Synthesis of hybrid ligands derived from benzil, thiosemicarbazide and heteroaromatic hydrazides and their reactivity with group 12 metals

Polyhedron 54 (2013) 39–46

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Synthesis of hybrid ligands derived from benzil, thiosemicarbazide and heteroaromatic hydrazides and their reactivity with group 12 metals David G. Calatayud 1, Elena López-Torres, M. Antonia Mendiola ⇑ Departamento de Química Inorgánica, C/Francisco Tomás y Valiente 7, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

a r t i c l e

i n f o

Article history: Received 11 December 2012 Accepted 9 February 2013 Available online 20 February 2013 Keywords: Dissymmetric thiosemicarbazones Metal complexes X-ray diffraction

Two new dissymmetric ligands were synthesized by successive condensations of 2,3-diphenylethanedione with 2-hydrazinepyridine or 2-hydrazinequinoline and thiosemicarbazide. As hydrochloric acid was necessary for the condensation reactions, the ligands were obtained as the chloride salts. While the pyridine derivative [H3BTsP]Cl was obtained in a reasonable yield, the quinoline-containing one [H3BTsQ]Cl was isolated in a small amount, so its reactivity with metal salts was not explored. By contrast, three new complexes with zinc, cadmium and mercury nitrates, [ZnCl(H2BTsP)]NO3 (1), [Cd(H2BTsP)(NO3)2] (2) and [Hg(H2BTsP)(NO3)]NO3 (3), were obtained with [H3BTsP]Cl. In all the complexes the ligand behaves as a neutral tetradentate donor giving rise to monomeric species in which the metal coordination environment is completed by chlorido or nitrato groups. The ligands and the complexes were characterized by elemental analysis, molar conductivity, mass spectrometry, IR, 1H and 13C NMR spectroscopy and most of them by X-ray single crystal diffraction. Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction The interest in thiosemicarbazone (TSCs) ligands and their complexes has increased steadily for the last years. The TSCs chemistry is not only interesting by their versatility as ligands [1–3], but also by their structural, optical and biological properties [2,4–6] that include antitumor, antibiotic, antifungal and antiviral activity [4,7,8]. They have been the subject of at least 12 patents mainly related to their antibacterial properties and it is well established that transition metal complexes of TSCs are potent pharmacological agents that normally show more activity than the free ligands. Pharmacological studies have shown that introduction of substituents in the N4 of the TSC branch of these ligands, influences their biological activity although it has not been established yet a relationship between activity and structure. Some ligands and complexes of thiosemicarbazone derivatives have also activity against parasitic protozoans, which cause diseases like malaria [9], sleeping sickness [10] etc., since they inhibit the activity of the cysteine proteases, which are necessary for the lifecycle of the parasite [10–12]. Recently, complexes of bis(TSC) with copper have been explored as imaging agents in positron emission tomography (PET) studies to identify hypoxic tissues [13–17].

⇑ Corresponding author. Tel.: +34 91 497 4844; fax: +34 91 497 4833. E-mail address: [email protected] (M. Antonia Mendiola). Present address: Departamento de Electrocerámica, Instituto de Cerámica y Vidrio, CSIC, C/Kelsen 5, Cantoblanco, 28049 Madrid, Spain. 1

0277-5387/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.poly.2013.02.025

The design and synthesis of dissymmetric double-Schiff-base ligands containing this TSC moiety has started during the last decade, but only a short number of research groups in the world have developed efficient strategies. The accessibility of such asymmetric ligands is often hampered by several synthethic problems, which is the reason why this field is not much developed. The problems found in the synthesis include ring-closure reactions or the obtaining of the corresponding symmetric ligands, as well as ligand mixtures that are very difficult to purify [18]. The asymmetric thiosemicarbazone molecules can be divided into two groups: mixed bis(thiosemicarbazone) ligands containing two dissimilar thiosemicarbazone functions [19,20], or molecules containing only one thiosemicarbazone arm and additional functional groups in the other one, which opens the posibility of incorporating different types of donor atoms to fit better the metal preferences [21,22]. The synthesis of these molecules is usually carried out in two steps. The first step is the obtaining of the open-chain [1 + 1] proligand, which contains a carbonyl group available for the condensation with another amine. These reactions are complicated and it is necessary to carefully control the reaction conditions such as the temperature, concentration or the solvent used, since small changes can yield undesired products, such as [1 + 1] heterocycles or the [1 + 2] symmetric ligands, which are normally more stable [18,23,24]. In previous papers we have detailed the synthesis of the dissymmetric ligands obtained by reaction of 2,3-butanedione, 4methyl-thiosemicarbazide and 2-hydrazinepyridine [25] or 2hydrazinequinoline [26] and explored their reactivity with group

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46

12 metal salts under different reaction conditions. Following our interest in the synthesis of bis(TSCs) derived from 2,3-diphenylethanedione (benzil) [27–31], in this paper we report the synthesis of the hybrid ligands obtained from benzil, thiosemicarbazide and 2-hydrazinepyridine or 2-hydrazinequinoline, as well the reactivity of the pyridine-containing ligand with zinc, cadmium and mercury nitrates.

