Organic Chemistry

Transcription

Organic Chemistry

Content
ORG: Organic and Green Chemistry
Tittle
Authors
Paper
ID
309 SYNTHESIS AND CHARACTERIZATION OF
STAR-SHAPED PYRENYL
TRIAZATRUXENES
166 OXIDATION OF THIOL INTO DISULFIDE
USING POLYSTYRENE-SUPPORTED
(DIACETOXYIODO)BENZENE
353
330
217
201
434
273
Thanachart Techajaroonjit,
Vinich Promarak,
Paitoon Rashatasakhon
Watanya Krailat,
Preecha Phuwapraisirisan,
Tirayut Vilaivan,
Mongkol Sukwattanasinitt,
Sumrit Wacharasindhu
Weerawat Sripet,
SYNTHESIS OF HEXAPHENYLBENZENE
DERIVATIVES CONTAINING IMINE MOIETY Mongkol Sukwattanasinit,
AS FLUORESCENCE TURN-ON PROBE FOR Sumrit Wacharasindhu
THE DETECTION OF METAL IONS
SYNTHESIS OF TRUXENE DERIVATIVES
Chomchanok Wongsilarat,
WITH DIPYRENYLCARBAZOLE PENDANTS Vinich Promarak, Paitoon
Rashatasakhon
Kananat Naksomboon,
CYCLIC ALKYL SULFIDE DIETHER
Krittaphat Wongma, Phairat
DERIVATIVE AS AN ELECTRON DONOR
Phiriyawirut, Tienthong
FOR ZIEGLER-NATTA CATALYST IN
Thongpanchang
OLEFIN POLYMERIZATION
ALPHA-BROMINATION OF KETONE USING Tipakorn Sangrawee,
HEXABROMOACETONE
Warinthorn Chavasiri
Natthida Maneechandra,
FRIEDEL–CRAFTS BENZYLATION OF
TOLUENE USING NdCl3 IMPREGNATED ON Warinthorn Chavasiri
ALUMINIUM PILLARED
MONTMORILLONITE
SYNTHESIS AND CHARACTERIZATION OF Patthira Sumsalee,
Pages
239-242
243-246
247-251
252-255
256-259
260-262
263-266
267-270
Paper
ID
209
172
342
Tittle
ISOINDIGO DERIVATIVES AS MOLECULAR
DONORS FOR ORGANIC PHOTOVOLTAICS
SYNTHESIS TOWARDS N-
Authors
Visit Waewsungnoen,
Vinich Promarak
Chalupat Jindakun,
HETEROAROMATIC THENA DERIVATIVE: Thanawon Chaisantikulwat,
INVESTIGATION ON [4+2]-CYCLOADDITION Jakapun Soponpong,
Kulvadee Dolsophon,
OF HIGHLY REACTIVE PYRIDYNE
Tienthong Thongpanchang
CHEMOSELECTIVE REDUCTIONS OF
Thamonwan Angkuratipakorn,
NITROBENZENE USING
Pawinna Chanthawong,
CHITOSAN-COATED METAL AS A
Jirada Singkhonrat
CATALYST
SYNTHESIS AND CHARACTERIZATION OF Chittranuch Pengsawad,
CYANURIC ACID SUBSTITUTED 1,8Mongkol Sukwattanasinitt,
NAPHTHALIMIDES
Paitoon Rashatasakhon
Pages
271-274
275-278
279-282
239
SYNTHESIS AND CHARACTERIZATION OF STAR-SHAPED PYRENYL
TRIAZATRUXENES
Thanachart Techajaroonjit1, Vinich Promarak2, Paitoon Rashatasakhon1*
1
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
School of Chemistry and Center of Excellence for Innovation in Chemistry, Institute of Science, Suranaree University of Technology,
Muang District, Nakorn Ratchasima, 30000, Thailand
2
*
Email: paitoon.r@chula.ac.th
Abstract: Triazatruxene derivatives have received
much attention in the research field of organic lightemitting diode (OLED) due to their unique optical
properties and excellent thermal stabilities. In this
research project, we designed and synthesized two
molecules of symmetrical triazatruxene derivatives
containing 2-ethyl hexyl or benzyl groups. The
triazatruxene has been synthesized from the Br2catalyzed cyclotrimerization of indole. A sequential
debromination-bromination thus provides a tribromo
triazatruxene core with a complete regioselectivity.
Alkylation of the N-H group and Suzuki crosscoupling with pyrene-1-boronic acid give rise to the
target compounds in good yields. After the
characterization by 1H-NMR, 13C-NMR, IR, and
mass-spectrometry, their photophysical properties
are investigated by UV-Vis and fluorescent spectrophotometry.
In this paper, a series of novel star-shaped
3,8,13-substituted triindoles were reported. They
were synthesized via a bromine-catalyzed
cyclotrimerisation of indole (Figure 1). The
substitution by pyrene and alkyl groups were later
performed in order to obtained the expected
compounds.
The
characterizations
and
photophysical property investigations were also
reported.
Br
N
H
N
H
HN
1. Introduction
Br
Research on organic light-emitting diodes
(OLEDs) has been continuously developed during
the last few decades. OLED display has thus
become a theme of interest due to its advantages
such as properties for large area, flexible,
lightweight, and energy efficient optoelectronics
[1,2]. π-Conjugated materials are extensively
investigated and explored for OLEDs because of
their potential in the creation of cost-effective,
power-efficient, and flexible electronic devices [35]. Nowadays aromatic cores with a large π-orbital
area are used as hole-transporting materials. These
molecules have a strong tendency to assemble in
highly ordered organizations caused by stacking,
which paves the way for a favorable overlap of πorbitals [6-8].
Carbazole derivatives are well-known holetransporting units because of their electrondonating capabilities associated with the nitrogen
atom [9,10]. From this reason, they were used as
important building blocks for OLED materials. One
of the electron-rich carbazole derivatives, 10, 15dihydro-5H-dihydro-5H-diindolo
[3,2-a:3’,2’c]carbazole or triindole, has became a newly
famous compound. It possesses aromatic surface
with three facile points for attachment of side
chains: the three indolic NH groups in the 5-, 10and 15-positions. Triindole core was synthesized
by cyclocondensation of either indolin-2-one or
indole through halogenations [11].
NH
N
H
NH
N
H
Figure 1. Br2-catalyzed cyclotrimerisation of indole
2. Experimental
2.1 Materials
All reagents were purchased from Aldrich,
Fluka and used without further purification.
2.2 Measurements
All 1H NMR spectras were recorded on Varian
Mercury 400 MHz NMR spectrometer (Varian,
USA) using CDCl3 and acetone-d6. 13C NMR
spectras were recorded at 100 MHz on Bruker 400
MHz NMR spectrometer using the same solvent.
Mass spectra were recorded on a Microflex
(Bruker
MALDI-TOF
mass
spectrometer
Daltonics) using doublyrecrystallized α-cyano-4hydroxy cinnamic acid (CCA) as a matrix.
Absorption spectras were measured by a Shimadzu
UV-2550 UV-Vis spectrophotometer. Fluorescence
spectras were obtained from an Agilent
technologies Cary Eclipse spectrofluorometer.
Pure and Applied Chemistry International Conference 2015 (PACCON2015)
240
2.3 Synthesis
2.3.1
10,15-Dihydro-5H-dihydro-5Hdiindolo[3,2-a:3’,2’-c]carbazole (4): A mixture of
indole 3 (2 g, 17 mmol) and CH3CN (5 mL) was
stirred at room temperature and solution of Br2 (1.3
mL, 51 mmol) in CH3CN (15 mL) was added over
5 min. The mixture was stirred overnight, and the
resulting dark-green solid was filtered and washed
with acetonitrile (250 mL). At this point, without
further purification, the crude product (3 g) was
mixed with Et3N (8.4 mL, 60.46 mmol), HCOOH
(2.28 mL, 60.46 mmol) and 10% Pd/C (400 mg,
0.36 mmol) in MeOH (50 mL), and the resulting
mixture was heated for 30 min under reflux. The
mixture was filtered through Celite, and the filtrate
was diluted with CH2Cl2, washed with aqueous
HCl (10%) and dried (Na2SO4), and the solvent was
evaporated under reduced pressure to give brown
solid (2 g). The crude product was dissolved in
methanol, adsorbed onto silica gel and purified by
chromatography (ethyl acetate/n-hexane, 15:85) to
give pure 4 as a pale-yellow solid (0.16 g, 16%). 1H
NMR (400 MHz, acetone) δ 11.16 (s, 3H), 8.57 (d,
J = 7.5 Hz, 3H), 7.74 (d, J = 7.8 Hz, 3H), 7.35 (dt,
J = 22.8, 7.2 Hz, 6H).
2.3.2 3,8,13-Tribromo-10,15-dihydro-5Hdiindolo [3,2-a:3’,2’-c]carbazole (5): A solution of
N-bromosuccinimide (NBS) (0.28 g, 1.55 mmol) in
dimethylformamide (2 mL) was added dropwise to
a mixture of 4 (0.17 g, 0.5 mmol) in acetone (10
mL) at 0 °C. The mixture was slowly warmed to
room temperature and stirred for an additional 30
min before it was poured into water. Then, the
organic phase was separated and dried over
anhydrous Na2SO4. After the solvent was
evaporated, the crude product was purified by
column chromatography using hexane/acetone
(8:2) as the eluent to afford 5 as a pale white solid
(0.22 g, 76%). 1H NMR (400 MHz, acetone) δ
11.34 (s, 3H), 8.39 (d, J = 8.3 Hz, 3H), 7.85 (s,
3H), 7.45 (d, J = 6.8 Hz, 3H).
2.3.3 5,10,15-Triethylhexyl-10,15-dihydro-5Hdiindolo[3,2-a:3’,2’-c]carbazole (6): A mixture of 5
(0.15 g, 0.25 mmol) and KOH (0.28 g, 5 mmol)
was stirred at room temperature, then a solution of
ethylhexylbromide (0.27 mL, 1.5 mmol) was added
slowly, the mixture was stirred overnight. The
mixture was poured into water and extracted with
EtOAc. The combined organic layer was dried over
anhydrous Na2SO4, filtered, and concentrated under
reduce pressure., the crude product was purified by
chromatography (EtOAc:n-hexane, 5:95) to give
the compound 6 as a yellow solid (0.22 g, 95%). 1H
NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.5 Hz,
3H), 7.52 (s, 3H), 7.46 (d, J = 8.6 Hz, 3H), 4.40 (s,
6H), 1.79 (s, 3H), 1.10 – 0.44 (m, 42H).
2.3.4.
5,10,15-Tribenzyl-10,15-dihydro-5Hdiindolo[3,2-a:3’,2’-c]carbazole (7): A mixture of 5
(0.15 g, 0.25 mmol), KOH (0.28 g, 5 mmol), and
[CH3(CH2)3]4N(HSO4) (0.0083 g, 0.025 mmol) was
heated to reflux in acetone (10 mL). Benzyl
bromide (0.2 mL, 1.68 mmol) was then added and
the mixture was stirred for 3 h. The mixture was
diluted with CH2Cl2, washed with 10% aqueous
HCl and with saturated aqueous NaCl solution, and
dried (Na2SO4), the solvent was then evaporated.
The residue was triturated with hexanes to give 7 as
a white solid (0.21 g, 98%). 1H NMR (400 MHz,
CDCl3) δ 8.12 (s, 3H), 7.89 (d, J = 7.0 Hz, 3H),
7.74 (d, J = 8.5 Hz, 3H), 7.47 (m, 9H), 7.10 (d, J =
7.2 Hz, 6H), 5.96 (s, 6H).
2.3.5 5,10,15-Triethylhexyl-3,8,13-tri(pyren-1yl)-10,15-dihydro-5H-diindolo[3,2-a:3',2'c]carbazole (1): To a degassed (N2) solution of 6
(0.09 g, 0.1 mmol) and Pd(PPh3)4 catalyst (0.012 g,
0.01 mmol) in toluene (5 mL), then pyreneboronic
acid (0.1476 g, 0.6 mmol) and 2 M aqueous K2CO3
solution (1 mL) were added via syringe. The
reaction mixture was stirred at 70 oC for 48 h. After
cooling, the product was extracted with CH2Cl2,
washed with water, and dried over anhydrous
Na2SO4. The solvent was evaporated, affording the
crude mixture. The crude product was purified by
column chromatography (CH2Cl2:n-hexane, 1:9) to
give the compound 1 as a yellow solid (83.1 mg,
65%). 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J =
9.2 Hz, 3H), 8.35 – 7.88 (m, 30H), 7.67 (s, 3H),
5.09 (s, 6H), 2.28 (d, J = 12.1 Hz, 3H), 1.70 (s,
6H), 1.41 (s, 3H), 1.2 – 0.55 (m, 39H). 13C NMR
(100 MHz, CDCl3) δ 150.2, 141.6, 136.5, 131.8,
131.31, 131.25, 130.6, 129.8, 129.1, 129.0, 128.3,
127.7, 127.6, 127.5, 126.5, 126.2, 126.0, 125.34,
125.25, 124.9, 124.8, 122.7, 122.2, 113.8, 51.1,
38.6, 34.5, 33.9, 28.5, 23.3, 14.0, 10.6. MALDITOF MS (m/z): calcd: (1282.693 [C96H87N3]);
found: (1281.797 [M+]).
2.3.6 5,10,15-Tribenzyl-3,8,13-tri(pyren-1-yl)10,15-dihydro-5H-diindolo[3,2-a:3',2'-c]carbazole
(2): To a degassed (N2) solution of 7 (85.2 mg, 0.1
mmol) and Pd(PPh3)4 catalyst (11.6 mg, 0.01
mmol) in toluene (5 mL), then pyreneboronic acid
(14.8 mg, 0.6 mmol) and 2 M aqueous K2CO3
solution (1 mL) were added via syringe. The
reaction mixture was stirred at 70 oC for 48 h. After
cooling, the product was extracted with CH2Cl2,
washed with water, and dried over anhydrous
Na2SO4. The solvent was evaporated, affording the
crude mixture. The crude product was purified by
column chromatography (CH2Cl2:n-hexane, 2:8) to
give the compound 2 as a yellow solid (0.06 g,
49%). 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J =
7.9 Hz, 3H), 7.90 (m, 30H), 7.70 (d, J = 9.2 Hz,
3H), 7.47 (s, 3H), 7.38 (d, J = 6.6 Hz, 6H), 7.28 (d,
J = 7.2 Hz, 6H), 6.04 (s, 6H). 13C NMR (100 MHz,
CDCl3) δ 141.8, 140.3, 138.2, 138.1, 136.4, 131.6,
131.1, 130.4, 129.3, 128.6, 128.1, 127.7, 127.5,
127.4, 127.3, 126.8, 126.0, 125.5, 125.02, 124.98,
124.7, 124.6, 123.4, 122.5, 121.7, 113.2, 103.5,
51.5. MALDI-TOF MS (m/z): calcd: (1216.459
[C93H57N3]); found: (1215.485 [M+]).
241
3.2 Photophysical properties of compound 1 and 2
The investigation of absorption properties of 1 and
2 in CHCl3 revealed a similar absorption
wavelength and molar extinction coefficient (Table
1 and Figure 2). However, the emission spectra of
compound 1 appeared at a slightly longer
wavelength with higher quantum efficiency than 2.
This might attribute to the steric hindrance of the
three 2-ethylhexyl groups that enhances the
solubility of the compound in organic solvents and
prevents aggregation-caused fluorescent quenching.
3. Results and Discussion
3.1 Synthesis of 1 and 2 (Scheme 1)
Our synthesis of triazatruxene relied on the
cyclotrimerization of indole, which was catalyzed
by Br2. The formation of dimer and several
oligomers of indole could be the main cause for the
poor efficiency of this reaction. Upon the reductive
de-bromination using trimethylammonium formate,
the regioselective tribromination using NBS
provide tribromoazatruxene 5 in 76%. The
following alkylation of the N-H group gave rise to
6 and 7. Finally, the Suzuki cross-coupling pyrene1-boronic acid afforded target compounds 1 and 2
in good yields.
Table 1: Photophysical properties of 1 and 2
Cpd.
1
Absorption
λmax
log ε
(M-1cm-1)
(nm)
344
4.52
Emission
λmax
ΦFa
(nm)
483
0.52
2
351
472
HN
1) Br2, MeCN, RT, 1d
N
H
N
H
2) Et3N, HCOOH, Pd/C,
MeOH, reflux, 30min
3
NH
quinine sulfate in 0.1 M H2SO4 (ΦF = 0.54) was
used as the standard.
acetone,
RT, 30 min
NBS, DMF
R
Br
N
0.61
a
4
Br
4.88
HN
Br
Br
a or b
N
R
N
H
N R
Br
Br
6 or 7
B(OH)2
NH
5
Pd(PPh3)4
K2CO3, toluene,
70 oC, 2d
Figure 2. Normalized absorption and emission
spectra of 1 and 2 in CHCl3
4. Conclusions
R
N
N
R
N R
R1 =
1
R2 =
In this research, two new symmetrical pyrenyl
triazatruxene derivatives were successfully
synthesized via Br2-catalyzed cyclotrimerization of
indole and Suzuki cross-coupling with pyrene-1boronic acid in good yields. The substitution of the
-NH position by 2-ethylhexyl and benzyl groups
could prevent the aggregation by pi-stacking. These
compounds were well soluble in organic solvents
and exhibited high quantum efficiencies.
Acknowledgements
2
Scheme 1. Synthesis of 1 and 2: Reagent and
conditions: (a) 2-ethyl hexylbromide, KOH,
DMSO, RT, overnight; (b) benzyl bromide, KOH,
Bu4N∙HSO4, acetone, reflux, 3h.
This work was financially supported by the Faculty
of Science, Chulalongkorn University. The
instruments were partly sponsored by the National
Research University Project of Thailand, Office of
the Higher Education Commission (AM1006A)
242
and the Thai Government Stimulus Package 2
(TKK2555, SP2).
References
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Rev., 110, 1, 479-526.
[2] Forrest, S. R. and Thompson, M.E., 2007.
Chem. Rev., 107, 4, 923-925.
[3] Gustafsson, G., Cao, Y., Treacy, G.M.,
Klavetter, F., Colaneri, N., and Heeger, A. J.,
1992, Nature, 357, 477-479.
[4] Martin, R.E. and Diederich, F., 1999, Angew.
Chem. Int. Ed., 38, 10, 1350-1377.
[5] Kraft, A., Grimsdale, A.C., and Holmes, A.B.,
1998, Angew. Chem. Int. Ed., 37, 4, 402-428.
[6] Zang, L., Che, Y., and Moore, J.S., 2008. Acc.
Chem. Res., 41, 12, 1596-1608.
[7] Schenning, A.P.H. J. and Meijer, E.W., 2005,
Chem. Comm., 26, 3245-3258.
[8] Wu, J., Pisula, W., and Muellen, K., 2007. Chem.
Rev., 107, 3, 718-747.
Zhang, Y., Wada, T., and Sasabe, H., 1998. J.
Mater. Chem., 8, 809-828.
[10] Grazulevicius, J.V., Strohriegl, P., Pielichowski, J.,
and Pielichowski, K., 2003, Prog. Polym. Sci., 28,
9, 1297-1353.
[11] Franceschin, M., Ginnari-Satriani, L., Alvino, A.,
Ortaggi, G., and Bianco, A., 2010, Eur. J. Org.
Chem., 1, 134-141.
[9]
243
OXIDATION OF THIOL INTO DISULFIDE USING POLYSTYRENESUPPORTED (DIACETOXYIODO)BENZENE
Watanya Krailat1, Preecha Phuwapraisirisan2, Tirayut Vilaivan2, Mongkol Sukwattanasinitt3
and Sumrit Wacharasindhu3*
1
Program of Petrochemistry and Polymer Science, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
2
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
3
Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science, Chulalongkorn
University, Bangkok, 10330, Thailand
*
E-mail: sumrit.w@chula.ac.th, Tel: +66-2218-7634, Fax : +66-2218-7598
Abstract: Disulfides are important compounds in
biological and chemical processes which can be prepared
by the oxidation of thiols. For this work, we have
developed a new preparative method for the disulfide
using inexpensive, recyclable, and relatively non-toxic
polymer-supported (diacetoxyiodo)benzene (PS-DIB) as
the oxidant under mild conditions. PS-DIB, a yellow
powder, was prepared from iodination of commercially
available polystyrene (MW=35,000) followed by oxidation
with either NaBO3.4H2O or Ac2O/H2O2 in 43% and 70%
yields, respectively. The structure of the prepared PS-DIB
was confirmed by FTIR, which exhibited two strong
bands at 1639 and 1712 cm-1 corresponding to the
carbonyl group. The loading of the (diacetoxyiodo)phenyl
group on polystyrene was determined by iodometric
titration and calculated to be 1.39 mmol/g. The reaction
conditions were optimized for solvent, time and
equivalent of PS-DIB using 4-chlorothiophenol as
substrate and the yields were determined using HPLC.
We discovered that, under the optimized condition (iPrOH as solvent, 1 equivalent of PS-DIB, open air, 1 h,
room temperature) for 4-chlorothiophenol, the
corresponding disulfide product was obtained in 79%
yield following chromatography. This methodology could
be extended to a variety of thiols, giving the
corresponding disulfides in good yields.
1. Introduction
Disulfides are important compounds that are widely
used in both biological and chemical processes. They
were used as reagents to stabilize polypeptide
secondary structure in peptide and protein synthesis.[1]
Moreover, disulfides are important reagents for
vulcanization in rubbers and elastomers.[2] Typical
synthesis of disulfides involves the conversion of the
corresponding thiols via the use of strong oxidizing
agent or metal catalyst such as cerium(IV)salts,
transition metal oxides,[3] H2O2,[4] 2,6-dicarboxy
pyridinium chlorochromate,[5] halogens[6] and
heterogeneous permanganate.[7] Those reagents are not
only toxic but also expensive in some cases.[8]
Therefore, the development of thiol oxidation under
mild and environmental friendly condition remain a
challenging. Recently, hypervalent iodine reagents
were introduced to organic synthesis as oxidizing
agents due to their low cost, mild and highly selective
oxidizing properties, environmental friendly character
and commercial availability.[9] We recently reported
the
use
of
a
hypervalent
iodine,
diacetoxyiodo(benzene) for oxidation of thiols into
disulfide in good yields.[2] Even though the reaction
condition is mild and may be carried out in open flask
condition, the difficulty to remove the iodobenzene byproduct from the desired disulfide makes the reuse of
the diacetoxyiodo(benzene) reagent cumbersome. To
overcome this problem, the hypervalent iodine is
bound onto a polymeric support. The desired product
can be obtained by simple filtration and the polymersupporting reagent could be regenerated and recycled.
Therefore, in this work we reported the synthesis of
polystyrene-supported diacetoxyiodo(benzene) (PSDIB) and its use as an oxidizing agent for a variety of
thiols into disulfides.
2. Materials and Methods
2.1. Materials
All starting materials were obtained from SigmaAldrich, Fluka (Switzerland) or Merck (Germany) and
used without further purification. Analytical thin-layer
chromatography (TLC) was performed on Kieselgel F254 pre-coated plastic TLC plates from EM Science.
