Hydrolysis study: Synthesis of novel styrenic Schiff bases derived from benzothiazole

2.1 Materials and equipments

Melting points were found using Gallenkamp .7 B .9144 B apparatus. The refraction indexes were measured by a refractometer (S-WAY Digital.ABBc model). IR spectra were recorded on a JASCO FT/IR4200 spectrophotometer with samples either as 1% dispersions in KBr pellets or as liquid films. The UV–Vis spectra were carried out on Spectronic® Genesys 5 TM, spectrophotometer with 10⁻⁴–10⁻⁵ mol/l in ethanol. The ¹H, ¹³C NMR spectra were recorded on a Bruker AC instrument (300 MHz, 400 MHz, 75 MHz) with compounds in DMSO-d₆ and CDCl₃ solutions. ¹H NMR chemical shifts are expressed as δ values (ppm) relative to TMS as an internal standard. Products separations were performed by column chromatography on silica gel 66 Merck 230–400 mesh and eluted with the n-hexane/ethyl acetate: 6/0.50 mixture. Hydrolysis of the imines was studied at 25 °C, in homogeneous aqueous solutions, buffered at pH 4.4, 7.4 and 8.5. The acetate and phosphate buffers were prepared in aqueous medium according to the methods described by Perrin (1963) and Michaelis and Mizutani (1925). They were followed on a Shimadzu UV-2401PC, dual beam spectrophotometer, in thermostated cells at 25 °C ± 0.1 °C. pH was measured using a digital pH meter (Beckman), calibrated at 25 °C with buffer solutions at pH 4.62 (acetate) and pH 9.00 (borax) with an accuracy of 0.01 pH units. The aromatic amines used in the following preparations are commercial products. The solvents used (ethanol, methanol, benzene, toluene, chloroform, methylene chloride) were purified according to the literature procedures (Furniss et al., 1968; Lund and Bjerrum, 1931).

2.2 Synthesis of 4-vinylbenzaldehyde 1

4-Vinylbenzaldehyde (yellow oil) was synthesised following the method of Sommelet (Ferruti, 1977) from the 4-chloromethylstyrene (CMS) with a 60% yield; IR (film on NaCl pellets) υ (cm⁻¹): 1700.91 (C⚌O), 2732.64 and 2826.2 (H—C⚌O), 1609.5 (C⚌C), 1839.76 (⚌CH₂, overtone), 988.33 (⚌C—H), 917.95 (⚌CH₂), 3008.41 and 840.81 (Ø—H); UV (Ethanol) λ₁ max (ɛ max) = 281 nm (20098), λ₂ max (ɛ max) = 218 nm (8987), λ₃ max (ɛ max) = 204 nm (12426); ¹H NMR (400 MHz, DMSO-d₆) δ (ppm):10(s, H₁), 7.9 (d, H₂ and H_2′; J = 8.19 Hz), 7.71 (d, H₃ and H_3′, J = 8.15 Hz), 6.85 (dd, H₄, J = 17.64 Hz, J = 10.96 Hz), 6.06(d, H₆, J = 17.5 Hz), 5.48 (d, H₅, J = 10.96 Hz).

2.3 General procedure for preparation of compounds 6, 7, 8 and 9

In a 100 ml flask equipped with a Dean-Stark, 77 mmol of 4-vinylbenzaldehyde and 66 mmol of aromatic amine were dissolved in 30 to 60 ml of benzene in the presence of 2 mg of 2,6-di-t-butyl catechol (antioxidant) and some traces of para toluene sulfonic acid (PTSA) as catalyst were reacted under reflux for 6 h. After evaporation of the solvent, the residue was recrystallized in ethanol or methanol or chromatographed on silica gel and eluted by the n-hexane/ethyl acetate: 6/0.50 mixture.

3.1 Preparation of compounds 6, 7, 8 and 9

The condensations of 4-vinylbenzaldehyde 1 on compounds 2, 3, 4 and 5 were performed in the presence of para-toluenesulfonic acid and 2,6-di-t-butylcatechol under reflux in benzene for 6 h according to reaction Scheme 1.

