Synthesis of sulfonamide derivatives of diphenyl ether

Abstract

Vancomycin is a front line antibiotic for treatment of life-threatening gram-pos. bacterial infections and many clin. isolates have become resistant to it, focusing interest on successors to vancomycin. The purpose of this paper is to report the synthesis of di-Ph ether derivs. carried out by undergraduate science students majoring in forensic science and biol. Di-Ph ethers are structural elements found in medicinally useful antibiotics such as vancomycin as well as in biol. toxins in the environment such as dioxins. The reported derivs. of di-Ph ethers serve as intermediates in the synthesis of these biol. active mols. Com. available p-cresol was converted into its potassium salt by heating with potassium hydroxide pellets and then reacted with p-chloronitrobenzene in the presence of copper and potassium iodide as catalyst, and DMF as a solvent under refluxing conditions to yield 4-methyl-4'-nitrodiphenyl ether as a product. The resulting product was chlorosulfonated regioselectively at the 2-position with chlorosulfonic acid at 0 Deg C to yield the corresponding sulfonyl chloride deriv. which was then further reacted with ammonium hydroxide under refluxing conditions to yield the corresponding sulfonamide deriv.