Job/Unit: O20570
/KAP1
Date: 25-07-12 10:38:43
Pages: 11
A. M. Costero, R. Martínez-Mañez et al.
FULL PAPER
raphy (hexane/EtOAc/Et3N, 97:1:2 Ǟ 83:15:2) over an Et3N
heated under reflux for 16 h. After this time, the solution was evap-
orated and the green oil obtained was purified by chromatography
washed silica phase to afford
5
(844 mg, 54%). 1H NMR
(500 MHz, CDCl3): δ = 7.42–7.38 (m, 2 H), 7.34–7.25 (m, 4 H), (alumina; EtOAc/MeOH, 9:1) to give 10 (154 mg, 79%) as a green
1
7.18 (d, J = 9.0 Hz, 2 H), 6.94 (dd, J = 5.1, 3.6 Hz, 1 H), 6.73 (dd,
J = 3.6, 1.2 Hz, 1 H), 6.66 (d, J = 9.0 Hz, 2 H), 2.95 (s, 6 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 153.09, 149.88, 147.03, 134.64,
128.27, 127.82, 127.28, 127.21, 126.51, 126.36, 125.28, 111.63,
79.94, 40.45 ppm. HRMS (EI): calcd. for C19H18NS [M – H2O +
H]+ 292.1160; found 292.1167.
oil. H NMR (300 MHz, MeOH): δ = 8.77 (d, J = 6.8 Hz, 1 H),
8.02 (d, J = 6.9 Hz, 1 H), 7.15 (d, J = 9.0 Hz, 2 H), 6.73 (d, J =
9.0 Hz, 2 H), 4.37 (s, 1 H), 2.93 (s, 6 H) ppm. 13C NMR (75 MHz,
MeOH): δ = 169.73, 152.05, 146.30, 134.13, 131.98, 130.46, 127.68,
113.71, 82.11, 48.79, 41.23 ppm.
Synthesis of Probe 11: Following the same experimental procedure
described for the synthesis of compound 10, and starting with 8
(145 mg, 0.48 mmol) and methyl iodide (149 μL, 2.38 mmol,
Synthesis of Probe 6: 4-Aminobenzophenone (450 mg, 2.28 mmol)
was dissolved in anhydrous THF (20 mL) in an argon atmosphere,
then a solution of 2-thienyllithium (1 m in THF, 22.8 mL) was
added. The mixture was allowed to react for 5 h. After this time,
water (100 mL) was added and the solvent was partially evapo-
rated. The residue was dissolved in dichloromethane, washed with
water and brine, and dried with MgSO4. The carbinol was purified
by flash chromatography (hexane/EtOAc/Et3N) over an Et3N
1
5 equiv.), probe 11 (100 mg, 47%) was isolated as a yellow oil. H
NMR (300 MHz, MeOH): δ = 8.79 (d, J = 6.7 Hz, 2 H), 8.07 (d,
J = 7.0 Hz, 2 H), 7.41–7.34 (m, 5 H), 7.12 (d, J = 9.1 Hz, 2 H),
6.76 (d, J = 9.1 Hz, 2 H), 4.39 (s, 3 H), 2.96 (s, 6 H) ppm. 13C
NMR (75 MHz, MeOH): δ = 169.23, 152.32, 146.59, 146.38,
133.56, 130.45, 129.81, 129.55, 129.44, 127.82, 113.65, 82.07, 48.65,
41.07 ppm.
washed silica phase to afford
6
(302 mg, 47%). 1H NMR
(300 MHz, CDCl3): δ = 7.43 (dd, J = 8.0, 1.8 Hz, 2 H), 7.38–7.30
(m, 3 H), 7.28 (dd, J = 5.1, 1.2 Hz, 1 H), 7.13 (d, J = 8.7 Hz, 2 H),
6.96 (dd, J = 5.1, 3.6 Hz, 1 H), 6.76 (dd, J = 3.6, 1.2 Hz, 1 H), 6.58
(d, J = 8.7 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.52,
147.52, 146.10, 137.53, 128.97, 128.27, 127.73, 127.70, 126.99,
126.82, 125.75, 114.98, 80.26 ppm.
General Procedure for Generating Carbocations: An acetonitrile
solution of carbinol (1 moldm–3) was treated with an equimolecu-
lar quantity of H2SO4, and was stirred for 30 min at 40 °C. After
evaporating the solvent, the corresponding carbocation was ob-
tained.
Carbocation 2a: 1H NMR (400 MHz, CDCl3): δ = 7.43 (d, J =
9.2 Hz, 4 H), 7.26 (d, J = 8.7 Hz, 2 H), 7.08 (d, J = 8.9 Hz, 4 H),
7.01 (d, J = 8.7 Hz, 2 H), 3.36 (s, 12 H), 1.02 (s, 9 H), 0.32 (s, 6
H) ppm.
Synthesis of Probe 7: 4-Cyanepyridine (870 mg, 8.36 mmol) was
dissolved in anhydrous THF (60 mL) in an argon atmosphere, then
Na (400 mg, 17.39 mmol) was freshly cut into small pieces and
added. The mixture was kept under sonication until radical anion
formation (a red colour developed after radical anion formation)
Carbocation 3a: 1H NMR (400 MHz, CDCl3): δ = 7.43 (d, J =
9.2 Hz, 4 H), 7.26 (d, J = 8.7 Hz, 2 H), 7.08 (d, J = 8.9 Hz, 4 H),
7.01 (d, J = 8.7 Hz, 2 H), 3.36 (s, 12 H), 1.02 (s, 9 H), 0.32 (s, 6
H) ppm.
and
then
4,4Ј-bis(dimethylamino)benzophenone
(2.58 g,
9.63 mmol) was added. The mixture was stirred for 24 h at room
temperature, then water (20 mL) was added and the white solid was
separated by filtration. The filtrate was extracted with dichloro-
methane (3ϫ20 mL) and the organic phase was dried with anhy-
drous MgSO4 and evaporated to obtain an additional portion of
solid. The product was purified by chromatography (alumina; hex-
Carbocation 5a: 1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J =
5.0 Hz, 1 H), 7.68 (m, 1 H), 7.55 (m, 2 H), 7.52 (m, 1 H), 7.43 (dd,
J = 4.90, 4.12 Hz, 1 H), 7.38 (m, 2 H), 7.35 (br. d, J = 9.4 Hz, 2
H), 7.04 (br. d, J = 9.4 Hz, 2 H), 3.51 (br. s, 6 H) ppm.
