Metal-directed syntheses of dithiadiazacyclotetradecane macrocycles with pendant alcohol and nitro or carboxylate groups involving macrocycle ring expansion

Abstract

Copper(II)-directed condensation of 4-hydroxymethyl-3,6-dithiaoctane-1,8-diamine with nitroethane or diethyl malonate and formaldehyde yielded (anti-6-methyl-6-nitro-1,11-dithia-4,8-diazacyclotetradecan-13-ol)copper(II) and (diethyl 13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6,6-dicarboxylate)copper(II) respectively in good yields. The latter was readily converted by decarboxylation and hydrolysis in aqueous base to the copper(II) complex of anti-13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6-carboxylic acid from which the free ligand can be obtained by zinc–acid reduction of the copper ion, whereas the former can be converted by zinc–acid reduction directly to the hydrochloride salt of the free anti-6-amino-6-methyl-1,11-dithia-4,8-diazacyclotetradecan-13-ol ligand. The condensations should yield a thirteen-membered macrocycle with a pendant hydroxymethyl group fused to a macrocyclic ring carbon, but the molecules undergo a Wagner–Meerwein or alternate carbon skeleton rearrangement to yield the fourteen-membered macrocycle with a pendant alcohol group. The pendant alcohol can act as an axial donor group, as illustrated in the crystal structure analyses of (anti-6-methyl-6-nitro-1,11-dithia-4,8-diazacyclotetradecan-13-ol)copper(II) and (anti-13-hydroxy-1,11-dithia-4,8-diazacyclotetradecane-6-carboxylato)copper(II) as perchlorate salts. The former complex crystallizes in the monoclinic P2₁/c space group, a= 8.703(2), b= 18.699(2), c= 13.293(2)Å, β= 105.15(1)° and the latter in the monoclinic P2₁/n space group, a= 7.450(1), b= 15.325(2), c= 16.772(1)Å, β= 98.38(1)°. In both complexes the alcohol is disposed anti to the nitro or carboxylate group. In the former, the copper ion lies in a distorted-octahedral environment of two sulfur donors (Cu–S_av 2.333 Å), two nitrogen donors (Cu–N_av2.016 Å), the pendant alcohol donor [Cu–O 2.365(3)Å] and a perchlorate anion [Cu–O 2.544(3)Å], whereas in the latter a dimer with each copper in a very distorted octahedral environment exists where each carboxylate bridges to the alternate copper ion [Cu–O 2.293(3)Å] and the alcohol is weakly bound [Cu–O 2.520(3)Å] in addition to the macrocycle heteroatoms (Cu–N_av 2.035, Cu–S_av 2.353 Å).