A kinetic study of the solvolyses of methyl and ethyl chloroglyoxalates

Article abstract of DOI:10.1021/jo050998m

Solvolyses of methyl and ethyl chloroglyoxylates proceed about 10 ⁶ times faster than the identical solvolyses of the corresponding chloroformates. The correlation parameters obtained from application of the extended Grunwald-Winstein equation are consistent with an addition-elimination (association-dissociation) mechanism over the full range of solvents, with the addition step being rate determining.

Full text of DOI:10.1021/jo050998m

tematic variation of the alkyl group of alkyl chloro-
formates.7-9 Chloroformate esters (ROCOCl) are fre-
quently employed in kinetic studies of nucleophilic
substitutions at an acyl carbon because they tend to react
at convenient rates at temperatures close to ambient.
This is in contrast to conventional acyl chlorides (RCOCl),
which tend to undergo rather rapid nucleophilic substitu-
tion reactions.10 The slower reaction is usually rational-
ized in terms of a resonance-based ground-state stabili-
zation, which is possible for ROCOCl but not for RCOCl
(eq 1).
A Kinetic Study of the Solvolyses of Methyl
and Ethyl Chloroglyoxalates
Dennis N. Kevill,*,† Byoung-Chun Park,† and
Jin Burm Kyong‡
Department of Chemistry and Biochemistry, Northern
Illinois University, DeKalb, Illinois 60115-2862, and
Department of Chemistry, Hanyang University, Ansan,
Kyunggi-do 425-791, Korea
dkevill@niu.edu
Received May 19, 2005
The mechanism of solvolysis is believed to involve an
addition-elimination (association-dissociation) process
for phenyl,11 methyl,8 and primary alkyl7 chloroformates
in all but the most ionizing solvents and those with the
lowest nucleophilicity. For tertiary alkyl chloroformates,
an ionization process, with loss of carbon dioxide, is
favored.4 Secondary alkyl chloroformates follow the ion-
ization pathway in all but the more nucleophilic and less
ionizing solvents (100% and 90% ethanol and methanol).9
Related compounds are chloroglyoxalate esters, with
the naming of the parent acid as chloroglyoxalic acid
being based on the replacement of the hydrogen of
glyoxalic acid by chlorine. Alternatively, they can be
named as chlorooxoacetate esters or as alkyl (or aryl)
oxalyl chlorides. Hydrolysis leads to monosubstituted
oxalic acid derivatives and, in contrast to the half-esters
of carbonic acid,12 this product is stable and can be
isolated.13 With alcohols or phenols, a disubstituted
oxalate ester is formed.14 Although there have been
studies of the rates of decomposition of chloroglyoxalate
esters in the gas phase15 or in inert solvents,14b,16 no
quantitative studies appear to have been made of the
kinetics of solvolysis in hydroxylic solvents. Conventional
aliphatic acyl chlorides are already reactive species and
further increases in the reactivity toward nucleophilic
species are to be expected upon the incorporation of the
powerfully electron-withdrawing alkoxycarbonyl (RCO2-)
group. It has previously been demonstrated, for example,
that the introduction of electron-withdrawing chloro-
Solvolyses of methyl and ethyl chloroglyoxylates proceed
about 106 times faster than the identical solvolyses of the
corresponding chloroformates. The correlation parameters
obtained from application of the extended Grunwald-
Winstein equation are consistent with an addition-elimina-
tion (association-dissociation) mechanism over the full
range of solvents, with the addition step being rate deter-
mining.
There have been numerous measurements of the
specific rates of solvolysis of chloroformate esters.1 Recent
studies have included solvent isotope effects,2,3 Grun-
wald-Winstein equation correlations,2,3 and product
selectivity values in mixed solvents.2,3 Other aspects have
included Hammett equation correlations,2 treatments in
terms of third-order rate coefficients,2 studies of ac-
companying decomposition with loss of CO2,3,4 the influ-
ence of sulfur-for-oxygen substitution,5 studies of the
corresponding fluoroformates,6 and the influence of sys-
† Northern Illinois University.
‡ Hanyang University.
