12604 J. Am. Chem. Soc., Vol. 118, No. 50, 1996
Richard et al.
MeOH/H2O was determined using authentic materials. A ratio of ꢀalkene
along with spectroscopic and analytical data for these compounds, are
given in the Supporting Information: Me2NC(S)-1-OH; Me2NC(O)-
2-OH; Me2NC(O)-1-OH; EtOC(O)-2-OH; Me2NC(S)-1-N3; Me2NC-
(S)-2-N3; Me2NC(S)-2-(4-nitrobenzoate); Me2NC(S)-2-(4-methoxyben-
zoate); Me2NC(O)-2-(4-nitrobenzoate); Me2NC(O)-2-(pentafluoro-
benzoate); EtOC(O)-2-(pentafluorobenzoate); Me2NC(S)-1-(4-nitroben-
zoate); Me2NC(S)-1-(3,5-dinitrobenzoate); Me2NC(S)-1-(pentafluo-
robenzoate); Me2NC(O)-1-(pentafluorobenzoate); Me2NC(S)-3; Me2-
NC(O)-3; EtOC(O)-3.
HPLC Analyses. The products of the reactions of R-1-Y and R-2-Y
were separated by HPLC as described previously,1,2,5,6 except that peak
detection was by a Waters 996 diode array detector. The products were
detected by their UV absorbance at the following wavelengths, which
are λmax for the corresponding alcohols: Me2NC(S)-1-Y, 271 nm; Me2-
NC(O)-1-Y, 275 nm; EtOC(O)-1-Y, 275 nm; Me2NC(O)-2-Y, 275 nm;
EtOC(O)-2-Y, 274 nm; CH3-2-Y, 273 nm. The products of the
reactions of Me2NC(S)-2-Y were detected at 266 nm, which is λmax
for Me2NC(S)-3.
/
ꢀRN ) 2.7 at 266 nm for Me2NC(S)-3 and Me2NC(S)-2-N3 was
3
calculated using eq 2, where ∆Aalkene and ∆ARN3 are the changes in the
HPLC peak areas for Me2NC(S)-3 and Me2NC(S)-2-N3, respectively,
observed for reaction of a constant amount of Me2NC(S)-2-(4-
nitrobenzoate) in the presence of increasing concentrations of azide
ion. The reproducibility of the extinction coefficient ratios determined
in different experiments was better than (10%. The relative extinction
coefficients of the alkene EtOC(O)-3 and the corresponding nucleophile
adducts EtOC(O)-2-Y were not determined.
Calculation of Rate Constant Ratios. Dimensionless rate constant
ratios for the reactions of nucleophiles Nu1 and Nu2 with R-1-Y and
R-2-Y were calculated from the product yields using eq 3. The rate
kNu /kNu ) [RNu1][Nu2]/[RNu2][Nu1]
(3)
1
2
constant ratios ke/ks for reaction of solvent as a Brønsted base to form
the elimination product (ke) and as a nucleophile to form the solvolysis
products (ks) were calculated directly as the ratio of the yields of these
products. Rate constant ratios kaz/ks (M-1) for partitioning of R-1-Y
and R-2-Y between reaction with azide ion and solvent were calculated
using eq 4. The estimated error in these rate constant ratios is (10%,
the uncertainty in A1/A2 (eq 1), plus any uncertainty in the value of
ꢀP /ꢀP (see above).
The products of the reaction of solvent and azide ion with R-1-Y
and R-2-Y were identified as described in earlier work.1,2,6 The azide
ion adducts Me2NC(S)-1-N3 and Me2NC(S)-2-N3 were also isolated
and characterized by NMR and IR spectroscopy (see Supporting
Information). The alkenes R-3 formed from the reactions of R-2-Y
were identified by comparison of their HPLC retention times with those
for authentic materials.
2
1
-
kaz/ks (M-1) ) [RN3]/ [ROSolv][N3
]
(4)
Procedures for Product Studies. Product studies were carried out
at room temperature (22 ( 2 °C). Control experiments showed that
the product ratios obtained at room temperature and at 25 °C are
identical. Aqueous solutions of sodium azide were adjusted to pH ≈
7 with concentrated HClO4 before use. Reactions were initiated by
making a 100-fold dilution of a solution of substrate (10-2-10-3 M)
in acetonitrile into 50:50 (v:v) TFE/H2O or 50:50 (v:v) MeOH/H2O at
I ) 0.50 (NaClO4). The reactions of Me2NC(S)-2-(4-nitrobenzoate)
in 50:50 (v:v) MeOH/H2O containing both azide and acetate ions were
buffered with 1 or 5 mM sodium phosphate. These solutions were
prepared by dilution of 20 mM sodium phosphate buffer in water at
pH ) 7.0 to the appropriate final concentration in 50:50 (v:v) MeOH/
H2O (I ) 0.50, NaClO4). The dehydration of Me2NC(S)-2-OH to give
Me2NC(S)-3 was carried out in 50:50 (v:v) TFE/H2O containing 0.05-
0.50 M perchloric acid (I ) 0.50, NaClO4).
∑
Rate constant ratios for partitioning of the carbocation intermediates
R-2+ of the reactions of R-2-Y in the presence of azide ion alone, or
in the presence of both azide and acetate ions, were determined from
the nonlinear least squares fit of the product data to the appropriate
equation (see Discussion), using SigmaPlot from Jandel Scientific.
