Scholarly article on topic 'Synthesis of new derivatized pyrazole based ligands and their catecholase activity studies'

Synthesis of new derivatized pyrazole based ligands and their catecholase activity studies Academic research paper on "Chemical sciences"

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Arabian Journal of Chemistry
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{"Nitrogen ligand" / Pyrazole / "Oxidation reaction" / "Catecholase activity and copper(II) salts"}

Abstract of research paper on Chemical sciences, author of scientific article — Abdelkhalek Zerrouki, Rachid Touzani, Sghir El Kadiri

Abstract A synthesis of three new tripodal ligands: 3-[bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propan-1-ol L1, 3-[bis-(5-methyl-3-carbomethoxy-pyrazol-1-ylmethyl)-amino]-propan-1-ol, L2 and 3-[bis-(5-methyl-3-carboethoxy-pyrazol-1-ylmethyl)-amino]-propan-1-ol L3 is reported. The in situ-generated copper(II) complexes of three new compounds (L1–L3) were examined for their catalytic activities and were found to catalyse the oxidation reaction of catechol to o-quinone with the atmospheric dioxygen. These activities depend on the nature of the ligand and the copper salts.

Academic research paper on topic "Synthesis of new derivatized pyrazole based ligands and their catecholase activity studies"

Arabian Journal of Chemistry (2011) 4, 459-464

ORIGINAL ARTICLE

Synthesis of new derivatized pyrazole based ligands and their catecholase activity studies

Abdelkhalek Zerrouki a, Rachid Touzani a b *, Sghir El Kadiri a'**

a Laboratoire de Chimie Appliquée et Environnement - URAC 18, Département de Chimie, Faculté des Sciences, Université Mohamed Premier, BP: 524, 60 000 Oujda, Morocco

b Faculte Pluridisciplinaire de Nador, Universite Mohamed Premier, BP: 300, Selouane 62700, Nador, Morocco

Received 23 June 2010; accepted 12 July 2010 Available online 17 July 2010

KEYWORDS

Nitrogen ligand; Pyrazole;

Oxidation reaction; Catecholase activity and copper(II) salts

Abstract A synthesis of three new tripodal ligands: 3-[bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propan-1-ol L1, 3-[bis-(5-methyl-3-carbomethoxy-pyrazol-1-ylmethyl)-amino]-propan-1-ol, L2 and 3-[bis-(5-methyl-3-carboethoxy-pyrazol-1-ylmethyl)-amino]-propan-1-ol L3 is reported. The in situ-generated copper(II) complexes of three new compounds (L1-L3) were examined for their catalytic activities and were found to catalyse the oxidation reaction of catechol to o-quinone with the atmospheric dioxygen. These activities depend on the nature of the ligand and the copper salts.

© 2010 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

* Corresponding author at: Laboratoire de Chimie Appliquée et Environnement - URAC 18, Departement de Chimie, Faculte des Sciences, Université Mohamed Premier, BP: 524, 60 000 Oujda, Morocco. Tel.: +212 677 968 240. ** Corresponding author.

E-mail addresses: touzanir@yahoo.fr (R. Touzani), elkadiri_sghir@ yahoo.fr (S. El Kadiri).

1878-5352 © 2010 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

Peer-review under responsibility of King Saud University. doi:10.1016/j.arabjc.2010.07.013

1. Introduction

It is now well-documented that copper containing metalloproteins play a very important role in transport, activation, and metabolism of dioxygen in living organisms (Albada et al., 2007; Chen and Solomon, 2004; Decker and Tuczek, 2000; Holm et al., 1996). A notable advance in the understanding of the properties of these proteins has been achieved through the comparison of synthetic models to the naturally occurring molecules (Decker et al., 2000; Kitaj-ima and Moro-oka, 1994; Van Gelder et al., 1997). Several catechol derivative substrates were used in the literature to understand the mechanisms of oxidase enzyme research (Gerdemann et al., 2002; Rompel et al., 1999). It was observed that the catalytic activities of the complexes are not only dependent on the organic ligand but also on the type of inorganic anion coordinated to the copper center (Koval et al., 2006). In this paper, we report the synthesis of three new pyrazolyl ligands. The copper(II) in situ-generated complexes of these new products, were examined as catalysts to-

ward atmospheric dioxygen oxidation reaction of catechol to o-quinone.

2. Results and discussion

2.1. Synthesis

Pyrazolyl and triazolyl derivatives N-C-N junction ligands L1-L3 (Scheme 1) were prepared using two different methods. The first one consists of condensation of l-(hydroxymethyl)-3,5-dimethylpyrazole (Dvoretzky and Richter, 1950), 1-hydroxymethyl-5-methyl-1H-pyrazole-3-carboxylic acid

methyl ester (Touzani et al., 2000), 1-hydroxymethyl-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester (Touzani et al., 1999) with a series of alcohol amines such as aminopro-panol in 2:1 ratio at room temperature during four days in ace-tonitrile (Touzani et al., 2001). In the second method, the similar reactions were carried out with some drops of solvent at 60 0C for 4 h. The target products were isolated with good yields in the two methods from 75% to 89% (Table 1).

