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A. Heynderickx et al.
PAPER
J7–8 = 8.0 Hz and J8–9 = 4.4 Hz, H8), 7.75–7.86 (m, 3 H, H5, H6 and
aromatic), 8.16 (dd, 1 H, J7–8 = 8.0 Hz and J7–9 = 1.7 Hz, H7), 8.25
(d, 1 H, J = 8.3 Hz, H3), 8.38 (d, 1 H, J = 8.3 Hz, H4), 9.08 (dd, 1 H,
J7–9 = 1.7 Hz and J8–9 = 4.4 Hz, H9).
Anal. Calcd for C21H18N2OS (346.45): C, 72.80; H, 5.24; N, 8.09.
Found: C, 72.76; H, 5.33; N, 8.05.
2-(2 -Ethylsulfonylbenzyl)-1,10-phenanthroline (6)
The synthesis of the titled compound has been accomplished by two
different methods (A and B).
Anal. Calcd for C21H16N2OS (344.43): C, 73.23; H, 4.68; N, 8.13.
Found: C, 73.14; H, 4.76; N, 8.05.
Method A:
2-(2 -Ethylthiobenzyl)-1,10-phenanthroline (4)
The synthesis of the title compound has been accomplished by two
different methods (A and B).
This product was isolated as a by-product from the oxidation of 4.
The crude product was purified by column chromatography (neutral
aluminium oxide; CH2Cl2–EtOAc, 5:2 gradient) and recrystallized
from ethanol–Et2O to afford 6.
Method A
A solution of 3 (2.4 g, 6.9 mmol), hydrazine monohydrate (1.5 mL)
and NaOH (1.46 g) in ethylene glycol (25 mL) was heated at 190 °C
for 5 h. After cooling, the solution was poured in H2O (100 mL) and
the aqueous layer was extracted with CH2Cl2 (2 25 mL). The ex-
tract was washed with H2O (10 mL), dried (MgSO4), and concen-
trated. The crude product was purified by column chromatography
(silica gel, eluted by CH2Cl2–EtOH, 5:0.1 gradient) to afford 4.
Yield: 55 mg, 0.15 mmol (25%); white crystals; mp 174 °C.
1H NMR (CDCl3): = 1.26 (t, 3 H, J = 7.4 Hz, CH3), 3.30 (q, 2 H,
J = 7.4 Hz, SO2CH2), 5.04 (s, 2 H, CH2 benzylic), 7.29–7.49 (m, 4
H, H3 and aromatic), 7.57 (dd, 1 H, J7–8 = 8.1 Hz and J8–9 = 4.4 Hz,
H8), 7.70 (m, 2 H, H5, H6), 8.07 (m, 2 H, H3 , H4), 8.19 (dd, 1 H, J7–
8 = 8.1 Hz and J7–9 = 1.7 Hz, H7), 9.15 (dd, 1 H, J7–9 = 1.7 Hz and
J8–9 = 4.4 Hz, H9)
Yield: 1.4 g, 4.2 mmol (60%); oil.
MS: m/z = 363.
Anal. Calcd for C21H18N2O2S (362.45): C, 69.59; H, 5.01; N, 7.73.
Found: C, 69.63; H, 5.10; N, 7.75.
Method B:
To a solution of (2-ethylthiobenzyl)tributyltin 10 (1.105 g, 2.5
mmol) in anhyd THF (10 mL) was added slowly at –100 °C a pre-
cooled solution (–75 °C) of methyllithium (commercial solution at
1.4 M, 1.78 mL, 2.5 mmol) in THF (25 mL). After 3 h at –75 °C, a
solution of 2-chloro-1,10-phenanthroline (0.23 g, 0.11 mmole) in
THF (10 mL) was added to the yellow benzyllithium solution. The
resulting mixture was allowed to warm to r.t. and stirred overnight
at 50 °C. After cooling and quenching with H2O (20 mL), the aque-
ous layer was extracted with CH2Cl2 (2 10 mL). The combined or-
ganic extracts were dried (MgSO4), filtered and evaporated to
dryness. After purification (see above), the compound 4 was isolat-
ed.
Method B:
To a solution of (2-ethylsulfonylbenzyl)tributyltin (11) (0.955 g, 2
mmol) in anhyd THF (10 mL) was added slowly at –100 °C a pre-
cooled solution (–75 °C) of methyllithium (commercial solution at
1.4 M, 1.44 mL, 2 mmol) in THF (20 mL). After 3 h at –75 °C, a
solution of 2-chloro-1,10-phenanthroline (0.19 g, 0.88 mmole) in
THF (10 mL) was added to the dark red benzyllithium solution. The
resulting mixture was allowed to warm to r.t. and stirred overnight
at 50 °C.
After cooling and quenching with H2O (20 mL), the aqueous layer
was extracted with CH2Cl2 (2 10 mL). The combined organic ex-
tracts were dried (MgSO4), filtered and evaporated to dryness. After
purification, the compound 6 was isolated in 20% yield.
Yield: 35%.
