Synthesis of benzene- and pyridinediboronic acids via organotin compounds

Article abstract of DOI:10.1021/om020163r

The synthesis of benzene- and pyridinediboronic acids via the organotin compounds was discussed. The organotin compound was dissolved in dry tetrahydrofuran (THF) and treated with a solution of borane in the same solvent under dry nitrogen. The physical characteristics of the compounds formed were found to be in agreement with those found in the literature.

Full text of DOI:10.1021/om020163r

4886
Organometallics 2002, 21, 4886-4888
Notes
Syn th esis of Ben zen e- a n d P yr id in ed ibor on ic Acid s via
Or ga n otin Com p ou n d s
Sandra D. Mandolesi,† Santiago E. Vaillard,‡ J ulio C. Podesta´,*,† and
Roberto A. Rossi*,‡
Departamento de Quı´mica and CONICET (Buenos Aires), Universidad Nacional del Sur,
Avenida Alem 1253, 8000 Bah´ıa Blanca, Argentina, and INFIQC (UNC-CONICET),
Departamento de Quı´mica Orga´nica, Facultad de Ciencias Qu´ımicas, Universidad Nacional
de Co´rdoba, Ciudad Universitaria, 5000 Co´rdoba, Argentina
Received February 26, 2002
Summary: 1,4- and 1,3-Bis(trimethylstannyl)benzenes as
well as 2,5- and 2,6-bis(trimethylstannyl)pyridines react
with borane in THF to give intermediates which on
hydrolysis lead to benzene- and pyridinediboronic acids
in 79-83% yield. While oxidation of the benzenedibo-
ronic acids with alkaline hydrogen peroxide gives the
corresponding 1,3- and 1,4-dihydroxybenzenes, the py-
ridinediboronic acids lead via a double Suzuki reaction
with 4-iodoanisole to 2,5- and 2,6-bis(4-methoxyphenyl)-
pyridines and react with pinacol to give the correspond-
ing pyridine-2,5-pinacol and pyridine-2,6-pinacol dibo-
ronic esters.
reaction between lithium and Grignard reagents of the
corresponding benzene dibromides and methyl borate
was reported in 1957.6 Other authors improved this
procedure by obtaining 1,4- and 1,3-benzenediboronic
acids in 50-60% yield.7 We now report a convenient
synthetic route to 1,4- and 1,3-benzenediboronic acids
(2 and 4) as well as to new 2,5- and 2,6-pyridinedibo-
ronic acids (6 and 8).
The easy access to bis(trialkylstannyl)-substituted
aryl and heteroaryl compounds via SRN1 reactions of
trimethylstannyl anions with aryl dichlorides,8 (chlo-
roaryl)trimethylammonium iodides,9a and aryl- and
heteroaryl diethyl phosphates9b in liquid ammonia
prompted us to study the reactions between these
diorganotins and borane in THF as a possible route to
arenediboronic acids.
In tr od u ction
During the 1970s a series of papers by Thorpe and
co-workers showed that it was possible to obtain are-
neboronic acids as well as other arylboron derivatives
from reactions between a variety of aromatic organo-
metallic compounds and borane in tetrahydrofuran
(THF).1 The synthesis of areneboronates has also been
reported through palladium-catalyzed borylation of aryl
halides or triflates with dialkoxyborane.2 More recently,
we reported a very convenient synthesis of arylboronic
acids via transmetalations between aryltrialkylstan-
nanes and borane in THF.3 Areneboronic and arenedi-
boronic acids are very useful intermediates in organic
synthesis4 and also in polymer chemistry.5 The first
synthesis of 1,4- and 1,3-benzenediboronic acids via
Resu lts a n d Discu ssion
The bis(trimethylstannyl)-substituted benzenes and
pyridines were prepared by photostimulated reactions
of the appropriate dichlorobenzenes and dichloropy-
ridines with Me3Sn- ions in liquid ammonia. Thus, 1,4-
(1, 88%) and 1,3-bis(trimethylstannyl)benzenes (3, 90%)
and 2,5- (5, 88%) and 2,6-bis(trimethylstannyl)pyridines
(7, 86%) were obtained by the SRN1 mechanism.8 In this
preliminary study we investigated the reactions of
borane with these bis(trimethylstannyl)-substituted
compounds according to Scheme 1.
