Synthesis and characterization of novel stilbene derivatives with 1,3,4-oxadiazole unit

Article abstract of DOI:10.1002/jccs.200900039

Four novel stilbene derivatives containing 1,3,4-oxadiazole unit have been synthesized in four steps with overall yields (2735%). The synthetic route involved one-step installation of 2,5-di-p-tolyl-1,3,4-oxadiazol via the direct coupling of p-toluic acid

Full text of DOI:10.1002/jccs.200900039

268
Journal of the Chinese Chemical Society, 2009, 56, 268-270
Synthesis and Characterization of Novel Stilbene Derivatives with
1,3,4-Oxadiazole Unit
Dao-Hang Hea* (
Zhuo-Ru Yanga (
), Yong-Chuang Zhua (
) and Ai-Xi Hub* (
),
)
aCollege of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
bCollege of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
Four novel stilbene derivatives containing 1,3,4-oxadiazole unit have been synthesized in four steps
with overall yields (27~35%). The synthetic route involved one-step installation of 2,5-di-p-tolyl-1,3,4-
oxadiazol via the direct coupling of p-toluic acid with hydrazine hydrate promoted by PPA, benzylic
bromination, conventional phosphonate formation, and Wittig-Horner olefination.
Keywords: Stilbene derivatives; 1,3,4-Oxadiazole unit; Synthesis.
INTRODUCTION
Stilbene derivatives have attracted much attention
RESULTS AND DISCUSSION
Scheme I presents a synthetic route. 2,5-Di-p-tolyl-
1,3,4-oxadiazole 4 was prepared directly by the treating of
p-toluic acid with hydrazine hydrate in polyphosphoric
acid (PPA) at 150 °C. The reaction could be monitored by
TLC. This result strongly implicates that the intermediate
N¢-benzoylbenzohydrazide was converted immediately to
2,5-di-p-tolyl-1,3,4-oxadiazole 4 by PPA as soon as it was
generated. The 1H NMR spectra data of 4 are identical with
those of literature.15 Then a mixture of compound 4 and
1,3-dibromo-5,5-dimethylhydantoin (DBDMH) in carbon
dichloride was refluxed for 15 h to give 2,5-bis(4-(bromo-
methyl)phenyl)-1,3,4-oxadiazole 3 with a yield of 75%.
The title compounds 1 were synthesized by reacting 2 with
various aromatic aldehydes. The 1H NMR spectrum of 1a
revealed a fine singlet at d: 6.07 ppm and doublet at d: 7.27
and d: 7.40 ppm accountable to the methylene and olefinic
protons (CH=CH) from stilbene, respectively. The reso-
nance peaks that appeared at d: 6.96, d: 7.12, d: 7.36, d:
7.81 and d: 8.13 ppm could be assigned to the contribution
of aromatic protons from stilbene moiety. The elemental
analysis of 1a was in good agreement with those calculated
values for the expected molecular formula C32H22N2O5.
The mass spectrum illustrated the molecular ion peak at m/z
515 (M+H). All the above spectral data supported the com-
pound 1a to be 2,5-bis(4-(2-(1,3-dihydroisobenzofuran-
5-yl)vinyl)phenyl)-1,3,4-oxadiazole. In the 1H NMR spec-
due to their diverse biological activities, including anti-mi-
crobial and insecticidal effects, vasodilation action, as well
as insect baculovirus synergists.1-5 In addition, they are
also one of the important organic two-photon absorption
materials which possess potential application in photo-
chemical therapeutics, micro- and nano-manufacture, two-
photon laser scanning fluorescence microscopy.6-10 More-
over, stilbenyl two-photon materials which demonstrate
distinctive blue emission properties become the current re-
search focus.11-13 However, their wide applications are still
limited due to the low quantum efficiency of fluorescence,
the short fluorescence lifetime and the weak luminous in-
tensity of fluorescence. Accordingly, it is of great need to
explore efficient two-photon materials which can induce
blue fluorescent emission.14 Based on the fact that 1,3,4-
oxadiazole unit has a good hole-transporting property, oxy-
gen and heat stability, especially high fluorescence quan-
tum yields, we envisioned that the introduction 1,3,4-oxa-
diazole unit into the stilbenyl skeleton can improve these
photoelectric properties.15-17 Herein, we report that the syn-
thesis of four novel stilbene derivatives containing the
1,3,4-oxadiazole unit were available in four-step with an
overall yield (27~35%) by an improved route. The title
products reported were characterized on the basis of MS,
1H NMR, 13C NMR and elemental analysis.
* Corresponding author. E-mail: axhu0731@yahoo.com.cn; daohanghe@yahoo.com.cn

