11436 J. Am. Chem. Soc., Vol. 118, No. 46, 1996
ToteVa and Richard
10-4 M) as an internal standard was monitored by withdrawal of an
aliquot (120 µL) of the reaction mixture at various times, which was
neutralized with 2 M sodium acetate before analysis by HPLC.
HPLC Analyses. The products of the spontaneous reactions of 1-Cl
and 1-O2CC6F5 and the acid-catalyzed reactions of 1-OH and 2 were
separated and quantified by HPLC analysis as described in previous
work.20,26,27 The reaction products were detected at 278 nm, which is
λmax for 1-OH.
were calculated from the ratio of product yields using eq 3. Rate
-
constant ratios (M-1) for partitioning of 1-X between reaction with N3
and solvent were calculated using eq 4, where ∑[1-Solv] is the sum of
the concentrations of the products of the reaction of solvent with 1-X.
A similar equation that treats the elimination reaction as a first-order
process was used to calculate rate constant ratios for partitioning of
1-X between nucleophilic substitution and alkene-forming elimination
reactions.
The alcohol (1-OH) and the disubstituted alkene (2) products of the
reactions of 1-X were identified by comparison of their HPLC retention
times with those of authentic materials. The ethers 1-OMe and
1-OCH2CF3 were identified as the peaks which appear during reaction
of 1-X in mixed MeOH/H2O and TFE/H2O solvents, respectively. The
trisubstituted alkene 3 was identified as the additional product peak
that appears during the acid-catalyzed reactions of 1-OH and 2 and
the spontaneous reactions of 1-Cl and 1-O2CC6F5.
kNu1/kNu2 ) ([1-Nu1][Nu2])/([1-Nu2][Nu1])
kaz/ks ) [1-N3]/(Σ[1-Solv][N3-])
(3)
(4)
The integrated HPLC peak areas and the rate constant ratios
calculated directly from the ratios of product peak areas are reproducible
to better than (5% and (10%, respectively. The product rate constant
ratios for reaction of N3- are estimated to be accurate to ( 20%, because
the yields of the azide ion adduct 1-N3 were determined from the
difference between the normalized areas of the product peaks for
reactions in the presence and absence of this nucleophile (see above).
Kinetic Studies. Kinetic studies were carried out at 25 °C and a
constant ionic strength of 0.50 maintained with sodium perchlorate.
The reactions of 1-Cl were initiated by making a 100-fold dilution
of a solution of substrate in acetonitrile into the reaction mixture to
give a final substrate concentration of ca. 6 × 10-4 M. Reactions in
the presence of perchlorate, lyoxide, and halide ions were monitored
spectrophotometrically by following the increase in absorbance at 234
nm. Reactions in 50:50 (v/v) MeOH/H2O in the presence of N3- were
monitored by following the protonation of a phenoxide anion indicator
(8 × 10-4 M) at 290 nm.30 Argon was bubbled through both the
aqueous salt solutions (1.0 M) and the methanol cosolvent immediately
before preparation of the mixed solvent used in the phenoxide indicator
assay, in order to minimize the amount of dissolved oxygen in the final
solvent. In most cases this eliminated the downward drift in the end
points for these reactions, which is probably due to oxidation of
phenoxide ion. In cases where the end point was unstable, it was
calculated by adding 3% to the change in A290 observed after five
reaction halftimes. Observed first-order rate constants, kobsd (s-1), for
the reaction of 1-Cl were calculated from the slopes of semilogarithmic
plots of reaction progress against time, which were linear for at least
three reaction halftimes. The values of kobsd were reproducible to within
(5%.
The reactions of 1-O2CC6F5 in 50:50 (v/v) TFE/H2O were carried
out as described for the product studies. The relative concentrations
of products (Σ[P]) and substrate ([S]0) were monitored by HPLC
analyses during the first 2% of this reaction, and kobsd was determined
as the slope of a plot of Σ[P]/[S]0 against time.
The acid-catalyzed reactions of 1-OH and 2 in 50:50 (v/v) TFE/
H2O were carried out as described for the product studies. The first-
order rate constant for conversion of 1-OH to 1-OCH2CF3 was
determined as the slope of a linear plot of A1-OTFE/A1-OH against time
during the first 12% of the approach to an equilibrium concentration
of 1-OCH2CF3, where A1-OTFE and A1-OH are the integrated HPLC
peak areas for 1-OCH2CF3 and 1-OH, respectively. The first-order
rate constant for the disappearance of 2 was determined as the slope
of a semilogarithmic plot of reaction progress against time which
covered three reaction halftimes.
