Martine Largeron
email: martine.largeron@parisdescartes.fr

Khac Minh

Huy Nguyen

M H Nguyen

Recent Advances in the Synthesis of Benzimidazole Derivatives from the Oxidative Coupling of Primary Amines

Keywords: oxidation, homogeneous catalysis, heterogeneous catalysis, cross-coupling, amine, imine, benzimidazole

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Nitrogen heterocycles are among the most privileged and significant structural components of pharmaceuticals. 2 A recent analysis of the nitrogen heterocyclic composition of U.S. FDA (Food and Drug Administration) approved drugs has revealed the relative frequency by which the various nitrogen heterocycles have been incorporated into approved drugs architecture. 3 Interestingly, benzimidazole was found to be the fifth most commonly used five-membered aromatic nitrogen heterocycles after thiazole, imidazole, indole and tetrazole. Benzimidazoles are found in thirteen U.S. FDA approved drugs exhibiting diverse pharmaceutical properties. Five of these drugs are structurally similar proton pump inhibitors including the well known omeprazole, also marketed as the single enantiomer sulfoxide variant esomeprazole (Figure 1).

Figure 1 Representative pharmaceuticals containing a benzimidazole scaffold

Five of the benzimidazole drugs, candesartan, telmisartan, azilsartan, medoxomil and mibefradil, are used as antihypertensives whereas astemizole and emedastine are antihistaminic agents. Lastly, bendamustine acts as an alkylating agent for the treatment of chronic lymphocytic leukemia and dabogatran elexilate mesylate is used to prevent the risk of stroke. Interestingly, almost all drugs are 1,2-disubstituted benzimidazole derivatives. synthesis of functionalized benzimidazole derivatives, which are traditionally prepared from o-aminoanilines by condensation with carboxylic acid derivatives under harsh dehydrating conditions or by oxidative coupling with aldehydes. 4 Although the oxidative condensation of o-aminoanilines with aldehydes remains the most popular way to prepare these targets, this strategy suffers some drawbacks such as air-sensitive catalysts, stoichiometric or excess amount of oxidants, low yields, high reaction temperature and the competitive formation of 2substituted and 1,2-disubstituted benzimidazoles. 5 Recent advances have been dominated by the development of improved procedures in terms of operational simplicity, atom economy and ecofriendly viability, which selectively lead to either 2substituted benzimidazoles 6 or 1,2-disubstituted benzimidazoles as the sole product. 7 The regiodefined 1,2-disubstitution on the benzimidazole scaffold being a structural characteristic of pharmaceuticals, numerous alternative strategies have been developed for the regiocontrolled synthesis of 1,2-disubstituted benzimidazoles. 8 In particular, catalytic amination of 2-haloacetatanilides and catalyzed intramolecular C-N cross-coupling reactions starting from amidines have widely been utilized. 9 However, these routes require special efforts to prepare the desired starting materials, thus limiting the potential applications of these methods.

Recently, oxidative cross-coupling reactions employing alcohols and o-aminoanilines as substrates have received great attention for selectively producing 2-substituted benzimidazoles without the concomitant formation of 1,2disubtituted benzimidazoles. 10 However, with few exceptions, 10d,h,j high reaction temperature (90-160 °C), oxygen pressure or expensive transition-metal catalysts are still required.

This review focuses on the utilization of primary amines as readily available substrates in the oxidative cyclocondensation reaction with o-aminoanilines to construct the benzimidazole framework (Scheme 1). The attractive features of this protocol include the use of commercially available amines, high atom economy and high selectivity towards the products. Furthermore, a large molecular diversity could be attained through the variation of both aliphatic amines and oaminoanilines.

Scheme 1 Oxidative cyclocondensation of primary amines with o-aminoanilines leading to benzimidazole derivatives

Different types of oxidative cross-coupling with oaminoanilines are presented, covering literature mainly published during the last five years. Catalyzed methods are organized into three sections, for metal-catalyzed, metal-free and bioinspired reaction types.

Catalyst-free oxidative coupling of primary amines

Sustainable development has been accepted as a common knowledge in current society. In response to this challenge, the development of green processes, which reduce chemical waste and handling costs, is highly desirable.

Accordingly, Nguyen and co-workers have reported simple solvent-free and catalyst-free procedures for the synthesis of substituted benzimidazoles. Especially, they have performed oxidation reactions of various aliphatic amines using elemental sulfur as a readily available, nontoxic and stable oxidant, in the presence of o-aminoanilines, which are not sensitive to sulfurmediated oxidation. 11 By heating an equimolar mixture of aliphatic amine and o-aminoaniline, at 150 °C, in the presence of an excess of elemental sulfur (3 equiv), under solvent-free conditions, 2-substituted benzimidazoles could be isolated in high yields. Using a slight excess of o-aminoaniline (1.5 equiv), the reaction temperature could be decreased to 130 °C and the isolated yield could reach 92% (Figure 2). Interestingly, aliphatic amines other than benzylic amines can be oxidized by elemental sulfur allowing introduction of alkyl substituents at the 2-position of the benzimidazole core.

Figure 2

Yields of representative benzimidazole derivatives prepared from sulfur-mediated cross-coupling of amines 11 The reaction mechanism involved the intermediary formation of a homocoupled thioamide (Scheme 2), as the result of the oxidation of aliphatic amine by elemental sulfur, followed by trans-thioamidation which was energetically facilitated by Template for SYNTHESIS © Thieme Stuttgart • New York 2020-11-26 page 3 of 13 subsequent cyclization and aromatization steps (Scheme 1). So sulfur was not incorporated in the final product but was used as a traceless oxidizing reagent. Interestingly, this protocol was also effective for the preparation of benzothiazoles and benzoxazoles, the thia-and oxa-analogues of benzimidazoles.

Scheme 2 Sulfur-mediated oxidative coupling of aliphatic amines with o-aminoanilines affording benzimidazoles

Nguyen and co-workers have also described a solvent-free autoxidation system for the synthesis of 2-substituted benzimidazoles by simply heating a mixture of benzylic primary amines and o-aminoanilines, at 110 °C, under 1 atm of O2 for 24 h, in the presence of acetic acid (20 mol%) as a cyclizing promoter. 12 Although this catalyst-free and solvent-free methodology was attractive from the viewpoint of sustainable chemistry, the substrate scope was limited to benzylic-type substrates. However, this solvent-free autoxidation system could also be applied to the synthesis of 2,3-dihydroquinazolin-4-(1H)-one and quinazolin-4-(3H)-one derivatives, in acceptable yields ranging from 60 to 72%, by changing o-aminoaniline to anthranilamide as the coupling partner, while increasing the amount of acetic acid to 40 mol% and the temperature to 120-150 °C (Scheme 3). Note the quinazoline framework is also part of the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. 3 Scheme 3 Solvent-free autoxidation of benzylic amines allowing the synthesis of quinazoline derivatives Yu and Lu have reported a similar catalyst-free and solventfree oxidative synthesis of 2-substituted benzimidazole derivatives. 13 Using an excess of tert-butyl hydroperoxide (TBHP, 4 equiv, 70% in H2O) as the oxidant instead of 1 atm O2, 12 a significant reduction of the reaction time (5-12 h against 24 h) was observed. Following the reaction scheme 1, various 2substituted benzimidazoles were synthesized at 100 °C starting from 1 equiv of benzylic or allylic primary amines and 1.5 equiv of o-aminoanilines (Figure 3).

Recently, Kamal and co-workers have developed a metal-free one-pot protocol for the synthesis of 2-substituted benzimidazole derivatives which proceeds through the oxidation of benzylic amines by an inexpensive mild oxidant phenyliodonium diacetate (PIDA). 14

Figure 3

Yields of representative 2-substituted benzimidazoles synthesized through TBHP-mediated oxidative cross-coupling 13 By heating 1.2 equiv of both PIDA and benzylic amine together with 1 equiv of o-aminoaniline, at 80 °C for 4 h, in a mixture of DMSO and H2O (1:1 ratio) as the solvent, 2-substituted benzimidazoles could be isolated in high yields ranging from 77 to 92%. The reaction mechanism involved the oxidative addition of PIDA with benzylamine substrate, followed by the formation of a benzaldimine intermediate which rapidly hydrolyzed to give the corresponding benzaldehyde (Scheme 4). Further oxidative cyclocondensation with o-aminoanilines led to the corresponding 2-substituted benzimidazole product. Interestingly, the methodology could be extended to the synthesis of biologically relevant quinazolinone derivatives, when anthranilamide was used instead of o-aminoanilines by heating the reaction mixture at 100 °C for 6 h.

Scheme 4

Proposed reaction mechanism for the PIDApromoted synthesis of 2-substituted benzimidazole derivatives A last example of catalyst-free oxidative coupling of primary amines merits special note because of the exceptionally mild reaction conditions utilized. Narender and co-workers have developed a simple method for the iodine-mediated synthesis of 2-substituted benzimidazole derivatives which allows the C-N bond formation at room temperature. 15 The oxidative crosscoupling of benzylic amine (1.5 equiv) with o-aminoaniline (1 equiv) was promoted by 2 equiv of iodine in acetonitrile, leading to the desired benzimidazole product in only 30 min. The initial step of the reaction mechanism involves the oxidation of the benzylic amine by iodine to give, after elimination of ammonia, an homocoupled imine intermediate which could be isolated (Scheme 5). After dynamic transimination, the generated crosscoupled imine underwent intramolecular cyclization and subsequent oxidation as shown in reaction scheme 1 affording 2-substituted benzimidazoles in good yields ranging from 58 to 82%. However, aliphatic primary amines other than benzylic amines failed to provide 2-substituted benzimidazoles under the same experimental conditions.

Scheme 5 Proposed reaction mechanism for the I2-mediated synthesis of 2-substituted benzimidazole derivatives

Replacing o-aminoaniline by mercaptoaniline, 2-substituted benzothiazoles could be prepared under similar reaction conditions. Furthermore, a new class of 2-benzyl-3-phenyl-3,4dihydro-2H-benzo[e] [1,2,4]thiadiazines was discovered in ethyl acetate, which involved both metal-free C-N and S-N bond formation, illustrating the efficiency of the process (Scheme 6). [1,2,4]thiadiazines During the last five years, new and more environmentally friendly strategies for the catalyst-free oxidative coupling of primary amines to construct the benzimidazole framework have been identified. [11][12][13][14][15] At the same time, significant progress has resulted from the discovery of selective catalytic systems that avoid using stoichiometric or excess amounts of specific oxidants, which adversely affect the economics as well as the ecofriendly nature of the reaction.

