Synthesis and characterization of fully conjugated schiff base macrocycles containing 1,3,4-oxadiazole moiety

Article abstract of DOI:10.1081/SCC-120014041

Conjugated schiff base macrocycles containing 1,3,4-oxadiazole moiety were prepared by [1 + 1] cyclic condensation. Two synthetic routes were studied.

Full text of DOI:10.1081/SCC-120014041

This article was downloaded by: [The University of Manchester Library]
On: 19 October 2014, At: 04:15
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
SYNTHESIS AND CHARACTERIZATION OF FULLY
CONJUGATED SCHIFF BASE MACROCYCLES CONTAINING
1,3,4-OXADIAZOLE MOIETY
Shu Wang a , Zhitao Li a & Wenting Hua b
a College of Chemistry and Molecular Engineering , Peking University , Beijing, 100871, P.R.
China
b College of Chemistry and Molecular Engineering , Peking University , Beijing, 100871, P.R.
China
Published online: 16 Aug 2006.
To cite this article: Shu Wang , Zhitao Li & Wenting Hua (2002) SYNTHESIS AND CHARACTERIZATION OF FULLY CONJUGATED
SCHIFF BASE MACROCYCLES CONTAINING 1,3,4-OXADIAZOLE MOIETY, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 32:21, 3339-3345, DOI: 10.1081/SCC-120014041
To link to this article: http://dx.doi.org/10.1081/SCC-120014041
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONS
Vol. 32, No. 21, pp. 3339–3345, 2002
SYNTHESIS AND CHARACTERIZATION
OF FULLY CONJUGATED SCHIFF BASE
MACROCYCLES CONTAINING
1,3,4-OXADIAZOLE MOIETY
*
Shu Wang, Zhitao Li, and Wenting Hua
College of Chemistry and Molecular Engineering,
Peking University, Beijing 100871, P.R. China
ABSTRACT
Conjugated schiff base macrocycles containing 1,3,4-oxadia-
zole moiety were prepared by [1 þ 1] cyclic condensation.
Two synthetic routes were studied.
Recently, much attention has been paid on the use of much rigid
electron-withdrawing aromatic 1,3,4-oxadiazole unit as building blocks in
development of new optoelectrical devices because of their many good
properties, such as high thermal and oxidative stability, strong fluorescence
and the high efficient electroluminescent behavior.[1–4] In the context of the
preparation of new molecules containing oxadiazole, we have been working
in the synthesis of macrocycles containing 1,3,4-oxadiazole moiety.[5–9]
In this paper, we report the synthesis of conjugated Schiff base macrocycles
containing 1,3,4-oxadiazole by using two methods.
*Corresponding author. E-mail: huawt@pku.edu.cn
3339
DOI: 10.1081/SCC-120014041
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3340
WANG, LI, AND HUA
Scheme 1.
Schiff base macrocycles 1 and 2 are synthesized by the condensation
of relating aldehyde and amine (Sch. 1). Reaction of 2-hydroxy-5-nitro-
benzoic acid and aminourea hydrochloride in polyphosphoric acid at
150–160ꢀC afforded cyclization product 2,5-di(2-hydroxy-5-nitro-phenyl)-
1,3,4-oxadiazole 2, which was reduced by SnCl2 in concentrated hydro-
chloric acid to yield 2,5-di(2-hydroxy-5-amino-phenyl)-1,3,4-oxadiazole 3.
Functionalization of hydroxy group of compound 2 was achieved by
refluxing compound 2 with n-bromobutane and K2CO3 in DMF to
afford 2,5-di(2-butoxy-5-nitro-phenyl)-1,3,4-oxadiazole 4. The compound
4 was reduced by Zn powder in the presence of CaCl2 to yield 2,5-di-
(2-butoxy-5-amino-phenyl)-1,3,4-oxadiazole 5. The [1 þ 1] macrocyclization