2. Experimental 2.1. Materials and general methods All reagents were obtained from standard commercial sources and were used as received. Caution! Mercury and cadmium are highly toxic cumulative poison, and their compounds should be handled carefully. Microanalyses were carried out using a LECO CHNS-932 Elemental Analyzer. IR spectra in the 4000–400 cm 1 range were recorded as KBr pellets on a Jasco FT/IR-410 spectrophotometer. Fast atom bombardment mass spectra were recorded on a VG Auto Spec instrument using Cs as the fast atom and m-nitrobenzylalcohol (m-NBA) as the matrix. Electrospray mass spectrometry experiments were performed with an ion trap instrument LCQ Deca XP plus (Thermo Instruments). An ESI source was used in positive ionization mode. Conductivity was measured using a freshly prepared DMF solution (ca. 10 3 M) at 25 °C with a Crison EC-Meter BASIC 30+ instrument. 1H and 13C NMR spectra were recorded on a spectrometer Bruker AMX-300 using DMSO-d6 or CDCl3 as solvents and using TMS as internal reference. 13C CP/MAS NMR spectra were recorded at 298 K in a Bruker AV400WB spectrometer equipped with a 4 mm MAS NMR probe (magic-angle spinning) and obtained using cross-polarization pulse sequence. The external magnetic field was 9.4 T, the sample was spun at 10–14 kHz and the spectrometer frequency was 100.61 MHz. For the recorded spectra a contact time of 4 ms and recycle delays of 4 s were used. Chemical shifts are reported relative to TMS, using the CH group of adamantane as a secondary reference (29.5 ppm).

2.2. X-ray crystallography Data for [H4BQ2]Cl2
2CH3OH, [H3BTsQ]Cl
2CH3OH, [H3BTsP]NO3
2CH3OH and complexes 1 and 2
CH3OH were acquired using a Bruker AXS Kappa Apex-II diffractometer equipped with an Apex-II CCD area detector using a graphite monochromator (Mo Ka radiation, k = 0.71073 Å). The substantial redundancy in data allows empirical absorption corrections (SADABS) [32] to be applied using multiple measurements of symmetry-equivalent reflections. The raw intensity data frames were integrated with the SAINT program, which also applied corrections for Lorentz and polarization effects [33]. The software package SHELXTL version 6.10 was used for space group determination, structure solution and refinement. The structures were solved by direct methods (SHELXS-97) [34], completed with difference Fourier syntheses, and refined with full-matrix least squares using SHELXL-97 minimizing x (F02 Fc2). Weighted R factors (Rw) and all Goodness-of-fit S are based on F2; conventional R factors (R) are based on F [35]. All non-hydrogen atoms were refined with anisotropic displacement parameters. CH and OH hydrogen atoms, except OH in [H3BTsQ]Cl
2CH3OH, were positioned geometrically after each cycle of refinement. The NH in all the complexes and OH in [H3BTsQ]Cl
2CH3OH were located in a difference Fourier map and their coordinates and isotropic thermal parameters subsequently refined. All scattering factors and anomalous dispersions factors are contained in the SHELXTL 6.10 program library.

2.3. Synthesis of the quinoline precursor and the proligands 2.3.1. 2-Hydrazinequinoline 2-Hydrazinequinoline was synthesized by reaction of 2-chloroquinoline with monohydrated hydrazine, following the previously described procedure [26]. 2.3.2. [H2BP]Cl To a solution in ethanol (65 mL) at 0 °C of benzil (1.00 g, 4.76 mmol) with conc. HCl (0.44 mL, 4.98 mmol), a solution of 2hydrazinepyridine (0.52 g, 4.76 mmol) in ethanol (20 mL) was added slowly. The solution was stirred at 0 °C for 18 h then half of the solvent was removed under vacuum. After 24 h at 18 °C a pale yellow solid precipitated which was filtered off and dried in vacuo. Yield: 71% (1.00 g). Elem. Anal. Calc. for C19H16N3ClO (337.80): C, 67.56; H, 4.77; N, 12.44. Found: C, 67.45; H, 4.64; N, 12.39%. IR (KBr, cm 1): 3178(m) m(NH), 1674(s) m(CO), 1644(s) m(CNpy). 1H NMR (300 MHz, DMSO-d6): d/ppm 13.92 (s, 1H, HNpy), 10.18 (s, 1H, NH), 8.22–7.14 (m, 14H, aromatic). 1H NMR (300 MHz, CDCl3): d/ppm 13.66 (s, 1H, HNpy), 9.85 (s, 1H, NH), 8.09–6.80 (m, 14H, aromatic). MS (FAB+): m/z 302.1 ([H2BP]+, 100%). 2.3.3. [H2BQ]Cl A solution of 2-hydrazinequinoline (0.50 g, 3.14 mmol) in methanol (40 mL) with conc. HCl (0.31 mL, 3.51 mmol) was added to a solution of benzil (0.66 g, 3.14 mmol) in methanol (50 mL) with 12 drops of conc. HCl. The solution was stirred at 15–18 °C for 24 h and partially concentrated until a yellow solid precipitated which was filtered off, washed with cold methanol and dried in vacuo. Yield: 80% (0.88 g). Elem. Anal. Calc. for C23H18N3ClO (387.86): C, 71.22; H, 4.68; N, 10.83. Found: C, 71.18; H 4.64; N, 10.75%. IR (KBr, cm 1): 3220(w), 3149(w) m(NH), 1678(m) m(CO), 1645(s) m(CNqui). 1H NMR (300 MHz, CDCl3): d/ppm 16.11 (s, 1H, NHqui), 12.48 (s, 1H, NH), 8.34 (d, 3JHH = 9.2 Hz, 1H, H6), 8.10–7.35 (m, 15H, aromatic). MS (FAB+): m/z 352.1 ([H2BQ]+, 100%). A yellow solid identified as [H4BQ2]Cl2 was isolated by partial evaporation of the mother liquor. 1H NMR (300 MHz, CDCl3): d/ ppm 16.42 (s, 2H, NHqui), 11.87 (s, 2H, NH), 8.17 (d, 3JHH = 9.4 Hz, 2H H6), 7.91 (d, 3JHH = 8.5 Hz, 2H, H9), 7.79–7.69 (m, 10H, aromatic), 7.58–7.45 (m, 8H, aromatic). MS (FAB+): m/z 493.1 ([H3BQ2]+, 100%). Suitable crystals for X-ray diffraction were obtained by slow evaporation of the mother liquor. This compound was also obtained by direct reaction between benzil and two equivalents of 2-hydrazinequinoline. Under other conditions the reaction did not progress or a mixture containing [H2BQ]Cl and [H4BQ2]Cl2 was obtained. If the reaction was carried out at 0 °C or without conc. HCl the reagents were recovered, and if the temperature was above 18 °C, [H4BQ2]Cl2 was obtained as the major product. 2.3.4. Reaction of benzil with thiosemicarbazide Attempts to synthesize the proligand derived from benzil with thiosemicarbazide (HBTs) were unsuccessful: if the reactions were carried out at low temperature the reagents were recovered; increasing the temperature above 18 °C 6-methoxy-1,6-diphenyl4-thio-3,4,5,6-tetrahydro-2,3,5-triazine HBTsOCH3 [36] was formed; different solvents were tested, such as water, methanol and ethanol, obtaining the initial reactants or the triazine-3-thione derivative; without acid the reactions did not progress. 2.4. Synthesis of the hybrid ligands 2.4.1. [H3BTsP]Cl A solution of thiosemicarbazide (0.20 g, 2.19 mmol) in methanol (35 mL) and conc. HCl (0.10 mL, 1.13 mmol) was added to a solution of [H2BP]Cl (0.73 g, 2.16 mmol) and conc. HCl

