Design and synthesis of novel molecular tweezer anion receptors based on diphenic acid carbonyl thiosemicarbazide

Article abstract of DOI:10.3184/030823410X12790364267642

Ten novel molecular tweezer anion receptors based on diphenic acid carbonyl thiosemicarbazide have been designed and synthesised in high yield and their binding properties were examined by UV-Vis spectra titration. Their structures were characterised by ¹H NMR, IR, MS spectra and elemental analysis.

Full text of DOI:10.3184/030823410X12790364267642

410 RESEARCH PAPER
JULY, 410–413
JOURNAL OF CHEMICAL RESEARCH 2010
Design and synthesis of novel molecular tweezer anion receptors based
on diphenic acid carbonyl thiosemicarbazide
Xiaorui Li, Zhigang Zhao*, Guohua Li and Peiyu Shi
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, P. R. China
Ten novel molecular tweezer anion receptors based on diphenic acid carbonyl thiosemicarbazide have been designed
and synthesised in high yield and their binding properties were examined by UV-Vis spectra titration. Their struc-
tures were characterised by 1H NMR, IR, MS spectra and elemental analysis.
Keywords: molecular tweezer, thiosemicarbazide, molecular recognition
Molecular recognition is one of the most fundamental
processes in many chemical and biochemical systems. Anions
play an important role in biology, pharmacy, catalysis and
environmental science.1 The study of artificial receptors for
the detection of biologically relevant anions is an important
challenge in modern bioorganic chemistry.2–6 Among the
various types of artificial receptors which have been synthe-
sised, molecular tweezers containing two arms connected by a
spacer are an increasingly interesting class of receptors.7–11
The natural occurring cavities of these molecular tweezers
receptors can provide appropriate microenvironment for
substrates.12,13 Hydrogen-bonding is one of the major driving
forces for molecular recognition. Although the energy of a
single hydrogen-bond is weak, the coordination of multiple
hydrogen-bonding will result in high selectivity in combining
with substrates. We have reported that arylhydrazide molecu-
lar tweezer receptors which contain four NH bond have good
recognition properties for anions.14 On the basis of this fact,
we designed and synthesised 10 novel carbonyl thiosemicar-
bazide type molecular tweezer artificial receptors 7a–j, which
contain six NH bonds. These receptors based on carbonyl
thiosemicarbazide as arms, have the NH groups directed
towards the centre of the cavity resulting in a high selectivity
in combining with the substrates. The recognition properties of
the receptors have been examined by UV-Vis spectra titration.
The preliminary results indicate that this kind of molecular
tweezer shows good recognition properties for NO3− and
H2PO4−. The synthesis shown in Scheme 1.
The variations in the UV-Vis absorption of these complex-
ing system has been used as an effective and simple method
to measure for the association constants of complexes in
supramolecular systems.
Titration experiments for the anion recognition of receptors
7a, 7b were performed using UV-Vis spectroscopy in CHCl3 at
25 °C. Using the linear fitting method, we obtained the asso-
ciation constants of the complex. The preliminary results
showed that these molecular tweezers possessed the ability to
form complexes with the guest anions which were examined
as shown Fig. 1. The supramolecular complexes consisted of
1:1 host and guest molecules. The association constants of
the molecular tweezer 7a, for example, is 638, 5345, 12124 L
mol−1 for CH3COO−, H2PO4−, NO3− anions respectively. The
main driving forces are the multiple hydrogen bonds in mole-
cular recognition. The UV-Vis plot of 7a for NO3− is shown in
Fig. 2.
The main reason is that when the host 7a is at minimum
energy, its conformation is a cleft, which has the ability to
form complex with guest molecules. The minimum energy
conformation of 7a has been investigated by computer-aided
molecular modelling using a Chem 3D program. This is shown
in Fig. 3 and the minimum energy conformation for the inclu-
sion complex of molecular tweezer 7a with NO3− as shown in
Fig. 4. The details of molecular recognition of compounds
7a–j are under further studies.
Experimental
Melting points were determined on a micro-melting point apparatus
and were uncorrected. IR spectra were obtained on 1700 Perkin-Elmer
1
Results and discussion
FTIR using KBr disks. H NMR spectra were recorded on a Varian
INOVA 400 MHz spectrometer using TMS as internal standard. Mass
spectra were determined on FinniganLCQDECA instrument. Elemental
analysis was performed on a Carlo-Erba-1106 autoanalyzer. Micro-
wave irradiation was carried out with a MCL-3 microwave oven which
was modified from domestic microwave oven and tested at full power
(700 W) to conform to the performance index before use. All the
solvents were purified before use.
In searching for the best reaction conditions of the synthesis of
molecular tweezer artificial receptors, we examined the
preparation of 7a–c. A series of experiments were carried out
to investigate the effect of temperature and solvent on synthesis.
The results are shown in the following tables.
As shown in Table 1, different temperatures were employed
under the similar reaction conditions. Although the results
were different: 40 °C was the best temperature to obtain a good
yield.
As shown in Table 2, the effect of CH2Cl2, CHCl3 and
CH3COCH3 on the reaction was investigated. This showed
that although different solvents were employed under similar
reaction conditions, the results did not differ much. When
CH2Cl2 was used, the yield was a little higher and hence CH2Cl2
was the best solvent for the reaction.
This provided an easy and effective method for the pre-
paration of carbonyl thiosemicarbazide type molecular
anion receptors. This method possesses the advantages of a
high yield, easy manipulation and easy purification of the
products.
Preparation of 3a–j; general procedure
The aromatic acid (5 mmol), thionyl chloride (0.2 mL) and ethanol
(15 mL) were placed in a dried round-bottomed flask and the mixture
was irradiated by microwaves (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. The melting points of the hydrazides 3a–j are shown in
Table 3.
Preparation of 7a–j; general procedure
NH4SCN (0.2300 g, 3 mmol), PEG-400 (0.0360 g, 3% with respect
to ammonium thiocyanate) and dichloromethane (10 mL) were added
in a dried round-bottomed flask and strirred at 40 °C. A solution of
compound 5 (1 mmol) in dichloromethane (5 mL) slowly added to the
mixture. After the addition was finished, the reaction was continued
* Correspondent. E-mail: zzg63129@yahoo.com.cn

