Side functionalization of diboronic acid precursors for covalent organic frameworks

Article abstract of DOI:10.1039/c3ce26494g

A series of substituted 1,4-benzenediboronic acids (BDBA) was synthesized and their thermal properties investigated. Two diboronic acids were studied as building-blocks for covalent organic framework (COF) formation, namely 2,5-dimethoxy-1,4-benzenediboronic acid and 2-nitro-1,4-benzeneboronic acid. Interestingly, substitution of the BDBA core caused a dramatic decrease of the polymerization temperature leading to the formation of a less organized structure.

Full text of DOI:10.1039/c3ce26494g

CrystEngComm
View Article Online
View Journal | View Issue
PAPER
Side functionalization of diboronic acid precursors for
covalent organic frameworks3
Cite this: CrystEngComm, 2013, 15,
2067
b
a
a
a
Thomas Faury,ab Frederic Dumur,* Sylvain Clair,* Mathieu Abel, Louis Porte
´ ´
and Didier Gigmesb
A series of substituted 1,4-benzenediboronic acids (BDBA) was synthesized and their thermal properties
investigated. Two diboronic acids were studied as building-blocks for covalent organic framework (COF)
formation, namely 2,5-dimethoxy-1,4-benzenediboronic acid and 2-nitro-1,4-benzeneboronic acid.
Interestingly, substitution of the BDBA core caused a dramatic decrease of the polymerization temperature
leading to the formation of a less organized structure.
Received 14th September 2012,
Accepted 24th January 2013
DOI: 10.1039/c3ce26494g
www.rsc.org/crystengcomm
reaction involving the formation of covalent bonds by
dehydration of boronic acids (see Fig. 1a). Directly related to
1. Introduction
During the past decade, covalent organic frameworks (COFs)
have triggered a great deal of interest as these nanoporous
materials of high specific surface area could find applications
in hydrogen gas storage,1 detection of various molecules such
as explosives,2 as templates in organic electronics,3,4 masks for
surface nanopatterning5,6 or as nanoreactors.7 For these
purposes, various synthetic approaches were investigated to
form the nanoporous networks by polymerization of low
molecular weight elemental units, most of these strategies
being based on metal surface-induced chemistry: reductive
coupling of halogenated precursors,8–10 dehydration of boro-
nic acids resulting in boroxine rings formation,11,12 reductive
the C3 symmetry of the boroxine ring, only 2D covalent
networks with the predetermined honeycomb-like structure
can be formed (see Fig. 1b and c). In the course of our
investigations, choice of the substrate, molecular flow and the
subtle balance between molecules adsorption and diffusion
were determined as factors strongly influencing the network
formation and its regularity.
To extend our work initially developed on the model
molecule BDBA towards more sophisticated diboronic acids,
N
homocoupling of CH2 radicals of termethylporphyrins,13
tautomerization14 or imidization of pyridine,15 imine16 or
amide17 formation and phthalocyanine macrocyclization.18
Our laboratory is involved in the development of 2D
polymer networks on metallic and insulating surfaces using
diboronic acids as elemental units.19 To date, our attention
was mostly focused on the well-known 1,4-benzenediboronic
acid (BDBA).11,20 For a better understanding of the polymer-
ization mechanisms and to get a deeper insight in the relation
existing between deposition speed, polymer growth and
network regularity, BDBA was notably deposited on different
metallic substrates (Au, Ag, Cu) by sublimation under ultra-
high vacuum (UHV). Subsequently to their deposition, 2D-
networks were examined by scanning tunneling microscopy
(STM). Generation of the boroxine rings is a three-component
aCNRS, ICR, UMR 7273, Aix-Marseille University, F-13397 Marseille Cedex 20,
France. E-mail: frederic.dumur@univ-amu.fr; Fax: +33 4 91 28 87 58;
Tel: +33 4 91 28 27 48
bCNRS, IM2NP, UMR 7334, Aix-Marseille University, F-13397 Marseille Cedex 20,
France. E-mail: sylvain.clair@univ-amu.fr; Tel: +33 4 91 28 85 38
Fig. 1 (a) Mechanism of the boroxine ring formation from the BDBA molecule
Electronic supplementary information (ESI) available. See DOI: 10.1039/
3
leading to the polymeric network observed by STM on Ag(111) (b) and (c).
c3ce26494g
This journal is ß The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 2067–2075 | 2067

View Article Online
Paper
CrystEngComm
introduction of functional groups in the COF pore walls was
targeted and the symmetric and dissymmetric peripheral
substitution of the BDBA core envisioned. To the best of our
knowledge, functionalization of the internal COF pore walls
has never been reported so far. Remarkably, all variations on
the BDBA core were only brought to the spacer between the
two boronic functions: extension of the conjugation by using
polycyclic aromatics consisting of benzene rings fused
together or polycyclic aromatics in a rectilinear arrangement.21
Herein, substitution of the benzene ring with functional
groups such as cyano, hydroxy, methoxy and nitro groups was
notably examined. It has to be noticed that, to date, only a
limited number of 1,4-benzenediboronic acids is reported in
the literature and it has to be related to the challenge that
consists to combine within a single molecule various functions
often requiring incompatible synthetic approaches to be
introduced.
In this paper, we report for the first time a COF exhibiting
functionalized pore walls. Prior to COF formation, our work
focused on synthesis of substituted BDBA molecules and the
different synthetic pathways investigated are reported.