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46 Ph

Ph

Ph

NH2 H3

HN HN

N

O

+

S H2N

Cl-

NH+

MeOH

C3 N3

19 ºC, 24 h

C5

Ph

H2 N4

N2

H6a

HN

H1a C1

ClN6+

C7

C2

N5

C4

C6

Ph

Ph

N1

N

N

OCH3

+

S1

+ NH+

H1b

Cl-

Cl-

N

+HN

NH HN

C8

C9

Ph

Ph

NH

S

C12 C10

C11

8%

Scheme 1. Synthesis of [H3BTsQ]Cl including atom labeling scheme.

semicarbazide (0.14 g, 1.54 mmol) in methanol (30 mL) with conc. HCl (0.18 mL, 2.04 mmol) was added. The solution was stirred at 19 °C for 24 h. Then a half of the solvent was evaporated and the solution was kept at 4 °C until a yellow solid precipitated, which was filtered off, washed with cold methanol and dichloromethane and dried in vacuo. Yield: 8% (0.06 g). In the mother liquor HBTsOCH3 [36] and the symmetric open chain molecule [H4BQ2]Cl2 can be detected in high yields (Scheme 1). Recrystallization in methanol gave single crystals suitable for X-ray diffraction. Elem. Anal. Calc. for C24H21N6SCl (460.98): C, 62.53; H, 4.59; N, 18.23; S, 6.96. Found: C, 62.45; H, 4.45; N, 18.20; S, 6.90%. IR (KBr, cm 1): 3346(m), 3262(m), 3183(m) m(NH), 1652(vs), 1618(s), 1581(m), 1534(m) m(CN + thioamide II), 851(w) m(CS). 1H NMR (300 MHz, DMSO-d6): d/ppm 10.07 (br s, 1H, H3), 8.66 (s, 1H, H2), 8.42 (s, 2H, H1a + H6), 8.18 (s, 1H, H1b), 8.04–7.78(m, 6H, H9 + H5 + Ph), 7.66–7.32 (m, 9H, H11 + H12 + H10 + Ph). 1H NMR (300 MHz, CDCl3): d/ppm 16.03 (s, 1H, H6a), 12.31 (s, 1H, H3), 8.61 (s, 1H, H2), 8.37 (d, 3JHH = 9.4 Hz, 1H, H6), 8.00 (d, 3JHH = 9.4 Hz, 1H, H9), 7.92 (s, 1H, H1a), 7.88–7.73 (m, 7H, H5 + H11 + H12 + Ph), 7.57–7.33 (m, 7H, H10 + Ph), 7.01 (t, 3JHH = 6.5 Hz,1H, H7), 6.60 (s, 1H, H1b). 13C NMR (300 MHz, DMSO-d6): d/ppm 179.5 (C1), 149.6 (C4), 143.8, 142.7 (C2 + C3), 133.4 (C6), 132.9 (C8), 131.7 (C11), 131.0 (C9), 129.6, 129.3, 127.7, 127.2 (Ph), 126.3 (C12), 123.1 (C10), 119.1 (C7), 113.4 (C5). MS (ESI+): m/z 425.2 [H3BTsQ]+.