JOURNAL OF CHEMICAL RESEARCH 2010 411
Scheme 1 The synthetic route of molecular tweezers 7a–j.
Table 1 The effect of reaction temperature on the yield of
compounds 7a–c
Table 2 The effect of solvent on the yield of compounds 7a–c
Entry
Solvent
Yield of
7a /%
Yield of
7b /%
Yield of
7c /%
Entry
temperature
Yield of
7a /%
Yield of
7b /%
Yield of
7c /%
1
2
3
CH3COCH3
CH2Cl2
CHCl3
73
81
75
81
86
72
71
80
75
1
2
3
0 °C
20 °C
40 °C
30
52
78
28
47
85
33
53
83
for 1 h, and then, compound 3 (3 mmol) was added dropwise. The
reaction mixture was stirred at room temperature for 0.5 h, and the
whole process was monitored by TLC. The mixture was evaporated
to give the crude product. The crude product was washed with cold
ethanol and recrystallised from ethanol to give a pure sample. The
physical and spectra data of the compounds 7a–j are as follows.
7a: White crystal; yield 81%, m.p. 215–216 °C; IR (KBr, cm−1):
3248, 3086, 2919, 1672, 1523, 1433, 1244, 1171, 1064, 778, 710; 1H
NMR (DMSO-d6, 400 MHz) δ: 11.82 (s, 2H, SCNHCO), 11.51 (s, 2H,
NH), 11.03 (s, 2H, NHCO), 7.87 (d, J = 7.2 Hz, 4H, ArH), 7.79 (d,
J = 7.2 Hz, 2H, ArH), 7.64–7.48 (m, 10H, ArH), 7.27 (d, J = 6.8 Hz,
2H, ArH); ESI-MS m/z (%): 597.10 ( [M+1]+, 100). Anal. Calcd for

412 JOURNAL OF CHEMICAL RESEARCH 2010
Fig. 1 Typical plot of 1/∆A versus 1/[G]0 for the inclusion
complex of molecular tweezer 7a with NO3– in CHCl3 at 25 °C.
C30H24N6O4S2: C, 60.39; H, 4.05; N, 14.08. Found: C, 60.21; H, 4.06;
N, 14.06%.
7b: Pale yellow crystal; yield 86%, m.p. 158–160 °C; IR (KBr,
cm−1): 3234, 3059, 2982, 1676, 1519, 1436, 1277, 1094, 750; 1H NMR
(DMSO-d6, 400 MHz) δ: 11.81 (s, 2H, SCNHCO), 11.51 (s, 2H, NH),
11.14 (s, 2H, NHCO), 7.88 (d, J = 8.4 Hz, 4H, ArH), 7.79 (d,
J = 7.6 Hz, 2H, ArH), 7.64–7.58 (m, 8H, ArH), 7.27 (d, J = 7.6 Hz,
2H, ArH); ESI-MS m/z (%): 1352.73 ( [2M+Na]+, 100). Anal. Calcd
for C30H22Cl2N6O4S2: C, 54.14; H, 3.33; N, 12.63. Found: C, 54.09;
H, 3.32; N, 12.66%.
Fig. 3 Minimum energy conformation of molecular tweezer
7a.
Fig. 2 UV-Vis spectra of molecular tweezers 7a (3×10–4 mol L–1) in the presence of NO3–. (a) 0 mol L–1; (b) 0.024×10–3 mol L–1; (c)
0.024×10–3 mol L–1; (d) 0.048×10–3 mol L–1; (e) 0.048×10–3 mol L–1; (f) 0.072×10–3 mol L–1; (g) 0.072×10–3 mol L–1 with λmax at 262.6 nm.