Scheme 6 I2-mediated formation of 2-benzyl-3-phenyl-3,4- dihydro-2H-benzo[e]

Catalytic oxidative coupling of primary amines

The development of processes that satisfy environmental constraints is in current demand from the pharmaceutical and chemical industries. In this respect, the use of low loadings of catalysts, with molecular oxygen atmosphere or, much better, ambient air as the sole oxidant, is particularly attractive from the viewpoint of green chemistry.

Metal-catalyzed reactions

For years, the major weakness of metal-catalyzed reactions has been the use of expensive precious-and rare-metal catalysts, which did not meet the requirements of sustainable and green chemistry. Recently, earth abundant or biocompatible metals, especially copper and iron, have attracted much attention due to their low cost and low toxicity. 16 Although the aerobic copper-catalyzed oxidation of primary amines to imines was previously described, 17 Zhou and coworkers were the first to report a Cu-catalyzed aerobic oxidative cyclocondensation of benzylic amines with oaminoanilines for the synthesis of 2-substituted benzimidazole derivatives. 18 The reactions were carried out in toluene, at 100 °C under air for 24 h, using benzylic amines (1.2 equiv) and oaminoanilines (1 equiv), in the presence of low loading of CuBr2 (1 mol%) as the catalyst. In the presence of o-aminoaniline, variously substituted benzylamines afforded the corresponding 2-substituted benzimidazoles in 79-92% yields regardless of the electronic character of the substituents (Figure 4). Likewise, the reaction was not significantly affected by the substituents on the aromatic ring of o-aminoaniline, when benzylamine was used as the amine substrate, producing the corresponding 2-substituted benzimidazole derivatives in high yields (80-93%). Furthermore, the methodology could be extended to the synthesis of their structural isosteres, benzothiazole and benzoxazole.

Figure 4

Yields of representative 2-substituted benzimidazoles synthesized through CuBr2-mediated oxidative cross-coupling 18 Xu and co-workers have reported a similar action of CuI (5 mol%) for the catalyzed oxidative cyclocondensation of benzylic amines (2 equiv) and o-aminoanilines (1 equiv) in toluene, at 100 °C under air for 48 h. 19 The yields of isolated 2-substituted benzimidazole derivatives were acceptable, ranging from 41 to 83%. Noteworthy, variously substituted benzothiazoles and benzoxazoles could also be prepared through this protocol. Obviously, CuI was less effective than CuBr2 to promote this kind of transformation. 18 Nevertheless, at a slightly more elevated temperature of 130 °C for 24 h, CuI was also able to catalyze the oxidation of 2-phenylethylamine, which, in the presence of o-aminoaniline, was converted into a six-membered 2-phenylquinoxaline product through a reaction mechanism recently reported by Gopalaiah and co-workers for their similar CuBr-catalyzed protocol (Scheme 7, dashed arrows). 20 In the presence of o-aminoaniline A, copper-catalyzed aerobic oxidation of 2-phenylethylamine would produce the crosscoupled imine B, which after copper-catalyzed benzylic oxidation, would lead to the formation of the keto-imine E via benzyl radical intermediate C and hydroperoxide D.

Scheme 7 CuI-catalyzed formation of 2-phenylquinoxaline

Interestingly, the CuBr-catalyzed oxidative coupling reaction of o-aminoanilines with 2-aryl/heteroarylethylamines described by Gopalaiah and co-workers was particularly efficient under 1 atm of molecular oxygen as the oxidant. Then, functionalized quinoxalines were isolated in high yields ranging from 78 to 97%. 20 The reaction proceeded rapidly within 5-16h, in chlorobenzene, at room temperature, using 2aryl/heteroarylethylamines (1.2 equiv) and o-aminoanilines (1 equiv), in the presence of CuBr (10 mol%) as the catalyst. Note that CuBr proved to be a more efficient catalyst than CuBr2 for this transformation. In the case of 2-phenylethylamine substrate, changing CuBr to CuBr2 led to a decreased yield in quinoxaline from 73 to 51%, under the same reaction conditions. 20 Note that different reaction pathways have been proposed for the copper-catalyzed formation of benzimidazoles (or quinoxalines) as shown in Scheme 8. Zhou and co-workers have envisioned the coordination of Cu II to benzylic amine followed by oxidation to generate the benzylimine intermediate, which reacts with o-aminoaniline giving the cross-coupled imine (path A). 18 Gopalaiah and co-workers have similarly suggested direct transimination to form cross-coupled imine (path A) for their CuBr/O2 system leading to quinoxalines, but they have also envisaged that 2-phenylethylimine may hydrolyze into phenylacetaldehyde, which, on further condensation with oaminoaniline, forms the cross-coupled imine (path B). 20 Xu and co-workers have proposed an alternative route in which the CuI-catalyzed aerobic oxidation of amines under air produces the homocoupled imine intermediate, which then reacts with oaminoaniline to give the cross-coupled imine through a transimination step (path C). 19 Because of the presence of benzaldehyde as the by-product in reactions with low conversion, Xu and co-workers have also envisaged that benzylimine can hydrolyze into benzaldehyde and then affords the cross-coupled imine by condensation reaction (path B). The last steps of the process leading to the target benzimidazole heterocycle would involve intramolecular cyclization and subsequent oxidation as reported in reaction scheme 1.

Scheme 8 Possible pathways for the copper-catalyzed aerobic cross-coupling of primary amines

In addition to copper systems, iron catalysts are also ideal candidates for such transformations, because iron shows variable valences and fulfills the requirements for green chemistry. Inspired by the iron-mediated catalytic system reported by Xu and co-workers for the preparation of imines through aerobic oxidative coupling of amines under air, 21 Lu and co-workers have demonstrated that the aerobic oxidative cyclocondensation of benzylic primary amines (1.2 equiv) and o-aminoaniline (1 equiv) can be achieved by the synergistic combination of Fe(NO3)3 (5 mol%) and electron-deficient 2,2,6,6-tetramethyl-1-piperidyl-1-oxy radical (TEMPO) (5 mol%), under solvent-free conditions, in open air. 22 Variously substituted benzylic amines were converted into 2-substituted benzimidazoles in high yields (78-93%), at 110 °C for 24-28 h. The first step of the proposed reaction mechanism consists of the aerobic Fe/TEMPO-catalyzed oxidation of benzylic amine to the corresponding benzylimine intermediate in a way reminiscent of that reported by Hu and Kerton for the aerobic Cu/TEMPO-catalyzed version (Scheme 9). 23 The mechanism pursues following reaction scheme 8 (path A or B). Recently, Gopalaiah and Chandrudu have described a significantly improved Fe-catalyzed protocol for the synthesis of 2-substituted benzimidazoles, without the need of adding TEMPO. 24 Through optimization studies, they have compared the ability of Fe II and Fe III (10 mol%) to catalyze the aerobic coupling of benzylamine (1.2 equiv) and o-aminonaniline (1 equiv), in chlorobenzene at 110°C for 18h under air. They have found that Fe II , especially FeBr2, is the best choice for the oxidative cyclocondensation reaction leading to 2phenylbenzimidazole in 78% yield. Using 1 atm of molecular oxygen instead of air atmosphere, the iron catalyst loading could be reduced to 5 mol%, while the yield of benzimidazole product significantly increased to 92% within only 4 h. A large molecular diversity could be attained through the variation of both benzylic amines and o-aminoanilines (Figure 5).

Figure 5

Yields of representative 2-substituted benzimidazoles synthesized through FeBr2-mediated oxidative cross-coupling 24 Interestingly, the non-activated primary amine n-octylamine was also a good substrate for this oxidative coupling reaction with o-aminoaniline, affording the corresponding benzimidazole in 73% yield. The proposed reaction mechanism was close to scheme 8 (path A or C) reported for the copper-mediated catalytic systems. Furthermore, the methodology could be applied to the synthesis of variously substituted benzothiazoles and benzoxazoles.

From the perspective of green chemistry and because metal residues may constitute a serious problem in the synthesis of pharmaceuticals and functional materials, chemists have shifted their attention to other eco-friendly protocols such as metal-free catalyzed reactions.

Metal-free catalyzed reactions

Alternative metal-free catalytic systems have been developed for the oxidative cross-coupling of primary amines including photocatalyzed and organocatalyzed reactions.

Heterogeneous metal-free catalysis

Owing to the natural abundance of carbon together with the need of minimizing the production of wastes and achieving optimal economic viability, the use of carbon catalysts has emerged in synthetic strategies. 25 Especially, graphene oxide (GO), a water-soluble derivative of graphene, has been utilized for the (GO)-mediated oxidative coupling of primary amines to imines. 26 However, most of the reactions require high weight loading of GO relative to the substrate, due to the moderate catalytic efficiency of GO when used as a substitute for metal catalysts. Loh and co-workers have reported a sequential base and acid treatment of GO that markedly improves its catalytic efficiency by generating porosity. Thanks to the utilization of porous graphene oxide (p-GO), 27 the oxidative cyclocondensation of benzylamine (1 equiv) and oaminonaniline (1.5 equiv) could be performed, under air in acetonitrile, at 90 °C, for 12h, affording 2-phenylbenzimidazole in 77% yield (Scheme 10). The extension of this protocol to other amine substrates has not been reported.