Preliminary experiments were first carried out using
compounds 1, 3, 5, and 7 under a variety of reaction
conditions to determine whether transmetalation oc-
curred and to find the optimum conditions. The orga-
notin compound was dissolved in dry THF and treated
with a solution of borane in the same solvent under dry
† Universidad Nacional del Sur.
‡ Universidad Nacional de Co´rdoba.
(1) (a) Breuer, S. W.; Leatham, M. J .; Thorpe, F. G. J . Chem. Soc.,
Chem. Commun. 1971, 1475. (b) Breuer, S. W.; Podesta´, J . C.; Thorpe,
F. G. Tetrahedron Lett. 1974, 3719. (c) Pickles, G. M.; Spencer, T.;
Thorpe, F. G.; Ayala A. D.; Podesta´, J . C. J . Chem. Soc. Perkin Trans.
1 1982, 2949. (d) Torpe, F. G.; Pickles, G. M.; Podesta´, J . C. J .
Organomet. Chem. 1977, 128, 305. (e) Bullen, N. P.; Chiheru, K. S.;
Torpe, F. G. J . Organomet. Chem. 1985, 195, 147. (f) Torpe, F. G.;
Breuer, S. W.; Pickles, G. M.; Spencer, T.; Podesta´, J . C. J . Organomet.
Chem. 1978, 145, C26. (g) Pickles, G. M.; Spencer, T.; Thorpe, F. G.;
Chopa, A. B.; Podesta´, J . C. J . Organomet. Chem. 1984, 260, 7.
(2) (a) Murata, M.; Watanabe, S.; Masuda, Y. J . Org. Chem. 1997,
62, 6458. (b) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J . Org.
Chem. 2000, 65, 164.
(5) (a) Miller, T. M.; Neenan, T. X.; Zayas, R.; Bair, H. E. J . Am.
Chem. Soc. 1992, 114, 1018. (b) Tour, J . M.; Lamba, J . J . S. J . Am.
Chem. Soc. 1993, 115, 4935.
(6) Nielsen, D. R.; McEwen, W. E. J . Am. Chem. Soc. 1957, 79, 3081.
(7) Todd, M. H.; Balasubramanian, S.; Abell, C. Tetrahedron Lett.
1997, 38, 6781.
(3) Faraoni, M. B.; Koll, L. C.; Mandolesi, S. D.; Zu´n˜iga; A. E.;
Podesta´, J . C. J . Organomet. Chem. 2000, 613, 236.
(4) Suzuki, A. In Metal-Catalyzed Cross-Coupling Reactions; Dieder-
ich, F., Stang, P. J ., Eds.; Wiley-VCH: Weinheim, Germany, 1997;
Chapter 2.
(8) (a) Yammal, C. C.; Podesta´, J . C.; Rossi, R. A. J . Org. Chem.
1992, 57, 5720. (b) Corsico, E. F.; Rossi, R. A. Synlett 2000, 227.
(9) (a) Chopa, A. B.; Lockhart, M. T.; Silbestri, G. Organometallics
2000, 19, 2249. (b) Chopa, A. B.; Lockhart, M. T.; Silbestri, G.
Organometallics 2001, 20, 3358.
10.1021/om020163r CCC: $22.00 © 2002 American Chemical Society
Publication on Web 10/03/2002

Notes
Organometallics, Vol. 21, No. 22, 2002 4887
Sch em e 1
Sch em e 2
nitrogen. The solution was stirred at room temperature
for 1 h and then heated under reflux for 3 h. After
completion of the reaction, water was added to decom-
pose the excess borane and to convert the intermediate
aryl- and heteroarylboranes into the corresponding
arene- and heteroarenediboronic acids 2/4 and 6/8,
respectively. The yields shown in Scheme 1 were
obtained using the ratio borane/organotin ) 3, but we
found no differences using higher ratios (4-7). On the
other hand, using lower ratios of borane/organotin such
as 1 and 1.1, we could not detect the formation of the
possible intermediate (trimethylstannyl)benzene-
boronic acid and (trimethylstannyl)pyridineboronic acid
of types A and B shown in Figure 1. This would indicate
that, if intermediates A and B were formed, they should
react with borane much faster than the starting bis-
(trimethylstannyl)-substituted aromatic compounds 1,
3, 5, and 7.
