Synthesis of 1,2,3-triazole-4-carboxamide-containing foldamers for sulfate recognition

Article abstract of DOI:10.1002/ejoc.201301838

A series of triazolecarboxamide-containing foldamers were synthesized from simple starting materials by means of repeated [3+2] cycloadditions) and acid-amine coupling reactions. Foldamer-anion binding behavior and affinities were determined by ¹H NMR titration in [D₂] dichloromethane. The selective recognition of sulfate by these motifs was studied by one- and two-dimensional (¹H, ¹H-¹H COSY and NOESY) NMR spectroscopy as well as UV/Visible and fluorescence titrations. The structures of the triazolecarboxamide-containing foldamers can be optimized for highly selective recognition of sulfate anions by changing the numbers of triazolecarboxamide units and by the introduction of electron-withdrawing substituents on the terminal benzene ring. These findings indicate the importance of the structural compatibility between the receptor and anions for the highly selective anion binding as well as the electronic effect on tuning the anion-binding affinities of receptors. A series of triazolecarboxamide-containing foldamers were synthesized. By increasing the numbers of triazolecarboxamide units and modification of the terminal benzene ring, the binding stoichiometry and binding affinity can be controlled. Copyright

Full text of DOI:10.1002/ejoc.201301838

FULL PAPER
DOI: 10.1002/ejoc.201301838
Synthesis of 1,2,3-Triazole-4-carboxamide-Containing Foldamers for Sulfate
Recognition
Li Cao,[a,b] Runsheng Jiang,[c] Yulan Zhu,*[a,b] Xinlong Wang,[a] Yongjun Li,*[c] and
Yuliang Li[c]
Keywords: Molecular recognition / Receptors / Host–guest systems / Sulfate anions / Titration
A series of triazolecarboxamide-containing foldamers were
synthesized from simple starting materials by means of re-
peated [3+2] cycloadditions) and acid–amine coupling reac-
tions. Foldamer–anion binding behavior and affinities were
determined by 1H NMR titration in [D2]dichloromethane. The
selective recognition of sulfate by these motifs was studied
by one- and two-dimensional (1H, 1H-1H COSY and NOESY)
NMR spectroscopy as well as UV/Visible and fluorescence
titrations. The structures of the triazolecarboxamide-contain-
ing foldamers can be optimized for highly selective recogni-
tion of sulfate anions by changing the numbers of triazole-
carboxamide units and by the introduction of electron-with-
drawing substituents on the terminal benzene ring. These
findings indicate the importance of the structural compatibil-
ity between the receptor and anions for the highly selective
anion binding as well as the electronic effect on tuning the
anion-binding affinities of receptors.
containing C–H bonds, have been incorporated in anion re-
cognition. The large dipole oriented along the triazole C–
H bond, as well as its polarization due to the electron-with-
drawing character of the three nitrogen atoms, generates a
potential C–H bond donor. Indeed, considerable efforts[13]
have been devoted to the preparation of these motifs. It was
shown that hosts incorporating two or more 1,2,3-triazole
groups can bind anions in moderately competitive solvents
solely through C–H···anion hydrogen bonds.
Introduction
Research into anion recognition has been attracting con-
siderable interest in recent years, due to its wide applica-
tions in many scientific areas, such as environmental sci-
ence, biology, and chemistry.[1] Anions are present every-
where in living systems and cause both beneficial and dele-
terious effects to human beings. With regard to the various
important anions, anion receptors specific to sulfate cur-
rently constitute an area of intense interest, due to the im-
portant roles the sulfate anion plays in biological systems
and disease,[2] in hydrometallurgy,[3] and as a pollutant.[4]
Typical anion recognition moieties containing NH groups,
such as pyrrole,[5] urea,[6] amide,[7] ammonium,[8] and imid-
azolium systems,[9] have been widely studied as hydrogen
donors to bind the anion species (N–H···X–). However, it is
a challenge to employ C–H groups for anion recognition
because of the low acidity of the C–H bond.
