TWO LIGAND OXIDIO-VANADIUM ( IV ) COMPLEXES AS NOVEL EFFICIENT CATALYSTS IN MULTICOMPONENT REACTIONS FOR SYNTHESIS OF TETRAHYDROBENZOPYRAN DERIVATIVES

Two ligand oxido-vanadium(IV) complexes, [VO(L)(bipy)] (Ι) and [VO(L)(phen)] (ΙΙ); [H2L: 4-bromo-2-(((5-chloro-2-hydroxyphenyl)imino)methyl)phenol, bipy: 2,2’-bipyridine and phen: 1,10phenanthroline], have been synthesized and characterized by elemental analysis, FT-IR, UV-Vis and conductivity measurements. These complexes, as new catalysts, were also used to synthesize the tetrahydrobenzopyran derivatives by three-component reaction of cyclic β-dicarbonyl compounds, malononitrile and aromatic aldehydes, in EtOH, at reflux. Inexpensiveness, stability and the potential of being easily obtained can be noted as preponderance of these catalysts. Furthermore, high conversions, short reaction times and cleaner reaction profiles, are some of the advantages of this method. These catalysts can be recovered and reused several times without loss of activity.


INTRODUCTION
The development of environmental safe and clean synthetic procedures has become the goal of present day organic synthesis.More than ever, the industry requests organic chemists the expansion of new strategies and technologies, to gain novel compounds in a fast, convergent and efficient way.One of the most attractive apparatus in modern organic chemistry is the use of multicomponent reactions (MCRs), which combine in one-pot at least three simple building blocks, provide a most powerful to make functionalized compounds [1][2][3][4][5][6][7].MCRs as efficient and effective methods are considered a vital technique in the synthesis of many important heterocyclic compounds such as tetrahydrobenzopyran derivatives nowadays.
Due to the important properties of tetrahydrobenzopyran derivatives, considerable attentions have been focused on the development of environmentally friendly procedures to synthesize tetrahydrobenzopyrans, by three-component reaction cyclic β-dicarbonyl compounds, malononitrile and aromatic aldehydes.Various catalytic systems such as potassium phthalimide-N-oxyl (POPINO) [19], CaCl 2 under ultrasonic irradiation [20], high surface area MgO [21], tetrabutylammonium bromide [22], Nano-ZnO [23], K 3 PO 4 [24], NaOCl under grinding [25], SiO 2 nanoparticles [26], triethylbenzylammonium chloride (TEBA) [27] and Ni(NO 3 ) 2 .6H 2 O [28] have been reported.Each of these methods has its own merits, but the use of toxic organic solvents, expensive catalysts, containing transition metals, difficult work up, high reaction time, and low yields are drawbacks of these procedures.Thus to expand a simple and green synthesis of tetrahydrobenzopyran derivatives it is necessary to remove these restrictions.
Herein we consider the synthesis of compound 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4a) for a representative example to show the advantage of this work in comparison with previously reported procedures.As shown in Table 1, our catalyst produces compound 4a with high yield in a short time.Also oxidio-vanadium(IV) complexes are a recyclable catalyst and ethanol was used as a green solvent.Moreover oxidiovanadium(IV) complexes are more stable in air and non-toxic compared with other catalysts.

EXPERIMENTAL
All chemicals and solvents were purchased from Aldrich and Merck and used without further purification.[H 2 L] and [VO(L)(bipy)] were prepared according to our previous work [33,34].Melting points were measured on an Electrothermal-9100 apparatus and are uncorrected.IR spectra were recorded on a Brucker FT-IR Tensor 27 infrared and FT-IR 8400-Shimadzu spectrophotometer. 1 H NMR spectra were recorded on a Brucker Avance III 400 MHz spectrometer. 13C NMR spectra were recorded on the same instruments at 100 MHz using TMS as an internal standard.Molar conductance measurements were made by means of a Metrohm 712 conductometer in DMSO.Elemental analyses were performed using a Heracus CHN-O-Rapid analyzer and Thermo Finnigan Flash Elemental Analyzer 1112EA.Electronic spectra of the complexes in DMSO solutions were recorded with a Shimadzu model 2550 UV-Vis spectrophotometer.

General procedure for preparation of the complexes
A 8 mL methanolic solution of H 2 L (0.1 mmol, 0.03 g) and equimolar quantity of VOSO 4 .3H 2 O (0.03 g) was refluxed for 1 h.Appropriate aromatic heterocyclic base (0.1 mmol, 0.02 g) was added to the resulting brown solution, and the reflux was continued for 3 h.After cooling, the formed solid was filtered off, washed with cold ethanol, and dried in a vacuum desiccator over CaCl 2 .(

Typical procedure for the preparation of tetrahydro-4H-chromene derivatives (4a-g')
A mixture of dimedone (1a) or 1,3-cyclohexanedione (1b) (2 mmol), malononitrile (2) (2 mmol), aromatic aldehydes (3a-r) (2 mmol), and appropriate oxido-vanadium(IV) complex (10 mol%) in EtOH (10 mL) was refluxed for the reported time in Table 5 (the progress of the reaction being monitored by TLC and hexane/ethyl acetate was used as an eluent).After completion of the reaction, the filtrate of the reaction mixture was achieved to recover oxidovanadium(IV) complexes and the reaction mixture was poured into ice-cold water; the crude product was filtered, dried and recrystallized from ethanol.