Following their syntheses and to determine the influence of
the substitution pattern on the polymerization process,
thermal properties of the different diboronic acids were
studied. Notably, their polymerization and sublimation tem-
peratures were determined as the experimental approach is
limited to sublimable molecules. Especially, sublimation
temperatures higher than the polymerization ones constitute
the primary impediment for the molecules to be vacuum
deposited. Based on these thermal requirements, only the
network prepared with 2-nitro-1,4-benzenediboronic acid on a
Ag (100) surface could be fully studied.
room temperature in 5 mm o.d. tubes on a Bruker Avance 400
spectrometer of the Spectropole: 1H (400 MHz) and 13C (100
MHz). The H chemical shifts were referenced to the solvent
1
peak DMSO-d6 (2.49 ppm), CDCl3 (7.26 ppm) and the 13C
chemical shifts were referenced to the solvent peak DMSO d6
(39.5 ppm) and CDCl3 (77 ppm). 5,59-dibromo-2,29-bipyri-
dine,22 1,4-dibromo-2,3,5,6-tetramethylbenzene 10,23 2,5-
dibromo-1,4-hydroquinone 1824 and 1,4-benzene-diboronic
acid 2025 were prepared following procedures previously
reported in the literature without modification and with
similar yields. 1,4-Dibromo-2,5-dimethoxybenzene 826 was
synthesized by following and adapting a literature procedure.
For differential scanning calorimetry (DSC) measurements,
a DSC 2920 TA Instruments was used. The heating and cooling
rates were recorded at a temperature ramp of 10 uC min21
.
Thermogravimetric analysis were performed on a TQA 500
from a TA instrument at a temperature ramp of 10 uC. Each
compound was analyzed at least three times by DSC and TGA
to determine the standard deviation. Standard deviations for
each of the temperatures quoted in the text are summarized in
the Table 1.
2-Nitro-1,4-benzeneboronic acid 24 was vapour deposited
under ultrahigh vacuum (1029 mbar) conditions on metallic
monocristalline substrates Ag(100), Au(111) and Cu(111).
Before the deposition, substrates were cleaned by Ar+ sputter-
ing and annealing. The sublimation temperature was around
130 uC and the dehydration of the boronic acids was activated
by annealing at 200 uC. The surface was characterized by room
temperature scanning tunnelling microscopy (STM) and the
images were partly processed with WSxM software.27
Synthesis of 2,5-dipentanoylbenzene 4
1.5 g (11.7 mmol) of 1,4-dicyanobenzene were suspended in 50
mL dry THF. The reaction mixture was cooled to 278 uC and
10.3 mL (2.2 eq.) of n-BuLi (2.5 M in hexanes) was slowly
added. The reaction was allowed to warm to room temperature
and stirring was maintained overnight. The reaction mixture
was cooled to 278 uC and 11 mL of triisopropyl borate was
added. The reaction mixture was refluxed for 2 h and a sticky
solid formed. It was hydrolyzed with water and acidified with
dilute HCl. The solution was extracted with ethyl acetate, the
organic phases were combined, dried over magnesium sulfate
and the solvent removed under reduced pressure. The residue
was purified by column chromatography (SiO2) using a
2. Experimental
All reagents and solvents were purchased from Aldrich or Alfa
Aesar and used as received without further purification. Mass
spectroscopy was performed by the Spectropole of Aix-
Marseille University (Marseille). ESI mass spectral analyses
were recorded with a 3200 QTRAP (Applied Biosystems SCIEX)
mass spectrometer. The HRMS mass spectral analysis was
performed with a QStar Elite (Applied Biosystems SCIEX) mass
spectrometer. 1H and 13C NMR spectra were determined at
Table 1 Comparative statement of the functional group influence on BDBA regarding polymerization and degradation properties measured by TGA and DSC for the
compounds 20, 24, 19, 17, 15, 16 and 14.
Compound
TGA
DSC
Polymerization Tu (uC)
Decomposition Tu (uC)
Weight loss
Polymerization Tu (uC)
Energy
J g21
579
540
283
216
488
680
260
%
g mol21
eV molecule21
0.99
1.18
0.57
0.40
1.14
1.40
0.61
20-BDBA
24-Nitro BDBA
19-Dimethyl BDBA
17-Methyl BDBA
15-Dimethoxy BDBA
16-Dihydroxy BDBA
14-Tetramethyl BDBA
218 (+/25)
146 (+/27)
116 (+/21)
102 (+/22)
100 (+/24)
98 (+/21)
496 (+/29)
302 (+/22)
180 (+/211)
380 (+/29)
139 (+/24)
98 (+/21)
21
17
14
10
17
34
12
34.8
35.8
27.1
18.0
38.3
67.2
26.2
198 (+/23)
162 (+/21)
116 (+/23)
106 (+/23)
110 (+/28)
120 (+/23)
84 (+/24)
45 (+/210)
103 (+/23)
2068 | CrystEngComm, 2013, 15, 2067–2075
This journal is ß The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
mixture of solvents CH2Cl2–pentane: 1/1 as the eluent. 1.47 g
of a brown oil was obtained in 47% yield. H NMR (400 MHz,
saturated aqueous bicarbonate and brine, dried over magne-
sium sulfate and the solvent removed under reduced pressure.
Addition of a minimum of acetone and cooling at 220 uC for a
night provided colorless crystals (2.77 g, 82% yield). NMR were
consistent with those previously reported.28 1H NMR (400
MHz, CDCl3, ppm): 0.29 (s, 18H), 7.59 (s, 2H) 13C NMR (100
MHz, CDCl3 d6, ppm): 0.21, 113.9, 118.7, 124.1, 147.2.
1
CDCl3, ppm): 0.95 (t, 6H, J = 7.2 Hz), 1.42 (qt, 4H, J = 7.5 Hz),
1.61 (qt, 4H, J = 7.5 Hz), 2.75 (t, 4H, J = 7.6 Hz), 7.78 (s, 4H) 13
C
NMR (100 MHz, CDCl3, ppm): 13.9, 22.4, 26.3, 38.6, 128.2,
140.1, 200.0 HRMS (ESI MS) m/z: theor: 247.1693 exp :
247.1695 ([M+H]+ detected).