Visualization was performed with a 254 nm ultraviolet
lamp. Gel column chromatography was carried out
with silica gel (60, 230-400 mesh) from ICN Silitech.
The 1H and 13C NMR spectra were recorded on a
Varian 400 or Bruker 400 in CDCl3.
2.2 Synthesis
2.1 Synthesis of poly (4-iodostyrene) (PS-I)
To a mixture of nitrobenzene (50 mL), CCl4 (10 mL),
H2SO4 (50%, 9 mL) were added polystyrene (4 g,
38.25 mmol), I2 (4.5 g, (17.75 mmol), and I2O5 (1.79 g,
5.36 mmol) at 90 °C and the reaction was stirred at that
temperature for 72 h. After the reaction was complete,
MeOH 400 mL was added into the reaction mixture
and the precipitate was collected by filtration and
washed with MeOH and dried.
244
2.2 Synthesis of polystyrene-supported
(diacetoxyiodo)benzene (PS-DIB)
Method A [9] A solution of poly (4-iodostyrene) (5.2
g), AcOH (113 mL), DCE (7 mL), and TfOH (135.66
mmol) was stirred at 40°C. Then, NaBO3.4H2O (135.7
mmol) was added slowly within 2 h. After evaporation
of DCE and AcOH, H2O 40 mL was added into the
reaction. The precipitate was filtered, washed with
MeOH and dried.
Method B [10] A solution of 30% H2O2 (27 mL,
895.01 mmol) was added dropwise into Ac2O (97 mL,
1030.91 mmol) and stirred at 40 °C for 4 h. Then,
poly(4-iodostyrene) (5.2 g) was added into the reaction
mixture and stirred overnight. Et2O 100 mL was then
added into the reaction. The precipitate was filtrated,
washed with MeOH and dried under vacuum.
2.3 Iodometric titration
The loading of the reagent was determined by
iodometric titration. A mixture of PS-DIB (0.031 g), KI
(0.250 g), deionized water (12.5 mL), H2SO4 (6 N, 1.25
mL), and CHCl3 (1.25 mL) were added in 50-mL flask
and stirred for 4 h. The reaction mixture was titrated
with 0.1 N sodium thiosulfate using starch solution as
indicator.
white solid: 1H NMR (CDCl3, 400 MHz) δ 8.40 (d, J =
8.1 Hz, 2H), 7.60-7.49 (m, 4H), 7.04 (m, 2H); 13C
NMR (CDCl3, 100 MHz) δ 159.0, 159.0, 149.6, 149.6,
137.4,137.4, 121.1, 121.1, 119.7, 119.7; IR (neat, cm-1)
3168, 3098, 1604, 1570, 1487, 1438; IR (neat, cm-1)
3046, 2987, 1574, 1556, 1444, 1414; LRMS (ESI)
calcd for C10H9N2S2, 221.01; found, 221.01.
3.1 Synthesis and characterization of polymersupported (diacetoxyiodo)benzene PS-DIB
To prepare PS-DIB, the commercially available
polystyrene (MW=35,000) was iodinated by I2/I2O5 in
the mixture of CCl4/nitrobenzene solution under acidic
condition as presented in Scheme 1. This resulted in
the formation of iodo-polystyrene (PS-I) as yellowish
green solid (Figure 1 (middle)). Then, the desired PSDIB was obtained by oxidation with either the use of
Ac2O/H2O2 or NaBO3.H2O as shown in Scheme 1.
After the reaction, the precipitate was collected by
filtration, washed with MeOH, and dried under
vacuum. Both oxidation procedures gave yellow
powder of PS-DIB as shown in Figure 1 (right).
A
2.4 Synthesis of disulfides (1-3) using PS-DIB
1,2-Bis(4-chlorophenyl)disulfane
(1):
4Chlorothiophenol (50.0 mg, 0.346 mmol) and PS-DIB
(249 mg, 0.346 mmol) were mixed in i-PrOH (5 mL) in
a round-bottomed flask with a magnetic stir bar and
stirred for 60 min. The solvent was removed by rotary
evaporation and the crude product was purified by
silica gel chromatography (100% hexane) to afford 1,2bis(4-chlorophenyl)disulfane (39 mg, 0.173 mmol,
79%) as a yellow solid; 1H NMR (CDCl3, 400 Hz) δ
7.40 (d, J = 8.7 Hz, 4H, Ar-H), 7.27 (d, J = 8.7 Hz, 4H,
Ar-H); 13C NMR (CDCl3, 100 Hz) δ 135.2, 133.7,
129.4, 129.3; IR (neat, cm-1) 3079, 2925, 1470, 1385.
6,6’-Disulfanediyldihexan-1-ol (2): 6-Mercapto-1hexanol (50.76 µL, 0.372 mmol) and PS-DIB (669 mg,
0.930 mmol) were mixed in i-PrOH (5 mL) in a roundbottomed flask with a magnetic stir bar and stirred for
60 min. The solvent was removed by rotary
evaporation and the crude product was purified by
silica gel chromatography (80% EtOAC/hexane) to
afford 6,6’-disulfanediyldihexan-1-ol (51 mg, 0.186
mmol, quantitative) as a yellow solid; 1H NMR
(CDCl3, 400 Hz) δ 3.58 (t, J = 6.5 Hz, 4H, CH2-OH),
2.62 (t, J = 8.0 Hz, 4H, CH2-S), 1.62 (m, 4H, -CH2-),
1.51 (m, 4H, -CH2-), 1.34 (m, 8H, -CH2-); 13CNMR
(CDCl3, 100 Hz) δ 62.8, 62.8, 39.1, 39.1, 32.6, 32.6,
29.1, 29.1, 28.2, 28.2, 25.4, 25.4; IR (neat, cm-1) 3346,
2934, 2859, 1465, 1053
2,2’-Dithiodipyridine (3): 2-Mercaptopyridine (50.0
mg, 0.450 mmol) and PS-DIB (324 mg, 0.450 mmol)
were mixed in i-PrOH (5 mL) in a round-bottomed
flask with a magnetic stir bar and stirred for 60 min.
The solvent was removed by rotary evaporation and the
crude product was purified by silica gel
chromatography (30% EtOAC/hexane) to afford of
2,2’-dithiodipyridine (37.2 mg 0.225 mmol, 75%) as a
Ac2O/30%H2O2
40oC, 4 h
I2, I2O5, CCl4
50% H2SO4, nitrobenzene
90 oC, 72 h
I
PS-I
NaBO3.H2O/TfOH/AcOH/DCE
AcO I OAc
40oC, 4 h
PS-DIB
B
Scheme 1. Synthesis of PS-DIB from method A and B
PS
PS-I
PS-DIB
Figure 1. Color and appearance of PS (left), PS-I
(middle) and PS-DIB (right)
The structure of PS-DIB was confirmed by FTIR
spectroscopy by comparision with unmodified
polystyrene (PS) and iodopolystyrene (PS-I) as shown
in Figure 2. The PS-I showed the reduction of C-H
(aromatic) streching peak at 3017 cm-1. These results
suggested the succesful iodination of the benzene ring
in polystyrene. Moreover, the structure of polystyrenesupported (diacetoxyiodo) benzene (PS-DIB) was
confirmed by the existence of peaks at 1639 and 1712
cm-1 which can be assigned as C=O streching in the
diacetoxy moiety.
245
PS
3.3 Utilization of PS-DIB for oxidization of thiols
PS-I
3.3.1 Optimization study
PS-DIB
Figure 2. Overlay of FT-IR spectra of PS, PS-I and PSDIB
3.2 Determination of the loading of functional group
of PS-DIB
+ K2SO4 + I2 +2HOAc
+ 2KI + H2SO4
AcO
I
I
OAc
2NaI + Na2S4O6
2Na2S2O3 + I2
Scheme 2. Iodometric titration
Table 1: The loading of functional group
Loading of diacetoxyiodo group
Washed
(mmol) in PS-DIB
time
Method A
Method B
2.13
1.87
1st
nd
2
2.28
1.61
3rd
2.36
1.19
4th
1.90
1.19
5th
1.41
1.19
The loading of the diacetoxyiodo group on
polystyrene was determined by iodometric titration and
the reaction equation was presented in Scheme 2. PSDIB and KI were dissolved in a solution of chloroform
and sulfuric acid to produce I2 via oxidation reaction.
Then, it was titrated with sodium thiosulfate with
starch solution as the indicator. The results from both
PS-DIB from method A and method B were depicted in
Table 1. In order to remove the excess reagents from
the prepared PS-DIB and to test the stability of the
diacetoxyiodo group bounded to the polymer, we
washed the PS-DIB for 5 times and the loading after
each washing was evaluated as shown in Table1. We
found that the amount of the loading of the
(diacetoxyiodo)phenyl group on the polystyrene
prepared from Method A decreased continually after
washing with MeOH while the PS-DIB obtained from
Method B remained constant after the third wash. In
Method A, the oxidation with Ac2O and H2O2 may not
be very efficient. The high loading observed before the
methanol rinse is perhaps due to the remaining
unreacted H2O2, which decreased eventually after the
washing. Based on this discovery, the oxidation with
NaBO3.H2O (Method B) was used as a standard
method for the preparation of PS-DIB throughout this
work.
Next, we investigated the PS-DIB reactivity for the
conversion of 4-chlorothiophenol (1) into 1,2-bis(4chlorophenyl)disulfane (1a). During the optimization,
the amount of PS-DIB and reaction time were varied
and the results were summarized in Table 2. When the
reaction was carried out in the presence of 0.7
equivalent of PS-DIB for 60 min, 72% yield of the
disulfide was obtained (Table 2, entry 1). Increasing
the amount of PS-DIB from 0.7 to 1.1 quivalent
resulted in the formation of the desired disulfide in
77% yield (Table 2, entry 2). However, if we
conducted the reaction only for 5 minute, the reaction
efficiency decreased (Table 2, entry 3). Therefore, the
utilization of 1.1 equivalent of PS-DIB for 60 minute
was considered as the optimized condition for
oxidization of thiols.
Table 2: Oxidation of 4-chlorothiophenol with PS-DIB
Entry
1
2
3
SH
Time
(min)
60
60
5
PS-DIB
Equivalent
0.7
1.1
1.1
Cl
PS-DIB
S
i -PrOH, rt
Cl
% yield
(HPLC)
72
77
67
(1)
Cl
S
(1a)
3.3.2 Substrate scope
With the optimized condition in hand, we next
explored the scope of PS-DIB oxidization. A variety of
thiols containing alkyl or heterocyclic substituent were
subjected to the optimized condition and the results
were shown in Table 3. 6-Mercapto-1-hexanol (2) was
treated with PS-DIB in i-PrOH and the corresponding
disulfide (2a) was generated in quantitative yield after
column chromatography (Table 3, entry1). For
heterocyclic substrate, 2-mercaptopyridine (3) was
oxidize into the corresponding disulfide (3a) in 75%
yield.
246
Table 3: Synthesis of disulfides from thiols
References
[1]
PS-DIB (1.1 eq.)
R-SH
(1-3)
i-PrOH, rt, 60 min
R-S-S-R
(1a-3a)
R= Alkyl, Aromatic, Heterocyclic
%Yielda
Thiols
Entry
SH
79
1
Cl
2b
HO
3
a
b
(1)
SH
(2)
Quantitative
75
N
SH
(3)
Thurow, S., Pereira, V.A., Martinez, D.M., Alves, D.,
Perin, G., Jacob, R.G. and Lenardão, E.J., 2011,
Tetrahedron Lett., 52, 640-643.
[2] Zhdankin, V. Z., 2009. ARKIVOC, (i), 1-62.
[3] Akdag, A., Webb, T. and Worley, S. D., 2006.
Tetrahedron Lett., 47, 3509–3510.
[4] He, Y., Hang, D. and Lu, M., 2012. Phosphorus Sulfur
Silicon Relat. Elem., 187, 9, 1118-1124.
[5] Tajbakhsh, M., Hosseinzadeh, R. and Shakoori, A.,
2004, Tetrahedron Lett., 45, 1889-1893.
[6] Hashmat Ali, M., McDermott, M., 2002, Tetrahedron
Lett., 43, 6271–6273.
[7] Walters, M. A., Chaparro, J., Siddiqui, T., Williams, F.,
Ulku, C. and Rheingold, A.L., 2006, Inorg. Chim.
Acta., 359, 3996–4000.
[8] Attri, P., Gupta, S. and Kumar, R., Green Chem. Lett.
Rev. 2012, 33-42.
[9] Chen, F.-E., Xie, B., Zhang, P., Zhao, J.-F., Wang, H.
and Zhao, L., 2007, Synlett, 4, 619-622.
[10] Hossain, M. D., Kitamura, T., 2006, Synthesis, 8, 12531256.
isolated yield
2.5 eq. PS-DIB were used.
4. Conclusions
We successfully synthesized polystyrene-supported
diacetoxyiodo(benzene) from commercially available
polystyrene in good yield with high loading of
(diacetoxyiodo)phenyl group. The polymer-supported
reagent was able to oxidize a variety of thiols into the
corresponding disulfides in good to excellent yields.
The reaction is not only efficient but also proceeds
smoothly under mild conditions in open flasks using
relatively less toxic i-PrOH solvent.
Acknowledgements
This work is financially supported by the Thailand
Research Fund (RSA5780055) and Nanotechnology
Center (NANOTEC), NSTDA, Ministry of Science and
Technology, Thailand, through its program of Center
of Excellence Network. This work is part of the Project
for Establishment of Comprehensive Center for
Innovative Food, Health Products and Agri-culture
supported by the Thai Government Stimulus Package 2
(TKK2555, SP2), the Higher Education Research
Promotion and National Research University Project of
Thailand, Office of the Higher Education Commission
(AM1006A-56),
the
Ratchadaphiseksomphot
Endowment Fund of Chulalongkorn University
(RES560530126-AM) and the 90th anniversary of
Chulalongkorn
University
Fund
(Ratchadaphiseksomphot Endowment Fund).
247
SYNTHESIS OF HEXAPHENYLBENZENE DERIVATIVES CONTAINING
IMINE MOIETY AS FLUORESCENCE TURN-ON PROBE FOR THE
DETECTION OF METAL IONS
Weerawat Sripet, Mongkol Sukwattanasinit, Sumrit Wacharasindhu*
Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science,
Chulalongkorn University, Bangkok 10330, Thailand
E-mail: sumrit.w@chula.ac.th, Tel. +662 2187634, Fax. +66 22187598
Abstract: Currently, the design and synthesis of new
fluorescent chemosensors for the efficient detection of
metal ions is one of the most important research topics in
environmental chemistry and biology. In this work, we
select hexaphenylbenzene (HPB) as a fluorophore and
imine moiety as a receptor for metal ions. The HPB
containing salicylaldehyde group (HPB-SW1) is
successfully obtained via Diels-Alder reaction between 2hydroxy-5(phenylethynyl)benzaldehyde
and
tetraphenylcyclopentadienone in 51% yield. The target
fluorophores [HPB-SW (2-4)] are received from
condensation of HPB-SW1 with the corresponding
amines such as 2-aminophenol, n-propylamine and
ethanolamine in 74-89% yields. These compounds are
characterized by 1H-NMR, 13C-NMR and HRMS. The
addition of Al3+ to sensor HPB-SW2 induces strong blue
fluorescence emission while the HPB-SW3 and 4 show
selective turn-on fluorescence toward Zn2+ ion.The
detection limit of HPB-SW4 is calculated to be 10.46 ppb
for Zn2+ which is lower than drinking water permission
concentration by world health organization (WHO).
1. Introduction
The development of fluorescent chemosensor
for metal ions has received considerable attention [1]
due to their biological and environment important
roles. Among various metal ions, zinc ion (Zn2+) has
attracted a great deal of attention ascribing to its
biological significance. Zinc ion plays significant role
in various fundamental biological processes, such as
gene transcription and DNA binding or recognition.
Also, excessive amount of zinc in human cause many
severe diseases such as Alzheimer’s disease,
Friedreich’s ataxia and Parkinson’s disease [2]. On the
other hand, aluminium is widely used in many
applications such as textile industry, medicines, paper
industry and food additive. An excess amount of
aluminium in human body not only damages the
central nervous system but also causes various
diseases such as Alzheimer’s, Parkinson’s and breast
cancer [2]. The traditional analytical methods, such as
atomic absorption spectroscopy, inductively coupled
plasma mass spectroscopy and electrochemical
analysis, have been reported for the trace-quantity
determination of metal ions. But, most of those
methods are expensive and time-consuming in
practice. In comparison, fluorescence spectroscopy is
widely used because of its high sensitivity and ability
to perform on-site analysis making fluorescence
approach superior to other analytical methods.
Therefore, it is of great importance to develop highly
specific fluorescence turn-on probe for the detection of
Zn2+ and Al3+ in aqueous media. Most reported
flurophores, however, exhibit aggregation causing
quenching (ACQ) phenomenon leading to low
quantum efficiency in solid state or at high water
content [3]. Until recently, there are reports on antiACQ
flurophore
molecules
such
as
tetraphenylethylene,
hexaphenylsilole
and
hexaphenylbenzene showing aggregation induced
emission effect [4]. These allow such flurophores to
perform the detection of metal ions in solid state or
aqueous solution. Herein we report the preparation of
novel
fluorescent
chemosensors
based
on
hexaphenylbenzene derivatives HPB-SW (2-4). These
compounds were attached with different imine
moieties as metal ion receptor as shown in Figure 1.
HPB-SW2 and HPB-SW4 demonstrate the specific
and sensitive fluorescence turn-on properties with Al3+
and Zn2+ ions, respectively
OH
N
OH
HPB-SW2
N
N
OH
OH
OH
HPB-SW3
HPB-SW4
Figure1. Structures of HPB-SW2, HPB-SW3 and
HPB-SW4
2.1 Instrument and reagents
All reagents were purchased from SigmaAldrich, Fluka® (Switzerland) or Merck® (Germany)
and used without further purification. Analytical thinlayer chromatography (TLC) was performed on
Kieselgel F-254 pre-coated plastic TLC plates from
EM Science. Visualization was performed with a 254
nm ultraviolet lamp. Column chromatography was
carried out with silica gel (60, 230-400 mesh) from
ICN Silitech. The 1H and 13C NMR spectra were
obtained on a Varian Mercury NMR spectrometer,
which operated at 400 MHz for 1H and 100 MHz for
13C nuclei (Varian Company, CA, USA). Mass
spectra were recorded on a Microflex MALDI-TOF
248
mass spectrometer (Bruker Daltonics) using doubly
recrystallized α-cyano-4-hydroxy cinnamic acid
(CCA) and dithranol as a matrix. Absorption spectra
were measured by a Varian Cary 50 UV-Vis
spectrophotometer. Fluorescence spectra were
obtained
from
a
Varian
Cary
Eclipse
spectrofluorometer.
2.2 Synthesis
Synthesis of 5-iodosalicylaldehyde (1)
Salicylaldehyde (0.870 mL, 8.189 mmol) was
dissolved in dichloromethane, and followed by
addition of iodine monochloride (0.692 mL, 13.228
mmol) at 0 oC to room temperature. The reaction
mixture was left overnight. After the reaction was
completed, the reaction mixture was extracted with
CH2Cl2 and the organic solution was washed with
Na2S2O3, respectively. The organic layer was dried
over anhydrous magnesium sulfate and solvent was
removed by evaporator then recrystallized from hot
hexane temperature to afford the white solid
compound 1 ( 65%). 1H NMR (400 MHz, CDCl3) δ
10.95 (s, 1H), 9.83 (s, 1H), 7.85 (s, 1H), 7.77 (d, J =
8.5 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H). 13C NMR
(101MHz, CDCl3) δ ppm 195.3, 161.3, 145.5, 142.0,
122.7, 120.1, 80.4 .
Synthesis of 2-hydroxy-5-(phenylethynyl)benzaldehyde (2)
5-Iodosalicylaldehyde (1.80 g, 7.258 mmol)
was mixed with Pd(PPh3)2Cl2 (0.457g, 0.653 mmol),
CuI (0.124 g, 0.653mmol) and PPh3 (0.085 g, 0.326
mmol) in round bottom flask under N2 atmosphere.
After that, THF and TEA were added and kept stirred
for 15 min. Then, phenylacetylene (2.38 mL, 21.77
mmol) was gradually added. The mixture was left
overnight. The rotary evaporator was used to evaporate
solvent from the mixture. The residue was purified by
column chromatography on silica gel (10% EtOAc in
hexane) to give compound 2 (79% yield). 1H NMR
(400 MHz, DMSO) δ (ppm) 11.17 (s, 1H), 10.25 (s,
1H), 7.78 (s, 1H), 7.65 (d, J = 8.5 Hz, 1H), 7.58 – 7.47
(m, 2H), 7.47 – 7.34 (m, 3H), 7.04 (d, J = 8.5 Hz, 1H).
13
C NMR (101 MHz, CDCl3) δ (ppm) 196.5, 162.8,
161.9, 140.3, 137.3, 132.0, 128.9, 123.4, 120.8, 118.3,
115.7, 89.7, 87.6.
Synthesis of compound HPB-SW1
A solution of compound 2 (0.300 g, 1.34
mmol) and tetraphenylcyclopenta-2,4-dienone (0.468 g
0.218mmol) in 3 mL of diphenylether was refluxed for
overnight under nitrogen atmosphere. The dark-brown
mixture was diluted with dichloromethane (2 mL),
poured in methanol (50 mL) and stirred; the off white
precipitate was filtered and recrystallized from
methanol to afford compound HPB-SW1 (51% yield).
1
H NMR (400 MHz, DMSO) δ (ppm) 10.29 (s, 1H),
9.89 (s, 1H), 7.09 (d, J = 1.8 Hz, 1H), 7.00 (d, J = 8.5
Hz, 1H), 6.95 – 6.72 (m, 25H), 6.45 (d, J = 8.5 Hz,
1H). 13C NMR (101 MHz, DMSO) δ (ppm) 191.13,
157.9, 140.1, 140.1, 139.9, 139.9, 138.7, 138.5, 131.6,
131.4, 130.8, 130.8, 130.7, 126.6, 126.4, 125.3, 125.2,
120.5, 115.5, 47.2.
General procedure for the synthesis of HPB-SW (24)
A clear solution of compound HPB-SW1 and
amine compounds in dry THF: EtOH (2:3) was stirred
at 65 °C. After 24 hrs, the reaction mixture turned
turbid. The reaction mixture was concentrated under
the reduced pressure and dry ethanol was poured into
it, solid appeared. The solid was filtered and
recrystallized from methanol to afford the compound
HPB-SW (2-4)
The compound HPB-SW1 (0.100 g, 0.173
mmol) reacted with 2-aminophenol (0.0283 g, 0.260
mmol) to afford the light yellow solid compound
HPB-SW2 (74% yield); 1H NMR (400 MHz, CDCl3)
δ (ppm) 8.20 (s, 1H), 7.17 (m, 1H), 6.99 (d, J = 7.4
Hz, 2H), 6.86 (d, J = 15.0 Hz, 26H), 6.67 (d, J = 7.5
Hz, 1H), 6.55 (d, J = 8.3 Hz, 1H), 6.31 (d, J = 7.6 Hz,
1H). 13C NMR (101MHz, DMSO) δ (ppm) 161.3,
158.1, 150.9, 140.3, 140.1, 140.0, 140.0, 139.0, 135.4,
134.8, 134.6, 130.9, 130.8, 130.7, 127.9, 126.6, 126.5,
126.4, 125.3, 125.2, 119.5, 119.4, 117.8, 116.5, 115.5,
114.9. HRMS (ESI); m/z calcd for C49H35NO2 + H+:
670.2668 [M+H+]: found, 670.2740.
