Intramolecular dehydrative condensation of dicarboxylic acids with brnsted base-assisted boronic acid catalysts

Article abstract of DOI:10.1071/CH11301

Bifunctional Brnsted base-assisted boronic acid catalysts, arylboronic acids bearing two sterically bulky (N,N-dialkylamino)methyl groups at the 2,6-positions, exhibit remarkable activities for the dehydrative intramolecular condensation of dicarboxylic acids. The steric bulkiness of the (N,N-dialkylamino)methyl groups of 1, which prevents the formation of less active species such as the N→B chelated species and triarylboroxines 3, is crucial for the high catalytic activity. This is the first successful method for the catalytic dehydrative self-condensation of di-and tetracarboxylic acids.

Full text of DOI:10.1071/CH11301

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2011, 64, 1458–1465
Full Paper
http://dx.doi.org/10.1071/CH11301
Intramolecular Dehydrative Condensation of Dicarboxylic
Acids with Brønsted Base-Assisted Boronic Acid Catalysts
A
B
B
Akira Sakakura, Risa Yamashita, Takuro Ohkubo,
C D
,
B D E
, ,
Matsujiro Akakura,
and Kazuaki Ishihara
A
EcoTopia Science Institute, Nagoya University, Furo-cho, Chikusa-ku, Nagoya,
464-8603, Japan.
B
Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku,
Nagoya, 464-8603, Japan.
C
Department of Chemistry, Aichi University of Education, Igaya-cho, Kariya,
Aichi, 448-8542, Japan.
D
Japan Science and Technology Agency (JST), CREST, Furo-cho, Chikusa-ku,
Nagoya, 464-8603, Japan.
E
Corresponding author. Email: ishihara@cc.nagoya-u.ac.jp
Bifunctional Brønsted base-assisted boronic acid catalysts, arylboronic acids bearing two sterically bulky (N,N-
dialkylamino)methyl groups at the 2,6-positions, exhibit remarkable activities for the dehydrative intramolecular
condensation of dicarboxylic acids. The steric bulkiness of the (N,N-dialkylamino)methyl groups of 1, which prevents
the formation of less active species such as the N-B chelated species and triarylboroxines 3, is crucial for the high
catalytic activity. This is the first successful method for the catalytic dehydrative self-condensation of di- and
tetracarboxylic acids.
Manuscript received: 7 July 2011.
Manuscript accepted: 6 October 2011.
Published online: 16 November 2011.
Introduction
In 2006, Whiting and colleagues reported arylboronic acid
1a bearing an (N,N-diisopropylamino)methyl group at the
2-position (Fig. 1) as an efficient catalyst for the dehydrative
amide condensation reaction.[7] In some cases, 1a is more
advantageous than electron-deficient arylboronic acids,
although the role of the (N,N-diisopropylamino)methyl group
in the amide condensation reaction is not clear. In 2008, Hall and
colleagues reported that 2-iodophenylboronic acid (Fig. 1) cat-
alyzes dehydrative amide condensation at ambient tempera-
ture.[8] The 2-iodo substituent is crucial for high catalytic
activity. A theoretical study suggested that the 2-iodo group
acts as a Brønsted base to promote hemiaminal dehydration,
which is predicted to be a rate-determining step.[9]
Based on these previous results, we envisioned that
an arylboronic acid of general type 1 bearing an (N,N-
dialkylamino)methyl group[7,10–15] would promote the dehydra-
tive condensation of dicarboxylic acids under mild conditions
through activation of the other carboxy group using the (N,N-
dialkylamino)methyl group as a Brønsted base in a monoacyl
boronate intermediate 2a (Fig. 2). As a result of investigation
into the catalytic activity of 1, we found that arylboronic acid 1b
bearing two 1-(2,2,6,6-tetramethylpiperidinyl)methyl groups at
the 2,6-positions showed remarkable catalytic activity for the
intramolecular dehydrative condensation of di- and tetracar-
boxylic acids (Scheme 1).[16] In addition, direct addition of
aniline to the reaction mixture of pyromellitic acid successfully
Carboxylic anhydrides are widely used as activated carboxylic
acids for the synthesis of carboxylic acid derivatives such as
(poly)esters, (poly)amides, and (poly)imides.[1] They are gen-
erally synthesized from the corresponding carboxylic acids
using stoichiometric amounts of dehydrating agents such as
acetic anhydride.[2] Alternatively, they can also be synthesized
by the thermal dehydration of carboxylic acids, which requires
an extremely high reaction temperature (220–2708C).[3] From
the perspective of green chemistry, the catalytic dehydrative
self-condensation of carboxylic acids should be an ideal method
for the synthesis of carboxylic anhydrides, since water is the
only byproduct.[4] However, no practical method for the cata-
lytic dehydrative self-condensation of carboxylic acids under
mild conditions has been reported to date.
