Application of nickel-catalysed reduction and azo dye reactions for the determination of tinidazole A V S S Prasad, P Muralidhar Reddy, K Shanker, R Rohini and V Ravinder* Department of Chemistry, Kakatiya University, Warangal-506 009, India Email: ravichemku@rediffmail.com Received: 30 March 2009; Accepted: 17 August 2009 A macrocyclic Schiff base nickel(II) complex was synthesised via template synthesis by treating acetylacetone with 1,8-diaminonaphthalene in the presence of nickel chloride in a 2:2:1 ratio in an aqueous methanol solution at 75 °C for 30 min. It was characterised by elemental, infrared, proton and carbon nuclear magnetic resonance and mass spectral analysis and used as a catalyst for the reduction of tinidazole. The reduced tinidazole was treated with nitrous acid and 2-naphthol and the resulting azo dye was used for the spectrophotometric determination of the reduction product of tinidazole. Introduction Azo dyes are widely used for the determination of drugs in pharmaceutical preparations [1,2]. Tinidazole is an anti-parasitic drug used against protozoan infections and it has the chemical structure 1-(2-ethylsulphonylethyl)-2- methyl-5-nitro-imidazole. Existing literature methods to produce tinidazole involve either tedious reduction procedures [3] or costly reagents for the spectrophotometric determination [4,5] by using reductants such as zinc ⁄ hydrogen chloride (Zn ⁄ HCl), palladium on carbon (Pd-C) ⁄ formic acid and copper sulphate ⁄ pyridine in acidic medium and colour reagents such as 4-dimethylaminobenzaldehyde, sodium 1,2- naphthaquinone-4-sulphonate, 3-methylbenzo thiazolin-2- onehydrazone and N-(1-naphthyl)ethylenediamine dihydrochloride. To the best of our knowledge, there is no report on the reduction of tinidazole by metal complexes and its determination with an azo dye reaction. In continuation of our efforts towards the synthesis of metal complexes, their catalytic applications and determination of drug substances through the formation of coloured derivatives [6,7], we have synthesised a macrocyclic nickel(II) [Ni(II)] complex by template method and used this for the reduction of tinidazole. The reduced tinidazole was converted to azo dye which was exploited for its spectrophotometric determination. Experimental Instrumentation The percentages of carbon, hydrogen and nitrogen in the macrocyclic Ni(II) complex were determined by using a Perkin-Elmer CHN analyser at 240 °C (Perkin-Elmer, USA). The infrared (IR) spectrum was recorded in a KBr pellet on a Perkin Elmer-283 spectrophotometer. The scanning rate was 6 min in the range of 4000–200 cm )1 . Brucker WH 300 (200 MHz) and Brucker WH 270 (67.93 MHz) spectrometers (Brucker, USA) were used for proton nuclear magnetic resonance ( 1 H-NMR) and carbon nuclear magnetic resonance ( 13 C-NMR) spectra, respectively. A Micromass-7070 spectrometer operating at 70 eV using a direct inlet system was used for mass spectrometry (Micromass Ltd, UK). Ultraviolet–visible spectra were recorded using a Shimadzu UV-160A double-beam spectrophotometer with matched quartz cells of path length 1 cm (Shimadzu, Japan). Materials, solutions and reagents Nickel chloride (NiCl 2 •6H 2 O) and 1,8- diaminonaphthalene were commercially available (Merck, India). Analytical grade samples of acetyl acetone, methanol, diethyl ether and dichloromethane (Qualigens, India) were used as supplied. Acetic acid solution (0.1 M) (Qualigens) was prepared by diluting 6.3 ml of glacial acetic acid to 1000 ml with double distilled water. Sodium nitrite (NaNO 2 ; 0.1 M) , 0.2 M sulphamic acid, 0.1 M of 2-naphthol and 10% w ⁄ v sodium hydroxide (Merck) solutions were prepared by dissolving the respective amounts in 100 ml of double distilled water. The standard drug solution was prepared by dissolving 100 mg of pure tinidazole in 100 ml of methanol. All other solvents and chemicals purchased from Merck, India and S.D Fine, India. Synthesis of macrocyclic Ni(II) complexes In a 100-ml round-bottom flask, 0.002 mol of acetyl acetone (AA), 0.002 mol of 1,8-diaminonaphthalene (DAN) in methanol and 0.001 mol of NiCl 2 •6H 2 O in methanol were added and the reaction mixture was stirred magnetically for ca. 60 min at 70 °C (Scheme 1). This solution was concentrated to 5 ml under reduced pressure and 10 ml of diethyl ether was added to initiate the crystallisation. The resulting precipitate was separated by suction filtration, washed with diethyl ether, dried in a vacuum to obtain the macrocyclic Ni(II) compound as a crystalline complex, which was recrystallised by using dichloromethane and diethyl ether. doi: 10.1111/j.1478-4408.2009.00208.x 284 ª 2009 The Authors. Journal compilation ª 2009 Society of Dyers and Colourists, Color. Technol., 125, 284–287