Synthesis , Characterization and Chelating Properties of Benzimidazole-Salicylic Acid Combined Molecule

Aminomethylation (i.e. Mannich reaction) of benzimidazole was carried out by treating benzimidalzole with formaldehyde and 4-aminosalicylic acid. The resultant compound was designated as 1-(4-carboxy-3-hydroxyphenyl aminomethyl) benzimidazole (BI-SA). The transition metal complexes of Cu, Co, Ni, Mn, Zn and Fe of BI-SA have been prepared and characterized by elemental analyses, spectral studies, magnetic moment determination, molar conductivity measurement and microbicidal activity.


INTRODUCTION
Benzimidazoles belonging to the fused heterocyclic system prepared from amino acids are associated with diverse pharmaceutical activities such as antibacterial 1 , insecticidal 2 , fungicidal 3 , antimicrobial 4 , asvitronectial receptes, antagonist 5 , anthelmintic [6][7][8] , anti-inflamonatary 9 , etc.Recently the benzimidazole derivative has been reported with remarkable antimicrobial activity 10 .The Mannich reaction of benzimidazole derivative with 4-N-methyl aminosalicylic acid has not been reported so far.Though 4amino salicylic acid is excellent anti T.B agent.Thus this may afford good chelating ligand with better microbicidal activity.Hence the preliminary work regarding this has been reported recently [].In extension of this work the present communication comprises the studies on benzimidazole-salicylic acid combined molecule and its metal chelates.The research work is illustrated in scheme-I.

EXPERIMENTAL Materials
Benzimidazole was prepared by method reported in literature 11 .p-Amino salicylic acid (PAS) (i.e.4-Nmethyl aminosalicylic acid) was obtained from local dealer.All other chemicals used were of analytical grade.

Measurements
The elemental analysis for C, H and N were carried out on elemental analyzer TF-EA.1101(Italy).IR spectra of BI-SA and its metal complexes were scanned on a Nicolet 760 FTIR spectrophotometer in KBr.The NMR spectrum of BI-SA was scanned on Brucker NMR spectrophotometer using DMSO solvent.The metal content of the metal chelate were performed by decomposing a weighed amount of each metal complexes followed by EDTA titration as reported in literature 12 .Magnetic susceptibility measurement of all the metal complex was carried out at room temperature by the Gouy mehod.Mercury tetrathiocynatocobalate (II) Hg [Co (NCS) 4 ] was used as a calibrant.The diffused reflectance spectra of solid metal complex were recorded on a Backman DK Spectrophotometer with a sodid reflectance attachment, MgO was employed as the reflectance compound.The electrical conductivity of all the complexes was measure in acetonitrile at 10 -3 M concentration.

Antifungal activity
The fungicidal activity of all the compounds was studied at 1000 ppm concentration in vitro plant pathogenic organisms listed in Table-3.The antifungal activities of all the samples were measured by cup plate method 13 .Each of the plant pathogenic strains on potato dextrose agar (PDA) medium.Such a PDA medium contained potato 200 gms, dextrose 20gms, agar 20gms and water 1 litre.5 days old cultures were employed.The compounds to be tested were suspended (1000ppm) in a PDA medium and autoclaved at 120° C for 15 min.at 15 atm pressure.These medium were poured into sterile Petri plate and the organisms were inoculated after cooling the Petri plate.The percentage inhabitation for fungi was calculated after 5 days using the formula given below.