It has been reported that electron-deficient arylboronic
acids such as 3,4,5-trifluorophenylboronic acid (Fig. 1) catalyze
dehydrative amide and ester condensation reactions through the
formation of monoacyl boronate intermediates.[5,6] However,
these electron-deficient arylboronic acids are not effective for
the catalytic dehydrative self-condensation of carboxylic acids
because carboxylic acids have a much lower nucleophilicity
than amines and alcohols. To catalyze the dehydrative self-
condensation of carboxylic acids, we must overcome a dilem-
ma: the nucleophilicity of one carboxylic acid should
be increased by a Brønsted base, and its counterpart should be
activated by a Lewis acid.
gave
a
1:1 isomeric mixture of the corresponding
Journal compilation Ó CSIRO 2011
www.publish.csiro.au/journals/ajc

Catalytic Dehydrative Condensation
1459
B(OH)2
B(OH)2
I
B(OH)2
condensation of dicarboxylic acids, we first investigated the
catalytic activities of various arylboronic acids 1 bearing a
dialkylamino group (10 mol-%) (Table 1). The reaction of
phthalic acid was conducted in nonane (bp 1518C) under azeo-
tropic reflux conditions with the removal of water. While 2-
iodophenylboronic acid[8] and 3,4,5-trifluorophenylboronic
acid,[5] highly active catalysts for dehydrative amide conden-
sation, showed low catalytic activities for the dehydrative con-
densation of phthalic acid (entries 2 and 3), arylboronic acids
1a[7] showed high catalytic activity as we reported previously
(entry 5). Arylboronic acid 1e also gave the phthalic anhydride
in high yield (entry 8). Interestingly, arylboronic acid 1f[17]
bearing a trioctylammonium group at the 2-position also showed
high catalytic activity (entry 9). The trioctylammonium group
might activate the carboxylic acid nucleophile by the formation
of an inner salt in the monoacyl boronate intermediate 2b
(Fig. 3). Although the trioctylammonium group would increase
the acidity of the boronic acid, the high acidity of the boronic
acid might not result in the improvement of the catalytic activity
as shown in Table 2, entries 3 and 4.
N(i-Pr)2
F
F
1a
F
Fig. 1. Representative arylboronic acids as catalysts for dehydrative amide
condensation.
CO2H
CO2H
R
R
H2O
Lewis acid
O
H
O
B(OH)2
O
O
•N•R'2
O
B
H
Brønsted base
•N•R'2
1
O
Monoacyl boronate
Based on our working hypothesis of Brønsted base-assisted
boronic acid catalysis, we first supposed that the spatial prox-
imity between the boronic acid moiety and the amino group of 1
should be important for the successful promotion of dehydrative
condensation. However, unexpectedly, arylboronic acids 1c and
1d bearing an (N,N-diisopropylamino)methyl group at the
3- and 4-positions also showed high catalytic activities (entries
6 and 7). Theoretical calculations suggested that the (N,N-
dialkylamino)methyl group at the 2- and 3-positions can form
hydrogen bonding with the carboxy group of the monoacyl
boronate intermediates generated from 1a and 1c (Fig. 4). In the
case of 1d, the 4-(N,N-dialkylamino)methyl group may interact
with the carboxy group with the aid of other molecules of 1d or
phthalic acid through hydrogen bonding. Detailed mechanistic
studies are in progress.
Although arylboronic acids 1a and 1c–e showed high cata-
lytic activity in nonane (bp 1518C), the use of heptane (bp 988C)
as a solvent significantly decreased the yield of phthalic anhy-
dride because of the low reaction temperature. Further investi-
gations to improve the catalytic activities of 1 under mild
reaction conditions revealed that the introduction of a methyl
group at the 6-position surprisingly increased the catalytic
activity, despite the steric hindrance around the boronic acid
moiety (catalyst 1g, entry 10).
