PAPER
Preparation and Reactions of 2-Carboxyphenylboronic Acid
13C NMR: = 167.8, 143.0, 131.0, 130.3, 129.5, 126.9.
1045
action with 4-bromochlorobenzene gave the expected
coupling product in 82% yield.
Coupling Reactions of 2-Carboxyphenylboronic Acids with Ar-
omatic Bromides; General Procedure
In conclusion, we have developed a practical method,
from readily available starting materials, for preparation
of 2-carboxyphenylboronic acid by oxidation of 2-tolyl-
boronic acid under mild conditions. The title compound
reacts with the electron-rich 4-bromoanisole to afford the
corresponding biaryl-2-carboxylic acid in modest yields
under several different conditions, and with a variety of
aryl bromides with electron-withdrawing groups to pro-
vide biaryl-2-carboxylic acids in fair to good yields.
Under N2, Pd(PPh3)4 (60 or 10 mg, 0.05 or 1.0 mmol), or Pd(OAc)2
(6.7 mg, 0.03 mmol) and Cy2P(bi-Ph) (21.0 mg, 0.06 mmol), was
(were) added to a solution of a bromide (1.0 mmol), 2-carboxyphe-
nylboronic acid (0.23 g, 1.4 mmol) and K2CO3 (0.42 g, 3.0 mmol)
in MeCN–H2O (10 mL, 3:1) at r.t. The mixture was heated to 90 °C
for 12 24 h, and then the hot mixture was filtered. Bulk of the sol-
vent was removed by rotatory evaporation. The residue was added
to aq 10% NaOH solution (10 mL) at 0 °C and extracted with
CH2Cl2 (3 10 mL). The aqueous layer was then washed with brine
and cooled down to 0 °C and acidified with conc. HCl to pH 2. The
white precipitate was filtered out and washed with cold H2O and
dried to give the product (Table).
All reactions were carried out in oven-dried glassware under N2. 2-
Tolylboronic acid was manufactured by Optima Chemical Group.
Pd(PPh3)4, Pd(OAc)2, Pd2(dba)3, 2-(dicyclohexylphosphino)biphe-
nyl [Cy2P(bi-Ph)] and 1,3-bis(2,4,6-trimethylphenyl)imidazolium
chloride were purchased from Strem Chemical Co. All other re-
agents used in the reactions were purchased from Aldrich and used
as received. Melting points were determined in an open capillary
tube on a MEL-TEMP 3.0 instrument and are uncorrected. 1H and
13C NMR data were recorded at 300 MHz spectrometer (75 MHz for
13C), and DMSO-d6 was used as the solvent and chemical shifts re-
ported in ppm with reference to TMS. Karl-Fisher tests were con-
ducted on a Mettler DL 70ES titrator.
4 -(Trifluoromethyl)[1,1 -biphenyl]-2-carboxylic Acid
Mp 168–170 °C.
1H NMR: = 12.88 (s, 1 H), 7.83–7.81 (m, 1 H), 7.76 (d, J = 8.1
Hz, 2 H), 7.65 7.59 (m, 1 H), 7.54 7.49 (m, 3 H), 7.40 (d, J = 7.5
Hz, 1 H).
13C NMR: = 160.9, 145.3, 140.0, 131.8, 131.3, 130.6, 129.6,
129.2, 128.1, 127.6 (q, 2JCF = 31 Hz), 124.9 (q, 3JCF = 3.4 Hz), 124.4
(q, 1JCF = 270 Hz).
4 -Methoxy[1,1 -biphenyl]-2-carboxylic Acid
Mp 140–142 °C (Lit.14 142–143 °C).
2-Carboxyphenylboronic Acid (2)
2-Tolylboronic acid (13.6 g, 0.1 mol) was dissolved in a solution of
50% aq NaOH (50 mL) and H2O (100 mL) at r.t. and the solution
was heated to 50 °C. A solution of KMnO4 (36.0 g, 0.23 mol) in
H2O (400 mL) was added in six portions over 1 h. The green-col-
ored solution was kept at 50 °C for an additional 3 h. It was cooled
to 0 °C and treated with concd HCl to pH 8, and then filtered
through a Celite pad to remove the precipitated MnO2. The filtrate
was further acidified dropwise with concd HCl to pH 2 at 0 °C. The
lightly brown solution was evaporated under reduced pressure to
nearly dryness and acetone (500 mL) was added. The salt was fil-
tered off and the solution was evaporated to give the crude product,
which was washed with a minimum amount of cold H2O to yield a
white solid. It was dried overnight in vacuum at 50 °C to give the
final product as a white solid (12.6 g, 76%); mp 159 162 °C.
1H NMR: = 12.78 (br s, 1 H), 7.67 (d, J = 7.5 Hz, 1 H), 7.54 (dd,
J = 7.8, 7.5 Hz, 1 H), 7.43 7.34 (m, 2 H), 7.26 (d, J = 8.1 Hz, 2 H),
6.97 (d, J = 7.8 Hz, 2 H), 3.79 (s, 3 H).