JOURNAL OF CHEMICAL RESEARCH 2010 413
7f: Pale crystal; yield 72%, m.p. 230–231 °C; IR (KBr, cm−1): 3258,
3054,2975, 1672, 1507, 1469, 1249, 1169, 1082, 777; 1H NMR
(DMSO-d6, 400 MHz) δ: 11.86 (s, 2H, SCNHCO), 11.57 (s, 2H, NH),
11.07 (s, 2H, NHCO), 8.39 (dd, J = 3.8 Hz, 6.2 Hz, 2H, ArH), 8.08 (d,
J = 8.4 Hz, 2H, ArH), 8.01 (dd, J = 3.2 Hz, 6.4 Hz, 2H, ArH), 7.83–
7.77 (m, 4H, ArH), 7.68–7.65 (m, 2H, ArH), 7.61–7.56 (m, 8H, ArH),
7.31 (d, J = 7.2 Hz, 2H, ArH); ESI-MS m/z (%): 1431.46 ( [2M+K]+,
100). Anal. Calcd for C38H28N6O4S2: C, 65.50; H, 4.05; N, 12.06.
Found: C, 65.39; H, 4.06; N, 12.03%.
7g: Pale crystal; yield 85%, m.p. 204–207 °C; IR (KBr, cm−1):
3245, 3067, 2971, 1671, 1522, 1434, 1255, 1173, 1025, 757; 1H NMR
(DMSO-d6, 400 MHz) δ: 11.84 (s, 2H, SCNHCO), 11.49 (s, 2H, NH),
10.89 (s, 2H, NHCO), 7.85 (d, J = 8.8 Hz, 4H, ArH), 7.78 (d,
J = 7.2 Hz, 2H, ArH), 7.65–7.56 (m, 4H, ArH), 7.27 (d, J = 7.6 Hz,
2H, ArH), 7.04 (d, J = 8.8 Hz, 4H, ArH), 3.82 (s, 6H, OCH3); ESI-MS
m/z (%): 1334.96 ( [2M+Na]+, 100). Anal. Calcd for C32H28N6O6S2: C,
58.52; H, 4.30; N, 12.80. Found: C, 58.47; H, 4.31; N, 12.77%.
7h: White crystal; yield 80%, m.p. 226–228 °C; IR (KBr, cm−1):
3239, 3045, 2983, 1672, 1532, 1438, 1245, 1182, 1064, 746; 1H NMR
(DMSO-d6, 400 MHz) δ: 11.83 (s, 2H, SCNHCO), 11.50 (s, 2H, NH),
10.96 (s, 2H, NHCO), 7.77 (d, J = 7.2 Hz, 6H, ArH), 7.64–7.57 (m,
4H, ArH), 7.31–7.27 (m, 6H, ArH), 2.36 (s, 6H, CH3); ESI-MS m/z
(%): 1271.27 ( [2M+Na]+, 100). Anal. Calcd for C32H28N6O4S2: C,
61.52; H, 4.52; N, 13.45. Found: C, 61.42; H, 4.51; N, 13.43%.
7i: White crystal; yield 78%, m.p. 207–208 °C; IR (KBr, cm−1):
3246, 3067, 2981, 1671, 1525, 1441, 1240, 1161, 1065, 756; 1H NMR
(DMSO-d6, 400 MHz) δ: 11.80 (s, 2H, SCNHCO), 11.50 (s, 2H, NH),
11.07 (s, 2H, NHCO), 7.95–7.91 (m, 4H, ArH), 7.79 (d, J = 7.2 Hz,
2H, ArH), 7.66–7.56 (m, 4H, ArH), 7.37 (t, J = 9.0 Hz, 4H, ArH), 7.27
(d, J = 6.8 Hz, 2H, ArH); ESI-MS m/z (%): 1303.19 ( [2M+K]+, 100).
Anal. Calcd for C30H22F2N6O4S2: C, 56.95; H, 3.50; N, 13.28. Found:
C, 57.04; H, 3.51; N, 13.24%.
7j: Pale yellow crystal; yield 83%, m.p. 252–256 °C; IR (KBr,
cm−1): 3159, 3017, 2934, 1655, 1528, 1446, 1246, 1182, 1044, 754,
652; H NMR (DMSO-d6, 400 MHz) δ: 13.08 (d, J = 7.2 Hz, 2H,
1
Fig. 4 Minimum energy conformation for the complex of
molecular tweezer 7a with NO3–.
SCNHCO), 11.81 (s, 2H, NH), 11.59 (d, J = 6.8 Hz, 2H, NHCO),