Scheme 10

One-pot aerobic p-GO catalyzed synthesis of 2phenylbenzimidazole. 27 The utilization of sunlight as a non polluting energy source for chemical transformations has recently attracted much attention. 28 Although several aerobic photocatalytic oxidation of primary amines to imines have been developed, 29 a sole photocatalyzed oxidative cross-coupling reaction for the synthesis of benzimidazoles has been reported to the best of our knowledge. Blechert and co-workers have demonstrated that the utilization of mesoporous graphite carbon nitride (mpg-C3N4) photocatalyst, and visible light, allowed the complete conversion of benzylic amines to imines in acetonitrile at 80 °C but under high oxygen pressure (0.5 MPa). 30 Interestingly, the mpg-C3N4 photocatalyst could be easily separated and reused three times, without loss of catalytic activity. In the presence of N-methyl-o-aminoanilines (3 equiv) (or mercaptoaniline), at 100 °C, the imines resulting from the oxidative coupling reaction could be engaged in situ, in an intramolecular cycloaddition reaction and subsequent oxidation to give 1,2-disubstituted benzimidazoles (or 2-substituted benzothiazoles) with high levels of conversion (91-99%) within 4-6 h (Scheme 11).

Synthesis

Scheme 11 One-pot aerobic photocatalytic synthesis of benzimidazoles and benzothiazoles

Homogeneous metal-free catalysis

The use of small organic molecules to catalyse organic transformations, is a relatively popular field within the domain of organic synthesis. [START_REF] Macmillan | For selected reviews[END_REF] However, reports of the use of organocatalysts to mediate the aerobic oxidative cross-coupling of amines giving benzimidazoles products are rather scarce.

Ogawa and co-workers have shown that the oxidative crosscoupling of primary amines could be achieved efficiently using salicylic acid derivatives as organocatalysts. Optimization studies revealed that 4,6-dimethoxysalicylic acid (5 mol %) was the most effective organocatalyst for the oxidative cyclocondensation reaction of benzylic amines (1.5 equiv) with o-aminoanilines (1 equiv), under an oxygen atmosphere (0.1 MPa), in toluene at 110°C for 12h. 32 Diverse substituents on the phenyl group of benzylamines or on the aromatic ring of oaminoanilines were well tolerated, affording 2-substituted benzimidazole derivatives in high yields ranging from 85 to 95% (Scheme 12). Through additional experiments, the authors have demonstrated that the oxidation of benzylamine proceeds following a radical mechanism.

Scheme 12

One-pot aerobic organocatalyzed cascade reaction affording 2-substituted benzimidazole derivatives.

Except for few exceptions, 11,30 the different oxidative crosscoupling protocols presented until now describe the synthesis of 2-substituted benzimidazole derivatives. A last example of homogeneous metal-free catalysis is attractive because it gives also access to pharmaceutically relevant 1,2-disubstituted benzimidazoles. Recently, Bharate and co-workers have developed a metal-free method for the synthesis of 1,2disubstituted benzimidazoles from benzylamine substrates and N-phenyl-o-aminoaniline, using an imidazolium-based ionic liquid as the reaction medium, which can be recycled several times without significant loss of catalytic activity. 33 The process involves the oxidative cyclocondensation reaction of the benzylamine substrate (2 equiv) with N-phenyl-o-aminonaniline (1 equiv), in 1-butyl-3-methylimidazolium tetrafluoroborate as the ionic liquid (0.5 mL), heated at 120 °C for 10h. Variously substituted benzylamines afforded the corresponding 1,2disubstituted benzimidazoles, in high yields (88-98%), without particular electronic or steric effects of the substituents (Figure 6). Note that non-activated aliphatic amines failed to produce the corresponding benzimidazole derivatives under the same experimental conditions. This ionic-liquid-mediated process could be also applied to the synthesis of 2-phenyl-quinazolin-4-(3H)-one derivatives, in excellent yields ranging from 88 to 98%, by changing o-aminoaniline to anthranilamide as the coupling partner (Scheme 13). Interestingly, it was observed that ionic liquid mediated all of the oxidation steps, whereas air did not play a role in the oxidation since the reaction could be performed under nitrogen or argon atmosphere.

Scheme 13 Ionic-liquid mediated synthesis of benzimidazole and quinazolin-4-(3H)-one derivatives Figure 6 Yields of representative 1,2-disubstituted benzimidazoles synthesized through ionic liquid-mediated oxidative cross-coupling 33 At this stage, with only few exceptions, 11,24 the major drawback of protocols based on the oxidative cross-coupling of amines is the difficulty of oxidizing non-activated primary amines. Accordingly, the molecular diversity is limited to derivatives bearing benzylic or allylic substituents at the 2position of the benzimidazole framework. This compromises the overall efficiency of the reported works, because the well known coupling between an aldehyde and o-aminoaniline is more direct. Another weakness of these protocols is that the syntheses of 1,2-disubstituted benzimidazoles are rather scarce, 11,30,33 while almost all pharmaceuticals are 1,2disubstituted derivatives. The discovery of biomimetic methods that utilize air as an environmentally benign oxidant, in a way reminiscent of enzyme catalysis, has proved to be effective to surpass these limitations.

Bioinspired catalyzed reactions

In 2012, Endo and Bäckvall have been the first to develop a biomimetic electron-transfer system for the rutheniumcatalyzed oxidative coupling of primary benzylic amines and ohydroxyanilines to give 2-substituted benzoxazoles in high yields. 34 Using 4-methylbenzylamine and o-aminoaniline as the amine substrates, they have been able to prepare the corresponding benzimidazole, though in 45% moderate yield (Scheme 14). The design of the system was inspired by the biological oxidation of alcohols. Instead of NAD + they have used a ruthenium complex as the substrate selective catalyst which dehydrogenates the benzylic amine to the corresponding benzylimine. The hydrogen atoms abstracted are transported to the electron-rich 2,6-dimethoxy-1,4-benzoquinone which serves as an electron-transfer mediator. The resulting hydroquinone is subsequently reoxidized by air with the assistance of an oxygen-activating cobalt complex. The molecular diversity accessible through this protocol has not been explored.

Scheme 14

Ru-catalyzed oxidative coupling to give benzimidazole by using a biomimetic oxidation system A noticeable progress has arisen from the development of biomimetic quinone-based catalytic systems inspired by natural copper amine oxidases (CuAOs), a family of metalloenzymes which catalyzes the selective oxidation of primary amines to aldehydes, through the cooperation of a quinone-based cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), and a copper ion. 35 During the last five years, organic chemists have developed various bioinspired quinone-based catalytic systems for the aerobic oxidation of amines to imines under 1 atm of dioxygen or, more preferably, ambient air as the sole oxidant, with two objectives: (a) to achieve sustainable aerobic oxidation reactions and (b) to expand the scope of possible substrates. [START_REF]For recent reviews or perspectives[END_REF] In this field, our group has recently described a bioinspired homogeneous catalytic system based on the cooperative action of a copper ion and a TPQ-like o-iminoquinone organocatalyst IMQ (Scheme 15), first discovered from electrochemical investigations. 37 This protocol is reminiscent of other biomimetic catalytic systems, that uses transition metals as substrate-selective catalysts coupled with electron transfer mediators. 38 Conversely, in our case, IMQ, which is generated in situ from the corresponding aminophenol AMQ, is the substrateselective catalyst while the copper ion serves as an electron transfer mediator. Low catalysts loadings are sufficient to oxidize benzylic, and non-activated aliphatic amines RCH2-NH2, to the homocoupled imine product at room temperature under ambient air. 39 The oxidation process starts with atmospheric oxygen and continues in a cascade-like manner by passing the oxidation potential of oxygen through the copper salt to the organic mediator IMQ, which finally oxidizes the amine substrate. In the presence of a second primary amine R'-NH2, the generated homocoupled imine intermediate could be converted into a cross-coupled imine with complete selectivity. 40 Template for SYNTHESIS © Thieme Stuttgart • New York 2020-11-26 page 9 of 13 Scheme 15 Cu(OAc)2/IMQ-catalyzed aerobic oxidative crosscoupling of primary amines to imines

The mild reaction conditions being highly favorable for trapping the unstable alkylimines in situ for further reactions, we have utilized our bioinspired co-catalytic system, in a one pot cascade reaction sequence, leading to 1,2-disubstituted benzimidazoles. Optimization studies realized from the aerobic oxidative cross-coupling of benzylamine (1 equiv) with Nphenyl-o-aminoaniline (1 equiv) indicated that higher yields were obtained by heating the coupling reaction mixture in methanol, at 45 °C under air, in the presence of 6 mol% of AMQ (4 mol% followed by a 2 mol% additional aliquot after 6h) and by using CuBr2 (0.4 mol%) as the copper catalyst. 41 The use of CuBr2 as the more efficient copper catalyst had also been observed by Zhou and co-workers. 18 A large molecular diversity could be attained through the variation of both coupling partners leading to 1,2-disubstituted benzimidazole derivatives in good yields. It is important to note that, with the exception of -branched alkylamines, non-activated primary aliphatic amines were found to be good coupling partners for the CuBr2/IMQmediated aerobic oxidative cyclocondensation reaction with Nsubstituted-o-aminoanilines provided a slightly elevated temperature of 60 °C was used (Figure 7). 41,42 Although MeOH proved to be the best solvent for the coupling reaction because it provides the ideal balance of IMQ solvation and reaction rate, when reactive N-alkyl-o-aminoaniline were used as in situ imine traps, a concomitant formation of Nalkylbenzimidazole by-product was observed, originating from the involvement of MeOH itself which acted as a carbon source. In these cases, the exclusive formation of 1,2-disubstituted benzimidazoles can be achieved in 2-propanol in the presence of water (10%), which markedly accelerates the cyclization rate to the benzimidazoline intermediate. 42 Accordingly, Barta and coworkers had previously reported a protocol for the preparation of benzimidazoles from a range of o-aminoanilines by simply heating these starting materials in supercritical MeOH, which acts both as a solvent and carbon source, in the presence of copper-doped porous metal oxides. 43 The reaction mechanism for the CuBr2/IMQ-mediated aerobic cross-coupling reaction involves the oxidation of the primary amine R 2 CH2NH2 to the homocoupled imine intermediate through a transamination mechanism analogue to that reported for natural CuAOs (Scheme 16). In the presence of oaminoaniline, the homocoupled imine intermediate is converted into cross-coupled imines through dynamic transimination. As a consequence, just one equivalent of each primary amine was sufficient to achieve exclusive formation of the cross-coupled imine product. Subsequent intramolecular cyclization to benzimidazoline and oxidation reactions as reported in reaction scheme 1 afford the 1,2-disubstituted benzimidazole derivatives with high atom economy. Note variously substituted 2benzimidazole derivatives could also be prepared using diverse o-aminoanilines. 42 Template for SYNTHESIS © Thieme Stuttgart • New York 2020-11-26 page 10 of 13

