Synthesis of a novel tripodal receptor based on 1,8-naphthyridine derivatives

Article abstract of DOI:10.1016/j.cclet.2009.08.005

A novel tripodal receptor, 1,3,5-tri((5,7-dimethyl-1,8-naphthyridin-2-yl-amino)methyl)-2,4,6-triethylbenzene (1) was synthesized from starting materials 2,6-diamino-pyridine (2) and 1,3,5-triethylbenzene (4) by three steps with an overall yield of 25%, and characterized by ESI-MS, FT-IR and ¹H NMR spectra. Additionally, its absorption and emission spectra were investigated.

Full text of DOI:10.1016/j.cclet.2009.08.005

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 23–26
www.elsevier.com/locate/cclet
Synthesis of a novel tripodal receptor based on
1,8-naphthyridine derivatives
Hui Fang Jie Li a,b, Wen Fu Fu a,b,c,
*
a Graduate University of Chinese Academy of Sciences, Beijing 100039, China
b Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
c College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650092, China
Received 4 May 2009
Abstract
A novel tripodal receptor, 1,3,5-tri((5,7-dimethyl-1,8-naphthyridin-2-yl-amino)methyl)-2,4,6-triethylbenzene (1) was synthe-
sized from starting materials 2,6-diamino-pyridine (2) and 1,3,5-triethylbenzene (4) by three steps with an overall yield of 25%, and
1
characterized by ESI-MS, FT-IR and H NMR spectra. Additionally, its absorption and emission spectra were investigated.
# 2009 Wen Fu Fu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Tripodal receptor; 1,8-Naphthyridine; Synthesis; Spectroscopy
The synthesis of effective and selective receptors for carbohydrate has been acknowledged as a subject of
significant importance to chemistry and biology [1]. Although much research has been done upon host molecules [2],
the recognition of carbohydrates by artificial receptors is still inadequate. The difficulty in designing these highly
selective receptors is the three-dimensional complexity of sugar structures. Meanwhile, it is also important that OH
groups in sugar structure as well as ring oxygen can participate host–guest interactions. 1,8-Naphthyridine derivatives
that possess several inherent hydrogen-bonding sites have been chosen as the ideal building blocks for recognition of
carbohydrates. Previous report has showed that 1,8-naphthyridines can form cooperative and secondary hydrogen-
bond pattern like Fig. 1, when they interact with carbohydrates [3]. Therefore, 1,8-naphthyridine derivative linked
with the phenyl spacer yields 1,3,5-substituted 2,4,6-triethylbenzene for matching the demand of three-dimensional
recognition of sugar structures. Six identical substituents are disposed above and below the benzene plane [4], which
directs the three binding arms toward the same side of the aromatic ring.
In this communication, a new tripodal receptor 1 based on 1,8-naphthyridine, was synthesized successfully by
reacting 5,7-dimethyl-2-amine-1,8-naphthyridin (3) with 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene (5) (Scheme
1). 3 was obtained in 85% yield by using 2,6-diaminopyridine (2) and acetylacetone as starting materials in solution of
acetic acid and sulfuric acid refluxed for 24 h [5]. 1,3,5-Tris-(bromomethyl)- 2,4,6-triethylbenzene (5) was generated
directly via the threefold bromomethylation of triethylbenzene with high yield [6]. However, the desired compound 1
was not obtained by using K2CO3, KOH or NaH as base in CH3CN, DMF, DMSO or toluene solution, and there was no
* Corresponding author at: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
E-mail address: wf_fu@yahoo.com.cn (W.F. Fu).
1001-8417/$ – see front matter # 2009 Wen Fu Fu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2009.08.005

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H.F.J. Li, W.F. Fu / Chinese Chemical Letters 21 (2010) 23–26
Fig. 1. Hydrogen-bond pattern for interaction of 1,8-naphthyridine with carbohydrate.
Scheme 1. Reagents and conditions: (a) HOAc and H2SO4, reflux, 24 h; (b) (CH2O)n and ZnBr2, HBr in HOAc (30%), 90 8C, 10 h; and (c) TBAB,
toluene and 50% KOH, 80 8C, 24 h.
improvement for the nucleophilic substitution reaction via prolonging reaction time, changing reaction temperature or
reagent concentration until tetrabutylammonium bromide (TBAB) was used as phase-transfer catalyst to yield the
tripodal receptor 1.
The changes of UV–vis absorption and fluorescent emission spectra for compound 1 in CH2Cl2 with the
addition CH3OH were shown in Fig. 2. Compound 1 displayed two absorption peaks at 341 and 355 nm
Fig. 2. Changes in the absorption (a) and emission (b) spectra of 1 (1.0 ꢀ 10ꢁ5 mol/L) in CH2Cl2 with addition of CH3OH.

