N,N′-Bis-(4-nitrophenylcarbamothioyl)phthalamide

Abstract

A novel colorimetric receptor linked to two nitrophenylurea groups was synthesized in good yields, characterized and their chromogenic properties investigated towards various anions (F⁻, Cl⁻, Br⁻, I⁻, OH⁻, AcO⁻, H₂PO₄⁻ and CN⁻) by UV-Vis techniques. The receptor, effectively and selectively, recognized and distinguished the biologically important F⁻ from other anions such as Cl⁻, Br⁻, I⁻ etc. in DMSO. This selectivity could be easily observed by the naked eye, indicating that receptor is potential colorimetric sensor for fluoride ion.

Anions are key to many biological processes, playing important roles in health [1]. They are also essential ingredients used by a variety of industries related to agricultural fertilizers and water. Therefore, in the past two decades, supramolecular chemistry of anions developed into a wide research field that has been extensively reviewed [2,3].

These receptors as known supramolecules are usually based on macrocyclic amides [4], ureas/thioureas [5,6,7], pyrroles [8], indoles and phenylhydrazones [9,10], etc. They exhibit such an obvious color change when anion is added that one can detect by naked-eye without resorting to spectroscopic instrumentation [11].

Some thiourea derivatives are widely used in many fields including pharmaceutical industry due to their biological properties such as antimicrobial, antibacterial [12] and plant-growth regulators [13]. Aroylthioureas usually coordinated to metal in bidentate manner through the sulfur and oxygen atoms [14,15].

In this paper, we report herein the synthesis, characterization and anion-hydrogen binding studies of a bisthiourea compound of N,N′-Bis-(4-nitrophenylcarbamothioyl)phthalamide as shown in Scheme 1. Its structure was characterized by elemental analysis, IR and ¹H- and ¹³C-NMR spectroscopic techniques.

Results and Discussion

The title compound, N,N′-Bis-(4-nitrophenylcarbamothioyl)phthalamide, has been synthesized and characterized by elemental analysis, IR and ¹H- and ¹³C-NMR spectroscopic analysis. The IR data of the title compound showed two N−H stretching bands at 3,392 and 3,247 cm⁻¹. The C=O stretching bands appeared at 1,669 cm⁻¹. The strong band at 1,542 cm⁻¹ was confirmed the amido stretching vibration. The strong bands at 1,313 and 750 cm⁻¹ were assigned to thioureido N-C=S and C=S stretching vibrations, respectively. The ¹H-NMR data showed that the chemical shifts of protons on nitrogen appeared in the low field, in the range between 11.12 and 10.30 ppm. The chemical shifts of protons on the nitro-substitute benzene ring are in lower field, in the range between 8.42 and 8.20 ppm than that of protons on the phthaloyl ring, in the range between 8.01 and 7.87 ppm. In the 13C-NMR signals, the carbon atoms of carbonyl (C=O) and thiocarbonyl (C=S) appear at 167 ppm and 181 ppm, respectively. (Supplementary material).

The interaction properties of title compound and to a series of anions such as F⁻, Cl⁻, Br⁻, I⁻, OH⁻, AcO⁻, H₂PO₄⁻ and CN⁻ (as their tetrabutylammonium salts) were investigated by using UV-Vis spectroscopic technique. Remarkable spectral changes were observed upon the addition of these anions to solutions of the title compound (see Figure 1).

Hydrogen binding of anions was resulted in a noteworthy change in the visible region of the spectrum (approximately 130 nm red shift), which could be detected by the ‘naked-eye’ (see Figure 2)

Binding ability of the receptor for F- was investigated by UV-Vis spectrometry in DMSO using a constant host concentration (5 × 10⁻⁵ M) and increasing concentrations of the F⁻ (0–5 equivalence). Upon the addition of F⁻, the intensity of the absorption peak at 352 nm decreased, whereas the intensity of 470 nm peak increased in UV-Vis spectrum of the receptor solution. The resulting titration revealed only one well-defined isosbestic point at 390 nm. The binding constant was determined by using nonlinear fitting analyses of the titration curves, 1:1 host-guest complexation as log K 6.640 ± 0.12. [16] (Figure 3).

Experimental

Materials and Measurements

All reagents for synthesis were obtained commercially and were used without further purification. In the titration experiments, all the anions were added in the form of tetra-n-butylammonium (TBA) salts, which were purchased from Merck Chemical Co. and Across, stored in a vacuum desiccator containing self-indicating silica and fully dried before using. The ¹H- and ¹³C-NMR spectra were recorded in DMSO-d at 25 °C on a Bruker NMR spectrometer operating at 400 and 101.6 MHz. MS spectra were obtained with an Agilent 5973 Inert Mass Selective Detector equipped with Direct Insertion Probe. Infrared spectrum was recorded using a Diamond ATR (attenuated total reflection) accessory on a Perkin Elmer BX II spectrophotometer. Melting point (m.p.) was measured in an Electro Thermal IA 9100 instrument using a capillary tube. Thin-layer chromatography was carried out on Merck aluminium sheets coated with silica gel 60 F₂₅₄. UV-Vis measurements were performed on a instrument Perkin-Elmer WinLab-25 series spectrophotometer with a quartz cuvette (path length: 1 cm). Dimethyl sulfoxide was dried with calcium hydride and then distilled at reduced pressure. The anion binding properties of N,N′-Bis-(4-nitrophenylcarbamothioyl)phthalamide have been studied by using UV-Vis spectroscopic titration techniques in dry DMSO.

Synthesis and Characterization of N,N′-Bis-(4-nitrophenylcarbamothioyl)phthalamide

A solution of phthaloyl dichloride (1.01 g, 5 mmol) in acetone (30 mL) was added dropwise to a suspension of potassium thiocyanate (0.97 g, 10 mmol) in acetone (20 mL) and the reaction mixture was refluxed for 30 min. After cooling to room temperature, a solution of the 4-nitroaniline (2.03 g, 10 mmol) in acetone (15 mL) was added and the reaction mixture was heated under reflux for 3 h. The resulting mixture was poured into a beaker containing cold water. The resulting orange precipitate was collected by filtration, washed several times with cold water and purified by recrystallized from acetone/tetrahydrofurane mixture (1:1). The product was obtained as yellow crystals.

Yield: 2.41 g, 71%; mp: 225–227 °C.

IR, (ν_max, cm⁻¹): 3392 (N-H), 3247 (N-H), 3023 (C_aromatic-H), 1669 (C=O), 1542 (N-CO), 1313 (N-CS, thioureido), 750 (C=S).

¹H-NMR (400 MHz, DMSO-d6) (δ/ppm): 11.12 (s, 2H, N-H), 10.30 (s, 2H, N-H), 8.42-8.20 (m, Ar_phenyl.-H); 8.01 (2H, C-H_phthaloyl, d, J = 5.9 Hz), 7.87 (2H, t, J = 6.0 Hz).

¹³C-NMR (100 MHz, DMSO-d6) δ: 181.7 (C=S), 167.7 (C=O), 156.1, 146.6, 142.9, 138.2, 136.4, 131.9, 128.5 (Ar).

MS (EI): (m/z) = 524.1 (M+1).

Anal. Calc. For C₂₂H₁₆N₆O₆S₂: C, 50.38; H, 3.07; N, 16.02; S, 12.23 Found: C, 50.30; H, 3.11; N, 16.08; S, 12.21.