New method of 5-mercaptotetrazoles functionalization

Abstract

Tetrazole derivatives containing a sulfur atom in the position 5 of the ring are promising as biologically active compounds and also as components of photomaterials [1][2][3][4]. At the same time the mercaptothiazoles are effi cient reagents in the schemes of the total synthesis of natural substances [4].A signifi cant attention was paid to the development of effi cient synthetic procedures for 5-(R-sulfanyl)tetrazoles (R = Alk, Bn) [1]. The traditional methods of preparation of these compounds are based on the alkylation of 5-mercaptotetrazoles with various electrophilic agents [1,2].The preparation methods of 5-(R-sulfanyl)tetrazoles (R = Ar) are poorly understood. A synthesis was reported of 5-arylsulfanyltetrazoles by the direct arylation of 5-mercapto tetrazoles by fluoro(chloro)nitrobenzenes [5], by the reaction of 5-mercaptotetrazoles with phenols under electrolysis conditions [6], and also by the reaction of 5-tosyltetrazoles with thiophenols [7]. These methods are not general for they make it possible to obtain 5-arylsulfanyltetrazoles only with defi nite substituents (R = Ar). Besides the necessity to use diffi cultly available reagents and special equipment, long reaction time and relatively low yield of target compounds reduce the effi ciency of the cited methods.Therefore the development of a general and effi cient method of the synthesis of 5-арилsulfanyltetrazoles is an urgent problem.At present one of the most promising methods of synthesis and functionalization of aromatic thioethers is their direct arylation with aryl halides catalyzed by palladium and copper complexes [6].We found that the arylation of 1-phenyl-5-mercaptotetrazole (I) with iodobenzene catalyzed by CuI (10 mol%) in the presence of a ligand (2 equiv of ethylenediamine) and a base (2 equiv of Cs 2 CO 3 ), made it possible to obtain 5-phenylsulfanyltetrazole (II) in a high yield (see the scheme).The developed method of the sysnthesis of 5-arylsulfanyl-tetrazoles can be used for the synthesis of 5-(R-sulfanyl)tetrazoles (R = Vin, Ht). By the Сu-catalyzed vinylation and hetarylation tetrazole I we obtained sulfanyltetrazoles III and IV in the yields of 92 and 85% respectively (see the scheme).Note that in contrast to the method of direct arylation of mercaptotetrazoles [5] the Cu-catalyzed arylation allows the preparation also of the other 5-(R-sulfanyl) tetrazoles with R = Vin and Ht, and also does not require the use of rare reagents and additional equipment.Synthesis of tetrazoles II-IV. General procedure. A dispersion of 2.8 mmol of tetrazole I, 0.28 mmol of CuI, 5.9 mmol of ethylenediamine, 5.9 mmol of Cs 2 CO 3 , 1 3.4 mmol of halide, and 2 ml of DMF was stirred for 1 h (TLC monitoring of conversion) at 85°С in an argon atmosphere. The reaction mixture was cooled to 20°С and poured into 20 ml of water. The obtained solution was extracted with ethyl acetate (2 × 8 ml). The combine extract was washed with brine (2 × 8 ml), dried with anhydrous Na 2 SO 4 , the solvent was removed in a vacuum. The residue obtained was dispersed in ...

Serendipitous One-Step Synthesis of Cyclopentene Derivatives from 5′-Deoxy-5′-heteroarylsulfonylnucleosides as Nucleoside-Derived Julia–Kocienski Reagents

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