phenols,11 this reaction was in fact studied by Kuivila
et al. during the 1950s12 and used by Thorpe et al.
during the 1970s.1,13
On the other hand, we could not obtain good mi-
croanalyses of the new 2,5- and 2,6-pyridinediboronic
acids (6 and 8). This is not surprising, because it has
been reported that boronic acids in general present a
host of difficulties with regard to analysis, the principal
one being their spontaneous condensation to boroxines
to varying degrees.7 To confirm, at least indirectly, the
structure of the pyridinediboronic acids obtained, we
first carried out a double Suzuki coupling14 of com-
pounds 6 and 8 with 4-iodoanisole. These reactions lead
to 2,5- and 2,6-bis(4-methoxyphenyl)pyridines (11 and
12, respectively) in yields of around 75%, as shown in
Scheme 2. The new 2,5-bis(4-methoxyphenyl)pyridine
(11) was characterized by microanalysis and IR and
NMR spectra. The physical characteristics of compound
11 were in agreement with those found in the litera-
ture.15 Then, through the reaction with pinacol (Scheme
2),16 we obtained the corresponding pyridine-2,5-pinacol
(13) and pyridine-2,6-pinacol (14) diboronic esters,
F igu r e 1. Possible intermediate (trimethylstannyl)ben-
zeneboronic acid and (trimethylstannyl)pyridineboronic
acid.
The diboronic acids 2, 4, 6, and 8 were recrystallized
from water, and they did not melt below 320 °C. The
1,4- and 1,3-benzenediboronic acids 2 and 4 were easily
identified by comparison of their properties with the
properties reported for these compounds in the litera-
ture.7,10 The regioselective oxidation of the benzenedi-
boronic acids 2 and 4 with alkaline hydrogen peroxide
gave the corresponding 1,4- and 1,3-dihydroxybenzenes
9 and 10, respectively, in good yields, as shown in
Scheme 2.
1
whose H NMR spectra confirmed the structure of the
starting pyridinediboronic acids 6 and 8.
(11) Simon, J .; Salzbrunn, S.; Prakash, G. K. S., Petasis, N. A.; Olah,
G. A. J . Org. Chem. 2001, 66, 633.
(12) (a) Kuivila, H. G. J . Am. Chem. Soc. 1954, 76, 870. (b) Kuivila,
H. G.; Armour, A. G. J . Am. Chem. Soc. 1957, 79, 5659. (c) Kuivila, H.
G. J . Am. Chem. Soc. 1955, 77, 4014.
(13) March, J . Advanced Organic Chemistry: Reactions, Mecha-
nisms, and Structure, 3rd ed.; Wiley-Interscience: New York, 1985; p
588, ref 66.
(14) Ishiyama, T.; Murata, M.; Miyaura, N. J . Org. Chem. 1995, 60,
7508.
It should be noted that although it has recently been
suggested that this oxidation of areneboronic acids with
hydrogen peroxide is a new method for the synthesis of
(15) (a) Newkome, G. R.; Fishel, D. L. J . Org. Chem. 1972, 37, 1329.
(b) Balasubrahmanyam, S. N.; J eyashri, B.; Namboothiri, I. N. N.
Tetrahedron 1994, 50, 8127.
(10) Morgan, A. B.; J urs, J . L.; Tour, J . M. Polym. Prepr. (Am. Chem.
Soc., Div. Polym. Chem.) 1999, 40(2), 553.
(16) Kobayashi, Y.; Mizojiri, R.; Eitatsu, I. J . Org. Chem. 1996, 61,
5391.

4888 Organometallics, Vol. 21, No. 22, 2002
Notes
Dou ble Su zu k i Cou p lin g of P yr id in ed ibor on ic Acid s
(6 a n d 8) w ith 4-Iod oa n isole. Syn th esis of 2,5- a n d 2,6-
Bis(4-m eth oxyp h en yl)p yr id in es (11 a n d 12). The following
is a representative procedure.
