8
14 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
A Practical Synthesis of 2,6-Dicarboxyfluorenone$
Kirstin F. Warner,* Ammiel Bachrach, Atiq-ur Rehman,
1998, 814±815$
Wayne F. K. Schnatter,% Abhijit Mitra and Charles Shimanskas
Department of Chemistry, Chemical Engineering and Material Science,
Polytechnic University Brooklyn, New York 11201, USA
Herein, we report a new and efficient method for the large scale synthesis of 2,6-dicarboxyfluorenone 5 in 95% yield
using 0.01 mol% of bis(triphenylphosphine)palladium(II) chloride, (PPh ) PdCl , as a catalyst, starting with the reaction
3
2
2
of 2,5-dimethylbromobenzene and 4-bromotoluene to give 2,4,5-trimethylbiphenyl 3, followed by oxidation and then
cyclization.
The synthesis of 2,6-dicarboxy¯uorenone 5, a potentially
useful compound in the synthesis of polymers and
dendrimers with asymmetric structures was undertaken. A
practical synthesis for the large scale (ca. 500 g) preparation
of this material has been developed. The preparation of
biphenyl derived structures via the palladium-catalyzed
cross-coupling reaction of appropriately substituted precur-
sors has emerged as a powerful tool in organic synthesis.
1
±4
For example, the coupling
of organostannanes with aryl
tri¯ates is an important method for the formation of
carbon±carbon bonds (Scheme 1).
The cross coupling reaction was conducted in dimethyl-
formamide with bis(triphenylphosphine)palladium(II) chloride,
Scheme 2
1a
(
3 2 2
PPh ) PdCl (4 mol%), as catalyst to give 3 in 85±90%
yield. Careful monitoring of the reaction revealed that
lower catalyst quantities were ineective and the reaction
did not proceed below 140 8C. The reaction required an
excess of tributyl(4-methylphenyl)stannane 1 and additional
treatment with ethyl acetate and potassium ¯uoride was
necessary to remove the tin byproduct. This method was
inecient for a large scale synthesis because high tempera-
tures were required, the turnover of the catalyst was poor
and puri®cation was tedious.
Scheme 3
The major impurity (<2%) 4,4'-dimethylbiphenyl was
removed by crystallization after distillation.
Subsequent oxidation of 2,4',5-trimethylbiphenyl 3 gave
2,4,5-tricarboxybiphenyl (4, 70±80% yield) followed by
We developed a more ecient route to 3, shown in
Scheme 2. We synthesized 3 in 85% yield in situ using
5
3
(
3
PPh )
2
PdCl
2
(0.01 mol%) as a catalyst in tetrahydrofuran.
cyclization with sulfuric acid to give 2,6-dicarboxy¯uorenone
5
(95% yield, Scheme 3).
Thus, this new method oers an ecient synthesis of 2,6-
dicarboxy¯uorenone via a palladium-catalyzed cross coup-
ling reaction. Advantages of this methodology include high
chemical yields, easy puri®cation and a short synthetic
sequence.}
1
}
(
(
Spectral data: tributyl(4-methylphenyl)stannane 1:
300 MHz, CDCl
6H, m), 2.5 (3H, d, J 8.1 Hz), 7.23 (2H, d, J 8.1 Hz), 7.45 (2H, d,
H
NMR
3
) d 0.99 (9H, m), 1.1 (6H, m), 1.4 (6H, m), 1.6
13
J 8.1 Hz). C NMR (75 MHz, CDCl
1
3
) d
c
9.5, 13.7, 21.4, 29.1,
28.9, 136.5, 137.5, 137.8. MS m/z (relative intensity) 313 (83), 285
(
75), 235 (96), 177 (100), 121 (25), 57 (8).
,5-Dimethylphenyl tri¯uoromethanesulfonate 2:
300 MHz, CDCl ) ꢀ
1
2
H
NMR
(
3
H
2.56 (3H, s), 2.58 (3H, s), 7.27±7.42 (2H, m),
3
1
7
1
2
3 c
.51±7.54 (1H, m). C NMR (75 MHz, CDCl ) ꢀ 15.9, 20.8, 116.5,
21.6, 128.9, 131.8, 137.9, 148.3, 149.6. MS m/z (relative intensity)
54 (100), 175 (26), 121 (100), 91 (91), 77 (91).
1
2
,4',5-Trimethylbiphenyl 3: H (300 MHz, CDCl
3
) ꢀ
H
2.58 (3H, s),
13
2
ꢀ
1
.66 (3H, s), 2.70 (3H, s), 7.30±7.60 (7H, m). C (75 MHz, CDCl
9.64, 13.90, 14.10, 126.74, 127.75, 128.61, 129.03, 129.34, 130.20,
30.60, 132.15, 133.82, 134.98, 136.0, 141.84. MS m/z (relative inten-
3
)
c
Scheme 1 THF tetrahydrofuran; Tf CF
3 2
SO ;
sity) 196 (88), 181 (100), 166 (72), 153 (24), 76 (12).
DMF dimethylformamide
13
2
2
,4,5-Tricarboxybiphenyl 4: C NMR (75 MHz, [ H
126.96, 128.44, 129.08, 129.92, 130.72, 132.96, 136.04, 140.10,
144.46, 166.36, 167.03, 168.611.
2,6-Dicarboxy¯uorenone 5: H NMR (300 MHz, [ H
7.5 (1H, m), 7.8 (2H, d, J 8.1 Hz), 7.9 (1H, d, J 8.1 Hz), 8.0 (1H,
6
] DMSO)
ꢀ
c
*To receive correspondence (e-mail: warnerk305@aol.com).
2
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
6 H
] DMSO) ꢀ
13
2
fore no corresponding material in J. Chem. Research (M).
%Current address: Department of Chemistry, Yeshiva University,
6 c
m), 8.1 (1H, d, J 8.1 Hz). C NMR (75 MHz, [ H ] DMSO) ꢀ
122.01, 122.52, 127.39, 129.72, 130.27, 131.85, 132.33, 133.75,
136.96, 137.16, 143.29, 147.16, 166.5, 166.9, 191.63.
5
00 W 185 St., New York, NY 10033, USA.
Warner, Kirstin F.