All the new compounds were characterized by *H NMR, 13C NMR and mass spectrometry. The proton NMR spectra of L1 product, show two signals at 4.90 and 4.36 ppm corresponding to methylene protons (N-CH2-N). When the pyraz-olic rings are linked to the ester (-CO2R) moieties (L2, L3), these proton signals appears between 5.06 and 5.29 ppm.

The metal complex solution and catechol reductant were added together in the spectrophotometric cell at 25 0C (El Kodadi et al., 2008; Bouabdallah et al., 2007; Boussalah et al., 2009a,b). Formation of o-quinone was monitored by the increase in absorbance at 390 nm as a function of time. Figs. 1-6 show the absorbance versus time spectrum for the first 60 min of the oxidation reaction, while the rates are shown in Table 2. In all cases, catecholase activity was noted.

As can be seen from Table 2, all of the complexes with pyrazolyl ligands catalyze the oxidation reaction of catechol to o-quinone with the rate varying from a high of 0.0289 imol substrate per mg catalyst per min for the L1[CuSO4] complex to a low of 0.0018 imol substrate per mg catalyst per min for L1[CuCl2]. These rates are comparable to the values reported by (Malachowski et al., 1996) from 0.018 to 0.186 imol substrate per mg catalyst per minute, for the similar tripodal li-gands. The catalytic activity depends strongly on both the R substituent and the type of inorganic anion. The copper complexes of ligand L1 were observed to be the lowest active, except in the case when we have used SO^anion. The order of reactivity for the oxidation of catechol by CuCl2 and Cu(NO3)2 complexes is L2 > L3 > L1. The order of reactivity for the oxidation of catechol by Cu(CH3COO)2 complexes is L1 with the other ligands the rate of activity decreases strongly. The order of reactivity for the oxidation of catechol by CuSO4 complexes is L1 > L2 > L3.

2.2. Catecholase studies

3. Conclusion

The progress of the catechol oxidation reaction is conveniently followed monitoring the strong absorbance peak of quinone in the UV/Vis spectrophotometer (Scheme 2).

We report the synthesis of amino acid functional tridentate ligands with good and excellent yields. The oxidation of catechol is very efficient to give quinone by complexes of

HO—(H2C)3-NH2 +

HO—(CH2)3-N L1

f NNr^CO2Me N ^

HO N ^'^N^C°2Me

-HO-(H2C)3—N L2

y-N-N^CO2Et

HO-(H2C)3-N L3

Scheme 1

Table 1 Comparison between reaction yields.

Products Method 1 (%) Method 2 (%)

L1 80 87

L2 78 88

L3 75 89

Catechol Quinone

Scheme 2

copper(II) with four functional tripodal pyrazole ligands. The complexes of copper(II) were generated in situ. We have demonstrated that the nature of the ester side chain has a large effect on the oxidation reaction rate. The study of various copper(II) salts shows that the catalytic activities are most controlled by the nature of the anion, too.

4. Experimental section

4.1. Apparatus

NMR spectra (1H, 13C) were recorded on a BRUKER 300 (operating at 300.13 MHz for 75.47 MHz for 13C) spectrometer. Chemical shifts are listed in ppm and are reported relative to tetramethylsilane (*H, 13C). Residual solvent peaks being used as internal standard. The mass spectra have been obtained on a Micromass LCT spectrometer.

4.2. General procedure

4.2.1. Method 1

A mixture of 1-(hydroxymethyl)-3,5-dimethylpyrazole; 1-hydroxymethyl-5-methyl-1H-pyrazole-3-carboxylic acid

methyl ester and 1-hydroxymethyl-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester with an alcohol amine in 2:1 ratio was stirred for four days in acetonitrile.

4.2.2. Method 2

A mixture of one equivalent of the appropriate amines (10 mmol) and two equivalents (20 mmol) of hydroxymethyl-derivatives in acetonitrile (1 mL), was heated in a water bath

Temps (mil

Figure 1 Oxidation of catechol by complexes of ligand L1.

Figure 2 Oxidation of catechol by complexes of ligand L2.

Temps (min)

Figure 3 Oxidation of catechol by complexes of ligand L3.

Figure 4 Oxidation of the catechol in presence of Cu(Cl)2.

at 65 0C for 4 h. The residual reactions were extracted with tions were concentrated under reduced pressure to give the yel-dichloromethane and washed with water. The organic solu- low oils.

Temps (n

Figure 6 Oxidation of the catechol in presence of CuSO4.

Table 2 Oxidation rates (imol L 1 min 1 of catechol L1-L3.

