Design and synthesis of novel diphenic acid-based molecular tweezers

Article abstract of DOI:10.3184/030823410X12664920874109

The design and synthesis of a new type of molecular tweezers is reported which have a 2,2′-diphenic acid backbone and two side chains that are attached to the backbone. This type of molecular tweezers has been to incorporate multiple hydrogen bonding groups into cleft to provide both orientation and selective complexation of substrate.

Full text of DOI:10.3184/030823410X12664920874109

106 RESEARCH PAPER
FEBRUARY, 106–108
JOURNAL OF CHEMICAL RESEARCH 2010
Design and synthesis of novel diphenic acid-based molecular tweezers
WeiJie Li, XiaoQing Wang, ZhiGang Zhao* and Tao Han
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, P. R. China
The design and synthesis of a new type of molecular tweezers is reported which have a 2,2’-diphenic acid backbone
and two side chains that are attached to the backbone. This type of molecular tweezers has been to incorporate mul-
tiple hydrogen bonding groups into cleft to provide both orientation and selective complexation of substrate.
Keywords: Molecular tweezers, multiple hydrogen-bonding, anion recognition
Anions play a pivotal role in bioorganic chemistry, clinical
diagnosis and in monitoring the environment. Consequently,
the recognition of anions is currently attracting great interest in
supramolecular chemistry.1–7 So far, the basic strategies that
have been exploited for the construction of anion-binding
receptors are electrostatic interaction, hydrogen bonding,
hydrophobicity, coordination to a metal ion, or a combination
of these interactions.8,9 Among these non-covalent interactions,
we have been interested in developing hydrogen bond-based
anion receptors. Although the energy of a single hydrogen-
bond is weak, the coordination of multiple hydrogen-bonding
will result in high selectivity or combining with the substrates.
A number of artificial receptors involving hydrogen bonding
have been reported in recent years,10–12 but arylhydrazide-type
molecular tweezers receptors have seldom been reported. In
view of these facts and as part of our work on the synthesis and
recognition study on molecular tweezers receptors, we report
here our results related to the preparation of arylhydrazide-
type molecular tweezers receptors based on diphenic acid. To
our knowledge, this has not been attempted up to now. Diphenic
acid-based molecular tweezers 6a–j, which contain four NH
bonds, were synthesised according to Scheme 1.
Scheme 1
* Correspondent. E-mail: zzg63129@yahoo.com.cn

JOURNAL OF CHEMICAL RESEARCH 2010 107
Result and discussion
than the other two solvents, we concluded that CH2Cl2 is the
best solvent to use in this reaction.
This provided a good methodology for the preparation of
arylhydrazide-type molecular anion receptors in ice water. It
possesses the advantages of a good yield, easy manipulation
and easy purification of the products.
A series of experiments were carried out to optimise the
reaction conditions. When we started our work, we used a
conventional reflux in CH Cl for 4 hours to produce 6a.
However, it gave a low yield2of243%. We then tried microwave
irradiation but the yield was also unsatisfactory at 40%.
We considered that the low yield and byproducts may be
caused by the vigorous conditions, so the reaction was carried
out in ice water and a satisfactory result was obtained as shown
in Table 1.
CH2Cl2, CHCl3 and THF were compared to evaluate the
solvent effect on the reaction. Different solvents were employed
under the similar reaction conditions, but the results did not
differ much as shown in Table 2. Considering that CH2Cl2 is
less toxic than CHCl3 and THF and is more easily removed
The recognition of molecular tweezers 6a, 6b for halogen
anions has been investigated by UV-vis spectra titration in
CHCl3 at 25 °C. Using the nonlinear least squares curve-fitting
method, we obtained the association constants for the com-
plex. The preliminary results showed that these molecular
tweezers possessed the ability to form a complex with guest
anions examined. The supramolecular complexes consisted
of 1:1 host and guest molecules. The association constants
of molecular tweezer 6a, for example, is 124.65, 326.31,
5771.27 mol L−1 for Cl−, Br−, I− anions respectively. The main
driving force is the multiple hydrogen bonds in molecular
recognition. The UV-vis plot of 6a for I− is shown in Fig. 1.
The main reason is that when the host 6a at the minimum
energy, its conformation is a cleft, which has the ability to
form complex with guest molecules. The minimum energy
conformation of 6a is shown in Fig.2. The details of molecular
recognition of 6a–j are being further studied.
Table 1 The effect of reaction conditions on the yield of
compounds 6a–c
Entry Reaction
Condition
Yield of 6a
Yield of 6b
Yield of 6c
/%
/%
/%
1
2
3
Conventional
43
40
75
40
38
85
51
35
81
heating
Microwave
irradiation
Ice water
Experimental
Melting points were determined on a micro-melting point apparatus
and the thermometer was uncorrected. IR spectra were obtained on
1700 Perkin-Elmer FTIR using KBr disks. 1H NMR spectra were
recorded on a Varian INOVA 400 MHz spectrometer using DMSO-d6
as solvent and TMS as internal standard. Mass spectra were deter-
mined on Finnigan LCQDECA instrument. Elemental analysis was per-
formed on a Carlo-Erba-1106 autoanalyser. Microwave irradiation
was carried out with a MCL-3 microwave oven at full power (700 W).
This was a modified domestic microwave oven and tested to conform
to the performance index before use. All solvents were purified before
use.
Table 2 The effect of solvent on the yield of compounds 6a–c
Entry Solvent
Yield of 6a
Yield of 6b
Yield of 6c
/%
/%
/%
1
2
3
THF
CH2Cl2
CHCl3
80
75
73
72
85
81
75
81
71
Fig. 1 UV-vis spectra of molecular tweezers 6a (1.6 × 10−5 mol L−1) in the presence of I−: (a) 0 mol L−1; (b) 0.24 × 10−3 mol L−1; (c)
0.48 × 10−3 mol L−1; (d) 0.48 × 10−3 mol L−1; (e) 0.72 × 10-3 mol L−1; (f) 0.96 × 10−3 mol L−1; (g) 1.20 × 10−3 mol L−1; (h) 1.44 × 10−3 mol L−1; (i)
1.68 × 10−3 mol L−1; (j) 1.92 × 10−3 mol L−1; (k) 2.16 × 10−3 mol L−1 with λmax at 256.9 nm.