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Scheme 1

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From 2 and 3, the reaction leads to N-(4-vinylbenzylidene)-benzothiazol-2-amine 6 and N-(4-vinylbenzylidene)-4-methoxy-benzothiazol-2-amine 7 in the form of two isomers whose proportions are, respectively, 1/0.5 and 1/0.91. However, the condensation of 1 with 4 and 5 provides N-(4-vinylbenzylidene)-4-methyl-benzothiazol-2-amine 8 and N-(4-vinylbenzylidene)-6-fluoro-benzothiazol-2-amine 9 with 42% and 53% yields, respectively.

3.2 Identification of products 6, 7, 8 and 9

Compounds 6 and 8 show similar ¹H NMR spectra features, close to those of products 7 and 9, allowing their structure to be easily deduced from ¹H NMR spectra. Imine protons of both isomers of products 6 and 7 appear as singlets in the range between 8.76 and 8.87 ppm, while those of 8 and 9 are located at 8.96 and 9.16 ppm, respectively. The ¹³C NMR spectra confirm the presence of two isomers in the case of 6 and 7, exhibiting, two peaks in between 165.38 and 166.71 ppm, while 8 and 9 ¹³C NMR spectra show both peaks at around 166 ppm due to the imine function. The vinyl protons of compounds 6, 7, 8 and 9 are easily identifiable; they resonate at 6.84, 5.85 and 5.27 ppm. The IR spectra of Schiff bases 6,7, 8 and 9 show an intense absorption band at 1526 cm⁻¹ and two other bands located in 3210–3222 cm⁻¹ and 916–988 cm⁻¹ regions characteristic of the vinyl group elongation and deformation vibrations, respectively. The absorption band of the azomethine imine is located around 1587 cm⁻¹, while the imine of the thiazole nucleus absorbs around 1685 cm⁻¹. This low value (1587 cm⁻¹) could reflect a strong polarization of the imine (C⚌N), which follows logically from the conjugation of the remaining C⚌N bond with the aromatic ring. The examination of the electronic spectra of compounds 6, 7, 8 and 9 shows similarities among them. A strong sharp peak at 225 nm attributed to the electronic transition π → π* is present. A second medium intensity band observed around 260 nm is due to a locally excited state of the molecule benzyliden moiety. A third low intensity band, whose maximum is located at 310 nm, is attributed to an excited state involving the whole of the molecule. Finally, these absorptions correspond to a spectral range close to that of di-substituted Schiff bases studied by several authors (Pitea et al., 1970; Ashraf El-Bayoumi et al., 1971; Belletête et al., 1977; Chafi et al., 1991).

3.3 Hydrolysis of derivatives 6 and 9

Figs. 1 and 2 show the UV absorption spectra of the imines 6, 9 in absolute ethanol, respectively, each one being associated with the 4-vinylbenzaldehyde 1 spectrum.

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Figure 1

UV absorption spectra of 4-vinylbenzaldehyde 1 and N-(4-vinylbenzylidene)-benzothiazol-2-amine 6 in absolute ethanol (C = 10⁻⁴ M).

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Figure 2

UV absorption spectra of 4-vinylbenzaldehyde 1 and N-(4-vinylbenzylidene)-6-fluoro-benzothiazol-2-amine 9 in absolute ethanol (C = 10⁻⁴ M).

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The analysis of these spectra shows that the low intensity band (I) which is a characteristic absorption band for each imine (λ₆ (I) = 375 nm and 9 λ₉ (I) = 365 nm) and those observed for 4-vinylbenzaldehyde 1 are well separated. Band (I) is located in a range of wavelengths where aldehyde, amine, and the buffer constituents do not absorb. This band is thus adequate to follow the hydrolysis kinetics. Hydrolysis reactions of imines 6 and 9 were studied in buffered aqueous solutions at pH 4.4, 7.4 and 8.5, and constant temperature (T = 25 °C) and ionic strength (μ = 0.01). The acetate and phosphate buffers were prepared in aqueous medium according to the methods described by Perrin (1963) and Michaelis and Mizutani (1925). Hydrolysis reactions at the different pH value being slow, complete UV spectra were then recorded over time intervals consistent with the advancement of reaction state. We also conducted several kinetic tests at the same pH values with varied initial Schiff base concentrations C₀, to verify that the optical density ${\mathbf{D}}_{\text{S}}^0$ , extrapolated to time zero, is effectively proportional to C₀. The ${\mathbf{D}}_{\text{S}}^0$ data found for different C₀ values are collected in Tables 1 and 2, respectively, for 6 and 9 at pH 4.4. Figs. 3 and 4 show clearly the linear behavior of ${\mathbf{D}}_{\text{S}}^0$ with respect to C₀ of the imines.