Scheme 16 Bioinspired CuBr2/IMQ-mediated cascade reaction sequence affording 1,2-disubstituted benzimidazoles Because the oxidation of the primary amine substrates by CuAOs is mediated by TPQ without involvement of the copper ion, 44 we have envisioned significant modifications of our initial protocol to develop procedures, avoiding contamination of the final products by metal residues. Accordingly, the use of a commercially available starting material rather than AMQ, the precursor of IMQ, whose the synthesis requires two steps from 2-nitroresorcinol, 37e would offer enhanced practicality while limiting the production of wastes. This is the reason why we have been drawn to the structure of natural purpurogallin (2,3,4,6-tetrahydroxy-5H-benzocyclohepten-5-one) as a potential precursor of a highly reactive o-quinone-based organocatalyst. However, its limited availability led us to concentrate on its biosynthesis, which involves the oxidative dimerization of pyrogallol generated from gallic acid. 45 Based on this insight, we have developed a double biomimetic reaction pathway resulting in the formation of 1,2-disubstituted benzimidazoles. 46 The reaction sequence starts from inexpensive commercially available pyrogallol and allows, under ambient air, the in situ generation of not easily accessible natural purpurogallin, which is further engaged in the transamination process analogue to that reported in reaction scheme 16, for producing, under single turnover, the active biomimetic organocatalyst IMQ' (Scheme 17). Dynamic transimination followed by intramolecular cyclization and subsequent oxidation reactions produced the 1,2-disubstituted benzimidazole derivatives.

Scheme 17 Bioinspired IMQ'-mediated cascade reaction sequence affording 1,2-disubstituted benzimidazoles Because the synthesis of aliphatic imines is challenging due to their instability and isomerization into the enamine tautomer, which decomposes under ambient air, we have focused on the aerobic oxidative cyclocondensation of non-activated aliphatic amines and N-methyl-o-aminoaniline. By mixing these amines substrates in the ratio 1:1, in the presence of 10 mol% pyrogallol, thus generating 5 mol% of IMQ', good yields of 1,2disubstituted benzimidazoles were obtained at 60°C within 60 h (Figure 8). Note this reaction had proved to be unsuccessful in the absence of Cu II cooperative catalyst when IMQ was used as the sole organocatalyst.

Conclusion

The oxidative cross-coupling of primary amines has received much attention over the last five years because it provides a straightforward protocol to synthesize substituted benzimidazole derivatives, through the variation of both commercially available cyclocondensation partners. Different methods have been presented including catalyst-free reactions together with catalyzed processes which encompasse metalcatalyzed, organocatalyzed, photocatalyzed and bioinspired catalyzed reaction types. Each method possesses its strengths and weaknesses.

Obviously, catalyst-free systems are very simple but still suffer from the requirement of stoichiometric or excess amounts of specific oxidants and/or high reaction temperatures.

The attention on highly abundant first-row transition metals such as copper or iron was raised to develop efficient metalcatalyzed methods but the presence of metal residues may constitute a serious problem in the synthesis of drugs and functional materials.

Alternative metal-free catalytic systems have been developed to avoid metal residues contamination. However, organocatalysis still requires high catalyst loadings while photocatalyzed reactions remain scarce despite the increasing interest for visible-light photocatalysis.

Bioinspired catalytic protocols have begun to emerge in synthetic strategies because of the capacity of natural CuAOs to perform controlled aerobic oxidation of amines under mild reaction conditions. The large molecular diversity accessible is interesting but the reaction times are still long.

Due to the prevalence of the benzimidazole framework in pharmaceuticals, the next few years will certainly see the advent of new protocols that will surpass the drawbacks of each method while increasing the scope and efficiency.

Scheme 9

 9 Scheme 9Proposed mechanism for Fe(NO3)3/TEMPO-catalyzed aerobic oxidation of benzylic amines to benzylimines

Review

Figure 7

 7 Figure 7 Yields of representative 1,2-disubstituted benzimidazoles synthesized through CuBr2/IMQ-mediated oxidative cross-coupling

42

 42

Figure 8

 8 Figure 8 Yields of representative 1,2-disubstituted benzimidazoles synthesized through IMQ'-mediated oxidative cyclocondensation reaction

Biosketches

Martine Largeron graduated from the Pierre et Marie Curie University (Paris 6), where she also received her PhD under the supervision of Pr Maurice-Bernard Fleury. After a postdoctoral position at Rhone-Poulenc Rorer (now Sanofi), she was enlisted as a researcher at CNRS and worked at the Paris Descartes University (Paris 5). In 2004, she became Research Director at CNRS. Her current interest is focused on the discovery of bioinspired oxidation catalytic systems for synthetic applications. She has received awards from the French Society of Chemistry in 1990 and 1995 and from the National Academy of Medicine in 2004 and 2014. Since 2012 she has been a member of the National Academy of Pharmacy. Khac Minh Huy Nguyen graduated from the Paris Descartes University where he also received his PhD in 2016 under the supervision of Dr Martine Largeron on the subject of bioinspired catalytic systems for the synthesis of N-heterocycles of pharmacological interest.

Since April 2016, he has been a Post-Doctoral Scholar at CEA-Saclay.

For Reviews, include photos and short biographical text for all authors. If the photo is of a group of people, specify who is shown where. For Short Reviews, restrict the photo and biographical text to the main (starred) author (s). If the photo displays coworkers, however, they can be mentioned briefly within the main author's short biography.


Liliane M Dongmo

Sherman L Z Jiokeng

Chancellin N Pecheu

Alain Walcarius

Ignas K Tonle

Amino-grafting of montmorillonite improved by acid activation and application to the electroanalysis of catechol

Keywords: Montmorillonite, Acid activation, Grafting, Organoclays, Electroanalysis, Catechol

In this work, a natural sodium-montmorillonite clay mineral (Mt-Na) was functionalized with amine groups, either by direct grafting (Mt-NH 2 ) or via acid activation followed by grafting (MtH-NH 2 ) of [3(2-aminoethyl)amino)]propyltrimethoxysilane (AEP-TMS). The morphology and structure of the resulting composite materials were characterized by scanning electron microscopy, X-ray diffraction, N 2 adsorption-desorption isotherms (BET method) infrared spectroscopy, CHN elemental analysis and thermogravimetric analyses (TGA). The obtained organoclays were then used to modify the surface of a glassy carbon electrode (GCE), and the permselectivity and accumulation properties of the resulting films were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS).

The results indicated that MtH-NH 2 modified GCE (GCE/MtH-NH 2 ) exhibited some charge selectivity features and can be applied to the electrochemical oxidation of catechol (CT). By plotting the double logarithmic variation of anodic peak currents (Ipa) versus potential scan rate, the obtained slope value of 0.49 revealed a diffusion-controlled electron-transfer mechanisms for the redox process. The electrochemical behavior of CT on the modified electrode was also studied using differential pulse voltammetry (DPV). The sensitivities of GCE/MtH-NH 2 for CT were 1.71, 3.87 and 1.35-fold greater than signals obtained on the bare GCE, GCE/Mt-Na and GCE/Mt-NH 2 respectively, due to the ability of the aminated materials to strongly accumulate CT. After optimization, GCE/MtH-NH 2 was used for CT determination by differential pulse voltammetry that gave rise to a linear response in the concentration range from 5 µM to 80 µM (R 2 = 0.999), and to a detection limit of 0.65 µM.

The proposed method was applied to CT detection in water samples and in a tea sample.

Introduction

Phenolic compounds are present at low levels in subterranean and drinking waters, as a result of their wide use in textiles, plastics, dyes, paper, herbicides and pesticides [START_REF] Shan | Polycrystalline bismuth oxide films for development of amperometric biosensor for phenolic compounds[END_REF][START_REF] Lu | A novel tyrosinase biosensor based on hydroxyapatite-chitosan nanocomposite for the detection of phenolic compounds[END_REF][START_REF] Zhao | A facile route to the synthesis copper oxide/reduced graphene oxide nanocomposites and electrochemical detection of catechol organic pollutant[END_REF]. As environmental pollutants, dihydroxybenzene isomers have been the subject of many studies due to their presence and difficult degradation [START_REF] Wang | Application of gold nanoparticles/TiO 2 modified electrode for the electrooxidative determination of catechol in tea samples[END_REF]. Catechol (CT, 1,2-dihydroxybenzene) is one of the most important phenolic compounds found in teas, vegetables, fruits and tobaccos. Considered as one of the key fragments of tea catechins, CT is contained in tea at various concentrations ranging from 0.1 mg.g -1 to 0.1 g.g -1 [START_REF] Montserrat | Diazonium-functionalized tyrosinase-based biosensor for the detection of tea polyphenols[END_REF][START_REF] Li | Sensitive and facile determination of catechol and hydroquinone simultaneously under coexistence of resorcinol with a Zn/Al layered double hydroxide film modified glassy carbon electrode[END_REF]. Tea also contains proteins, amino acids, alkaloids, carbohydrates, lipoids, organic acids and inorganic elements. CT is of great biological importance with respect to anti-oxidant properties, antivirus and enzyme activities; however, an excessive intake may cause some health problems (Chambers, 1988;[START_REF] Yue | Carbon nanotubes/carbon paper composite electrode for sensitive detection of catechol in the presence of hydroquinone[END_REF]. CT is considered as an environmental pollutant by the European Union (EU) [START_REF] Xie | Simultaneous determination of positional isomers of benzenediols by capillary zone electrophoresis with square wave amperometric detection[END_REF]. It is responsible for renal tube degeneration and liver function decrease [START_REF] Aziz | Selective determination of catechol in the presence of hydroquinone at bare indium tin oxide electrodes via peak-potential separation and redox cycling by hydrazine[END_REF]. At low concentration in foods and cigarets, it can cause mutagenesis and cancerous alterations [START_REF] Hirakawa | Catechol and hydroquinone have different redox properties responsible for their differential DNA-damaging ability[END_REF]. Thus, it is critical to establish highly sensitive and selective analytical tools to identify and quantify traces of catechol in environmental samples.