In recent years, with the development of click chemis-
try,[10] groups such as triazole[11] or triazolium systems,[12]
[a] Institute of Functional Material Chemistry, Faculty of
Chemistry, Northeast Normal University,
Changchun 130024, P. R. China
E-mail: ylzhu1998@126.com
http://chem.nenu.edu.cn/
[b] Jiangsu Key Laboratory for Chemistry of Low-Dimensional
Materials, Huaiyin Normal University,
Huaian 223300, P. R. China
[c] Beijing National Laboratory for Molecular Sciences (BNLMS),
CAS Key Laboratory of Organic Solids, Institute of Chemistry,
Chinese Academy of Sciences,
Beijing 100190, P. R. China
E-mail: liyj@iccas.ac.cn
http://english.ic.cas.cn/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301838.
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FULL PAPER
In previous studies, we have developed a versatile anion 4 with NaN3 and a catalytic amount of sodium ascorbate
receptor building block combining the characteristics of and CuI provided 5. By repetition of a sequence based on
urea and triazole – triazolecarboxamide – that can be used a [3+2] cycloaddition and an acid–amine coupling reaction,
extensively for the construction of numerous receptor sys- compound 9 was afforded. The [3+2] cycloaddition between
tems appended with functional groups.[14] The association compound 9 and 1-azopyrene[15] gave compound L1 in 56%
of hydrogen bonding, π–π stacking, and dipole–dipole in- yield, and subsequent reactions produced compounds L2
teraction in L0 can result in changes in tetrahedral sulfate and L3 in 45% and 43% yields. The COSY and NOESY
anion binding from 2:1 to 1:1 complexation,[14a] which is a spectra were used to assign protons of the receptor L2 in
good start for the construction of foldamer-like sulfate detail (Figure S1 in the Supporting Information).
anion receptors.
L1, similar to L0 but containing an extra triazole group
(connected to the pyrene unit), also showed a 2:1 binding
process with sulfate. Upon addition of 0.5 equiv. of bis-
(tetrabutylammonium) sulfate (TBA2SO4), the triazole pro-
ton (ΔδHf = 1.0 ppm, ΔδHk = 0.47 ppm, ΔδHa =
0.41 ppm) and the amide proton (ΔδHe = 1.39 ppm, ΔδHj
= 1.32 ppm) showed downfield shifts (Figure 1). Upfield
shifts of protons on the pyrene ring and a proton of the
benzene ring close to the pyrene ring (ΔδHg = 0.1 ppm)
In this manuscript we present new triazolecarboxamide-
containing foldamers for highly selective recognition of
sulfate anions. By increasing the numbers of triazolecarbox-
amide units and modifying the terminal benzene ring, the
binding stoichiometry and binding affinity can be con-
trolled.
Results and Discussion
Unlike in the case of the previous receptor L0, here we were observed (smaller than that in the case of L0). With
designed new sulfate receptors containing two and three tri- the addition of another 0.5 equiv. of sulfate (1.0 equiv. to-
azolecarboxamide units connected through benzene units in tal), the signals of the central amide NH (ΔδHf = 1.39 ppm,
the middle as the binding motif, the photoactive pyrene ring ΔδHk = 0.58 ppm, ΔδHa = 0.66 ppm) and triazole CH pro-
attached to the triazole terminal as a fluorescent handle tons (ΔδHe = 1.89 ppm, ΔδHj = 1.97 ppm) migrated further
and π–π stacking unit, and a terminal benzene ring to pro- downfield, and the upfield-shifted signals moved back to
vide convenience for the investigation of substitution effects their original position (Figure S2 in the Supporting Infor-
on binding affinity. The synthesis of the triazolecarbox- mation). These results clearly indicate that in the presence
amide derivatives was performed by a stepwise strategy as of 0.5 equiv. of sulfate the formation of a 2:1 host–guest
shown in Scheme 1. Treatment of 4-tert-butyl-2-nitroaniline complex occurred, though with less stability than in the
(1) with ICl gave compound 2, which was treated with case of L0. This complex is gradually replaced by a 1:1
NaNO2 in H2SO4 and ethanol to yield 3. Reduction of the complex as the sulfate/L1 ratio increases from 0.5 to 1 and,
nitro group with SnCl2 afforded iodoamine 4. Treatment of ultimately, the 1:1 complex prevails thereafter.[14a]
Scheme 1. Preparation of L1, L2, and L3. Reaction conditions: a) ICl, C2H4Cl2, 95%; b) NaNO2, H2SO4, ethanol, 82%; c) SnCl2, ethanol,
81%; d) NaN3, sodium ascorbate, CuI, N,N-dimethylethane-1,2-diamine, DMSO/H2O (5:1), room temp., 1 h, 67%; e) CuSO4, sodium
ascorbate, ethanol/H2O (2:1), room temp., 12 h, 89%; f) N,N-dicyclohexylcarbodiimide (DCC), 4-(dimethylamino)pyridine (DMAP),
CH2Cl2, 65%; g) CuSO4, sodium ascorbate, THF/H2O (10:1), room temp., 12 h, 67%; h) DCC, DMAP, CH2Cl2, 53%; i) CuI, 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU), 1-azopyrene, toluene, 56%; j) trimethylaluminum, aniline/p-iodoaniline, toluene, 2 h.