Based on the results that the introduction of a methyl group at
the 6-position surprisingly increased the catalytic activity, we
next examined the catalytic activities of arylboronic acids
bearing two (N,N-dialkylamino)methyl groups at the 2,6-
positions (Table 2). As a result, the use of arylboronic acids
1h and 1b bearing two (N,N-diisopropylamino)methyl groups or
1-(2,2,6,6-tetramethylpiperidinyl)methyl groups successfully
improved the reactivity (entries 2 and 5). In propionitrile (EtCN,
bp 978C), only 1 mol-% of 1h or 1b was sufficient to catalyze the
reaction to give phthalic anhydride in respective yields of 71 and
99 %. However, the introduction of an electron-withdrawing
group at the 4-position of 1h did not improve the catalytic
activities (entries 3 and 4), although the acidities of the boronic
acids were increased. The combination of phenylboronic acid
(10 mol-%) and 1,2,2,6,6-pentamethylpiperidine (20 mol-%)
showed no catalytic activity in heptane (entry 6). This control
experiment indicates that an intramolecular Lewis basic func-
tion on 1b was essential for the successful promotion of
condensation.[7a]
intermediate 2a
R
O
O
Fig. 2. Brønsted base-assisted boronic acid catalysis for the dehydrative
condensation of dicarboxylic acids.
B(OH)2
N
N
O
O
1b
(1 mol-%)
HO2C
HO2C
CO2H
CO2H
O
O
n-PrCN, 12h
azeotropic reflux
O
O
90 %
1b (1 mol-%), n-PrCN, 12 h
HO2C
HO2C
CO2H
CO2H
azeotropic reflux
then PhNH2 (3 equiv)
rt, 3 h
PhHNOC
HO2C
CONHPh
HO2C
CONHPh
CO2H
ϩ
CO2H
PhHNOC
99 % (1:1 mixture)
Scheme 1. 1b-catalyzed dehydrative condensation of pyromellitic acid
and one-pot synthesis of bis(amidocarboxylic acid)s (previous work).
bis(amidocarboxylic acid)s in 99 % yield (Scheme 1). We report
here detailed investigations of arylboronic acid catalysts bearing
(N,N-dialkylamino)methyl groups for the intramolecular dehy-
drative condensation of dicarboxylic acids and insights into the
mechanism of the Brønsted base-assisted boronic acid catalysis.
Results and Discussion
To evaluate the role of the dialkylamino groups of the aryl-
boronic acid catalysts for the intramolecular dehydrative

1460
A. Sakakura et al.
B(OH)2
Table 1. Catalytic dehydrative condensation of phthalic acidA
ϩ
N(C8H17 3
)
O
CO2H
CO2H
BϪr
catalyst (10 mol-%)
1f
O
CO2H
CO2H
solvent (0.25 M), time
azeotropic reflux
H2O
HBr
O
H2O
Entry
Catalyst
YieldB [%]
B(OH)2
Condition AC
Condition BD
O
ϩ
H
O
N(C8H17 3
)
O
1
2
3
4
No catalyst
0
21
35
12
—
—
—
—
O
OϪ
ϩ
COϪ2
B
2-IC6H4B(OH)2
3,4,5-F3C6H2B(OH)2
2,4,6-(i-Pr)3C6H2B(OH)2
N(C8H17 3
)
CO2H
B(OH)2
2b
O
CO2H
CO2H
N(i-Pr)2
5
79
8
O
1a
O
B(OH)2
Fig. 3. Plausible catalysis by 1f bearing a trioctylammonium group.