The
compound
HPB-SW1
(0.150g,
0.259mmol) reacted with propan-1-amine (0.023g,
0.388mmol) to afford the light yellow solid compound
HPB-SW3 (88% yield); 1H NMR (400 MHz, CDCl3)
δ (ppm) 7.78 (s, 1H), 6.76 (s, 26H), 6.66 (d, J = 8.6
Hz, 1H), 6.54 (s, 1H), 6.36 (d, J = 8.0 Hz, 1H), 3.33
(d, J = 5.8 Hz, 1H), 1.13 (d, J = 6.2 Hz, 6H). 13C NMR
(101MHz, CDCl3) δ (ppm) 161.9, 140.6, 140.4, 140.3,
139.2, 134.1, 131.3, 126.9, 126.7, 126.6, 125.2, 125.2,
24.0. HRMS (ESI); m/z calcd for C46H37NO + H+:
620.2875 [M+H+]: found, 620.2958.
The compound HPB-SW1 (0.100 g, 0.173
mmol) reacted with 2-aminoethanol (0.0158 g, 0.260
mmol) to afford the light yellow solid compound
HPB-SW4 (89% yield);1H NMR (400 MHz, DMSO)
δ (ppm) 13.26 (s, 1H), 8.10 (s, 1H), 6.99 – 6.73 (m,
249
27H), 6.31 (d, J = 8.6 Hz, 1H), 4.70 (d, J = 4.9 Hz,
1H), 3.54 (t, J = 4.5, 2H), 3.50 (t, J = 4.5 Hz, 2H). 13C
NMR (101 MHz, DMSO) δ (ppm) 165.7, 158.3, 140.3,
140.1, 140.1, 139.9, 139.9, 139.1, 134.7, 133.8, 130.8,
130.2, 126.5, 126.4, 125.3, 125.3, 116.9, 114.8, 60.8,
60.5. HRMS (ESI); m/z calcd for C45H35NO2 + H+:
622.2668 [M+H+]: found, 622.2745.
The preparations of compounds HPB-SW2,
HPB-SW3 and HPB-SW4 are depicted in Scheme 1.
Initially, HPB-SW1 were obtained from [4+2]
cycloaddition reaction between tetraphenylcyclopenta2,4-dienone (3) and diphenylacetylene (2) in 51%
yield as a white solid after recrystallized from
methanol. Then the target HPB-SW2, HPB-SW3 and
HPB-SW4 were synthesized from HPB-SW1 via the
imine formation with the corresponding amine such as
2-aminophenol, n-propylamine and 2-aminoethanol in
74-89 % yields, respectively. To confirm the structure
of the prepared compounds, the 1H NMR, 13C NMR,
and HRMS were performed. The mass analysis data
correspond to all prepared compounds. 1H NMR
analysis of HPB-SW1 and HPB-SW4 (Figure2.)
confirms the success of imine formation showing that
phenolic group shift downfield from 10.31 to 13.28
ppm and the aldehyde peak at 9.91 ppm disappeared.
Also the new peaks at 8.17, 4.74, 3.56 and 3.51 ppm
are corresponding to imine, primary alcohol and
methylene protons, respectively.
3.1 Effect of water content on photophysical
properties
The HPB derivatives are well-known
flurophores that can exhibit aggregation induced
emission (AIE) due to their restricted intramolecular
rotations behaviors (RIR) [4]. Therefore, we began the
investigation of the AIE effect on our flurophore
HPB-SW2, HPB-SW3 and HPB-SW4 by studying
the relationship between the amount of water in THF
solution toward the relative fluorescence intensity
(I/I0) (Figure 3.). In case of HPB-SW2, it showed an
obvious fluorescence enhancement upon increasing the
ratio of water from 0 to 60%, suggesting the AIE
effect (Figure1.). However, the addition of water
higher than 60% led to a decrease in the emission
intensity. This result may be attributed to the low
solubility of HPB-SW2 in the solvent mixture, leading
to a decrease in the number of emissive molecules per
unit volume. In this case, intramolecular rotations are
restricted in aqueous media because of the formation
of aggregates, which block the nonradiative channels
and populate the radiative excitons, thereby making
the molecule emissive in their aggregated state [5].
OH
OH
CHO
CHO
I-Cl/CH2Cl2
0
0C
PdCl2(PPh3)2, CuI,PPh3
OH
TEA. rt, N2, overnigth
to rt,overnigth
CHO
I
1
2
O
2
R
NH2
OH
Diphenylether, 260 oC
CHO
-CO
dry THF:EtOH (2:3)
Stirr. 65 oC
HPB-SW (2-4)
Figure3. Fluorescence intensity of HPB-SW2 (λem 524
nm), HPB-SW3 (λem 460 nm) and HPB-SW4 (λem 470
nm) 20 µM in THF: H2O mixtures at different water
contents. All compounds were excitated at 280 nm.
HPB-SW1
Scheme 1. Synthetic route of compound HPB-SW2,
HPB-SW3 and HPB-SW4
Figure2. Overlay 1H NMR spectra of HPB-SW1 (top)
and HPB-SW4 (bottom) in d6-DMSO
On the other hand, the fluorescence intensity
of HPB-SW3 and HPB-SW4, gradually decreased as
the fraction of THF in the mixed THF/water solution
decrease (100:0 to 10:90 v/v) (Figure 3.). The strong
emission of HPB-SW3 and HPB-SW4 in 100%THF
may be attributed to non-aggregated molecules. In
contrast, the decreasing fluorescence intensity of
HPB-SW3 and HPB-SW4 along with a slight red shift
from 455 to 500 nm was observed. To the best of our
knowledge, these are the first example of HPB
derivatives that have no AIE effect. We hypothesized
that the imine linkage possesses imine isomerization
along with the free rotation from alkyl side chain
resulting to the non-radiactive decay [7]. This behavior
not only reduces the fluorescence intensity but also
suppress the aggregation. Therefore, flurophore HPB-
250
SW3 and HPB-SW4 should be suitable for the design
of “turn-on” fluorescence sensor.
3.2 Fluorescent chemosensor
To demonstrate the sensing ability of
compound HPB-SW2, HPB-SW3 and HPB-SW4, we
firstly evaluated the relative fluorescence intensity
(I/I0) of those probe toward various metal ions such as
Cr3+, Al3+, Zn2+, Ni2+, Co2+, Ag+, Ba2+, Pb2+, Ca2+,
Cu2+, Cd2+, Hg2+, Mg2+, Na+, K+, Fe3+ and Fe2+ in pure
water. When excited at 280 nm, the HPB-SW2 alone
displayed a weak emission band at 453 nm in
THF/water (4:6 v/v) solution. Upon the addition of 10
equivalent of each metal ions, only Al3+ induced a 1.3fold enhancement in emission intensity while other
metal ions showed either no or slight fluorescence
intensity change (Figure 4a.inset). Similarly, the HPBSW3 and HPB-SW4 alone displayed a very weak
emission band at 453 and 457 nm respectively with
excitation at 280 nm in THF/water (1:1 v/v) solution.
Upon the addition of 10 equivalents of each metal ion,
only Zn2+ induced large fluorescence enhancement of
HPB-SW3 and HPB-SW4 to 15-fold and 25-fold
respectively. There was no observable change upon the
addition other metal ions (Figure 4). Importantly,
visual evidence of the specific and strong turn-on
fluorescence of the probe HPB-SW4 with Zn2+ were
observed as strong blue emission of solution under the
black light as seen in figure 4b. From these
observation, HPB-SW4 probe prove to be the best
turn-on florescence sensor for detection of Zn2+
showing higher selectivity and sensitivity in the
comparison with HPB-SW2 and HPB-SW3.
Moreover, this result suggests that the hydroxyl moiety
and flexible alkyl side chain in the imine receptor
facilitate the binding efficiency with Zn2+ ion.
280 nm. The insert bar graph represents the change of
the relative emission intensity of compound HPBSW2 in THF: H2O (4:6, v/v) λex 280 nm. 4b.
Photographs show selectivity of HPB-SW4 (50 μM)
upon mixing with different other metal cations (10eq)
in THF:H2O (1:1, v/v) under illumination by a UV
lamp.
To quantify the sensing ability of HPB-SW4
sensor, the fluorescence titration with Zn2+ was carried
out (Figure5). The emission intensities of HPB-SW4
gradually increased as the concentration of Zn2+
increased. Fluorescence intensity increased linearly up
to addition of 30 equiv of Zn2+ indicating that the it
might not be a simple 1:1 complex. Thus we
hypothesized that after the formation of complex HPBSW4-Zn2+, the excess Zn2+ also induced the formation
of aggregates in solution. However, we need to further
investigate their morphorlogy in order to confirm our
hypothesis. Fianlly, the detection limit of HPB-SW4
as a fluorescence chemosensor for analysis of Zn2+ was
found to be 0.160 µM which is far below the World
Health Organization guideline (76 µM) [6].
Figure5. Change in the fluorescence spectra of HPBSW3 (20 μM) upon a gradual increase in the
concentration of Zn2+ in THF: H2O (1:1, v/v)
4. Conclusions
Figure 4a. Bar graph representing the change of the
relative emission intensity of compounds HPB-SW3
and HPB-SW4 (20μM) upon mixing with different
other metal ions (10eq.) in THF: H2O (1:1, v/v) λex
We have successfully synthesized novel
flurogenic probe HPB-SW2, HPB-SW3 and HPBSW4 based on hexaphenylbenzene. The HPB-SW2
containing hydroxyphenyl imine demonstrated turn-on
fluorescence for Al3+ with high selectivity. Moreover,
the HPB-SW4 composed of 1-imineethanol moiety,
exhibited an excellent selectivity and sensitivity
toward Zn2+ ions as turn-on fluorescence mode. These
sensors might have the potential application for the
detection of Al3+ and Zn2+ in water quality monitoring.
251
Acknowledgements
This work is financially supported by the
Thailand Research Fund (RSA5780055) and
nanotechnology Center (NANOTEC), NSTDA,
Ministry of Science and Technology, Thailand,
through its program of Center of Excellence Network.
This work is part of the Project for Establishment of
Comprehensive Center for Innovative Food, Health
Products and Agriculture supported by the Thai
Government Stimulus Package 2 (TKK2555, SP2), the
Higher Education Research Promotion and National
Research University Project of Thailand, Office of the
Higher Education Commission (AM1006A-56) and
the Ratchadaphiseksomphot Endowment Fund of
Chulalongkorn University (RES560530126-AM).
References
[1] Chen, X., Pradhan, T., Wang, F., Kim, J and Yoon J.,
2012, Chem Rev., 112, 19101-956.
[2] Choi, Y.W., Park, G.J., Na, Y.J., Jo, H.Y., Lee ,S.A.,
You G.R and Kim, C., 2014, Sensors and Actuators B:
Chemical., 194, 343-352.
[3] Hong, Y, Lam, J.W.Y. and Tang, B.Z., 2011, Chem.
Soc. Rev., 40, 5361–5388.
[4] Kumar, M., Vij, V. and Bhalla, V., 2012, Langmuir., 28,
12417−12421.
[5] Dong, S., Li, Z. and Qin, J. 2009, J. Phys. Chem. B.,
113, 434-441.
[6] Kumar, Y. K., King, P. and Prasad, V. S. K. R., 2006,
Chem. Eng. J., 124, 63-70.
[7] Jiasheng, W., Weimin, L., Jiechao, Ge., Hongyan, Z.
and Pengfei W. 2011, Chem. Soc. Rev., 40, 3483–3495.
252
SYNTHESIS OF TRUXENE DERIVATIVES WITH
DIPYRENYLCARBAZOLE PENDANTS
Chomchanok Wongsilarat1, Vinich Promarak2, Paitoon Rashatasakhon3*
1
Program in Petrochemistry and Polymer Science, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
School of Chemistry and Center of Excellence for Innovation in Chemistry, Institute of Science, Suranaree University of Technology,
Muang District, Nakorn Ratchasima, 30000, Thailand
3
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330 Thailand
2
*
E-mail: paitoon.r@chula.ac.th, Tel. +6622817620
Abstract: Derivatives of truxene exhibited excellent
photophysical properties along with good thermal and
electrochemical stabilities suitable for application in
optoelectronic devices. In this paper, we reported the
synthesis and characterization of truxene derivatives
with
different
numbers
of
dipyrenylcarbazole
substituents. The truxene core is readily accessible via the
dehydro-cyclotrimerization of hydrocinnamic acid. The
solubility in organic solvents is enhanced when the
methylene units of truxene are substituted by n-butyl
groups. The dipyrenylcarbazole pendant is prepared
from iodination of carbazole followed by a Suzuki
coupling with the commercially available pyrene-1boronic acid. The Cu-catalyzed C-N coupling between
the iodinated truxene core and dipyrenylcarbazole thus
provides the target 1 and 2 which are characterized by
1
H NMR, 13C NMR and MALDI-TOF mass
spectroscopy. The photophysical properties of both
compounds are examined by UV-visible and fluorescence
spectroscopy.
1. Introduction
Organic light–emitting devices (OLEDs) have been
more interesting because of their applications in flat
panel displays. There have been extensive studies on
layered organic electroluminescent (EL) devices to
enhance device performances [1-2]. High efficiency
and good durability are generally important for
practical applications. One of the main reasons for the
degradation of the OLED device is the morphological
change in the amorphous organic layers, especially of
the hole transport layer, caused by Joule heating
during device operation. In order to solve this issue, it
is necessary to develop amorphous materials with a
high glass transition temperature (Tg). Therefore,
different synthetic approaches have been studied to
produce novel high Tg hole-transport materials
(HTMs) to generate thermally stable OLEDs. Recent
development in emissive materials has focused on the
blue electroluminescence (EL) as a number of new
fluorescent blue light-emitting materials, such as
triphenylfluoranthene, fluorene, triarylamine and
pyrene derivatives have been reported. However,
pyrene derivatives are more attractive to their strong
fluorescence, high quantum efficiency, carrier
mobility, and hole-transporting ability [3, 8]. On the
other hand, it is well-known that carbazole is a good
hole-transporting and electroluminescent group, and
many LED materials contain carbazole moieties as the
key constructing block. The exceptional holetransporting ability of the carbazole-containing
derivatives is attributed to the electron donating
capabilities of carbazole moieties. Furthermore, the
chemical and thermal stabilities of carbazole
derivatives are extremely high, and the carbazole ring
can be easily functionalized at the 3-, 6-, and 9positions [4-7, 9-10]. On the other hand, truxene or
10,15-dihydro-5H-diindenol[1, 2-a:10, 20-c]-fluorene
is a planar heptacyclic polyarene. It can be formally
regarded to as a C3-symmetrically fused fluorene
trimer. Because its unique three-dimensional topology
which could be comfortably functionalized by
different substituents at C-2, -7, -12 positions and at C5, -10, -15 positions, truxene has been thoroughly
developed as an attractive building block and starting
material for numerous functional organic materials
such as OLEDs, fluorescence sensor, organic solar
cells as well as large pi-conjugation dendrimer
macromolecular [9-13]. For these reasons, we
designed and synthesized two novel compounds by a
combination of 3,6-dipyrenylcarbazole units with
truxene core and hypothesized that they could serve as
hole-transporting materials in OLEDs. To emphasize
our progress of this project, the synthesis and
characterization of these compounds are reported
herein.
2.1 Chemical and instruments
All reagents were purchased from Aldrich, Fluka and
used without further purification. All 1H NMR spectra
were recorded on Varian Mercury 400 MHz NMR
spectrometer (Varian, USA). 13C NMR spectra were
recorded at 100 MHz on Bruker NMR spectrometer.
Mass spectra were recorded on a Microflex MALDITOF mass spectrometer (Bruker Daltonics) using
doubly recrystallized α-cyano-4-hydroxy cinnamic
acid (CCA) as a matrix. Absorption spectra were
measured by a Varian Cary 50 UV-Vis
spectrophotometer. Fluorescence spectra were
obtained
from
a
Varian
Cary
Eclipse
spectrofluorometer.
253
2.2 Synthesis
2.2.1 3,6-Diiodo-9H-carbazole (4)
To a stirred solution of carbazole (5.0 g, 29.9 mmol)
in acetic acid was added potassium iodide (6.6 g, 39.8
mmol). Then, potassium iodate (9.6 g, 44.9 mmol) was
added in small portions over a period of 5 min and the
resulting mixture was refluxed for 20 min. The
reaction was allowed to cool to room temperature and
diluted with EtOAc. The combined organic layer was
dried over MgSO4 filtered, and concentrated under
reduced pressure to give a brown solid residue. The
crude product was purified by recrystallization from
acetone and hexane to yield 4 as light brown crystals
(12.3 g, 98%).1H NMR (400 MHz, DMSO) δ 11.56 (s,
1H), 8.57 (s, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.35 (d, J =
7.6 Hz, 2H) ppm.
2.2.2 3,6-Di(pyren-1-yl)-9H-carbazole (5)
A mixture of 4 (1.4 g, 3.3 mmol), pyrene-1-boronic
acid (2.0 g, 8.1 mmol), Pd(PPh3)4 , 2M K2CO3 aqueous
solution was heated refluxing in THF conditions for 24
h. After the reaction was cooled to room temperature,
the resulting brown solution was extracted with
CH2Cl2. The combined organic layer was dried over
MgSO4, filtered, and concentrated under reduced
pressure. The crude product was purified by flash
chromatography using hexane: CH2Cl2 (3:1) as the
eluent to yield 5 as pale green solid (1.23 g, 66%). 1H
NMR (400 MHz, DMSO) δ 11.69 (s, 1H), 8.49 (s, 2H),
8.36 (d, J = 7.9 Hz, 2H), 8.30 – 8.11 (m, 14H), 8.06 (t,
J = 7.6 Hz, 2H), 7.77 (d, J = 8.2 Hz, 2H), 7.68 (d, J =
8.3 Hz, 2H) ppm. MALDI-TOF MS: C44H25N found
567.004 ([M]+ calcd: 567.198)
2.2.3 10,15 dihyhro-5H-diindeno[1,2-a:1’,2’-c]
fluorene (Truxene) (6) [11,12]
3-Phenylpropionic acid (10.02 g, 66.72 mmol) was
mixed with polyphosphoric acid (50 g) and heated at
60 °C for 30-40 min in nitrogen atmosphere. Water (5
mL) was then added to the reaction and temperature
was raised to 160 °C for 3 h. After the reaction was
cooled to room temperature, the mixture was poured
into ice water and grey powder was filtered off under
suction and washed with water. The residue was
recrystallized from toluene to yield 6 as light-yellow
power (11.12 g, 49%). 1H NMR (400 MHz, CDCl3) δ
7.93 (d, J = 7.1 Hz, 1H), 7.68 (d, J = 7.2 Hz, 1H), 7.49
(d, J = 7.6 Hz, 1H), 7.40 (d, J = 7.3 Hz, 1H), 4.22 (s,
2H) ppm.
2.2.4 5,5,10,10,15,15-Hexabutyl-truxene (7)
A solution of truxene (6) (1.00 g, 2.92 mmol) in
DMF (50 mL) at 0 °C under nitrogen, NaH (1.19 g,
29.8 mmol) was added and the solution was allowed to
warm to room temperature and stirred for 30 min, then
n-butyl bromide (3.2 mL) was added for 24 h. The
mixture was poured into water and extracted with
EtOAc. The combined organic layer was dried over
MgSO4, filtered, and concentrated under reduce
pressure. The crude product was purified by silica gel
column chromatography using hexane as the eluent to
yield 7 as white solid (1.48 g, 75%). 1H NMR (400
MHz, CDCl3) δ 8.38 (d, J = 7.3 Hz, 1H), 7.46 (m, 2H),
7.38 (m, 2H), 3.04 – 2.91 (m, 2H), 2.15 – 2.04 (m,
2H), 0.96 – 0.79 (m, 4H), 0.62 – 0.36 (m, 10H) ppm.
2.2.5 5,5,10,10,15,15-Hexabutyl-2-iodo-truxene (8)
5,5,10,10,15,15-Hexabutyl-2,7-diiodo-truxene (9)
A mixture of truxene (7) and solvent
(CH3COOH:H2SO4:H2O:CCl4) = 100:5:20:8) was
heated to 40 °C. After adding HIO3 and I2 to the
mixture, the mixture was heated to 80 °C and stirred
for 4 h at this temperature. After the reaction was
completed, the mixture was cooled to room
temperature and filtered off under suction, washed
with water. Then the residue refluxed in methanol for
2h and followed by cooling to room temperature,
filtered off under suction, and white power was
obtained (68% yield 8). 1H NMR (400 MHz, CDCl3) δ
8.4-8.3 (m, 2H), 8.14 - 8.04 (d, J = 8.5 Hz, 1H), 7.77
(s, 1H), 7.75 - 7.68 (d, J = 8.2 Hz, 1H), 7.49 - 7.42 (m,
2H), 7.43 - 7.32 (m, 4H), 3.05 - 2.78 (m, 6H), 2.1 1.95 (m, 6H), 0.98 - 0.8 (m, 12H), 0.62 - 0.34 (m,
30H) ppm.
(64% yield 9) 1H NMR (400 MHz, CDCl3) δ 8.48.3 (m, 1H), 8.14-7.97 (d, J = 8.5 Hz, 2H), 7.77 (s,
2H), 7.73 - 7.61 (d, J = 8.2 Hz, 2H), 7.50 - 7.42 (m,
1H), 7.43 - 7.29 (m, 2H), 3.03 - 2.28 (m, 6H), 2.13 1.90 (m, 6H), 1.03 - 0.68 (m, 12H), 0.61 - 0.20 (m,
30H) ppm.
2.2.6 Compound 1 and 2
A mixture of 8 or 9, dipyrenylcarbazole, 1 mol%
CuI, 10 mol% diamine ligand and K3PO4 in
dioxane ( 1 M) at 110°C for 24 h. The resulting
light yellowish green mixture was allowed to cool to
room temperature and extracted with CH2Cl2 (3 ×
50 mL). The combined organic layer was dried
over MgSO4, filtered, and concentrated under
reduce pressure.