1H NMR (CDCl3): = 1.42 (t, 3 H, J = 7.3 Hz, CH3), 2.94 (q, 2 H,
J = 7.3 Hz, SCH2), 4.84 (s, 2 H, CH2 benzylic), 7.43 (m, 5 H, H3 and
aromatic), 7.61 (dd, 1 H, J7–8 = 8.0 Hz and J8–9 = 4.4 Hz, H8), 7.71
(m, 2 H, H5, H6), 8.06 (d, 1 H, J3–4 = 8.3 Hz, H4), 8.22 (dd, 1 H,
2-(2 -Ethylsulfonyl-4 -nitrobenzyl)-1,10-phenanthroline (7)
To a cooled (–5 °C) and well-stirred solution of 6 (200 mg, 0.55
mmol) in concd sulfuric acid (96%; 4 mL) was added gradually a
cooled solution of red fuming nitric acid (density 1.5, 0.5 mL, 12
mmol) in concd H2SO4 (96%) (2 mL) at –5 °C. After complete ad-
dition, the mixture was stirred at r.t. for 2 h, and then poured onto
about 10 g of ice. The resulting solution was basified (pH 10) by
adding a sat. aq NaOH, and extracted with CH2Cl2 (3 10 mL). The
combined extracts were dried (MgSO4), filtered, and concentrated
under reduced pressure. The crude product was purified by column
chromatography (neutral aluminium oxide; CH2Cl2–EtOH, 10:1
gradient) to afford 7.
J7–8 = 8.1 Hz and J7–9 = 1.7 Hz, H7), 9.24 (dd, 1 H, J7–9 = 1.7 Hz and
J8–9 = 4.4 Hz, H9).
Anal. Calcd for C21H18N2S (330.45): C, 76.33; H, 5.49; N, 8.48.
Found: C, 76.30; H, 5.53; N, 8.45.
2-(2 -Ethylsulfinylbenzyl)-1,10-phenanthroline (5)
To a solution of sulfide 4 (200 mg, 0.6 mmol) in HOAc (5 mL) was
added dropwise a solution of 35% hydrogen peroxide (0.13 mL).
The mixture was stirred at 20 °C for 16 h. After cooling, the solution
was reduced in vacuo and diluted time-to-time with H2O. The con-
centrated solution was adjusted to pH 8 with NaHCO3, and extract-
ed with CH2Cl2. The combined organic extracts were dried
(MgSO4) and concentrated in vacuo to provide crude sulfoxide 5.
The product was purified by column chromatography (neutral alu-
mine oxide, eluted by CH2Cl2–EtOAc–MeOH, 5:2:0.5 gradient) to
afford 5.
Yield: 202 mg, 0.49 mmol (90% overall); oil, which crystallized by
trituration with Et2O; mp 173 °C.
1H NMR (CDCl3): = 1.32 (t, 3 H, J = 7.4 Hz, CH3), 3.47 (q, 2 H,
J = 7.4 Hz, SO2CH2), 5.10 (s, 2 H, CH2 benzylic), 7.51 (d, 1 H,
J3–4 = 8.2 Hz, H3), 7.58 (dd, 1 H, J7–8 = 8.1 Hz and J8–9 = 4.3 Hz,
H8), 7.64 (d, 1 H, J = 8.5 Hz, H6 ), 7.72 (m, 2 H, H5, H6), 8.13 (d, 1
H, J3–4 = 8.2 Hz, H4), 8.17–8.24 (m, 2 H, H7 and H5 ), 8.88 (d, 1 H,
J = 2.4 Hz, H3 ), 9.11 (dd, 1 H, J7–9 = 1.7 Hz and J8–9 = 4.3 Hz, H9).
13C NMR (CDCl3): = 7.12, 41.13, 50.98, 123.03, 123.50, 125.82,
126.25, 126.53, 127.34, 127.73, 128.93, 134.13, 136.12, 137.28,
138.71, 145.74, 146.28, 146.82, 150.20, 158.47.
Yield: 84 mg, 0.24 mmol (40%); solid; mp 126 °C.
1H NMR (CDCl3): = 1.18 (t, 3 H, J = 7.4 Hz, CH3), 2.71 (m, 1 H,
SOCHaHb), 2.95 (m, 1 H, SOCHaHb), 4.64 (s, 2 H, CH2 benzylic),
7.16–7.49 (m, 4 H, H3 and aromatic), 7.57 (dd, 1 H, J7–8 = 8.1 Hz
and J8–9 = 4.4 Hz, H8), 7.69 (m, 2 H, H5, H6), 7.95 (dd, 1 H, J = 7.8
Hz and J = 1.2 Hz, H3 ), 8.08 (d, 1 H, J = 8.3 Hz, H4), 8.19 (dd, 1 H,
MS: m/z = 408 (M+ + 1)
J7–8 = 8.1 Hz and J7–9 = 1.7 Hz, H7), 9.15 (dd, 1 H, J7–9 = 1.7 Hz and
J8–9 = 4.4 Hz, H9).
Anal. Calcd for C21H17N3O4S (407.44): C, 61.90; H, 4.21; N, 10.31.
Found: C, 61.86; H, 4.36; N, 10.27.
Synthesis 2002, No. 12, 1747–1751 ISSN 0039-7881 © Thieme Stuttgart · New York