6
94
4
active than 1a for the catalytic dehydrative amide condensation,
showed N-B chelation (Fig. 5).[7a,10–13] It is conceivable that
N-B chelation of the N,N-dimethylamino group may have
decreased the Lewis acidity of the boronic acid group. On the
other hand, the steric hindrance of the N,N-diisopropylamino
group of 1a might prevent intramolecular interaction between
the boronic acid group and the N,N-diisopropylamino group
(N-B chelation). The crystal structure of 1h shows that the
N,N-diisopropylamino groups interact with protons of the
boronic acid group (Fig. 6). Saito and colleagues also reported
intramolecular hydrogen bonding between (N,N-dialkylamino)
methyl groups and boron-coordinated water in aqua-
aminoorganoboron compounds.[14a]
N(i-Pr)2
1c
B(OH)2
7
97
16
N(i-Pr)2
1d
N
(OH)2B
N
The high catalytic activities of 1b and 1h bearing two bulky
substituents at the 2,6-positions could be evaluated by 1H NMR
analysis (Fig. 7). Arylboronic acid 1d bearing an (N,N-diiso-
propylamino)methyl group at the 4-position gave rather com-
plicated 1H NMR spectra, which showed that the solution of 1d
included significant amounts of oligomeric species (Fig. 7a). In
contrast, the pinacol ester of 1d, which was prepared by mixing
8
9
91
93
9
1e
B(OH)2
Br
ϩ
N
7
13
1
7
1d with 1 equivalent of pinacol in situ, gave clear H NMR
7
spectra (Fig. 7b). The pinacol ester of 1d must be monomeric in
solution. In addition, arylboronic acid 1h bearing two (N,N-
diisopropylamino)methyl groups at the 2,6-positions also gave
clear 1H NMR spectra (Fig. 7c). These 1H NMR analyses
indicated that the introduction of two sterically bulky substitu-
ents at the 2,6-positions would prevent the formation of less
active oligomeric species such as triarylboroxines 3[10c,11b,12b]
(Fig. 8). Since sterically hindered 2,4,6-(i-Pr)3C6H2B(OH)2
showed quite low catalytic activity (Table 1, entry 4), the high
catalytic activities of 1b and 1h should be attributed to the
function of the intramolecular (N,N-dialkylamino)methyl
groups as proposed in Fig. 2. The steric bulkiness around the
boronic acid moiety would maintain the high catalytic activity
under the reaction conditions.
1f
B(OH)2
N(i-Pr)2
10
99
40
1g
AThe reaction of phthalic acid (2.5 mmol) was conducted in the presence of
an arylboronic acid (10 mol-%) in solvent (10 mL).
BDetermined by 1H NMR analysis.
CCondition A: nonane (1518C), 1.5 h.
DCondition B: heptane (988C), 12 h.
Whiting and colleagues reported that 1a showed no N-B
chelation, either in solution or in the solid state, while
phenylboronic acid bearing a sterically less hindered (N,N-
dimethylamino)methyl group at the 2-position, which was less
Thermoplastic aromatic polyimides, which are some of the
most widely used polymers in our daily life, are synthesized
from aromatic carboxylic dianhydrides and diamines.[18] These
aromatic carboxylic dianhydrides are synthesized industrially

Catalytic Dehydrative Condensation
1461
Table 2. Catalytic activities of bis(N,N-dialkylamino)methylphenyl-
boronic acidsA
diamine, since the diamine preferentially reacts with acetic
anhydride or acetic acid to give the corresponding acetamide
or ammonium acetate. As we reported in the previous paper,
Brønsted base-assisted boronic acid catalyst 1b (1 mol-%)
successfully promoted the dehydrative condensation of aromat-
ic tetracarboxylic acids, such as pyllometic acid and 4,40-
oxydiphthalic acid, to give the corresponding dianhydrides in
almost quantitative yields. This catalytic process should be
superior to those currently used, since the reaction mixture
can be used for the subsequent reaction with a diamine without
any purification procedures.
O
CO2H
catalyst (1 or 10 mol-%)
O
solvent (0.25 M), 12 h
CO2H
azeotropic reflux
O
Entry Catalyst
YieldB [%]
Condition AC Condition BD
Based on the present method, the direct synthesis of diimides
from a tetracarboxylic acid and a primary amine could be
achieved (Scheme 2). When the 1b-catalyzed condensation of
4,40-oxydiphthalic acid was conducted in the presence of aniline
or n-octylamine (2 equiv), the corresponding diimides 4a and 4b
were obtained in respective yields of 98 and 97 % by simple
filtration of the reaction mixture. For the synthesis of diimide 4a,
catalyst 1b could be easily recovered by concentration of the
filtrate, and could be reused repeatedly without any loss of
activity.