Synthesis of 1-bromo-4-butyl-2-nitrobenzene 5
Synthesis of 1,4-dibromo-2,5-dimethoxybenzene 8
2.5 g (8.90 mmol) of 1,4-dibromo-2-nitrobenzene were dis-
solved in 50 mL dry THF. The solution was cooled to 260 uC
and 12 mL n-BuLi (2.5 M in hexanes) was slowly added. The
reaction mixture was stirred at room temperature overnight.
The solution was cooled to 260 uC and 5 mL (21.7 mmol) of
triisopropyl borate was added. The reaction mixture was
allowed to warm to room temperature and stirring was
maintained overnight. The solution was quenched onto 50
mL HCl (2N) and THF was removed under reduced pressure. A
brown oil was obtained. The residue was purified by column
chromatography (SiO2) using a gradient of solvent (from
pentane to DCM). The target molecule was isolated as a brown
oil in 63% yield (1.45 g). 1H NMR (400 MHz, CDCl3, ppm): 0.90
(t, 3H, J = 7.3 Hz), 1.25–1.35 (m, 2H), 1.41–1.65 (m, 2H), 2.71–
2.78 (m, 2H), 7.29 (d, 1H, J = 8.5 Hz), 8.00 (dd, 1H, J = 2.3 Hz, J
= 8.5 Hz), 8.31 (d, 1H, J = 2.3 Hz) 13C NMR (100 MHz, CDCl3,
ppm): 13.7, 22.3, 31.4, 35.8, 121.9, 124.3, 127.6, 130.3, 146.3,
149.7 HRMS (ESI MS) m/z: theor: 257.0051 exp : 257.0047 (M+
detected).
8.03 g (30 mmol) of 2,5-dibromo-1,4-hydroquinone 18 were
suspended in 20 mL DMSO. 3.37 g (60 mmol) of potassium
hydroxide were added. After 5 min, 4 mL (65 mmol) of
iodomethane were added and the reaction mixture was stirred
at 75 uC for a night. After cooling, the solution was poured in
water, extracted with DCM. The organic phases were com-
bined, dried over magnesium sulfate and the solvent removed
under reduced pressure. 7.1 g of a white solid were obtained in
80% yield. 1H NMR (400 MHz, CDCl3, ppm): 3.87 (s, 6H, OMe),
7.12 (s, 2H), 1H NMR (400 MHz, MeOD, ppm): 3.84 (s, 6H,
OMe), 7.25 (s, 2H), 1H NMR (400 MHz, DMSO d6, ppm): 3.82 (s,
6H, OMe), 7.35 (s, 2H), 13C NMR (100 MHz, DMSO d6, ppm):
56.9, 109.9, 117.0, 149.9. HRMS (ESI MS) m/z : theor: 294.8964
exp: 294.8960 ([M+H]+ detected).
Synthesis of 4-bromo-2,5-dihydroxyphenylboronic acid 11
In a 250 mL flask were added 4.11 g (10 mmol) of the ((2,5-
dibromo-1,4-phenylene) bis (oxy)) bis (trimethylsilane) 7, 20
mL (40 mmol) of iPrMgCl 2 M in THF and 100 mL of THF. The
mixture was heated to reflux for one day. Then 2.35 mL (20
mmol) of triisopropylborate were added and reflux was
maintained for 24 h. The solution was quenched with 100
mL aq. HCl 2 M. The solvent was removed under reduced
pressure. White crystals of the product were filtered off, dried
Synthesis of 4-bromo-3-nitrophenylboronic acid 6
1,4-Dibromonitrobenzene (2 g, 7.12 mmol) was dissolved in
dry THF (30 mL) and the resulting solution was cooled to 260
uC, to which was added PhMgCl (2 M in THF, 7.83 mL, 15.66
mmol). The reaction was allowed to warm to room tempera-
ture and stirring was maintained for 3 h. After cooling to 260
uC, trimethyl borate (3.61 mL, 15.66 mmol) was added
dropwise into the reaction solution. The reaction mixture
was stirred for 30 min at 260 uC and then quenched with 2 M
aq HCl (4 mL) at 220 uC. The reaction was extracted with Et2O
(3 6 20 mL), and the organic layers were combined, dried over
Na2SO4, filtered, and concentrated under reduced pressure.
The sticky residue was dissolved in a minimum of THF and
addition of conc. HCl precipitated a white solid which was
filtered off and dried under vacuum. 0.63 g of a white powder
1
with pentane and dried under vacuum (1.09 g, 47% yield). H
NMR (400 MHz, DMSO d6, ppm): 6.94 (s, 1H), 7.17 (s, 1H).
Synthesis of 4-bromo-2,5-dimethoxyphenylboronic acid 12
To 6 g (20 mmol) of 1,4-dibromo-2,5-dimethoxybenzene 8
dissolved in anhydrous THF (100 mL) were added under inert
atmosphere at 260 uC 17.8 mL (44 mmol) of n-BuLi 2.5 M in
hexane. The mixture was stirred for one day at room
temperature. 10.3 mL (44 mmol) of triisopropylborate and
the solution was stirred for two more days and finally
quenched with HCl 6N (50 ml) at 0 uC. After the solvent was
removed, a brown powder is obtained. 1H NMR (400 MHz,
DMSO d6, ppm): 6.81 (s, 1H), 6.69 (s, 1H), 3.66 (s, 3H) 3.62 (s,
3H) 11B NMR (128 MHz, DMSO d6, ppm): 18.14.
