2000) and then extrapolates the next 100 points (ln absorbance
vs. time) to obtain the effective absorbance at zero time. This
procedure avoids the effect of any side-reactions that take place
during mixing and shortly after. We tested this procedure by
replacing the methyl iodide with low concentrations of acetic
acid (one of the proposed base-consuming impurities1) and
found that the acid–base reaction was complete during the time
of mixing. However, this and other possible side-reactions
would cause the yields of product measured by the HPLC
technique1 to appear low at short times. On the other hand, our
kinetic results are not influenced by these rapid reactions.
Conclusions
All of the data reported in our previous communication,2 as
well as that presented here, strongly support our conclusions
that the S2 reaction between p-nitrophenoxide ion (0.000025–
0.00006 M) and methyl iodide (0.5–2.0 M) in acetonitrile, in the
presence and the absence of intentionally added water, follows
the reversible consecutive second-order mechanism represented
in eqn. 4. The reaction does not reach the steady-state before
late in the first half-life. Application of our recently developed
non-steady-state kinetic method,7 facilitates the resolution of
the apparent rate constants into the microscopic rate constants
for the individual steps. Conventional kinetic analysis as
proposed by others1 is not suitable for the elucidation of subtle
mechanistic nuances. The criticism of our work2 by Humeres
and Bentley does not appear to be justified.1
Fig. 3 Extent of reaction–time profiles for the reaction of p-nitro-
phenoxide ion (0.00006 M) with methyl iodide (1.0 M) in acetonitrile
containing water (0.04%). Solid squares (experimental data) and line
(theoretical data for mechanism illustrated in eqn. 4), solid circles and
line (simple 1-step Sn2 mechanism).
The results of a molecular dynamics study of the reactions
of methyl chloride with chloride ion in the gas phase, in aque-
ous solution, and in DMF solution led to the conclusion by
Jorgensen8 that in DMF the reaction proceeds in two steps
involving the intermediate formation of an ion–dipole complex.
Bordwell9 found no direct relationship between the size of
Brönsted βNu and the extent of bond making or bond breaking
in the transition states for several S2 reactions in DMSO and
suggested the two stage mechanism involving an ion–dipole
complex for these reactions. These studies8,9 provide additional
support for the reversible consecutive mechanism (eqn. 4) for
the reaction between p-nitrophenoxide ion and methyl iodide in
acetonitrile.
Fig. 4 Plot of ln absorbance vs. time (3.0 half-lives) for the reaction
between p-nitrophenoxide ion (0.0006 M) with methyl iodide (1.0 M) in
acetonitrile containing water (0.6%) at 298 K. There are 2 lines in this
figure; one is for experimental data (2000 points) and the other is the
linear least squares fit of the data (solid line). The two lines can only be
distinguished at very short times.
Acknowledgements
We gratefully acknowledge the National Science Foundation
(CHE-0074405) for support of this work. We express our
appreciation to Doug Tanner for assistance with the stopped-
flow measurements.
(1.0 M) in acetonitrile at 298 K can only be distinguished from
the linear least squares fit of the data at very short times. The
non-steady-state treatment of the data corresponding to the
first half-life gives results similar to those illustrated in Fig. 3.
The data in Fig.4 serves a further purpose. Humeres and
Bentley1 suggested that diffusion of unreacted reagents into the
spectrophotometer cell at long times could affect our kinetic
results. Other than the deviation from first-order kinetics at
short times, excellent first-order kinetics over three half-lives are
illustrated by Fig. 4.
References
1 E. Humeres and T. W. Bentley, Org. Biomol. Chem., 2003, 1,
1969–1971.
2 Y. Lu, K. L. Handoo and V. D. Parker, Org. Biomol. Chem., 2003, 1,
36–38.
3 G. J. Janz and M. J. Tait, Can. J. Chem., 1967, 45, 1101–1107.
4 R. Fernandez-Prini, in Physical Chemistry of Organic Solvent
Systems, A. K. Covington and T. Dickenson, eds., Plenum Press,
London, ch. 5, Part 1, 1973 .
5 B. L. Murr, Jr. and V. J. Shiner, Jr., J. Am. Chem. Soc., 1962, 84,
4672–4677.
6 R. E. Roberson, Prog. Phys. Org. Chem., 1967, 4, 213–280.
7 Y. Zhao, Y. Lu and V. D. Parker, J. Am. Chem. Soc., 2001, 123,
1579–1586; Y. Lu, Y. Zhao and V. D. Parker, J. Am. Chem. Soc., 2001,
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Org. Chem., 2001, 14, 604–611.
8 J. Chandrasekhar and W. L. Jorgensen, J. Am. Chem. Soc., 1985, 107,
2974–2975; W. L. Jorgensen, Acc. Chem. Res., 1989, 22, 184–189.
9 F. C. Bordwell and D. L. Hughes, J. Am. Chem. Soc., 1986, 108,
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Comments on the validity of the HPLC1 experiments to
determine yield of product during kinetic measurements
at short time intervals after mixing
We agree that the yield of ArOCH3 in the presence, depending
upon concentration, of any inadvertent base-quenching react-
ants will be lowered when measured at short times after mixing.
Under those conditions, some ArOϪ is consumed in rapid acid–
base reactions giving rise to decreased yields at short times.
These reactions take place during the time of mixing. Our data
handling procedure ignores the first seven data points (out of
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 6 2 1 – 2 6 2 3
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