The Pd-catalyzed amination of 2,6-dibromopyridine with various linear polyamines and oxapolyamines was studied. In this way polyazamacrocycles 3 containing one pyridine and one polyamine moiety were synthesized using equimolar amounts of starting compounds. Two alternative approaches were elaborated and compared for synthesis of macrocycles 11 comprising two pyridine and two polyamine fragments: via intermediate formation of Nα,Nω-bis(6-halopyridin-2-yl)polyamines 7, 8 or via 2,6-bis(polyamino)-substituted pyridines 10. A series of N-(6-tert-butoxypyridin-2-yl)-substituted polyamines 12 and Nα,Nωbis(6-tert-butoxypyridin-2-yl)-substituted polyamines 13 were obtained by similar procedures, and the possibilities of N,N-dihetarylation of such compounds using 2-bromopyridine and 2-bromo-6-tert-butoxypyridine were studied. The yields of linear and cyclic products were shown to be strongly dependent on the nature of starting polyamines and of the halogen atom.

Polyazamacrocycles containing pyridine moieties have been synthesized through the Pd-catalyzed reaction of 2,6-dihalopyridines with various linear polyamines.The synthesis and the coordination properties of polyazamacrocycles containing an endo pyridine nitrogen atom in the macrocyclic ring have been studied by different groups. [1][2][3][4][5][6][7][8] The presence of the pyridine moiety strongly influences the thermodynamic properties and the complexation kinetics by changing the basicity of the ligand and increasing the conformational rigidity of the macrocycle. Indeed, it has been shown that the basicity of ligands containing pyridine is lower than that of corresponding tetraazacycloalkanes. It has also been observed that the metal complexes of such ligands are usually less stable than those of the corresponding tetraazacycloalkanes, while the latter show slower kinetics of formation. In these macrocycles incorporating pyridine, nitrogen atoms are linked to the aromatic ring via one methylene or methyne group. To our knowledge, there is only one report of a macrocycle containing amine-type N atoms directly linked to the pyridine moiety. 9 This compound has been obtained in 25% overall yield after reduction of the corresponding diamide resulting from the reaction of 2,6-diaminopyridine with the suitable diacyl dichloride under high dilution conditions. Devising a straightforward and general route towards such macrocycles is a great challenge.We have recently shown that Pd-catalyzed amination of various aryl dihalides by linear polyamines is a powerful tool for the synthesis of a wide range of nitrogen and oxygen containing macrocycles. 10 Such ligands containing nitrogen atoms directly bonded to an arene moiety may present original complexing properties and serve as new metal sensors. We wish to report herein the synthesis of a wide range of new polyazamacrocyclic compounds incorporating a pyridine ring by using the Pd-catalyzed reaction of 2,6-dihalopyridines with linear tri-, tetra-, pentaand hexaamines, as well as dioxa-and trioxadiamines. Some examples of catalytic amination of halopyridines involving either palladium 11-14 or nickel complexes have been reported previously. 15 First, we investigated the reaction of 2,6-dibromopyridine 1a with tetraamine 2a, which has been successfully used in previously studied amination reactions. The easily available and versatile catalytic system Pd(dba) 2 /BINAP has been chosen. 16 The reactions were carried in refluxing dioxane, in the presence of 4-8 mol% Pd(dba) 2 , 4.5-12 mol% BINAP and sodium tert-butylate, to yield the desired macrocycle 3a (Scheme 1). Scheme 1The progress of the reaction, monitored by 1 H NMR, showed that 2,6-dibromopyridine was entirely consumed after 4-5 hours (c = 0.02 M). Longer heating (up to 22 h) did not significantly change the reaction mixture composition ratio. 2-Amino-6-tert-butoxypyridine (4a) and 2,6-di-tert-butoxypyridine (6) were formed as side-products, through the compound 5. The formation of 2-bromo-6-tert-butoxypyridine (5)...

A new class of polyazamacrocycles is obtained by Pd-catalyzed amination of (II). The method is also applicable to other linear tri-, tetra-, penta-and hexaamines, as well as dioxa-and trioxadiamines. -(BELETSKAYA*, I. P.; AVERIN, A. D.; PLESHKOVA, N. A.; BORISENKO, A. A.; SEREBRYAKOVA, M. V.; DENAT, F.; GUILARD, R.; Synlett 2005, 1, 87-90; Dep. Chem., Lomonosov Moscow State Univ., Moscow 119992, Russia; Eng.) -S. Adam 22-171