(1) For a review of early work, see: Kevill, D. N. In The Chemistry
of the Functional Groups: The Chemistry of Acyl Halides; Patai, S.,
Ed.; Wiley-Interscience: New York, 1972; Chapter 12.
(2) Koo, I. S.; Yang, K.; Kang, K.; Lee, I. Bull. Korean Chem. Soc.
1998, 19, 968.
(7) (a) Kevill, D. N.; D’Souza, M. J. J. Org. Chem. 1998, 63, 2120.
(b) Kyong, J. B.; Won, H.; Kevill, D. N. Int. J. Mol. Sci. 2005, 6, 87.
(8) Kevill, D. N.; Kim, J. C.; Kyong, J. B. J. Chem. Res., Synop. 1999,
150.
(3) Kyong, J. B.; Park, B.-C.; Kim, C.-B.; Kevill, D. N. J. Org. Chem.
2000, 65, 8051.
(4) Kevill, D. N.; Kyong, J. B.; Weitl, F. L. J. Org. Chem. 1990, 55,
4304.
(9) Kyong, J. B.; Kim, Y.-G.; Kim, D. K.; Kevill, D. N. Bull. Korean
Chem. Soc. 2000, 21, 662.
(5) (a) Ostrogovich, G.; Csunderlik, C.; Bacaloglu, R. J. Prakt. Chem.
1975, 317, 62. (b) Csunderlik, C.; Bacaloglu, R.; Ostrogovich, G. J.
Prakt. Chem. 1975, 317, 73. (c) Queen, A.; Matts, T. C. Tetrahedron
Lett. 1975, 1303. (d) Queen, A.; McKinnon, D. M.; Bell, A. W. Can. J.
Chem. 1976, 54, 1906. (e) Kevill, D. N.; Bond, M. W.; D’Souza, M. J. J.
Org. Chem. 1997, 62, 7869. (f) Kevill, D. N.; D’Souza, M. J. Can. J.
Chem. 1999, 77, 1118. (g) An, S. K.; Yang, J. S.; Cho, J. M.; Yang, K.;
Lee, J. P.; Bentley, T. W.; Lee, I.; Koo, I. S. Bull. Korean Chem. Soc.
2002, 23, 1445.
(6) (a) Queen, A.; Nour, T. A. J. Chem. Soc., Perkin Trans. 2 1975,
935. (b) Orlov, S. I.; Chimishkyan, A. L.; Grabarnik, M. S. J. Org.
Chem. USSR (Engl. Transl.) 1983, 19, 1981. (c) Kevill, D. N.; Kyong,
J. B. J. Org. Chem. 1992, 57, 258. (d) Kevill, D. N.; D’Souza, M. J. J.
Chem. Soc., Perkin Trans. 2 2002, 240.
(10) Kivinen, A. In The Chemistry of the Functional Groups: The
Chemistry of Acyl Halides; Patai, S., Ed.; Wiley-Interscience: New
York, 1972; Chapter 6.
(11) Kevill, D. N.; D’Souza, M. J. J. Chem. Soc., Perkin Trans. 2
1997, 1721.
(12) Faurholt, C.; Gjaldbaek, J. C. Dan. Tidsskr. Farm. 1945, 19,
255; Chem. Abstr. 1946, 40, 513.
(13) Stolle´, R. Chem. Ber. 1914, 47, 1130.
(14) (a) Simon, M. S.; Seyferth, H. McC. J. Org. Chem. 1958, 23,
1078. (b) Kevill, D. N.; Weitl, F. L. J. Chem. Soc., Perkin Trans. 1 1972,
2162.
(15) Cordova, T.; Rotinov, A.; Chuchani, G. J. Phys. Org. Chem.
2004, 17, 148.
(16) Rhoads, S. J.; Michel, R. E. J. Am. Chem. Soc. 1963, 85, 585.