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Synthesis of Foldamers for Sulfate Recognition
Figure 1. a) Illustration of the sulfate-binding process of receptor L1; b) 1H NMR (CD2Cl2, 400 MHz) spectra of L1 in the presence of
2–
SO4
.
With an increase in the numbers of triazolecarboxamide observed, these signals must correspond to contacts due to
units, as in L2, three amide NH and triazole CH groups the folding of the molecular chain.[16]
in combination with one CH group from each of the two
To investigate the electronic effects on the binding affin-
connecting benzene groups can interact with a sulfate anion ities of foldamers of this kind for sulfate, iodide was intro-
in a 1:1 ratio through eight hydrogen bonds. The complex- duced into the terminal benzene ring. Iodide-substituted re-
ation behavior of host L2 with the sulfate anion was studied ceptor L3 showed similar binding behavior with SO42–. The
by 1H NMR titration in [D2]dichloromethane at 25 °C. Fig- titration curve is best fitted for a 1:1 host–guest complex,
ure 2 shows the 1H NMR spectra of L2 with different yielding an apparent binding constant of
K
=
amounts of TBA2SO4. In general, π–π stacking results in 2200Ϯ100 m–1, which is bigger than that obtained from L2.
upfield shifting of protons, whereas hydrogen-bonding in- This result indicated that the electron-withdrawing group
teraction results in downfield shifting of protons. Upon the could enhance the binding affinity (see Figure S3 in the
addition of 1.0 equiv. of TBA2SO4, the amide protons Supporting Information).
(ΔδHi = 1.84 ppm, ΔδHn = 1.88 ppm, ΔδHd = 1.16 ppm),
The binding behavior of L2 with other anions was also
1
the triazole protons of the triazolecarboxamide unit (ΔδHo investigated by H NMR titration as shown in Figures S4–
= 0.92 ppm, ΔδHj = 0.89 ppm, ΔδHe = 0.69 ppm), and two S9 in the Supporting Information. Addition of tetrabut-
benzene protons (ΔδHg = 0.02 ppm, ΔδHm = 0.06 ppm) ylammonium nitrate to L2 in [D2]dichloromethane resulted
1
showed downfield shifts, due to the multiple hydrogen in only very small perturbations in the H NMR spectra
bonding between sulfate and L2. The upfield shifts of pro- (Figure S4 in the Supporting Information), which is due to
tons Ha and Hb on the terminal benzene ring and Hp–x size and geometry mismatch between nitrate and L2, be-
on the pyrene system evidently indicated the π–π stacking cause nitrate is big and flat. Titration of fluoride anions
between these terminal aromatic rings due to folding of mo- induced similar folding of molecular L2 through hydrogen
lecule L2 upon complexation, as shown in Figure 2 (a, bonding of triazole protons and the middle benzene ring
right).
protons, whereas the amide protons Hi, Hn, and Hd disap-
The stable 1:1 L2·SO42– complex allowed for a structural peared due to the fast oscillation of F– in the cavity formed
1
investigation in solution by NOESY NMR spectroscopy. by the foldamer at the same H NMR timescale at 298 K.
