Improved synthetic methods to mixed-donor thiacrown ethers

A series of azathia- and azaoxathiacrown ether macrocycles have been prepared in good yields via the use of N-boc-bis(2-chloroethyl)amine as a precursor, which minimises undesirable side reactions and facilitates subsequent deprotection to the free cyclic amine. The mono-aza macrocycles, [12]aneNS(3), [12]aneNOS(2), [15]aneNS(4), [15]aneNO(2)S(2) and [16]aneNS(4) have been prepared via this route. The single-crystal X-ray structure of [12]aneNS(3) (.) HBr (.) 2H(2)O confirms the macrocycle to be distorted quadrangular with the S-centres lying along the edges and six out of 12 torsion angles less than 90 degrees. The synthesis of di-aza macrocycles utilising the diamide precursors, N,N'-bis(chloroacetyl)-1,2-diaminoethane and N,N'-bis(chloroacetyl)-1,3-diaminopropane, affords the free macrocycles [12]aneN(2)S(2), (15janeN(2)S(3), [15]aneN(2)OS(2), [16]aneN(2)S(3) and [19]aneN(2)S(4) after reduction of the intermediate cyclic amides. Reaction of 3,6-dioxa-1,8-octanediamine with the dimethyl ester of thiadiglycolic acid followed by reduction affords [15]aneN(2)O(2)S, while the hydroxy-substituted macrocycles [20]aneS(6)(OH)(2), [13]aneS(4)(OH), and [26]aneS(8)(OH)(2) have been prepared by reaction of 1,3-dichloro-2-hydroxypropane with the appropriate dithiol. The crystal structure of [20]aneS6(OH)2 shows two endo- and four exo-dentate S-centres as observed in the parent [18]aneS6. The N-aryl substituted macrocycles N-4-NO2Ph-[12]aneNS(3) (N-4-nitrophenyl-7-aza-1,4,10-trithiacyclododecane) and N-4-NH2COPh-[12]aneNS(3) (N-4-benzamido-7-aza-1,4,10-trithiacyclododecane) have been prepared by reaction of 4-substituted bis-tosylated N,N-bis(2-hydroxyethyl) aniline with 3-thia-1,5-pentanedithiol. (c) 2005 Elsevier Ltd. All rights reserved.