7.99 (dd, J = 1.6 Hz, 8.0 Hz, 2H, ArH), 7.77 (d, J = 7.2 Hz, 2H, ArH),
7.66–7.54 (m, 6H, ArH), 7.30 (t, J = 8 Hz, 4H, ArH), 7.17 (t,
J = 7.6 Hz, 2H, ArH), 4.03 (s, 6H, OCH3); ESI-MS m/z (%): 657.15
([M+1]+, 100). Anal. Calcd for C32H28N6O6S2: C, 58.52; H, 4.30;
N, 12.80. Found: C, 58.55; H, 4.29; N, 12.83%.
Table 3 The melting points of hydrazides 3a–j
Entry
Compound
Yield/%
M.p. / °C
Lit. m.p. / °C
1
2
3a
3b
3c
3d
3e
3f
85
78
85
88
80
83
82
78
80
83
112–114
117–118
63–65
98–100
249–251
160–163
135–137
116–118
160–163
78–80
112.515
118–12015
62–6415
3
We thank the Natural Science Foundation of the State Ethnic
Affairs Commission of P.R.China (Project No.09XN08) for
the financial support.
4
101–10315
251–25315
160–162.515
137–13915
11515
5
6
7
3g
3h
3i
8
Received 18 May 2010; accepted 7 June 2010
Paper 1000139 doi: 10.3184/030823410X12790364267642
Published online: 28 July 2010
9
162–16615
78–8015
10
3j
7c: Yellow crystal; yield 80%, m.p. 210–213 °C; IR (KBr, cm−1):
3162, 3067, 2983, 1672, 1527, 1462, 1243, 1179, 1038, 750; 1H NMR
(DMSO-d6, 400 MHz) δ: 13.24 (d, J = 8.4 Hz, 2H, SCNHCO), 11.80
(s, 2H, NH), 11.44 (d, J = 8.0 Hz, 2H, NHCO), 8.02 (dd, J = 1.8 Hz,
7.8 Hz, 2H, ArH), 7.78 (d, J = 6.8 Hz, 2H, ArH), 7.66–7.54 (m, 6H,
ArH), 7.29 (t, J = 6.6 Hz, 4H, ArH), 7.15 (t, J = 7.4 Hz, 2H, ArH),
4.33 (q, J = 7.0 Hz, 4H, OCH2), 1.54 (t, J = 7.0 Hz, 6H, CH3); ESI-
MS m/z (%): 685.32 ( [M+1]+, 100). Anal. Calcd for C34H32N6O6S2:
C, 59.63; H, 4.71; N, 12.27. Found: C, 59.70; H, 4.59; N, 12.25%.
7d: White crystal; yield 80%, m.p. 183–185 °C; IR (KBr, cm−1):
3261, 3054, 2922, 1670, 1524, 1438, 1247, 1198, 1168, 1059, 732; 1H
NMR (CDCl3, 400 MHz) δ: 13.00 (s, 2H, SCNHCO), 9.82 (s, 2H,
NH), 9.50 (s, 2H, NHCO), 7.80–7.78 (m, 2H, ArH), 7.63–7.54 (m,
8H, ArH), 7.39–7.34 (m, 4H, ArH), 7.26–7.22 (m, 2H, ArH), 2.42 (s,
6H, CH3); ESI-MS m/z (%): 625.15 ( [M+1]+, 100). Anal. Calcd for
C32H28N6O4S2: C, 61.52; H, 4.52; N, 13.45. Found: C, 61.62; H, 4.51;
N, 13.41%.
7e: Pale yellow crystal; yield 87%, m.p. 237–240 °C; IR (KBr,
cm−1): 3253, 3075, 2922, 1672, 1520, 1453, 1242, 1167, 1053, 710; 1H
NMR (DMSO-d6, 400 MHz) δ: 11.81 (s, 2H, SCNHCO), 11.50 (s,
2H, NH), 11.14 (s, 2H, NHCO), 7.80–7.72 (m, 12H, ArH), 7.63–7.57
(m, 4H, ArH); ESI-MS m/z (%): 755.12 ( [M+1]+, 100). Anal. Calcd
for C30H22Br2N6O4S2: C, 47.76; H, 2.94; N, 11.14. Found: C, 47.70;
H, 2.94; N, 11.17%.
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