Strong NOE connections were observed between Ht/v and Cl– and Br– induced similar but weaker H NMR spectra
1
He, between Hn and Hd, and between Ho and Hc, which shifts. As the methyl group of the acetate anion prefers to
supported the formation of the folded circle conformation form a hydrogen bond with the nitrogen atom of the tri-
(see the bracketed cross peaks in Figure 3). Because the dis- azole, thus repelling the two triazole C–H bonds to the out-
tances between Hd and Hn and between Hc and Ho of the side, AcO– binds with the half-circle formed by the central
linear chain are much too long for any cross peak to be triazolecarboxamide unit and the terminal triazolecarbox-
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L. Cao, R. Jiang, Y. Zhu, X. Wang, Y. Li, Y. Li
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Figure 2. a) Illustration of the sulfate-binding process of receptor L2; b) 1H NMR (CD2Cl2, 400 MHz) spectra of L2 in the presence of
2–
SO4
.
tive to Hd (Figure S8 in the Supporting Information). The
stability constant of the F– complex (79Ϯ8 m–1) was calcu-
lated by fitting the chemical shifts of proton He (as shown
in Figure S5 in the Supporting Information), and the sta-
bility constants of the Cl– (39Ϯ6 m–1), Br– (5.3Ϯ0.8 m–1),
2–
–
AcO– (18Ϯ2 m–1), SO4 (1300Ϯ100 m–1), and H2PO4
(590Ϯ50 m–1) complexes were obtained by analysis of the
signal shifts of amide NH (Hi) with use of a 1:1 binding
model with the WinEQNMR2[17] software, as summarized
in Figure 4. With increasing halide size, the binding stability
decreased, whereas L2 showed the greatest selectivity
towards sulfate, due to the association effects of eight hy-
2–
Figure 3. Intramolecular NOE contacts in the L2·SO4 complex
and partial NOESY spectrum (600 MHz) of L2 + SO42– in CD2Cl2
at 288 K (mixing time: 1 s).
Figure 4. Comparison of the binding constants of L2 with various
1
amide connected with the pyrene group, as indicated by the
anions (determined by H NMR spectroscopy) in CD2Cl2 at room
more strongly downfield shifts of protons Hi and Hn rela- temperature.
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Synthesis of Foldamers for Sulfate Recognition
6.51 (s, 2 H), 1.29 ppm (s, 9 H). 13C NMR (100 MHz, CDCl3): δ
= 143.8, 141.9, 141.3, 131.5, 123.2, 87.6, 34.0, 31.20 ppm. MS (EI):
m/z = 320. C10H13IN2O2 (320.13): calcd. C 37.52, H 4.09, N 8.75;
found C 37.65, H 4.13, N 8.69.
drogen bonds and the π–π stacking between the terminal
groups.
UV/Vis experiments were carried out in CH2Cl2 to evalu-
ate the binding properties of L2 towards sulfate (Figure S11
in the Supporting Information): L2 exhibits weak increases
in the absorption of the pyrene band (λmax = 344 nm) and
the triazolecarboxamide band (λmax = 277 nm). The bind-
ing stoichiometry of the sulfate–L2 interactions was calcu-
lated to be 1:1 from the Job’s plot (Figure S12 in the Sup-
porting Information). L2 exhibits an emission band of py-
rene at λmax = 386 nm (Figure S13 in the Supporting Infor-
mation), which is quenched upon the addition of SO42– due
to electron transfer from the electron-rich sulfate anions to
the pyrene chromophore.
Compound 3: NaNO2 (10 g, 145 mmol) was slowly added at 0 °C
to a suspension of compound 2 (22.33 g, 70 mmol) in concentrated
sulfuric acid (60 mL). After additional stirring for 15 min at 0 °C,
the mixture was allowed to reach room temperature and stirred at
this temperature for an additional 3 h. The black viscous mixture
was slowly added to ethanol (500 mL) at reflux. After complete
addition, most of the solvent was evaporated and the mixture was
poured into dichloromethane/water (500/500 mL). The organic
phase was extracted with CH2Cl2, washed with water and brine,
and dried with MgSO4. The crude residue was subjected to flash
silica gel column chromatography (CH2Cl2/petroleum ether 1:15)
1
to yield solid 3 (82%). H NMR (400 MHz, CDCl3): δ = 8.37 (s, 1
H), 8.20 (s, 1 H), 8.01 (s, 2 H), 1.35 ppm (s, 9 H). 13C NMR
(100 MHz, CDCl3): δ = 155.2, 148.5, 140.7, 129.6, 120.0, 93.5, 35.2,
30.9 ppm. MS (EI): m/z = 304. C10H12INO2 (305.11): calcd. C
39.36, H 3.96, N 4.59; found C 39.51, H 4.01, N 4.53.