RESULTS AND DISCUSSION
The parent ligand BI-SA was an amorphous brown powder, soluble in various solvents like dioxane, DMSO and DMF.The results of elemental analysis of the ligand are reported in experimental part.They are consistent with the predicted structure as shown in Scheme-I.
Examination of IR spectrum (not shown) of BI-SA reveals that broad band of phenolic hydroxyl stretching is observed at 3200-3600 cm -1 as well as additional absorption bands at 3030, 1500 and 1600 are characteristics of the salicylic acid 10,11  Inspection of the IR Spectra (not shown) of metal chelates reveals that all the spectra are identical in all respects.The comparison of IR spectrum of the parent ligand BI-SA with that of its each metal chelates has revealed certain characteristics differences.
One of the significant differences to be expected between the IR spectrum of the 8parent ligand and its metal chelates is the presence of more broadened bands in the region of 3200-3600 cm -1 for the metal chelates as the oxygen of the O-H group of the ligands forms a coordination bond with the metal ions [13][14][15] .This is explained by the fact that water molecule might have strongly absorbed to the metal chelates samples during their formation.Another noticeable difference is that the bands due to the COO -anion at 1600 cm -1 in the IR spectrum of the each metal chelates.The band at 1400 cm -1 in the IR Spectrum of HL assigned to inplane OH determination [13][14][15] is shifted towards higher frequency in the spectra of confirmed by a week bands at 1105 cm -1 corresponding to C-O-M starching [13][14][15] .Thus all of these characteristics features of the IR studies suggested the structure of the metal chelates as shown in scheme.
Examination of data of the metal content in each compound revealed a 1:2 metal: ligand (M: L) stoichiometry in all of the chelate of divalent metal ions and 1:3 metal: ligand stoichiometry for Fe 3+ .Magnetic moment (µ eff ) of each of the metal chelates is given in Table -2.Examination of these data reveals that all chelates other than that of Zn 2+ , are Para magnetic while those of Zn 2+ are diamagnetic.The diffuse electronic spectrum of the [Cu HL (H 2 O) 2 ] metal complex shows broad bands at 15860 and 22685 cm -1 due to the 2 T→ 2 T 2 g transition and charge transfer, respectively suggesting a distorted octahedral structure [16][17][18] for the [Cu HL (H 2 O) 2 ] complex.Which is further confirmed by the higher value of µ eff of the [Cu HL (H 2 O) 2] complex.The [Ni HL (H 2 O) 2 ] and [Cu HL (H 2 O) 2 ] complex gave two absorption bands respectively at 15601, 22983, and 15375, 22715, cm -1 corresponding to 4 T 1 g→ 2 T 1 g and 4 T 1 g (p) transitions.Thus absorption bands at the diffuse, reflectance spectra and the value of the magnetic moments µ eff indicate and octahedral configuration for the [NiHL (H 2 O) 2 ] and [Cu HL (H 2 O) 2 ] complex.The spectra of [Mn HL (H 2 O) 2 ] shows weak bands at 15374, 17649, and 22960 cm -1 assigned to the transitions 6 A 1g → 4 T 1g (4G), 6 A 1g → 4 T 2g (4G) and 6 A 1g (F) → 4 T 1 g , respectively suggesting an octahedral structure for the [Mn HL (H 2 O) 2 ] chelate.The spectrum of Fe 3+ complex has not been adequately characterized.The spectrum comprised the band ground 19012cm -1 and other weak band ground 23001 cm -1 .The latter has not very long tail.These may have the transition 6 A 1g → 4 T 2g (4G) and 6 A 1 → 4 T 1 (4G).The high intensities of the bands suggests that they might be charge transfer in origin µ eff Vol.2, No.4 (2009), 895-900 BENZIMIDAZOLE-SALICYLIC ACID COMBINED MOLECULE Kamlesh V. Patel and Arun Singh 898 is found to be lower than normal range.In the absence of low temperature moments it is difficult to give any significance.As the spectrum of the [Zn HL (H 2 O) 2 ] polymer is not well resolved, it is not interpreted but it is µ eff value shows that it is diamagnetic as expected.
Conductivities of all the complexes were measured in acetonitrile solvent and all the complexes were found to be electrolytic 19 in nature of 1:2 type and molar conductivity values are in the range of 25.3-39.1 Ohm -1 Cm -1 .
The antifungal activity of all the compounds measured for various plant pathogens.Inspection of the result shown in Table -3 indicates that all compounds are good toxic for fungi.Out of all the compounds copper chelates is more toxic than other.These compounds almost inhibit the fungi about 70%.Hence produced metal chelates can be employed as garden fungicides.Further work in the direction is in progress.

ACKNOWLEDGMENTS
The author thanks to Principal, Govt.Geetanjali P.G.

Vol. 2 ,
No.4 (2009), 895-900 BENZIMIDAZOLE-SALICYLIC ACID COMBINED MOLECULE Kamlesh V. Patel and Arun Singh 897 Percentage of inhibition =100 (X-Y) X Where, X: Area of colony in control plate Y: Area of colony in test plateThe fungicidal activity all compound are shown in Table-3

Synthesis of metal chelates of BI-SA
BENZIMIDAZOLE-SALICYLIC ACID COMBINED MOLECULE Kamlesh V. Patel and Arun Singh 896 Acid Value Theoretical: 195.8 mg KOH/1g.Sample.Found: 194 KOH/1g Sample.water and air dried.It was amorphous powder.Yield was almost quantitative.The detail are given in Table-1.
. The strong bands at 1680 for C=O and band at 3400 for sec.NH.The NMR data (shown in experimental part) also confirm the structure of BI-SA.8The Metal chelate of BI-SA with ions Cu 2+ ,Co 2+ , Ni 2+ , Mn 2+ , Zn 2+ , Fe 3+ vary in colours.On the basis of the proposed structure as shown in Scheme-1, the molecular formula of the BI-SA ligand is C 15 H 13 O 3 N 3 .Which upon complexion coordinates with one central metal atom at four coordination sites and with two water molecules.Therefore the general molecular formula of the resulting metal chelate is [C 15 H 12 O 3 N 3 ] 2 M.2H 2 O for divalent metal ions.This has been confirmed by results of elemental analysis reported in Table-1.The data are in agreement with the calculated values.
Collage, Bhopal for providing necessary research facilities.
BENZIMIDAZOLE-SALICYLIC ACID COMBINED MOLECULEKamlesh V. Patel and Arun Singh

Table - 1
: Analytical Data of the Metal Chelates of HL 1 (i.e.BI-SA)

Table - 2
Magnetic Moment and Reflectance Spectral data of Metal Chelates of BI -SA ligand