1
was obtained in 36% yield. H NMR (400 MHz, CDCl3, ppm):
7.32 (d, 1H, J = 2.5 Hz), 7.64 (d, 1H, J = 8.5 Hz), 8.49 (dd, 1H, J =
8.5 Hz, J = 2.5 Hz) 1H NMR (400 MHz, DMSO d6, ppm): 6.82 (d,
1H, J = 8.6 Hz), 7.15 (d, 1H, J = 8.6 Hz), 7.32 (s, 1H) 11B NMR
(128 MHz, DMSO d6, ppm): 19.9 HRMS (ESI MS) m/z: theor:
243.9422 exp: 294.9424 ([M2H]2 detected).
Synthesis of 2-methyl-1,4-benzenediboronic acid 13
At 278 uC was added to a solution of 1.86 g (7 mmol) 1,4-
dibromotoluene 9 in THF (20 mL) and under inert atmo-
sphere, 10 ml of n-BuLi (2.5 M in hexane). The solution was
stirred for 1 h at 278 uC then 2 h at room temperature and
finally the mixture was refluxed for 2 h two more. The mixture
was cooled down to 278 uC and trimethylborate (10 mL, 90
mmol) was added. The flask was warmed to room temperature
and stirred for 2 h. The solution was then quenched with 40 ml
of HCl 2 M. After filtration, the reaction was extracted with
AcOEt (3 6 40 mL). The organic layers were combined, dried
Synthesis of 1,4-dibromo-2,5-bis(trimethylsilyloxy)benzene 7
To a mixture of 2,5-dibromo-1,4-hydroquinone 18 (2.22 g, 8.2
mmol) in 18 mL of dry acetonitrile was successively added
chlorotrimethylsilane (2.31 mL, 18.26 mmol), and hexamethyl-
disilazane (3.87 mL). The resulting solution was stirred at
room temperature for 16 h and the solvent removed under
reduced pressure. Pentane was added and the resulting
precipitate was filtered off. The solution was washed with
This journal is ß The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 2067–2075 | 2069

View Article Online
Paper
CrystEngComm
over MgSO4, filtered and the solvent was remove under
reduced pressure. A white powder is obtained in 60% yield.
1H NMR (400 MHz, DMSO d6, ppm): 7.52 (d, 2H, J = 7.7 Hz),
7.38 (d, 1H, J = 7.3 Hz), 2.37 (s, 3H) 11B NMR (128 MHz, DMSO
d6, ppm): 19.37 13C NMR (100 MHz, DMSO d6, ppm): 139.48,
134.89, 131.99, 130.16, 22.17 HRMS (ESI MS) m/z: theor:
179.0695 exp: 179.0693 ([M2H]2 detected).
Synthesis of 2,5-dimethyl-1,4-benzenediboronic acid 19
Under an inert atmosphere were added in a 250 mL flask 5.3 g
(20 mmol) of 1,4-dibromoxylene 21, 1 g (50 mmol) of Mg, few I2
crystals and anhydrous THF (50 mL). The mixture was refluxed
and stirred for 20 h. At 278 uC were added 14 mL (61 mmol) of
triisopropylborate and the mixture was once again heated to
reflux. The mixture was finally quenched with 15 mL HCl 2 M,
filtered and extracted with Et2O (3 6 30 mL) The organic
layers were combined, dried over MgSO4 and the solvent was
removed under reduced pressure. The product was precipi-
tated in pentane and a white solid was obtained in 35% yield.
1H NMR (400 MHz, DMSO d6, ppm): 7.18 (s, 2H), 2.33 (s, 6H)
Synthesis of 2,3,5,6-tetramethyl-1,4-benzenediboronic acid 14
To 5.9 g (20 mmol) of 1,4-dibromo-2,3,5,6-tetramethylbenzene
10 dissolved in anhydrous THF (50 mL) were added under an
inert atmosphere 1 g (50 mmol) of Mg and few I2 crystals. The
mixture was then refluxed for 20 h. At 278 uC 14 mL (61 mmol)
of triisopropylborate were added and the solution was refluxed
and stirred for 2 h and then quenched with HCl 2 M (25 mL).
The mixture was extracted with Et2O (3 6 20 mL). The
combined organic layers were dried over MgSO4, filtered and
the solvent was removed under reduced pressure to yield a
brown oil which precipitated in chloroform. After filtration a
yellow solid is obtained in 10% yield. 1H NMR (400 MHz,
DMSO d6, ppm): 2.10 (s, 12H) 13C NMR (100 MHz, DMSO d6,
ppm): 132.88, 19.75 11B NMR (128 MHz, DMSO d6, ppm): 18.82
HRMS (ESI MS) m/z: theor: 221.1166 exp: 221.1164
([M2H]2detected).
13C NMR APT (100 MHz, DMSO d6, ppm): 27.2, 134.4, 136.7 11
B
NMR (128 MHz, DMSO d6, ppm): 18.66 HRMS (ESI MS) m/z:
theor: 193.0852 exp: 193.0848 ([M2H]2 detected).
Synthesis of (4-bromo-2,5-dimethylphenyl)boronic acid 23
Under an inert atmosphere were added in a 250 mL flask 5.3 g
(20 mmol) of 1,4-dibromoxylene 21, 1 g (50 mmol) of Mg, a few
I2 crystals and anhydrous THF (50 mL). The mixture was
refluxed and stirred for 20 h. At 278 uC were added 14 mL (61
mmol) of triisopropylborate and the mixture was once again
heated to reflux. The mixture was finally quenched with 15 mL
HCl 2 M, filtered and extracted with Et2O (3 6 30 mL) The
organic layers were combined, dried over MgSO4 and the
solvent was removed under reduced pressure. The product is a
byproduct of the reaction and was obtained by precipitation in
water followed by filtration in 2% yield. 1H NMR (400 MHz,
DMSO d6, ppm): 2.23 (s, 3H), 2.33 (s, 3H), 6.99 (s, 1H), 7.22 (s,
1H) 11B NMR (128 MHz, DMSO d6, ppm): 19.24.
