1
80 J . Org. Chem., Vol. 67, No. 1, 2002
J ia et al.
Ta ble 3. Mea su r ed Isotop e Effects a t 30.00 ( 0.03 °C a n d
Mech a n istic Assign m en ts for th e Ba se-P r om oted
Rea ction s of 1-OAc a n d 1-Cl
Exp er im en ta l Section
Gen er a l P r oced u r es. NMR spectra were recorded at 25
°
C with a Varian Unity 300 or 400 MHz spectrometer.
substrate
Chemical shifts are indirectly referenced to TMS via the
solvent signal (chloroform-d 7.26 and 77.0 ppm). The high-
1
-OAc
1-Cl
1
H
D
H
Mechanism k /kD
k35/k37
performance liquid chromatography analyses were carried out
with a Hewlett-Packard 1090 liquid chromatograph equipped
with a diode-array detector on an Inertsil 5 ODS-3 (3 × 100
mm) reversed-phase column. The mobile phase was a solution
of acetonitrile in water. The reactions were run at a constant
temperature controlled by a HETO 01 PT 623 thermostat bath.
The ratio of chlorine isotopes was measured using a modified,
hybrid model MI 1201E FAB isotope ratio mass spectrometer
k /k
Mechanism
pyridine
TEA
MeO
E1cB
E1cB
?
5.6
8.4
7.1
E1cB
E2
E2
7.3a
6.5
1.0101
1.0087
c
c
-
b
a
From ref 7. b From ref 24. c From Tables 1 and 2.
Ir r ever sible E1cB Rea ction w ith a La r ge Am ou n t
of Hyp er con ju ga tion ? It has been suggested that the
effect of the leaving group on the rate of irreversible E1cB
reactions is only a polar one, i.e., an inductive effect on
(PO Electron, Ukraine).
Ma ter ia ls. Diethyl ether and tetrahydrofuran were distilled
under nitrogen from sodium and benzophenone. Methanol and
acetonitrile were of HPLC quality and HPLC UV gradient
quality, respectively. Isooctane was of HPLC grade. Sodium
methoxide solution was prepared by dissolving clear-cut pieces
of sodium in methanol under dry nitrogen. Triethylamine
1
the rate-limiting hydron-abstracting step. Accordingly,
any positive element effect in addition to this polar effect
has been suggested to be evidence for an E2 mechanism.
However, theoretical calculations have shown that a
partial bond breaking to the putative leaving group (L)
occurs in the transition state of hydron-abstracting
reactions and that periplanar positioning between the
base and L is preferred.14 This assistance to hydron
removal by hyperconjugative interaction from the electron-
withdrawing group L implies some resemblance between
E2 and E1cB transition-state structures.2
(
Merck, p.a.) was purified by drying over KOH overnight
2
4
followed by distillation from 3,5-dichlorobenzoyl chloride. All
other chemicals used for the kinetic experiments were of p.a.
quality and used without further purification.
1-(2-Ch lor o-2-p r op yl)in d en e (1-Cl). Compound 1-Cl and
1-isopropylideneindene (2) were prepared by previously pub-
lished methods.5
Deter m in in g th e Ch lor in e Kin etic Isotop e Effects. The
leaving group isotope effects were determined for the base-
promoted elimination reaction of 1-(2-chloro-2-propyl)indene
,3,5,15-19
Accordingly, a hypothetical E1cB reaction of a sub-
strate with a chloride leaving group is expected to involve
some bond-breaking to the chloride leaving group in the
rate-limiting ionization transition state. However, it is
very difficult to accommodate in a stepwise mechanism
such very large chlorine leaving group isotope effects as
(
1-Cl) at 30.00 ( 0.03 °C by the following procedure. The
reaction was initiated by addition of prethermostated base
solution (2 mL of 0.11 mM sodium methoxide or 10 mL of 4.00
M TEA buffered with 0.12 M TEA‚HOAc) to a prethermostated
solution of the substrate (38 or 30 mL, respectively) in a 50
mL reaction vessel placed in a water thermostat bath. The
reaction was quenched by quickly pouring the reaction solution
into a separatory funnel containing 100 mL of water, 2 mL of
0
.86 and 1.01%, as measured for the reaction of 1-Cl with
strong bases (see Appendix). We find it most likely that
these large isotope effects, combined with the large
hydrogen isotope effects, are strongly indicative of a
synchronous E2 mechanism. Consistently, there are large
HNO (concentrated), and 40 mL of isooctane. After separation,
3
the aqueous phase was extracted three times with 10 mL
portions of isooctane. The combined isooctane phases were
placed in the freezer for later analysis.
Potassium nitrate (8 g) was added to the aqueous phase,
and the volume was reduced to about 50 mL using an
evaporator. Silver nitrate solution (5 mL, 1.0 M) was then
added to the warm solution (50 °C), which was placed in a
dark place overnight prior to filtration through a preweighed
sintered glass filter. Finally, the filter with the AgCl precipi-
tate was weighed and the amount of AgCl calculated.
element effects: kBr/kCl ) 10 with methoxide ion and kBr
/
1
7
k
Cl ) 5 with TEA. The situation resembles the concerted
2 reaction in which there is a synergism between an
S
N
efficient entering nucleophile and an efficient departing
leaving group.2
0,21
Previous reports on chlorine isotope effects include the
The fraction of reaction was determined by analyzing the
combined isooctane phases, obtained in the separation step
described above, employing HPLC. The analysis showed only
two components, 1-Cl and 2, which were baseline separated.
The alkene 2 was the sole product after a long reaction time.
The relative response factors were determined by analyzing
mixtures of the two pure components prepared by weighing.
The mass spectrometric analysis of the chlorine isotopes was
carried out by a previously published method.25 The silver plate
that is mounted on the tip of the probe of the isotope ratio
mass spectrometer was washed with nitric acid, water, and
acetone. Then, approximately 5 mg of silver chloride was
deposited on the clean silver plate and the plate was heated
gently to melt the sample. Precautions were taken not to
exceed 480 °C and to keep the dimensions of the samples
constant (about 0.2 mm thick and 4 mm in diameter). The
silver plate with the adhered solid sample was mounted on
the tip of the direct insertion probe. Xenon atoms (6 keV)
hitting the surface of the probe at an incidence angle of 45°
were used for ionization. The negative ions formed in this way
were accelerated through a 5 kV potential and detected in a
dehydrochlorination reaction of PhCH(Me)CH
2
Cl with
ethoxide ion in ethanol,22 k /k ) 1.00590 ( 0.00013 (75
C), and the reaction of (4-NO CHCHCl with
methoxide ion in methanol, k /k ) 0.99995 ( 0.00026
30 °C). The E2 and the irreversible E1cB mechanism,
respectively, were assigned to these reactions.
35
37
°
2
C
6
H
4
)
2
2
2
3
35 37
(
(
(
(
(
(
(
9) More O’Ferrall, R. A. J . Chem. Soc. B 1970, 274.
10) J encks, W. P. Chem. Rev. 1972, 72, 705.
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(
(
(
(
(
(
(
(
15) Ahlberg, P. Chem. Scr. 1973, 2, 183.
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(
Jia, .Zhi Sheng