Conclusions
In summary, we have successfully optimized the struc-
tures of triazolecarboxamide-containing foldamers for se-
lective recognition of sulfate anions and demonstrated that
the binding stoichiometry and binding affinity can be tuned
by increasing the numbers of triazolecarboxamide units and
by modification of the terminal benzene ring. The struc-
tural compatibility between the receptor and anions greatly
influenced the binding strength and selectivity. The triazole-
carboxamide units can give rise to quite strong oxyanion
receptors; this system could open the way to the construc-
tion of numerous receptor systems when triazolecarbox-
amides are preorganized into shape-persistent macrocyclic
structures in the future.
Compound 4: SnCl2·2H2O (9.06 g, 40.0 mmol) was added to a solu-
tion of compound 3 (2.44 g, 8 mmol) in ethanol (5 mL). The reac-
tion mixture was heated at reflux until the reaction was complete
(indicated by TLC analysis). The solvent was removed under re-
duced pressure and the crude residue was partitioned between ethyl
acetate and KOH (2 m). The aqueous layer was extracted with ethyl
acetate and the combined organic extracts were washed with brine
and water, dried (MgSO4), and concentrated under reduced pres-
sure. The crude residue was subjected to flash silica gel column
chromatography (ethyl acetate in petroleum ether, 20%) to yield
solid 4 (82.9%). 1H NMR (400 MHz, CDCl3): δ = 7.11 (s, 1 H),
6.88 (s, 1 H), 6.65 (s, 1 H), 3.69 (s, 2 H), 1.25 ppm (s, 9 H). 13C
NMR (100 MHz, CDCl3): δ = 154.5, 147.4, 125.0, 121.1, 112.0,
95.3, 34.6, 31.2 ppm. MS (EI): m/z = 275. C10H14IN (275.13):
calcd. C 43.65, H 5.13, N 5.09; found C 43.69, H 5.07, N 5.22.
Experimental Section
Compound 5: Compound
8 mmol), sodium ascorbate (44.6 mg, 0.2 mmol), CuI (76 mg,
0.4 mmol), and N,NЈ-dimethylethane-1,2-diamine (53 mg,
4 (1.1 g, 4 mmol), NaN3 (520 mg,
Materials and Characterization: All reagents were obtained from
commercial suppliers and used as received unless otherwise noted.
Column chromatography was performed on silica gel (160–
200 mesh), and thin-layer chromatography (TLC) was performed
on precoated silica gel plates with observation under UV light. Nu-
clear magnetic resonance (NMR) spectra were recorded with a
Bruker Avance DPS 400 spectrometer at room temperature
(298 K). Chemical shifts were referenced to the residual solvent
peaks. Matrix-assisted laser desorption/ionization reflectron time-
of-flight (MALDI-TOF) mass spectrometry was performed with a
Bruker Biflex III mass spectrometer. Electronic absorption spectra
were measured with a JASCO V-579 spectrophotometer. Fluores-
cence excitation and emission spectra were recorded with a Hitachi
F-4500 instrument. Compound 1 was synthesized by literature pro-
cedures.[18]
0.6 mmol) were added to degassed DMSO/H2O (5:1, 10 mL). The
reaction mixture was stirred at room temp. for 1 h. The crude reac-
tion mixture was taken up in a mixture of brine and EtOAc. The
aqueous phase was extracted with EtOAc. The combined organic
phases were concentrated in vacuo and the residue was purified by
flash chromatography over silica gel (CH2Cl2 in petroleum ether,
1
25%) to yield solid 5 (67.2%). H NMR (400 MHz, CDCl3): δ =
6.49 (s, 1 H), 6.45 (s, 1 H), 6.18 (s, 1 H), 1.27 ppm (s, 9 H). 13C
NMR (100 MHz, CDCl3): δ = 154.4, 147.5, 140.4, 109.3, 106.7,
102.8, 34.4, 31.2 ppm. MS (EI): m/z = 190. C10H14N4 (190.25):
calcd. C 63.13, H 7.42, N 29.45; found C 63.22, H 7.54, N 29.33.