Synthesis of 2,5-dimethoxy-1,4-benzenediboronic acid 15
3 g (10.14 mmol) of 1,4-dibromo-2,5-dimethoxybenzene 8 were
dissolved in 50 mL dry THF. The solution was cooled to 260 uC
and 8.9 mL n-BuLi (2.5 M in hexanes) was slowly added. The
reaction mixture was stirred at room temperature overnight.
The solution was cooled to 260 uC and 5.15 mL (22.32 mmol)
triisopropylborate was added. The reaction mixture was
allowed to warm to room temperature and stirring was
maintained for 48 h. The solution was quenched onto 50 mL
HCl (2 N) and THF was removed under reduced pressure. After
cooling in the fridge, a brown precipitate formed. It was
filtered off and dried. The resulting precipitate was dissolved
in acetone and addition of pentane precipitated a light brown
solid which was filtered off and dried under vacuum. 1.26 g of
Synthesis of 2-nitro-1,4-benzenediboronic acid 24
The product was synthesized by adapting literature proce-
dures.29 To a mixture of concentrated HNO3 (1.5 mL), H2SO4
(4.5 mL), and urea (0.62 mg, 0.1 mmol) was slowly added a
solution of 1,4-benzenediboronic acid 20 (2 g, 10.5 mmol) in
acetic anhydride (25 mL) at such a rate to maintain the
temperature below 215 uC. Stirring was maintained at 215 uC
for 3 h. Then 30% aqueous solution of NaOH was added to
adjust pH = 3–5 while maintaining the temperature at 215 uC.
Water was added, and products were extracted with AcOEt (3
6 50 mL), dried over Na2SO4. Filtration and evaporation of the
solvent afforded a crude oil. Addition of ether precipitated a
white solid in 65% yield which was filtered off and dried in
compound was obtained in 55% yield. NMR characterizations
ref. 28
were consistent with those previously reported in
.
1H
NMR (400 MHz, CD3OD, ppm): 3.86 (s, 6H), 5.05 (s, 4H, OH),
1
7.21 (s, 2H) 11B NMR (128 MHz, CD3OD, ppm): 18.8 H NMR
(400 MHz, DMSO d6, ppm): 3.79 (s, 6H), 5.59 (s, 4H, OH), 7.18
(s, 2H) 11B NMR (128 MHz, DMSO d6, ppm): 20.14 13C NMR
(100 MHz, DMSO d6, ppm): 55.9, 116.7, 124.4, 157.3 HRMS
(ESI MS) m/z: theor: 227.0892 exp: 227.0894 ([M+H]+ detected).
1
vacuum. H NMR (400 MHz, DMSO d6, ppm): 7.52 (d, 1H, J =
7.3 Hz), 8.10 (dd, 1H, J = 7.3 Hz, J = 1 Hz), 8.54 (s, 1H) 11B NMR
(128 MHz, DMSO d6, ppm) 28.80 HRMS (ESI MS) m/z: theor:
234.0351 exp: 234.0351 ([M+Na]+ detected).
Synthesis of 2,5-dihydroxy-1,4-benzenediboronic acid 16
0.9 g (4 mmol) of 2,5-dimethoxy-1,4-benzenediboronic acid 15
were dissolved in 33% HBr (25 mL) and the mixture was stirred
2 h. The solvent was removed from the solution under reduced
pressure. The residue was dissolved in water and filtered to
remove insoluble compounds the water was removed under
3. Results and discussion
A series of mono and polysubstituted 1,4-benzenediboronic
acids was prepared for the controlled functionalization of the
COF pore walls with organic groups. To reach this objective,
different synthetic approaches were developed to introduce
one or several substituents such as methyl, nitro or methoxy
groups in the ortho position of the boronic functions. Two
1
reduced pressure to yield a red powder in 10% yield. H NMR
(400 MHz, DMSO d6, ppm): 6.61 (s, 2H) 11B NMR (128 MHz,
DMSO d6, ppm): 18.25 13C NMR (100 MHz, DMSO d6, ppm):
149.7, 115.7 HRMS (ESI MS) m/z: theor: 197.0437 exp: 197.0442
([M2H]2 detected).
2070 | CrystEngComm, 2013, 15, 2067–2075
This journal is ß The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
Fig. 2 Structure of diboronic acids 1–3.
strategies were mainly investigated: the post-functionalization
of 1,4-benzenediboronic acid by proceeding via electrophilic
aromatic substitution (Friedel and Craft reaction) or the
preparation of the conveniently substituted dibrominated
derivative further converted to the corresponding diboronic
acid. No general method could be utilized for the rapid
synthesis of a wide range of diboronic acids as the presence of
these substituents on the aromatic ring could generate
undesired electron effects or by the incompatibility of some
of these substituents with a lithiation approach. To illustrate
this point, a great deal of interest was devoted to the synthesis
of diboronic acids 1–3 (see Fig. 2).
In the first case, lithiation of 1,4-dicyanobenzene resulting
in a nucleophilic addition of n-BuLi on the cyano groups, thus
producing diketone 4 in 47% yield. While using a non-
nucleophilic base such as lithium 2,2,6,6-tetramethylpiperi-
dide (LTMP), no deprotonation in the ortho-position of the
nitrile group occurred and the starting material was entirely
recovered after reaction (see Scheme 1).30 Similarly, while
using two equivalents of n-BuLi with 1,4-dibromo-2-nitroben-
zene, the nucleophilic substitution of one bromine was
obtained instead of the metal–halogen exchange and provided
1-bromo-4-butyl-2-nitrobenzene 5 in 63% yield. Attempts to
perform a halogen-Grignard exchange with phenylmagnesium
chloride31 followed by quenching with trimethyl borate only
furnished the monoboronic acid 6 in 36% yield. As the last
example, a complete deactivation induced by the pyridine
moieties was observed and addition of n-BuLi on
5,59-dibromo-2,29-bipyridine did not induce any metal–halo-
gen exchange. Finally, organocatalyzed synthesis of boronic
acid only resulted in the complexation of the catalyst as a
result of the strong chelating ability of the bipyridine.