108 JOURNAL OF CHEMICAL RESEARCH 2010
Calcd for C36H26N4O4: C 74.73, H 4.53, N 9.68. Found: C 74.78,
H 4.56, N 9.70%.
6d: White solid, yield 76%, m.p. 242–244 °C; 1H NMR (DMSO-d6,
400 MHz, δ ppm): 10.39 (s, 2H, PhCONH), 10.34 (s, 2H, PhCONH),
6.98–7.84 (m, 16H, ArH), 3.81 (s, 6H,CH3); IR (KBr, cm−1): 3230,
3019, 1641, 1620, 1494, 1178, 852, 760; ESI–MS m/z (%): 539.33
[(M+1)+, 100]. Anal. Calcd for C30H N4O6: C 66.91, H 4.87, N 10.40.
Found: C 66.82, H 4.89, N 10.34%.26
6e: White solid, yield 80%, m.p. 264–266 °C; 1H NMR (DMSO-d6,
400 MHz, δ ppm): 10.40 (s, 4H, PhCONH), 7.23–7.76 (m, 16H, ArH),
2.34 (s, 6H,CH3); IR (KBr, cm−1): 3237, 3021, 1679, 1630, 1565,
1518, 1494, 1185, 770; ESI–MS m/z (%): 505.33 [(M-1)−, 100]. Anal.
Calcd for C30H26N O4: C 71.13, H 5.17, N 11.06. Found: C 71.25,
H 5.19, N 11.08%.4
6f: White solid, yield 77%, m.p. 253–255 °C; 1H NMR (DMSO-d6,
400 MHz, δ ppm): 10.41 (s, 4H, PhCONH), 7.23–7.66 (m, 16H, ArH),
2.33 (s, 6H,CH3); IR (KBr, cm−1): 3256, 1690, 1641, 1586, 1519,
1333, 1292, 943, 773; ESI–MS m/z (%): 505.40 [(M-1)−, 100]. Anal.
Calcd for C30H26N O4: C 71.13, H 5.17, N 11.06. Found: C 71.26,
H 5.20, N 10.99%.4
6g: Pale yellow solid, yield 63%, m.p. 277–279 °C; 1H NMR
(DMSO-d6, 400 MHz, δ ppm): 10.57 (s, 2H, PhCONH), 10.43 (s, 2H,
PhCONH), 7.23–7.87 (m, 16H, ArH); IR (KBr, cm−1): 3235, 3021,
1629, 1499, 1290, 1176, 854, 759; ESI–MS m/z (%): 545.60 [(M-1)−,
100]. Anal. Calcd for C28H Cl2N4O4: C 61.44, H 3.68, N 10.24,
Cl 12.95. Found: C 61.33, H 230.70, N 10.29%.
Fig. 2 Minimum energy conformation of molecular tweezer
6a.
General procedure for preparation of 3a–j
The aromatic acid (5 mmol), ethanol (15 mL) and thionyl chloride
(0.2 mL) were placed in a dried round-bottomed flask and the mixture
was irradiated by microwave (75 W) for 4 min. On completion of the
reaction, the mixture was cooled to room temperature. The excess
thionyl chloride was removed. Then the reaction mixture was added to
85% hydrazine hydrate (2 mL) and subjected to microwave irradiation
(75 W) for 3 min. The mixture was evaporated to give the crude
product. The crude product was recrystallised from ethanol to give a
pure sample.
6h: Pale yellow solid, yield 68%, m.p. 269–271 °C; 1H NMR
(DMSO-d6, 400 MHz, δ ppm): 10.57 (s, 2H, PhCONH), 10.43 (s, 2H,
PhCONH), 7.23–7.79 (m, 16H, ArH); IR (KBr, cm−1): 3231, 3021,
1624, 1592, 1565, 1503, 1481, 1299, 843, 748; ESI–MS m/z (%):
635.36 [(M+1)+, 100]. Anal. Calcd for C H20Br2N4O4: C 52.85,
H 3.17, N 8.81, Br 25.12. Found: C 52.78, H238.20, N 8.84%.
6i: Pale yellow solid, yield 65%, m.p. 292–294 °C; 1H NMR
(DMSO-d6, 400 MHz, δ ppm): 10.85 (s, 2H, PhCONH), 10.53 (s, 2H,
PhCONH), 7.25–8.33 (m, 16H, ArH); IR (KBr, cm−1): 3203, 2992,
1687, 1644, 1602, 1527, 1348, 1109, 847, 769; ESI–MS m/z (%):
567.31 [(M-1)−, 100]. Anal. Calcd for C H N6O8: C 59.16, H 3.55,
