Synthesis, Crystal Structure and Recognition Properties of 2-(5-(4-Chlorophenyl)- 1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine①

ZHONG Li-Qun ZHANG Shu-Shu TAO Qing HU Sheng-Li



Synthesis, Crystal Structure and Recognition Properties of 2-(5-(4-Chlorophenyl)- 1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine①

ZHONG Li-Qun ZHANG Shu-Shu TAO Qing HU Sheng-Li②

(435002)

The title compound 2-(5-(4-chlorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-pyridine (C20H16ClN3,M= 333.81) has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group21/with= 10.9925(12),= 11.0378(12),= 14.2751(18) Å,= 98.074(11)°,= 1714.9(3) Å3,= 4,D= 1.293 g/cm3,(Mo) = 0.228 mm-1,(000) = 696, the final= 0.0521 and= 0.1349 for 3495observed reflections with> 2(). Intermolecular C–H×××interactions andstacking interactions stabilize the crystal structure. The binding study by fluorescence spectroscope titration showedthat the title compound can selectively recognize Fe3+in THF solution with fluorescence quenching.

crystal structure, pyrazoline, recognition properties

1 INTRODUCTION

The development of highly selective sensors for metal ions is particularly important, since metal ions can have detrimental effects on humans and the environment[1]. Fe3+provides the oxygen-carrying capacity of heme and acts as a cofactor in many enzymatic reactions involved in the mitochondrial respiratory chain, and both its deficiency and excess can induce a variety of diseases[2]. Thereby, it is very important to detect iron ions.

1,3,5-Triaryl-2-pyrazolines with rigid but only partly unsaturated central pyrazoline ring are well- known fluorescent compounds widely used in fluorescent dyes emitting blue fluorescence with high fluorescence quantum yield[3-4]. However, only a few examples have been reported on the interac- tions between pyrazoline derivatives and metal ion[5–7]. In this paper, a new pyrazoline derivative 1 was synthesized and its structure was determined by single-crystal X-ray diffraction. Its binding proper- ties studied by fluorescence spectroscope titration showed that 1possesses a highly selective response of fluorescence quenching toward Fe3+in THF solution.

2 EXPERIMENTAL

2. 1 Synthesis of the title compound

Melting points were determined on an XT4A Meltemp apparatus and are uncorrected.1H NMR was recorded in CDCl3on a Varian Mercury 400 spectrometer MS and measured on a Finnigan Trace MS spectrometer. IR was recorded on a PE-983 infrared spectrometer as KBr pellet with absorption in cm-1.

The synthesis route of the title compound 1 is outlined in Scheme 1.

Scheme 1

The synthetic route to compound 1 is shown in Scheme 1. Starting material chalcone (2)[8]was pre- pared according to the literature. To a stirred solu- tion of chalcone 2 (0.243 g, 1.0 mmol) in AcOH (15 mL) was added phenylhydrazine (3) (0.108 g, 1.0 mmol). The reaction mixture was refluxed for 4 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled to room temperature and the solvent was evaporated in vacuo, and the crude product was washed with water, and consequently recrystallized from ethanol to afford pure compound 1as a yellow solid, yield 62%. m.p.: 106～107 ℃. IR (max, KBr, cm-1): 1640, 1564, 1390, 1324, 1120, 826, 743.1H NMR (CDCl3),(ppm): 8.52～8.54 (m, 1H, Ar-H), 8.12～8.16(m,1H, Ar–H), 7.68～7.73(m,1H,1.5Hz), 7.17～7.31(m,7H, Ar–H), 7.04～7.08 (m,1H,Ar–H), 5.33(dd, 1H,= 8.1, 8.1 Hz, pyrazoline-H), 3.97(dd,1H,= 12.6, 12.6 Hz, pyrazoline-H), 3.30(dd, 1H,= 8.2, 8.2 Hz, pyrazoline-H).13C NMR (CDCl3),(ppm): 43.03, 63.94, 113.54, 118.83, 120.69, 122.80, 127.24, 129.03, 129.31, 133.27, 136.10, 140.72, 143.98,147.85, 148.98, 151.81. ESI mass spectrometry: m/z 333.1 (100% [M+H]+); M+calculated 333.1. Anal. Calcd. (%) for C20H16ClN3(333.1): C, 71.96; H, 4.83; N, 12.59. Found (%): C, 71.94; H, 4.81; N, 12.56. The single crystals of the title compound were obtained by slow evaporation from the ethanol solution.