In conclusion, these preliminary studies demonstrate
that the transmetalation of bis(trimethylstannyl)ben-
zenes and bis(trimethylstannyl)pyridines with borane
in THF is an excellent method for the synthesis of highly
pure valuable benzenediboronic acids and new py-
ridinediboronic acids. The studies also include the first
example of a successful double Suzuki reaction that
involves the use of pyridinediboronic acids as starting
material.
2,5-Bis(4-m eth oxyp h en yl)p yr id in e (11). 4-Iodoanisole
(0.33 g, 1.4 mmol), 2,5-pyridinediboronic acid (0.11 g, 0.66
mmol), and triphenylphosphine (0.037 g, 0.14 mmol) were
dissolved in 1,2-dimethoxyethane (1.6 mL). Then, K2CO3 (2
mL of a 2 M aqueous solution, 3.7 mmol) was added and the
mixture was purged with nitrogen. Palladium acetate (0.0082
g, 3 × 10-5 mmol) was added and the mixture refluxed for 20
h. The two phases were separated, and the aqueous phase was
extracted with ethyl acetate (3 × 5 mL). The combined organic
phases were washed with water (5 mL) and brine (5 mL) and
were dried over magnesium sulfate. After evaporation of the
solvent, the oily residue was purified by column chromatog-
raphy (silica gel 60), 11 being eluted with 9/1 hexane/ethyl
acetate (yield 0.15 g, 0.46 mmol, 77%). Mp: 125-126 °C
(EtOH). 1H NMR (CDCl3; δ): 8,2 (d, 1H, J ) 1.5 Hz), 7.80-
7.12 (m, 2H), 6.94-6.82 (m, 8H), 3.77 (s, 3H), 3.75 (s, 3H). 13C-
{1H} NMR (CDCl3; δ): 159.9, 159.1, 150.0, 141.4, 138.5, 134.8,
132.7, 130.7, 122.3, 128.6, 125.9, 114.1, 113.5, 55.3. Anal. Calcd
for C19H17NO2 (291.33): C, 78.32; H, 5.88. Found: C, 78.48;
H, 6.04. Under the same reaction conditions 2,6-bis(4-meth-
oxyphenyl)pyridine (12) was obtained in 75% yield.
Exp er im en ta l Section
NMR spectra were obtained in a Bruker ARX 300 instru-
ment. Infrared spectra were recorded with a Nicolet Nexus
FT spectrometer. Chemical ionization mass spectra determi-
nations were obtained in a HP 5989 A spectrometer at the
Faculty of Pharmacy (Barcelona University, Barcelona, Spain).
Microanalyses were performed at Dortmund University (Dort-
mund, Germany). The refractive indices were measured with
a Universal Abbe Zeiss J ena VEB instrument, and the melting
points were determined in a Kofler hot stage and are uncor-
rected. All the solvents and reagents used were analytical
reagent grade.
Rea ction s of Bis(tr im eth ylsta n n yl)-su bstitu ted Ben -
zen es (1/3) a n d P yr id in es (5/7) w ith Bor a n e in THF .
Syn th esis of Ben zen edibor on ic acids (2/4) an d P yr idin ed-
ibor on ic a cid s (6/8). The following is a representative
procedure.
Rea ction of P yr id in ed ibor on ic Acid s (6 a n d 8) w ith
P in a col. Syn th esis of P yr id in e-2,5-p in a col a n d P yr id in e-
2,6-p in a col Dibor on ic Ester s (13 a n d 14). The following is
a representative procedure.
Syn th esis of 2,5-P yr id in ed ibor on ic Acid (6). To a
stirred solution of 5 (0.5 g, 1.2 mmol) in dry THF (10 mL) was
added a solution of borane in THF (3.70 mmol, 3.2 mL of a
1.15 M solution). The preparation was carried out under an
atmosphere of nitrogen. The mixture was left at room tem-
perature for 1 h and then refluxed for 3 h. Then the solvent
and Me3SnH (bp 59 °C) thus formed were removed under
reduced pressure and a white jellylike residue was obtained.
Diethyl ether (10 mL) and water (0.1 mL) were added, the
solution was dried with magnesium sulfate, and the solvent
was removed under vacuum. The solid 2,5-pyridinediboronic
acid was recrystallized from water (0.163 g, 0.98 mmol, 82%).
