2-formylpynacolic acid

To a 50 mL two-neck round bottom was added 6-methylpyridin- 2-carboxilic (100 mg, 0.73 mmol) and selenium dioxide (161 mg, 1.46 mmol) followed by 25 mL of Dioxane:Water (4:1). The resulting mixture was heated to reflux for 4 h. The reaction was allowed to cool down and the solid formed was filtered and washed with chloroform (3x2 mL). The filtrates were combined and the solvent removed under reduced pressure. Column chromatography using silica gel and CHCl3: MeOH ([95:5]) afforded the desire product 5 (57 mg, 54%). FT-IR (KBr) υ (cm^-1): 3100 (=C-H), 2910 (=C-H), 1740 (C=O), 1700 (C=O), 1580 and 1438 (C=N and C=C). ¹H NMR (400 MHz, CDCl ) δ ppm: 10.18 (s, 1 H, CHO), 8.51 (d, J = 4.78 Hz, 1 H, H-5), 8.27 (d, J = 4.78 Hz, 1 H, H-5), 8.20 (m, 1 H, H-4). 13C NMR (100 MHz, CDCl3) δ ppm: 191.5, 163.1, 151.28, 146.8, 139.83, 128.07, 125.45. Elemental analysis calculated (%) for C₈H₁₂N₂O: C 61.75, H 5.92, N 20.58; found: C 61.62, H 5.84, N 20.13.

4,6-dihydrazino-2-phenylpyrimidine

To a 50 mL two-neck round bottom was added 4,6-dichloro-2-phenylpyrimidine (100 mg, 0.44 mmol) and ethanol 25 mL followed by hydrazine monohydrate (0.043 mL, 0.89 mmol). The resulting mixture was heated to reflux for 3 days. The reaction was allowed to cool down and concentrated under reduced pressure. The hydrazine excess was removed by decantation obtaining a solid. Recrystallization from methanol afforded the desire product 4 (62 mg, 64%) as a white solid. m.p.: 142 ºC. ¹H NMR (400 MHz, CDCl ) δ ppm: 8.26 (m, 2 H, NH), 7.41 (m, 3 H, H-5), 6.74 (s, 2H, H-X), 5.81 (s, 1 H, H-pyr), 3.7 (brs, 4H, NH ).¹³C NMR (100 MHz, CDCl₃) δ ppm: 166.6, 163.3, 138.3, 130.0, 128.2, 127.9, 78.0. MS (70 eV) m/z (%) 216 (16), 164 (23), 103 (100), 46 (58). Elemental analysis calcd (%) for C₁₀H₁₂N₆: C 55.54, H 5.59, N 38.86; found: C 56.10, H 5.50, N 39.09.

2-phenylpyridimine-4,6-yl-bis-(hydrazine-2-yl-1-ilydine-bis-(metaniylinde) dypynacolic acid

To a 50 mL neck round bottom was added 2-formylpynacolic acid (161 mg, 1.46 mmol) and 4,6-dihydrzin-2-phenylpyrimidine (72 mg, 0.33 mmol) and followed by 25 mL of methanol. The resulting mixture was heated to reflux for 3 h. The reaction was allowed to cool down and the solid formed was filtered and washed with ethanol (3x2 mL). Recrystallization from methanol afforded the desire product 1 (131 mg, 82%) as a white solid. m.p. 242º C.¹H NMR (400 MHz, CDCl ) δ ppm: 11.68 (s, 2 H, N-H), 8.34 (t, 2 H, H-3), 8.27 (s, 2 H, H imino), 8.24 (dd, 2 H, H-10), 8.09 (t, 2 H, H-11), 8.00 (dd, 2 H, H-12), 7.51 (m, 3 H, H-1, H-2), 6.99 (s, 1 H, H-7). ¹³C NMR (100 MHz, CDCl₃) δ ppm: 163.4, 162.7, 154.3, 148.8, 141.9, 18.6, 138.2, 10.8, 128.7, 128.0, 124.8, 123.0, 81.3. Elemental analysis calculated (%) for C₂₄H₁₈N₈N₄: C 59.75, H 3.75, N 23.23; found: C 59.10, H 3.50, N 22.89.

