crystals. Purity (GC/NMR): >99%. 1H and 13C NMR spectra
were identical with the literature.14,28
9-(3-Phenyl-propyl)-9H-fluorene (4d). In a 1-L 2-necked
round-bottomed flask was suspended fluorene (1) (250 g, 1.50
mol) in 3-phenyl-1-propanol (2d) (450 mL, 3.30 mol) and
3-phenylpropionaldehyde (3d) (39 g, 0.29 mol). KOH pellets
(120 g, 2.14 mol) were added, and the mixture was stirred at
185 °C for 4 h. During the reaction the mixture changed its
colour from yellow to orange, red, and brown and turned yellow
in the end again. The stirred reaction mixture was cooled to
ambient temperature and neutralized with concentrated HCl.
Toluene (1 L) and water (1 L) were added, and the organic
phase separated, washed with water (1 × 1 L) and dried over
MgSO4. After removal of the volatiles at 50 °C in vacuo,
methanol (500 mL, technical grade) was added to the warm
oily product. The solution was cooled to 4 °C under stirring,
and after 10 min crystallisation of product started. The suspen-
sion was stirred for additional 1 h at that temperature, and then
the product was separated via filtration with suction (glass frit
G3), washed with ice-cold MeOH (3 × 200 mL), and dried at
50 °C in vacuo to afford the title compound 4d (389 g, 91%)
9-(3,4,5-Trimethoxybenzyl)-9H-fluorene (4b). In a 250-
mL 2-necked round-bottomed flask was suspended fluorene (1)
(20 g, 0.120 mol) in 3,4,5 trimethoxybenzyl alcohol (2b) (50
mL, 0.311 mol) and 3,4,5-trimethoxybenzaldehyde (3b) (5.0
g, 0.025 mol). KOH pellets (10 g, 0.178 mol) were added, and
the mixture was stirred at 185 °C for 3 h. During the reaction
the mixture changed its colour from yellow to dark brown and
finally to cream (after 20 min). The stirred reaction mixture
was cooled to 95 °C, water (125 mL) was added, and the
mixture was cooled to room temperature and stirred for another
0.5 h to get a suspension. The product was separated via
filtration (glass frit G3) and washed with water (3 × 75 mL),
giving a beige crude product. This crude product was recrystal-
lized from hot EtOH using 1 g of charcoal to decolorize
affording 9-(3,4,5-trimethoxybenzyl)-9H-fluorene (4b) (36.8 g,
89%) as off-white crystals. Purity (GC/NMR): > 99%. 1H NMR
(500 MHz, CDCl3) δ 7.71 (d, 3J ) 7.5 Hz, 2 H, CH, ar), 7.33
1
as off white crystals. Purity (GC/NMR): >99%. H and 13C
4
3
(ddt, J ) 0.5 Hz, J ) 1.5 Hz, J ) 7.5 Hz, 2 H, CH, ar),
7.27–7.20 (m, 4 H, CH, ar), 6.34 (s, 2 H, CH, ar), 4.20 (t, 3J )
7.0 Hz, 1 H, 9-Flu H), 3.83 (s, 3 H, OCH3), 3.73 (s, 6 H, OCH3),
3.07 (d, 3J ) 7.0 Hz, 2 H, CH2); 13C{1H} NMR (125.8 MHz,
CDCl3) δ 153.3, 147.0, 141.4, 136.9, 135.4, 127.6, 127.0, 125.3,
120.3, 106.9, 61.3, 56.5, 49.1, 40.6; HRMS calcd for C23H22O3
346.1568, found 346.15881.
NMR spectra were identical to those in the literature.28
9-Butylidene-9H-fluorene (5). In a 2-L 3-necked round-
bottomed flask were suspended fluorene (1) (166 g, 1.0 mol)
and KOtBu (119 g, 1.06 mol) in xylene (1.5 L) under an argon
atmosphere. The reaction mixture was refluxed for 5 min under
stirring. The formed orange suspension was cooled to 25 °C,
and under stirring n-butyraldehyde (3e) (300 mL, 3.33 mol)
was added dropwise during 5 min. The colour changed to
greenish. The reaction mixture was refluxed for 5 min again,
cooled to 25 °C, and neutralized with concentrated HCl. The
reaction mixture was transferred into a separation funnel and
washed with water (1 × 1 L). The organic layer was dried over
MgSO4, and the volatiles of the clear colourless filtrate were
removed at 80 °C in vacuo to afford a slightly yellowish oil.
