O-alkylation of 4-hydroxybenzolsulfonamide by N-substituted 2-chloroacetamides and 5-(chloromethyl)-3-aryl-1,2,4-oxadiazoles

The paper presents a method for the synthesis of new representatives of the primary benzenesulfonamides class. They are promising agents for the treatment of open-angle glaucoma and neurodegenerative diseases. The authors have developed a mechanism for the O-alkylation of 4-hydroxybenzene sulfonamide with alkylating agents of different nature. The method provides mild conditions and selectivity of the process. The paper shows the necessity of activation of N-substituted 2-chloroacetamides and 5-(chloromethyl)-3-aryl-1,2,4-oxadiazoles by catalytic addition of potassium iodide in O-alkylation reactions of phenols. The authors demonstrated the applicability of the developed methodology on 12 examples of O-alkyl derivatives of 4-hydroxybenzene sulfonamide obtained in yields from 28 to 86%. The research proved the purity and structure of the new compounds by the combined methods of 1H NMR, 13C NMR, and elemental analysis.