Zn Complex [Zn(C ₂₄ H ₁₈ N ₈ N ₄ )( CF ₃ SO ₃ ) ₄

To a 50 mL neck round bottom was added 1 (100 mg, 0.21 mmol) and 40 mL of acetonitrile followed by 2 mL methanolic solution of Zn(OTf)₂ (158 mg, 0.44 mmol). The resulting mixture was heated to reflux for 4 h. The reaction was allowed to cool down and concentrated under reduced pressure. The solid formed was filtered and washed with ether (3x2 mL) afforded the desire product 6a (205 mg, 82%) as a white solid. m.p.: 242 ºC. ¹H NMR (400 MHz, CDCl ) δ ppm: 11.69 (s 2H, N-H), 8.36 (m 2H, H-3), 8.29 (s 2H, H_imidine), 8.27 (m 2H, H-10), 8.11 (t 2H, H-11), 8.03 (d 2H, H-12), 7.54 (t 3H H-1 and H-2),7.02 (s 1 H, H-7). Elemental analysis calcd (%) for C₂₈H₁₈F₁₂N₈O₁₆S₄Zn₂: C 27.81, H 1.50, N 9.26; found: C 27.4, H 1.64, N 9.13.

Cd Complex [Zn(C ₂₄ H ₁₈ N ₈ N ₄ )( CF ₃ SO ₃ ) ₄

To a 50 mL neck round bottom was added 1 (100 mg, 0.21 mmol) and 40 mL of acetonitrile followed by 2 mL methanolic solution of Cd(OTf)₂ (174 mg, 0.42 mmol).. The resulting mixture was heated to reflux for 3 h in atmosphere inert. The reaction was allowed to cool down and concentrated under reduced pressure. The solid formed was filtered and washed with ether (3x2 mL) afforded the desire product 6b (183 mg, 68%) as a brown solid. m.p.: 242º C. ¹H NMR (400 MHz, CDCl ) δ ppm: 11.69 (s 2H, N-H), 8.36 (m 2H, H-3), 8.29 (s 2H, H_imino), 8.27 (m 2H, H-10), 8.11 (t 2H, H-11), 8.03 (d 2H, H-12), 7.54 (t 3H H-1 and H-2),7.02 (s 1 H, H-7). Elemental analysis calculated (%) for C₂₈H₁₈F₁₂N₈O₁₆S₄Cd: C 25.80, H 1.39, N 8.60; found: C 25.11, H 1.66, N 8.37.

Pb Complex [Pb(C ₂₄ H ₁₈ N ₈ N ₄ )( CF ₃ SO ₃ ) ₄

To a 50 mL neck round bottom was added 1 (100 mg, 0.21 mmol) and 40 mL of acetonitrile followed by 2 mL methanolic solution of Zn(OTf)₂ (262 mg, 0.52 mmol). The resulting mixture was heated to reflux for 3 h in atmosphere inert. The reaction was allowed to cool down and concentrated under reduced pressure. The solid formed was filtered and washed with ether (3x2 mL) afforded the desire product 6c (241 mg, 78%) as a brown solid. m.p.: 242º C. ¹H NMR (400 MHz, CDCl3) δ ppm: 11.69 (s 2H, N-H), 8.36 (m 2H, H-3), 8.29 (s 2H, H_imino), 8.27 (m 2H, H-10), 8.11 (t 2H, H-11), 8.03 (d 2H, H-12), 7.54 (t 3H H-1 and H-2),7.02 (s 1 H, H-7).

Elemental analysis calculated (%) for C₂₈H₁₈F₁₂N₈O₁₆S₄Pb₂: C 25.80, H 1.39, N 8.60; found: C 25.11, H 1.66, N 8.37.