The crude product was purified by alumina
chromatography using hexane:CH2Cl2 (3:1):
(43% yield 1). 1H NMR (400 MHz, CDCl3) δ 8.75 8.65 (m, 2H), 8.54 - 8.49 (s, 2H), 8.38 – 8.35 (d, 2H),
8.27 (s, 2H), 8.23 – 8.02 (m, 14H), 7.90
– 7.87 (m, 2H), 7.83-7.79 (m, 4H),7.79 – 7.71 (s,
1H), 7.65 – 7.40 (m, 6H), 3.35 – 2.85 (m, 6H), 2.32 2.05 (m, 6H), 1.15 - 0.82 (m, 24H), 0.75 - 0.55 (m,
18H) ppm. 13C NMR (101 MHz, CDCl3) δ 156.4,
156.3, 156.1, 155.9, 153.8, 153.7, 146.1, 145.9, 145.8,
145.7, 145.4, 145.3, 144.9 , 144.7, 140.9, 140.4, 140.2,
140.1, 140.1, 139.9, 139.8 , 139.7, 139.7, 139.6, 139.1,
139.0, 138.8, 138.5, 138.1 , 138.0, 137.8, 136.2, 136.0,
135.6, 135.4, 133.6,131.8, 131.2, 130.6, 129.3, 129.1,
128.3, 127.6, 127.4, 126.9 , 126.8, 126.3, 126.1, 125.8,
125.2, 125.2, 124.9, 123.9, 122.8, 122.5, 120.9, 110.1,
92.9, 92.7, 92.6, 56.4, 55.8, 36.9, 36.6 ,
254
29.9, 26.9, 26.7, 23.1, 22.8, 14.0 ppm. MALDITOF MS: C95H89N found 1244.909 ([M]+ calcd:
1244.702)
(38% yield 2). 1H NMR (400 MHz, CDCl3) δ 8.79 8.68 (m, 1H), 8.53 - 8.84 (s, 4H), 8.39 – 8.36 (d, 4H),
8.27-8.25 (s, 4H), 8.23 – 8.02 (m, 28H), 7.97 – 7.91 (s,
4H), 7.88-7.79 (m, 8H),7.79 – 7.71 (s, 2H), 7.59 – 7.41
(m, 3H), 3.25 – 3.06 (m, 6H), 2.43 – 2.28 (m, 6H), 0.87
– 0.84 (m, 12H), 0.69 – 0.55 (m, 24H) ppm. 13C NMR
(101 MHz, CDCl3) δ 156.6, 156.5, 156.4, 156.3, 154.1,
154.0, 146.3, 146.2, 146.19, 146.1, 145.9, 145.8 ,
141.3, 140.6, 140.5, 140.3, 140.2, 140.1, 140.0, 139.9,
139.8, 139.7, 139.5, 138.9, 138.6 , 138.6, 138.4, 138.4,
136.6, 134.0, 132.1, 131.6, 131.3, 130.93, 129.6, 129.4,
129.2, 128.7, 127.9, 127.8,
solution in 0.01 M H2SO4 (ΦF = 0.54) as a standard are
0.72 and 0.59, respectively
I
I
a
N
H
b
N
H
98%
67%
N
H
4
3
5
Key: (a) KI, KIO3,AcOH, refluxing, 20 min; (b) Pyrene-1-boronic
acid, [Pd(PPh3)4], 2M K2CO3, refluxing THF, 24 h.
Scheme 1. Synthesis of 3,6-di(pyren-1-yl)-9Hcarbazole
R
R
CH2CH2COOH
127.39, 127.33,
126.9, 126.8, 126.6, 126.5,
126.5, 126.1, 125.6, 125.5, 125.2, 124.3, 123.0,
121.4 , 121.3, 110.5, 56.6, 56.5, 56.3, 39.3, 38.1, 37.8,
37.6, 37.3, 37.2, 33.3, 33.2, 32.7, 32.4, 30.9,
30.5, 29.8, 27.6, 27.4, 27.1, 26.9, 24.9, 23.9,
23.2, 14.6, 14.5, 14.4, 11.44, 11.4 ppm. MALDITOF MS: C139H112N2 found 1809.868 ([M]+ calcd:
1809.885)
a
b
49%
75%
R
R
R
6
7
c 68%
d
R
R
R
R
R
R
R
3.2 Photophysical properties of compounds 1 and 2
The normalized absorption and emission spectra of 1
and 2 in CHCl3 are illustrated in Figure 1 and the
pertinent data are collected in Table 1. The absorption
band of the two-branched dipyrenylcarbazole truxene
(2) appeared at a longer wavelength compared to the
one-branched analog (1). This red-shift is attributed to
the extension of conjugation upon the increment of the
dipyrenylcarbazole unit. Compound 1 and 2 exhibited
a maximum emission wavelength at 421 and 423 nm,
respectively. Photoluminescence quantum yields yields
of compounds 1 and 2 determined in CHCl3 solution
(A<0.1) at room temperature using quinine sulfate
64%
I
I
R
R
R
R
8
3.1 Synthesis of 1 and 2
We began with a regioselective diiodination of
carbazole using KI/KIO3 in refluxing acetic acid,
followed by a Suzuki coupling with the commercially
available pyrene-1-boronic acid to afford compound 5
in 66% yield (Scheme 1).
Hereupon truxene was prepared from 3phenylpropionic acid according to the reported
procedure then the methylene units were alkylated by
excess amount of n-butylbromide to afford 7 in 75%.
This hexaalkylated compound exhibit greater
solubility in organic solvents, and also prevent the
aggregation by pi-stacking leading to low quantum
efficiency. Iodination of 7 with 1 eq. of HIO3 and I2
produced the core compound 8 and 2 eq. of the same
reagents produced the core compound 9 in 68% and
64% yield, respectively (Scheme 2).
The target compounds 1 and 2 were then
accomplished by the Cu-catalyzed C-N coupling of 5
with 8 and 9 in 43% and 38% yield, respectively.
R
e
9
N
N
R
R
R
R
R
R
I
f 38%
43%
R
R
R
R
R
R
R
N
Compound 1 : R = nC4H9
Compound 2 : R = nC4H9
Key: (a) PPA, 160°C, 3 h; (b) n-BuBr, NaH, DMF, RT, 24 h; (c)(d)
HIO3 and I2, CH3COOH:H2SO4:H2O:CCl4 , 80°C, 4 h; (e)(f)
dipyrenylcarbazole, 1 mol% CuI, 10 mol% diamine ligand, K3PO4,
dioxane ( 1 M), 110°C for 24 h.
Scheme 2. Synthesis of compounds 1 and 2
Table 1: Photophysical properties of compounds 1-2
Cmpd
1
2
[a]
[b]
ΦF [d]
Absorption
Emission
λmax [nm] (log ε)
Solution [a]
λmax [nm]
243 (4.39), 282
(4.23), 319 (4.23),
348 (4.14)
246 (4.76), 280
(4.66), 349 (4.55)
421 [b]
0.72
423 [c]
0.59
Measured in a dilute CHCl3 solution.
Excited at 348 nm.
255
[c]
[d]
Excited at 349 nm.
Quinine sulfate in 0.01 M H2SO4 as a standard (ΦF = 0.54)
4. Conclusions
We have successfully synthesized and characterized
one- and two-branched dipyrenylcarbazole substituted
truxene derivatives. These compounds exhibited
similar absorption maxima around 348 - 349 nm and
emission maxima around 421 - 423 nm in CHCl3
solution. High photoluminescence quantum yields
suggested that they could serve as good emissive
materials in OLEDs application.
[11] Earmrattana,
N.,
Sukwattanasinitt,
M.
and
Rashatasakhon, P., 2012, Dyes Pigments., 93, 14281433.
[12] Gomez-Lor, B., Defrutos, O., Ceballos, P.A., Granier,
T. and Echavarren, A.M., 2001, Eur. J. Org. Chem.,
2107-2114.
[13] a) Klapars, A., Huang, X. and Buchwald, S.L., 2002, J.
Am. Chem. Soc., 124, 7421 – 7428; b) Klapars, A.,
Antilla, C.J., Huang, X. and Buchwald, S.L., 2001, J.
Am. Chem. Soc., 123, 7727 – 7729.
Figure 1. Normalized absorption and emission spectra
of 1 and 2 in CHCl3 solution.
Acknowledgements
project
is
supported
by
the
This
Ratchadapiseksomphot
Endowment
Fund
of
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256
CYCLIC ALKYL SULFIDE DIETHER DERIVATIVE AS AN ELECTRON
DONOR FOR ZIEGLER-NATTA CATALYST IN OLEFIN
POLYMERIZATION
Kananat Naksomboon1, Krittaphat Wongma1, Phairat Phiriyawirut2
and Tienthong Thongpanchang1*
1
Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
2
The Siam Cement Pcl., Bangsue, Bangkok, 10800, Thailand
*
E-mail: tienthong.tho@mahidol.ac.th, Tel. +66 2201 5130, Fax. +66 2201 5139
Abstract: Electron donor or Lewis base is one of the key
components in propylene polymerization using ZieglerNatta catalyst. In this research, a novel electron donor
based on 1,3-diether conjugated with cyclic alkyl sulfide
framework was designed and synthesized and it was
introduced to the polymerization reaction of propylene in
a lab scale. The resulting PPs were characterized and
compared to the systems without electron donor and with
commercial electron donor, 2,2-diisobutyl-1,3-dimethoxypropane (DIBDMP). By using DIBDMP as a benchmark,
isotacticity of PP from sulfur donor 1 is similar, with 92%
of mmmm characterized by 13C NMR analysis and 91% of
I.I. determined from the weight of insoluble polymers.
,
, and
Polymer melting point (Tm) is 158 °C and
MWD are 2.89 × 104, 4.63 × 105, and 16.02, respectively.
These numbers are inferior as compared to the
commercial donor but similar to the PP from the system
without donor. The activity of the catalyst donor 1 is 1943
gPP/gTih.
1. Introduction
Polypropylene (PP) is one of the most important
polyolefins because of its diverse properties such as
transparency, density, and tensile strength[1-2].Such
polymer is generally prepared on industrial scale using
Ziegler-Natta (ZN) catalyst on MgCl2 support and more
than 50 million tons of isotactic polypropylene (iPP),
which is semi-crystalline polymer, are produced
annually from this catalyst system[3]. The stereochemistry of the resulting polymer is one of the most
important factors that determine the processability,
mechanical properties and chemical resistance[4].
To control the tacticity of PP, electron donors or Lewis
bases are often added to regulate the polymerization
process[5]. Various types of donors such as
monoesters[6], phthalate esters[7], alkoxysi-lanes[3],
and 1,3-diethers[7-8] have been reported and studied
for propylene polymerization (Figure 1). Many models
were proposed to account for the influence of electron
donor on PP properties but the widely accepted one is
the three-site model described by Busico et al. in which
electron donors could coordinate to metal atoms (Ti or
Mg) neighboring to Ti active site to control the
alignment of the incoming propylene[9]. The Ti active
site can be obtained by reducing pre-catalyst (Ti4+) to
by
co-catalyst
(e.g.
active
species
(Ti3+)
triethylaluminum (AlEt3))[10].
O
O
OR
R'
R'
OR
OR
R'
R'
RO
OR
Si
RO
OR
O
Monoesters
Phthalate esters
Alkoxysilanes
1,3-Diethers
R, R' = alkyl, aryl
Figure 1. General structures of monoesters, phthalate
esters, alkoxysilanes, and 1,3-diethers.
Among these electron donors, the structures with 1,3diether scaffold displayed intriguing properties since
they can bind strongly to the surface of the solid
support in the presence of co-catalyst, rendering a
stable catalyst structure[11]. Moreover, this type of
donors enhances the catalyst activity, isospecificity of
polymer, and narrower molecular weight distribution
(MWD) than others[12].
Due to the ability of electron donors to tune the
polymer properties through the control of
polymerization process, this research focuses on the
synthesis of novel electron donor 1 and its role in
polymerization. This electron donor was designed
based on 1,3-diether which is expected to strongly
adhere to the catalyst surface. The incorporation of
sulfur atom in the structure is to tune the
stereospecificity and catalytic activity via the donation
of electron from sulfur to the solid support either
through bond or space.
S
S
OMe
MeO
1
Figure 2. Structure of the designed electron donor 1
grafted with sulfur.
2.1 Materials
TiCl4 on MgCl2 support, AlEt3, propylene gas, and
2,2-diisobutyl-1,3-dimethoxypropane(DIBDMP) were
provided by The Siam Cement Group (SCG). Hexanes, methanol (MeOH), dichloromethane (DCM),
ethyl acetate (EtOAc), and n-heptane were from RCI
Labscan. 1,2-Ethanedithiol was from Fluka. Sodium
methoxide (NaOMe), oxone, 2-iodobenzoic acid, boron
257
trifluoride
diethyl
etherate
(BF3.Et2O),
epichlorohydrin were from Aldrich.
and
dried over anhydrous Na2SO4, filtered, and evaporated
to dryness. Column chromatography on silica gel using
EtOAc and hexanes (EtOAc : hexanes, 1 : 9 v/v) as an
eluent gave sulfur electron donor model 1 (0.43 g, 65%
yield): 1H NMR (CDCl3) δ 3.25 (s, 4H), 3.42 (s, 6H),
3.66 (s, 4H); 13C NMR (CDCl3) δ 38.7, 59.4, 68.4,
76.9; ESI cald for C7H14NaO2S2+ [M+Na]+ = 217.0333.
Found [M+Na]+ = 217.0349.
2.2 Synthesis of sulfur electron donor 1
2.2.1 Synthesis of alcohol 3
Epichlorohydrin 2 (11.50 g) was added dropwise to a
solution of NaOMe (16.80 g) in anhydrous MeOH (130
mL). After 2 h, the reaction was evaporated to dryness
and the mixture was extracted with DCM and washed
with water (3x50 mL). The organic layer was dried
over anhydrous sodium sulfate (Na2SO4), filtered, and
evaporated to dryness[13]. The crude product was
purified by distillation to afford a clear solution of 3
(10.40 g, 70% yield): 1H NMR (CDCl3) δ 3.39 (s, 6H),
3.41-3.48 (m, 4H), 3.93-3.99 (m, 1H); 13C NMR
(CDCl3) δ 58.6, 68.6, 73.6; ESI cald for C5H12NaO3+
[M+Na]+ = 143.0684. Found [M+Na]+ = 143.0699.
O
NaOMe, MeOH
Cl
reflux, 2 h, 70%
2
3
2.2.2 Synthesis of ketone 4
To the solution of alcohol 3 (0.51 g) in EtOAc (30.0
mL) was added 2-iodoxybenzoic acid (IBX)[14] (3.59
g). The reaction was heated to reflux for 5 h and then
cooled to room temperature, filtered and washed with
EtOAc[15]. The filtrate was evaporated to dryness to
obtain the product in 82% yield (0.41 g): 1H NMR
(CDCl3) δ 3.42 (s, 6H), 4.18 (s, 4H); 13C NMR (CDCl3)
δ 59.5, 76.2, 205.7; ESI cald for C5H10NaO3+ [M+Na]+
= 141.0528. Found [M+Na]+ = 141.0549.
OH
OMe
IBX, EtOAc
OMe
reflux 5 h, 82%
4
3
OMe
MeO
1
2.4 Characterization of PP
The isotacticity of polymers was characterized by high
temperature 13C nuclear magnetic resonance
spectroscopy (13C NMR) and n-heptane extraction
technique. The polymer molecular weight was
determined by gel permeation chromatography (GPC).
Melting temperature (Tm) and crystallization
temperature (Tc) were obtained from differential
scanning calorimetry (DSC).
O
MeO
0 C, 2 h, 65%
2.3 Polymerization of PP
To the solution of hexanes (100 mL) was added AlEt3
1.25 mL (1.0 M in heptane) under nitrogen atmosphere
and then the reaction was saturated with propylene gas
at 1 atm. The electron donor (0.1 M, 1.25 mL) was
introduced into the reaction followed by the addition of
Ti catalyst slurry (Ti : donor : Al = 1 : 3 : 30). The
reaction was stirred under propylene blanket at 30 oC.
After 30 min, the reaction was quenched with 25% HCl
in MeOH solution to precipitate PP. The resulting PP
was washed with water (3x500 mL) and dried under
reduced pressure at 60 °C for 6 h or until the constant
weight was obtained.
Scheme 1. The synthesis of alcohol 3.
MeO
S
S
o
Scheme 3. The synthesis of sulfur electron donor 1.
OMe
MeO
1,2-ethanedithiol
BF3.Et2O, DCM
4
OH
O
OMe
MeO
Scheme 2. The synthesis of ketone 4.
2.2.3 Synthesis of thioacetal derivative 1
BF3·Et2O (0.43 mL) was added to the mixture of
ketone 4 (0.40 g) and 1,2-ethanedithiol (0.30 mL) in
DCM (20 mL) at 0 °C. The reaction was stirred at the
same temperature for 2 h and then quenched by 5%
NaOH (10 mL), and extracted with DCM (3x20 mL).
The combined organic layers were washed with water,
The sulfur electron donor 1 could be synthesized from
commercially available starting materials in 3 steps
through Williamson ether synthesis, oxidation of
alcohol to provide ketone, and thioacetal formation
giving 37% yield overall.
The polymerization of propylene was performed in
hexanes with electron donor 1 and with commercialTable 1: Effects of electron donors on the catalytic activities and polymer properties.
Donor
PP weight (g)
Activity
(gPP/gTih)
%mmmma
%I.I.b
-
2.56
2,528
85
DIBDMP
2.57
2,519
93
MWDc
Tmd
Tcd
2.78
16.37
159
114
5.27
12.22
160
115
(x105)c
(x104)c
85
4.55
95
6.46
1.96
1,943
92
91
4.63
2.89
16.02
158
115
1
%mmmm was characterized by 13C NMR.
b
%I.I. was determined from Soxhlet extraction of 0.5 g of product using n-heptane as solvent under nitrogen
atmosphere for 6h.
c
,
, and MWD were characterized by GPC.
d
Tm and Tc were characterized by DSC.
a
258
ized electron donor DIBDMP (Figure 3) and in the
absence of electron donor for the purpose of
comparison. The catalyst activity and properties of the
resulting PPs are summarized in Table 1.
MeO
OMe
DIBDMP
Figure 3. The structure of commercially used donor in
industry (DIBDMP).
The effects of electron donors on the catalytic
activities were investigated by the determination of the
weight of PP. The polymerizations with commercial
electron donor, i.e. DIBDMP, and without gave similar
PP weight implying that the catalytic activities were
not affected by the addition of electron donor. In
contrast, the use of sulfur donor 1 as an electron donor
decreased both the PP weight and activity to 1.96 g and
1,943 gPP/gTih, respectively. This is presumably due to
the poisoning of sulfur atom of electron donor to the Ti
catalyst[16].
a)
1
2
CH2 CH
CH3
3
in comparison to other stereoisomers[16]. As shown in
Figure 4a, the spectrum features 3 main peaks of PP
carbons labeled with numbers corresponding to the
labeled carbon in the monomeric propylene structure.
To calculate %mmmm, the integrated peak area of
methyl carbon or C3 labeled as mmmm in the expanded
NMR spectrum (Figure 4b) is determined as percentage
in comparison to the integrated peak areas of other
stereoisomers[17]. Another parameter to indicate
isotacticity of PP is %isotacticity index (%I.I.), this
data can be obtained by determining a fraction of
insoluble polymer in n-heptane which is isotactic PP to
the overall polymer weight. %mmmm increases from
85, 92 to 93 and %I.I. increases from 85, 91 to 95 for
the reactions with no donor, sulfur donor and
commercial donor, respectively. This result indicates
that the polymers obtained from the reactions with
electron donors are isotactic[18]. Although the reaction
with sulfur electron donor 1 displayed low catalytic
activity, a comparable stereoselectivity was still
obtained.
The number average molecular weight ( ) and
weight average molecular weight ( ) were
determined from GPC. The polymer obtained from the
reaction without donor and with sulfur electron donor 1
and
in comparison to commercial
yielded lower
electron donor. In addition, PP synthesized from the
reaction with DIBDMP displayed the narrowest
distribution as compared to the reaction with sulfur
donor and no donor.
The crystallinity of the PPs was evaluated from Tm and
Tc obtained from DSC analyses. Tm and Tc of all PPs
from the reaction with and without donors are quite
similar indicating that the obtained PPs are of
comparable crystallinity.
4. Conclusions
The sulfur electron donor 1 was successfully
synthesized in 3 steps in satisfactory yield. This novel
electron donor was introduced to the propylene
polymerization reaction and the obtained polymer
, and
showed high %mmmm and %I.I. while the
are not better than that of the reaction with
DIBDMP.
b)
Acknowledgements
Figure 4. 13C NMR spectrum of PP obtained using
sulfur derivative 1 as electron donor (a) PP 13C NMR
(b) the expanding spectrum of methyl carbon (C3).
Financial support from Development and Promotion of
Science and Technology talents project (DPST) and
facilities support from the Center of Excellence for
Innovation in Chemistry (PERCH–CIC) are gratefully
acknowledged. Authors also thank SCG for materials
and PP characterization and Dr. Tossapol Khamnaen
for valuable suggestion.
The other important characteristic of PP is tacticity
since it is related to the physical properties of the
polymer. The polymer tacticity was identified from 13C
NMR by determining the %pentad tacticity (%mmmm)
259
References
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Macromolecules, 29, 3341-3345.
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Macromol. Rapid Commun., 21, 1046-1049.
[12] Malpass, D.B. and Band, E., 2012, Introduction to
Industrial Polypropylene: Properties, Catalysts
Processes, Wiley.
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Simpson, W.R. and Strohschein, R.J., 2000, J. Med.
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[16] Dunleavy, J.K., 2006, Platinum Metals Rev., 50, 110.
[17] Asakura, T., Demura, M. and Nishiyama, Y., 1991,
Macromolecules, 24, 2334-2340.
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and Waymouth, R.M., 1995, Angew. Chem. Int. Ed.
Engl., 34, 1143-1170.
260
ΑLPHA-BROMINATION OF KETONE USING HEXABROMOACETONE
Tipakorn Sangrawee1, Warinthorn Chavasiri2,*
1
Program in Petrochemistry and Polymer Science, Faculty of Science, Chulalongkorn University,
Bangkok 10330, Thailand
2
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
* Email: warinthorn.c@chula.ac.th
Abstract: An efficient method for the preparation of αbromoketone has been disclosed. Propiophenone, a model
substrate was treated with hexabromoacetone (HBA)
with the ratio of substrate to HBA as (1:1) in THF at RT
for 5 min under UV (254 nm) irradiation. 2Bromopropio- phenone was obtained as a sole product in
high yield. Various parameters including reaction time,
solvent and ratio of substrate to HBA were scrutinized.
1. Introduction
α-Bromination of carbonyl compounds is one of
important transformations in organic synthesis as αbrominated
products
are
useful
synthetic
intermediates.1 Previously, α-brominated carbonyl
compounds could be prepared by using Br2 in protic
solvent in the presence of Lewis acid,2 Nbromosuccinimide (NBS)3 and cupric bromide.4
Recently, various methods have been reported using
NBS-NH4OAc,5 NBS-photochemical,6 NBS-silica
supported sodium hydrogen sulfate,8 and NBSPTSA,11 However, the disadvantages of those
procedures are in some cases the substrates or products
being intolerance to acid, requiring high temperature
and forming undesired by-product.
In 1969, HBA was first synthesized; nevertheless
without utilizing as a reagent in organic chemistry.12
Until 2008, our research group explored the utilization
of this reagent coupled with PPh3 as a new and
efficient brominating agent for alcohol under mild
conditions with short reaction time.13 In 2009, other
researchers reported the use of this reagent as
tribromoacetylating agent of alcohols and amines and
as mediator in the conversion of carboxylic acid into
amides14 with moderate to good yields. In 2011,
another group addressed the preparation of benzyl
bromides from alcohols with high conversion rates and
short reaction time.15 Up to date, HBA has not been
employed as a brominating agent for α-bromination of
ketone. Herein, we report a novel, mild and high
yielding synthetic method for α-bromination of ketone
by using propiophenone as a model substrate.