2. 2 Crystal data and structure determination

A yellow crystal of the title compound having approximate dimensions of 0.40mm × 0.20mm × 0.12mm was mounted on a glass fiber in a random orientation at 293(2) K. The determination of unit cell and the data collection were performed with Moradiation (= 0.71070 Å) on a BRUKER SMART APEX-CCD diffactometer. A total of 8598 reflections were collected in the range of 6.24<<52.74º at room temperature, and 3495 independent reflections (int= 0.0446) with> 2() were used in the structure determination and refinements. The structure was solved by direct methods with SHE- LXS-97 program and refined on2with SHE- LXL-97 program. The non-hydrogen atoms were refined anisotropically, and the hydrogen atoms were determined with theoretical calculation. A full- matrix least-squares refinement gave the final= 0.0521,= 0.1349 (= 1/[2(F2) + (0.0754)2+ 0.1831], where= (F2+ 2F2)/3),= 0.0637 and= 0.1486 for all data. In the final circle of re- finement, the largest parameter shift (Δ/)maxis 0.000. The goodness-of-fit indicator is 1.061. The maximum and minimum peaks in the final dif- ference Fourier map are 0.218 and –0.405 e/Å3, respectively. All calculations were performed on a PC with SHELXTL program.

3 RESULTS AND DISCUSSION

3. 1 Description of structure

The view of the crystal structureof the title compound is shown in Fig. 1. The selected bond len- gths and bond angles are listed in Tables 1 and 2, res- pectively. Table3 shows the selected torsion angles among the atoms of the title compound, and Table 4 lists the hydrogen-bonding interaction distances.

Table 1. Selected Bond Lengths (Å)

Table 2. Selected Bond Angles (°)

Table 3. Selected Torsion Angles (°)

Table 4. C–H×××π Interactions in the Crystal (Å,o)a

aCg(4), Cg(1), and Cg(3) denote phenyl ring C(15)～C(20), pyrazoline ring N(2)/N(3)/C(8)/C(7)/C(6), and phenyl ring C(9)～C(14), respectively

In the structure of 1, the C(6), C(7), C(8), N(2) and N(3) atoms form a five-membered pyrazoline ring, with the C(8)–N(3) in 1.472(2) Å belonging to a C–N single bond. The bond length of C(6)=N(2) is 1.288(2) Å, close to that of typical C=N bond (1.28 Å). One 4-chlorobenzene and a pyridine moiety are bonded to the pyrazoline ring at the atoms of C(6), C(8) and N(3), respectively, consistent with a pro- nounced electronic interaction. Owing to the exis- tence of conjugate system, the C(15)–N(3) bond in 1.387 Å is between the normal C=N double bond (1.27 Å) and C–N single bond (1.47 Å)[9–10], indicating the N(3) atom is partially characterized by2hybridization. The torsion angle C(15)–N(3)– C(8)–C(9) of –68.0(2)oshows C(9) in the 4-chloro- benze moiety adopts an antiperiplanarconformation with respect to the C(15) atom of the benzene ring. In the asymmetric unit, the pyrazoline ring, pyridine ring and benzene are almost coplanar. And the pyrazoline ring makes dihedral angles with benzene and pyridine of 5.43(11)and 3.74(12)o, respectively, while the dihedral angle between the pyrazoline and benzene moieties is 79.21(10)o.

The packing diagram of the title compound is shown in Fig. 2. The molecules are linked together by weak intermolecular C–H···interaction (Table 4) into a one-dimensional structure extending along theaxis, which is important for the packing modes, and further assigned into layers viastacking interactions (Table 5).

Table 5. π-π Interactions in the Crystal (Å,o)a

aCg(4), Cg(2), and Cg(1) denote phenyl ring C(15)～C(20), pyridine ring N(1)/C(1)/C(2)/C(3)/C(4)/C(5), and pyrazoline ring N(2)/N(3)/C(8)/C(7)/C(6), respectively

Fig. 1. Molecular structure of the title compound 1

Fig. 2. Packing structure of the title compound 1

3. 2 Recognition properties

Binding affinities of compound 1 toward various metal ions were firstly evaluated by UV-vis spectro- scopy measurements. As shown in Fig. 3, the absorption spectrum of compound 1 exhibits a broad band at 368 nm at room temperature inTHF. In the case of K+, Na+, Cr3+, Zn2+, Cd2+, Co2+, Hg2+, Mg2+, Mn2+, Ni2+, and Pb2+,the absorption curve did not obviously change, and the addition of Cu2+caused a new absorption band at 294 nm but did not cause a change of absorption intensity at 368 nm. However, in the case of Fe3+, the addition of Fe3+ion resulted in a new absorption band at 452 nm and caused an increase of absorption intensity at 368 nm, accom- panied by the obvious hypsochromic shift of the absorption peak (from 368 to 350 nm), indicating the formation of a new complex between compound 1 and Fe3+.