When the reactions of 1-Cl and 1-O2CC6F5 were carried out in the
presence of increasing concentrations of NaN3, there was no change in
the normalized peak area for 3, but there was an increase in the
normalized area of the peak for 2 that was identical, within experimental
error, with the accompanying decrease in the sum of the normalized
peak areas for the solvent adducts (1-Solv). This suggests that 1-N3
and 2 have nearly identical retention times. A partial resolution of the
peaks for 1-N3 and 2 was achieved by use of very long HPLC analysis
times, but these conditions were not practical for the routine determi-
nation of product yields. The extinction coefficients of 1-Solv and
1-N3 at 278 nm are identical (see below). Therefore, the peak areas
for 1-N3 were estimated as either (a) the difference between the sum
of the normalized areas for the solvent peaks (1-Solv) for reactions in
-
the presence and absence of N3 or (b) the difference between the
normalized peak areas for the mixture of 1-N3 and 2 for reactions in
the presence of N3- and the peak area for 2 for reactions in the absence
of N3-. As required by mass balance, there is good agreement between
these two determinations.
The ratios of product yields were calculated using eq 1, where A1
and A2 are the HPLC peak areas for the products P1 and P2 and ꢀ2/ꢀ1
is the ratio of the extinction coefficients for P2 and P1 at 278 nm, the
[P]1/[P]2 ) (A1/A2)(ꢀ2/ꢀ1)
(1)
wavelength used for these analyses. A ratio of ꢀ1-OH/ꢀ1-Cl ) 1.0 was
determined from HPLC analysis using authentic 1-OH and 1-Cl, and
-
ratios of ꢀ1-OH/ꢀ1-X ) 1.0 were used for the N3 (1-N3) and alkoxide
ion (1-OMe and 1-OCH2CF3) adducts, because it has been shown in
previous work that, at λmax, the extinction coefficients of R-substituted
4-methoxybenzyl alcohols do not change when the hydroxy group is
replaced by azido or simple alkoxy groups.20,27-29 A ratio of ꢀ1-OH/ꢀ2
) 1.0 at 278 nm was determined by showing that the decrease in the
normalized HPLC peak area for 2 during its acid-catalyzed (0.50 M
HClO4) reaction in 50:50 (v/v) TFE/H2O is identical, within experi-
mental error, with the increase in the sum of the normalized peak areas
for the reaction products, which are mostly the solvent adducts 1-OH
and 1-OCH2CF3 (97%). A ratio of ꢀ1-Cl/ꢀ3 ) ꢀ1-OH/ꢀ3 ) 0.82 was
calculated using eq 2, where A1-Cl is the initial normalized HPLC peak
area for 1-Cl, and A1-Solv, A2, and A3 are the final normalized peak
areas of the products of the complete reaction of 1-Cl in 50:50 (v/v)
MeOH/H2O. The 7% increase in absorbance that is observed when
the reaction of 1-Cl in 50:50 (v/v) TFE/H2O is followed spectropho-
tometrically at 278 nm is consistent with the conclusion that the
extinction coefficient for 3 at 278 nm is slightly larger than that for
1-Cl.
Results
The first-order rate constants for the reaction of 1-Cl at 25
°C in 50:50 (v/v) TFE/H2O, determined by monitoring the
increase in absorbance at 234 nm, are kobsd ) 3.1 × 10-4 s-1 (I
) 0.50, NaClO4) and 2.1 × 10-4 s-1 (I ) 0). Figure 1 shows
the dependence of kobsd/k0 for the reaction of 1-Cl at 25 °C on
the concentration of added Cl- in 50:50 (v/v) MeOH/H2O (I )
0.50, NaClO4) and on the concentration of added Cl- or Br- in
50:50 (v/v) TFE/H2O (I ) 0.50, NaClO4), where k0 is the rate
constant for reaction in the absence of added halide ion.
ꢀ1-Cl/ꢀ3 ) (A1-Cl - A1-Solv - A2)/A3
(2)
Calculation of Rate Constant Ratios. Dimensionless rate constant
ratios for the reactions of 1-X with nucleophilic reagents Nu1 and Nu2
(26) Richard, J. P.; Amyes, T. L.; Jagannadham, V.; Lee, Y.-G.; Rice,
D. J. J. Am. Chem. Soc. 1995, 117, 5198-5205.
(27) Richard, J. P. J. Am. Chem. Soc. 1989, 111, 1455-1465.
(28) Richard, J. P.; Amyes, T. L.; Vontor, T. J. Am. Chem. Soc. 1992,
114, 5626-5634.
(29) Richard, J. P.; Jagannadham, V.; Amyes, T. L.; Mishima, M.; Tsuno,
Y. J. Am. Chem. Soc. 1994, 116, 6706-6712.
(30) Amyes, T. L.; Jencks, W. P. J. Am. Chem. Soc. 1989, 111, 7900-
7909.