B(OH)2
N(i-Pr)2
1
40
51
1g
B(OH)2
(i-Pr)2N
N(i-Pr)2
2
52
71
Conclusion
1h
B(OH)2
In conclusion, bifunctional Brønsted base-assisted boronic acid
catalysts, arylboronic acids bearing two sterically bulky
(N,N-dialkylamino)methyl groups at the 2,6-positions, exhib-
ited remarkable activities for the dehydrative intramolecular
condensation of dicarboxylic acids. The steric bulkiness of the
(N,N-dialkylamino)methyl groups of 1, which prevented the
formation of less active species such as the N-B chelated
species and triarylboroxines 3, was crucial for the high catalytic
activity. To the best of our knowledge, this is the first successful
method for the catalytic dehydrative condensation of di- and
tetracarboxylic acids. In addition, the present Brønsted base-
assisted boronic acid catalysis could be applied to direct cata-
lytic synthesis of diimides 4 as model reactions for the synthesis
of thermoplastic aromatic polyimides.
(i-Pr)2N
N(i-Pr)2
3
—
64
F
1i
B(OH)2
(i-Pr)2N
N(i-Pr)2
4
—
62
NO2
1j
Experimental
General
B(OH)2
Arylboronic acids 1a,[7] 1b,[16] 1c,[16] 1d,[16] 1f,[17] 1g,[16] and
1h[16] were prepared as described in the literature. Diimide 4a
has been reported previously.[16] IR spectra were recorded on a
N
N
5
6
75
99
—
1
JASCO FT/IR-460 plus spectrometer. H NMR spectra were
1b
measured on a Varian Gemini-2000 spectrometer (300 MHz) or
a JEOL ECS-400 spectrometer (400 MHz) at ambient temper-
ature. Data were recorded as follows: chemical shift in ppm from
tetramethysilane as an internal standard on the d scale, multi-
plicity (s ¼ singlet, d ¼ doublet, t ¼ triplet, m ¼ multiplet),
coupling constant (Hz), and integration. 13C NMR spectra were
measured on a VXR 500 (125 MHz), or a JEOL ECS-400
(100 MHz). Chemical shifts were recorded in ppm from the
solvent resonance used as an internal standard (CDCl3 at
77.0 ppm). High-resolution mass spectrometric analysis
(HRMS) was performed at Chemical Instrument Facility,
Nagoya University. Dry tetrahydrofuran and toluene were pur-
chased from Kanto as the ‘anhydrous’ form and stored under
nitrogen. Propionitrile, butyronitrile, and valeronitrile were
freshly distilled over calcium hydride. 1,2-dimethoxyethane
(DME) was freshly distilled from sodium and benzophenone.
B(OMe)3 and aniline were freshly distilled.
PhB(OH)2
0 (0)E
AThe reaction of phthalic acid (2.5 mmol) was conducted in the presence of
an arylboronic acid (10 mol-%) in solvent (10 mL) for 12 h.
BDetermined by 1H NMR analysis.
CCondition A: 10 mol-% catalyst loading, heptane (988C).
DCondition B: 1 mol-% catalyst loading, EtCN (978C).
EData in parentheses represent the conversion yield in the presence of
1,2,2,6,6-pentamethylpiperidine (20 mol-%).
from the corresponding tetracarboxylic acids using excess acetic
anhydride as a dehydration reagent. In this case, however,
remaining acetic anhydride and the resultant acetic acid should
be completely removed before the subsequent reaction with a

1462
A. Sakakura et al.
(a)
(b)
(c)
1.944 Å
1.667 Å
1.820 Å
1.735 Å
1.661 Å
1.816 Å
1.848 Å
Fig. 4. B3LYP/6-31G* optimized geometry of acylboronate intermediates 2. (a): Monoacyl 2-(N,N-dimethylamino)methylphenylboronate. (b): Monoacyl
3-(N,N-dimethylamino)methylphenylboronate. (c): Monoacyl 4-(N,N-dimethylamino)methylphenylboronate (a complex with two molecules of 4-(N,N-
dimethylamino)methylphenylboronic acid). B ¼ yellow, N ¼ blue, O ¼ red.
OH
B
B(OH)2
HO
O H
(a)
(b)
(c)
HO
NR'2
B
NR'2
Oligomers
(R' ϭ Me)
less Lewis acidic
form of 1
(R' ϭ i-Pr)
N(i-Pr)2
1d
more Lewis acidic
form of 1
Fig. 5. N-B Interaction versus N-HO interaction in the arylboronic
acid catalysts.