Methanol (70 mL) was added to the oily crude product, and
the solution was stirred at 0 °C. After some minutes the title
compound crystallized, and the suspension was stirred for an
additional 1 h at 0 °C. The product is separated via suction
filtration (glass frit G3) and dried in vacuo (the product melts
at 50 °C) to afford 5 (138 g, 63%) as a white solid. Purity (GC/
NMR): >99%. HRMS calcd for C17H16 220.1252, found
2-(9H-Fluoren-9-ylmethyl)-pyridine (4c). In a 500-mL
2-necked round-bottomed flask was suspended fluorene (1)
(37.4 g, 0.225 mol) in 2-pyridinemethanol (2c) (90 mL, 0.926
mol) and 2-pyridinecarbaldehyde (3c) (12.8 g, 0.141 mol). KOH
pellets (18 g, 0.321 mol) were added, and the mixture was stirred
at 185 °C for 2 h. The stirred reaction mixture was cooled to
100 °C, water (125 mL) was added, and the mixture was cooled
to room temperature and stirred for another 0.5 h. The product
was suspended as slightly turquoise pellets in the reaction
mixture. The crude product was separated via filtration (glass
frit G3) and washed with water (3 × 75 mL). The crude product
was dissolved in a mixture of ice (700 g) and concentrated HCl
(200 mL). The solution was extracted with methylene chloride
(400 mL) to remove remaining 2c and 3c (4c·HCl is to be
found in the organic phase). The organic layer was brought to
pH 9 with NaOH, washed with water (2 × 200 mL), and dried
over MgSO4. The volatiles were stripped off from the clear
colourless filtrate at 50 °C in vacuo to afford 4c (55 g, 95%) as
white crystals. Purity (GC/NMR): >99%. 1H NMR (500 MHz,
1
220.12700. H and 13C NMR spectra were identical to those
the literature.29
9-Butyl-9H-fluorene (6). 9-Butylidene-9H-fluorene (5) (80
g, 0.136 mmol) was dissolved in EtOAc (120 mL, technical
grade). Five percent Pd on carbon (2.0 g) was added, and the
mixture was hydrogenated at 20–25 °C (external cooling with
ice), 2 bar H2 for 1.5 h. The catalyst was filtered off via celite,
and the filtrate was evaporated at 50 °C in vacuo to afford 6
(80 g, 100%) as a clear colorless oil that solidified at room
temperature. Purity (GC/NMR): >99%. 1H NMR (500 MHz,
3
CDCl3) δ 8.68 (dq, J ) 5.0 Hz, J ) 1.0 Hz, 1 H, CH, ar),
7.74 (dt, 3J ) 7.5 Hz, J ) 1.0 Hz, 2 H, CH, ar), 7.59 (td, 3J )
7.5 Hz, J ) 2.0 Hz, 1 H, CH, ar), 7.33 (tt, 3J ) 7.5 Hz, J ) 1.0
Hz, 2 H, CH, ar), 7.22–7.17 (m, 3 H, CH, ar), 7.07 (dq, 3J )
7.5 Hz, J ) 1.0 Hz, 2 H, CH, ar), 7.01 (dt, 3J ) 7.5 Hz, J )
1.0 Hz, 1 H, CH, ar), 4.63 (t, 3J ) 7.5 Hz, 1 H, 9-Flu H), 3.22
3
CDCl3) δ 7.73 (dq, J ) 7.5 Hz, J ) 1.0 Hz, 2 H, CH, ar),
3
(d, J ) 7.5 Hz, 2 H, C H2); 13C{1H} NMR (125.8 MHz,
7.49 (ddt, 3J ) 7.5 Hz, J ) 2.0 Hz, J ) 1.0 Hz, 2 H, CH, ar),
7.34 (tddd, 3J ) 7.5 Hz, J ) 1.0 Hz, J ) 1.0 Hz, J ) 1.0 Hz,
2 H, CH, ar), 7.28 (td, 3J ) 7.5 Hz, J ) 1.0 Hz, 2 H, CH, ar),
3.96 (t, 3J ) 6.0 Hz, 1 H, 9-Flu H), 2.02–1.96 (m, 2 H, CH2),
1.31–1.23 (m, 2 H, CH2), 1.19–1.12 (m, 2 H, CH2), 0.82 (t, 3J
CDCl3) δ 160.3, 150.0, 147.5, 141.2, 136.6, 127.5, 127.1, 125.1,
124.8, 122.1, 120.2, 47.6, 43.0; 15N NMR (50.69 MHz, CDCl3)
δ -68.4; HRMS calcd for C19H15N 257.1205, found 257.12060.
(28) Licht, E. H.; Alt, H. G.; Karim, M. M. J. Organomet. Chem. 2000,
599, 275.
(29) Malladi, R. R.; Kabalka, G. W. J. Chem. Res. Synop. 2002, 5, 224.
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Vol. 12, No. 3, 2008 / Organic Process Research & Development