Kinetic Methods. Kinetic studies were carried out in 50:50 (v:v)
TFE/H2O or 50:50 (v:v) MeOH/H2O at 25 °C and I ) 0.50 (NaClO4).
Aqueous solutions of sodium azide were adjusted to pH ≈ 7 with
concentrated HClO4 before use. The reactions were initiated by making
a 100-fold dilution of a solution of substrate (10-2-10-3 M) in
acetonitrile into the appropriate reaction mixture. For reactions that
were monitored by HPLC analysis, the reaction mixture also contained
ca. 10-5 M of 9-hydroxy-9-methylfluorene or 9-methoxyfluorene as
an internal standard to correct for small variations in the HPLC injection
volume.
The yields of the products of the reaction of Me2NC(S)-2-(4-
methoxybenzoate) with azide ion in 50:50 (v:v) MeOH/H2O were
determined during the first 3 h of the reaction, because at later times
there was significant conversion of the azide ion adduct to the alkene
Me2NC(S)-3. For all other R-1-Y and R-2-Y, the products were shown
to be stable for at least three halftimes of the reaction of the substrate.
Ratios of product yields ([P1]/[P2]) were calculated using eq 1, where
A1/A2 and ꢀP /ꢀP are the ratios of the peak areas from HPLC analysis
The reactions of substituted benzoate esters were monitored by
following either (a) the change in UV absorbance at the following wave-
lengths: Me2NC(S)-1-(pentafluorobenzoate), 275 nm; Me2NC(S)-2-
(4-nitrobenzoate), 274 nm; or (b) the disappearance of the substrate
by HPLC at the following wavelengths: Me2NC(S)-2-(4-methoxyben-
zoate), 266 nm; Me2NC(S)-1-(4-nitrobenzoate), 269 nm; Me2NC(S)-
1-(3,5-dinitrobenzoate), 271 nm; Me2NC(O)-2-(4-nitrobenzoate), 262
nm; Me2NC(O)-2-(pentafluorobenzoate), 273 nm; Me2NC(O)-1-(pen-
tafluorobenzoate), 273 nm; EtOC(O)-2-(pentafluorobenzoate), 273 nm;
EtOC(O)-1-(pentafluorobenzoate), 273 nm.
The progress of the dehydration of Me2NC(S)-2-OH to give Me2-
NC(S)-3 in 50:50 (v:v) TFE/H2O containing 0.05 - 0.50 M perchloric
acid (I ) 0.50, NaClO4) was monitored by HPLC analysis at 271 nm.
For all reactions, good first-order kinetics were observed over at
least three half-lifes. First-order rate constants were determined from
the slopes of linear semilogarithmic plots of reaction progress against
time. The second-order rate constant for the acid-catalyzed dehydration
of Me2NC(S)-2-OH was determined as the slope of the linear plot of
2
1
and the extinction coefficients of the two products at the wavelength
of the analysis, respectively. The reproducibility of the product ratios
[P1]/[P2] ) (A1/A2)(ꢀP /ꢀP )
(1)
(2)
2
1
ꢀalkene/ꢀRN ) ∆Aalkene/∆ARN
3
3
from HPLC analysis was (10%. For R-1-Y, EtOC(O)-2-Y, and CH3-
2-Y, the extinction coefficients of the alcohols and the corresponding
methanol and azide ion adducts were shown to be identical by
solvolyzing the corresponding benzoate esters in the presence of
increasing concentrations of methanol or azide ion and showing, by
HPLC analysis of a constant amount of total product, that the decrease
in the HPLC peak area for the alcohol product is equal to the increase
in the HPLC peak area for the methanol or azide ion adduct. The
extinction coefficients of Me2NC(O)-2-N3 and Me2NC(O)-2-OH at 275
nm were assumed to be identical because the absorbance of these
compounds at this wavelength is due primarily to the 4-methoxyphenyl
k
obsd against [HClO4]. Rate constants determined spectrophotometrically
were reproducible to (5%, and rate constants determined by HPLC
analysis were reproducible to (10%.
Ab Initio Calculations. The potential energy surfaces of R-sub-
stituted 1-phenylethanols and the corresponding R-substituted styrenes
were examined with the semiempirical AM1 Hamiltonian7 using
MOPAC 4.08 on an IBM ES9121-400 computer at Miami University,
group. A ratio of ꢀalkene/ꢀROH ) (12 600 M-1 cm-1)/(1800 M-1 cm-1
)
(7) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. G.; Stewart, J. P. J. Am.
Chem. Soc. 1985, 107, 3902-3909.
(8) Stewart, J. J. P.; Seiler, F. J., MOPAC 4.0 (QCPE 455), Quantum
Chemistry Program Exchange: Department of Chemistry, Indiana Univer-
sity.
) 7.0 at 275 nm for Me2NC(O)-3 and Me2NC(O)-2-OH in 50:50 (v:v)
(5) Amyes, T. L.; Richard, J. P. J. Am. Chem. Soc. 1990, 112, 9507-
9512.
(6) Richard, J. P. J. Am. Chem. Soc. 1989, 111, 1455-1465.