Mild Aliphatic and Benzylic Hydrocarbon C-H Bond Chlorination Using Trichloroisocyanuric Acid

作者：Combe Sascha H; Hosseini Abolfazl; Parra Alejandro; Schreiner Peter R

来源：Journal of Organic Chemistry, 2017, 82(5): 2407-2413.

DOI：10.1021/acs.joc.6b02829

We present the controlled monochlorination of aliphatic and benzylic hydrocarbons with only 1 equiv of substrate at 25-30 degrees C using N-hydroxyphthalimide (NHPI) as radical initiator and commercially available trichloroisocyanuric acid (TCCA) as the chlorine source. Catalytic amounts of CBr4 reduced the reaction times considerably due to the formation of chain-carrying CBr3 radicals. Benzylic C-H chlorination affords moderate to good yields for arenes carrying electron-withdrawing (50-85%) or weakly electron-donating groups (31-73%); cyclic aliphatic substrates provide low yields (24-38%). The products could be synthesized on a gram scale followed by simple purification via distillation. We report the first direct side-chain chlorination of 3-methylbenzoate affording methyl 3(chloromethyl)benzoate, which is an important building block for the synthesis of vasodilator taprostene.

• 出版日期2017-3-3