Synthesis of the Novel 3-Benzotriazole-5-yl difluoromethyl-5-trifluoromethyl benzotriazole Nucleosides

Triazole ring is a quite important five-membered heterocycle with three nitrogen atoms, possesses aromaticity and is an electron rich system. Triazole derivatives have been frequently becoming clinical drugs or candidates for the treatment of various types of diseases. Synthesis of the novel of 3-Benztriazole-5-yl difluoromethyl-5-trifluoromethyl benztriazole compound (3). Synthesis and chara-cterization of two new benzotriazole nucleosides with good yields by silyation method.


Introduction
More and more triazole derivatives, with strong pharmacological activity, low toxicity, less adverse effects, fewer multi-drug resistances, high bioavailability, good pharmacokinetics property and drug-targeting, diversity of drug administration, broad spectrum, better curative effect etc., A large number of triazole compounds as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, Triazole compounds as medicinal drugs, including antifungal, anticancer, antibacterial, antitubercular, antiviral, anti-inflammatory and analgesic,anticonvulsant, antiparasitic, antidiabetic, anti-obesitic, antihista-minic, anti-neuropathic, antihypertensive as well as other biological activities (Zhou &Wang, 2012 andKhabnadideh et al, 2012).In fact several benzotriazoles have shown potential biological activities such as antimycobacterial (Sanna et al, 2002), antitumor (Handratta et al, 2005) and anti-inflammatory (Dawood et al, 2006) activities.
In recent years, the use of antifungal drugs in human medicine has increased, especially with the advent of AIDS epidemic.Efforts have focused on the development of new, less toxic and more efficacious antifungal drugs with novel mechanism of action (Khabnadideh et al, 2012).Biological activities of ribavirin and homo-N-nucleosides, a novel 1,2,4-triazole nucleoside drug derivative as a potential antiviral agent and anticancer activities (Chun et al, 2005;Xia et al, 2010;Konstantinova et al, 2013;Mosselhi &Neidlein, 2009 andKristinsson et al, 1994).
The purpose of this study was to synthesize of some new nucleoside benzotriazole and study their charactrazition.

Material and Methods
All chemicals were supplied by Sigma-Aldrich and Merck (Germany).IR spectra were recorded for KBr discs on Fourier Transform infrared and Pye Unicam SP 300 Infrared Spectrophotometers at Taif University.1H NMR spectra were obtained on a Varian (850 MHz) EM 390 USA instrument at King Abdel-Aziz University by using TMS as internal reference.13C NMR spectra were recorded on a JNM-LA spectrometer (850 MHz) at King Abdel-Aziz University, Saudi Arabia.Elemental analyses were obtained on an Elementar Vario EL 1150C analyzer.Mass spectra were recorded on a JEOL-JMS-AX500 at King Abdel-Aziz University, Saudi Arabia.Purity of the compounds was checked by thin layer chromatography (TLC).Thin layer chroma-tegraphy (TLC) was performed on silica gel sheets F1550 LS 254 of Schleicher & Schull and column chromatography on Merck silica gel 60 (particle size 0.063-0.20.Melting points were measured on Gallenkamp melting point apparatus (UK) and are uncorrected.The starting materials 4-Amino-3-nitrobenzotrifluoride (1) was prep-ared Pubchem CID: 67865.

Experimental
The method for reduction of aromatic nitro compounds employing NaBH4/ Raney nickel system or Raney nickel only is simple, inexpensive, easily scaled-up and applicable for large scale preparation of different heterocyclic aryl amines (Chang et al, 1970;Mi et al, 2008;Mi et al, 2007 andWang &Zhou, 2011).

3,4-Diaminobenzotrifluoride (2)
A mixture of 4.46 g. (0.0216 mole) of 4-Amino-3-nitrobenzotrifluoride (1), 50 ml. of absolute ethanol, and 1g. of Raney nickel and 5 ml of hydrazine hydrate was added.the temperature is rapidly raised to 60-70°, Owing to the strong exothermic reaction.The reaction mixture was reflexed at 100-120° for 3h.After the reaction mixture has cooled, the catalyst is separated from the reaction mixture by filtration through a Büchner funnel.The alcohol and water are removed by distillation, and the product was purified by flash column chromatography (silica gel 100 g, chloroform /ethyl acetate 90: 10) to give 3.3 g (Ayyangar et al, 1984;Dauben et al, 1963 andAllen &James, 1955).
Deprotection of the latter by using dry absolute methanol and sodium metal gave new free N-nucleosides (9) and (10), respectively, in moderate yields.Nucleosides obtained have been identified by their spectral analysis.