Study of Synthetic Progress for Stilbene Derivatives
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 269
Scheme I Synthetic route of compounds 1
COOH
DBDMH
PPA
O
+
NH2NH2H2O
150 oC, 15 h
carbon dichloride, ref, 15 h
N
4
N
O
O
BrH2C
CH2Br
CH2P(OEt)2
(EtO)2PCH2
P(OC2H5)3
ref, 5 h
O
O
N
N
N
N
2
3
Ar
Ar
ArCHO
O
t-BuOK, DMF
N
N
1
O
1a
Ar=
1b Ar=
Cl
1d
Ar=
Ar=
1c
O
O
methanol giving 9.4 g of compound 4 as white crystals,
yield 60%, m.p. 176~177 °C, 1H NMR (CDCl3): d 2.43 (s,
6H, CH3), 7.32 (d, J = 8.4 Hz, 4H, C6H4 3,5-H), 8.01 (d, J =
8.4 Hz, 4H, C6H4 2,6-H); APCI MS (m/z) 251 (M+1, 100),
252 (M+2, 18).
trum of the compounds 1a, 1b, 1c, and 1d, it was found that
their olefinic protons (CH=CH) from stilbene had the same
coupling constant (J = 16.2 Hz), which indicated the differ-
ent substituents on benzene had no effect on proton-proton
coupling. The structures of the other compounds (1b, 1c,
1d) were also confirmed by their analytical and spectral
data.
Synthesis of 2,5-bis(4-(bromomethyl)phenyl)-1,3,4-
oxadiazole 3
Amixture of compound 4 (5 g, 20 mmol), DBDMH (4
g, 20 mmol) and carbon dichloride (70 mL), was refluxed
for 15 h until the disappearance of the starting material by
TLC. The mixture was filtered while still hot. The residue
was washed with ethanol and the solvents were removed
under reduced pressure. The obtained solid was recrystal-
lized from THF/ethanol giving 6 g of compound 3 as white
crystals, yield 75%, m.p. 227~228 °C, 1H NMR (CDCl3): d
4.55 (s, 4H, CH2Br), 7.57 (d, J = 8.4 Hz, 4H, C6H4 3,5-H),
8.13 (d, J = 8.4 Hz, 4H, C6H4 2,6-H); APCI MS (m/z) 409
(M+1, 100).
EXPERIMENTAL SECTION
Melting points were determined using RY-1 melting
1
point apparatus and were uncorrected. H NMR spectra
were recorded in CDCl3 or DMSO-d6 on a Bruker
AVANCE-600 MHz NMR spectrometer using TMS as in-
ternal standard. Mass spectra were obtained with a HPLC/
MS LCQDECA spectrometer (APCI). Elemental analyses
were performed on a Vario EL III CHN elemental analyzer.
The purity of the compounds was checked by TLC on silica
gel ‘G’ coated glass plates.
Synthesis of diethyl 4-(5-(4-((diethoxyphosphino)meth-
yl)phenyl)-1,3,4-oxadiazol-2-yl)benzylphosphonate 2
A mixture of compound 3 (5 g, 14.7 mmol) and tri-
ethyl phosphite (13 mL, 76.6 mmol) was refluxed for 5 h.
Hexane was added after the excess triethyl phosphite was
evaporated under reduced pressure, then the mixture was
filtered. The resulting precipitate was recrystallized from
THF/hexane giving 6.2 g of compound 2, yield 80%, m.p.
Synthesis of 2,5-di-p-tolyl-1,3,4-oxadiazole 4
p-Toluic acid (17 g, 125 mmol) and 80% hydrazine
hydrate (4 mL, 66 mmol) were added to 60 mL of stirred
phosphoric acid respectively, then the resulting mixture
was reacted at 150 °C for 15 h until the disappearance of the
starting material by TLC. After cooling, the mixture was
poured into cold water, and then neutralized by 5% Na2CO3.
After filtration, the residue was recrystallized from CHCl3/