1H NMR (DMSO-d6; δ): 8.30-7.42 (m, 3H), 6.82 (s, 4H). 13C-
{1H} NMR (DMSO-d6; δ): 141.5, 126.4, 95.8, 80.1, 43.8. IR
(KBr, cm-1): ν 3231; 1479.
Under the same reaction conditions 2,6-pyridinediboronic
acid (8) was obtained in 79% yield. 1H NMR (DMSO-d6; δ):
7.55-7.47 (m, 3H), 6.02 (s, 4H). 13C{1H} NMR (DMSO-d6, δ):
122.0, 109.6, 77.6. IR (KBr, cm-1): ν 3320, 1510.
Oxid a tion of 1,4- a n d 1,3-Ben zen ed ibor on ic Acid s (2
a n d 4) to 1,4- a n d 1,3-Dih yd r oxyben zen es (9 a n d 10). The
following is a representative procedure.
1,4-Dih yd r oxyben zen e (9). A mixture of a 3 M sodium
hydroxide solution (0.6 mL) and 30% hydrogen peroxide (1.9
mL) was added slowly to a solution of 2 (0.2 g, 1.2 mmol) in
THF (6 mL) and the resulting mixture stirred for 30 min.
Ether (6 mL) was added and the mixture extracted with a 3
M sodium hydroxide solution (3 × 2 mL). The combined
aqueous extracts were acidified with dilute hydrochloric acid
and extracted with ether (3 × 4 mL). The ether extracts were
combined, and the solvent was removed under vacuum. The
solid residue was recrystallized from benzene (0.096 g, 0.86
mmol, 72%). Under the same reaction conditions 1,3-dihy-
droxybenzene (10) was obtained in 70% yield.
P yr id in e-2,5-p in a col Ester (13). To a stirred suspension
of 2,5-pyridinediboronic acid (6; 0.2 g, 1.2 mmol) in benzene
(4 mL) were added pinacol (0.285 g, 2.4 mmol) and magnesium
sulfate (1.75 g). The mixture was stirred overnight at room
temperature and filtered. The filtrate was concentrated in
vacuo to afford 13 as an oil. The compound was purified by
column chromatography (silica gel 60), 13 being eluted as a
colorless oil with 1/1 hexane/ethyl ether (yield 0.31 g, 0.94
20
mmol, 78%). ηD ) 1.3565. MS (CI/CH4): m/z (%) 332.30 (2)
[M+ + 1]. 1H NMR (CDCl3; δ): 8,98 (s, 1H), 7.955 (d, 1H,
3
3J (H,H) ) 7 Hz), 7.93 (d, 1H, J (H,H) ) 7 Hz), 1.26 (s, 12H),
1.15 (s, 12H). 13C{1H} NMR (CDCl3; δ): 131.87, 124.50, 83.78,
74.06, 29.31, 23.84, 23.79. IR (film, KBr, cm-1): 1472 (νB-C),
1375 (νB-O), 1157 (νB-C), 1091 (νB-C). Under the same reaction
conditions pyridine-2,6-pinacol ester (14) was obtained in 75%
yield. ηD ) 1.3583. MS (CI/CH4): m/z (%) 332.25 (4) [M+
+
20
1
1]. H NMR (CDCl3; δ): 7.64 (m, 1H), 7.46 (m, 1H), 7.11 (m,
1H), 1.20 (s, 12H), 1.17 (s, 12H). 13C{1H} NMR (CDCl3; δ):
131.46, 129.86, 82.13, 74.06, 23.83, 23.53. IR (film, KBr, cm-1):
1468 (νB-C), 1367 (νB-O), 1126 (νB-C), 1091 (νB-C).
Ack n ow led gm en t. This work was supported by
CONICET (Capital Federal, Argentina), CONICOR
(Co´rdoba, Argentina), Universidad Nacional de Co´rdoba
(Co´rdoba, Argentina), and Universidad Nacional del Sur
(Bah´ıa Blanca, Argentina). The support for the chemical
ionization mass spectra determinations of Dra. Asuncio´n
Mar´ın (Facultad de Farmacia, Barcelona University,
Barcelona, Spain) is gratefully acknowledged. A travel
grant for a short scientific visit to Dortmund University
by one of us (J .C.P.) from the DAAD (Germany) is also
acknowledged.
OM020163R