Up to now, the most commonly used analytical methods include spectrophotometry [START_REF] Nagaraja | A sensitive and selective spectrophotometric estimation of catechol derivatives in pharmaceutical preparations[END_REF], gas chromatography [START_REF] Moldoveanu | Gas chromatography/mass spectrometry versus liquid chromatography/fluorescence detection in the analysis of phenols in mainstream cigarette smoke[END_REF] and high-performance liquid chromatography (HPLC) [START_REF] Marrubini | Direct analysis of phenol, catechol and hydroquinone in human urine by coupled-column HPLC with fluorimetric detection[END_REF]. These techniques have some disadvantages, such as complicated operation, poor selectivity and high cost and require highly skilled manpower. Electroanalytical methods may be of interest owning to their sensitivity, rapidity, simplicity and low cost [START_REF] Fekadu | Electrochemical determination of catechol in tea samples using anthraquinone modified carbon paste electrode[END_REF]. Thus, some electrochemical methods have been developed for the sensitive detection of CT [START_REF] Wang | Simultaneous determination of dihydroxybenzene isomers at single-wall carbon nanotube electrode[END_REF][START_REF] Lin | Sensitive and rapid determination of catechol in tea samples using mesoporous Al-doped silica modified electrode[END_REF][START_REF] Zhao | Simultaneous determination of hydroquinone and catechol at PASA/MWNTs composite film modified glassy carbon electrode[END_REF][START_REF] Zhao | A facile route to the synthesis copper oxide/reduced graphene oxide nanocomposites and electrochemical detection of catechol organic pollutant[END_REF][START_REF] Yue | Carbon nanotubes/carbon paper composite electrode for sensitive detection of catechol in the presence of hydroquinone[END_REF][START_REF] Yuan | Preparation of graphitic mesoporous carbon for the simultaneous detection of hydroquinone and catechol[END_REF]. They are mostly based on the use of chemically modified electrodes, such as anthraquinone modified carbon paste electrode [START_REF] Fekadu | Electrochemical determination of catechol in tea samples using anthraquinone modified carbon paste electrode[END_REF], multi-walled carbon nanotube modified carbon paste electrode [START_REF] Yongqing | Poly(sulfosalicylic acid)/multi-walled carbon nanotube modified electrode for the electrochemical detection of catechol[END_REF] and mesoporous Al-doped silica modified electrode [START_REF] Lin | Sensitive and rapid determination of catechol in tea samples using mesoporous Al-doped silica modified electrode[END_REF].

The modification of the electrode surface is intended to enhance both sensitivity and selectivity of the detection, but the above examples are based on the use of rather costly modifiers. The development of new composite materials, cheap and easy to prepare, likely to be used as effective electrode modifiers for the sensitive detection of CT is still needed.

Clay minerals are considered nowadays as interesting adsorbent materials due their low cost, abundance, their morphology ensuring a high surface-to-volume ratio and thus developing large active surface areas. In that context, for instance, [START_REF] Kong | A novel palygorskite modified carbon paste amperometric sensor for catechol determination[END_REF] reported a palygorskite modified carbon paste electrode for the determination of CT. However the adsorption capacities and the intrinsic selectivity of natural clays towards organic and inorganic pollutants can be low, restricting the extensive use of these materials [START_REF] Guggenheim | Definition of clays and clay minerals: Joint of AIPEA and CMS nomenclature Committees[END_REF]. In the aim to get more efficient adsorbents, the elaboration of organicinorganic hybrid materials based on the chemical modification of surface properties of natural clays with organo-functional moieties has become a promising way during the past decades [START_REF] Tonle | Functionalization of natural smectite-type clays by grafting with organosilanes: physico-chemical characterization and application to mercury (II) uptake[END_REF][START_REF] Tonle | Preconcentration and voltammetric analysis of mercury(II) at a carbon paste electrode modified with natural smectite-type clays grafted with organic chelating groups[END_REF]. The so-called organoclays can be obtained by modifying clays and clay minerals with organic groups through several processes: intercalation (or insertion), ion exchange, pillaring or surface grafting [START_REF] Park | Modification of external surface of laponite by silanegrafting[END_REF][START_REF] Piscitelli | Sodium montmorillonite silylation: unexpected effect of the aminosilane chain length[END_REF]. On the other hand, organoclay modified electrodes have been largely exploited in electroanalysis [START_REF] Tonle | Organoclay-modified electrodes: preparation, characterization and recent electroanalytical applications[END_REF], and most studies reported to date have been focused on layered clay minerals (smectite and kaolinite being the most investigated ones), which can be grafted via the hydroxyl groups localized at the outer surfaces or on the edges of clay particles (for smectitetype clays) or along the unshared plane of the alumina sheets in kaolinite.

In this study, amino-functionalized montmorillonites (Mt-NH 2 and MtH-NH 2 ) have been prepared by grafting [3(2-aminoethyl)]propyltrimethoxysilane (AEP-TMS) on purified clay mineral sample (Mt-Na), then on the same clay sample chemically activated in acid medium (MtH). For MtH-NH 2 material, the acid activation was performed before the grafting process to increase its surface area and enrich its structure with -OH binding sites (Gonzalez et al., 1984;[START_REF] Rodriguez | Acid activation of a Spanish sepiolite: physicochemical characterization, free silica content and surface area of products obtained[END_REF][START_REF] De Mello | Smectite organofunctionalized with thiol groups for adsorption of heavy metal ions[END_REF]. This may further result in an enhancement of the amount of grafted organosilanes. After characterization of the starting and modified clay materials, it was demonstrated that MtH-NH 2 can be used as prominent modifier for a GCE, and exploited for the preconcentration and sensitive detection of CT in water and tea samples.

Experimental

Clay mineral, materials and chemicals

The Na-montmorillonite clay mineral used in this work was obtained from the Source Clays Repository, University of Missouri-Columbia (Columbia, MO 65211, USA). The Namontmorillonite has the chemical formula NaSi 16 (Al 6 FeMg)O 20 (OH) 4 [START_REF] Van Olphen | Data handbook for clay materials and other non-metallic minerals[END_REF]. All chemicals were obtained commercially and used without further purification. Catechol (C 6 H 6 O 2 , 99%, Sigma-Aldrich), H 3 BO 3 (98%, Fisher Scientific International), HCl (36%, Phillip Harris), CH 3 COOH (Prolabo), KCl (99.5%, Fisher Scientific International), H 3 PO 4 (63%, Prolabo), K 2 HPO 4 (99% Prolabo), KH 2 PO 4 (99% Prolabo), (CH 3 COONa) (99% Prolabo), Hexaammineruthenium(III) chloride (Ru(NH 3 ) 6 Cl 3 , 98%, Sigma-Aldrich), and potassium hexacyanoferrate(III) (K 3 Fe(CN) 6 , Fluka) served as redox probes for permeability characterization of the film modified electrodes. Various electrolytes such as acetate buffer solution (0.1 M AB), phosphate buffer solution (0.1 M PB), and Britton-Robinson buffer solution (0.1 M BRB) were prepared from the appropriate chemicals mentioned above. The grafting agent propyl]trimethoxysilane, AEP-TMS, ≥ 98%) used for clay modification was obtained from Sigma-Aldrich. A tea sample was purchased from local market and treated as follow. Briefly, the tea sample was powdered with a mortar and a weighed portion (0.055 g) was used for catechol extraction with 50 mL of 90% ethanol/water solution for 24 h shaking at 80°C. The mixture was filtered and the volume made up to 25.0 mL for further measurement. All solutions were prepared with distilled water and experiments were carried out at room temperature.

Preparation of grafted materials

Before the grafting process, 1.5 g of sodium montmorillonite (Mt-Na) was activated with 150 mL of a 0.1 M HCl solution. This suspension was stirred for 4 h. Acid activation was used to remove sodium ions from the interlayer region. Then, 1 g of acid-activated montmorillonite, previously dried at 130°C for 4 h, was dispersed in 50 mL of 0.1 M AEP-TMS in dry toluene. The resulting mixture was heated and allowed to reflux under stirring for 72 h in an inert N 2 atmosphere. The solid obtained was washed successively with toluene, ethyl alcohol and then filtered. The product MtH-NH 2 was finally dried for 2 h at 120°C in an inert nitrogen atmosphere and stored in a flask. The same procedure was applied to get Mt-NH 2 , using the purified clay without the acid activation step.

Preparation of the working electrodes

The elaboration of sensors involved the deposition of each organoclay films onto glassy carbon electrode (GCE) surfaces by "drop coating". The GCE was first polished with alumina pastes and then rinsed for 5 min in a 1:1 water-ethanol mixture under sonication in order to remove any remaining alumina particles. Subsequently, aqueous dispersions of either raw Mt-Na, Mt-NH 2 or MtH-NH 2 (at 5 mg.mL -1 ) were prepared and 6 µL (30 µg of clay) were drop-coated onto the top of the GCE (surface area: 0.071 cm 2 ), which was dried at 110°C for 4 min in an oven prior to use. Throughout the text, the modified electrodes are referred to as GCE/Mt-Na, GCE/Mt-NH 2 and GCE/MtH-NH 2 for the GCE modified by raw Mt-Na, Mt-NH 2 and MtH-NH 2 , respectively.

Electrochemical procedures and apparatus

Cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) measurements were performed using the palmsens 3 potentiostat, equipped with the PS Trace 4.2 electrochemical analysis system and connected to a computer.

