Synthesis of Sulfur-Containing Macrocycles Using Cesium Thiolates

Article abstract of DOI:10.1021/jo00335a032

In dimethylformamide (DMF) solution 1,ω-dithiols are deprotonated by cesium carbonate.Reaction with 1,ω-dibromide in the same solvent leads to excellent yields of the corresponding macrocyclic (di)sulfides.The reaction is normally carried out by adding the dithiol (4x1E-2 M in DMF) and dibromide (4x1E-2 M in DMF) simultaneously to a 10percent excess of cesium carbonate (8.8x1E-3 M suspended in DMF) at 45-50 deg C over a period of 12-15 h.In this fashion there was obtained, for example, 1,12-dithiacyclodocosane (1d) in 85percent yield from the reaction of decane-1,10-dithiol with 1,10-dibromodecane.Other compounds obtained from the combination HS(CH2)mSH and Br(CH2)nBr are 1a (m=3, n=4), 1b (m=n=5), 1c (m=5, n=10), 1e (m=10, n=16), 1f (m=n=10), and 1g (m=16, n=18) in yields ranging from 45 to 90percent.By means of the same approach using various 1,ω-dithiols and o-xylene α,α'-dibromide, a series of macrocycles was prepared in yields ranging from 64-88percent.Various thia crown ether compounds have been prepared as well as ligands like 1,4,8,11-tetrathiacyclotetradecane (15), prepared from 3,7-dithianonane-1,9-dithiol and 1,3-dibromopropane in 76percent yield as compared to the literature yield of 7.5percent.This ability of cesium to promote ring closure appears to be unique certainly in cases where long chains devoid of heteroatoms are involved.This method makes available a variety of sulfur-containing ligands and the potential for scaling up the reaction has also been demonstrated.