10.1021/jo050998m CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/29/2005
9032
J. Org. Chem. 2005, 70, 9032-9035

TABLE 1. Specific Rates of Solvolysis (k) of Methyl and Ethyl Chloroglyoxalates and NT and YCl Values of the Solvents
at Various Temperatures
solventa
T, °C
102kMe,b s-1
102kEt,b s-1
NT
YCl
c
d
100% EtOH
-61.2
-69.2
-76.2
25.0e
-76.2
-61.2
-69.2
-76.2
25.0e
-76.2
-76.2
-76.2
-76.2
25.0
10.1 ( 0.5
6.79 ( 0.39
5.05 ( 0.17
1.71 ( 0.08
3.18 ( 0.11
1.26 ( 0.05
0.37
0.16
-2.52
-0.94
9.1((2.6) × 103
4.2((0.6) × 103
90% EtOH
100% MeOH
3.25 ( 0.22
3.22 ( 0.25
18.7 ( 0.1
15.7 ( 1.0
7.75 ( 0.31
6.58 ( 0.18
3.02 ( 0.13
3.09 ( 0.09
0.17
-1.17
19.1((1.5) × 103
7.6((0.3) × 103
90% MeOH
60T-40Ef
40T-60Ef
20T-80Ef
100% TFE
97% TFEh
3.60 ( 0.13
3.32 ( 0.12
-0.01
-0.94
-0.34
0.08
-0.18
0.63
-0.48
-1.42
0.178 ( 0.010
0.409 ( 0.013
0.965 ( 0.043
0.0519 ( 0.0047
2.13 ( 0.08
0.108 ( 0.004
0.333 ( 0.017
0.769 ( 0.045
0.0359 ( 0.0016g
1.72 ( 0.06
25.0
0.0
0.486 ( 0.011
0.109 ( 0.004
5.09 (( 0.06) × 10-4
2.87 ( 0.10
0.374 ( 0.007
0.0756 ( 0.0012
2.74 (( 0.10) × 10-4
2.04 ( 0.04
0.811 ( 0.011
0.313 ( 0.010
15.5 (( 0.7) × 10-4
-21.2
-76.2e
-10.0
-21.2
-31.2
-76.2e
-3.30
-2.55
2.83
2.85
90% TFEh
1.15 ( 0.04
0.462 ( 0.018
26.0 (( 0.6) × 10-4
a On a volume-volume basis (at 25.0 °C), unless otherwise stated. b With associated standard deviations. c Values from refs 18 and 19.
d Values from refs 20 and 21. e From an Arrhenius equation extrapolation of values at other temperatures. f Mixtures of 2,2,2-trifluoroethanol
and ethanol in the proportions stated. g Titration of the production of acid as a function of time led to a specific rate of 3.40((0.23) × 10-4
s-1 h On a weight-weight basis.
.
TABLE 2. Enthalpies (∆H#, kcal mol-1) and Entropies (∆S#, cal mol-1 K-1) of Activation for the Solvolyses of Methyl
and Ethyl Chloroglyoxalatesa
MeOCOCOCl
EtOCOCOCl
solvent
∆H#
∆S#
∆H#
∆S#
100% EtOHb
100% MeOHb
97% TFEc
9.41 ( 0.17
9.68 ( 0.05
9.03 ( 0.02
10.38 ( 0.06
-18.0 ( 1.0
-15.5 ( 0.3
-35.9 ( 0.1
-25.9 ( 0.1
8.93 ( 0.09
8.62 ( 0.03
9.51 ( 0.02
10.66 ( 0.03
-21.1 ( 0.5
-20.9 ( 0.2
-34.7 ( 0.1
-25.5 ( 0.1
90% TFEd
a Each calculation uses the three experimental specific rate values from Table 1; errors quoted are standard errors. b Values calculated
at -76.2 °C. c Values calculated at 25.0 °C. d Values calculated at -10.0 °C.
substituents greatly increases the rate of methanolysis
of acetyl chloride.17 In the present communication, we
report upon the kinetics of the solvolysis reactions of
methyl and ethyl chloroglyoxalates (eq 2) and compare
the specific rates, activation parameters, and parameters
from an extended Grunwald-Winstein treatment18 with
those previously obtained from studies of chloroformate
esters, especially the methyl8 and ethyl7a esters.
mined at higher temperatures. For both 97% TFE and
90% TFE, an extrapolated specific rate of solvolysis at
-76.2 °C was calculated. Both the experimentally deter-
mined and the extrapolated values for the specific rates
of solvolysis plus solvent nucleophilicity (NT) values18,19
and solvent ionizing power (YCl) values20-22 are reported
in Table 1. The enthalpies and entropies of activation for
the four solvolyses which were studied at three temper-
atures are reported in Table 2.