Ligands Copper salt (2 x 10-3 M) V (mol L-1 min-1)

L1 CuCl2 1.80 x 10-6

Cu(NO3)2 2.77 x 10-6

Cu(CH3COO)2 14.44 x 10-6

CuSO4 28.99 x 10-6

L2 CuCl2 15.03 x 10-6

Cu(NO3)2 17.70 x 10-6

Cu(CH3COO)2 -

CuSO4 9.9 x 10-6

L3 CuCl2 5.96 x 10-6

Cu(NO3)2 12.75 x 10-6

Cu(CH3COO)2 -

CuSO4 7.01 x 10-6

4.3. Characteristic data of new compounds

4.3.1. 3-(Bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino)propane-1-ol: L1

Yield: 80%; *H NMR (CDCl3) d ppm: 5.78 (s, 2 H, PzH); 4.90 (s, 2 H, N-CH2-N); 4.36 (s, 2 H, N-CH2-N); 3.81 (t, 2 H, CH2-CH2-OH, J = 5.37 Hz); 2.96 (t, 2 H, CH2-CH2-N, J = 5.63 Hz); 2.23 (s, 6 H, 2CH3); 2.23 (s, 6 H, 2 CH3); 1.65 (m, 2 H, -CH2-CH2-CH2-, J = 5.46 Hz); 13C NMR (CDCl3) d ppm: 147.68 (CPz-CH3); 139.71 (CH3-CPz); 105.75 (CPzH); 67.79 (N-CH2-N); 64.89 (CH2-OH); 47.21 (CH2-N); 22.61 (CH2-CH2-CH2); 12.09 (CH3Pz); 0.97 (CH3Pz); MS (ES) m/ z: 291.73 (65%); 195.93 (100); 180.93 (5%); 97.20 (45%).

4.3.2. 1-[((3-Hydroxypropyl)[3-(methoxycarbonyl)-5-methyl-1H-pyrazol-1-yl]methylamino)methyl]-5-methyl-1H-pyrazole-3-carboxylate de methyle: L2

Yield: 78%; *H NMR (CDCl3) d ppm: 6.56 (s, 2 H, PzH); 5.29 (s, 2 H, N-CH2-N); 5.08 (s, 2 H, N-CH2-N); 3.89 (s, 6 H, OCH3); 3.82 (t, 2 H, CH2-CH2-OH, J = 5.37 Hz); 2.97 (t, 2 H, CH2-CH2-N, J = 5.62 Hz); 2.35 (s, 6 H, 2 CH3); 1.65 (m, 2 H, -CH2-CH2-CH2-, J = 5.55 Hz); 13C NMR (CDCl3) d ppm: 163.09 (CO); 142.19 (CPz=N); 140.70 (CPz=C); 108.96 (CPzH); 67.79 (N-CH2-N); 66.93 (CH2-OH); 51.90 (CH3-O); 47.10 (CH2-n); 22.63 (CH2-CH2-CH2); 11.20 (CH3Pz); MS

(ES) m/z (%): 379.64 (10); 337.60 (25); 294.80 (50); 280.87 (100); 239.93 (25); 184.20 (30); 141.07 (45); 100.07 (20).

4.3.3. 1-[((3-Hydroxypropyl)[3-(ethoxycarbonyl)-5-methyl-1H-pyrazol-1-yl]methylamino)methyl]-5-methyl-1H-pyrazole-3-carboxylate d'ethyle: L3

Yield: 75%; 1H NMR (CDCl3) d ppm: 6.55 (s, 2 H, CPzH); 5.29 (s, 2 H, N-CH2-N); 5.06 (s, 2 H, N-CH2-N); 4.30 (q, 4 H, O-CH2-CH3, J = 7.1 Hz); 3.62 (t, 2 H, CH2-CH2-OH, J = 5.03 Hz); 2.99 (t, 2 H, CH2-CH2-N, J = 5.00 Hz); 2.27 (s, 6 H, 2CH3); 1.33 (t, 6 H, -CH2-CH3, J =7.1 Hz); 1.65 (m, 2 H, -CH2-CH2-CH2-, J = 5.55 Hz); 13C NMR (CDCl3) d ppm: 162.67 (CO); 142.51 (CPz=N); 140.59 (CPz=C); 108.85 (CPzH); 67.76 (N-CH2-N); 66.82 (CH2-OH); 60.78 (CH2-O): 47.10 (CH2-N); 22.62 (CH2-CH2-CH2); 14.24 (-CH2-CH3) 11.16 (CH3Pz); MS (ES) m/z (%): 407.47 (5); 308.8 (100) 294.93 (15); 250.93 (15); 155.07 (15); 97.20 (5).

4.4. Catecholase activity measurements

Kinetic measurements were made spectrophotometrically on a UV-Visible spectrophotometer (In the COSTE: Centre de l'Oriental des Sciences et Technologies de l'Eau), following the appearance of o-quinone over time at 25 0C (390 nm absor-bance maximum, e = 1600 M-1 cm-1 in methanol). The metal complex (prepared in situ from copper(II) salt and the ligand, 0.3 mL of 10-3 M methanol solution) and a 2mL solution (10-1 M methanol solution) of catechol were added together in the spectrophotometric cell.

Acknowledgments

The authors would like to thank la Commission Universitaire pour le Developpement (CUD, Belgium) for its support. They also thank the American chemical society for its invitation to the Pittcon 2010 in Orlando, Florida.

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