5
360 J . Org. Chem., Vol. 63, No. 16, 1998
Gobbi et al.
in competing with the ligand for the metal ion, and thus
mercial product, stored over molecular sieves, under nitrogen.
Karl Fischer titrations showed a water content e20 ppm.
Deoxybenzoin (1), alkylating agents 2-4, benzylphenyl ether,
and tetradecane were utilized as purchased.
R,R′-Dideuteriodeoxybenzoin (1c) was prepared by adding,
in a 50 mL flask, solid MeONa (0.15 g, 2.78 mmol) to a solution
of deoxybenzoin (1) (1.0 g, 5.10 mmol) in monodeuteriometha-
nol (10 mL) under a nitrogen atmosphere at room temperature.
2
2,23
in determining cation selectivity.
The trend we found
+
+
in chlorobenzene (Na > K ) parallels that obtained by
2
4
other authors for 18-crown-6 in THF and the gas
phase2
5,26
(Li > Na > K > Rb > Cs ). It reflects the
+
+
+
+
+
intrinsic cation selectivity of these macrocycles and
+
+
+
contrasts the well-known sequences (K > Na ∼ Rb >
Cs ) by Pedersen and Izatt8 in polar solvents (H
+
27
O,
2
After 90 min of stirring, D
mixture was extracted with ethyl ether (3 × 10 mL). The
organic phase was washed with D
O (2 × 10 mL), then dried
over Na SO , and evaporated under reduced pressure. The
2
O (5 mL) was added and the
methanol). In fact, in the latter the reversed order is
2
mainly due to the specific solvation of the cation by the
medium that increases with increasing charge density.23
2
4
R,R′-dideuteriodeoxybenzoin (1c) was obtained as a white solid
Distr ibu tion of th e Alk yla tion P r od u cts. As Table
1
(
7
0.79 g, 78%): mp 53-54 °C; H NMR (300 MHz, CDCl
3
) δ
3
shows, the distribution of the alkylation products,
.22-8.10 (m, 10H).
C-alkylated 5 and O-alkylated 6, is also related, in the
low polar chlorobenzene, to the ability of the ligand to
separate cation from anion in the ion pair. With crown
ether 7 the preferential association of the complexed
cation with the center of the ambident O/C enolate anion
with the maximum electron density, the oxygen, hinders
reaction at this site. As a result, alkylation of the less
electronegative center, the carbon, is favored and only
the C-alkylation product 5 is obtained.
Deter m in a tion of th e En ola te 1a ,b F or m a tion .
A
standardized chlorobenzene solution (10 mL) of R,R′-dideute-
riodeoxybenzoin (1c) (0.1 M), PHDB18C6 7 (0.05 M), and
benzyl phenyl ether (0.1 M) as internal standard was magneti-
cally stirred under a nitrogen atmosphere with an aqueous
solution of 13 M KOH (7 mL) in a flask thermostated at 25 (
0
.1 °C. Samples (1 mL) were withdrawn at various times, by
stopping the stirrer for 20-40 s to allow adequate separation,
and analyzed by 1H NMR (chlorobenzene, C
as external
reference). The H/D exchange percentage was evaluated by
following the appearance of the singlet at δ 3.82 (-COCH
Ph) and using the singlet of phenyl benzyl ether at δ 4.80
OCH Ph) as standard. An analogous experiment was per-
6
D
6
By contrast, the regioselectivity of reaction 1 noticeably
2
-
drops with the more efficient complexing agent [2.2.2,C10
]
(
2
8
. In this case, owing to the better cation-anion separa-
formed in parallel without ligand.
tion realized by this ligand, the nucleophilicity of the
enolate O-center increases, as does the quantity of
O-alkylated product (Table 3). Also with n-BuOMes (4)
the quantity of 6 increases slightly on going from crown
ether to cryptand. However, as was expected,28 with this
A standardized chlorobenzene solution (15 mL) of deoxy-
benzoin (1) (0.2 M) and catalyst 7-9 (0.01-0.04 M) was
magnetically stirred under nitrogen with the appropriate
aqueous or solid base (40-50 molar equiv) in a flask thermo-
stated at 25 ( 0.1 °C. At various times, aliquots of the organic
phase (2-3 mL) were withdrawn, after stopping the stirring
for 20-40 s, quenched in ice-cold MeOH (50 mL) and poten-
tiometrically titrated with 0.01 N HCl.
“harder” alkylating agent, the O-alkylated product, de-
rived from the “harder” O-terminus of the ambident
anion, was the main product in all cases.29
In a flask thermostated at 25 ( 0.1 °C a standardized
-
4
chlorobenzene solution (15 mL) of deoxybenzoin (1) (2 × 10
-
4
Exp er im en ta l Section
M) and catalyst 7-9 (4-6 × 10 M) was magnetically stirred
under nitrogen with the appropriate base. At various times,
samples of the organic phase (3 mL) were withdrawn, after
phase separation, placed in a 1 cm cuvette, previously purged
with argon, and analyzed by UV-vis spectroscopy (Table 2).