Instrumental: Thin layer chromatography (TLC) was
performed on aluminum sheets pre-coated with silica
gel (Merck Kieselgel 60 PF254). Column
chromatography was carried out on silica gel (Merck
Kieselgel 60, 70-230 mesh). The 1H-NMR spectra
were performed in CDCl3 with tetramethylsilane
(TMS) as an internal reference on a Varian nuclear
magnetic resonance spectrometer, model Mercury plus
400 NMR spectrometer which operated at 399.84
MHz for 1H.
Chemicals: All solvents were purified by standard
methods before use unless those were reagent grades.
The reagents for synthesis were purchased from Fluka
or Sigma-Aldrich and used without further
purification.
General procedure: In a quartz cell (cylinder tube 2.5
x 13.5 cm), propiophenone 17 µL (0.125 mmol) was
mixed with HBA 67 mg (0.125 mmol) in THF (1 mL).
The reaction mixture was stirred at RT under the
irradiation of UV light (254 nm, 6W) for 5 min
(Scheme 1). The reaction was monitored by TLC and
at appropriate time was quenched by adding NaHCO3
(1 mL) and extracted twice with Et2O (5 mL). The
product yield was analyzed by GC using naphthalene
as an internal standard.
O
O
Br3C
CBr3
0.125 mmol
O
THF, UV (254 nm), 5 min
Br
0.125 mmol
Scheme 1. α-Bromination of propiophenone using
HBA
Table 1 reveals the effect of types of brominating
agent on the conversion of propiophenone into 2bromopropiophenone. The reaction with HBA
provided a high yield of the desired product (entry 1)
while other common brominating agents (entries 2-6)
gave low yields of the target molecule.
Table 1: Effect of types of brominating agent
Entry
Brominating
% Recovery of
%
agent
propiophenone
Yield
1
HBA
38
72
2
NBS
94
0.1
3
CBr4
90
17
4
Br3CCO2H
88
10
5
C2H5Br
97
0
6
BrCCl3
99
7
Reaction conditions: Propiophenone (0.125 mmol),
brominating agent (0.125 mmol), Et2O (1 mL) 5 min,
UV, RT
261
Effect of reaction time with UV-irradiation
As presented in Table 2, the reaction in the
absence of UV light (entry 1) generated the target
product in poor yield. The yield of this product
increased when the reaction was prolonged. The
optimal reaction time was observed to be 10 min
(entries 2-4). The yield decrease while the undesirable
formation of α,α-dibromination product increased after
prolonged irradiation to be 15 min (entry 4). This
result clearly demonstrated that irradiation by UV light
was important for this reaction.
Table 2: Effect of reaction time with UV-irradiation
Entry
Reaction
% Recovery of
%
time (min)
propiophenone
Yield
1
5
98
5
(without UV)
2
5
38
72
3
10
6
100
4
15
6
94
HBA (0.125 mmol), Et2O (1 mL), reaction time and
UV (vary), RT
target product based on the amount of HBA, the
formation of 2-bromopropiophenone was increased
when low amount of HBA was employed. In addition,
this experiment was set up to observe the efficiency of
HBA. In entry 1, with the mole ratio of propiophenone
to HBA 1:1, the target product could be attained in
very high yield based on the mole of brominating
agent used. These results displayed a good efficiency
of this brominating agent.
Table 5: Effect of molar ratio of propiophenone: HBA
Molar ratio
of
propiophenone: HBA
% Yield
%
Recovery
of propiophenone
Based
on
HBA
1
1.00: 1.00
3
97
97
2
14
81
163
2.00: 1.00
3
32
57
170
3.00: 1.00
4
36
63
377
6.00: 1.00
Reaction conditions: propiophenone:HBA (vary), THF
(1 mL), 5 min, UV, RT
Entry
Based on
propiophenone
Step I (Initiation)
Effect of solvent
As displayed in Table 3, the reaction in Et2O
generated the target product in poor yield (entry 1),
while THF provided the best result (entry 6).
O
Br
Br
Br
Attempting to reduce the reaction time in THF to
2 min did not give good yield of the desired product
(Table 4, entry 1). Thus, the optimal reaction time
should be 5 min.
Table 4: Effect of reaction time with UV-irradiation
Entry
Reaction
% Recovery of
% Yield
time (min)
propiophenone
1
2
36
69
2
5
3
97
HBA (0.125 mmol), THF (1 mL), UV, RT
Effect of the molar ratio of propiophenone: HBA
Table 5 reveals that when the ratio of
propiophenone to HBA was increased or using less
HBA, the yield of the desired product was decreased.
This was clearly demonstrated that the amount of HBA
was essential for this reaction. Considering the yield of
Br
Br
Br
Br
Br
Br
O
O
Br
H
H
Table 3: Effect of solvent
Entry
% Recovery of
solvent
% Yield
propiophenone
1
Et2O
98
5
2
DCE
98
6
3
DCM
95
4
4
Hexane
75
11
5
CH3CN
62
38
6
THF
3
97
7
Benzene
100
5
HBA (0.125 mmol), solvent (1 mL), 5 min, UV, RT
O
Br
Br
Br
HBr
H
Step II (Propagation)
O
O
Br
Br
H
Br
O
O
Br
Br
Br
H
Br
Br
Br
O
O
O
BrCCCBr3
H
H
Br
H
O
BrCCCBr3
H
Step III (Termination)
O
O
Br
Br
H
Br
Br
O
Br
Br
H
Br
O
Br3CCCBr2
H
H
Br
O
Br2CCCBr2
H
O
Br2CCCBr2
H H
H
Br
Br2
Scheme 2. The proposed mechanistic pathway for αbromination of propiophenone using HBA
4.
Br
Br
Br
Conclusions
HBA was disclosed as an efficient brominating
agent for a clean and rapid α-bromination of
propiophenone under the irradiation of UV light with
short reaction time. This bromination reaction could
proceed cleanly and rapidly to give the desired product
in excellent yield under mild conditions.
262
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263
FRIEDEL–CRAFTS BENZYLATION OF TOLUENE USING NdCl3
IMPREGNATED ON ALUMINIUM PILLARED MONTMORILLONITE
Natthida Maneechandra1, Warinthorn Chavasiri2*
1
Program in Petrochemistry and Polymer Science, 2Department of Chemistry, Faculty of Science, Chulalongkorn University,
Bangkok, 10330, Thailand
*
E-mail: warinthorn.c@chula.ac.th, Tel. 02-2187625, Fax 02-2187598
Abstract: 2%NdCl3 impregnated on aluminium pillared
montmorillonite (2%NdCl3/Al-PLM) was prepared as a
catalyst for Friedel–Crafts benzylation of toluene with
benzyl alcohol. The appropriate amount of 2%NdCl3/AlPLM was investigated. Its basal spacing was
characterized by XRD technique. The reaction was
performed using 0.8%mol of 2%NdCl3/Al-PLM at 170°C
for 1 h with 8:1 molar ratios of toluene and benzyl
alcohol. This reaction yielded quantitative yield of benzyl
toluene with a ratio ortho:para of 1.52. In addition, this
clay catalyst was easy to separate and could be reused for
at least 5 times without losing catalytic activity.
OH
0.8% mol of 2% NdCl /Al-PLM
3
+
toluene
benzyl alcohol
+
+
sealed tube, 170oC, 1 h
o-benzyl toluene
p-benzyl toluene
O
benzyl ether
Keywords NdCl3; Aluminium Pillared Montmorillonite;
Clay; Friedel-Crafts Benzylation
1. Introduction
Lewis acid clay has been used as a catalyst in
various reactions for years. It has also widely become
interest due to its advantages such as the
environmental friendliness and the applicability in the
desired catalytic condition.1 There are several methods
to develop the clay catalyst such as cation-exchange,
pillaring and impregnation. However, the activity of
these clay catalysts depends on the nature of the metal
cation in acid treated clays.2 Herein, we observed high
activity of NdCl3 impregnated on aluminium pillared
montmorillonite (NdCl3/Al-PLM), in benzylation of
toluene.
Friedel-Crafts benzylation of aromatics is an
important reaction for generating a wide variety of
diphenylmethane derivatives which are key synthetic
intermediates in pharmaceutical and fine chemical
industries. Conventionally, these benzylations are
carried out industrially by dangerous homogeneous
acid catalysts such as AlCl3, BF3, H2SO4, HF, HNO3,
etc. These catalysts generate high volume of waste
materials. Moreover, they also pose several problems
such as corrosion, toxicity, difficulty in separation,
disposal, and reusability of the catalysts.3-7
The present work aims to develop a highly efficient
and reusable catalyst by using 2% NdCl3/Al-PLM for
the selective Friedel-Crafts benzylation between
toluene and benzyl alcohol to afford diphenylmethane.
Herein, we reported simple preparation of this catalyst,
the appropriate amount of catalyst, temperature, time,
mole ratio, and reusability cycle number. In addition, a
comparison of the benzylating agents was also
described.
2.1 Materials and reagents
Bentonite clay (Cernic International Co. Ltd.) with
the typical chemical analysis of (%wt): SiO2 63.60,
Al2O3 17.60, Fe2O3 3.10, CaO 3.00, Na2O 3.40, K2O
0.50, was purified by fractionated centrifugation in
order to discard quartz and impurities to get
montmorillonite. Then, montmorillonite from the
previous step was suspended in 5 M NaOH with the
ratio of clay to NaOH solution as 1 g : 50 mL for 24 h
at room temperature and repeated for three times to get
Na-montmorillonite. For the preparation of catalysts,
AlCl3⋅6H2O (Sigma Aldrich), NaOH (Merck) and
NdCl3⋅6H2O (Sigma Aldrich) were of laboratory
grade. De-ionized water was used throughout the
study. The prepared catalysts were characterized by a
X-ray
powder
Rigaku,
Dmax
2200/utima+
diffractometer with a monochromater and Cu K ∝
radiation. The 2θ was ranged from 2 to 30° with the
scan speed of 3°/min and the scan step of 0.02°.8
For catalytic study, toluene (Merck), benzyl
alcohol (Carlo ERBA), benzyl ether (Fluka), benzyl
chloride (Merck) were purchased as laboratory reagent
grade. Products were monitored by Shimadzu GC
(FID, SGE BP1 column).
2.2 Preparation and characterization of 2%NdCl3/AlPLM
Al-PLM was synthesized by the intercalation
aluminium pillaring precursors, followed by
calcination at high temperature. Na-clays were
dispersed in deionized water (10%wt) by continuous
stirring for 1 day at room temperature. Al-pillaring
agent was prepared by hydrolysis of NaOH and
AlCl3⋅6H2O with a mole ratio of OH/Al 1.9. Then, the
mixture was added slowly to the clay suspension for
24 h at room temperature. The products were collected
by centrifugation and washed with deionized water
until chloride ions were eliminated, checked the
disappearance of chloride ion by AgSO4. The
intercalated product (Al-PLM) was dried at 100°C for
24 h and calcined at 500°C at the rate of 5°C/min for 1
264
h. Next, the Al-PLM was impregnated by using a
solution of 2%NdCl3 in amount of minimized EtOH.
The slurry mixture was dried at 60°C and calcined at
450°C at the rate of 5°C/min for 4 h to obtain
2%NdCl3/Al-PLM.8
2.3 General benzylation procedure
In a sealed tube with a magnetic stirring bar, 2%
NdCl3/Al-PLM, benzylating agent 0.5 mmol and
toluene 8 mmol were mixed and heated. The reaction
mixture was filtered and washed with acetone. The
benzylation products were quantified by GC analysis.
Then, catalyst was activated by calcination at 450 °C
at the rate 5°C/min for 4 h.
3.1 Characterization of catalysts
Figure 1 represents the XRD patterns of
montmorillonite (a), Na-montmorillonite (b), Al-PLM
(c), and 2%NdCl3/Al-PLM (d) of 001 peak at 2θ. Namontmorillonite (b) shows peak shifted to lower 2θ
comparing with montmorillonite (a), while d001 basal
spacing of Na-montmorillonite (b) became increasing
of 11.4 Å to 12.5 Å. The different clearance space of
clay layers was resulted by solvating of Na ions
dispersion for balancing charge. The broad peak of AlPLM (c) was shown 13.2 Å which was shifted to the
larger basal spacing comparing with the d001 peak of
Na-montmorillonite (b). The resulting of larger basal
spacing of Al-PLM with Na ion between the layers of
montmorillonite could be exchanged by aluminium
polyoxocations. The OH/Al was intercalated into the
clay
layer
and
converted
to
Al-pillared
montmorillonite during calcination process. The d001
basal spacing of NdCl3/Al-PLM was 15.8 Å which
larger than that of Al-PLM. The d001 peak was broader
because of the re-calcination process which caused the
pillared stucture to collapse slightly and also the
impregnation of NdCl3 further increases distance
between the interlayer spacing of clay.
Figure 1. X-ray diffraction pattern of: (a)
montmorillonite; (b) Na-montmorillonite; (c) Al-PLM;
(d) 2%NdCl3/Al-PLM
3.2 Catalytic activity of 2%NdCl3/Al-PLM on FriedelCrafts benzylation of toluene
The Friedel-Crafts benzylation of toluene with benzyl
alcohol mainly produced benzyl toluene and benzyl
ether in different pathways. The benzyl ether was
formed by self-condensation of benzyl alcohols. On
the other hand, benzyl toluenes were produced
between toluene and benzyl alcohol by using 2%
NdCl3/Al-PLM which played the important role as
Lewis acid in this reaction.
The effect of catalyst amount, 2%NdCl3/Al-PLM in
Friedel-Craft benzylation of toluene and benzyl
alcohol was investigated as shown in Table 1. The
products were not observed in the absence of
2%NdCl3/Al-PLM (entry 1). However, 0.4% mol (10
mg) of 2%NdCl3/Al-PLM yielded benzyl toluene and
benzyl ether (entry 2). It could be rationale that the
acidity of 0.4% mol of this catalyst was too low for the
production of benzyl toluene. Hence, benzyl ether was
formed by self-condensation from the remaining
benzyl alcohols. On the other hand, increasing amount
of 2%NdCl3/Al-PLM to 0.8%mol (20 mg) and 2%mol
(50 mg) affected 100% conversion of benzyl alcohol
and none of benzyl ether was detected (entries 3-4).
Mass balance (MB) more than 95% indicated that
there was no undesired products occurred in the
reaction.
3.3 The effect of reaction temperature
From Table 2, the reaction temperature of 170°C gave
100% conversion of benzyl alcohol. It means that
monobenzylation of toluene underwent efficiently
(entry 4). However, at lower temperature, only trace
products were occurred (entries 1-3).
3.4 The effect of reaction time
The reaction time was investigated (Table 3). The
yield of products was increased when the reaction time
increased. For 15 min, high amount of recovered
benzyl alcohol and 18% yield of products were
observed (entry 1). When the reaction time was
extended to 30 min, the products were formed almost
100% (entry 2). The better yields of products could be
accomplished but little yield of benzyl ether was
occurred. This could be described that benzyl ether
which was formed from benzyl alcohol also functioned
as a benzylating agent in the reaction. The benzylation
of toluene with benzyl alcohol required 1 h for 100%
conversion of substrate to benzyl toluene (entry 3).
3.5 The efffect of mole ratio
Friedel-Crafts benzylation of toluene with benzyl
alcohol was carried out by varying the mole ratio of
toluene to benzyl alcohol as follows: 8:1, 16:1, 32:1
and 64:1 (entries 1-4). The conversion of benzyl
alcohol was found to increase with the higher reactant
mole ratio as shown in Table 4 (entries 2-4). Further
increase in mole ratio had affected on the reduction of
benzyl ether formation which is noticeable in the mole
265
ratio of 8:1 (entry 1). This means that there was no
sufficient toluene to react with benzyl alcohol.
Table 1: The effect of 2%NdCl3/Al-PLM amount on Friedel-crafts benzylation of toluene
Amount of
% products
2% NdCl3/
Mass
% recovery
% o-benzyl
% p-benzyl
% benzyl
Al-PLM (%
balance
toluene
toluene
ether
mol, mg)
0
96.9
0
0
0
96.9
0.4, 10
29.2
23.8
16.1
28.2
97.3
0.8, 20
0
59.3
39.0
0
98.3
2, 50
0
62.9
42.3
0
105.2
Reaction conditions: toluene (8 mmol), benzyl alcohol (0.5 mmol), sealed tube, 170 °C, 1 h
o:p-
(o-+p-)/
benzyl
ether
1.48
1.52
1.49
1.41
-
Table 2: The effect of temperature on Friedel-Crafts benzylation of toluene
% products
(o-+p-)/
Tempera
Mass
o% recovery
benzyl
% o-benzyl
% p-benzyl
% benzyl
balance
:pture (°C)
ether
toluene
toluene
ether
RT (30)
92.6
0
0
0
92.6
70
92.2
0
0
0
92.2
120
92.2
1.0
0.7
1.2
94.4
1.43
1.42
170
0
59.3
39.0
0
98.3
1.52
Reaction conditions: toluene (8 mmol), benzyl alcohol (0.5 mmol), sealed tube, 1 h, 2%NdCl3/Al-PLM (0.8% mol,
20 mg)
Table 3: The effect of time on Friedel-Crafts benzylation of toluene
% products
(o-+p-)/
Mass
oTime
benzyl
% recovery
% o-benzyl
% p-benzyl
% benzyl
balance
:p(min)
ether
toluene
toluene
ether
15
75.3
7.0
4.6
6.4
93.3
1.52
1.81
30
0
60.7
41.4
5.5
107.6
1.47
18.56
60
0
59.3
39.0
98.3
1.52
Reaction conditions: toluene (8 mmol), benzyl alcohol (0.5 mmol), sealed tube, 170 °C, 2%NdCl3/Al-PLM (0.8%
mol, 20 mg)
Table 4: The effect of mole ratio on Friedel-Crafts benzylation of toluene
Ratio of
% products
(o-+p-)/
toluene:
Mass
o% recovery
benzyl
% o-benzyl
% p-benzyl
% benzyl
benzyl
balance
:pether
toluene
toluene
ether
alcohol
8:1
15.8
33.5
22.5
32.7
104.5
1.49
3.54
16:1
0
59.3
39.0
98.3
1.52
32:1
0
62.8
37.1
99.9
1.69
64:1
0
67.1
43.7
110.8
1.53
Reaction conditions: toluene (8 mmol), benzyl alcohol, sealed tube, 170 °C,1 h, 2%NdCl3/Al-PLM (0.8% mol, 20
mg)
Table 5: The effect of benzylating agent on Friedel-Crafts benzylation of toluene
% products
Benzylating
Mass balance
o-:p% recovery
% o-benzyl
% p-benzyl
agent
toluene
toluene
Benzyl alcohol
0
59.3
39.0
98.3
1.52
Benzyl chloride
0
58.8
42.2
101
1.39
Benzyl ether
104.3
0.6
0.3
105.2
1.81
Reaction conditions: toluene (8 mmol), benzylating agent (0.5 mmol), sealed tube, 170°C, 1 h, 2%NdCl3/Al-PLM
(0.8% mol, 20 mg)
3.6 The effect of benzylating agent
There was no recovery of benzyl alcohol and benzyl
choride within 1 h (Table 5, entries 1-2). However, the
trace products were observed when benzyl ether was a
substrate due to the inefficient leaving group of benzyl
ether (entry 3). Thus, the capability of benzylating
266
agent in this reaction is as follows: benzyl alcohol ≈
benzyl chloride > benzyl ether.
Although both benzyl alcohol and benzyl chloride
gave good yields in the first 1 h, benzyl chloride was
3.7 Recovery and reuse of 2%NdCl3/Al-PLM
2%NdCl3/Al-PLM could be easily recovered by
filtration. After washing with acetone, drying at 80°C
in oven and calcination at 450°C at the rate of 5°C/min
for 4 h, the recovered 2%NdCl3/Al-PLM was used in
the next run. The catalyst can be reused at least 5 times
without appreciable loss of activity (entries 1, 2, 3, 6,
9-11). The results are shown in Table 6. The first and
second reuses of the catalyst under the same optimized
conditions showed 100% conversion (entries 1,4),
whereas the efficiency for the third run was not good
and showed 95% recovery of benzyl alcohol (entry 7).
According to the results, the efficiency of catalysts
was reduced when the reusability cycle numbers were
increased. It could be described that 2% NdCl3/AlPLM could not display the same activity because of
corrosive and released HCl. In addition, HCl formed in
Friedel-Crafts benzylation could cause the structural
damage of the clay catalyst.9
the high temperature in processing recovery, which
may cause the structural deterioration and
consequently lowered its activity. Hence, it was
reasonable to add higher amount of catalyst to 4% mol
(100 mg) of 2%NdCl3/Al-PLM in the next run (entries
9-14). On the other hand, the forth and fifth reused
catalyst could give high yield of benzyl toluene
(entries 10-11). The sixth and seventh reused catalyst
still exhibited 100% conversion but the high amount of
benzyl ether was detected as a result of insufficient
Lewis acid in the catalytic process (entries 12-13). The
eighth reused catalyst was inefficient for Friedel-Crafts
benzylation of toluene with benzyl alcohol since there
was 8.8% recovery of substrate benzyl alcohol (entry
14). This indicated that the catalyst can be reused at
least five times without appreciable loss of activity.
Table 6: Activity of regenerated 2%NdCl3/Al-PLM on Friedel-Crafts benzylation of toluene
% products
Amount of
%
2% NdCl3/
% o% p%
MB
o-:pTimes
Al-PLM
recovery
benzyl
benzyl
benzyl
(% mol, mg)
toluene
toluene
ether
1
0.8, 20
0
60.9
39.6
0
100.5
1.54
2, 50
0
67.1
44.1
0
111.1
1.52
4, 100
0
63.8
41.1
0
104.9
1.55
2
0.8, 20
0
58.1
37.8
5.9
101.8
1.54
2, 50
0
63.7
40.2
1.9
105.9
1.58
4, 100
0
64.2
42.1
0
106.3
1.53
3
0.8, 20
95.1
0.6
0.4
0.5
96.7
1.49
2, 50
5.6
42.6
27.8
29.8
105.8
1.53
4, 100
0
60.8
38.8
0
99.6
1.57
4
4, 100
0
61.8
40.5
0.9
103.2
1.53
5
4, 100
0
63.6
40.8
0.9
105.3
1.56
6
4, 100
0
56.5
36.9
6.5
99.9
1.53
7
4, 100
0
56.1
35.8
12.5
104.4
1.57
8
4, 100
8.8
43.1
27.4
20.9
100.2
1.57
Reaction conditions: toluene (8 mmol), benzyl alcohol (0.5 mmol), sealed tube, 170 °C, 1 h
4. Conclusions
The aim of this research was to study the catalytic
benzylation of toluene by using 2%NdCl3/Al-PLM as
the catalyst. The catalyst was synthesized by
intercalation of aluminium polyoxocations into clay
layers and then impregnation of 2%NdCl3. The
synthetic clay was characterized with XRD technique.