(0.20 mL, 2.27 mmol) in methanol (15 mL). The solution was stirred at room temperature for 24 h. The yellow solid formed was filtered off, washed with methanol and dried in vacuo. Yield: 47% (0.41 g). Elem. Anal. Calc. for C20H19N6SCl (410.92): C, 58.46; H, 4.66; N, 20.45; S, 7.80. Found: C, 58.36; H, 4.50; N, 20.40; S, 7.75%. IR (KBr, cm 1): 3332(m), 3271(m), 3160(m) m(NH), 1644(s), 1607(vs), 1555(m), 1532(w) m(CN + thioamide II), 839(w) m(CS). 1H NMR (300 MHz, DMSO-d6): d/ppm 11.69 (br s, 1H, H3), 10.21 (s, 1H, H2), 8.63 (s, 1H, H1a), 8.38 (s, 1H, H1b), 8.30 (d, 3 JHH = 5.6 Hz, 1H, H8), 8.12 (ddd, 3JHH = 8.7 Hz, 3JHH = 7.2 Hz, 4 JHH = 1.3 Hz, 1H, H6), 7.91–7.76 (m, 4H, Ph), 7.53–7.35 (m, 7H, H5 + Ph), 7.20 (t, 3JHH = 6.3 Hz, 1H, H7). 1H NMR (300 MHz, CDCl3): d/ppm 16.08 (s, 1H, H6a), 11.91 (s, 1H, H3), 8.60 (s, 1H, H2), 8.04 (t, 3 JHH = 7.8 Hz, 1H, H6), 7.92 (d, 3JHH = 9.0 Hz, 1H, H5), 7.85 (d, 3 JHH = 5.9 Hz, 1H, H8), 7.82 (s, 1H, H1a), 7.73 (m, 4H, Ph), 7.54– 7.33 (m, 6H, Ph), 7.01 (t, 3JHH = 6.5 Hz,1H, H7), 6.60 (s, 1H, H1b). 13 C NMR (300 MHz, DMSO-d6): d/ppm 179.8 (C1), 150.9 (C4), 146.0, 145.1 (C2 + C3), 141.6 (C8), 138.8 (C6), 133.5, 133.0, 131.1, 130.7, 129.4, 127.6, 127.3 (Ph), 116.6 (C7), 113.1 (C5). MS (ESI+): m/z 375.1 [H3BTsP]+. 2.4.2. [H3BTsQ]Cl To a solution of [H2BQ]Cl (0.60 g, 1.55 mmol) in methanol (35 mL) with conc. HCl (0.18 mL, 2.04 mmol), a solution of thioPh

Ph

NH2 HN

HN

N

+

O

S H2N

Cl-

NH+

MeOH r.t., 24 h

Ph Ph

H3

Ph

N3 N

HN

N

NO3

Zn N

Cl

C5

Zn(NO3)2.6H2O NH

S

NH2

EtOH, reflux, 24 h

C2

N5

H2 N4

C4

C6

+

Ph

N2

H6a

Ph

H1a C1

ClN6

C7

Ph C3

Cd(NO3)2.4H2O

N1

S1

H1b

HN

N

ONO2 N

N

MeOH, r.t., 48 h

NH2

Cd

C8

N

Hg(NO3)2.H2O EtOH, r.t., 24 h

HN

O

[Cd(H2BTsP)(NO3)2] 2

Ph

N

N

NH

NO3

Hg N

O

N

[ZnCl(H2BTsP)]NO3 1 Ph

O

S H

S

ONO2

NH2

Hg(H2BTsP)(NO3)]NO3 3

Scheme 2. Synthesis of [H3BTsP]Cl and its complexes, including atom labeling scheme.

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46

2.5. Synthesis of the complexes with [H3BTsP]Cl All the reactions were carried out following the same general procedure: a solution of 0.15 mmol of the corresponding metal nitrate in 2 mL of solvent was added over a solution of 0.15 mmol of [H3BTsP]Cl in 20 mL of the same solvent. The particular conditions of each reaction and yields are described below and are summarized in Scheme 2. 2.5.1. [ZnCl(H2BTsP)]NO3 (1) The methanolic solution was stirred under reflux for 8 h, partially concentrated and then cooled at 4 °C for 1 h. The orange crystals formed, suitable for X-ray diffraction, were filtered off, washed with cold methanol and dried in vacuo. Yield: 27% (22 mg). By concentration of the mother liquor pale-yellow crystals corresponding to [H3BTsP]NO3 were formed. The compound could be obtained with better yield (51%, 41 mg) in ethanol under reflux for 24 h and keeping the resulting yellow solution at 4 °C. When the reaction was carried out at room temperature only [H3BTsP]NO3 and ZnCl2 were formed. Mp: 197 °C (decomposition). KM = 68.0 X 1 cm2 mol 1. Elem. Anal. Calc. for ZnC20H18N7SO3Cl (537.33): C, 44.71; H, 3.38; N, 18.25; S, 5.97. Found: C, 44.48; H, 3.65; N, 18.10; S, 5.72%. IR (KBr, cm 1): 3357(m), 3261 (m), 3234(m), 3171(m) m(NH), 1645(m), 1616(vs), 1574(m), 1557(m) m(CN + thioamide II), 828(w) m(CS). 1H NMR (300 MHz, DMSO-d6): d/ppm 10.52 (br s, 1H, H3), 9.64 (s, 1H, H2), 8.56 (s, 1H, H1a), 8.29 (s, 1H, H1b), 8.07 (s, 1H, H8), 7.80 (s, 1H, H6), 7.69 (m, 2H, Ph), 7.58 (m, 2H, Ph), 7.39–7.26 (m, 7H, H5 + Ph), 6.92 (s, 1H, H7). 13C NMR (300 MHz, DMSO-d6): d/ppm 179.5 (C1), 154.3 (C4), 143.5 (C2 + C3), 142.2 (C8), 141.6 (C6), 134.0, 133.7, 130.7, 130.3, 129.5, 129.3, 127.4, 126.6 (Ph), 116.6 (C7), 110.7 (C5). MS (ESI+): m/z 437.1 [Zn(HBTsP)]+. 2.5.2. [Cd(H2BTsP)(NO3)2] (2) The methanolic solution was stirred at room temperature for 48 h, and then the solvent was removed under reduced pressure to approximately 2 mL and cooled to -18 °C for 48 h. A yellow solid was obtained, which was filtered off and dried in vacuo. Yield: 52% (50 mg). Slow evaporation of the mother liquor gave crystals of the complex, which were suitable for X-ray diffraction. Mp: 178 °C (decomposition). KM = 20.2 X 1 cm2 mol 1. Elem. Anal. Calc. for CdC20H18N8SO6 (610.88): C, 39.32; H, 2.97; N, 18.44; S, 5.25. Found: C, 39.40; H, 2.75; N, 18.76; S, 5.49%. IR (KBr, cm 1):