Literature protocols mostly use Grignard- or lithiated
reagents as precursors for the synthesis of aromatic boronic
acids and the two synthetic pathways were investigated. In a
first approach, combination of the halogen-metal exchange
with n-butyl lithium followed by borate treatment was
envisioned as a straightforward and high-yielding synthetic
route. However, despite our efforts, this method proved to be
unsuitable for the synthesis of numerous diboronic acids and
monoboronic acid was obtained as the main product when 7–
10 were used as the dibrominated precursors, producing 11–
14. Only diboronic acids 15, 16 and 17 could be obtained in 55,
10 and 60% yield respectively using this approach. It has been
noticed recently, that synthesis of boronic acid 17 has been
reported while using the same method.32 Briefly, synthesis of
diboronic acids 15 was achieved starting from 8 as the
Scheme 1 Different attempts of synthesis of diboronic acids 1–3.
dibrominated precursor, this molecule being prepared in two
steps by alkylation of 2,3-dibromo-1,4-hydroquinone 18 or by
bromination of 1,4-dimethoxybenzene.33 Then, diboronic acid
16 was obtained in one step by effecting
a complete
demethylation of the aryl methyl ether 15 in refluxing
concentrated hydrobromic acid (Scheme 2).
As an alternative to lithiation, we employed a technique
that was used in the early years of boronic acid synthesis with
the preparation of a Grignard reagent further engaged in
reaction with a trialkyl borate to furnish after hydrolysis in
acidic conditions the targeted boronic acid (Scheme 3). Using
this procedure, diboronic acids 19 and 20 were successfully
obtained with yields ranging from 10 to 40%, starting from
dibrominated 21 and 22. As previously, the monoboronic acid
23 was also obtained as a side-product during the synthesis of
19. Finally, for the substituents that do not tolerate the
lithiation step, a post-functionalization of 1,4-benzenediboro-
nic acid 20 was attempted. Interestingly, 20 is stable in
strongly acidic conditions (conc. H2SO4) and nitration of 20 in
sulphuric acid provided 24 in 65% yield. Surprisingly, all
attempts of Friedel and Kraft reactions on 20 were unsuccess-
ful and introduction of an acetyl group (25, 26) or halogens
(27, 28) was not achieved by this method. These different
This journal is ß The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 2067–2075 | 2071

View Article Online
Paper
CrystEngComm
Scheme 3 The different synthetic pathways investigated for the synthesis of the
diboronic acids via the Grignard approach and the post-functionalization
method.
With TGA, the polymerization reaction was identified by the
mass loss corresponding to 36 g mol21 which equals the loss
of two water molecules, each boronic acid moiety loses the
equivalent of a water molecule to form the boroxine rings. In
the case of BDBA (20), this reaction takes place at a
temperature of 218 uC. When substituted, the polymerization
temperature was lowered and this decrease strongly depended
on the additional function type and number. Notably, this
temperature dropped to 146 uC for the diboronic acid when
substituted with a nitro group (24), to 99 uC when substituted
by two methoxy groups (15). It thus appears that the reduction
of the polymerization temperature can be directly linked to the
increase of the molecular weight or to the number of
functional groups on the diboronic motif. In parallel, a
dramatic decrease of the polymer stability was also observed.
As evidenced by TGA, additional mass losses following the
initial mass loss attributable to the polymerization reaction
(dehydration) can be confidently assigned to the polymer
Scheme 2 The different synthetic pathways investigated for the synthesis of the
diboronic acids via the lithiation method.
failures proved all the limitations of the post-functionalization
strategy.
Subsequent to their syntheses, the different diboronic acids
were subjected to differential scanning calorimetry (DSC) and
thermogravimetric analysis (TGA) (see Fig. 3, Table 1 and ESI ).
3
2072 | CrystEngComm, 2013, 15, 2067–2075
This journal is ß The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
Fig. 3 TGA thermograms of 20 (a), 24 (b) and 16 (c); DSC thermograms of 20
(d), 24 (e) and 16 (f).
decomposition and it thus allows the determination of the
stability range of each polymer. The polymer formed from
BDBA at a temperature of 258 uC was stable up to 496 uC which
makes a stability range of about 238u. This range of stability
dropped to 120u (302 uC–182 uC) when the boronic acid was
substituted with a nitro group, and to nearly 0 when
substituted with two methoxy groups. No stability range was
observed for the dihydroxy BDBA (16), the polymerization and
the decomposition occurring simultaneously. The presence of
substituents on the diboronic motif therefore induces an
anticipated initiation of the polymerization process and a
decrease of the stability range.
Fig. 4 STM images of nitro-BDBA 24 deposition at room temperature (a) on
Au(111), (b) schematic representation of the lattice; (c) on Ag(100); (d) arbitrary
position of the nitro groups in the lattice (e) deposition of 24 on Cu(111) at rt (f);
STM images after annealing at 200 uC on Ag(100).
The DSC measurements confirmed the results obtained by
TGA concerning the polymerization temperatures. The poly-
merization of BDBA is an endothermic process requiring a net
energy of 0.99 eV per molecule. In the case of compounds 24
and 15, the same process necessitates a similar energy of 0.93
eV and 1.14 eV per molecule, respectively. The DSC of 16 shows
two close peaks barely indistinguishable, thus confirming that
polymerization and decomposition occur simultaneously.