8.0
8.0
8.0
7.0
7.0
7.0
6.0
5.0
4.0
4.0
4.0
3.0
3.0
3.0
O
O
B
1.933 Å
N(i-Pr)2
Pinacol ester of 1d
6.0
5.0
B(OH)2
Fig. 6. ORTEP plot of 1h. B ¼ yellow, N ¼ blue, O ¼ red. Protons, except
for those in the boronic acid group, are omitted for clarity.
(i-Pr)2N
N(i-Pr)2
1h
Computational Method
Theoretical calculations were performed using the Gauss-
ian03[19] programs. Geometry optimization of the intermediates
from (N,N-dimethylamino)methylphenylboronic acids and
phthalic acid was performed using gradient-corrected
density functional theory (DFT) calculations with Becke’s
three-parameter exchange with the Lee, Yang, and Parr
6.0
5.0
Fig. 7. 1H NMR spectra of 1d (a), the pinacol ester of 1d (b), and 1h (c).

Catalytic Dehydrative Condensation
1463
R''
R'2N
for the structure reported in this paper have been deposited with
Cambridge Crystallographic Data Centre. Copies of the data can
be obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [Fax: þ44(1223)336-033;
Email: deposit@ccdc.cam.ac.uk]. Supplementary publication
no. CCDC-787831.
O
B
B
O
O
R''
B
NR'2
R''
NR'2
B(OH)2
R''
NR'2
Synthesis of [2-(1-Methyl-1H-imidazol-2-yl)phenyl]boronic
Acid 1e
3
ϩ
Monomeric form
To a solution of 2-iodo-1-methylimidazole (2.97 g, 14.3 mmol),
2-bromophenylboronic acid (2.87 g, 14.3 g), and triphenylpho-
sphine (510 mg, 1.94 mmol) in DME (21 mL) was added 2 M
aqueous K2CO3 (21 mL, 42 mmol), and the mixture was
degassed. To this solution was added Pd(OAc)2 (109 mg,
0.49 mmol), and the solution was refluxed for 39 h. After the
resultant reaction mixture was cooled to ambient temperature,
the aqueous layer was extracted with EtOAc. The combined
organic layers were dried over Na2SO4 and concentrated under
vacuum. The residue was purified by column chromatography
on silica gel (hexane/EtOAc 5:1 - 1:2). The product was dis-
solved in EtOAc and extracted with 1 M aqueous HCl. After the
pH of the aqueous extracts was adjusted to 10 with Na2CO3, the
solution was extracted with EtOAc. The organic layer was
dried over Na2SO4 and concentrated under vacuum to give
2-(2-bromophenyl)-1-methylimidazole (730 mg, 22 % yield).
Other stable
intermediates
of 1
Fig. 8. Formation of inactive species.
HO2C
HO2C
O
CO2H
ϩ PhNH2
CO2H
O
O
O
1b (1 mol-%)
RN
NR
n-PrCN, 12 h
azeotropic reflux
O
O
5
4a (R ϭ Ph)
To
a
solution of 2-(2-bromophenyl)-1-methylimidazole
Run
1
2
3
4
Reusability of 1b
(474 mg, 2.00 mmol) in toluene/THF (4:1 w/w, 4.0 mL) was
added a 1.6 M solution of n-BuLi in hexane (1.9 mL, 3.0 mmol)
at ꢁ788C, and the mixture was stirred for 0.5 h. To the reaction
mixture was added B(OMe)3 (0.45 mL, 4.0 mmol) at ꢁ788C,
and the mixture was stirred at ambient temperature for 1 h. After
the reaction mixture was concentrated under vacuum, the resi-
due was purified by column chromatography on aluminum ox-
ide (EtOAc/MeOH 1:0 - 5:1) to give 1e (186 mg, 46 % yield):
nmax (KBr)/cmꢁ1 1561, 1481, 1430, 1279, 1166, 1115. dH
(400 MHz, CDCl3) 4.84 (s, 3H), 7.18 (s, 1H), 7.25 (s, 1H), 7.30–
7.40 (m, 2H), 7.52 (d, J 6.4, 1H), 7.72 (d, J 7.4). dC (100 MHz,
CDCl3) 35.2, 121.3, 121.8, 126.4, 128.7, 130.9, 131.6, 132.0.
