Deprotonation of Substituted 2-Tetralones
J. Am. Chem. Soc., Vol. 119, No. 52, 1997 12723
nitric acid, the reaction mixture was removed from the cooling bath
and stirred for an additional 20 min before being poured onto ice.
Chloroform was used as the eluent in column chromatography.
Recrystallization from ethyl acetate/hexane gave 480 mg of product
(54%), mp 141-143 °C (lit.16c 141-141.5 °C). TLC (chloroform/
methanol, 100:1), Rf ) 0.60. 1H NMR (CDCl3): δ 3.66 (s, 4H, H1
and H3), 7.48 (d, J ) 8.1 Hz, 1H, H8), 8.18 (d, J ) 8.1 Hz, 2H, H4 and
Scheme 1
H8). IR (KBr): ν 3080, 2920, 2850, 1715, 1605, 1525, 1340 cm-1
.
Anal. Calcd for C9H7O3N: C, 61.01; H, 3.95; N, 7.90. Found: C,
61.53; H, 4.11; N, 7.86. UV (1 N NaOH): λmax 513 nm.
6-Chloro-2-tetralone (1c) was prepared by the reaction of 4-chlo-
rophenylacetyl chloride (8.93 g, 47.2 mmol) with excess ethylene and
anhydrous AlCl3 (13 g) in anhydrous dichloromethane (120 mL).17,18
Column chromatography (silica, Merck 60, CH2Cl2), followed by
recrystallization gave pure 1c (7.11 g, 84%), mp 67.0-67.5 °C (lit.:
68-70 °C).17 TLC (CH2Cl2), Rf ) 0.24. 1H NMR (CDCl3): δ 2.54
(t, J ) 6.6 Hz, 2H, H4), 3.04 (t, J ) 6.6Hz, 2H, H3), 3.54 (s, 2H, H1),
7.05 (d, J ) 8.1Hz, 1H, H8), 7.19 (dd, J ) 2.1 Hz, 8.8 Hz, 1H, H7),
7.23 (s, 1H, H5). IR (CH3Cl): ν 3010, 2950, 2900, 2850, 1710, 1595,
than for the enolate of benzyl methyl ketone.15 In the present
work, we describe the effects of ring substituents on the kinetic
and equilibrium acidities of 2-tetralone, and we discuss the
nature of charge distribution in both the anion and the transition
state for abstraction of the R proton by hydroxide ion.
1480, 1410, and 1330 cm-1
.
7-Chloro-2-tetralone (1f). 3-Chlorophenylacetyl chloride (5.54 g,
32.5 mmol) was reacted with ethylene and anhydrous AlCl3 (8 g) in
anhydrous dichloromethane (120 mL) as for 1c.17 The product was
purified by column chromatography (silica, Merck 60, 9:1 hexane/ethyl
acetate) and recrystallized from ethyl acetate/hexane (3.58 g, 61%),
mp 38-39 °C. TLC (hexane/ethyl acetate, 9:1), Rf ) 0.16. 1H NMR
(CDCl3): δ 2.54 (t, J ) 6.6 Hz, 2H, H4), 3.03 (t, J ) 6.6 Hz, 2H, H3),
3.55 (s, 2H, H1), 7.12-7.18 (mult, 3H, H5, H6, H8). IR (CH3Cl): ν
3040, 3020, 2950, 2910, 2870, 2850, 1715, 1595, 1470, 1390, and 850
Experimental Section
Unless otherwise mentioned, all chemicals were reagent grade or
better and were purchased commercially. 1H NMR spectra were
recorded at 300 MHz in CDCl3 referenced to TMS as an internal
standard using a General Electric QE-300 spectrometer. Melting points
were determined on a Mel-Temp apparatus and are uncorrected. Thin
layer chromatography (TLC) was carried out on precoated (0.20 mm)
silica gel (Merck 60 F-254) plates. Spectral titrations were performed
on Gilford Response or Response II UV/vis spectrophotometers.
Kinetic measurements were made using a Hi-Tech QP/SF-53 stopped-
flow spectrophotometer. 4-Nitrobenzyl methyl ketone (4b) was
purchased from Lancaster Synthesis Inc., mp 63-64 °C, TLC (CHCl3),
Rf 0.23, and 6-methoxy-2-tetralone (1d) was a gift from Dr. Mark Gold.
The synthesis of 5,7-dinitro-2-tetralone (1g) will be described in a
separate publication.
cm-1
. Anal. Calcd for C10H9ClO: C, 66.49; H, 5.02; Cl, 19.62.
Found: C, 66.21; H, 5.16; Cl, 19.49.
NMR Determinations. 13C proton decoupled NMR experiments
were run on a General Electric QE-300 spectrometer at 25.0 ( 0.5 °C.
Concentrations of 2-tetralone varied from 0.02 M to 0.85 M. For
determinations in CD3OD/D2O, the 49.0 ppm peak of methanol was
used as an internal standard. For solvents containing d6-DMSO, the
DMSO peak at 39.5 ppm was used as an internal standard.
6-Nitro-2-tetralone (1b) and 7-Nitro-2-tetralone (1e). Compounds
1b and 1e were prepared by nitration of 2-tetralone (99%, Aldrich) as
follows: 2-Tetralone (730 mg, 5.0 mmol) was slowly added to cold
(-30 °C) concentrated nitric acid (8 mL, 90%) with vigorous stirring.