The voltammograms were recorded under quiescent conditions immediately after the immersion of the working electrode in a conventional single compartment cell containing the "analyte + electrolyte" solution, a pseudo reference electrode (Ag/Ag + ) and a platinum wire auxiliary electrode. Differential pulse voltammetry (DPV) measurements were performed in a 25 mL electrochemical cell containing 0.1 M Britton-Robinson buffer (BRB) solution (pH 4) and catechol at appropriate concentrations, in the potential range from -0.2 V to 0.8 V. All experiments were conducted at room temperature (25°C). EIS were carried out in5mM [Fe(CN) 6 ] 3-/4-(1:1) solution containing 0.1 M KCl over the frequency range of 0.1 Hz-10 kHz.The morphology of modified GCEs was analyzed by scanning electron microscopy (SEM) using a JEOL JCM-6000 apparatus (acceleration voltage of 15 kV). Fourier transform infrared spectroscopy (FTIR) was applied to assess the presence of organic groups in the final materials, using a Nicolet 8700 apparatus equipped with a specular reflectance accessory (Smart Collector). The crystallinity of raw and modified clay materials was determined by Xray diffraction analysis using a Stoe Stadi-p X-ray powder diffractometer (Stoe & Cie GmbH, Darmstadt, Germany), with Cu Kα1 radiation (40 kV, 30 mA and λ Cu =1.54056 Å). The Brunauer-Emmett-Teller (BET) surface areas of the samples were determined by means of N 2 adsorption at 77.13 K using a micrometrics model sorptometer (Thermo Electron Corporation, Sorptomatic Advanced Data Processing). Before N 2 adsorption, the samples were degassed at 307.13 K under vacuum. The surface area was defined from linear part of the BET equation. CHN elemental analysis was performed using CHNS Analyzer Euro EA 3000. The thermal behavior of the clay mineral before and after its modification was investigated by the thermogravimetric analysis (STA 409 C equipment Netzsch Geratebeau GmbH, Germany). Approximately 10 mg of each dried sample were heated from 25 to 1000 °C under nitrogen atmosphere with a heating rate of 10 °C/min. The pH of solutions was monitored using an Inolab pH-meter.

Results and discussion

Physico-chemical characterization of composite materials

FTIR spectroscopy was used to identify and compare the functional groups present in natural montmorillonite (Mt-Na), acid treated Mt (MtH) and modified montmorillonite (Mt-NH 2 and MtH-NH 2 ) as shown in Fig. 1. On the spectrum of raw clay mineral (Fig. 1a), one can observe a stretching vibration band at 3620 cm -1 , which is characteristic of Al-OH stretching of the octahedral sites of natural montmorillonite [START_REF] Biernacka | Organo-laponites as novel mesoporous supports for Manganese(III) salen catalysts[END_REF], while the bending mode of such hydroxyl groups appears at 916 cm -1 [START_REF] Qin | Influences of thermal pretreatment temperature and solvent on the organosilane modification of Al 13 -intercalated/Al-pillared montmorillonite[END_REF]. The peaks observed at 3404 and 1640 cm -1 are attributed to the -OH stretching and bending vibrations of physisorbed water in the interlamellar space of montmorillonite, respectively. Others observed bands, appearing on all investigated materials between 700 and 450 cm -1 correspond to Si-O-Si stretching (690 cm -1 ) and deformation (516 and 468 cm -1 ) of tetrahedral sites [START_REF] Mendelovici | Infrared study of attapulgite and HC1 treated attapulgite[END_REF]. The signals at 885, 843 and 777 cm -1 are due to Al-OH deformation, Fe-OH deformation and Mg-OH deformation respectively [START_REF] Amarasinghe | Molecular hydraulic properties of montmorillonite: a polarized Fourier transform infrared spectroscopic study[END_REF][START_REF] Katti | Relationship of swelling and swelling pressure on silica-water interactions in montmorillonite[END_REF]. After acid activation, some changes in the FTIR spectra (Fig. 1b) can be observed. The band intensity at 3620 and 1640 cm -1 increased slightly, thus suggesting that the MtH sample is more hydrophilic than the Mt-Na. The appearance of a shoulder around 3150 cm -1 traduces the presence of Si-OH groups arising upon Si-O-Al bonds breaking during the acid pretreatment. The OH stretching region of Mt is sensitive to the effects of interlayer modification, and the intercalation followed by the grafting of the organosilane on the internal surface -OH groups of MtH should have a major influence on the OH stretching pattern of the grafted organoclays. As a matter of fact, upon grafting of AEP-TMS, some pronounced changes occurred in the spectra of amino-montmorillonite clays samples (Mt-NH 2 and MtH-NH 2 ) (Fig. 1c and1d): the new absorption band at 2928 cm -1 is due to the antisymmetric stretching of -CH 2 bonds [START_REF] Qin | Influences of thermal pretreatment temperature and solvent on the organosilane modification of Al 13 -intercalated/Al-pillared montmorillonite[END_REF][START_REF] Xue | Effective NH 2 -grafting on attapulgite surfaces for adsorption of reactive dyes[END_REF] while the bands appearing at 1473 cm -1 and 1316 cm -1 are assigned to -CH 2 -scissoring deformation (symmetric and asymmetric respectively), both from the silane coupling agent. The symmetric stretching of -CH 2 bonds are also visible at 2840 cm -1 [START_REF] Qin | Influences of thermal pretreatment temperature and solvent on the organosilane modification of Al 13 -intercalated/Al-pillared montmorillonite[END_REF]. Comparing curves (c) & (d) of Figure 1 enables to point out qualitatively the interest of the acidic treatment on the efficiency of the functionalization (slightly more intense C-H bond for the MtH-NH 2 sample). The grafting process leads to a decrease in the intensity of the bands characteristics of OH stretching and bending vibrations of adsorbed water and the hydroxyl groups (respectively at 3404 and 1640 cm -1 ) and a very small deviation of the positions of these bands. This is due in one hand to the involvement of the hydroxyl groups in the grafting process, and in another hand to the removal of cations from the octahedral layer which causes some loss of water molecules.

(Figure 1 nm at 2θ = 6.5°) (Fig. 2A,curve c). This slight difference is probably due to a small amount of AEP-TMS in the interlamellar space of the clay mineral. Usually, the intercalation of guest species in montmorillonite layers induces significant changes in the basal spacing [START_REF] Mercier | Preparation, characterization and applications as heavy metals sorbents of covalently grafted thiol functionalities on the interlamelar surface of montmorillonite[END_REF]. The acid activation used in MtH-NH 2 synthesis resulted in a much bigger increase in the basal spacing of the MtH and MtH-NH 2 samples (1.30 nm to 1.80 nm) (Fig. 2A, curve c), probably due to AEP-TMS incorporated in basal spacing. It may indicate that the silane molecules were mainly hydrolyzed and condensed with the hydroxyl groups on the external surface of Mt. Another explanation could be that the interlayer organosilane molecules were hydrolyzed and condensed to form a cross-linked structure, causing small increase on the basal spacing and influencing the grafting of AEP-TMS on MtH. The TGA curves (Fig. 2B) revealed a significant increase in the loss of adsorbed water mass on the MtH (Fig. 2B, curve b) compared to raw Mt (Fig. 2B, curve a). Usually, the increase in water content leads to an increase in the basal spacing. This increase in water molecules is explained by the replacement of sodium ions in the interlayer space by water molecules. On the materials Mt-NH 2 (Fig. 2B,curve c) and MtH-NH 2 (Fig. 2B, curve d), the mass losses of absorbed water are comparable to that of the raw clay. Our hypothesis is that for the Mt-NH 2 sample, the organosilane was grafted on the surface without replacement of sodium ions while for the MtH-NH 2 , there was replacement of water molecules in the interlayer space of MtH and grafting on the surface.

(Figure 2 near here)

Elemental analysis was performed on the amino-grafted materials (Mt-NH 2 and MtH-NH 2 ) for C, H and N. The results obtained were 11.07 % C, 2.60 % H, 4.66 % N for Mt-NH 2 and 9.73 % C, 2.44 % H, 3.89 % N for MtH-NH 2 . This was evidence of the presence of nitrogencontaining moieties. To determine the structural formula of the grafted clay using the the chemical formula of Mt, NaSi 16 (Al 6 FeMg)O 20 (OH) 4 , we assumed grafting via one, two, three or four methoxy groups on one clay mineral structural unit as usually obtained during silylation of montmorillonite surfaces [START_REF] Su | Locking effect: A novel insight in the silylation of montmorillonite surfaces[END_REF]. The theoretical content of C: 11.34%, H: 2.72%, N: 3.78% for Mt-NH 2 and 10.04 % C, 2.46 % H, 3.90 % N for MtH-NH 2 is in accordance with the mechanism proposed in Scheme 1, supporting the idea that the chemical bonding of AEP-TMS on the clay material was effective as revealed by infrared results. The The sodium montmorillonite clay sample is mesoporous with a specific surface area of 31.48 m 2 /g. After direct grafting, the specific surface area of the synthesized material (Mt-NH 2 ) decreased to 8.49 m 2 /g, suggesting that the organosilane is covalently bound to the individual -OH groups at the edge of clay platelets, as shown by a previous work [START_REF] Celis | Heavy metal adsorption by functionalized clays[END_REF]. It is known that the low silanol surface density of montmorillonite clay mineral is a main factor limiting the covalent grafting of organic ligands and that better performance can be obtained by grafting organic functions in the interlayer region of montmorillonite [START_REF] Celis | Heavy metal adsorption by functionalized clays[END_REF][START_REF] Mercier | Preparation, characterization and applications as heavy metals sorbents of covalently grafted thiol functionalities on the interlamelar surface of montmorillonite[END_REF]. Another sample of sodium montmorillonite was activated in (Figure 3 near here)

Permeability properties of various modified electrodes

The electrochemical behavior of redox species at clay modified electrodes is expected to be affected by three main parameters: the concentration of the analyte, the accessible area of the working electrode and the speed of mass transfer for the probe within the film [START_REF] Fitch | Clay-modified electrodes: a review[END_REF]. indicating the progressive accumulation of [Fe(CN) 6 ] 3-that leveled off after about 50 scans, with steady-state peak current values larger by one order of magnitude than on bare GCE (Fig. 4A). Such accumulation is due to the electrostatic attraction between the negative redox probe [Fe(CN) 6 ] 3-and the positively charged amino groups present in the AEP-TMS chain grafted onto the montmorillonite surface (which are protonated in the acidic analysis medium used here, in the form of -NH 3 + groups). As also shown in Fig. 4A, the electrochemical signal after 50 scans on GCE/MtH-NH 2 (Ipa 22.22 µA, Ipc 23.66 µA) is significantly higher than those obtained on GCE/Mt-NH 2 (Ipa 14.79 µA, Ipc 17.74 µA). This difference is due to a larger content of AEP-TMS groups grafted onto the acid-treated montmorillonite.