HRMS (FAB, ester of 1e with propane-1,3-diol) Calc. for
C13H17BN2O2 [M þ H]þ: 244.1386. Found: 244.1358.
Yield (%) 98 94 98 95 93
HO2C
HO2C
O
CO2H
ϩ n-C8H17NH2
CO2H
O
RN
O
O
1b (1 mol-%)
NR
n-PrCN, 12 h
azeotropic reflux
O
O
4b (R ϭ n-C8H17
)
97 %
Scheme 2. Direct catalytic synthesis of diimides 4.
Synthesis of 2,6-Bis[(N,N-diisopropylamino)methyl]-
4-fluorophenylboronic Acid 1i
correlation functional (B3LYP),[20] using the 6-31G* basis set.
After satisfactory geometry optimization, the vibrational spec-
trum of each species was calculated.
Catalyst 1i was synthesized from 2-bromo-5-fluoro-1,3-
dimethylbenzene[21] according to the same manner as 1h.[16]
nmax (KBr)/cmꢁ1 3290, 1591, 1467, 1422, 1365, 1270, 1111,
1040. dH (300 MHz, CDCl3) 1.09 (d, J 6.9, 24H), 3.04 (sept,
J 6.9, 4H), 3.77 (s, 4H), 6.93 (d, J 9.6, 2H). dC (100 MHz,
CDCl3) 19.9, 47.1, 52.1, 118.0 (d, J 19.1), 145.8 (d, J 6.7), 162.3
(d, J 246). HRMS (FAB, ester of 1i with propane-1,3-diol) Calc.
for C23H41BFN2O2 [M þ C3H5]þ: 407.3245. Found: 407.3222.
Crystal Data for 2,6-Bis[(N,N-diisopropylamino)methyl]
phenylboronic Acid 1h
A Bruker SMART APEX diffractometer with CCD detector
˚
(graphite monochromator, MoKa radiation, l 0.71073 A) was
used for X-ray crystal analysis. The structure was solved by
direct methods and expanded using Fourier techniques. Formula
C20H37BN2O2, colourless, crystal dimensions 0.40 ꢀ 0.35 ꢀ
Synthesis of 2,6-Bis[(N,N-diisopropylamino)methyl]-
4-nitrophenylboronic Acid 1j
0.30 mm3, orthorhombic, space group Pnn2(#34), a 11.198(3),
3
˚
˚
A mixture of 1h (0.50 mmol), HNO3 (0.38 mL, 9 mmol) and
H2SO4 (0.51 mL, 9.5 mmol) was stirred at 708C for 3.5 h. After
the pH of the reaction mixture was adjusted to ,12 by the ad-
dition of aqueous NaOH, the mixture was extracted twice with
EtOAc. The combined organic phase was washed twice with
water, dried over Na2SO4, and concentrated under vacuum. The
obtained crude product was purified by column chromatography
b 11.845(3), c 8.277(2) A, b 90.08, V 1097.9(5) A , Z 2, and Dcalc
1.054 g cmꢁ3, F(000) 384, m 0.066 mmꢁ1, T 173(2) K. 2610
reflections collected, 2475 independent reflections with
I . 2s(I) (2ymax 28.378), and 123 parameters were used for the
solution of the structure. The non-hydrogen atoms were refined
anisotropically. R1 ¼ 0.0387 and wR2 ¼ 0.1060, goodness of fit
(GOF) 1.032. Crystallographic data (excluding structure factors)

1464
A. Sakakura et al.
on silica gel (NH; hexane–EtOAc 10:1 - 3:1) to give 1j
(129 mg, 65 % yield): nmax (KBr)/cmꢁ1 1519, 1341, 1174, 1038.
dH (400 MHz, CDCl3) 1.11 (d, J 6.9, 24H), 3.03 (sept, J 6.9, 4H),
3.90 (s, 4H), 8.06 (s, 2H). dC (125 MHz, CDCl3) 20.0, 47.4, 52.1,
125.2, 145.1, 147.5. HRMS (FAB, ester of 1j with propane-1,3-
diol) Calc. for C23H41BN3O4 [M þ C3H5]þ: 434.3190. Found:
434.3216.