The range of solvents which could be studied was
limited by the need to measure the specific rates of
solvolysis in solvents without a fluoro alcohol component
at low temperatures, below the freezing point of most of
the commonly used alcohol-water or acetone-water
combinations. The corresponding chloroformate esters
were conveniently studied at or near ambient tempera-
ture.7,8 The factors which reduce the rates of solvolysis
of chloroformate esters relative to those of conventional
acyl chlorides must be absent during the solvolyses of
The specific rates of solvolysis of methyl and ethyl
chloroglyoxalate were determined in several pure and
binary hydroxylic solvents at temperatures below -60
°C. For ethanol and methanol, approximate values at 25.0
°C were obtained by extrapolation using the Arrhenius
equation. Reactions in solvents rich in 2,2,2-trifluoro-
ethanol (TFE) would be very slow at these low temper-
atures and values in 100% and 97% TFE were deter-
(19) Kevill, D. N.; Anderson, S. W. J. Org. Chem. 1991, 56, 1845.
(20) Bentley, T. W.; Llewellyn, G. Prog. Phys. Org. Chem. 1990, 17,
121.
(21) (a) Bentley, T. W.; Carter, G. E. J. Am. Chem. Soc. 1982, 104,
5741. (b) Kevill, D. N.; D’Souza, M. J. J. Chem. Res., Synop. 1993, 174.
(22) Koo, I. S.; Bentley, T. W.; Kang, D. H.; Lee, I. J. Chem. Soc.,
Perkin Trans. 2 1991, 296.
(17) Kevill, D. N.; Kim, C.-B. J. Chem. Soc., Perkin Trans. 2 1988,
1353.
(18) For a discussion of this treatment, see: Kevill, D. N. In
Advances in Quantitative Structure-Property Relationships; Charton,
M., Ed.; JAI Press: Greenwich, CT, 1996; Vol. 1, pp 81-115.
J. Org. Chem, Vol. 70, No. 22, 2005 9033

the chloroglyoxalate esters. The resonance stabilization
of chloroformate esters (eq 1) will also be present in
chloroglyoxalate esters (eq 3), but it is away from the
reaction center and it will be maintained at the transition
state of substitution reactions taking place at the carbo-
nyl carbon bonded to the chlorine. The major influence
of the additional carbonyl group will be one of electron
withdrawal from the carbonyl carbon reaction center,
intensifying the positive charge and, therefore, favoring
nucleophilic attack and disfavoring ionization.
The methanolysis and ethanolysis of the two chloro-
glyoxalates were studied at three temperatures, and a
long Arrhenius equation extrapolation allows the estima-
tion of values at 25.0 °C (Table 1). These values can be
compared to the corresponding values for methyl6b,23 and
ethyl6b,7a,23,24 chloroformates. The kMeOCOCOCl/kMeOCOCl ra-
tios are 12((1) × 105 for methanolysis and 21((7) × 105
for ethanolysis. For the ethyl esters, the corresponding
ratios are 8.5((0.4) × 105 and 17((3) × 105. The values
are consistent with a mechanism involving a rate-
determining nucleophilic attack at carbonyl carbon, as-
sisted by the electron-withdrawing influence of the
adjacent carbonyl group. Indeed, the specific rates are
considerably faster than those of the corresponding acyl
halides. Using a specific rate for ethanolysis of acetyl
chloride at 25.0 °C (147 × 10-3 s-1) from the literature,25
we find the relative specific rates for MeCOCl:MeOCOCl:
MeOCOCOCl to be 1.0:2.9 × 10-4:6.2 × 102.
