Tetrahedron Letters,Vol.30,No.l7,pp zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 2209-2212,1989 oo40-4039/ 89 $3.00 + .OO Printed in Great Britain Pergamon Press plc zyxwvutsrqpon Synthesis of Macrobicyclic Cryptates incorporating Bithiazole, Bisimidazole and Bipyrimidine Binding Subunits Jean-M arie Lehn* and Jean-Bernard Regnouf de Vains Insfifuf Le Bef, UniversifC zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCB Louis Pasteur, CNRS URA 422, 4, rue Blaise Pascal, 67000 Sfrasbourg, France The sodium cryptates of several novel macrobicycles containing 2,2’-bithiazole, 2,2’-bisimidazole and 2,2’-bipy- rimidine subunits have been synthesized by a macrobicyclisation procedure; some of their properties are described. Heterocyclic rings have been extensively used as subunits in a large number of macrocyclic compoundsl. Because of their varied and pronounced complexation features towards transition metal ions, directly linked bis-heterocyclic groups are of special interest as metal binding sites for macrocyclic ligands. Incorporation of such units into macropolycyclic .structures allows to combine within the same ligand the special complexation features of cryptands with the rich photophysical and photochemical properties displayed by the complexes of the bis-heterocycles. Among those, the 2,2’-bipyridine (bpy) unit has been most actively studied and has been introduced into the framework of macrobicyclic ligands forming cryptate type inclusion complexes with various metal ions 2r3. Of particular interest are the cryptates obtained with the luminescent lanthanide ions such as Eu(II1) and Tb(III), which possess a unique combination of structural, photophysical and thermodynamic properties and function as light conversion molecular devices*f5. Macrobicyclic cryptands containmg l,lO-phenanthroline2Jj and 2,2’- biisoquinoline3 groups as well as N,N’-bipyrazole7 units have also been reported. In order to further explore the features of such cryptands and take advantage of the variety of properties offered by different heterocyclic subunits, we have investigated several new types of structures. We report here the synthesis of the macrobicyclic cryptands 1-S incorporating 2,2’- bithiazole (bthaz), 2,2’-bisimidazole (him) and 2,2’-bipyrimidine (bpym) subunits; functionalized bis-heterocycles have also been obtained, as well as the macrotricyclic cryptand 6. Synthesis of the 2,2’-Bithiazole Cryptands 1,2,3 and 6 The bis-bromomethyl-2,2’-bithiazole 7 was obtained in a single step although in low yield (7- 14%; m.p. 180-181’) by condensation (refluxing acetone; 6h) of 1,3-dibromoacetone (2 eq.)8 with dithiooxamide (1 eq.) in the presence of CaC03 (I eq.) (see also 9). The bis-chloromethyl analogue of 7 was also obtained following the reported procedure9 (26% yield) and reacted (DMSO, 70°, 25h) with NaN3 (4 eq.) to give the bis-azide 8 (92% yield; m:p. iO9- 110” ). Triphenylphosphine (2 eq.) was added to a solution of 8 in diethylether and the mixture w as heated at reflux (25h). The resulting bisphosphinimine w as directly hydrolyzed (EtOH/ H20/ conc. NC1 60/ 5/ Z; reflux, 150h) g iving after work-up (addition of water; extraction with CH2C12 to remove phosphine compounds; precipitation with EtOH) a precipitate of the bis- hydrochloride of 9 (70% yield). The free diamine 9 was obtained by passing an aqueous solution of the salt over an anion exchange resin (basic form OH-) (92% yield; m.p. 146147’). 2209