3303(m), 3150(m) m(NH), 1637(m), 1611(s), 1578(w), 1558(w), 1531(m) m(CN + thioamide II), 817(w) m(CS). 1H NMR (300 MHz, DMSO-d6): d/ppm 11.50 (br s, 1H, H3), 10.07 (s, 1H, H2), 8.60 (s, 1H, H1a), 8.40 (s, 1H, H1b), 8.21 (s, 1H, H8), 8.06 (s, 1H, H6), 7.86 (m, 4H, Ph), 7.50–7.37 (m, 7H, H5 + Ph), 7.13 (t, 3JHH = 6.5 Hz, 1H, H7). 13C NMR (300 MHz, DMSO-d6): d/ppm 179.7 (C1), 152.2 (C4), 143.9 (C2 + C3), 142.0 (C8), 140.1 (C6), 133.4, 133.1, 131.2, 130.8, 129.5, 129.4, 127.4, 127.3 (Ph), 116.7 (C7), 113.1 (C5). MS (ESI+): m/z 487.0 [Cd(HBTsP)]+. 2.5.3. [Hg(H2BTsP)(NO3)]NO3 (3) The ethanolic suspension was stirred at room temperature for 24 h. The scarce amount of solid was separated by filtration and discarded. Then the solvent was removed under reduced pressure leading to the obtaining of an oil. Diethyl ether was added to the oil and stirred vigorously. The pale yellow solid formed was filtered off and dried in vacuo. Yield: 54% (54 mg). If the reaction was carried out at room temperature the reactants were recovered. Mp: 117 °C (decomposition). KM = 70.1 X 1 cm2 mol 1. IR (KBr, cm 1): 3272(m), 3147(m), 3138(sh) m(NH), 1649(s), 1616(s), 1558(m), 1531(sh) m(CN + thioamide II), 803(w) m(CS). 13C CP/MAS NMR (400 MHz): d/ppm 175.1 (C1), 149.8 (C4), 146.7, 144.2 (C2 + C3), 137.7 (C8 + C6), 132.9, 128.0 (Ph), 116.3 (C7), 113.3 (C5). MS (ESI+): m/z 575.1 [Hg(HBTsP)]+. 3. Results and discussion 3.1. Proligands The synthesis of the proligand derived from benzil and thiosemicarbazide is hampered by the formation of the triazine-3-thione or by the reagents recovery. Therefore, the strategy followed was to prepare the proligands by reaction between benzil and the aromatic amines, 2-hydrazinepyridine and 2-hydrazinequinoline. Unlike to the reactions with 2,3-butanedione, in which both neutral or protonated forms of the proligands could be synthesized [25,26], the reactions with benzil need the presence of conc. HCl, leading to the protonation of the aromatic ring, so only [H2BQ]Cl and [H2BP]Cl were obtained. In addition, in the reaction of benzil with 2-hydrazinequinoline, which yields [H2BQ]Cl, the symmetric ligand [H4BQ2]Cl2 is always obtained as a by-product. The analytical data of the proligands confirm the formation of the chloride salts, and together with the mass spectra, support

Table 1 Crystal data and structure refinement for [H4BQ2]Cl2
2CH3OH, [H3BTsQ]Cl
2CH3OH, [H3BTsP]NO3
2CH3OH, 1 and 2
CH3OH.