FIGURE 1. Plot of log k for solvolyses of methyl chlorogly-
oxalate at -76.2 °C against (1.45NT + 0.30YCl).
given solvent and in 80% ethanol (arbitrarily chosen27
as the standard solvent), l is the sensitivity to changes
in solvent nucleophilicity (NT values), m is the sensitivity
to changes in solvent ionizing power (YX for a leaving
group X), and c is a constant (residual) term.
The specific rates directly measured or obtained by
extrapolation to -76.2 °C (Table 1) have been analyzed
by using eq 4. The nine data points are on the borderline
of the minimum needed for a meaningful two-term
correlation, but they do have the advantage of covering
a good selection of solvent types. Since it was not possible
to obtain a value for 80% ethanol, log k rather than log-
(k/k0) was plotted. In this way, the log k0 value is
incorporated into the c value. The values obtained for the
solvolyses of methyl chloroglyoxalate lead to values of
1.45 ( 0.16 for l, 0.30 ( 0.11 for m, and -1.54 ( 0.13 for
c; the multiple correlation coefficient (R) was 0.994 and
the F-test value was 237. The corresponding values for
the ethyl chloroglyoxalate solvolyses were 1.57 ( 0.19 for
l, 0.35 ( 0.14 for m, and -1.57 ( 0.16 for c; the R value
was 0.992 and the F-test value was 192. The errors
quoted are standard errors, and the errors associated
with the m values were such that there are only low
probabilities (0.038 and 0.043, respectively) that the
contribution from the mYCl term is statistically insignifi-
cant. The two correlations are plotted in Figures 1 and
2.
Since TFE freezes at -23 °C, it is fortunate that the
considerably slower solvolyses allow measurements to be
made at higher temperatures, as high as 25.0 °C for 100%
and 97% (w/w) TFE. For 97% and 90% TFE, the specific
rates were determined at three temperatures and Ar-
rhenius parameters (Table 2) and specific rates at -76.2
°C (Table 1) were calculated. The eight sets of Arrhenius
parameters (Table 2) contain entropies of activation in
the range of -15 to -36 cal mol-1 K-1, consistent with
the proposed bimolecular attack of solvent on the sub-
strate. For comparison, values for the ethanolysis of
methyl and ethyl chloroformates of -37.0 and -32.3 cal
mol-1 K-1, respectively, have been reported6b and the
methanolysis of methyl chloroformate23 has a value of
-27.9 cal mol-1 K-1
.
While a bimolecular mechanism for the solvolyses is
strongly indicated by the much slower reactions in TFE-
rich solvents and by the appreciably negative entropies
of activation, it is not established whether the process
involves a stepwise addition-elimination (association-
dissociation) or a concerted (SN2) pathway. A powerful
test in considering detailed mechanisms of solvolysis is
to carry out a correlation analysis using the extended
Grunwald-Winstein equation (eq 4 ).26 In eq 4, k and k0
One possible cause for concern is that the NT and YCl
scales are being used at a temperature more than 100
°C lower than those at which they were experimentally
determined. We have previously shown,28 in a study of
the solvolyses of cyclohexyl p-toluenesulfonate at a
variety of temperatures, that the l and m values do not
log(k/k0) ) lNT + mYX + c
(4)
are the specific rates of solvolysis of a substrate RX in a
(26) Winstein, S.; Grunwald, E.; Jones, H. W. J. Am. Chem. Soc.
1951, 73, 2700.
(27) Grunwald, E.; Winstein, S. J. Am. Chem. Soc. 1948, 70, 846.
(28) Kevill, D. N.; Abduljaber, M. H. Croat. Chim. Acta 1992, 65,
539.
(23) Leimu, R. Chem. Ber. 1937, 70, 1040.
(24) Kivinen, A. Acta Chem. Scand. 1965, 19, 845.
(25) Euranto, E. K.; Leimu, R. S. Acta Chem. Scand. 1966, 20, 2028.