The UV-vis absorption spectra of 1 (1 × 10-5M) in THF in the presence of various concentrations of Fe3+(0～20 × 10-5M) are shown in Fig. 4. The inset in Fig. 4 shows the plots of changes as a function of increasing the concentration of Fe3+.As shown in Fig. 4, the UV absorbance at 368 nm enhanced from 0.25 to 1.19 when increasing the concentration of Fe3+from 0 to 20 × 10-5M. A satisfactory linear relationship between UV-vis absorbance and Fe3+concentration was observed with the correlation coefficient as high as 0.9978.

Fig. 3. UV-vis spectral changes of compound 1 (1×10-5M) in THF in the presence of various metal ions (10×10-5M)

Fig. 4. UV absorbance spectra of 1 (1 ×10-5M) in THF upon the addition of various amounts of Fe3+. The inset shows the absorbance intensity atmax= 368 nm as a function of Fe3+concentration for 1

Fig. 5. Fluorescence emission spectra of 1(excitation at 368 nm) (1×10-5M) in THF in the presence of Fe(H2O)6Cl3. The concentration of Fe3+: 0-20×10-5M

The fluorescence titration spectra of 1 with Fe3+show an emission maximum peak at 462 nm (Fig. 4). The fluorescence quantum yield of compound 1 in the absence of Fe3+was calculated to be 0.60 with respect to the quinine sulphate in 0.1 N H2SO4solution (s= 0.54)[11]. As the Fe3+ion was gra- dually titrated, the fluorescence intensity of com- pound 1 gradually decreased and when the amount of Fe3+ion added was about 20 × 10-5M, the fluo- rescence intensity almost reached minimum. The quantum yield of 1 was calculated to be 0.022 in the presence of Fe3+ion (20 × 10-5M) and almost reduced to 3.6% of the initial one. To determine the stoichiometry of compound 1and Fe3+ion in the complex, Job’s method[12]was employed by using the emission changes at 462 nm as a function of the molar fraction of Fe3+. A maximum emission was observed when the molar fraction of Fe3+reached 0.5 (Fig. 5), indicating that Fe3+ions form a 1:1 complex with the sensing compound. Based on the above fluorescence titration of 1 with Fe3+, the association constant was calculated to be 2.6×104M-1(error limits ≤ 10%) by a Benesi-Hildebrand plot[13](Fig. 6).

The selectivity and tolerance of compound 1 for the Fe3+ion over other metal cations such as K+, Na+, Cr3+, Mg2+, Hg2+, Cd2+, Zn2+, Co2+, Ni2+, Pb2+, Mn2+, and Cu2+ions were investigated by adding metal cations (10×10-5M) to the solution of compound 1 (10 × 10-5M). As depicted in Fig. 7, Fe3+produced significant quenching in the fluorescent emission of 1, while the other tested metals only show relatively insignificant changes, which means that the sensor 1 has a high selectivity to Fe3+ion.

To investigate the mechanism of the fluorescence quenching for 1, Fe3+may easily establish coor- dinative interactions with the pyridine andpyrazo- line moieties than other metal ions examined. The capture of Fe3+resulted in the electron transfer from 1 to Fe3+; thus, 1 showed quenching of the fluore- scence for Fe3+and provided a high selectivity for Fe3+over the other tested metal ions.

Fig. 6. Benesi-Hildebrand linear analysis plots of 1 at different Fe3+

Fig. 7. Fluorescence emission changes of 1(1 × 10-5M) in THF in the presence of 10 × 10-5M various metal ions

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24 October 2013;

2 January 2014 (CCDC 936327)

① The project was supported by the Hubei Province Education Ministry Foundation of China (No. D20112507) and the Science Technology Foundation for Creative Research Group of HBDE (No. T201311)

. Hu Sheng-Li, professor. E-mail: hushengli168@126.com