water, with TFE having both a much larger steric effect and a much lower
nucleophilicity.3 The S values are towards the lower limit for determination by the titration
technique, and, indeed, the even lower values for 3 (again consistent with a larger influence
of the steric effect) could not be determined.10
CONCLUSIONS
Under identical conditions, at 25.0◦C, the solvolyses of 2-chloro-1,3,2-
dioxaphospholane-2-oxide (1), with the chlorine situated on the phosphorus of a
five-membered diester ring, proceeded two to 80 times faster than those studied earlier for
the open chain dimethyl phosphorochloridate (3).10 In turn, 3 reacted faster, by factors

1414
H. J. KOH ET AL.
of 20 to 100, than in four corresponding solvolyses of 2-chloro-5,5-dimethyl-1,3,2-
dioxaphosphorinane-2-oxide (2).
Correlations (Table V) using the extended Grunwald–Winstein equation [Eq. (1)] led
to sensitivities towards changes in solvent nucleophilicity (l) of 1.16 0.06 (at 25.0◦C) for
1 and 1.03 0.05 (at 50.0◦C) for 2, similar to the value10 of 1.27 0.14 (at 25.0◦C) for 3.
The corresponding sensitivities towards changes in solvent ionizing power (m) of 0.60
0.03 for 1 and 0.43 0.02 for 2 are also similar to the value of 0.47 0.08 for 3.
Consideration of both the relative rates and the Grunwald–Winstein equation corre-
lations suggests that the solvolyses of 1 can be best rationalized in terms of the SN2 attack
at phosphorus usually proposed10 for solvolytic displacement of chloride from phosphorus.
Selectivity values [Eq. (3)] for 2, show that, in ethanol/water and methanol/water,
there is a slight preference for the alcohol to function as the nucleophile. In contrast, the S
values10 for solvolyses of 3 (at a 25.0◦C lower temperature) show a slight preference for
reaction with the water component. As one would expect from its low solvent nucleophilic-
ity,3 TFE in TFE/water mixtures competes only poorly against the water component for
reaction with 2. The rather small differences in S values for solvolyses of 2 and 3 can be
rationalized in terms of reduced steric interactions when the attack is at the phosphorus of
a tied-back ring system in 2.
EXPERIMENTAL
The 2-chloro-1,3,2-dioxaphospholane-2-oxide (1, Aldrich Technical Grade)
and 2-chloro-5,5-dimethyl-1,3,2-dioxaphosphorinane-2-oxide (2, Aldrich 96%) were
used as received. Compound 1 was reported to contain up to 10% of 2-chloro-1,3,2-
dioxaphospholane, a cyclic phosphorochloridite with the same structure as 1, except that
there is no oxygen atom attached to the phosphorus. Phosphorochloridites solvolyze ex-
tremely rapidly. For example, the ethanolyses of the dimethyl and diethyl esters [(RO)2PCl;
R = Me or Et] have been shown to be “practically instantaneous at 0◦C.”31 Accordingly, the
impurity in 1 will have solvolyzed completely at 25.0◦C before homogeneity is established
and before the kinetic runs were initiated. Solvents were purified as previously described.7
The kinetic runs were carried out as previously reported,32 except that, for solvolyses
of 1, 12 µL of a stock solution in acetonitrile were added to 12.5 mL of temperature-
equilibrated solvent. Values reported are averages of duplicate determinations. The multiple
regression analyses were carried out using commercially available statistical packages.
The product studies for solvolyses of 2, based on infinity titers, were also determined
as previously reported.10
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