Formula M Crystal system Space group a (Å) b (Å) c (Å) a (°) b (°) c (°) U (Å3) Z Dcalc (Mgm 3) Absorption coefficient (mm 1) F(0 0 0) Goodness-of-fit (GOF) on F2 Reflections collected Independent reflections (Rint) Final R1 and wR2 [I > 2r(I)] Residual electron density (min. max) (e Å

3

)

[H4BQ2]Cl2
2CH3OH

[H3BTsQ]Cl
2CH3OH

[H3BTsP]NO3
2CH3OH

1

2
CH3OH

C36H38N6O2Cl2 657.62 triclinic  P1

C26H29N6SO2Cl 525.06 triclinic  P1

C22H27N7SO5 501.57 triclinic  P1

ZnC20H18N7SO3Cl 537.29 triclinic  P1

CdC21H22N8SO7 642.93 triclinic  P1

11.3486(8) 12.4388(10) 12.9475(96) 114.246(2) 97.638(3) 92.894(3) 1640.5(2) 2 1.331 0.241 692 1.049 40468 7193 (0.0405) 0.0649, 0.1716 0.658, 1.275

9.933(3) 10.761(3) 13.235(4) 95.702(8) 100.324(9) 107.491(99 1309.6(7) 2 1.332 0.261 552 1.000 12520 5310 (0.0518) 0.0441, 0.1043 0.327, 0.292

8.4180(6) 10.8682(8) 13.9949(9) 85.301(3) 76.974(3) 83.806(47) 1237.95(15) 2 1.346 0.178 528 1.087 62188 7444 (0.0369) 0.0355, 0.0968 0.357, 0.497

9.2420(16) 11.732(2) 11.9014(18) 89.439(7) 70.885(6) 67.999(6) 1121.3(7) 2 1.592 1.346 548 1.030 24501 5749 (0.0354) 0.0400, 0.0936 0.597, 0.861

10.5055(7) 10.8453(7) 11.9664(8) 92.044(3) 100.350(3) 111.510(3) 1240.10(14) 2 1.722 1.024 648 1.094 46451 63769 (0.0344) 0.0264, 0.0638 0.878, 1.142

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46

Fig. 1. Molecular structure of one of the [H4BQ2]Cl2 molecules. Thermal ellipsoids at 50% probability. The solvent molecules have been omitted for clarity.

Table 2 Selected ligand bond distances in [H4BQ2]Cl2
2CH3OH, [H3BTsQ]Cl
2CH3OH, [H3BTsP]NO3
2CH3OH, 1 and 2
CH3OH.

N(1)–C(1) C(1)–S(1) C(1)–N(2) N(2)–N(4) N(4)–C(2) C(2)–C(3) C(3)–N(5) N(5)–N(3) N(3)–C(4) C(4)–N(6)

[H4BQ2]Cl2
2CH3OH

[H3BTsQ]Cl
2CH3OH

[H3BTsP]NO3
2CH3OH

1

2
CH3OH

– – – – – 1.471(5) 1.289(3) 1.370(3) 1.350(3) 1.351(4)

1.327(3) 1.678(3) 1.360(3) 1.377(3) 1.278(3) 1.504(4) 1.291(3) 1.371(3) 1.350(3) 1.334(3)

1.3200(13) 1.6824(11) 1.3612(14) 1.3702(12) 1.2889(14) 1.5000(14) 1.2919(13) 1.3663(12) 1.3567(13) 1.3389(14)

1.314(3) 1.712(3) 1.366(3) 1.351(3) 1.291(3) 1.492(4) 1.278(3) 1.339(3) 1.383(3) 1.349(3)

1.320(3) 1.694(2) 1.365(3) 1.357(2) 1.284(3) 1.481(3) 1.288(3) 1.343(2) 1.387(3) 1.341(3)

the formation of the open chain [1 + 1] condensation products. The IR spectra of the compounds show one band corresponding to the carbonyl group, indicating that one of the two CO groups from the starting diketone remains in the proligands, and additional bands provided by the aromatic amines. The signals observed in their 1 H NMR spectra confirm the presence of the amine groups and the expected aromatic hydrogen atoms. The formation of the chloride salts is supported in the IR spectra by the appearance of one new NH stretching vibration and the displacement of the signals corresponding to the pyridine or quinoline ring, as well as by the additional NH signal observed in the 1H NMR spectra. 3.2. Dissymmetric ligands The hybrid thiosemicarbazone ligands containing 2-hydrazonepyridine and 2-hydrazonequinoline arms were obtained in the protonated forms by reaction of thiosemicarbazide with the corresponding protonated proligand in the presence of hydrochloric acid. The reaction with the pyridine-containing proligand yielded the desired dissymmetric ligand in a reasonable yield. However, the quinoline derivative is only obtained as a by-product in a reaction in which the symmetric ligand [H4BQ2]Cl2 and the triazine-3-tione HBTsOCH3 are the major compounds (Scheme 1). The mass spectra of the ligands show the peaks corresponding to [M]+, confirming the formation of the open chain [1 + 2] hybrid ligands, as well as other peaks corresponding to successive fragmentations. The absence in the spectra of the m(CO) of the starting

monoketones about 1700–1665 cm 1 and the presence of more bands between 3346–3160 cm 1 corresponding to the N-H stretching vibrations, together with the thioamide bands, confirm the formation of the hybrid ligands. The changes produced by the protonation of the aromatic nitrogen can be clearly observed, in particular by the presence of a new signal between 1644 and 1652 cm 1. The 1H NMR spectra were registered in DMSO-d6 and CDCl3 in which the H6a hydrogen can be clearly observed, confirming the protonation of the heteroaromatic ring. The 1H NMR spectra with some drops of D2O were also recorded for the unambiguous assignment of the acidic hydrogens. Schemes 1 and 2 show the numeration scheme used in the assignment of the signals. 13C NMR spectra of both ligands show the absence of the corresponding ketone carbon, confirming the formation of the double Schiff-bases. Moreover, the presence of one signal over 176 ppm corresponding to the CS group, signals corresponding to the CN groups between 158 and 145 ppm and several signals corresponding to the aromatic carbons, support the formation of the hybrid ligands. 3.3. Complexes Analytical data of complexes 1 and 2 confirm the 1:1 stoichiometry. In addition, data of complex 1 show the presence of a NO3 group and suggest substitution of the other nitrate by a chloride, and therefore that the ligand is a neutral donor. Nevertheless, analytical data of complex 2 show the presence of two nitrate groups,