For catalytic reaction, 2%NdCl3/Al-PLM exhibited
highly reactive in the Friedel-Creafts benzylation of
toluene and could be recovered at least five times by
adding 4%mol of 2%NdCl3/Al-PLM in the next run.
References
[1] Ahmed, O.S. and Dutta, D.K., 2005, J. Mol. Cat. A.,
229, 227-231.
(o-+p)/
benzyl
ether
16.19
53.69
1.92
2.36
113.83
110.71
14.33
7.38
3.37
[2] Shrigadi, N.B., Shinde, A.B. and Samant, S.D., 2003,
Appl. Clay Sci. A., 252, 23-35.
[3] Kumar, CH. R., Rao, K.T. V., Prasad, P.S. S. and
Lingaiah, N., 2011, J. Mol. Cat. A., 337, 17-24.
[4] Salavati-Niasari, M., Hasanalian, J. and Najafian, H.,
2004, J. Mol. Cat. A., 209, 209-214.
[5] Sreekumar, R.. and Pillai, C.N., 1993, Catal Lett., 19,
281-291.
[6] Choudhary, V.R. and Jana, S.K., 2002, J. Mol. Cat. A.,
180, 267-276.
[7] Li, J., Xu, C., Lou, L.L., Zhang, C., Yu, K., Qi, B., Liu,
S. and Wang, Y., 2013, Catal. Commun., 38, 59-62.
[8] Keawbuarom, P. “Regioselectivity of phenol alkylation
using metal impregnated aluminium pillared bentonite”
Master’s Thesis, Department of Petrochemistry and
Polymer Science, Faculty of Science, Chulalongkorn
University, 2011.
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267
SYNTHESIS AND CHARACTERIZATION OF ISOINDIGO DERIVATIVES
AS MOLECULAR DONORS FOR ORGANIC PHOTOVOLTAICS
Patthira Sumsalee1, Visit Waewsungnoen2 and Vinich Promarak3*
School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand
E-mail: pattypatthira@hotmail.com
Abstract: Isoindigo was directly used as the building
block for oligomers or polymers, and less attention was
paid on the manipulation on its core structure. Still,
modification on isoindigo core may have influence on its
electric properties. In this work, we design new high
performance isoindigo-containing donor molecules
employing a novel molecular architecture with two
isoindigo chromophores in the conjugated backbone.
Three isoindigo derivatives containing aromatic cores
were synthesized using a combination of aldol
condensation, alkylation and Suzuki cross coupling
reactions. The different core moieties, anthracene,
benzothiadiazole and fluorene, were used in order to
increase molar absorptivity of desired molecules. They
were characterized by 1H NMR, 13C NMR, FT-IR and
mass spectrometry. The optical properties were studied
in dichloromethane solution. The desired compounds
exhibited wide absorption spectra in UV-visible region
(300-600 nm) with high molar extinction coefficient. The
results suggest that the synthesized compounds can be
used as donor molecules in organic photovoltaic devices.
1. Introduction
Organic photovoltaics (OPVs) have achieved
remarkable progress due to unique advantages such as
low cost, light weight and applications in flexible
large-area devices. Nitrogen-containing electrondeficient dyes, isoindigo, have attracted an increasing
attention as building blocks for organic photovoltaic
materials. High charge carrier mobility was obtained
for conjugated polymers based on isoindigo
derivatives. In this work, we synthesized and
characterized the novel isoindigo derivatives as
electron donor for organic photovoltaics. The different
core moieties, anthracene, benzothiadiazole and
fluorene, were used in order to increase molar
absorptivity of desired molecules.
2.1 Materials and instruments
Tetrahydrofuran
(THF)
was
refluxed
with
benzophenone and Na. Reagent and chemical were
purchased from chemical industry. 1H NMR and 13C
NMR were record by a Bruker Advance 500 mHz.
UV-Vis spectra were measured by Perkin-Elmer UV
lambda 25 spectrometer.
2.2 Experimental section
2.2.1 (E)-6,6'-dibromoisoindigo (3) [1]
A solution of 6-bromoisatin (0.5332 g, 2.21 mmol), 6bromooxindole (0.5031g, 2.36 mmol) and HCl 0.1 ml
as catalyst were added in 15 ml of acetic acid. The
reaction was refluxed for 15 h. The solution was
cooled and poured into water to give brown solid as
96% yield.
2.2.2 Iisoindigo derivatives (4)
(E)-6,6'-dibromoisoindigo (3) (0.8377g, 5.95mmol)
and K2CO3 (0.8223 g 5.95 mmol) were dissolved in
DMF 40 ml then 1-bromo-2-ethyl hexane 0.5 ml was
added. The solution was heated at 100 oC for 15 h. The
organic solvent was collected and dried over Na2SO4.
The crude product was purified by column
chromatography with hexane and dichloromethane as
eluent (2:1) to give red solid as 84% yield. 1H NMR
(500 mHz, CDCl3) δ = 9.03 (2H, d, J=10.0 Hz), 7.15
(2H, d, J=10.0 Hz), 6.89 (2H, s), 3.62 (4H, m), 1.82
(2H, s), 1.29 (16H, m) and 0.89 (12H, m) ppm.
2.2.3 (E)-6,6’-dibromoisoindigo thiophene (5)
A solution of compound (4) (0.5 g, 0.75 mmol) and 2thiopheneboronic acid (0.048 g, 0.38 mmol) were
dissolved in THF 20 ml. Catalyzed Pd2(PPh3)4 (0.021
g, 0.02 mmol). 2M Na2CO3 2.58 ml as base were
added into solution. The reaction was refluxed for 24 h
under N2 atmosphere. The solution was cooled and
poured into water. The organic layer was collected
and dried over Na2SO4. The crude product was
purified by chromatography with hexane and
dichloromethane (2:1) as eluent to give red-deep solid
as 51% yield. 1H NMR (500 mHz, CDCl3) δ = 9.13
(1H, d, J=5 Hz), 9.02 (1H, d J=10.0 Hz), 7.41 (1H, d,
J=5.0 Hz), 7.36 (1H,d, J=5.0 Hz) 7.28 (1H, d, J=5.0),
7.16 (2H, d, J=0 Hz), 7.11 (2H, m), 6.95 (1H, s), 6.87
(1H, s), 3.63 (4H, m), 1.83 (2H, t), 1.13 (16H, m) and
0.92 (12H, m) ppm.
2.2.4 IDTA
A solution of compound (5) (0.17 g, 2.64 mmol),
anthracene-9,10-diboronic acid bis(pinacol) ester
(0.05 g, 2.12 mmol) was dissolved in THF 20 ml.
Cs2CO3 (0.39 g, 1.2 mmol) and Pd2(PPh3)4 (0.014 g,
0.012 mmol) were added. . The reaction was refluxed
for 24 h under N2 atmosphere. The solution was cooled
and poured into water. The organic layer was collected
and dried over Na2SO4. The crude product was
purified by column chromatography with hexane and
dichloromethane (2:1) as eluent to give black solid as
36% yield. 1H NMR (500 mHz, CDCl3) δ = 9.17 (4H,
d, J=10.0 Hz), 8.34 (2H, d, J=5.0 Hz), 7.82 (2H,
d,J=5.0 Hz), 7.44 (3H, s), 7.38 (4H, d), 7.32 (3H, d,
268
J=5.0 Hz), 7.14 (4H, d, J=5.0 Hz), 7.01 (4H, s), 3.72
(8H, m), 1.90 (4H. s), 1.28 (32H, m) and 0.92 (24H,
m) ppm13C NMR (500 mHz, CDCl3) δ = 168.6
(4xC=O), 145.7 and 144.1 (Cq), 137.8 (Cq), 134.1
(Cq), 132.0 (Cq), 130.2 (CH), 128.3 (CH), 127.2 (CH),
126.1 (CH), 124.2 (CH), 121.0 (Cq), 119.3 (CH), 44.1
(CH2), 37.7 (CH), 30.8 (CH2), 29.7 (CH2) and 28.88
(CH2), m/z MALDI-TOF 1310.67
119.4 (CH), 44.1 (CH2), 37.1 (CH), 31.9 (CH2), 29.7
(CH2), 23.8 (CH2), 14.1 (CH3), 11.1 (CH3), m/z
MALDI-TOF 1268.60
2.2.2.6 IDTF
In 50 mL two-necked flask, (5) (0.12g, 0.2 mmol) and
9,9-dihexylfluorene-2,7-diboronic acid (0.05 g, 0.09
mmol), Pd(PPh3)4 (0.01 g, 0.009 mmol) as catalyst
Cs2CO3 (0.29 g, 0.9 mmol) as base were dissolved in
THF 20 ml. The mixture was refluxed for 24 h under
nitrogen atmosphere. The reaction mixture was cooled
and added 20 ml of water. The reaction was extracted
with CH2Cl2 and washed with water, dried over
anhydrous Na2SO4. Crude product was purified by
column
chromatography
with
hexane
and
dichloromethane (2:1) as eluent to give black solid as
54% yield. 1H NMR (500 mHz, CDCl3) δ = 9.24 (4H,
d, J=10.0 Hz), 7.51 (4H, s), 7.45 (4H, d, J=5.0 Hz),
7.41 (4H, d), 7.22 (4H, s), 7.09 (4H, s), 1.98 (4H, s),
1.49 (40H, m) and 1.04 (30H, m) ppm.13C NMR (500
mHz, CDCl3) δ =168.6 (4xC=O), 145.7 (Cq), 144.1
(Cq), 137.8 (Cq), 132.0 (Cq), 130.2 (Cq), 128.2 (CH),
126.1 (CH), 124.2 (CH), 121.0 (Cq), 44.1 (CH2), 37.8
(CH), 30.8 (CH2), 29.7 (CH2), 28.8 (CH2), 24.2 (CH2),
23.0 (CH2), 14.1 (CH3), 10.8 (CH3), m/z MALDI-TOF
1466.86
2.2.5 IDTB
A mixture of compound (5) (0.14 g, 0.22 mmol) and
2,1,3-benzothiadiazole-4,7-bis(boronic acid pinacol
ester) (0.04 g, 0.1 mmol) were dissolved in 20 mL of
THF. Pd(PPh3)4 (0.012 g, 0.01 mmol) and Cs2CO3
(0.33 g, 1.0 mmol) were added into reaction and
refluxed for 24 h under N2 atmosphere. The solution
was cooled and poured into water. The solution was
extracted with CH2Cl2. The combined organic layers
were washed with water, dried over anhydrous
Na2SO4. Crude product was purified using column
chromatography with hexane and dichloromethane
(2:1) as eluent gave black solid as 32% yield. 1H NMR
(500 mHz, CDCl3) δ = 9.25 (4H, d, J=10.0 Hz), 7.51
(4H, d, J=5.0 Hz), 7.45 (4H, d, J=5.0 Hz), 7.39 (4H, d,
J=10.0 Hz), 7.22 (4H, t), 7.09 (4H, s), 3.82 (8H, m),
1.98 (4H, s), 1.50 (32H, m) and 0.99 (24H, tt) ppm.
13
C NMR (500 mHz, CDCl3) δ = 168.6 (C=O), 145.7
(Cq), 144.1 (Cq), 137.7 (Cq), 132.0 (Cq), 130.2 (CH),
128.3 (Cq), 126.1 (CH), 124.2 (CH), 123.9 (CH),
Br
Br
Br
NH
O
O
CH3COOH
(2)
O
K2CO3
DMF
O
96 %
O
N
Br
O
conc. HCl
NH
+
(1)
H
N
Br
N
H (3)
Br
O
N
84%
S
O
O
N
O
O
Ar
51%
O
B
O
S
N
N
2M Na2CO3
Pd(PPh3)4
THF
B(OH)2
Ar
N
S
O
B
Br
(4)
S
N
O
O
Cs2CO3, Pd(PPh3)4
THF
O
N
Br
(5)
Ar
=
N
S
N
IDTA
IDTB
IDTF
36%
32%
54%
Figure 1. Synthesis pathway of IDTA, IDTB and IDTF
3. Resultsand Discussion
3.1 Synthesis and Characterization
The synthesis of three organic photovoltaic materials
is showed in Figure 1. The (E)-6,6'-dibromoisoindigo
(3) was synthesized by the presence of acid-catalyst
aldol condensation of 6-bromooxindole and 6-
bromoisatin in acetic acid[1]. The crude product was
purified by column chromatography to give brown
solid.
Then
alkylation
reaction
of
6,6’dibromoisoindigo using 1-bromo-2-ethylhexane in
DMF give isoindigo derivatives (4)[1]. 1H NMR
showed H of alkyl group near nitrogen atom at
chemical shift 3.62 ppm (4H) and 1.82-0.89 ppm.
Isoindigo derivatives were attached by Suzuki cross
269
in Figure 3 showed 3o amine stretching vibration was
observed in the region 3500 cm-1which was the
characteristic of lactam. C=O stretching vibration is
improved at 1500 cm-1.
IDTA
IDTB
IDTF
80
70
60
Transmittance
coupling reaction of (4) and 2-thiopheneboronic acid
in the presence of Pd(PPh3)4 as catalyst in THF to give
(5). The target molecules were obtained by Suzuki
cross coupling reaction of (5) and aryl diboronic ester
in THF the presence of Pd(PPh3)4 as catalyst and
Cs2CO3 as base. The 1H NMR spectra of IDTA, IDTB
and IDTF showed in Figure 2. 1H-NMR spectrum of
IDTA showed doublet signal at chemical shift 9.17
ppm (2H) assigning of H atom which carbonyl group.
8.35-1.01 ppm showed the aromatic proton. Multiplet
peak at 3.72 ppm (8H) showed protons of alkyl. 1H
NMR spectrum of IDTB showed doublet at 9.25 ppm
(2H) which indicated the signal aromatic protons of Hbond and carbonyl group. Chemical shift 7.09-7.52
ppm showed aromatic protons. Chemical shift 3.82
ppm (8H) protons of alkyl groups near nitrogen
atom.1H NMR spectrum of IDTF showed doublet
signal at chemical shift 9.24 ppm (2H) proton
assigning as aromatic which is bonding with carbonyl
groups. Chemical shift 7.09-7.51 ppm was aromatic
proton. Chemical shift 3.81 ppm (8H) showed
multiplet which protons of alkyl near nitrogen atom
and chemical shift 1-1.98 ppm as proton of alkyl
chains.
50
40
30
20
C=O
10
o
0
4000
3 N-C
3500
3000
2500
2000
1500
1000
500
wavenumber (cm-1)
Figure 3. IR spectra of IDTA, IDTB and IDTF
3.2 Optical properties
The UV-Vis absorption spectra of organic photovoltaic
materials in dilute CH2Cl2 solution are shown in
Figure 4. The absorption spectra of all organic
photovoltaic materials showed relative large molar
extinction coefficient in visible region (300-600 nm).
IDTF showed highest molar absorptivity relative to
IDTB and IDTA. The synthesized molecules
exhibited very low photoluminescence indicating these
molecules can be used as donor materials in OPVs.
80000
IDTA
IDTF
IDTB
70000
(a)
molar absorptivity
60000
50000
40000
30000
20000
10000
0
300
400
500
600
700
800
wavelength (nm)
(b)
Figure 4. Absorption spectra of IDTA, IDTB and
IDTF in CH2Cl2 solution.
4. Conclusions
In summary, we have successfully synthesized three
organic photovoltaic materials which contained
isoindigo bearing various core moieties (anthracene,
benzothiadiazole and fluorene) as electron donors. The
organic photovoltaic materials showed visible region
(300-600 nm) in UV-Vis absorption spectra.
(c)
Figure 2. H NMR spectra of (a) IDTA, (b) IDTB and
(c) IDTF
The 13C NMR of IDTA, IDTB and IDTF showed
chemical shift at 168.66 ppm assigning of carbonyl
groups. The FT-IR spectra of IDTA, IDTB and IDTF
1
Acknowledgements
This work was financially supported by Suranaree
University of Technology.
270
References
[1] Christos, P., Xaver, P. and Helv, B.,1998,Chim Acta.,
71, 1079–1083.
[2] Wang, D., Ying, W., Zhang, X., Hu, Y., Wu, W. and
Hua J., 2015 Dyes Pigm., 112, 327-334.
[3] Wang, G., Tan, H., Zhang, Y., Wu, Y., Hu, Z., Yu, G.
and Pan, C., 2014, Synth. Met., 187, 17-23.
[4] Zhao, N., Qiu, L., Wang, X., An, Z. and Wan, X., 2014,
Tetrehedron Lett., 1040-1044.
271
SYNTHESIS TOWARDS N-HETEROAROMATIC THENA DERIVATIVE:
INVESTIGATION ON [4+2]-CYCLOADDITION OF HIGHLY
REACTIVE PYRIDYNE
Chalupat Jindakun, Thanawon Chaisantikulwat, Jakapun Soponpong, Kulvadee Dolsophon,
Tienthong Thongpanchang*
Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
*E-mail: tienthong.tho@mahidol.ac.th Tel. +66 2201 5130, Fax. +66 2201 5139
Abstract: Analogous to 1,2,3,4-tetrahydro-1,4-epoxy
naphthalene-1-carboxylic acid (THENA), a novel chiral
derivatizing agent (N-THENA 4) bearing a pyridine
moiety as an anisotropic group was first designed and
synthesized with the main objective to study the
anisotropic effect of heteroaromatic moiety in the
absolute configuration analysis. The key synthetic step is
the formation of bicyclic compound 3, which was directly
synthesized from [4+2]-cycloaddition reaction of a highly
reactive 2,3-pyridyne intermediate 1 and an electron
deficient methyl furan-2-carboxylate 2. A variety of
conditions to generate 2,3-pyridyne intermediate from 3(trimethylsilyl)pyridin-2-yl triflate were investigated and
the bicyclic compound 3 was prepared in 5% yield under
the optimal condition.
O
O
CO2 Me
+
1
2
O
[4+2]
cycloaddition
N
At present, there are a number of common CDAs
generally used to determine the configuration of chiral
compounds such as -methoxy--trifluoromethyl-phenylacetic acid (MTPA) or acid chloride derivative
(MTPACl), both of which are usually called
Mosher’s reagents[2a‒b], -methoxy--phenylacetic
acid (MPA)[2b‒c] and -(9-anthryl)--methoxyacetic
acid (9-AMA)[3] (Figure 2). Their conformations are
presumably controlled by the stereoelectronic effect of
elecron-withdrawing groups (trifluoromethyl or
methoxy groups) and steric effect of the aryl ring,
which orient high electronegative group syn-periplanar
to the carbonyl group[4].
steps
CO 2Me
3
N
CO 2H
N
N-THENA 4
1. Introduction
Determining the absolute configuration of chiral
compounds is essential for natural products and
asymmetric syntheses. There are several instrumental
methods to define the absolute configuration such as
chiroptical methods[1a‒b], X-ray crystallography
[1c‒d] or chiral HPLC[1e‒g]. NMR spectroscopy is
reportedly a powerful technique due to its convenience
and no reference standard requirement[1h‒i]. To
determine the configuration via the NMR technique,
chiral compounds with undefined stereochemistry are
derivatized with a pair of enantiomers of a chiral
derivatizing agent (CDA) to generate two diastereomeric forms. As a result of the anisotropic effect of the
aromatic moiety of CDA, 1H-NMR spectra of the
diastereomers display the distinct signals of which the
differences (L1 and L2) could indicate the
absolute configuration of chiral compounds (Figure 1).
Figure 2. Common chiral derivatizing agents
Recently, our group has synthesized a novel
CDA, tetrahydro-1,4-epoxynaphthalene-1-carboxylic
acid (THENA), for defining the chirality of secondary
alcohols (Figure 3)[5]. The conformation of THENA
was locked with covalent bonds in a bicyclic form,
resulting in only the deshielding effect to play a vital
role in differentiating spectroscopic signals. Although
most CDAs depend on the anisotropic effect of the
aromatic hydrocarbon, the effect of heteroaromatic
moiety has never been investigated. Based on the rigid
structure of THENA, the new CDA bearing pyridine
ring (N-THENA 4) is designed and synthesized to study
the effect of pyridine moiety in configuration analysis
(Figure 3).
O
CO 2H
THENA
O
CO2 H
N
N-THENA 4
Figure 3. New chiral derivatizing agent bearing
N-heteroaromatic moiety (N-THENA 4).
Figure 1. Concept of chiral derivatizing agent (CDA)
for determining the absolute configuration by NMR
spectroscopy.
Relating to the synthesis of THENA, the
retrosynthetic analysis of N-THENA 4 was shown in
Scheme 1. The desired target molecule 4 can be
272
achieved by hydrolysis and hydrogenation of the
Diels-Alder adduct 3, which could be obtained from
[4+2]-cycloaddition of 2,3-pyridyne 1 and methyl
furan-2-carboxylate 2. Apparently, the Diels-Alder
reaction of 2,3-pyridyne 1 with furan carboxylate 2 is
of great challenge due to the electron deficient nature
of the diene.
Diels-Alder
O
O
hydrolysis
CO2H
N
N-THENA (4)
and
hydrogenation
O
CO2Me
N
3
CO2Me
+
N
1
2
Scheme 1. The retrosynthetic analysis of N-THENA 4
Reportedly, the pyridyne intermediate could be
generated from two types of precursors[6‒7] as
depicted in Scheme 2. A sequential halogen-metal
-elimination of 3-bromo-2exchange
and
chloropyridine 6 with strong base (Method A) yielded
the 2,3-pyridyne intermediate 1[6a]. An alternative
milder condition was fluoride-induced desilylationelimintation of 3-(trimethylsilyl)pyridin-2-yl triflate 7
with anhydrous CsF (Method B) which also generated
the desired 2,3-pyridyne 1 [7].
Scheme 2. Two reported methods for 2,3-pyridyne
intermediate formation.
2.1 General Experiment
Merck silica gel 60H was used for column
chromatography. 1H-NMR spectra were recorded on
Bruker Ascend 400 MHz spectrometer in deuterated
solvents. All reactions were conducted in oven-dried
glasswares, unless otherwise instructed in the
procedure. All solvents were distilled before use.
In case of tetrahydrofuran (THF), it was freshly
distilled over sodium/benzophenone under nitrogen
atmosphere.
2.2 Synthetic Method
2.2.1 Synthesis of methyl 5,8-dihydro-5,8-epoxy
quinoline-8-carboxylate 3
Method A: The method was modified from that
reported in ref.[6a]. A 1.6 N solution of n-butyllithium
in hexane (0.71 mL, 1.14 mmol) was added dropwise
to a solution of 3-bromo-2-chloropyridine 5 (200 mg,
1.04 mmol) in THF (3 mL) at ‒78oC over 15 min
under nitrogen atmosphere and left stirring for 30 min.