Compound 6: CuSO4·5H2O (24.5 mg, 0.1 mmol) and sodium as-
corbate (40 mg, 0.2 mmol) were added to a solution of compound
5 (570 mg, 3 mmol) and methyl propiolate (252 mg, 3 mmol) in eth-
anol/H2O (2:1). The mixture was stirred at room temp. for 12 h.
Ethanol was removed in vacuo and CH2Cl2 was added. The organic
phase was washed with water and dried (MgSO4). The residue was
purified by silica gel chromatography (ethyl acetate in petroleum
ether, 25%) to afford 6 (89%) as a solid. 1H NMR (400 MHz,
CDCl3): δ = 8.47 (s, 1 H), 7.05 (s, 1 H), 6.93 (s, 1 H), 6.8 (s, 1 H),
1.33 ppm (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 161.1, 154.8,
147.6, 139.9, 137.1, 125.5, 113.1, 108.2, 104.7, 52.4, 34.7, 31.1 ppm.
MS (EI): m/z = 274. C14H18N4O2 (274.32): calcd. C 61.30, H 6.61,
N 20.42; found C 61.38, H 6.57, N 20.31.
Compound 2: Iodomonochloride (25 g, 154 mmol) was slowly
added at 70 °C under N2 to a solution of compound 1 (27.16 g,
140 mmol) in dichloroethane (150 mL). The mixture was stirred for
an additional 3 h and cooled to room temperature. The crude reac-
tion mixture was washed with saturated NaCl solution. The aque-
ous layer was extracted with CH2Cl2 and the combined organic
extracts were washed with brine and water, dried (MgSO4), and
concentrated under reduced pressure. The crude residue was sub-
jected to flash silica gel column chromatography (CH2Cl2/petro-
leum ether 1:2) to yield solid 2 (95%). 1H NMR (400 MHz,
CDCl3): δ = 8.14 (d, J = 2.2 Hz, 1 H), 7.96 (d, J = 2.2 Hz, 1 H),
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Compound 7: Propiolic acid (100 mg, 1.4 mmol) and DCC (290 mg,
1.4 mmol) were combined in CH2Cl2 (10 mL), the solution was
stirred for 10 min, and then compound 6 (384 mg, 1.4 mmol) and
DMAP (5 mg) were added. The reaction mixture was stirred for
30 min, and then the precipitate was filtered off and the solvent
was removed in vacuo. The residue was purified by silica gel
chromatography (CH2Cl2/methanol 50:1) to afford 7 (65%) as a
solid. 1H NMR (400 MHz, CDCl3): δ = 8.56 (s, 1 H), 8.01 (s, 1 H),
7.61 (s, 1 H), 7.53 (s, 1 H), 4.0 (s, 3 H), 2.98 (s, 1 H), 1.36 ppm (s,
9 H). 13C NMR (100 MHz, CDCl3): δ = 161.0, 154.7, 150.1, 140.4,
stirred at room temperature for 30 min, and then a solution of L1
(405 mg, 0.5 mmol) in toluene was added at room temperature and
the reaction mixture was heated to 100 °C for 2 h. The reaction
mixture was cooled to room temperature, quenched cautiously with
water (0.1 mL), and stirred at room temperature for 10 min. Evapo-
ration of the solvent gave a residue, and then the residue was puri-
fied by silica gel chromatography (CH2Cl2/ethyl acetate 10:1) to
afford L2 (45%) as a solid. 1H NMR (400 MHz, CD2Cl2): δ = 9.39
(s, 1 H, NH), 9.25 (s, 1 H, NH), 9.03 (s, 1 H, NH), 8.75 (s, 2 H,
CH), 8.70 (s, 1 H, CH), 8.47 (s, 1 H), 8.41 (s, 1 H), 8.38–8.15 (m,
138.5, 136.6, 125.9, 117.9, 114.6, 109.9, 74.8.6, 52.4, 35.3, 31.0, 9 H), 7.76 (s, 1 H), 7.74 (s, 1 H), 7.73 (s, 1 H), 7.67 (d, J = 6.9 Hz,
ppm. MS (EI): m/z = 326. C17H18N4O3 (326.35): calcd. C 62.57, H 2 H), 7.62 (s, 1 H), 7.40 (t, J = 7.7 Hz, 2 H), 7.17 (t, J = 7.4 Hz, 1
5.56, N 17.17; found C 62.51, H 5.63, N 17.31.