Pb Complex 7c, [Pb ₄ (14) ₄ ](CF ₃ SO ₃ ) ₈

to a solution of 1 (100 mg, 0.21 mmol) in ethanol (40mL) was added 1 mL solution 1 M of Pb(OTf)₂ in methanol. The reaction mixture was heated for 4 h in Ar atmosphere. The solvent was removed by pressure reduced resulting a brown solid, which was washed with ether (3x2 mL) afforded the desire product 7c (1.5 g, 72%). ¹H NMR (400 MHz, CDCl ) δ ppm: 11.70 (s 2H, N-H), 8.36 (m 2H, H-3), 8.30 (s 2H, H_imine; m 2H, H-10), 8.10 (t 2H, H-11), 8.05 (d 2H, H-12), 7.53 (t 3H H-1 and H-2),7.03 (s 1 H, H-7). Elemental analysis calculated (%) for C₁₂₈H₁₄₄F₂₄N₃₂O₄₀Pb₄S₈: C, 35.65; H, 3.37; N, 10.39; found: C, 34.50; H, 3.55; N, 10.18.

pH-Dependence of hydrazone derivative 1

To an aliquot of the solution of 1 was diluted in solutions of known pH and the UV-vis spectra were recorded. The buffer solutions at pH between 2 and 12 were prepared according to the literature ³ (Table 1).

Deprotonation Study of 7c

To a solution of 7c in DMSO-d6 was added 0.5 equivalents of a solution 4% of NaOD in deuterated water and NMR spectra were immediately recorded. The procedure was repeated until add 2.0 equivalents of NaOD.

Electrochemical study of metal complexes

The measurements were performed using a 0.1 M solution of tetrabutylammonium hexafluorophosphate in acetonitrile. It was employee a glassy carbon electrode, a platinum wire and a silver wire as working; counter electrode and pseudo-reference electrode respectively. The solutions were degassed before each measurement and added at the end of ferrocene as an internal standard measures. The scan rate was 100 mV/s. The electrochemical properties were measured at 25° C and -10° C.

Synthesis and purification of bis-(hydrazone) 1

Hydrazone derivative 1 was prepared in a multistep synthetic procedure. The first step required the preparation of hydrazine and aldehyde derivatives 4 and 5 as shown in Scheme 1. Compound 2 was obtained as reported by Lehn´s group ^10-16 and immediately used to form the hydrazine 4 in a 64 % yield. On the other hand, the partial oxidation of the methyl group of 6-methyl-2-pyridinecarboxylic acid (3) with SeO₂ led to the formation of the aldehyde derivative 5 in a 52 % yield. The corresponding bis-(hydrazone) derivative 1 was synthesized by condensation of 4 with 5 (2 equivalents) in reflux of ethanol with the addition of catalytic amounts of glacial acetic acid, obtaining exclusively the E-isomer.

Scheme 1. Synthesis of bis-(hydrazone) 1.

Compounds 4, 5 and 1 were characterized by ¹H, ¹³C and COSY NMR, FT-IR, and elemental analysis (see experimental section and supporting information). ¹H-NMR of compound 1 exhibits 8 of the 9 expected signals, the carboxylic proton is not observed due to fast proton exchange with the solvent. The -N-H protons appears at 11.66 ppm as other protons of E configuration found in the literature ^3-16. The imine proton is observed at 8.27 ppm and the pyrimidine (C7) proton is found at 6.99 ppm. ¹³C-NMR shows 14 signals corresponding to the equivalent carbons of the framework (see supporting information). Assignment of the signals was based on COSY and by comparison with other bis- (hydrazone) analogues found in the literature.

Synthesis and characterization of metal complexes

Metal complexes were obtained through the reaction of 1 with transition divalent metal salts (Zn^II, Cd^II, and Pb^II) in methanol in a stoichiometric ratio 1:2 (Scheme 2). It has been known that bis-(hydrazones) show a transoid conformation, ^6-16 however, formation of metal complexes requires a conformational change in the molecule from transoid to cisoid^6,7. After precipitation, the complexes were washed with ethyl ether and cold ethanol with yields between 68-78 %. These compounds were characterized by FT-IR and NMR spectroscopy and elemental analysis (see experimental section).

Scheme 2 Synthesis of metal complexes of bis-hydrazone 1. 

