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Abstract-The antioxidant properties of substituted diarylamines in the benzo [b]thiophene series were evaluated by their reducing power and free radical scavenging activity. The results were compared with those of standards: acid ascorbic for the first method and BHA and BHT for the second. For both methods it was possible to establish some structure-activity relationships (SARs) based on the position of the arylamination on the benzo[b]thiophene moiety, the presence of different substituents on the phenyl ring (F, 1 or 2 OMe) and on the thiophene ring (H, CO 2 Et, CO 2 H). Ó 2005 Elsevier Ltd. All rights reserved.The search for new molecules with antioxidant properties is a very active domain of research, since they can protect the human body from free radicals and retard the progress of many chronic diseases, such as vascular diseases, some forms of cancer and oxidative stress responsible for DNA, protein and membrane damage. 1,2 The radical scavenging activity (RSA) using DPPH radical (2,2-diphenyl-1-picrylhydrazyl radical) and the reducing power are two established in vitro methods employed for the evaluation of antioxidant activity. Some authors have observed a direct correlation between antioxidant activities and the reducing power, either for certain plant extracts 3 or chitosan sulfates. 4 The presence of reducers (i.e., antioxidants) causes the conversion of the Fe 3+ /ferricyanide complex used in this method to the ferrous form. Therefore, by measuring the formation of PerlÕs Prussian blue at 700 nm we can monitor the Fe 2+ concentration; a higher absorbance at 700 nm indicates a higher reducing power. The free radical DPPH possesses a characteristic absorption at 517 nm (purple in colour), which decreases significantly on exposure to radical scavengers (by providing hydrogen atoms or by electron donation). A lower absorbance at 517 nm indicates a higher radical scavenging activity of the compound. This test is a standard assay in antioxidant activity studies and offers a rapid technique for screening the RSA of pure synthetic compounds. 5 Herein, we report the reducing power and the free radical scavenging activity of nine diarylamines in the benzo[b]thiophene series, earlier prepared by us, as an evaluation of their in vitro antioxidant activity. Recently, we described the structure-activity relationship of diarylamines 1 and 2 as antimicrobial agents. 6,7 However, it is the first time that a study on their antioxidant properties is reported, regarding especially the influence of the compound structure on the results. Differently substituted diarylamine derivatives of 2,3,5-trimethylbenzo[b]thiophene 1a-d were obtained in good to high yields, by C-N palladium-catalyzed cross-coupling using either the 6-bromobenzo[b]thiophene or the 6-amino derivative as coupling component (Scheme 1). 8 The same reaction conditions were also used to obtain diarylamines 2a,b,d,e in moderate to high yields, coupling ethyl 3-bromobenzo[b]thiophene-2-carboxylate or

Several diarylamines in the benzo [b]thiophene series were prepared in good to high yields by palladium-catalysed amination of ethyl 3-bromobenzo[b]thiophene-2-carboxylate with anilines and 5-aminoindole in the presence of Pd(OAc) 2 , BINAP and Cs 2 CO 3 in toluene. The presence of the ester group at the 2-position of the benzo[b]thiophene moiety increases the yields and lowers the heating times relative to the reactions performed with 3-bromobenzo[b]thiophene. When aminopyridines were used instead of anilines, the ligand and the solvent need to be changed to XANTHPHOS and dioxane in the amination reaction. With 2-aminopyridine a onepot C−N coupling and intramolecular cyclization involving the nitrogen atom of the pyridine ring occurred, with loss of

Di(hetero)arylamides have been synthesized in short reaction times by palladium-catalysed multicomponent aminocarbonylation of either electron-deficient or electron-rich heteroaryl halides and p-iodoanisole with several arylamines bearing either electron-donating or -withdrawing groups and aminopyridines using [Mo(CO) 6 ] as a solid CO source and conventional heating. Starting from heteroaryl bromides, a palladacycle with tBu 3 PHBF 4 as ligand is required together with DBU as a base in dioxane and a temperature of 125°C. From (hetero)aryl iodides, Pd(OAc) 2 without a ligand and DBU were used in dioxane at 110°C. Under the latter conditions we were able to apply this reaction to deactivated aminopyridines to obtain the corresponding di(hetero)arylamides.