270 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
He et al.
111~112 °C, 1H NMR (CDCl3): d 1.27 (t, J = 7.2 Hz, 12H,
CH3), 3.43 (d, J = 22.2 Hz, 4H, CH2), 4.02~4.08 (m, 8H,
OCH2), 7.49 (dd, J = 2.4 Hz, J = 8.4 Hz, 4H, C6H4 3,5-H),
8.09 (d, J = 8.4 Hz, 4H, C6H4 2,6-H).
16.2 Hz, 2H, CH=CH), 7.31 (t, J = 7.8 Hz, 2H, C6H4 1-H),
7.40 (t, J = 7.8 Hz, 4H, C6H4 2,6-H), 7.57 (d, J = 7.8 Hz,
4H, C6H4 3,5-H), 7.68 (d, J = 8.4 Hz, 4H, C6H4 3,5-H), 8.15
(d, J = 8.4 Hz, 4H, C6H4 2,6-H); 13C NMR (150 MHz,
CDCl3): d 122.65, 126.80, 127.04, 127.30, 127.45, 128.28,
128.82, 131.03, 136.74, 140.72, 164.42 (C=N); APCI MS
(m/z) 427 (M+1, 100), 428 (M+2, 34), 429 (M+3, 7); Anal.
Calcd for C30H22N2O (426.5): C, 84.48; H, 5.20; N, 6.57.
Found: C, 77.82; H, 5.17; N, 6.28.
Typical procedure for the synthesis of compounds 1
A mixture of aromatic aldehydes (3.4 mmol) and the
intermediate 2 (0.9 g, 1.7 mmol) was dissolved in anhy-
drous N,N-dimethylformamide (15 mL), then a solution of
t-BuOK (2 g, 3%) in ethanol was added under nitrogen at-
mosphere. The reaction mixture was stirred at room tem-
perature overnight. The resulting mixture was diluted with
ethanol, filtered and purified by recrystallization from eth-
anol/DMSO giving compounds 1. All the compounds gave
analytical and spectral data.
ACKNOWLEDGEMENT
The authors are thankful to Chinese Postdoctoral
Science foundation (No. 2003033425) and Guangdong
Provincial Natural Science Foundation of China (No.
04300531) for the financial assistance.
2,5-bis(4-(2-(1,3-dihydroisobenzofuran-5-yl)vinyl)phen-
yl)-1,3,4-oxadiazole 1a
1
(0.85 g): yield 98%, m.p. 284~285 °C, H NMR
Received April 8, 2008.
(DMSO-d6): d 6.07 (s, 4H, CH2), 6.96 (d, J = 7.8 Hz, 2H,
C6H3 6-H), 7.12 (d, J = 7.8 Hz, 2H, C6H3 5-H), 7.27 (d, J =
16.2 Hz, 2H, CH=CH), 7.36 (s, 2H, C6H3, 3-H), 7.40 (d, J =
16.2 Hz, 2H, CH=CH), 7.81 (d, J = 8.4 Hz, 4H, C6H4
3,5-H), 8.13 (d, J = 8.4 Hz, 4H, C6H4 2,6-H); APCI MS
(m/z) 515 (M+1, 100), 516 (M+2, 42), 517 (M+3, 10);
Anal. Calcd for C32H22N2O5 (514.5): C, 74.70; H, 4.31; N,
5.44. Found: C, 74.06; H, 4.33; N, 5.55.
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