A Convenient Synthesis of Trifluoroacetamide Derivatives of Diaza[32]cyclophanes and Triaza[33]cyclophanes

Abstract

The diaza[32]cyclophane skeleton has been constructed by the bis-N-alkylation of 1,4-bis[(4-nitrophenylsulfonylamino)methyl]benzene with 1,4-bis(halomethyl)benzene in the presence of sodium hydride. The 4-nitrophenylsulfonyl (Ns) amides in the bridge chains of the cyclophane were effectively deprotected by sodium ethanethiolate and the resulting free amine moieties were reprotected as the trifluoroacetamide under mild conditions to afford 3,7-bis(trifluoroacetyl)-3,7-diaza-1,5(1,4)-dibenzenacyclooctaphane in 26% overall yield. This Ns-amide method has also been applied for the preparation of a higher homologue, the trifluoro­acetamide derivative of triaza[33]cyclophane, 3,5,7-tris(trifluoroacetyl)-3,7,10-triaza-1,5(1,3,5)-dibenzenabicyclo[3.3.3]undeca­-phane, in 18% overall yield. Thus, the present procedure provides a convenient synthetic route to azacyclophane derivatives possessing trifluoroacetamide groups in the bridge chains.