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Figure 3

Optical density according to the initial concentration of derivative 6 at pH 4.4.The line is a linear fit.

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Figure 4

Optical density according to the initial concentration of derivative 9 at pH 4.4. The line is a linear fit.

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Examples of the UV spectra evolution recorded during the hydrolysis of compounds 6 and 9 are reproduced in Figs. 5 and 6, respectively. The first spectrum is attributed to the pure Schiff base since the hydrolysis is slow. The final spectrum 8 is consistent with the mixture of 4-vinylbenzaldehyde and amine. The final state of the hydrolysis reaction for each of the derivatives 6 and 9 is established by recording the spectrum of equimolar mixture of 4-vinylbenzaldehyde and the corresponding amine at total concentration of 10⁻⁴ mol/l in Figs. 7 and 8, respectively. The comparison of the latter mixture spectra with the kinetic test spectra appearing in Figs. 5 and 6 shows that complete hydrolysis occurred. The experiment indicates in all cases that the chosen imine absorption band (I) disappears completely when time is long enough, suggesting that the reaction is complete in the present operating conditions.

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Figure 5

Temporal evolution of the N-(4-vinylbenzylidene)-benzothiazol-2-amine 6 UV absorption spectrum at pH 4.4; C₀ = 0.8 × 10⁻⁴ M.

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Figure 6

Temporal evolution of the N-(4-vinylbenzylidene)-6-fluoro-benzothiazol-2-amine 9 UV absorption spectrum at pH 4.4; C₀ = 0.8 × 10⁻⁴ M.

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Figure 7

UV absorption spectrum of benzothiazol-2-amine and 4-vinylbenzaldehyde mixture buffered at pH 7; C₀ = 0.8 × 10⁻⁴ M.

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Figure 8

UV absorption spectrum of 6-fluoro-benzothiazol-2-amine and 4-vinylbenzaldehyde mixture buffered at pH 7; C₀ = 0.8 × 10⁻⁴ M.

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During hydrolysis, the presence of isosbestic points (i) on the time dependent spectra corresponding to the concentration variation of our compounds show that there is no accumulation of any intermediate.

The use of band (I) optical density enables the determination of the observed apparent hydrolysis constants k_obs. It was verified that the reaction order is of the first kind with respect to the imine by plotting $\mathrm{Log}{\mathbf{D}}_{\text{S}}^{\text{C}}$ as a function of time, where ${\mathbf{D}}_{\text{S}}^{\text{C}}$ is the optical density corrected for the always weak ${\mathbf{D}}_{\text{S}}^{\infty }$ value read at infinite time ( ${\mathbf{D}}_{\text{S}}^{\text{C}}={\mathbf{D}}_{\text{S}}-{\mathbf{D}}_{\text{S}}^{\infty }$ ). Indeed the ${\mathbf{D}}_{\text{S}}^{\text{C}}$ data vs t plotted in Figs. 9 and 10 for products 6 and 9, respectively show linear behavior; they are fitted to the equation: $$\mathrm{Log}{\mathbf{D}}_{\text{S}}^{\text{C}}=\mathrm{Log}{\mathbf{D}}_{\text{S}}^{0\text{,C}}-\frac{k_{\text{obs}}}{2\text{,}3}t$$ The linear fit provides access to the determination of the initial corrected optical density ${\mathbf{D}}_{\text{S}}^{0\text{,C}}$ by extrapolation to time t = 0 and to k_obs from the slope. The values of kinetic parameter k_obs obtained from Figs. 9 and 10 are reported in Table 3.

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Figure 9

$\mathrm{Log}{\mathbf{D}}_{\text{S}}^{\text{C}}$ variation as a function of time of compound 6 at different pH. The lines are linear fits.

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Figure 10

$\mathrm{Log}{\mathbf{D}}_{\text{S}}^{\text{C}}$ variation as a function of time of compound 9 at different pH. The lines are linear fits.

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According to the results, the hydrolysis is first order process at any pH value. Since k_obs increases as pH decreases, the reaction is catalyzed by the acidity. It should also be noted that at pH 4.4, the hydrolysis rate of compound 9 is greater than that of compound 6, while an opposite effect is observed at pH 7.4 and 8.5 (see Table 3).