N 14.78. Found: C 59.27, H 3.53, N 14.8258%2.0
General procedure for preparation of 6a–j
Compound 3 (3 mmol), dichloromethane (10 mL) and pyridine
(0.2 mL) were placed in a dried round-bottomed flask and the mixture
was put in a beaker which was filled with ice water. The solution of 5
(1 mmol) in dichloromethane(5 mL) was added slowly to the mixture
and a solid was obtained. After addition was completed, the reaction
for 2 hours. The solid was collected by suction filtration and washed
with cold ethanol. The crude product was recrystallised from ethanol
to give a pure sample. The progress of the reaction was monitored
by TLC. The physical and spectra data of the compounds 6a–j are as
follows.
6j: Pale yellow solid, yield 67%, m.p. 234–236 °C; 1H NMR
(DMSO-d6, 400 MHz, δ ppm): 10.91 (s, 2H, PhCONH), 10.55 (s, 2H,
PhCONH), 7.25–8.67 (m, 16H, ArH); IR (KBr, cm−1): 3250, 3090,
1629, 1526, 1351, 1076, 769; ESI–MS m/z (%): 567.47 [(M-1)−, 100].
Anal. Calcd for C28H20N6O8: C 59.16, H 3.55, N 14.78. Found:
C 59.19, H 3.58, N 14.73%.
We thank the Natural Science Foundation of the State Ethnic
Affairs Commission of P. R. China (Project No.09XN08) for
the financial support.
6a: White solid, yield 75%, m.p. 261–263 °C; 1H NMR (DMSO-d6,
400 MHz, δ ppm): 10.48 (s, 2H, PhCONH), 10.41 (s, 2H, PhCONH),
7.24–7.85 (m, 18H, ArH); IR (KBr, cm−1): 3236, 3049, 1693, 1636,
1602, 1579, 1519, 1125, 914, 773; ESI–MS m/z (%): 477.40 [(M-1)−,
100]. Anal. Calcd for C28H N4O4: C 70.28, H 4.63, N 11.71. Found: C
70.21, H 4.56, N 11.76%. 22
Received 9 November 2009; accepted 4 January 2010
Paper 090868 doi: 10.3184/030823410X12664920874109
Published online: 1 March 2010
6b: White solid, yield 85%, m.p. 254–256 °C; 1H NMR (DMSO-d6,
400 MHz, δ ppm): 10.55 (s, 2H, PhCONH), 10.45 (s, 2H, PhCONH),
7.26–7.96 (m, 26H, ArH); IR (KBr, cm−1): 3237, 3026, 1678, 1626,
1562, 1484, 1466, 1192, 856, 746, ESI–MS m/z (%): 629.41 [(M-1)−,
100]. Anal. Calcd for C40H30N4O4: C 76.17, H 4.79, N 8.88. Found:
C 76.08, H 4.82, N 8.83%.
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6c: White solid, yield 81%, m.p. 258–260 °C; 1H NMR (DMSO-d6,
400 MHz, δ ppm): 10.46 (s, 2H, PhCONH), 10.45 (s, 2H, PhCONH),
7.33–8.30 (m, 22H, ArH); IR (KBr, cm−1): 3245, 3020, 1673, 1621,
1496, 1135, 870, 771; ESI–MS m/z (%): 577.67 [(M-1)−, 100]. Anal.
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Table 3 The physical data of hydrazides prepared
Entry
Product
Yield/%
M.p. /°C
Lit M.p. /°C
1
2
3a
3b
3c
3d
3e
3f
86
77
83
81
79
82
83
82
77
79
112–114
221–223
161–163
134–136
116–118
96–98
116–118
249–251
210–212
150–153
112.513
225–22713
160–162.513
137–13913
11513
3
4
5
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6
101–10313
118–12013
251–25313
21013
7
3g
3h
3i
8
9
10
3j
153–15413

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