The case of the compounds substituted with one (17), two
(19) or four methyl groups (14) is more complex. A weight loss
is initially measured, corresponding however to a fraction only
of the two water molecules required for polymerization. The
corresponding endothermic energy is also much lower as
compared to the case of BDBA, indicating that the polymeriza-
tion is at best incomplete. At higher temperatures, additional
peaks in DSC and TGA data indicate additional degradation
reactions that can hardly be identified. In fact, the nitro and
methoxy substituent groups should induce the formation of
additional hydrogen bonds as well as a particular molecule
conformation (rotation of the boronic groups with respect to
the phenyl ring).34,35 These effects represent probably impor-
tant factors influencing the mechanism of polymer formation
and its stability.
To estimate the ability of these functionalized molecules to
form covalent structures, deposition tests were conducted
under UHV by direct sublimation from a quartz crucible onto
metal surfaces. In this way, the supramolecular self-assembly
and the 2D polymerized form can be directly observed by STM.
However, an important drawback of such an approach
concerns the sublimation temperature of the molecular
precursors that must be lower than the polymerization
temperature inside the crucible.
The sublimation temperature is related to the molecular
weight and the addition of functional groups will increase it
while decreasing the polymerization temperature (as evi-
denced by the thermal behavior analyses). In fact, trials to
sublimate 15 were unsuccessful due to its reduced polymer-
ization temperature. Nevertheless, 24 could be successfully
deposited on different metal surfaces, as the nitro group is
only one of a few impacting the thermal properties of the
molecule. On Au(111), a well-extended dense supramolecular
This journal is ß The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 2067–2075 | 2073

View Article Online
Paper
CrystEngComm
phase was observed at room temperature (Fig. 4a) with a
rhombic unit cell (21 Å 6 39 Å) comprising eight molecules in
a flat-lying position (see Fig. 4b). The exact position of the
nitro groups could not be determined from the STM images.
On Ag(100), the molecules self-assembled in small anisotropic
domains (y20 nm wide, Fig. 4c) that did not present long
range order. Within 1D row, three different intermolecular
spacings were measured: 5.6, 8.3 and 11 Å. These distances
could be correlated to different possible conformations
associated with the positions of the nitro groups, see Fig. 4d.
On Cu(111), no supramolecular phase was observed and the
molecules reacted directly in small clusters (Fig. 4e) due to the
high reactivity of this surface, similar to the case of BDBA
(20).12
further investigations on COF formation. One way to get more
regular structures could consist in the use of functional groups
that could delay the polymerization or promote mobility. For
this purpose, molecules synthesized with methyl groups as
substituents should exhibit a higher mobility than those based
on the nitro function and could therefore lead to networks of
higher organization.
Acknowledgements
The authors would like to thank ANR (under grant JCJC-2010-
1001-1 ‘‘Covanet’’), Aix-Marseille University and the centre
national de la recherche scientifique (CNRS) for financial
support.
The polymerization reaction could be activated in situ by
annealing at 200 uC, as shown in Fig. 4f on Ag(100). On Au(111)
however, annealing induced complete desorption of the
molecules before any reaction could take place. The behavior
of 24 can be compared to that of 20 (BDBA)12 and to a certain
extend to the 2D polymerization system reported by Bieri
et al.:36 the high reactivity of copper and the reduced
diffusivity on this surface lowers the polymerization tempera-
ture and prevents the formation of extended networks. Finally,
the polymer obtained on Ag(100) (Fig. 4f) differs considerably
from an ideal 2D honeycomb network and from the network
obtained with BDBA (20) on the same surface. The presence of
the nitro moiety therefore favors an increased interaction with
the metal surface, impeding the formation of an extended
network.
References
1 S. Soo Han, H. Furukawa, O. M. Yaghi and W. A. Goddard,
J. Am. Chem. Soc., 2008, 130, 11580.
2 Z. Xiang and D. Cao, Macromol. Rapid Commun., 2012, 33,
1184.
3 E. L. Spitler and W. R. Dichtel, Nat. Chem., 2010, 2, 672.
4 D. L. Jiang, S. Wan, J. Guo, J. Kim and H. Ihee, Angew. Chem.,
Int. Ed., 2008, 47, 8826.
5 S. H. Joo, S. J. Choi, I. Oh, J. Kwak, Z. Liu, O. Terasaki and
R. Ryoo, Nature, 2001, 412, 169.
6 S. Clair, O. Ourdjini, M. Abel and L. Porte, Adv. Mater.,
2012, 24, 1252.
7 S. B. Lei, K. Tahara, J. Adisoejoso, T. Balandina, Y. Tobe
and S. De Feyter, CrystEngComm, 2010, 12, 3369.
8 L. Grill, M. Dyer, L. Lafferentz, M. Persson, M. V. Peters and
S. Hecht, Nat. Nanotechnol., 2007, 2, 687.
Conclusions
9 R. Gutzler, H. Walch, G. Eder, S. Kloft, W. M. Heckl and
M. Lackinger, Chem. Commun., 2009, 45, 4456.
10 M. Bieri, S. Blankenburg, M. Kivala, C. A. Pignedoli,
P. Ruffieux, K. Mullen and R. Fasel, Chem. Commun.,
2011, 47, 10239.
11 N. A. A. Zwaneveld, R. Pawlak, M. Abel, D. Catalin, D. Gigmes,
D. Bertin and L. Porte, J. Am. Chem. Soc., 2008, 130, 6678.
12 S. Clair, O. Ourdjini, M. Abel and L. Porte, Chem. Commun.,
2011, 47, 8028.
13 M. I. Veld, P. Iavicoli, S. Haq, D. B. Amabilino and R. Raval,
Chem. Commun., 2008, 1536.
14 M. Matena, T. Riehm, M. Stohr, T. A. Jung and L. H. Gade,
Angew. Chem., Int. Ed., 2008, 47, 2414.
15 M. Treier, N. V. Richardson and R. Fasel, J. Am. Chem. Soc.,
2008, 130, 14054.