Cyclic voltammetry of cationic probe [Ru(NH 3 ) 6 ] 3+ (Fig. S2 in Supplementary data) was also carried out in the potential range of -0.5 V to 0.0 V in the same electrolyte solution as above (0.1 M KCl/HCl, pH 1). For GCE coated with Mt-Na, a progressive accumulation was observed, reaching steady-state current values after about 50 scans (Fig. S2a). The peak currents at saturation (Ipa 19.33 µA, Ipc 18.06 µA) were much larger than those obtained at the bare GCE (Ipa 1.46 µA, Ipc 1.95 µA), as explained by favorableelectrostatic attraction between the cationic redox probe and the negatively charged montmorillonite platelets. This behavior results from both true physical diffusion of the analyte upon ion exchange in the coating, and mass-charge transfer phenomena arising from potential scanning [START_REF] Tonle | From clay to organoclay film modified electrodes: tuning charge selectivity in ion exchange voltammetry[END_REF]. On the opposite, when using GCE/Mt-NH 2 and GCE/MtH-NH 2 in the same conditions (Fig. S2 b &c), the protonated organoclay films acted as electrostatic barrier preventing the uptake of the cationic [Ru(NH 3 ) 6 ] 3+ species. This resulted in much lower redox peak currents on GCE/Mt-NH 2 (Ipa 3.81 µA, Ipc 4.81 µA) and GCE/MtH-NH 2 (Ipa 2.21 µA, Ipc 3.62 µA) than for the non-grafted clay film electrode GCE/Mt-Na (Fig. 4B), as explained by the electrostatic repulsions between the positively charged redox probe and the -NH 3 + groups of the organoclays. Again, the permselective effect was more intense for GCE/MtH-NH 2 electrode, supporting the idea that acid activation prior to AEP-TMS grafting resulted in more effective montmorillonite modification.

(Figure 4 near here)

EIS results

Electrochemical impedance spectroscopy (EIS) was used to evaluate the electrochemical properties of the various electrodes. In EIS, the semicircle portion at higher frequencies corresponds to the electron-transfer limited process (equals the charge-transfer resistance, R ct ), and the linear part at lower frequencies corresponds to the diffusion process. Fig. 5 shows the Nyquist plots of EIS for the bare GCE, GCE/Mt-Na, GCE/Mt-NH 2 and GCE/MtH-NH 2 electrodes, as recorded in 0.1 M KCl containing 5 mM [Fe(CN) 6 ] 3-/4-(1:1) solution over the frequency range of 0.1 Hz-10 kHz. At the bare GCE (curve (a) in Fig. 5), the probe is easy to transfer electron on the electrode surface, yet with a non-negligible R ct value of 4736 Ω.

The charge-transfer resistance was even larger (R ct = 5263 Ω) when using GCE/Mt-Na (curve (b) in Fig. 5), which is explained by some shielding behavior of the positively charged Mt 6

). This indicates the interest of the amino-grafted materials for enhancing the CT oxidation signal, suggesting the existence of accumulation effects originating from the grafted material, which are likely to improve the detection of CT, yet with slightly better response for GCE/MtH-NH 2 than for GCE/Mt-NH 2 (compare curves (c) & (d) on Fig. 6). This demonstrates the interest of the acid activation used during the grafted process to prepare MtH-NH 2 material, and also for CT detection. Such improvement is similar to that observed for the negatively charged redox probe discussed above (Fig. 4A), but in the present case "simple" electrostatic considerations cannot explain the phenomenon as catechol is neutral at pH values below its pKa (9.14) [START_REF] Nurchi | Effect of substituents on complex stability aimed at designing new iron(III) and aluminum(III) chelators[END_REF], and deprotonated at pH above that pKa.

The CV results indicate a clear positive effect of the ethylenediamino groups grafted on the clay material, and this was also confirmed for CT detection by DPV (see section 3.5.1). A possible explanation could be a favoured incorporation of CT in the organoclay as a result of larger interlayer distance between the clay sheets upon grafting (see section 3.1 and Fig. 2)

and also a more hydrophobic environment generated by the acidic treatment (in comparision to the hydrophilic Mt-Na material). The O and N groups of Mt-NH 2 and MtH-NH 2 acted as electron transfer mediators by possibly forming hydrogen bonding interactions with hydroxyl groups of CT. They have contributed to weakening the hydroxyl bond energies and facilitated the electron transfer through O--HO and N--HO [START_REF] Ding | Direct simultaneous determination of dihydroxybenzene isomers at C-nanotube-modified electrodes by derivative voltammetry[END_REF].

The Mt-NH 2 and MtH-NH 2 modifiers might also contribute to accelerate the electron transfer ratesfor catechol oxidation, as suggested from slightly lower overpotentials with respect to bare GCE (compare peak potentials of curves c & d to curve a in Fig. 6), also in agreement with the much lower charge transfer resistance values observed by EIS for the modified electrodes (see section 3.3). Due to its better performance with respect to CT detection, the GCE/MtH-NH 2 electrode was used for further experiments.

(Figure6 near here)

Effect of scan rate on the electrochemical response of catechol at GCE/MtH-NH 2

The influence of potential scan rate on the electrochemical response of catechol was studied by cyclic voltammetry and the results obtained are shown in Fig. 7. The peak currents increased with the scan rate in the studied range (Fig. 7a), remaining linear with the square root of the scan rate (v 1/2 ) (Fig. 7b). This indicates a diffusion-controlled process, phenomenon that was also confirmed by plotting the double logarithmic of Ipa vs scan rate (Fig. 7c), giving a slope (∂log(Ipa)/∂log(v)) equal to 0.49, close to 0.5, the characteristic value for a diffusion-controlled electron-transfer mechanism [START_REF] Shih | Flow injection analysis of zinc pyrithione in hair care products on a cobalt phthalocyanine modified screen-printed carbon electrode[END_REF].

(Figure 7 near here)

Differential pulse voltammetry study

Importance of the modification of Mt and effect of the detection medium

In order to evaluate the ability of AEP-TMS grafted Mt to accumulate quantitatively CT and the interest of the acid activation step before grafting, DPVs of 0.1 mM CT were recorded in 0.1 M BRB solution (pH 4) on bare GCE, GCE/Mt-Na, GCE/Mt-NH 2 and GCE/MtH-NH 2 (Fig. 8). Peak currents were found to decrease from the bare GCE (1.7 µA) to GCE/Mt-Na (0.75 µA), and increase when passing from GCE/Mt-Na (0.75 µA) to GCE/Mt-NH 2 (2.15 µA) and to GCE/MtH-NH 2 (2.9 µA). Meanwhile, the peak potentials shifted towards less anodic values: from +0.358 V on bare GCE to +0.271 V on GCE/Mt-Na, to +0.270 V on GCE/Mt-NH 2 and to +0.260 V on GCE/MtH-NH 2 . This indicates an the ability of Mt-NH 2 and MtH-NH 2 to induce effective enhancement of CT oxidation signal and improve the electron transfer rates, confirming the existence of both accumulation and electrocatalytic effects as suggested above, originating from the organoclay materials with respect to the detection of CT. Note that acid activation improved somewhat further the electrochemical detection of CT by increasing the current peak signal.

(Figure 8 near here)

Some optimization studies were also performed. Although the composition of the detection medium was not really critical (on the basis of three different buffer solutions), the BRB solution (pH 4) was found to be more sensitive to CT detection (see Fig. S3, Supplementary data). It will be thus used for further experiments. Fig. S4 (Supplementary data) shows the dependence of DPV peak currents on the accumulation time for the analysis of 0.1 mM CT at GCE/MtH-NH 2 electrode. The response was very fast, and the electrode was saturated after 30 s, reaching a plateau up to 140 s preconcentration. Fast adsorptive equilibrium is probably due to low resistance to mass transport in such highly porous film electrode. A duration of 30 s was used afterwards for the accumulation of CT.

Influence of pH on the peak current and potential

The influence of the pH of the detection medium on the electrochemical response of CT was studied in the range from 2 to 8 in BRB solution. Fig. 9a and curve (2) on Fig. 9b show that the oxidation peak potentials of CT on GCE/MtH-NH 2 shifted negatively with an increase in the solution pH, indicating that protons are involved in the reaction process at the electrode surface. The linear regression equation was Ep(V) = -0.0521 pH + 0.4819 (R 2 = 0.998),

demonstrating that equal number of electrons and protons are involved in the oxidation of CT.

This is in agreement with the previously reported mechanism for CT, that is oxidized to 1,2benzoquinone (Scheme 2) [START_REF] Temerk | Cathodic adsorptive stripping voltammetric determination of the antitumor drug rutin in pharmaceuticals, human urine and blood serum[END_REF][START_REF] Unnikrishnan | Electrochemically synthesized Pt-MnO 2 composite particles for simultaneous determination of catechol and hydroquinone[END_REF][START_REF] Yue | Carbon nanotubes/carbon paper composite electrode for sensitive detection of catechol in the presence of hydroquinone[END_REF].

Curve (1) on Fig. 9b shows the variation of the peak current of CT with pH. The peak intensity was high in acidic media, for pH values below 5, with a maximum at pH 2. The

Calibration

The calibration graph for CT detection was plotted from DPV analyses performed under the optimal conditions obtained above, in the concentration range from 5 μM to 80 μM, using the GCE/MtH-NH 2 electrode. As shown by the inset in Fig. 10, a linear variation of peak current (Ip) vs CT concentration was obtained in the explored range, with a sensitivity of 0.0468 µA.µM -1 and a correlation coefficient of 0.999. The detection limit, defined by the relation 3S b /m (where S b represents the standard deviation on the blank and m the slope on the calibration graph) as the analyte concentration yielding such smallest detectable signal [START_REF] Ghoneim | Mn, Ni, Co and Fe in water samples by differential pulse stripping voltammetry at a hanging mercury drop electrode[END_REF] was estimated to 0.65 µM. This demonstrates that GCE/MtH-NH 2 can be exploited for the electroanalysis of CT in aqueous media in the µM range. The analytical performance of GCE/MtH-NH 2 electrode is comparable or better than some data reported in previous literature as shown in Table 1. A relative standard deviation (RSD) of 3.1 % for parallel detections of 0.1 mM CT using five distinct electrodes (see Fig. S5 in Supplementary data) was obtained, indicating a good reproducibility and repeatability of the modified electrode. The anodic peak current of CT lost 4.6 % of its initial value, after 5 consecutive DPV measurements on the same electrode and in the same conditions. This result shows that the proposed electrode is mechanical stable and reliable for the determination of CT. The performance of the method proposed herein is comparable, and even better than some data already reported on the quantification of CT using other modified electrodes [START_REF] Figueiredo | Online molecularly imprinted solid phase extraction for the selective spectrophotometric determination of catechol[END_REF][START_REF] Sun | Application of carbon ionic liquid electrode for the electrooxidative determination of catechol[END_REF][START_REF] Li | Sensitive and facile determination of catechol and hydroquinone simultaneously under coexistence of resorcinol with a Zn/Al layered double hydroxide film modified glassy carbon electrode[END_REF][START_REF] Yang | Simultaneous determination of hydroquinone and catechol using poly(p-aminobenzoic acid) modified glassy carbon electrode[END_REF].

