AMIDES AND SULFONAMIDES - EFFICIENT MOLECULAR PADLOCKS FOR THE TEMPLATE SYNTHESIS OF AZACYCLAM (1,3,5,8,12-PENTAAZACYCLOTETRADECANE) MACROCYCLES

Amides and sulfonamides, both aliphatic and aromatic, acted as efficie nt locking fragments. in the presence of formaldehyde and base (trieth ylamine), in closing the open-chain tetramine 1,9-diamino-3,7-diazonon ane around labile metal centres prone to a square type of co-ordinatio n, i.e. Ni(II) and Cu(II), to give a pentaazamacrocyclic complex of th e azacyclam family. The product of the copper(II) template reaction in volving methanesulfonamide as a locking fragment 8,12-pentaazacyclotet radecane)dinitratocopper(II), was obtained in crystalline form and its crystal and molecular structure determined from single-crystal X-ray diffraction data, collected with the use of Cu-Kalpha radiation: trigo nal, space group R3c, a = b = c = 14.997(3) angstrom, alpha = beta = g amma = 98.48(2)-degrees, Z = 6. Only the four secondary amine nitrogen atoms of the macrocycle are bound to the Cu(II), giving a regular squ are stereochemistry. The tertiary nitrogen atom N(1), which presents d istinct sp2 structural features, is not involved in the coordination. The axial positions of the elongated octahedron are occupied by oxygen atoms of the nitrate ions. A kinetic investigation was carried out on the copper(II) template reactions involving diprotic acids as locking fragments. including amides, amines and carbon acids, such as nitroet hane and diethyl malonate: for the systems investigated the rate of th e template reaction seems to be related to the strength of the diproti c acid. This suggests that the monodeprotonated form of the acid is pr esent in the rate-determining step of the cyclisation process.