Metal Catalyzed Synthesis of Pentose-Sugar-Based Chiral 2-Substituted-1H-Benzimidazoles CURRENT STATUS: POSTED

A metal catalyzed synthetic protocol has been developed using Ti(OBu) 4 -CeCl 3 combo for chemoselective cyclocondensation cumoxidation under mild reaction conditions toward synthesis of a new class of optically pure compounds, 2-(6-benzyloxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-6a,10a-dihydro-1 H -anthra[1,2-d] imidazole-6,11-dione. All pentose-sugar-based aldehydes react with varies substituted dimethyl, 4-benzoyl and benzoquinoyl o -aromatic diamines (OAD) to afford desired chiral benzimidazoles with excellent isolated yield (77%-88%). In this suitable method chiral 2-Substituted-1 H -Benzimidazoles were syntheses in high yields without using any hazardous chemicals or harmful acids. Normal aromatic aldehyde also reacts with varies o -aromatic diamines (OAD) give rise to known 2-Aryl-1 H -benzimidazoles. All the target chiral 2-Substituted-1 H Benzimidazoles were characterized by FT-IR, NMR spectral and HR-MS data and also verified M.P of normal aromatic 2-Substituted-1 H -benzimidazoles from literature. 3 . Infrared spectra were recorded on a Perkin-Elmer spectrometer as KBr disc. Optical rotations of all sugar-based chiral 2-substituted-1 H -benzimidazoles were measured on Polarimeter (Perkin-Elmer). Organic solvent was dried with Magnesium sulfate. Mass spectra were obtained using high-resolution electrospray ionization in positive ion mode. The chromatographic stationary phase was silica gel. Solvents were evaporated under reduced pressure.


Introduction
Syntheses of several benzimidazoles and their analogues have been achieved in the last few decade to examine their biological activities. 1,2 Developing several methods for the synthesis of benzimidazoles in previous years The chirally modified benzimidazoles are getting tremendous importance due to their potential biological activity and other applications. From the earliest synthesis 1 sugar -based chiral benzimidazoles are found applications in new drug design. To development of sugar-based valuable compounds as drugs and other biological active compounds are very important in recent time. They have also widespread applications in fluorescence 3 chemosensing, 4 crystal engineering, 5 and corrosion science. 6 In the treatments of viral, bacterial and fungal infection used benzimidazoles like heterocycle and their analogues. 7 Benzimidazolines the reduced version of the heterocycles is often called organic hydrides, can act as good reducing agents and good hydrogen storage materials in many organic reactions. [8][9][10] In this paper I am developing a chemoselective catalytic system under the milder and acid-free reaction conditions toward synthesis of the new pentose sugar base chiral benzimidazoles because there are some weaknesses in the 3 current methods. In presences of harmful acids, hazardous chemicals or high temperature sugar molecules can easily decompose. Mostly methods are some limitations mainly in terms of drastic reagents used and reaction conditions, formation of undesired 1,2-disubstituted byproducts (3′, Scheme 1). In this connection, an oxidative cyclization processes are found for affording the sugar based chiral benzimidazoles under the acid-free reaction conditions. To designed and synthesis of the sugar-based chiral benzimidazoles was found in such a way that it must be inexpensive, easily accessible. Two protocols are usually followed. One of them is the coupling of o-aromatic diamines (OAD) with carboxylic acids or their derivatives 1 and the second route involves condensation of aldehyde with OAD followed by oxidative cyclo-dehydrogenation. 11 Among the two methods the second approach has become more popular probably because of the ease accessibility of a variety of substituted aldehydes. In recent times investigations involving metal catalyzed cyclization processes are very encouraging. Cyclocondensation cum oxidation is a powerful synthetic tool for synthesis of novel heterocyclic skeletons in one step. [12][13][14] Griess and Harrow was first reported synthesis of sugarbased benzimidazoles by through condensation of D-glucose and o-phenylenediamine (OPD) in the presence of hydrochloric acid more than one hundred years ago to afford the open chain sugar derivative as the minor product, and in fact it was the first report for synthesis of benzimidazoles. 1a,15 However, Maiti and co-workers have established glycal-based chiral benzimidazoles by using Vo(acac) 2 -CeCl 3 Combo catalyst. 16 Cerium is a useful element which have been extensively used in synthetic chemistry. CeCl 3 is a very useful metal catalyst, whose unique behavior is used to synthesis Synthesis of the Glucose-based protected pentose-sugar aldehyde precursors (4a,b) is depicted in Scheme 2. 24,25 Glucose was converted into diacetonide (A) upon treatment with dry acetone and concentrated sulfuric acid (Scheme 2). This protected form was O-alkylated (B, R= benzyl/ methyl,) after formation of alkoxide using NaH in DMF. It was selectively deprotected to C by treatment of 70% aqueous acetic acid. Finally, oxidation with NaIO 4 resulted the desired aldehydes, 6-alkyloxy-2,2-

Synthesis of pentose-sugar-based chiral benzimidazoles:
Chemoselective synthetic procedure is applied toward synthesis of chiral benzimidazole utilizing commonly used pentose sugars (Scheme 3). Glucose-based protected pentose-sugar aldehyde, 6- under similar reaction condition with dimethyl, 4-benzoyl and benzoquinoyl (1b-d) to afford desired chiral benzimidazoles with excellent isolated yield (77-88%, entry 1-5, Table 2). In all cases the reaction was very clean. The products are determined by FT-IR, NMR and HR-MS methods after purification by column chromatography. A number of new pentose-sugar-based chiral benzimidazoles are synthesized in this mild catalytic approach. All the compounds are reported in first time.

Experimental
All chemicals and solvents are used AR grade. 1 H -NMR spectra were recorded on Bruker 300 MHz spectrometer in CDCl 3 . Infrared spectra were recorded on a Perkin-Elmer spectrometer as KBr disc.
Optical rotations of all sugar-based chiral 2-substituted-1H-benzimidazoles were measured on Polarimeter (Perkin-Elmer). Organic solvent was dried with Magnesium sulfate. Mass spectra were obtained using high-resolution electrospray ionization in positive ion mode. The chromatographic stationary phase was silica gel. Solvents were evaporated under reduced pressure.

Conclusion
In this paper, I have described an efficient synthesis protocol for synthesis of sugar-base aldehyde   Tables.pdf