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3511. doi:10.1021/MA000085O
(d) K. Ishihara, S. Kondo, H. Yamamoto, Synlett 2001, 1371,
doi:10.1055/S-2001-16788
(e) K. Ishihara, S. Ohara, H. Yamamoto, Org. Synth. 2002, 79, 176.
(f) T. Maki, K. Ishihara, H. Yamamoto, Synlett 2004, 1355,
doi:10.1055/S-2004-825615
General Procedure for the Dehydrative Condensation
of Phthalic Acids
(g) T. Maki, K. Ishihara, H. Yamamoto, Org. Lett. 2005, 7, 5043.
doi:10.1021/OL052060L
(h) T. Maki, K. Ishihara, H. Yamamoto, Org. Lett. 2005, 7, 5047.
doi:10.1021/OL052061D
(i) T. Maki, K. Ishihara, H. Yamamoto, Org. Lett. 2006, 8, 1431.
doi:10.1021/OL060216R
(j) T. Maki, K. Ishihara, H. Yamamoto, Tetrahedron 2007, 63, 8645.
doi:10.1016/J.TET.2007.03.157
A 20 mL, single-necked, round-bottomed flask equipped with a
Teflon-coated magnetic stirring bar and a 5 mL pressure-
equalizing addition funnel [containing a cotton plug and ,3 g of
molecular sieves 4A (pellets)] mounted with a reflux condenser
was charged with phthalic acid (2.5 mmol) and 1b (1 mol-%) in
EtCN (10 mL). The mixture was heated for 12 h under azeo-
tropic reflux conditions (oil bath temperature: ,1308C) with the
removal of water. After the reaction mixture was cooled to
ambient temperature, the solvent was removed under reduced
pressure. The yield of phthalic anhydride was evaluated by
1H NMR analysis.
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Direct Catalytic Synthesis of Diimides 4
[7] (a) K. Arnold, B. Davies, R. L. Giles, C. Grosjean, G. E. Smith,
A. Whiting, Adv. Synth. Catal. 2006, 348, 813. doi:10.1002/ADSC.
200606018
The reaction of 4,40-oxydiphthalic acid (2.5 mmol) and aniline
(2.5 equiv) was conducted in the presence of 1b (1 mol-%) in
n-PrCN (10 mL) for 12 h under azeotropic reflux conditions as
described above. After the reaction mixture was cooled to
ambient temperature, pure diimide 4a was obtained by filtration
in 98 % yield as a colorless solid. Catalyst 1b was recovered by
concentration of the filtrate under reduced pressure. Recovered
1b was used repeatedly under the same reaction conditions.
Diimide 4b: nmax (KBr)/cmꢁ1 1767, 1707, 1613, 1476, 1438,
1393, 1356, 1264, 1230, 1094, 1033. dH (400 MHz, CDCl3) 0.87
(t, J 6.9, 6H), 1.19–1.39 (m, 20H), 1.67 (tt, J 6.9, 7.3, 4H), 3.67
(t, J 7.3, 4H), 7.36 (dd, J 1.8, 8.2, 2H), 7.42 (d, J 1.8, 2H), 7.87 (d,
J 8.2, 2H). dC (100 MHz, CDCl3) 14.4, 22.9, 27.1, 28.9, 29.4,
32.1, 38.6, 113.8, 124.4, 125.8, 127.9, 135.3, 161.1, 167.6,
167.8. HRMS (FAB) Calc. for C32H41N2O5 [M þ H]þ:
533.3015. Found: 533.3022.
(b) K. Arnold, A. S. Batsanov, B. Davies, A. Whiting, Green Chem.
2008, 10, 124. doi:10.1039/B712008G
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(d) I. Georgiou, G. Ilyashenko, A. Whiting, Acc. Chem. Res. 2009, 42,
756. doi:10.1021/AR800262V
(e) H. Charville, D. Jackson, G. Hodges, A. Whiting, Chem. Commun.
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Accessory Publication
Copies of 1H and 13C NMR spectra of compounds 1e, 1i, 1j, and
4b are available on the Journal’s website.
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Acknowledgements
Financial support for this project was partially provided by JSPS.KAKENHI
(20245022 and 23350039), NEDO and the Global COE Program of MEXT.
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