General aspect
Schematic diagram for synthesis of [VO(L)(bipy)] and [VO(L)(phen)] complexes are shown in Scheme 2. These complexes were obtained in good yields of 67-71%.They are partially soluble in common organic solvents, but have excellent solubility in DMF and DMSO.These complexes showed non-electrolyte behavior in DMSO (10 -3 M).

Spectral characterization
Assignments of selected prominent IR bands in the 400-4000 cm -1 region for complexes are gathered in the Experimental section.In the FT-IR spectra of complexes, bands observed in the region of 2885-3448 cm -1 are assigned to CH vibrations.The bands at 948-949 cm -1 are due to v(V=O) of the vanadyl moiety [35].The stretching vibration of the C-O bond is disclosed at 1288 and 1296 cm -1 for Ι and ΙΙ, respectively [36].The strong band at 1597 cm -1 is related to azomethine vibration of [VO(L)(bipy)] and it appeared at 1605 cm -1 in [VO(L)(phen)] [37].
In the electronic spectra of complexes, the bands at 276 and 263 can be related to a π→π* transition.The bands appeared at ca 444 nm, are assigned to LMCT charge transfer.The Peaks at 658 nm in Ι and 664 nm in ΙΙ are related to d-d transitions [36].

Catalytic activity
To optimize the reaction conditions, we used some polar and nonpolar solvents in the threecomponent reaction of dimedone 1a, malononitrile 2 and benzaldehyde 3a in the presence of catalysts such as [VO(L)(phen)] and [VO(L)(bipy)] as model reactions to investigate the effects of solvent for preparing compound 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile 4a.In each case, the substrates were mixed together with 10 mol% [VO(L)(phen)] and [VO(L)(bipy)] agitated with 10 mL solvent under reflux.The results are shown in Table 2.The best results in terms of reaction time and yield of the desired product 4a was obtained when the reaction was conducted in ethanol.
We also optimized the quantity of catalysts.The best results were obtained when the reactions were carried out in the presence of 10 mol% [VO(L)(phen)] and [VO(L)(bipy)].The results are shown in Table 3.
We also attempted to reuse the catalysts by a variety of methods (Table 4).Direct reuse of the catalysts (Table 4, entry 2, 6) led to a greater than 20% decrease in activity, while washing of the catalysts with dichloromethane and ethyl acetate, prior to reuse also resulted in lower conversions (Table 4, entry 3, 4, 7, 8).This phenomenon probably arose because the reactant and product were not completely desorbed from [VO(L)(phen)] and [VO(L)(bipy)] and therefore, the active sites were blocked.
Table 3. Optimized the quantity of catalysts on the three-component reaction for the synthesis of 4a.To rely on our collected data, we decided to apply this method for synthesis of tetrahydrobenzopyran derivatives by using three-component reaction of dimedone (1a) or 1,3cyclohexanedione (1b), malononitrile (2) and aromatic aldehydes (3a-r), in EtOH, at reflux, in the presence of 10 mol% [VO(L)(phen)] and [VO(L)(bipy)] (Table 5

CONCLUSION
The present study reports, synthesis and characterization of two mixed ligand oxidovanadium(IV) complexes containing ONO tridentate Schiff base, 4-bromo-2-(((5-chloro-2hydroxyphenyl)imino)methyl)phenol (H 2 L) and appropriate aromatic hetrocylic base, 2,2'bipyridine and 1,10-phenanthroline for [VO(L)(bipy)] and [VO(L)(phen)], respectively.We have also investigated the use of these complexes as new and effective catalysts, for threecomponent reaction of dimedone or 1,3-cyclohexanedione, malononitrile and aromatic aldehydes, which leads to the synthesis of tetrahydrobenzopyran derivatives.These reactions were carried out in EtOH at reflux.High yields, clean reaction conditions in comparison with existing methods and reusability of the catalyst with consistent activity are advantages of this procedure that make it a useful practical process for the synthesis of these compounds.

Mehdi
Scheme 2. Schematic diagram for the complexation process.

Table 1 .
Comparison results of oxidio-vanadium(IV) complexes with other catalysts reported in the literature for the synthesis of compound 4a.
).In these reactions, in first step Knoevenagel condensation takes place to form the 2arylidenemalononitrile derivatives (A).The active methine of cyclic β-dicarbonyl compounds react with the electrophilic C=C double bond of 2-arylidenemalononitrile to give the intermediate (B) which tautomerizes into C.The next step is cyclized by nucleophilic attack of the negative oxygen atom on the cyano (CN) moiety, giving intermediate D. The expected product 4a-4g' (tetrahydrobenzopyrans), is afforded by tautomerization.Here, the catalytic activity of the complexes was established for Knoevenagel condensation and Michael addition reactions.Whereas V 5+ as a Lewis acid, coordinated to the oxygen of carbonyl group of aldehyde and nitrogen of cyano (CN) moiety, polarized the π-electron cloud carbonyl and cyano (CN) group, which leads to attack by nucleophiles easier to carbonyl group and cyano (CN) moiety (Scheme 3).Scheme 3. Proposed mechanism for the synthesis of tetrahydrobenzopyran derivatives catalyzed by oxido-vanadium(IV) complexes (Ι and ΙΙ).