Kin etic Mea su r em en ts. In a typical LL-PTC procedure,
the reaction flask thermostated at 25 ( 0.1 °C was charged
with an aqueous solution (8 mL) of 19 M NaOH or 13 M KOH
and a standardized chlorobenzene solution (15 mL) of deoxy-
benzoin 1 (0.2 M), catalyst 7-9 (0.0015-0.02 M), alkylating
agent 2-4 (0.3 M), and tetradecane (0.1 M) as internal
standard. The heterogeneous mixture was mechanically stirred
at 1300 ( 50 rpm under nitrogen. Samples of the organic phase
Gen er a l Meth od s. Potentiometric titrations were per-
formed with a Metrohm 670 Titroprocessor by using a com-
bined glass electrode isolated with a potassium chloride bridge.
Karl Fischer analyses were carried out with a Metrohm 684
1
KF coulometer. H NMR spectra were recorded on a Bruker
AC 300 spectrometer, using C
6 6
D and tetramethylsilane as
external and internal standards, respectively. GLC data were
1
obtained with a Perkin-Elmer 8310 equipped with a 50 × /
8
in. OV-101-5% on Chromosorb WHP 100/120 mesh column.
UV-vis spectra were recorded on a Perkin-Elmer LAMBDA
6
spectrophotometer.
Melting points (Pyrex capillary) were determined on a B u¨ chi
melting point apparatus and have been corrected.
Ma ter ia ls a n d Solven ts. Inorganic bases (KOH, NaOH)
were Analar grade commercial products used as such. Cata-
lysts 7-9 were commercially available products, used without
further purification. Chlorobenzene was Analar dry com-
(0.5 mL) were withdrawn at various times, stopping the stirrer
for 40-60 s, and quenched with an acidic and saturated
aqueous solution of KBr (1 mL). The organic phase was
separated after centrifugation and analyzed by GLC (see
General Methods).
An analogous procedure was followed under SL-PTC condi-
tions using ground solid NaOH or KOH (40-50 molar equiv)
instead of the aqueous bases. Reaction rates were determined
following the disappearance of the substrate 1 and/or the
appearance of the alkylation products (5 and 6). The pseudo-
first-order rate constants (kobsd) were computer generated by
plotting log [substrate] vs time and determining the slope of
(
22) Takeda, Y.; Ohyagi, Y.; Akabori, S. Bull. Chem. Soc. J pn. 1984,
7, 3381.
23) Solov’ev, V. P.; Strakhova, N. N.; Raevsky, O. A.; R u¨ diger, V.;
Schneider, H. J . J . Org. Chem. 1996, 61, 5221.
5
(
(
(
24) Smid, J . Angew. Chem., Int. Ed. Engl. 1972, 11, 112.
25) Glendening, E. D.; Feller, D.; Thompson, M. A. J . Am. Chem.
-1
-1
Soc. 1994, 116, 10657.
26) Lee, S.; Wyttenbach, Von Helden, G.; Bowers, M. T. J . Am.
Chem. Soc. 1995, 117, 10159.
27) (a) Pedersen, C. J . J . Am. Chem. Soc. 1967, 89, 7017. (b)
Pedersen, C. J .; Frensdorff, H. K. Angew. Chem., Int. Ed. Engl. 1972,
1, 16.
the straight lines. The second-order rate constants k (M
s )
(
were evaluated by dividing kobsd by the complexed enolate
concentration.
(
In the kinetic measurements under homogeneous condi-
tions, a standardized chlorobenzene solution (5 mL) of alky-
lating agent 2 (0.045-0.18 M) and tetradecane (0.03-0.09 M)
was added, in a flask thermostated at 25 ( 0.1 °C under
nitrogen, to a standardized chlorobenzene solution (10 mL) of
deoxybenzoin (1) (0.03-0.09 M) and catalyst 7 or 8 (0.033-
1
(
(
28) Ho, T. Chem. Rev. 1975, 75, 1.
29) An analogous rationale was previously given by Kornblum et
al. to explain the different O/C ratio found in the alkylation of
phenoxides and â-naphthoxides with alkyl halides on changing solvent
polarity. These authors attributed the effect of the medium on
orientation to the different specific solvation, and hence activation, of
0
.099 M), previously stirred with ground solid NaOH for 10-
3
0
+
-
the atom with higher charge density.
15 m, to generate the enolate complex (M ⊂Lig)R . Timing