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
MACROCYCLES CONTAINING 1,3,4-OXADIAZOLE MOIETY
3341
of dialdehyde 6 with an equimolar amount of diaminoxadiazole 3 or 5 via
the barium(II) ion template was carried out under refluxing in MeOH.
Macrocycle 1 (76%) and 2 (30%) were obtained as yellow powders.
We also tried to obtain macrocycle compound by refluxing compound
6 and 2,5-di(3-aminophenyl)-1,3,4-oxadiazole. However, it was not successful
to prepare the macrocycle by this method. This was due to the weak nucleo-
philic ability of the amine group that was adjacent to the electron-withdrawing
aromatic oxadiazole. In compound 3 or 5, the nucleophilic ability of the
amine group is much stronger than that in compound 6 because of the
presence of hydroxy group or the butoxide group, and so they could react
with the dialdehyde to yield Schiff base macrocycles.
It is reported that the elimination of a tosyl group from a sulfonamide
under base condition can form Schiff base,[10,11] and so we chose this method
to synthesize the macrocycle (Sch. 2). The study of the effect of bases on
sulfonamides suggested that bases might abstract a proton from the
carbon atom adjacent to the nitrogen atom and that the carbanion formed
might then extrude a p-toluenesulphinyl anion yielding a Schiff base.
Scheme 2.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3342
WANG, LI, AND HUA
Macrocyclization of 2,5-di(2-chloromethyl-5-nitrophenyl)-1,3,4-oxadiazole
and an equimolar amount of sodium compound 11 was carried out in
refluxing DMF (N,N0-dimethylformamide) for 5 h to lead directly to the
macrocycle 3. In our study the precursor macrocycle compound 12 was
not isolated which suggested that the sodium compound 11 acted not only
as the substrate but also as the base, so that the Schiff base macrocycle 3 was
formed. These results suggested that an a-carbon atom (with respect to
nitrogen) activated by electron-withdrawing oxadiazole and nitro group
was necessary for the formation of the Schiff base. The efficient synthetic
method described in this paper provides a way to form potentially important
conjugated Schiff base macrocycles that cannot be synthesized by the
condensation of aldehydes and amines.
In summary, two conjugated Schiff base macrocycles 1 and 2 were
synthesized by typical condensation of aldehydes and amines. Macrocycles
3 was synthesized by elimination of a tosyl group from a sulfonamide under
base condition. The second way provides a general method to synthesize
conjugated Schiff base macrocycles that cannot be synthesized by direct
condensation of aldehydes and amines.
EXPERIMENTAL
Melting points were determined on an XT-4 electrothermal apparatus
and uncorrected. Elemental analyses were carried out on a Italy Carlo-Erbla
1160 elemental analyser. IR spectra were recorded on a Nicolet Magna 750 IR
Spectrometer (KBr). 1H-NMR spectra were obtained with a Bruker ARX400
Spectrometer (Me4Si). Mass spectra were recorded on a VG-ZAB-HS
mass spectrometer (EI or FAB). Compound 7,[12] 2,5-di(3-formylphenyl)-
1,3,4-oxadiazole[9] and 2,5-di(2-chloromethyl-5-nitro-phenyl)-1,3,4-oxa-
diazole[5] were synthesized according to literature.
Synthesis of compound 2: P2O5 (15 g) was added to phosphoric acid
(10 mL) under stirring to afford polyphosphoric acid solution. To this
solution compound 1 (1 g, 5.4 mmol) and aminourea hydrochloride (0.62 g,
5.4 mmol) was added. The resulting mixture was stirred at 150–160ꢀC for
2 h and then was poured into ice water. The product 2 was filtered and
washed with water, and then crystallized by acetic acid to give white crystals
(0.85 g, 90%), m.p. 290–291ꢀC; IR (KBr, cmÀ1) 3100–3450, 3086, 1634,
1515, 1358; 1H-NMR (DMSO-d6): ꢀ 12.3 (br, 2H), 8.71 (d, 2H), 8.34
(q, 2H), 7.26 (d, 2H); m/z (EI): 344 (Mþ); Found: C, 47.88; H, 2.56; N,
1
15.70. C14H8Cl2N4O7 Á ⁄2H2O requires C, 47.60; H, 2.57; N, 15.86%.
Synthesis of compound 3: To a stirred mixture of concentrated HCl
(15 mL) and compound 2 (0.9 g, 2.6 mmol), SnCl2 (4 g) in EtOH (5 mL) was