H),1.45 (s, 9 H, CH3), 1.43 ppm (s, 9 H, CH3). 13C NMR
(100 MHz, CD2Cl2): δ = 159.4, 159.2, 159.0, 156.0, 155.9, 145.2,
144.7, 144.5, 140.2, 140.1, 139.0, 138.2, 134.0, 132.4, 131.8, 131.4,
130.9, 130.6, 130.3, 128.2, 127.7, 126.2, 125.9, 125.7, 124.7, 121.8,
121.2, 119.2, 119.0, 115.3, 111.0, 109.3, 36.5, 32.2 ppm. MS
(MALDI-TOF): m/z = 895.3 [M + Na]. C51H44N12O3 (872.99):
calcd. C 70.17, H 5.08, N 19.25; found C 70.34, H 5.14, N 19.14.
Compound 8: CuSO4 (24.5 mg, 0.1 mmol) and sodium ascorbate
(40 mg, 0.2 mmol) were added to a solution of compound 7
(326 mg, 1 mmol) and compound 5 (190 mg, 1 mmol) in THF/H2O
(10:1, 15 mL). The mixture was stirred at room temp. for 12 h. THF
was removed in vacuo and CH2Cl2 was added. The organic phase
was washed with water and dried (MgSO4). The residue was puri-
fied by silica gel chromatography (CH2Cl2/ethyl acetate 5:1) to af-
Compound L3: Trimethylaluminum (2 m solution in toluene,
0.25 mL, 0.5 mmol) was added dropwise to a solution of p-iodoani-
line (110 mg, 0.5 mmol) in dry toluene (30 mL). The solution was
stirred at room temperature for 30 min, and then a solution of L1
(405 mg, 0.5 mmol) in toluene was added at room temperature and
the reaction was heated to 100 °C for 2 h. The reaction was cooled
to room temperature, quenched cautiously with water (0.1 mL),
and stirred at room temperature for 10 min. Evaporation of the
solvent gave a residue, and then the residue was purified by silica
gel chromatography (CH2Cl2/ethyl acetate, 10:1) to afford L3
1
ford 8 (67%) as a solid. H NMR (400 MHz, CDCl3): δ = 9.17 (s,
1 H), 8.6 (s, 1 H), 8.55 (s, 1 H), 8.28 (s, 1 H), 7.65 (s, 1 H), 7.60 (s,
1 H), 7.09 (s, 1 H), 6.92 (s, 1 H), 6.82 (s, 1 H), 4.01 (s, 3 H), 1.41
(s, 9 H), 1.34 ppm (s, 9 H). 13C NMR (100 MHz, CDCl3): δ =
161.1, 158.1, 154.8, 154.7, 143.2, 140.4, 138.6, 137.1, 136.8, 126.0,
124.3, 117.7, 114.3, 113.4, 109.6, 108.1, 104.5, 52.4, 35.3, 31.1 ppm.
MS (MALDI-TOF): m/z = 539.1 [M + Na]. C27H32N8O3 (516.60):
calcd. C 62.77, H 6.24, N 21.69; found C 62.59, H 6.17, N 21.72.
Compound 9: Propiolic acid (100 mg, 1.4 mmol) and DCC (290 mg,
1.4 mmol) were combined in CH2Cl2 (10 mL), the solution was
stirred for 10 min, and then compound 6 (384 mg, 1.4 mmol) and
DMAP (5 mg) were added. The reaction mixture was stirred for
30 min, and then the precipitate was filtered off and the solvent
was removed in vacuo. The residue was purified by silica gel
chromatography (CH2Cl2/ethyl acetate 5:1) to afford 9 (55%) as a
solid. 1H NMR (400 MHz, CDCl3): δ = 9.17 (s, 1 H), 8.62 (s, 1 H),
8.60 (s, 1 H), 8.28 (s, 1 H), 8.05 (s, 1 H), 7.86 (s, 1 H), 7.65 (s, 1
H), 7.61 (d, J = 5.9 Hz, 2 H), 7.52 (s, 1 H), 4.01 (s, 3 H), 2.99 (s,
1 H), 1.41 (s, 9 H), 1.38 ppm (s, 9 H). 13C NMR (100 MHz,
CDCl3): δ = 161.0, 157.3, 154.8, 140.4, 138.6, 136.8, 126.0, 124.5,
117.9, 117.8, 114.7,114.4, 110.0, 109.6, 74.8, 52.4, 35.3, 31.1 ppm.