1
ane/EtOAc, 7:3) to give 7 (2.6 g, 90%) as a white solid. H NMR
1
(300 MHz, CD3CN): δ = 8.84 (d, J = 5.1 Hz, 1 H), 7.61 (d, J =
5.3 Hz, 1 H), 7.40 (d, J = 9.4 Hz, 2 H), 7.02 (d, J = 9.5 Hz, 2 H),
3.33 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 157.29, 150.11,
149.35, 134.37, 129.13, 123.11, 112.16, 81.10, 40.85 ppm.
Carbocation 6a: H NMR (300 MHz, [D6]acetone): δ = 7.70–7.61
(m, 5 H), 7.49 (d, J = 9.5 Hz, 2 H), 7.38 (d, J = 9.0 Hz, 2 H), 7.16
(d, J = 9.5 Hz, 2 H), 7.02 (d, J = 9.1 Hz, 2 H), 3.44 (s, 6 H) ppm.
Carbocation 7a: 1H NMR (300 MHz, CD3CN): δ = 8.81 (d, J =
5.1 Hz, 2 H), 7.57 (d, J = 5.7 Hz, 2 H), 7.37 (d, J = 9.5 Hz, 4 H),
6.99 (d, J = 9.6 Hz, 4 H), 3.31 (s, 12 H) ppm.
Synthesis of Probe 8: Following the same experimental procedure
described for the synthesis of compound 7, and starting with 4,4Ј-
bis(dimethylamino)benzophenone (2.76 g, 12.25 mmol) and 4-cya-
nopyridine (1.02 g, 9.8 mmol), probe 8 was isolated as a white solid
1
Carbocation 8a: H NMR (300 MHz, [D6]acetone): δ = 9.10 (d, J
1
= 7.0 Hz, 2 H), 8.30 (d, J = 7.0 Hz, 2 H), 7.85 (d, J = 9.1 Hz, 2
H), 7.69 (d, J = 9.1 Hz, 2 H), 7.44–7.32 (m, 5 H), 3.48 (s, 6 H) ppm.
(3.0 g, 80%). H NMR (300 MHz, CDCl3): δ = 8.50 (dd, J = 4.5,
1.6 Hz, 2 H), 7.31–7.25 (m, 7 H), 7.03 (d, J = 9.0 Hz, 2 H), 6.63 (d,
J = 9.0 Hz, 2 H), 2.93 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 156.37, 150.39, 149.79, 146.38, 133.70, 129.21, 128.46, 128.11,
127.88, 123.06, 112.16, 81.40, 40.77 ppm.
1
Carbocation 9a: H NMR (300 MHz, [D6]acetone): δ = 9.03 (d, J
= 7.0 Hz, 2 H), 8.24 (d, J = 6.9 Hz, 2 H), 7.28 (d, J = 9.0 Hz, 4
H), 6.92 (d, J = 9.0 Hz, 4 H), 3.80 (s, 6 H) ppm.
Synthesis of Probe 9: Following the same experimental procedure
described for the synthesis of compound 7, and starting with 4,4Ј-
bis(methoxy)benzophenone (1.21 g, 5.0 mmol) and 4-cyanopyr-
idine (430 mg, 4.13 mmol), probe 9 (1.43 g, 89%) was isolated as a
white solid. 1H NMR (300 MHz, CDCl3): δ = 8.36 (dd, J = 4.5,
1.7 Hz, 2 H), 7.18 (dd, J = 4.7, 1.5 Hz, 2 H), 7.08 (d, J = 9.0 Hz,
4 H), 6.76 (d, J = 9.0 Hz, 4 H), 3.72 (s, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 159.35, 156.49, 149.65, 138.52, 129.49,
123.01, 113.83, 80.96, 55.70 ppm.
Synthesis of Ketone 12: An acetonitrile solution of carbocation 2a
(1 moldm–3) was treated with an equimolar quantity of tetrabu-
tylammonium fluoride in an argon atmosphere and was stirred for
30 min at room temperature. After this time, the solvent was evapo-
rated, yielding ketone 12 as a blue solid. Ketone 12 was strongly
solvatochromic and presented a pink colour in acetonitrile/water
1
(9:1). H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 9.0 Hz, 4 H),
7.20 (d, J = 8.9 Hz, 2 H), 7.14 (d, J = 8.5 Hz, 2 H), 6.82 (d, J =
9.3 Hz, 4 H), 3.26 (s, 12 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 180.29, 156.27, 140.61, 138.97, 126.85, 117.73, 117.12, 114.84,
112.62, 40.47 ppm. HRMS: calcd. for C23H25N2O [M + H]+
345.1971; found 345.1967.
Synthesis of Probe 10: Compound 7 (139 mg, 0.40 mmol) was dis-
solved in anhydrous acetonitrile (30 mL) and then methyl iodide
(27.5 μL, 0.44 mmol, 1.1 equiv.) was added. The green solution was
8
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