9034 J. Org. Chem., Vol. 70, No. 22, 2005

order of magnitude are indeed very small when compared
to the change of approximately 6 orders of magnitude
observed in the rates of solvolysis after inserting a
carbonyl group into methyl or ethyl chloroformate to give
the corresponding chloroglyoxalate. The observations are
very plausibly explained by the operation of an SN2
mechanism for the solvolyses at sp3-carbon and of an
addition-elimination mechanism, with the addition step
being rate determining, for the solvolyses at sp2-carbon.
In conclusion, the solvolyses of methyl and ethyl
chloroglyoxalates proceed about 106 times faster than the
corresponding solvolyses of the chloroformate esters. The
extended Grunwald-Winstein equation (eq 4) was used
to correlate the data and the rather large sensitivities to
changes in solvent nucleophilicity (1.45 and 1.57) and the
modest sensitivities to changes in solvent ionizing power
(0.30 and 0.35) are consistent with an addition-elimina-
tion (association-dissociation) mechanism, with the ad-
dition step being rate determining.7,8,11
Experimental Section
The methyl and ethyl chloroglyoxalates (methyl chlorooxo-
acetate, Aldrich, 96%; and ethyl chlorooxoacetate Aldrich, 98%)
were used as received. Runs were performed with ca. 5 × 10-3
M substrate. The titrimetric determination of specific rates and
the purifications of the solvents were as previously described.19
The low-temperature experiments were carried out by allowing
a solid CO2-acetone slush in a Dewar flask to slowly warm to
room temperature. At just below the required temperature, the
reaction vessel containing 25 mL of the solvent was immersed
and stirring was started. After temperature equilibration and
warming to the desired temperature, 12 µL of substrate was
added and the conductivity changes measured as a function of
time. Conductance measurements at appropriate time intervals
were used, in conjunction with the infinity value, to obtain
integrated rate coefficients and all values from duplicate runs
for up to 80% reaction were used to obtain the reported averages
(Table 1). Temperatures were monitored using a factory-
calibrated alcohol thermometer. The runs were sufficiently fast
(half-lives of 4 s to 6 min) for temperature variation during the
runs to be negligible. Runs at temperatures above -22 °C were
carried out with immersion of the conductivity cell in a conven-
tional low-temperature constant-temperature bath, and tem-
peratures were determined using a standardized mercury
thermometer.
FIGURE 2. Plot of log k for solvolyses of ethyl chlorogly-
oxalate at -76.2 °C against (1.57NT + 0.35YCl).
vary appreciably when unchanged NT and YOTs values are
used over a 50 °C range, and this suggests that the
influence on the correlation of working at a rather low
temperature could well be small. Nonetheless one must
be cautious, in any mechanistic assignment, of small
differences between the sensitivity values of the present
study and earlier studies of related systems at consider-
ably higher temperatures.
It is of interest to compare the effect of introduction of
a carbonyl group at the reaction center for solvolysis
reactions taking place at sp2- and sp3-hybridized carbon.
Studies29,30 have shown that, for bimolecular solvolyses
at sp3-carbon, the carbonyl group has only a very minor
effect upon the reaction rate, which is plausibly explained
in terms of a balance of electronic effects between
assistance to the nucleophilic attack and hindrance to
the departure of the leaving group in a close to synchro-
nous concerted process. For example,30 the introduction
of a benzoyl group into methyl tosylate reduces the rate
of ethanolysis at 62.5 °C by a factor of 8.1, while changing
the 2-methylene group of 2-phenylethyl bromide to a
carbonyl group increases the rate of solvolysis in 80%
ethanol by a factor of 7.0. These changes of less than 1
The apparatus for measurement of the conductance as a
function of time consisted of an efficiently stirred conductivity
cell (capacity 10-50 mL) connected to a TENMA multimeter (72-
602 model with 72-6251 connector, linked to a PC through an
RS232C port and with a Simpson 420 function generator). The
multiple regression analyses were performed using commercially
available statistical packages.
Acknowledgment is made to the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for support of this research.
(29) Pasto, D. J.; Garves, K.; Serve, M. P. J. Org. Chem. 1967, 32,
774.
(30) Kevill, D. N.; Kim, C.-B. J. Org. Chem. 2005, 70, 1490.
JO050998M
J. Org. Chem, Vol. 70, No. 22, 2005 9035