Then methyl furan-2-carboxylate 2 (0.9 mL, 8.41
mmol) was slowly dropped to the reaction mixture at
‒78oC over 5-10 min, and the reaction mixture was
allowed to stir at room temperature for 1 h. After that,
the reaction was quenched with water and extracted
with dichloromethane (3x20 mL). All organic layers
were combined, dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude product was
purified by column chromatography with 1:6:13
MeOH:EtOAc:hexane as an eluent to afford 54 mg (25
%) of (2-chloropyridin-3-yl)(furan-2-yl)methanone 8
as a brown solid and 53 mg (16%) of (2-chloropyridin3-yl)di(furan-2-yl)methanol 9 as a brown solid
1
H NMR of 8 (CDCl3) δ: 8.51 (dd, 3J = 4.8 Hz, 4J =
1.9 Hz, 1H), 7.79 (dd, 3J = 7.5 Hz, 4J = 1.9 Hz, 1H),
7.69 (d, 3J = 0.9 Hz, 1H), 7.36 (dd, 3J = 4.8 Hz, 7.52
Hz, 1H), 7.12 (d, 3J = 3.6 Hz, 1H), 6.59 (dd, 3J = 1.6
Hz, 3.6 Hz, 1H). 13C NMR (CDCl3) δ: 181.1, 152.5,
151.9, 149.3, 148.8, 138.8, 134.6, 122.8, 122.3, 113.6.
1
H NMR of 9 (CDCl3) δ: 8.39 (dd, 3J = 4.5 Hz, 4J =
1.5 Hz, 2H), 7.73 (dd, 3J = 7.9 Hz, 4J = 1.7 Hz, 2H),
7.51 (d, 3J = 1.1 Hz, 1H), 7.28 (dd, 3J = 4.7 Hz, 7.9
Hz, 2H), 6.42 (dd, 3J = 3.3 Hz, 4J = 1.4 Hz, 1H), 6.20
(d 3J = 3.3 Hz, 1H). 13C NMR (CDCl3) δ: 152.8, 149.2,
148.8, 143.2, 139.6, 136.9, 122.3, 111.0, 110.9, 76.6.
Method B: A mixture of methyl furan-2carboxylate 2 (2 mL, 18.7 mmol) and 3(trimethylsilyl)
pyridin-2-yl triflate 7 (500 mg, 1.67 mmol)[7] was
slowly transferred to flame-dried cesium fluoride at
room temperature under nitrogen atmosphere. The
reaction was allowed to stir vigorously at ambient
temperature for 3 h. Then the reaction mixture was
diluted with EtOAc (20 ml) and washed with water
twice. The aqueous layer was extracted back with
EtOAc twice and the organic layers were combined,
dried with Na2SO4 and concentrated in vacuo. The
excess furan ester 2 was removed by Kugelrohr
distillation under reduced pressure and the residue was
purified by flash column chromatography using 1:6:13
MeOH:EtOAc:hexane as an eluent to afford methyl
5,8-dihydro-5,8-epoxyquinoline-8-carboxylate 3 as a
yellow solid in 8.4 mg (5.1 %yield)
1
H NMR of 3 (MeOD-d4) δ: 7.97 (d, 3J = 5.3 Hz,
1H), 7.65 (d, 3J = 7.2 Hz, 1H), 7.23‒7.19 (m, 2H),
7.03 (dd, 3J = 5.4 Hz, 7.2 Hz, 1H) 5.94 (d, 3J = 1.48
Hz, 1H), 3.97 (s, 3H). 13C NMR (MeOD-d4) δ: 172.1,
168.1, 146.3, 144.1, 143.4, 141.8, 135.8, 121.6, 91.8,
83.1, 53.4.
2.2.2 Synthesis of methyl 5,6,7,8-tetrahydro-5,8-epoxy
quinoline-8-carboxylate 12
A mixture of compound 12 (69 mg, 0.34 mmol)
and 10% Pd/C (7 mg) in methanol (5 mL) was allowed
to stir at room temperature for 16 h under hydrogen
atmosphere. The reaction mixture was filtered through
a pack of Celite pad and washed with MeOH. The
filtrate was then concentrated in vacuo to give 70 mg
(quantitative) of the desired product as yellow oil. The
crude product was used in the next step without further
purification.
1
H NMR of 12 (MeOD-d4) δ: 8.25 (dd, 3J = 5.2 Hz,
4
J = 1.3 Hz, 1H), 7.76 (dd, 3J = 7.4 Hz,4J = 1.3 Hz,
1H), 7.27 (dd, 3J = 5.3 Hz, 7.5 Hz 1H), 5.59 (d, 3J =
4.4 Hz, 1H), 3.94 (s, 1H), 2.31‒2.21 (m, 2H),
1.78‒1.73 (m, 1H), 1.55‒1.50 (m, 1H). 13C NMR
(MeOD-d4) δ: 169.9, 165.2, 147.5, 140.2, 129.2, 123.9,
88.0, 79.5, 53.2, 29.3, 28.7.
273
2.2.3 Synthesis of 5,6,7,8-tetrahydro-5,8-epoxy
quinoline-8-carboxylic acid (N-THENA) 4
Pulverized potassium hydroxide (95 mg, 1.7 mmol)
was added to a solution of 12 (70 mg, 0.34 mmol) in
1,4-dioxane and MeOH (1:1, 0.6 mL). Then the
reaction was allowed to stir at room temperature for 3
h. The reaction mixture was diluted with MeOH and
acidified with 1 N HCl to pH 1-2 at room temperature
and evaporated to dryness. The crude product was
desalinated by adding a mixture of EtOAc/MeOH
(1:1) and filtration. The mother liquor was evaporated
and the obtained solid was recrystallized in hot acetone
to give 71 mg (75% yield) of N-THENA as a white
crystal.
1
H NMR of 4 (MeOD-d4) δ: 8.23 (d, 3J = 4.8 Hz,
1H), 7.66 (d, 3J = 7.3 Hz, 1H), 7.16 (dd, 3J = 5.5 Hz,
7.1 Hz 1H), 5.46 (d, 3J = 4.9 Hz, 1H), 2.25‒2.20 (m,
1H), 2.16‒2.12 (m, 1H), 1.77‒1.71 (m, 1H), 1.48‒1.44
(m, 1H). 13C NMR (MeOD-d4) δ: 170.6, 163.3, 145.2,
142.0, 131.8, 124.8, 87.6, 79.5, 29.8, 28.5.
From Table 1, treatment of acetonitrile solution of
pyridyne precursor 6 with CsF in the presence of furan
ester 2 gave only a trace of Diels-Alder adduct 3 (entry
1). An increased amount of 2 under neat condition
gave a better yield of the desired product 3 as expected
(entries 2 and 3). In addition, flame-dried CsF under
vaccum gave a better yield than normal dried CsF
under vaccum (entries 5 and 6). This may be due to the
presence of water in the normal dried CsF.
Table 1: Diels-Alder reaction condition of 6 with 2a
Fsource
furan 2
(equiv)
1
CsF
4.0
2
CsF
3
A halogen-metal exchange-elimination sequence of
dihalopyridine 5 with strong base (Method A) was first
carried out. In this study, no Diels-Alder adduct was
observed. Instead, our result indicated that the lithiated
pyridine 7 underwent 1,2-addition with furan
carboxylate 2 to yield ketone 8 and alcohol 9 (Scheme
3). This observation suggested that, under our reaction
condition, the 1,2-addition (pathway B) of pyridyl
lithium 8 to carbonyl group is preferable than the 1,2elimination (pathway A) to form pyridyne
intermediate[6].
4
pathway A
N
1
Br
Li
n-BuLi
N
5
Cl THF, 78 oC
30 min
N
Cl
7
N
O
O
pathway B
MeO 2C
O
N
+
Cl
OH
Cl
N
2
78oC to rt
8 (25%)
Cl
O
9 (16%)
Scheme 3. Two possible competitive reactions of (2bromopyridin-3-yl)lithium 7, trapping with furan 2.
The mild and effective method for in situ pyridyne
formation was achieved from treatment of 3(trimethylsilyl)pyridin-2-yl triflate 6 with anhydrous
CsF[7]. Triflate 6 was synthesized from 2hydroxypyridine 11 in high yield over 2 steps (Scheme
4)[7b].
Scheme 4. Synthetic route of a pyridyne precursor 6.
Entry
Time
(h)
Yieldb
(%)
18
0.7
4.0
Solvent
(mL)
MeCN
(1.7 mL)
neat
18
2.4
CsF
11.1
neat
18
4.1
CsF
11.1
neat
1
1.7
5
c
CsF
11.1
neat
1
4.1
6c
CsF
11.1
neat
3
5.3
7
TBAF
1M
TBAF
11.1
neat
3
2.3
11.1
THFd
18
0
8
a
All reaction using 1.67 mmol of 6 reacting with 4 equiv of Fsource at ambient temperature under neat condition.
b
isolated yield of 3.
c
Anhydrous CsF was dried with Bunsen-flame under vacuum prior
to use.
d
solvent was from 1M TBAF in THF.
Tetrabutylammonium fluoride (TBAF), consisting
of more hydrophobic moiety, was used to allow the
reaction to perform as a homogeneous solution (entry
7). The desired product, however, was produced in
lower yield. Additionally, when commercially
available 1M solution of TBAF in THF was used, the
desired product cannot be detected (entry 8). It is
possible that moisture in the commercial reagent could
potentially impede the reaction[7a].
The position of nitrogen atom in 3 was confirmed
by 2D NOESY experiment. The result showed a crossrelaxation peak between H-4 ( = 7.65 ppm) and the
bridgehead proton (H-b,  = 5.95 ppm) as shown in
Figure 4. Another adduct with different regiochemistry
could also be formed. However, the pure compound
could not be isolated from other uncharacterized byproducts.
Figure 4. Key NOESY cross relaxation peak of 3.
274
The unsaturated bicyclic 3 was then reduced by
catalytic hydrogenation to provide the saturated
bicyclic ester 5 in quantitative yield. In the final step,
hydrolysis of ester 5 was conducted by potassium
hydroxide in a mixture of dioxane and methanol to
obtain the target product in 75% yield (Scheme 5).
[5]
[6]
[7]
Scheme 5. Reactions of 3 toward N-THENA 4 by
catalytic hydrogenation and subsequent hydrolysis.
Sungsuwan, S., Ruangsupapichart, N., Prabpai, S.,
Kongsaeree, P. and Thongpanchang, T., 2010,
Tetrahedron Lett., 51, 4965‒4967.
(a) Cook, J. D. and Wakefield, B. J., 1969, J. Chem.
Soc. C, 1973‒1978. (b) Walter, M. A. and Shay, J. J.,
1995, Tetrahedron Lett., 36, 7575‒7578. (c) Connon,
S. J. and Hegarty A. F., 2001, Tetrahedron, 42,
735‒737. (d) Connon, S. J. and Hegarty, A. F., 2004,
Eur. J. Org. Chem., 3477‒3483
(a) Walters, M. A. and Shay, J., 1997, Syn. Comm., 27,
3573‒3579. (b) Carroll, F. I, Robinson, T. P.,
Brieaddy, L. E., Atkinson, R. N., Mascarella, S. W.,
Damaj, M. I., Martin, B. R. and Navarro, H. A., 2007,
J. Med. Chem., 50, 6383‒6391. (c) Effenberger, F. and
Daub, W., 1991, Chem. Ber., 124, 2119‒2125.
4. Conclusions
A reaction of pyridyne and electron-deficient diene
was first reported. It was found that 6 was the only
pyridyne precursor able to provide the desired product
3 in 5% yield while 5 could not generate the 2,3pyridyne intermediate. The key compound 3 was
subsequently reduced and hydrolyzed to afford NTHENA 4 in 75% yield over 2 steps. The structure of
product was assured by NMR experiments.
Acknowledgements
Financial and facility support from Faculty of Science,
Mahidol University and The Center of Excellent for
Innovation in Chemistry (PERCH-CIC) are gratefully
acknowledged.
References
[1]
[2]
[3]
[4]
Instrumental techniques for the determination of the
absolute configuration: Chiral optical methods
(a) Polavarapu, P. L., 2002, Chirality, 14, 768‒781 (b)
Sundararaman, P., Barth, G. and Djerassi, C., 1981, J.
Am. Chem. Soc., 103, 5004‒5007.; X-ray
crystallography (c) Harada, N., 2008, Chirality, 20,
691‒723. (d) Bijuvoet, J. M., Peerdeman, A. F. and
Bommel, A. J. 1951, Nature, 168, 271‒272.; Chiral
HPLC (e) Roussel, C., del Rio, A., Pierrot-Sanders, J.,
Piras, P. and Vanthuyne, N., 2004, J. Chromatogr. A,
1037, 311‒328. (f) Kobayashi, J., Hosoyama, H.,
Katsui, T., Yoshida, N. and Shigemori, H., 1996,
Tetrahedron, 52, 5391‒5396. (g) Luesch, H., Yoshida,
W. Y., Moore, R. E. and Paul, V. J., 2000, J. Nat.
Prod., 63, 1437‒1439.; and NMR (h) Seco, J. M.,
Quiñoá, E. and Riguera, R., 2004, Chem. Rev., 104,
17‒117. (i) Parker, D., 1991, Chem. Rev., 91,
1441‒1457.
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Org. Chem., 34, 2543‒2549. (b) Dale, J. A. and
Mosher, H. S., 1973, J. Am. Chem. Soc., 95, 512‒519.
(c) Dale, J. A. and Mosher, H. S., 1968, J. Am. Chem.
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Seco, J. M., Latypov, Sh. K., Quiñoá, E. and Riguera,
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Riguera, R., 1995, J. Org. Chem., 60, 504‒515. (b)
Seco, J. M., Latypov, Sh. K., Quiñoá, E. and Riguera,
R., 1997, Tetrahedron, 53, 8541‒8564.
275
CHEMOSELECTIVE REDUCTIONS OF NITROBENZENE USING
CHITOSAN-COATED METAL AS A CATALYST
Thamonwan Angkuratipakorn, Pawinna Chanthawong, Jirada Singkhonrat*
Department of Chemistry, Faculty of Science and Technology, Thammasat University, KlongLaung, Pathumthani, 12120, Thailand
*E-mail: jirada@tu.ac.th, Tel. +662 564440 ext 2417, Fax. +662 564 4483
Abstract: A micellar technology for chemoselective
reductions has been developed using chitosan-coated
metal as a catalyst. Our works focus, in part, on the
design of nonionic surfactants that enable transitionmetal-catalyzed reactions to be performed in water at
room temperature (rt), rather than in traditional organic
solvents. Several applications of micellar technology to an
array of valued organic transformations have already
been developed. To further expand the scope of these
micellar surfactant conditions, zinc mediated reductions
of nitrobenzene offer 100% conversion within 2 hours at
rt.
functionalization. Herein, we attempt to develop a
transition-metal-free approach for reduction of
nitroarenes in H2O employing a modified chitosan as a
hydrogen source (Scheme 1). The use of modified
chitosan as reducing agent for transition metal-free
reduction is inspiring. Therefore, carrying out the
reaction in water without employing any metal or with
low loading of metal could make the present method
highly attractive.
1. Introduction
2.1 Chemicals
All commercially available compounds were used
as
received.
A
representative
hydrophobic
nitrobenzene was examined in a 2% w/v of aqueous
solution of the designed surfactant PGS oligomer,
which is a bio-surfactant developed in our research
group (Scheme 2). Addition of zinc dust and
ammonium chloride to a solution of nitrobenzene 1
resulted in a clean conversion to aminobenzene 2 upon
stirring for 2 h at rt (Scheme 1).
Aromatic and heteroaromatic primary amines are
important as building blocks for the synthesis of a
wide range of pharmaceuticals, polymers, special and
fine chemicals. While a wide range of protecting
groups are available to bound amine reactivity, one
popular approach involves their masking as
nitroarenes. This approach offers multiple benefits,
including facile nitrogen introduction via early stage
nitration, tremendousatom economy, good stability of
the nitro group under numerous reaction conditions,
and directed arene functionalization resulting from the
associated electronics of the nitromoiety[1]. Catalytic
hydrogenation using transition metal catalysis has
received high interest, but this approach exhibits
limited selectivity in the presence of other reducible
functional groups, similar to transfer hydrogenation
processes which often show a decrease in yields in the
presence of other reducible groups [2].
In addition, the major drawbacks linked to some of
those conditions are the difficulty to handle reactants
and the utilization of toxic or expensive reagents, for
example, though the high toxicity, potential
flammability, and instability of hydrazine. In the
search of new methodologies to reduce organic
molecules, the utility of micellar technology was
studied. The micellar surfactant conditions have been
already identified as efficient reactants to promote
reductions in the presence of transition metals [3].
One of the major challenges in academia and
industry is the development of environmentally
friendly synthetic processes. This communication aims
at developing an efficient method to reduce
nitrobenzene selectively into aminobenzene employing
micellar technology catalyzed by chitosan-coated Zn
bead nanoparticles. Thus, selecting one method
amongst the two specific conditions should provide a
powerful and helpful toolbox for selective
NO2
2 equiv. NH4Cl
H2O
NH2
4%wt PGS oligomers
chitosan - Zn dust
RT , 2h
Nitrobenzene 1
100% conversion
Aminobenzene 2
Scheme 1: Reduction of nitrobenzene in green
solvents (water) at rt
Monitoring the reaction products by GCMS
(GCMS-QP2010 Ultra SHIMADZU using Column
HP-5MS (30 m x 0.25 mm x 0.25 µm) with
temperature limits from 60 to 325oC) revealed that no
residual nitroso 3a-3c or hydroxylamine intermediates
was found at full conversion (Table 1, entry 6). The
amino product 2 in more than 95% yield was obtained
by using simple workup including filtration through a
silica gel plug followed by rinsing with a minimal
volume of ethyl acetate and aqueous ammonium
hydroxide. The organic layer was recovered by simple
decantation, dried over MgSO4, filtered, and
evaporated under reduced pressure. Alternatively,
extraction with a minimal volume of organic solvent
led to the isolated product with similar purity and
yield.
276
2.2 Modification of chitosan (CS)
Modified chitosan was prepared as follows:
Chitosan (CS, 0.4 g) was dissolved in distilled water
(50 mL) 2% acetic acid with constant stirring for
approximately 24 h at rt. The homogeneous solutions
were poured and precipitated with bentonite solution
to obtain CS-immobilized on bentonite (CIB). The
bead polymers were allowed to dry at 60°C for 24 h.
The dried chitosan matrix was heated at 100°C under
moderate vacuum for 2 h. Modified chitosans were
studied for their structural characteristics using X-ray
Diffractometry (XRD) and Fourier Transform Infrared
Spectroscopy (FTIR). Thermogravimetric analyses
were performed with a Netzsch TG 209 C apparatus.
Surface modification of Zn dust with chitosan (CS)
Zn dust was used for coating procedure. 1% Bare Zn
dust was dispersed in 0.5% and 1% (w/v) CS
solution in 2% (v/v) acetic acid (1:1 and 1:2 of
CS:Zn). The Zn dust was activated by 0.1M HCl. The
mixture was ultrasonicated for 30 min. After
ultrasonication, the CS-coated Zn dust (CS-Zn) was
allowed to settle, and was washed with distilled
water (3 times) in order to remove excess CS.
These CS-Zn catalysts were then separated (wet CS
coated-Zn) and dried at 50°C for 24 h (dried CS
coated-Zn) used in the reaction as initial Zn weight for
preparation above. The Catalysts are under
investigation for their structural characteristics using
X-ray Diffractometry (XRD), Fourier Transform
Infrared Spectroscopy (FTIR), Thermo-Gravimetric
Analysis (TGA), Scanning Electron Microscopy (SEM
as showed in scheme 3), and Transmission Electron
Microscopy (TEM).
C14H29
O
O
O
OH
HO
(b)
Scheme 3. SEM micrographs of (a) Zn dust and (b)
chitosan-coated Zn dust (dried CS coated-Zn)
at 0.5 M substrate concentration. Low yield was
observed in the reaction condition with unactivated Zn
and with activated Zn under th e conventional workup
(Table 1, entries 1-2 and entries 3-4, respectively). A
suspension formed in the aqueous phase during the
extraction with ethyl acetate was due to the inherent
insolubility of the catalyst.
OH
O
O
(a)
O
2
O
O
O
O
MW = 910
OH
Scheme 2. Molecular structure of palmitoyl-(PGS)3glycerol (PG1.5SF0.32) [4]
Procedure for Reduction of nitroarenes.
To a solution of 4.87 mmol (0.5 M) of nitrobenzene in
water (10 mL) were added 9.74 mmol (2 equiv) of
NH4Cl, PG1.5SF0.32 4wt% and Zn dust 48.7 mmol (10
equiv). The mixture was stirred at room temperature
for the desired time (Table 1). A simple workup entails
filtration through a silica gel plug followed by rinsing
with a minimal volume of ethyl acetate and
ammonium hydroxide. The product was extracted with
ethyl acetate. The ethyl acetate layer was evaporated at
reduced pressure on a rotary evaporator.
In the first set of the experiments, the reactivity of
substrate 1 in aqueous micellar conditions was studied
at rt in water. The nitrobenzene was a model substrate
Scheme 4. Possible pathways for the reduction of
nitrobenzene by Zn dust in PG1.5SF0.32/H2O and NH4Cl
at rt
Therefore, the reduced intermediates 3a-3c and
reduced product 2 were trapped within micelle. The
use of silica gel filtration was introduced for work-up
step. For reduction in aqueous media, it was reasoned
that micelles acted as carriers of the insoluble substrate
from the solution to the catalyst surface and improved
the diffusion to reactive centers. The reduced product
2 was then expelled from the micelles as its water
277
solubility was increased and extracted with ethyl
acetate and ammonium hydroxide solution during
work-up process to achieve higher yield (Table 1,
entries 5-6). In the absence of added additives, the
conversion of nitrobenzene 1 was quantitative when
the reaction was carried out in water for 3 and 2 hours
employing both 2%wt and 4%wt surfactants (PGS
oligomer), respectively (Table 1, entries 5 and 6).
Additionally, to investigate the reduction pathway,
the reduction of nitrobenzene 1 was monitored by GCMS. Masses corresponding to the intermediates would
be able to suggest transformation under which
reduction conditions, i.e., direct or condensation
pathway is carried out. When the reaction of
nitrobenzene catalyzed by the Zn dust was performed
successfully under the conditions described in Scheme
1, no traces of azoxybenzene 3a or diazene 3b were
detected (GC-MS). When the reduction of
nitrobenzene 1 was carried out under the optimum
reaction conditions albeit with low Zn dust loading, no
reduced product 2 was formed, but also provided
reduced intermediate 3 (azoxybenzene 3a and diazene
3b) as the major products (Table 1, entries 7-8).
Therefore, these results clearly suggested that the
condensation route was predominant in the present
reaction conditions (Scheme 4).
Lowering the catalyst loading (5 equiv.) showed to
be ineffective in terms of substrate conversion or yield
of reduced product 2 (Table 1, entry 7) and revealed
no effect or improvement from higher amount of the
surfactant (Table 1, entry 8). Problems of
azoxybenzene 3a accumulation are more frequently
encountered for low catalyst loading due to the low
reduction capacity. The reactivity of Zn was inhibited
by the presence of hydrophobic surrounding protecting
the intermediate 3a from the formation of intermediate
3b as observed for reduction in low catalyst loading (5
equiv.). The Zn dust cannot be reuse in this study as
indicated by the low reduction power to achieve
intermediates 3a-3b (Table 1, entry 9).