MS (MALDI-TOF): m/z = 591.2 [M + Na]. C30H32N8O4 (568.63):
calcd. C 63.37, H 5.67, N 19.71; found C 63.24, H 5.62, N 19.77.
1
(43%) as a solid. H NMR (400 MHz, [D6]DMSO): δ = 11.00 (s,
1 H, NH), 10.88 (s, 1 H, NH), 10.70 (s, 1 H, NH), 9.55 (s, 1 H,
CH), 9.53 (s, 1 H, CH), 9.45 (s, 1 H, CH), 8.61 (s, 1 H), 8.57 (s, 1
H), 8.52 (d, J = 8.2 Hz, 1 H), 8.46–8.31 (m, 6 H), 8.18 (t, J =
8.2 Hz, 1 H), 8.10 (s, 1 H), 8.04 (s, 1 H), 7.79 (d, J = 9.3 Hz, 1 H),
7.74–7.67 (m, 6 H), 1.38 (s, 9 H, CH3), 1.36 ppm (s, 9 H, CH3).
13C NMR (100 MHz, [D6]DMSO): δ = 159.3, 159.2, 158.9, 154.2,
154.1, 144.1, 143.7, 140.4, 140.3, 139.1, 138.0, 137.0, 132.8, 130.8,
130.6, 130.4, 129.8, 129.6, 128.9, 127.9, 127.8, 127.5, 127.0, 126.7,
125.8, 124.9, 124.7, 123.9, 123.4, 121.5, 118.8, 114.0, 110.6, 88.4,
35.8, 31.6 ppm. MS (MALDI-TOF): m/z = 1021.3 [M + Na].
C51H43IN12O3 (998.88): calcd. C 61.32, H 4.34, N 16.83; found C
61.48, H 4.26, N 16.71.
Supporting Information (see footnote on the first page of this arti-
cle): Synthesis information for all key intermediates and final prod-
uct, UV/Vis spectra and fluorescence spectra of compound L2 with
sulfate anions, the 1H NMR and 13C NMR spectra for key interme-
Compound L1: CuI (38 mg, 0.2 mmol) and DBU (0.7 mL,
4.0 mmol) were added to a solution of compound 9 (568 mg,
1 mmol) and 1-azopyrene (243 mg, 1 mmol) in toluene (50 mL).
The mixture was stirred at room temp. for 5 h, and then the solvent
was removed in vacuo and the residue was purified by silica gel
chromatography (CH2Cl2/ethyl acetate 10:1) to afford L1 (56%) as
1
diates, H NMR spectra of L2 with various anions.
Acknowledgments
1
a solid. H NMR (400 MHz, CDCl3): δ = 9.38 (s, 1 H, NH), 9.20
(s, 1 H, NH), 8.71 (s, 1 H, CH), 8.67 (s, 1 H, CH), 8.60 (s, 1 H,
CH), 8.35 (s, 1 H), 8.32–8.08 (m, 9 H), 7.81 (d, J = 9.1 Hz, 1 H),
7.73 (s, 1 H), 7.66 (s, 2 H), 7.62 (s, 1 H), 4.00 (s, 3 H, OCH3), 1.44
(s, 9 H, CH3), 1.40 ppm (s, 9 H, CH3). 13C NMR (100 MHz,
CDCl3): δ = 171.2, 161.1, 158.2, 157.9, 154.7, 138.6, 130.2, 129.4,
129.2, 126.8, 126.3, 125.9, 124.7, 124.5, 123.2, 117.7, 109.8, 109.5,
52.3, 35.3, 31.16 ppm. MS (MALDI-TOF): m/z = 834.1 [M + Na],
850.2 [M + K]. C30H32N8O4 (568.63): calcd. C 63.37, H 5.67, N
19.71; found C 63.50, H 5.69, N 19.65.
This study was supported by the National Basic Research 973 Pro-
gram of China (grant number 2011CB932302) and the National
Nature Science Foundation of China (NSFC) (grant numbers
201031006, 20971127).
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Received: December 10, 2013
Published Online: February 2, 2014
Eur. J. Org. Chem. 2014, 2687–2693
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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