13C NMR: = 169.9, 158.6, 140.4, 133.0, 132.3, 130.7, 130.3,
129.4, 128.9, 126.8, 113.6, 55.1.
4 -Cyano[1,1 -biphenyl]-2-carboxylic Acid
Mp 216–218 °C (Lit.15 215–218 °C).
1H NMR: = 12.93 (br s, 1 H), 7.86 (m, 3 H), 7.63 (dd, J = 7.5, 7.2
Hz, 1 H), 7.56 7.51 (m, 3 H), 7.40 (d, J = 7.5 Hz, 1 H).
13C NMR: = 168.7, 146.1, 139.9, 131.9, 131.5, 131.4, 130.5,
129.7, 129.4, 128.3, 118.9, 109.9.
1H NMR: = 7.70 (m, 4 H), 5.13 (br s, 3 H).
2 -Cyano[1,1 -biphenyl]-2-carboxylic Acid
Mp 168–170 °C (Lit.16 170–172 °C).
1H NMR (DMSO-d6–D2O): = 7.69 (d, J = 7.5 Hz, 1 H), 7.28 (dd,
J = 7.2, 7.2 Hz, 1 H), 7.41 (d, J = 7.2 Hz, 1 H), 7.35 (dd, J = 7.2, 7.5
Hz, 1 H).
1H NMR: = 12.94 (br s, 1 H), 8.01 (d, J = 7.2 Hz, 1 H), 7.87 (d,
J = 7.8 Hz, 1 H), 7.76 7.67 (m, 2 H), 7.66 7.60 (m, 1 H), 7.57
7.52 (m, 1 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.37 (d, J = 7.5 Hz, 1 H).
13C NMR: = 167.4, 145.3, 139.0, 133.1, 132.2, 132.1, 131.1,
130.3, 129.5, 128.9, 127.9, 118.2, 111.2.
13C NMR (DMSO-d6–D2O): = 170.3, 134.1, 132.1, 130.7,
129.4(d, 1JCB = 45 Hz), 128.0, 127.3.
Anal. KF Test: found 21.8% (cacld 21.7%).
3 -Nitro[1,1 -biphenyl]-2-carboxylic Acid
Diphenic Acid (3)
Mp 154–156 °C (Lit.17 155–157 °C).
2-Tolylboronic acid (0.68 g, 5.0 mmol) was dissolved in a solution
of 50% aq NaOH solution (5 mL) and H2O (10 mL) at r.t. The solu-
tion was heated to 60 °C and treated with three portions of a solu-
tion of KMnO4 (2.0 g) in H2O (30 mL) over 30 min and then heated
at reflux for 20 h. It was cooled down to r.t. and filtered through a
Celite pad. The filtrate was cooled to 0 °C and acidified with conc.
HCl to pH 2 to give a white precipitate, which was filtered and
washed with cold H2O to give a white solid (0.51 g). It was then dis-
solved in MeOH and filtered. Evaporation of the solvent afforded
the title compound (0.26 g) as a white solid; mp 222 224 °C (Lit.13
mp 220 221 °C).
1H NMR: = 12.99 (br s, 1 H), 8.22 (d, J = 7.8 Hz, 1 H), 8.11 (s, 1
H), 7.86 (d, J = 7.5 Hz, 1 H), 7.79 (d, J = 7.8 Hz, 1 H), 7.72 7.61
(m, 2 H), 7.54 (dd, J = 7.5, 7.5 Hz, 1 H), 7.45 (d, J = 6.9 Hz, 1 H).
13C NMR: = 168.7, 147.5, 142.7, 139.2, 135.2, 131.6, 131.5,
130.8, 129.9, 129.6, 128.4, 122.9, 122.1.
4 -Nitro[1,1 -biphenyl]-2-carboxylic Acid
Mp 232–235 °C (Lit.18 231 °C).
1H NMR: = 13.02 (br s, 1 H), 8.26 (d, J = 7.8 Hz, 2 H), 7.88 (d,
J = 7.5 Hz, 1 H), 7.68 7.53 (m, 4 H), 7.43 (d, J = 7.5 Hz, 1 H).
13C NMR: = 168.6, 148.2, 146.6, 139.6, 131.5, 130.5, 129.9,
129.8, 128.5, 123.1.
1H NMR: = 12.47 (br s, 2 H), 7.86 (d, J = 7.5 Hz, 2 H), 7.53 (dd,
J = 7.5, 7.5 Hz, 2 H), 7.41 (dd, J = 7.5, 7.5 Hz, 2 H), 7.14 (d, J = 7.5
Hz, 2 H).
Synthesis 2002, No. 8, 1043–1046 ISSN 0039-7881 © Thieme Stuttgart · New York