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46

m(CN) shows coordination of these groups to the metal. Moreover, a band at 1385 cm 1 corresponding to NO3 can be observed. The 1 H NMR spectra of complexes 1 and 2 show two signals corresponding to the acidic hydrogen atoms, confirming that the ligand behaves as a neutral donor. It was not possible the acquisition of a well-resolved spectrum for complex 3 in any solvent, probably due to its decomposition in solution. 13C NMR spectra of complexes 1 and 2 were recorded in solution, while for complex 3 it was acquired in the solid state. In spite of these data do not clearly support the N3S coordination of the ligand, it could be confirmed in the crystal structure determination of complexes 1 and 2. Taking into account the data obtained by different techniques and the structures found in related complexes [25,26], in the structure proposed for complex 3 the mercury atom is bound to one neutral tetradentate ligand and one monodentate NO3 in the apex of a square-base pyramid with one nitrate as counterion. 3.4. X-ray diffraction

Fig. 2. Molecular structure of [H3BTsQ]Cl
2CH3OH. Thermal ellipsoids at 50% probability.

so the ligand is also neutral. Conductivity measurements in DMF show complex 2 is a molecular species, while complexes 1 and 3 are 1:1 electrolytes [37]. Mass spectra show a peak corresponding to [M(HBTsP)]+, supporting the 1:1 stoichiometry and the calculated and theoretical isotopic splitting patterns are identical. In the IR spectra, the shift of the bands corresponding to m(CS) and

Crystallographic and refinement data are summarized in Table 1. Full lists of bond lengths and angles, as well as the hydrogen bond tables, are in the Supplementary data. The molecule [H4BQ2]Cl2
2CH3OH crystallizes in the triclinic system. The asymmetric unit of the compound is formed by two crystallographically different half molecules, which grow by symmetry to give two [H4BQ2]Cl2 molecules (Fig. 1). There are not important differences in the bond distances and angles in both molecules, so only selected bond distances of one of them are shown in Table 2. The dihedral angles of the phenyl rings with respect to the quinoline arms are around 60°. The N–N distances are shorter than 1.44 Å and the azomethine C@N bond lengths are likewise short enough to imply a partial double bond. The chloride ions are linked to the ligands by hydrogen bonds with N(3), N(6), N(7) and N(9), and there are p–p interactions between the quinoline rings leading a 3D structure. The crystal structure of [H3BTsQ]Cl is made up by one [H3BTsQ]+ cation, one chloride and two methanol molecules (Fig. 2), linked by hydrogen bonds (see ESI). The compound is in the thione form,

Fig. 3. Molecular structure of [H3BTsP]NO3
2CH3OH. Thermal ellipsoids at 50% probability. The solvent molecules have been omitted for clarity.

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46

which is supported by the C(1)–S(1) bond distance (Table 2) and the presence of the hydrazinic hydrogen H(2). The azomethine C@N bonds are 1.278(3) and 1.291(3) Å, which are in agreement with double bonds and the N–N bonds are shorter than 1.44 Å, which agrees well with those of similar thiosemicarbazones. The two arms of the molecule are at the same side of the C(2)–C(3) bond, probably due to the formation of hydrogen bonds with the solvent molecules and the Cl ions, and the conformation around the C(1)–N(2) is E. N(2) forms hydrogen bonds with the S(1) of a neighbor molecule, giving dimers that are linked through double p–p interactions between the quinoline rings (distance between centroids 3.667 Å) and an extended network of hydrogen bonds involving N(1), N(3), N(6), the chloride ions and the solvent molecules, leading to the formation of a 3D network. As it was previously described, in the reaction of [H3BTsP]Cl with Zn(NO3)2.6H2O, crystals in which the chloride present in the free ligand was replaced by a nitrate were obtained. The crystal structure consists on a [H3BTsP]+ cation, one NO3 anion and two methanol molecules (Fig. 3). As the ligand [H3BTsQ]Cl, it is in the imine-thione form, although with some electronic delocalization (Table 2), and the conformation around C(1)–N(2) is E. Both thiosemicarbazone and hydrazonepyridine limbs are almost planar with a dihedral angle of 82.22°. This disposition is very close to the one found in [H3BTsQ]Cl. There is an extended network of hydrogen bonds between the amine groups, the sulfur atom, the nitrate group and the methanol molecules, giving rise to a tridimensional structure. In complexes 1 and 2
CH3OH the ligand behaves as a N3S chelate, leading to the formation of three five-member chelate rings that confers high stability. The asymmetric unit of complex 1 is made up by a [ZnCl(H2BTsP)]+ cation and one nitrate as counterion (Fig. 4, Table 3). The zinc is penta-coordinate by one neutral ligand occupying the base of a square-base pyramid (sbp) with the chlorido in the apex, with s = 0.081 (s = 0 for sbp and s = 1 for trigonal bipyramid) [38]. The ligand is slightly buckled with the sulfur 0.039 Å under the least-square plane defined by C(1)–N(2)–N(4)– C(2)–C(3)–N(5)–N(3)–C(4)–N(6), and with the Zn 0.546 Å above the same plane. There is a hydrogen bond between N(3) and Cl(1) of a neighboring molecule, giving rise to the formation of dimers that are linked by hydrogen bonds between N(1) and N(2) with the oxygen atoms of the nitrate group, leading to infinite chains running along the (1, 0, 1) direction.