The results using two different additives (NH4Cl
and N2H4.H2O; Table 1, entry 5 and entry 10,
respectively) were also compared in water micellar
conditions at rt. Lower hydrogen transfer ability of
hydrazine was found in this this study for the optimum
condition with high composition of diazene 3b and
low conversion of 19% to the reduced products 2.
Table 1 : Reduction of nitrobenzenea (Optimization of zinc-mediated reductions)
Condition
Untreated
Zn with
Conventional
Entry
1
2
Zn dust
(equiv)
10
5
PG1.5SF0.32
(wt%)
2
2
Additives
Time
(h)
6
4,6
1
-
3a
-
%conversion*
3b
-
2
-
10
2
6
0.2%
0.3%
99.5%
10
2
2
10
2
3
100%
NH
Cl
4
10
4
2
100%
5
2
3
73%
27%
5
4
3
Activated
10b
4
2
8%
89%
3%
Zn with
(Reused)
silica plug
10 c
10
2
N2H4.H2O
3
1%
72%
8%
19%
work-up
11d
10
2
CIB/water
6
86%
7%
7%
12e
10
CIB/methanol
3
13f
10
CIAB/methanol
3
96%
4%
14g
5
4
CIB/water
2
91.5%
8.5%
15h
10
4
NH4Cl
2
32%
24%
42%
2%
Wet CS-Zn (1:1)
16i
10
4
NH4Cl
2
0.4%
3%
96.6%
Dried CS-Zn (1:2)
Conditions at room temperature with *GC Analysis: a0.5M nitrobenzene, PG1.5SF0.32/H2O, NH4Cl 2 equiv .bReused Zn from entry 8
c
Replaced NH4Cl with N2H4.H2O 2 equiv.dUse of chitosan immobilized on bentonite (CIB) as a hydrogen source and a reducing agent in water
e
similar to entry 11 in methanol fUse of chitosan immobilized on activated bentonite (CIAB) in methanol gPG1.5SF0.32/H2O, NH4Cl 2 equiv and
CIB 1 gram. hWet CS-coated Zn dust in PG1.5SF0.32/H2O, NH4Cl 2 equiv. iDried CS-coated Zn dust in PG1.5SF0.32/H2O, NH4Cl 2 equiv.
work-up
3
4
5
6
7
8
9
3c
-
278
Compared to its unstable anhydrous form,
hydrazine hydrate is relatively safe and easy to handle
and was applied to this study. In the past few years,
several protocols for the reduction of nitroarenes
employing a combination of hydrazine and iron
catalysts have been reported at higher temperature.
Herein, hydrazine-Zn mediated protocols showed low
conversion leading to mainly diazene 3b, and revealed
hydrazine 3c (Table 1, entry 10). Other additives such
as chitosan were applied (Table 1, entries 11-15).
The use of modified chitosan as a hydrogen source
and reducing agent for transition metal-free reduction
is introduced. Beads of modified chitosans were
immobilized on bentonite directly and performed in the
reaction (Table 1, entries 11-13). The thermal stability
of native chitosan (CS sample), chitosan bead (CSbead) and chitosan immobilized on bentonite (CIB
sample) was studied by TGA. Two major weight-loss
stages at approximately 40–250°C and 250–670°C
were observed in the tested temperature range. The
first weight loss at approximately 40–250°C is due to
the volatility of small molecules, such as physically
absorbed water and acetic acid. The second weight loss
is due to the degradation of CS, CS-bead and CIB
catalyst, which can be assigned to the structural
collapse of the chitosan and the thermal decomposition
of the polymeric network. The chitosan immobilized
on bentonite (CIB sample) showed significant
improvement in the thermal stability. The CIB catalyst
is therefore stable and selected at the desired operating
condition. It exhibited to lower reducing power of Zn
dust and gave intermediate 3b with insufficient
hydrogen source to reduced product 2 (Table 1, entry
11).
To observe the reaction conditions of CIB catalyst,
the reduction of nitrobenzene 1 without micellar
surfactant was carried out in the presence of methanol.
No reaction was occurred (Table 1, entry 12). The
procedure for activated bentonite was then carried out
to prepare the CIB and was used in the reaction in the
absence of micellar surfactant (Table 1, entry 13)
obtaining similar result as entry 11 with azoxybenzene
3a accumulation. Poor results were observed with the
attempt to improve reducing power by using Zn dust
based on micellar technology (Table 1, entry 14).
Finally, in order to increase the reducing power and
offer higher ability to transfer hydrogen, CS-coated Zn
dust was employed as initially prepared in Zn equiv.
under the optimized conditions (Table 1, entry 6). The
intermediates 3a-3c were observed i9n higher
hydrogen transfer ability for wet CS coated-Zn (Table
1, entry 15). The performance of dried CS-coated Zn
dust as potential reducing agent with good hydrogen
source were achieved (Table 1, entry 16).The ability of
the CS coated-Zn as reusable materials based on
micellar technology is in progress.
stirring for 3 hours. The break-through reported in this
paper aims at developing a commutative strategy based
on micellar technology using PGS oligomer as nonionic surfactants and CS coated Zn as catalyst for
reducing agent. Further studies on the modified
chitosan in catalytic application are being carried out
in our laboratory.
Acknowledgements
The authors are thankful to Department of
Chemistry, Faculty of Science and Technology,
Thammasat University.The authors also gratefully
acknowledge the partial support provided by Central
Scientific Instrument center (CSIC) Faculty of Science
and Technology Thammasat University. Contract No
001/2556.
References
1. Lipshutz, B. H., Ghorai, S., Abela, A. R., Moser, R.,
Nishikata,T., Duplais, C., Krasovskiv, A., Gaston, R. D.
and Gadwood, R. C., 2011, J. Org. Chem., 76, 43794391.
2. (a) Sheldon, R. A., 2007, Green Chem., 9, 1273. (b)
Lipshutz, B. H., Isley, N. A., Fennewald, J. C. and Slack,
E. D., 2013, Angew. Chem., Int. Ed., 52, 10952-10958.
3. Kelly, S.M. and Lipshutz, B. H., 2014, Org. Lett., 16, 98101.
4. Khongphow C., Theerakul, J., Puttamat, S. and
Singkhonrat, J., 2015, Characterization of poly(glycerolsuccinate) oligomers as bio-based non-ionic surfactants
by nuclear magnetic resonance and mass spectrometry,
Colloids Surf. A: Physicochem. Eng Asp., 468, 301-308.
4. Conclusions
In summary, the optimized conditions were set at
0.5 M nitrobenzene, 10 equiv. of fresh zinc dust, 2%wt
PGS oligomer and 2 equiv. of ammonium chloride at rt
279
SYNTHESIS AND CHARACTERIZATION OF CYANURIC ACID
SUBSTITUTED 1,8-NAPHTHALIMIDES
Chittranuch Pengsawad1, Mongkol Sukwattanasinitt2, Paitoon Rashatasakhon2*
1
Program in Petrochemistry and Polymer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
2
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
*E-mail: paitoon.r@chula.ac.th Tel. +66 2218 7596, Fax +66 2218 7598
Abstract: Two novel fluorescent sensors (1 and 2) are
designed as potential sensors for melamine. They are
successfully synthesized from 1,8-naphthalimide as
fluorophore and cyanuric acid as receptor for melamine.
The synthesis involves an imidation of 1,8-naphthalic
anhydride with ethanolamine, transformation of the
hydroxyl group to a bromo group, and N-alkylation of
isocyanuric acid by the bromo group. The target
compounds are characterized by 1H-NMR, 13C-NMR,
mass spectroscopy, and elemental analysis. The
photophysical properties are investigated by UV-Vis and
fluorescence spectroscopy. The difference in substitution
at the 4-position of the naphthalimide moiety plays an
important effect on the emission wavelengths and
fluorescence efficiencies. Progress on the optimization of
a sensing system for melamine will be presented.
1. Introduction
Melamine (C3H6N6) is a high nitrogen-containing
compound (66% by mass) which is essential for the
production of melamine-formaldehyde resins used in
plastic, paints, adhesives, and fire retardant. Recently,
melamine was contaminated in milk product and infant
formula for the false increase of protein levels as
determined by the nitrogen contents. Although
melamine has low toxicity, it can be associated with
cyanuric acid to from high molecular weight network
complexes. The complex has poor aqueous solubility
and precipitates in renal tubes, causing damage to the
urinary system developing kidney stones, and ultimate
death [1]. Therefore, The U.S. Food and Drug
Administration (FDA) set a safe contamination level
of melamine at 1 mg kg-1 for powdered infant milk
formula and at 2.5 mg kg-1 for other foods [2].
Nowadays, several methods for melamine
detection [3] have been reported such as gas
chromatography/mass spectrometry (GC-MS) [4],
high-performance liquid chromatography (HPLC) [5],
liquid chromatography (LC) [6], and enzyme-linked
immunosorbent assay (ELISA) [7]. Most of these
methods are highly sensitive, but they require highcost instruments, complicated sample preparation, and
well-trained technicians or instrument users.
Therefore, the development of a rapid, easy, and
inexpensive method for melamine detection has
become essential. With respect to its high sensitivity
and reasonable instrument cost, fluorescence
technique has become a favorite technique of
detection. Since the strong H-bonding between
cyanuric acid and melamine has been reported [8], we
designed and synthesized new 1,8-naphthalimide
fluorophores having a cyanuric acid pendant as a
receptor for melamine. The synthesis and
characterization of these new materials are reported
herein.
2.1 Materials
1,8-Naphthalic anhydride, 4-bromo-1,8-naphthalic
anhydride, ethanolamine, ethanol, cyanuric acid,
potassium hydroxide (KOH), phosphorus tribromide
(PBr3), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),
N,N-dimethylformamide (DMF), dimethyl sulfoxide
(DMSO), magnesium sulphate (MgSO4), and 1,4dioxane were reagent grade and purchased from Sigma
Aldrich. Organic solvents such as dichloromethane
(CH2Cl2), hexane, and ethyl acetate (EtOAc) were
commercial grade purchased from local suppliers and
distilled prior to use.
2.2 Instrumentation
The 1H NMR was measured by using 400 MHz 1H
NMR spectrophotometer (Varian, USA) and reported
as ppm in CDCl3 and DMSO-d6. The 13C NMR was
measured on Bruker Mercury NMR spectrophotometer
(Bruker, Germany) which were equipped at 100 MHz
with chemical shifts reported as ppm in CDCl3 and
DMSO-d6. A UV-2550 UV visible spectrophotometer
(SHIMADZU,Japan) was used for the absorption
studies. Emission spectra were acquired by a Carry
Eclipse Fluorescence Spectrophotometer (Agilent
Technologies).
2.3 Synthesis and Characterization
2.3.1. 2-(2-Hydroxyethyl)-1Hbenzo[d,e] isoquinoline 1,3(2H)-dione, (3)
1,8-Naphthalic anhydride (2.0 g, 10 mmol) and 3
mL ethanolamine were add into a round bottom flask,
the mixture was heated 170 ºC under reflux conditions
for 2 h. after the reaction was completed it was left to
cool down to room temperature. The mixture was
poured into 100 ml of cool water and the solid
precipitate was filtered by vacuum filtration, and
washed with cool water. After vacuum drying,
compound 3 was obtained as brown solid in 91%
yield; 1H NMR (400 MHz, CDCl3) δ (ppm): 8.64 (d, J
= 7.3 Hz, 2H), 8.26 (d, J = 8.3 Hz, 2H), 7.79 (t, J = 7.8
Hz, 2H), 4.54 (m, 2H), 4.02 (t, J = 5.3 Hz, 2H). This
280
data was in good agreement with the literature report
[9].
2.3.2. 2-(2-Bromoethyl)-1H-benzo[d,e]isoquinoline1,3(2H)-dione (4)
Compound 3 (0.15 g, 0.62 mmol) was dissolved in
20 mL of dichloromethane and then phosphorus
tribromide (0.5 eq) was added drop wise. The reaction
was stirred in an ice bath for 15 min. After the reaction
was completed, it was diluted with water and extracted
with CH2Cl2. The combined organic phase was dried
over anhydrous MgSO4, filtered, and concentrated
under reduced pressure. The crude product was
purified by column chromatography using CH2Cl2 :
Hexane (50:50) as the eluent to give 4 as white solid in
35% yield. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.62
(dd, J = 7.3 and 1.0 Hz, 2H), 8.23 (dd, J = 8.3 and 0.9
Hz, 2H), 7.77 (dd, J = 8.1 and 7.4 Hz, 2H), 4.61 (dd, J
= 9.2 and 5.1 Hz, 2H), 3.67 (t, J = 7.2 Hz, 2H).
1-(2-(1,3-Dioxo-1H-benzo[de]isoquinolin-2
2.3.3
(3H)-yl)ethyl)-1,3,5-triazinane-2,4,6-trione (1)
To a mixture of cyanuric acid (0.35 g, 2.7 mmol)
and 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU, 0.08
ml, 0.5 mmol) in DMF (4 mL) at room temperature.
The mixture was stirred at 100 ºC. The compound 3
(80 mg, 0.27 mmol) was added in the reaction for 24 h.
The mixture was poured into water and extracted with
EtOAc. The combined organic phase was dried over
anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The crude substance was dissolved
with DMSO and was poured into 100 ml of cool water,
the white solid were collected by vacuum filtration and
then dried overnight at room temperature in a vacuum
oven to obtain 1 as white solid in 45% yield. 1H NMR
(400 MHz, DMSO-d6) δ (ppm): 11.35 (s, 2H), 8.49 (d,
J = 7.2 Hz, 2H), 8.45 (d, J = 8.3 Hz, 2H), 7.86 (t, J =
7.8 Hz, 2H), 4.31 (brt, 2H), 4.06 (brt, 2H). 13C NMR
(100 MHz, DMSO-d6) δ (ppm): 163.9, 150.0, 148.4,
134.4, 131.3, 130.8, 127.5, 127.2, 121.8, 39.1, 38.0.
Elemental analysis : Calculated for C17H12N4O5 (MW
352.30) C 57.96, H 3.4, N 15.90%; found C 58.22, H
3.22, N 15.52%.
2.3.4. 6-Bromo-2-(2-hydroxyethyl)-1H-benzo [de]isoquinoline- 1,3(2H)-dione (5)
The reaction of 4-bromo-1,8-naphthalic anhydride
(5.01 g, 18.11 mmol) in 1,4 dioxane (25 mL) and 3 mL
ethanolamine were added into a round bottom flask,
the mixture was heated at 105 ºC under reflux
conditions for 6 h. after cooling it down to room
temperature. The mixture was poured into 100 mL of
cool water and the solid precipitate was filtered by
vacuum filtration and washed with cool water and then
dried overnight at room temperature in a vacuum oven
to give 5 as yellow solid in 95%yield. 1H NMR (400
MHz, CDCl3) δ (ppm): 8.67 (d, J = 7.3 Hz, 1H), 8.59
(d, J = 8.5 Hz, 1H), 8.43 (d, J = 7.8 Hz, 1H), 8.05 (d, J
= 7.8 Hz, 1H), 7.89 (m, 1H), 4.45 (t, J = 5.3 Hz, 2H),
3.99 (t, J = 5.3 Hz, 2H) [10].
2.3.5. 6-Ethoxy-2-(2-hydroxyethyl)-1H- benzo[de]isoquinoline-1,3(2H)-dione (6)
Compound 5 (1.01g, 3.16 mmol) was added into
30 mL of EtOH with KOH (0.17g, 3.1 mmol) and
reflux for 4 h. Pour the mixture into 50 mL of water.
And filtrate to collect the precipitant. The precipitant
was washed with 30 mL of cool water and dried
overnight at room temperature to afford 6 as dark
yellow solid in 73%yield. 1H NMR (400 MHz, CDCl3)
δ (ppm) : 8.61 (d, J = 7.9 Hz, 2H), 8.55 (d, J = 8.3 Hz,
1H), 7.71 (t, J = 7.8 Hz, 1H), 7.03 (d, J = 8.3 Hz, 1H),
4.48 (m, 2H), 4.36 (q, J = 7.0 Hz, 2H), 4.00 (m, 2H),
1.62 (t, J = 7.0 Hz, 3H).
2.3.6. 2-(2-Bromoethyl)-6-ethoxy-1H-benzo[d,e]isoquinoline-1,3(2H)-dione (7)
Compound 6 (0.1 g, 0.36 mmol) was dissolved in
30 ml dichloromethane and then dropwise phosphorus
tribromide (0.5 eq) was added drop wise. The reaction
was stirred in an ice bath for 15 min. the reaction was
completed, it was diluted with water and extracted
with CH2Cl2. The combined organic phase was dried
over anhydrous MgSO4, filtered, and concentrated
under reduced pressure. The crude product was
purified by column chromatography using EtOAc :
Hexane (50:50) as the eluent to give 7 as pale yellow
solid in 42%yield. 1H NMR (400 MHz, CDCl3) δ
(ppm): 8.60 (d, J = 7.7 Hz, 2H), 8.54 (d, J = 8.3 Hz,
1H), 7.70 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H),
4.58 (t, J = 7.2 Hz, 2H), 4.33 (q, J = 6.8 Hz, 2H), 3.64
(t, J = 7.2 Hz, 2H), 1.60 (t, J = 7.0 Hz, 3H).
2.3.7. 1-(2-(6-Ethoxy-1,3-dioxo-1H-benzo[d,e]
isoquinolin-2(3H)-yl)ethyl)-1,3,5-triazinane-2,4,6trione (2)
To a mixture of cyanuric acid (0.33 g, 2.6 mmol)
and 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU, 2 eq.)
in DMF (4 mL) at room temperature. The mixture was
stirred at 100 ºC. The solid compound 6 (90 mg, 0.26
mmol) was added in the reaction. Reaction took place
for 24h. After the reaction was completed, it was
diluted with water and extracted with EtOAc. The
combined organic phase was dried over anhydrous
MgSO4, filtered, and concentrated under reduced
pressure. The crude substance was dissolved with
DMSO and was poured into 100 mL of cool water, the
white solid was collected by vacuum filtration and
then dried overnight at room temperature in a vacuum
oven to provide 2 as pale yellow solid in 68%yield.
1
H NMR (400 MHz, DMSO-d6) δ (ppm): 11.37 (s,
2H), 8.55 (d, J = 8.3 Hz, 1H), 8.50 (d, J = 7.2 Hz, 1H),
8.44 (d, J = 8.3 Hz, 1H), 7.82 (t, J = 7.8 Hz, 1H), 7.31
(d, J = 8.4 Hz, 1H), 4.43 (m, 2H), 4.30 (brt, 2H), 4.05
(brt, 2H), 1.51 (t, J = 6.9 Hz, 3H). 13C NMR (100
MHz, DMSO-d6) δ (ppm): 164.1, 163.4, 159.7, 149.9,
148.4, 133.4, 131.1, 128.8, 128.5, 126.3, 122.9, 121.7,
113.8, 106.9, 64.8, 37.8, 14.3. Elemental analysis :
Calculated for C19H16N4O6 (MW 396.35) C 57.58, H
4.07, N 14.14%; found C 58.01, H 3.66, N 13.80%.
281
3. Results and discussion
3.1 Synthesis the compound 1 and 2
The synthesis of new target molecules were
successfully conducted as shown in Scheme 1. The
first reaction starting from commercially available 1,8naphthalic anhydride reacted with ethanolamine at
172oC to afford the 1,8-naphthalimide derivative 3 and
then bromination reaction with phosphorus tribromide
to provide 4 . The N-alkylation of 4 with cyanuric acid
using DBU as a base in DMF gave fluorophore 1 in
moderate yield. Fluorophore 2 was prepared via
nucleophilic aromatic substitution of 4-bromo-1,8naphthalic anhydride with ethanolamine furnished 5,
and nucleophilic replacement of bromine with an
alkylether. The compound 2 is different from
compound 1 in order to improve the quantum yield
afforded 6. Next, 1,8-naphthalimide derivative 2 was
prepared in good yield from 7 using the same
condition described for compound 1.
Figure 1. Normalized absorption and emission spectra
of compound 1 and 2 in acetonitrile
O
HN
Br
OH
O
O
O
OH
H2N
N
O
O
O
N
NH
N
O
N
O
O
O
O
PBr3
CH2Cl2
O
91%
35%
3
HN
4
O
NH
N
H
1, 45%
O
DBU,DMF
O
HN
OH
O
O
O
H2N
N
O
OH
N
OH
Br
95%
5
O
O
N
N
O
O
PBr3
CH2Cl2
KOH
reflux,1,4-dioxane
Br
O
O
Br
OH
O
O
NH
N
O
73%
O
O
O
42%
7
6
2, 68%
Scheme 1. Synthesis of 1 and 2
3.2 Photo physical tests
The absorption and emission spectra of each
fluorophore were shown in Figure 2 and the related
data were summarized in Table 1. The compounds
exhibited maximum wavelength of absorption band at
332 nm of 1 and 366 nm of 2. An appearance of a
longer wavelength, the maximum emission band of 2
at 430 nm, may cause from the effect of electron
donating group (-OR), resulting in a bathochromic
shift phenomenon [11]. And alkoxy was electron
donating and electron
withdrawing (imide)
substituents which typically have charge-transfer
lowest excited states. In addition, the quantum yield of
the compound 2 is larger than that of the compound 1.
Table 1: Photophysical properties of 1 and 2 in
acetonitrile
Cpd. Absorption Emission
λabs (nm) ε (M-1 cm-1) λems (nm) Φ
1
332
5243
375
0.06 a
2
366
11,958
430
0.49b
2-Aminopyridine in 0.1 M H2SO4 (Φ = 0.60) and b
Quinine sulphate in 0.1 M H2SO4 (Φ = 0.54) were
used as references.
a
282
4. Conclusions
The compound 1 and 2 were successfully
synthesized and characterized. Both of them have
photo properties so they can be used for fluorescent
sensor application. The compound 2 was found that
the quantum yield more than the compound 1. It is
dependent on the substituents at the 4-position.
Acknowledgements
This project is supported by the
Ratchadapiseksomphot
Endowment
Fund
of
References
Suchý, P., Straková, E., Herzig, I., Staňa, J., Kalusová,
R. and Pospíchalová, M., 2009, Interdisciplinary
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[2] Tyan, Y-C., Yang, M-H., Jong, S-B., Wang, C-K. and
Shiea, J., 2009, Anal. Bioanal. Chem., 395, 729-735.
[3] Liu, Y., Todd, E. D., Zhang, Q., Shi, J.-R. and Liu, X.J., 2012, J. Zhejiang Univ. Sci. B., 13, 525-532.
[4] Li, J., Yang Qi, H. and Ping Shi, Yan., J., 2009, J.
Chromatogr. A., 1216, 5467-5471.
[5] Gao, L. and Jönsson, J. Å., 2012, Analytical Letters,
45, 2310-2323.
[6] Goscinny, S., Hanot, V., Halbardier, J. F., Michelet, J.
Y. and van Loco, J., 2011, Food Control., 22, 226-230.
[7] Garber, E. A. E., 2008, J. Food Prot., 71, 590-594.
[8] Sanji, T., Nakamura, M., Kawamata, S., Tanaka, M.,
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[9] Wan, X., Liu, T. and Liu, S., 2011, Langmuir 27,
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[10] Li, H.-T., Jiang, Z.-Q., Zheng, J., Wang, X., Pan, Y.,
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[1]

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