As observed in the FT-IR spectra shown in Figure 2, complexation of 1 with metal ions causes a shift in the N-H and double bonds (C=C and C=N) bands towards more and less energetic regions, respectively, which confirms the formation of the complexes 6a-c. Such shift is due to the increase of the ionic radius of the metal which provokes a shift in these frequencies.¹⁷ It can be also observed shift and widening in some signals depending on the nature of the metal ion due to the formation of the metal complex (see supporting information).

Figure 2 FT-IR (left) and UV-vis (right) spectra of bis-(hydrazone) 1 and its metal complexes. 

On the other hand, the UV-vis spectra shows an increase in the maximum absorption band which is accompanied by the appearance of new bands in the visible region corresponding to the metal d-d absorptions. Additionally, the increase of the ionic radius results in a decrease in the spectral onset (see supporting information). ^3-5

Alternatively, the ¹H-NMR spectra shows a marked dependence of the chemical shifts on the nature of the metal ions present in the complex. Widening of some signals is due to the unpaired electrons in the metal ions, which causes significantly changes on the local magnetic field (Figure 3). Noteworthy, NMR is not conclusive about the nature of the complexes and therefore it is not possible to determine a possible structure. However, the molecular structure of the complexes was corroborated by elemental analysis in all cases.

Figure 3 ¹H-NMR spectra (400 MHz) of 1 and its metal complexes 6a-c in DMSO-d₆.  

We planned to synthesize metal-grids [2x2] changing the molar ratio of 1 and metal ions (1:1) as depicted in Scheme 2. Nevertheless, when the reaction was carried out with Zn²⁺ and Cd²⁺ only the linear complexes were obtained with. The resistant to yield grid- like complexes is explained by the small ionic radii of these metals (88 and 109 pm, for Zn²⁺ and Cd²⁺, respectively) ¹⁸ and the also preference to coordinate in a tetrahedral manner. It is important to remember that compound 1 is able to coordinate in both arms through four atoms, three nitrogen atoms of the pyridine-imine and pyrimidine framework and a fourth one from the carboxylic group, thus the four sites of coordination prefer to generate a more stable tetrahedral complex around the ion (Zn²⁺ or Cd²⁺) than a complex of coordination 8 that would have in a grid-type complex. On the other hand, Pb²⁺ has an ionic radius of 133 pm and prefers the octahedral coordination, which facilitates to obtain metalo-grids ^11,19.

As shown in the Figure 4a, the ¹H-NMR spectrum showed a widening of the signals caused by the diamagnetic effect provoked by the lead atom on the external magnetic field of NMR. Besides, the UV-vis spectrum also showed a bathochromic shift in the main absorption peak respect to 1 due to the charge transference between the metal center and ligand (Figure 4b). While, 7c exhibits an increasing on the absorption peak when compared with 6c.

Figure 4 Square wave voltammetry for 6 a-c and 7c in acetonitrile at 25( C (left) and 10( C (right) 

Electrochemical studies of metal complexes

The electrochemical properties of compounds 6a-c and 7c were studied by cyclic voltammetry (CV) and Osteryoung Square Wave Voltammetry (OSWV). The complexes exhibit irreversible oxidation peaks corresponding to hydrazone group. The complexes also presented two irreversible reduction peaks which correspond to the reduction of the imine group and to the M²⁺/M⁺ events. If we compare the Pb²⁺ complexes (linear vs grid) an anodic shift of 260 mV is observed, being easier to oxidize the grid. While the reductions showed a cathodic shift in the first reduction potential and an anodic shift in the second reduction.

On the other hand, the Cd²⁺ and Zn²⁺ complexes showed a similar behavior, where the Cd complex is oxidized and reduce easier than its counterparts (Table 2). We also investigated the temperature effect on electrochemical properties of these compounds. Thus, we carried out the electrochemical studies at -10° C. However, we found that the decrease of temperature has not a significant effect on the number of peak potentials of oxidation-reduction. In general, we can say that a lowering of the temperature causes a small anodic shift on both oxidation ad reduction potentials.