Application of the Photo-Fries Reaction as a Key Step in the Preparation of Valuable Aryloxyethyl Selenocyanates

A multistep sequence leads to the preparation of a series of aryl selenocyanate WC-9 homologues, which are interesting compounds with potential biological activity against Trypanosoma cruzi, the etiological agent of Chagas disease. The synthetic sequence involves the application of the photo-Fries rearrangement reaction as a key step for the preparation of a series of 2-hydroxyphenones bearing alkyl chains of different length and a phenyl group. These intermediates are obtained upon direct irradiation (254 nm) of 4-phenoxyphenyl esters in different solvents at room temperature. Then, reaction of the 2-hydroxyphenones with 2-(2-bromoethoxy)tetrahydro-2H-pyran followed by acid deprotection, tosylation (or mesylation) reaction and, finally, nucleophilic attack with potassium selenocyanate provides the target aryloxyethyl selenocyanate homologues in good yields. A multistep straightforward sequence involving the photo-Fries rearrangement reaction as a key step has been developed for the preparation of aryl selenocyanate WC-9 analogues. Derivatization the resulting 2-hydroxyphenones bearing alkyl chains and a phenyl group, followed by acid deprotection, tosylation (or mesylation) and finally treatment with potassium selenocyanate provided the target analogues in good yields. image