Fig. 4. Molecular structure of [ZnCl(H2BTsP)]NO3. Thermal ellipsoids at 50% probability.

Table 3 Selected bond distances (Å) and angles (°) in complexes 1 and 2
CH3OH.

M(1)–S(1) M(1)–N(4) M(1)–N(5) M(1)–N(6) M(1)–Cl(1) M(1)–O(1) M(1)–O(4) M(1)–O(6) N(6)–M(1)–N(5) N(6)–M(1)–N(4) N(5)–M(1)–N(4) N(6)–M(1)–S(1) N(5)–M(1)–S(1) N(4)–M(1)–S(1) N(6)–M(1)–Cl(1) N(4)–M(1)–Cl(1) N(5)–M(1)–Cl(1) Cl(1)–M(1)–S(1) N(6)–M(1)–O(6) O(1)–M(1)–O(6) N(5)–M(1)–O(6) O(4)–M(1)–O(6) N(4)–M(1)–O(6) S(1)–M(1)–O(6) O(1)–M(1)–N(5) N(6)–M(1)–O(4) O(1)–M(1)–O(4) N(5)–M(1)–O(4) O(1)–M(1)–N(4) N(6)–M(1)–O(1) O(4)–M(1)–N(4) O(1)–M(1)–S(1) O(4)–M(1)–S(1)

1

2
CH3OH

2.3669(8) 2.149(2) 2.157(2) 2.088(2) 2.2951(9) – – – 74.97(8) 139.74(9) 71.05(8) 117.99(6) 144.57(6) 81.29(6) 105.74(6) 102.41(8) 103.03(7) 104.22(3) – – – – – – – – – – – – – – –

2.5469(6) 2.4236(17) 2.4106(16) 2.3261(19) – 2.3659(16) 2.4174(15) 2.6625(16) 68.63(6) 132.93(6) 64.80(6) 152.50(4) 138.79(4) 74.48(4) – – – – 81.67(5) 141.68(5) 122.74(4) 50.25(5) 130.10(6) 79.22(4) 88.24(6) 80.80(6) 164.67(5) 76.70(5) 81.18(6) 91.10(6) 94.78(6) 91.75(5) 101.46(4)

Complex [Cd(H2BTsP)(NO3)2] 2 crystallizes with one methanol molecule. The cadmium is hepta-coordinated to one N3S neutral ligand, one monodentate and one bidentate nitrato groups in a capped octahedral environment (Fig. 5). As can be observed in Table 3, the bidentate nitrato group exhibits a significant asymmetry,

Fig. 5. Molecular structure of [Cd(H2BTsP)(NO3)2]
CH3OH. Thermal ellipsoids at 50% probability. The solvent molecule has been omitted for clarity.

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D.G. Calatayud et al. / Polyhedron 54 (2013) 39–46

as is usually observed in cadmium complexes with NO3 as a ligand [39]. To difference to complex 1, the ligand is significantly buckled. The [Cd(H2BTsP)(NO3)2] units are linked through hydrogen bonds between all the NH and the nitrate groups, leading sheets in the ac plane.

References [1] [2] [3] [4] [5]

4. Conclusions Reaction of 2,3-diphenylethanedione with 2-hydrazinequinoline or 2 hydrazinepyridine in the presence of hydrochloric acid yielded the corresponding Schiff base with one carbonyl group ready to a second condensation reaction with thiosemicarbazide, leading to the obtaining of two new hybrid ligands as the corresponding chloride salts. The pyridine derivative could be obtained with a reasonable yield, while the quinoline derivative was obtained as a by-product in a reaction yielding the benzil bis(2-hydrazidequinolinium) chloride salt and the corresponding triazine-3-thione. Reaction of [H3BTsP]Cl with group 12 nitrates lead to the formation of three new metal complexes in which the ligand coordinates as a neutral tetradentate chelate. In the zinc derivative the coordination sphere is completed by a chlorido provided by the ligand in the apex of a square-base pyramid. The cadmium complex contains two nitrato groups, one monodentate and one bidentate giving rise to a capped octahedron. The mercury complex could not be crystallographically characterized but we propose a structure similar to the one described for complex 1 in which the chloride was replaced by a monodentate nitrato group, which is analogous to other complexes structurally characterized with related ligands.

[6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25]

Acknowledgements We thank César J. Pastor from ‘‘Servicio Interdepartamental de Investigación’’ (SidI) of the Universidad Autónoma de Madrid (Spain) for the crystal measurements. We also thank MINECO, Instituto de Salud Carlos III, for funding (Project PS09/00963).

Appendix A. Supplementary material CCDC 908407–908411 contain the supplementary crystallographic data for [H3BTsQ]Cl
2CH3OH, [H4BQ2]Cl2
2CH3OH, [H3BTsP]NO3, 1 and 2
CH3OH respectively. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/ retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336 033; or e-mail: [email protected]. Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.poly.2013.02.025.

[26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39]

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