16 R. Tanoue, R. Higuchi, N. Enoki, Y. Miyasato, S. Uemura,
N. Kimizuka, A. Z. Stieg, J. K. Gimzewski and M. Kunitake,
ACS Nano, 2011, 5, 3923.
17 C. H. Schmitz, J. Ikonomov and M. Sokolowski, J. Phys.
Chem. C, 2011, 115, 7270.
18 M. Abel, S. Clair, O. Ourdjini, M. Mossoyan and L. Porte, J.
Am. Chem. Soc., 2011, 133, 1203.
To conclude, the BDBA core was successfully modified to
functionalize the COF pore walls with various functional
groups and this new strategy is reported for the first time.
Despite difficult chemistry, various substituents were added
such as methyl, methoxy, hydroxy and nitro moieties.
Following this synthesis, the influence of additional groups
on COF preparation was investigated. Two of the synthesized
molecules (2,5-dimethoxy-1,4-benzenediboronic acid and
2-nitro-1,4-benzeneboronic acid) were studied and comparison
with the parent BDBA established. Thermal behavior of these
functionalized molecules was studied by TGA and DSC to
determine the influence of these additional groups on the
polymerization process as well as the stability of the resulting
COF. Architectures of the structures formed by sublimation
under UHV were examined by STM. Results showed that
substitution of BDBA caused a dramatic decrease of the
polymerization temperature as well as a substantial loss of
stability of the resulting polymer. These property changes
negatively affected the polymerization and resulted in the
formation of less regular 2D structures compared to those
initially obtained with BDBA. Nevertheless, 2-nitro-1,4-benze-
nediboronic acid showed a behavior similar to that of BDBA
and this monomer seems to be a promising candidate for
19 T. Faury, S. Clair, M. Abel, F. Dumur, D. Gigmes and L. Porte,
J. Phys. Chem. C, 2012, 116, 4819.
2074 | CrystEngComm, 2013, 15, 2067–2075
This journal is ß The Royal Society of Chemistry 2013

View Article Online
CrystEngComm
Paper
20 O. Ourdjini, R. Pawlak, M. Abel, S. Clair, L. cheng, N. Bergeon,
M. Sassi, V. Oison, J. M. Debierre, R. Coratger and L. Porte, Phys.
Rev. B: Condens. Matter Mater. Phys., 2011, 84, 125421.
21 J. F. Dienstmaier, D. D. Medina, M. Dogru, P. Knochel,
T. Bein, W. M. Heckl and M. Lackinger, ACS Nano, 2012, 6,
7234.
L. Torsi, M. C. Tanese, P. G. Zambonin, O. O. Hassan and L. Valli,
WO Pat., 096239A1, 2008.
29 (a) P. Appukkuttan, W. Dehaen and E. Van der Eycken,
Chem.–Eur. J., 2007, 13, 6452; (b) D. Tomita, K. Yamatsugu,
M. Kanai and M. Shibasaki, J. Am. Chem. Soc., 2009, 131,
6946; (c) J. W. J. Kennedy and D. G. Hall, Synlett, 2002, 477.
30 S. Lulinski, J. Serwatowski and M. Szczerbinska, Eur. J. Org.
Chem., 2008, 1797.
31 S. E. Collibee and J. Yu, Tetrahedron Lett., 2005, 46, 4453.
32 (a) K. Yao, Y. Chen, L. Chen, H. Kong, W. Zhou, F. Li, X. He
and Y. Wei, J. Polym. Sci., Part A: Polym. Chem., 2010, 48,
434; (b) E. L. Sahkulubey, Y. Y. Durmaz, A. L. Demirel and
Y. Yagci, Macromolecules, 2010, 43, 2732.
¨
22 J. I. Bruce, J.-C. Chambron, P. Kolle and J.-P. Sauvage, J.
Chem. Soc., Perkin Trans. 1, 2002, 1226.
23 G. P. Miller and I. Kaur, US Pat., 130593A1, 2011.
24 M. Vetrichelvan and S. Valiyaveettil, Chem.–Eur. J., 2005, 11,
5889.
´ ´
25 J.-F. Lemonnier, L. Guenee, C. Beuchat, T. A. Wesolowski,
P. Mukherjee, D. H. Waldeck, K. A. Gogick, S. Petoud and
C. Piguet, J. Am. Chem. Soc., 2011, 133, 16219.
26 G. T. Hwang, H. S. Son, J. K. Ku and B. H. Kim, J. Am. Chem.
Soc., 2003, 125, 11241.
33 P. Lopez-Alvarado, C. Avendano and J. Carlos Menendez,
Synth. Commun., 2002, 32, 3233.
34 S. Soundararajan, E. N. Duesler and J. H. Hageman, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 1993, 49, 690.
´
´
´
27 I. Horcas, R. Fernandez, J. M. Gomez-Rodrıguez, J. Colchero,
´
35 M. K. Cyranski, P. Klimentowska, A. Rydzewska, J. Serwatowski,
´
J. Gomez-Herrero and A. M. Baro, Rev. Sci. Instrum., 2007, 78,
´
´
A. Sporzynski and D. K. St˛epien, CrystEngComm, 2012, 14, 6282.
013705.
¨
¨
36 M. Bieri, M. T. Nguyen, O. Groning, J. Cai, M. Treier, K. Aıt-
Mansour, P. Ruffieux, C. A. Pignedoli, D. Passerone, M. Kastler,
K. Mu¨llen and R. Fassel, J. Am. Chem. Soc., 2010, 132, 16669.
28 (a) H. C. Ko, S. Kim, H. Lee and B. Moon, Adv. Funct. Mater., 2005,
15, 905; (b) F. Babudri, G. M. Farinola, F. Naso, F. Palmisano,
This journal is ß The Royal Society of Chemistry 2013
CrystEngComm, 2013, 15, 2067–2075 | 2075