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
MACROCYCLES CONTAINING 1,3,4-OXADIAZOLE MOIETY
3343
added dropwise, and was the reaction temperature below 30ꢀC. After
stirring at room temperature for 12 h, at 40ꢀC for 8 h, the product was
filtered, dissolved in DMF, and washed with ammonia solution to pH ¼ 7,
and then water was added. The product 3 was filtered to give white crystals
(0.66 g, 89%), m.p. 292–294ꢀC; IR (KBr, cmÀ1) 3421, 3343, 3627, 1635;
1H-NMR (DMSO-d6): ꢀ 9.35 (s, 2H), 7.05 (d, 2H), 6.72–6.89 (m, 4H),
5.00 (s, 4H); m/z (EI): 284 (Mþ); Found: C, 53.81; H, 4.95; N, 17.71.
C14H12Cl2N4O3 Á 1.5H2O requires C, 54.02; H, 4.86; N, 18.00%.
Synthesis of compound 4: A mixture of compound 2 (0.4 g, 1.16 mmol)
and K2CO3 (0.4 g, 2.86 mmol) and n-bromobutane (0.3 mL, 2.32 mmol)
in DMF (15 mL) was refluxed for 4 h and then was poured into water.
The precipitate formed was filtered and crystallized by EtOH to give
powder (0.3 g, 60%), m.p. 150–152ꢀC; IR (KBr, cmÀ1) 3084, 2960, 2874,
1615, 1516, 1344, 1285; 1H-NMR (CDCl3): ꢀ 8.97(d, 2H), 8.40 (q, 2H), 7.17
(d, 2H), 4.27 (t, 4H), 1.97–2.01 (m, 4H), 1.57–1.63 (m, 4H), 0.97 (t, 6H); m/z
(EI): 456 (Mþ); Found: C, 58.95; H, 5.55; N, 12.03. C22H24N4O7 requires C,
57.89; H, 5.30; N, 12.27%.
Synthesis of compound 5: To a stirred solution of 95% EtOH (15 mL)
and compound 4 (0.1 g, 0.22 mmol), CaCl2 (0.04 g) in water (1 mL) and Zn
powder (1 g) was added, and resulting mixture was refluxed for 1 h, and then
was filtered to yield the fresh solution of compound 5.
Synthesis of compound 8: To a stirred mixture of concentrate H2SO4
(8 mL) and compound 7 (2.5 g, 10 mmol), HNO3 (2.4 mL) was added drop-
wise, and was the reaction temperature below 30ꢀC. After stirred at room
temperature for 5 h, at 80ꢀC for 1 h, the solution was poured into 200 g ice
water. The product was filtered and washed with water, 10% sodium bicar-
bonate, and then recrystallized from DMF/H2O to give white crystals
(2.99 g, 88.1%), m.p. 247–248ꢀC; IR (KBr, cmÀ1) 1626, 1526, 1351;
1H-NMR (DMSO-d6): ꢀH 8.68 (s, 2H), 8.37 (d, 2H), 7.77 (d, 2H), 2.57
(s, 6H); MS (EI): 340 (Mþ); Found: C, 55.46; H, 3.45; N, 16.64.
1
C16H12N4O5 Á ⁄4H2O requires C, 55.74; H, 3.65; N, 16.25%.
Synthesis of compound 9: A mixture of compound 8 (3.40 g, 10 mmol),
iron powder (3.36 g, 60 mmol) and 150 mL of EtOH was heated to 70ꢀC,
while 7.5 mL of concentrated HCl was added slowly, then stirred and
refluxed for 2 h. The mixture was filtered while still hot. The residue was
washed with DMF. The filtrate was neutralize with sodium acetate to
pH ¼ 5–6, and then recrystallized from DMF/H2O to give white powders
(2.20 g, 78.6%), m.p. 272–274ꢀC; IR (KBr, cmÀ1): 3228, 3449, 1584;
1H-NMR (DMSO-d6): ꢀH 7.13–7.30 (d, 6H), 5.26 (s, 4H), 2.11 (s, 6H);
MS (EI): 280 (Mþ).
Synthesis of compound 10 and its sodium compound 11: TsCl (4.5 g,
24 mmol) was added to a stirred solution of compound 9 (1.68 g, 6 mmol)