After the addition was completed, the reaction mixture was stirred for
8 min, poured onto a mixture of sodium hydroxide (6.5 g) in water
and ice (ca. 50 mL), and then extracted twice with ethyl acetate. The
combined extracts were washed with water until neutral and dried over
magnesium sulfate. After filtration and evaporation of the solvent under
reduced pressure, the products were purified by column chromatography
(silica, Merck 60) using hexane/ethyl acetate (4:1) as the solvent. The
first compound eluted was 6-nitro-2-tetralone (1b), which was recrystal-
lized from ethyl acetate (260 mg, 27%), mp 70-72 °C. TLC (hexane/
ethyl acetate, 2:1), Rf ) 0.37. 1H NMR (CDCl3): δ 2.60 (t, J ) 6.6
Hz, 2H, H4), 3.19 (t, J ) 6.6 Hz, 2H, H3), 3.69 (s, 2H, H1), 7.30 (d, J
) 8.4 Hz, 1H, H8), 8.10 (dd, J ) 2.1, 8.4 Hz, 1H, H7), 8.13 (br s, 1H,
H5). IR (KBr): ν 3070, 2960, 2910, 1710, 1610, 1590, 1510, 1340
Kinetic Measurements. All kinetic measurements were performed
at 25.0 ( 0.1 °C and µ ) 1.0 M (NaCl, 1.6% MeOH). Solutions of
ketones (ca. 85 µM, 1.6% MeOH) were prepared before each experi-
ment. Base solutions (µ ) 1.0 M, NaCl) were prepared from 1.0 N
standardized NaOH (J. T. Baker) and titrated with potassium hydrogen
phthalate. Rates of enolate formation were determined by rapidly
mixing solutions of the ketones with various concentrations of base in
a 1:5 ratio (5:1 for 4-nitrobenzyl methyl ketone) in a HiTech QP/SF
53 stopped-flow spectrophotometer. The change in absorbance, cor-
responding to formation of the enolate ion, was monitored for at least
10 half-lives. Pseudo-first-order rate constants (kobs) for the approach
to equilibrium were obtained by monitoring the change in absorbance
due to formation of the enolate at the absorbance maximum and fitting
the data to the integrated form of the first-order rate equation by
nonlinear least-squares regression. All compounds showed excellent
fits to pseudo-first-order kinetics, except 2b, which showed a noticeable
drift of the infinity absorbance. A base line correction to account for
this second reaction was included in the equation.
cm-1
. Anal. Calcd for C10H9O3N: C, 62.82; H, 4.74; N, 7.32.
Found: C, 62.58; H, 4.84; N, 7.33. UV (1 N NaOH) λmax 514 nm.
7-Nitro-2-tetralone (1e) eluted as a second major product and was
recrystallized from ethyl acetate/hexane (370 mg, 40%), mp 97-98
°C (lit.16a,b 94-96 °C; 96-97 °C). TLC (hexane/ethyl acetate, 2:1),
Rf ) 0.32. 1H NMR (CDCl3) δ 2.60 (t, J ) 6.6 Hz, 2H, H4), 3.18 (t,
J ) 6.6 Hz, 2H, H3), 3.69 (s, 2H, H1), 7.41 (d, J ) 8.1 Hz, 1H, H5),
8.03 (br s, 1H, H8), 8.10 (dd, J ) 2.1, 8.1 Hz, 1H, H6). IR (KBr): ν
3080, 2950, 2900, 1710, 1610, 1590, 1515, 1340 cm-1. Anal. Calcd
for C10H9O3N: C, 62.82; H, 4.74; N, 7.32. Found: C, 62.50; H, 4.82;
N, 7.40. UV (1 N NaOH) λmax 298.5 nm.
Spectral Determination of pKa’s. Stock solutions of ketones (50
µL ca. 1.25 mM in methanol) were added to either aqueous sodium
hydroxide (3.00 mL, µ ) 1.0 M, NaCl, [OH-] ) 0.1-1.0 M) or buffer
solutions (pH ) 6.1-10.7, [buffer] ) 0.2 or 0.3 M, µ ) 1.0 M with
NaCl) and the absorbance determined at the λmax of the enolate. Buffers
used were N-(carbamoylmethyl)iminodiacetic acid (ADA, pKa 6.6),
2-morpholinoethanesulfonic acid (MES, pKa 6.1), 2-[N-[tris(hydroxym-
ethyl)methyl]amino]ethanesulfonic acid (TES, pKa 7.4), 3-[N-[tris-
(hydroxymethyl)methyl]amino]propanesulfonic acid (TAPS, pKa 8.4),
2-(N-cyclohexylamino)ethanesulfonic acid (CHES, pKa 9.3), and 3-(cy-
clohexylamino)-1-propanesulfonic acid (CAPS, pKa 10.4). pH values
for all buffer solutions were measured with a Radiometer PHM85
Precision pH meter and corrected for the concentration of sodium ion.
5-Nitro-2-indanone (2b) was prepared as above from 2-indanone
(700 mg, 5.0 mmol), except that after addition of 2-indanone to the
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