(Figure 10 near here)

(Table 1 near here)

Interference of some organic molecules and real samples analysis

The effect of potential interfering molecules including hydroquinone, ascorbic acid, dopamine, citric acid, uric acid, D-glucose and quercetin on the DPVs response of CT has been studied. The results obtained are presented in Table 2. The tolerance limit was defined as the concentration ratio of the additive over CT causing less than 5.0 % relative error. Each interfering species was added in the supporting electrolyte in a concentration 5-fold higher than CT concentration. The results obtained showed that the oxidation peak of CT is greatly affected by the presence of hydroquinone, ascorbic acid and quercetin. Catechol and hydroquinone are two isomers of phenolic compounds. The broad DPV response obtained at the GCE/MtH-NH 2 indicated a very tiny sign of multiple components that were not easily separated. However, the selectivity of the proposed sensor was evidenced by the neglected responses toward interfering species, by considering the tolerance limit defined earlier.

(Table 2 near here)

The proposed method was applied to the determination of CT in one tea sample. In this experiment, the concentration of CT was calculated using the standard addition method. The concentration of CT in tea sample was 0.851 mg.g -1 . The detection of CT was also evaluated for the analysis of tap and lake water samples after filtering with a Whatman paper (diameter: 125mm). In DPV, no signal of CT was detected in the natural (non-spiked) water samples when using GCE/MtH-NH 2 , indicating that their CT contents were below the detection limit (0.65 µM). Therefore, recovery experiments were performed by measuring the DPV responses from samples to which known concentrations of CT were added. The quantitative results are summarized in Table 3. Recovery percentages of more than 110% obtained in the case of lake water are due to intensive agricultural activities around the lake where other organic compounds are found upon leaching. Yet, the amino groups on the organoclay has high affinity with many biomolecules, a fact that could explain such a result.

(Table 3 near here)

Conclusion

The aim of this work was to develop a voltammetric sensor based on amino-montmorillonite and apply it to the detection of catechol. (1) , 10, 15, 20, 25, 30, 40, 50, 60, 70 and 80 μM. Accumulation time: 30 s. Inset shows the corresponding calibration graph.

Figure caption

  near here) XRD patterns of raw Mt-Na, acid treated Mt (MtH), Mt-NH 2 and MtH-NH 2 are shown in Fig. 2. A comparison of the results obtained indicates that the original structure has been retained after modification. An approximate value of 1.21 nm (2θ = 7.3°) was estimated for the basal spacing d 001 of the Mt-Na sample (Fig. 2A, curve a). The acid activation led to an increase in the basal spacing (1.21 to 1.30 nm), most likely due to water adsorption. The increased hydrophilic feature of the MtH (Fig. 2A, curve b) with respect to the starting Mt was previously indicated by the IR results. Direct grafting of AEP-TMS onto Mt-Na showed a minimal difference in basal spacing between the Mt-Na and Mt-NH 2 samples (1.21 nm to 1.36

  Scheme 1. Proposed mechanism for the grafting of AEP-TMS on (a) Mt and (b) MtH.

  acid medium (MtH) and then functionalized (MtH-NH 2 ). A specific surface area of 19.66 m 2 /g obtained for the MtH-NH 2 material suggests a low graft rate on the surface of the material but the increase in basal spacing obtained in XRD analysis from 1.36 nm (Mt-NH 2 ) to 1.80 nm (MtH-NH 2 ) confirms the intercalation followed by the concomitant coupling of the organosilane moieties on the -OH groups found the internal surface of on the clay layers, and on the borders of the clay platelets.SEM micrographs of the GCE modified in turn by Mt-Na, acid treated Mt (MtH), Mt-NH 2 and MtH-NH 2 respectively are shown in Fig.3. On the micrographs of GCE/Mt-Na and GCE/MtH (Fig.3a& 3b), one can observe the strong tendency toward aggregation and the compact aspect of the material, with particles arranged in the form of agglomerates of irregular shape and flat surface. For the Mt-NH 2 and MtH-NH 2 modified GCEs (Fig.3c & 3d), the particles are even more agglomerated and present onto the electrode surface as big aggregates, suggesting that the functionalization of clay may have contributed to enhance the edge-to-edge and face-to face interactions between organoclay platelets.

  Figure 4(A) & (B)). The peak current values obtained are I pa 3.06 µA (anodic), I pc 2.9 µA

  clay particles on the anionic [Fe(CN) 6 ] 3-/4-species. With the grafting of AEP-TMS on Mt-Na, the resistance decreased (see curves (c) and (d) of Fig.5), implying that Mt-NH 2 and MtH-NH 2 promote the transport properties of the [Fe(CN) 6 ] 3-/4-probes. This resulted in lower R ct values (R ct = 114.35 Ω with GCE/MtH-NH 2 and R ct = 167.84 Ω with GCE/Mt-NH 2 ), the small difference between them being again due to the fact that acid activation allowed the binding of a greater amount of AEP-TMS moieties on the Mt clay.(Figure5near here)3.4. Preliminary studies on the electrochemical behavior of catechol3.4.1. Direct electrochemistry of catecholThe electrochemical behaviour of catechol on various electrodes was carried out in 0.1 M Britton-Robinson buffer (BRB) solution at pH 4 in the potential range from -0.2 V to 0.8 V, and the results are shown in Fig.6. A pair of quasi-reversible redox peaks are observed on all CV curves, indicating that the electroactive substance can reach and be detected on all electrode surfaces. Nevertheless, significant variations in peak intensity were observed depending on the electrode type. Peak currents were almost 2-fold lower on GCE/Mt-Nathan on bare GCE (curves(a) & (b) on Fig.6), whereas significantly more intense signals were observed when passing to GCE modified by amino-grafted materials (curves(c) & (d) on Fig.

  Scheme 2. Mechanism of catechol oxidation

  [3(2-aminoethyl)]propyl groups were grafted onto the surface of Na-montmorillonite and acid-activated montmorillonite clays. The results of the analyses by infrared spectroscopy, X-ray diffraction and EIS confirmed the effectiveness of the grafting process. It was demonstrated by CV and DPV that the detection of CT is improved when using the aminated montmorillonite (MtH-NH 2 ) obtained after acid activation, in comparison to the bare glassy carbon electrode. With DPV, the peak current of GCE/MtH-NH 2 was 1.71-fold greater than signal obtained on the bare GCE. After optimization of the factors affecting the accumulation/detection steps, the proposed method was applied to the detection of catechol in real water samples and in a commercial tea sample.

  Figure 1

Fig. 1 .

 1 Fig. 1. Infrared spectra of raw (a): Mt-Na, (b): MtH, (c): Mt-NH 2 and (d): MtH-NH 2 .

Fig. 2 .Fig. 3 .Fig. 4 .Fig. 5 .

 2345 Fig. 2. (A) Powdered X-ray diffraction patterns, and (B) TGA curves of (a): Mt-Na, (b): MtH, (c): Mt-NH 2 and (4): MtH-NH 2 .

Fig. 6 .

 6 Fig. 6. Cyclic voltammograms recorded at 50 mV.s -1 for 0.2 mM CT in 0.1 M BRB solution (pH 4) on (a): bare GCE, (b): GCE/Mt-Na, (c): GCE/Mt-NH 2 and (d): GCE/ MtH-NH 2 .

Fig. 7 .

 7 Fig. 7. (a) Cyclic voltammograms recorded for 0.2 mM CT in 0.1 M BRB solution (pH 4) on GCE/MtH-NH 2 at different scan rates (10, 15, 25, 35, 50, 65, 75 and 100 mV.s -1 ), (b) Peak current as a function of v 1/2 and (c) log(Ipa) as a function of log(v).

Fig. 8 .

 8 Fig. 8. DPVs of 0.1 mM CT recorded in 0.1 M BRB solution (pH 4) on (a): bare GCE, (b): GCE/Mt-Na, (c): GCE/Mt-NH 2 and (d): GCE/MtH-NH 2 (c). Accumulation time: 5 s. The dot line represents the signal of the bare GCE in blank solution.

Fig. 9 .

 9 Fig. 9. (a) DPV curves of 0.1 mM CT (obtained in triplicate) in 0.1 M BRB solution on GCE/MtH-NH 2 at various pH; (b) effect of pH, (1): on the peak current and (2): on the peak potential. Accumulation time: 5 s.

Fig. 10 .

 10 Fig. 10. DPV curves recorded under optimized conditions in 0.1 M BRB solution (pH 2) on GCE/MtH-NH 2 for different concentrations of CT (a-l): 5, 10, 15, 20, 25, 30, 40, 50, 60, 70

Acknowledgments

Financial support from UNESCO and The World Academy of Sciences for the Advancement of Science in Developing Countries (RGA 19-257 RG/CHE/AF/AC_G-FR3240310134 awarded to I.K. Tonle) is gratefully acknowledged. A.T. Kamdem (Dr. A. Osorio Group, University of Freiburg, Germany) and G. Doungmo (Prof Dr H. Terraschke Group, Christian-Albrechts-Universität zu Kiel, Germany) are thanked for facilitation in samples analyses.