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3344
WANG, LI, AND HUA
in pyridine (20 mL) at room temperature. The reaction mixture was heated
at 50ꢀC for 2 h with stirring and then poured into ice water. The precipitate
was filtered, washed with water and recrystallized with DMF/H2O to give
small slightly yellow crystals (3.05 g, 86.4%), m.p. 214–218ꢀC; IR (KBr,
1
cmÀ1): 3289, 1598, 1334, 1165; H-NMR (DMSO-d6): ꢀH 10.80 (s, 2H),
8.52–8.72 (m, 8H), 8.33 (d, 6H), 3.28 (s, 6H), 3.00 (s, 6H); MS (FAB):
1
589 (Mþ þ 1); Found: C, 60.27; H, 4.93; N, 8.96. C30H28N4O5S2 Á ⁄2H2O
requires C, 60.29; H, 4.89; N, 9.38%.
Enough fresh EtONa/EtOH was added to a suspension of compound
11 in EtOH and stirred at reflux for 0.5 h. The precipitate was filtered and
dried under vacuum to give the sodium compound 11. Yield was almost
quantitative.
Synthesis of macrocycle 1: A mixture of compound 3 (50 mg,
0.18 mmol) and 2,5-di(3-formylphenyl)-1,3,4-oxadiazole (50 mg, 0.18 mmol)
in dry MeOH (25 mL) was refluxed until the solid dissolved completely. To
this solution Ba(ClO4)2 (0.2 mmol) in MeOH (10 mL) was added dropwise.
The reaction solution was refluxed for 3 h. The precipitate formed was
filtered, washed with MeOH, and then dried in vacuum at room temperature
to give yellow powders (70 mg, 76%), m.p.>340ꢀC; IR (KBr, cmÀ1) 3346,
1
1628; H-NMR (TFA-d1): ꢀ 9.86 (s, 2H), 9.55 (s, 2H), 9.21 (d, 2H), 8.89
(d, 2H), 8.70–8.80 (m, 2H), 8.58 (d, 2H), 8.27 (q, 2H), 8.12 (t, 2H), 7.59
(d, 2H); m/z (FAB): 527(M þ 1); Found: C, 64.99; H, 3.63; N, 14.92.
C30H18N6O4 Á 1.5H2O requires C, 65.10; H, 3.82; N, 15.18%.
Synthesis of macrocycle 2: A mixture of fresh solution of compound 5
and 2,5,-di(3-formylphenyl)-1,3,4-oxadiazole (50 mg, 0.18 mmol) in dry
MeOH (25 mL) was refluxed until the solid dissolved completely. To this
solution Ba(ClO4)2 (0.2 mmol) in MeOH (10 mL) was added dropwise. The
reaction solution was refluxed for 3 h. The precipitate formed was filtered,
washed with MeOH, and then dried in vacuum at room temperature to give
yellow powders (40 mg, 30%), m.p.>340ꢀC; IR (KBr, cmÀ1) 2957, 2928,
1
1627, 1282; H-NMR (TFA-d1): ꢀ 9.70 (s, 2H), 9.49 (d, 2H), 9.14 (t, 2H),
8.74 (d, 2H), 8.40 (s, 2H), 8.15–8.35 (m, 2H), 7.96 (t, 2H), 7.46 (t, 2H), 4.46
(d, 4H), 1.93 (d, 4H), 1.49 (d, 4H), 0.94–0.98 (m, 2H); m/z (FAB):
1
639 (M þ 1); Found: C, 54.06; H 4.89; N, 10.74. C38H34N6O4 Á ⁄2Ba-
(ClO4)2 Á 2H2O requires C, 54.15; H, 4.54; N, 9.97%.
Synthesis of macrocycle 3: A solution of compound 11 (0.71 g,
and
1.2 mmol)
2,5-di(2-chloromethyl-5-nitro-phenyl)-1,3,4-oxadiazole
(0.58 g, 1.2 mmol) in dry DMF (50 mL) was refluxed for 5 h. The precipitate
formed was filtered, washed with DMF and water, and then dried under
vacuum to give a orange powers (two-step 0.125 g, 16.6%), m.p.>360ꢀC; IR
1
(KBr, cmÀ1): 1600, 1520, 1345; H-NMR (TFA-d1): ꢀH 10.15 (s, 2H), 9.04
(s, 2H), 8.51 (s, 2H), 8.43 (d, 2H), 8.15 (t, 4H), 7.43 (d, 2H), 2.43 (s, 6H);

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
MACROCYCLES CONTAINING 1,3,4-OXADIAZOLE MOIETY
3345
MS (MALDI-TOF): 613 (M þ 1); Found: C, 60.02; H, 3.67; N, 16.72.
C32H20N8O6 Á 1.5H2O requires C, 60.09; H, 3.62; N, 17.51%.
REFERENCES
1. Peng, Z.; Bao, Z.; Galvin, M.E.; Chandross, E.A. Chem. Mater. 1998,
10, 1201.
2. Peng, Z.; Bao, Z.; Galvin, M.E. Adv. Mater. 1998, 10, 680.
3. Chung, S.-J.; Kwon, K.-Y.; Lee, S.-W.; Jin, J.-I.; Lee, C.H.; Lee, C.E.;
Park, Y. Adv. Mater. 1998, 10, 1112.
4. Wang, S.; Hua, W.; Zhang, F.; Wang, Y. Synth. Met. 1999, 99, 249.
5. Wang, S.; Zheng, S.; Meng, H.; Hua, W. Synth. Met. 1998, 93, 181.
6. Zheng, S.; Wang, S.; Hua, W. J. Heterocycl. Chem. 1998, 275–277.
7. Wang, S.; Hua, W.; Li, Z. Chin. Chem. Lett. 1999, 10, 367–370.
8. Zhou, J.; Hua, W.; Yang, Q. Chem. J. Chin. Univ. 1996, 17, 1721.
9. Meng, H.; Hua, W. Chin. J. Org. Chem. 1998, 18, 153.
10. Holmes, E.L.; Ingold, C.K. J. Chem. Soc. 1926, 1305.
11. Fenton, G.W.; Ingold, C.K. J. Chem. Soc. 1928, 3295.
12. Baltazzi, E.; Wysocki, A. Chem. Ind. 1963, 26, 1680.
Received in Japan August 27, 2001

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.