H.F.J. Li, W.F. Fu / Chinese Chemical Letters 21 (2010) 23–26
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Fig. 3. Changes in emission spectra of 1 (1.0 ꢀ 10ꢁ5 mol/L) in CH3OH with addition of D-glucose in CH3OH (3.4 ꢀ 10ꢁ2 mol/L).
Fig. 4. Probable molecular configuration of 1 with CH3OH or D-glucose.
(emax = 65,048 L molꢁ1 cmꢁ1) as depicted in Fig. 2a, which could be ascribed to intraligand charge transfer (ILCT)
p ! p* transition. Upon addition CH3OH to the CH2Cl2 solution of 1, the absorption was red-shifted, and emission
intensity increased. The emission spectrum with lmax at 386 nm was red-shifted to 398 nm upon excitation at 340 nm
(Fig. 2b), indicating the presence of weak interaction between 1 and polar solvent CH3OH.
As shown in Fig. 3 fluorescence intensity of 1 in CH3OH changed with addition of D-glucose in the same solvent. 1
exhibits one emission peak at 398 nm in CH3OH, the fluorescence intensity decreased obviously with increasing D-
glucose concentration while absorption spectrum remained unaltered. As the flexible framework of 1, the mutual
repulsion of methanol molecules and the three-dimensional feature of D-glucose structure lead to changes in molecular
configuration of 1 as depicted in Fig. 4. The quenched luminescence can be tentatively assigned to the intermolecular
interaction of 1 and D-glucose.
In conclusion, an effective method for synthesis of the new tripodal receptor bearing 1,8-naphthyridine via N-
alkylation was performed. The advantages of this approach are few by-product and easy experiment. And the
recognition of D-glucose in CH3OH by this tripodal receptor was realized. Detail mechanism of quenching effect on
fluorescence emission of 1 in CH3OH with addition of D-glucose and further applications of this new tripodal receptor
in recognition of other carbohydrate are in progress.
1. Experimental
1H NMR spectrum was recorded on Bruker DPX-400 (400 MHz) at 298 K and chemical shifts (d) were obtained
relative to tetramethylsilane (TMS). Mass spectra were recorded on BIFLEX-III MALDI-TOF mass spectrometer for
matrix-assisted laser desorption/ionization (MALDI). UV–vis absorption spectra were taken on a Hitachi U-3010

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H.F.J. Li, W.F. Fu / Chinese Chemical Letters 21 (2010) 23–26
spectrophotometer and emission spectra were recorded with a Hitachi F-4500 fluorescence spectrophotometer. IR
spectra were measured on Varian 3100 FT-IR System at 298 K.
A solution of 3 (0.590 g, 3.4 mmol) TBAB (0.137 g, 0.85 mmol) and 5 (0.375 g, 0.85 mmol) in toluene (50 mL)
and 50% aqueous KOH (8.5 mL) was stirred at 80 8C for 24 h under nitrogen atmosphere. Then organic phase was
separated after cooled, washed with water for three times and dried over anhydrous sodium sulfate. After filtration and
removal of the solvent under reduced pressure, the crude product was purified by chromatography on silica gel (200–
300 mesh), using CH2Cl2/C2H5OH (v/v, 20/1) as eluent to give the pure product as pale yellow powder. Yield: 30%.
MALDI-TOF-MS: [M+H]+, 718.1; [M+Na]+, 740.1; [M+K]+, 756.1. FT-IR (KBr, cmꢁ1): 3427.5, 2960.4, 2923.6,
2361.3, 2337.7, 1630.6, 1570.3, 1385.1, 1097.9. 1H NMR (400 MHz, DMSO-d6, 298 K, relative to Me4Si): d 1.51 (t,
9H, CH3), 2.57 (s, 18H, CH3), 2.82 (q, 6H, CH2), 4.41 (s, 6H, CH2), 4.52 (br, 3H, NH), 7.00 (d, 3H, J = 9.12 Hz,
naphthyl-H), 7.14 (s, 3H, naphthyl-H), 8.11 (d, 3H, J = 9.12 Hz, naphthyl-H).
Acknowledgments
We are grateful to the National Natural Science Foundation of China (Nos. 20671094 and 90610034) and the
foundation (No. GJHZ05) for Bureau of International Co-operation of Chinese Academy of Science.
References
[1] (a) B. Ernst, G.W. Hart, P. SinaK, Carbohydrates in Chemistry and Biology, Part I, vol. 2, Wiley–VCH, Weinheim, 2000;
(b) B. Ernst, G.W. Hart, P. SinaK, Carbohydrates in Chemistry and Biology, Part II, vol. 4, Wiley–VCH, Weinheim, 2000.
[2] (a) R.P. Bonar-Low, J.K.M. Sanders, J. Am. Chem. Soc. 117 (1995) 259;
(b) A.P. Davis, R.S. Wareham, Angew. Chem. Int. Ed. 37 (1998) 2270;
(c) J.C. Morales, S. Penades, Angew. Chem. Int. Ed. 37 (1998) 654;
(d) A.P. Davis, R.S. Wareham, Angew. Chem. Int. Ed. 38 (1999) 2978;
(e) M. Inouye, K. Takahashi, H. Nakazumi, J. Am. Chem. Soc. 121 (1999) 341.
[3] M. Mazik, W. Sicking, Chem. Eur. J. 7 (2001) 664.
[4] For a recent review on benzene-based tripodal receptor, see: G. Hennrich, E.V. Anslyn, Chem. Eur. J. 8 (2002) 2218.
[5] R.A. Henry, P.R. Hammond, J. Heterocyclic Chem. 14 (1977) 1109.
[6] A. Vacca, C. Nativ, M. Cacciarini, R. Pergoli, S. Roelens, J. Am. Chem. Soc. 126 (2004) 16456.