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

Abstract

We present the controlled monochlorination of aliphatic and benzylic hydrocarbons with only 1 equiv of substrate at 25-30 °C using N-hydroxyphthalimide (NHPI) as radical initiator and commercially available trichloroisocyanuric acid (TCCA) as the chlorine source. Catalytic amounts of CBr reduced the reaction times considerably due to the formation of chain-carrying ·CBr 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.

Metal‐Free Preparation of α‐H‐Chlorinated Alkylaromatic Hydrocarbons by Sunlight

“…Encouraged by these results, the side‐chain chlorination of N ‐heterocycles was examined. Despite the results reported by Schreiner and Jeromin, in our reaction conditions 2‐methylpyridine provided the corresponding 2‐(chloromethyl)pyridine 3 p in 61% yield. Similarly, both 2‐methylquinoline and 1‐methylisoquinoline were effectively chlorinated (Scheme , 3 q, 3 r).…”

“…In a continuously search for alternative processes, Whiting and co‐workers have reported a selective chlorination of α‐H of alkylarenes by the use of nano Ag/AgCl in aqueous NaCl/HCl under sunlight or visible light irradiation (Scheme , path 2) . A mild chlorination of toluene which makes use of trichloroisocyanuric acid as the chlorine source, N ‐hydroxyphthalimide (NHPI) as radical initiator, catalytic amounts of CBr 4 and Cu(OAc) 2 as a catalyst was also proposed (Scheme , path 3) . All of these new methodologies bring significant improvements in the chlorination of toluene, especially for the selectivity.…”

Selective C−H Halogenation with a Highly Fluorinated Manganese Porphyrin

“…[3] Classical radical halogenation reactions are severely limited, however, by poor regioselectivity,o ften harsh conditions,a nd undesirable polyhalogenation. [4,5] Nature utilizes metalloenzymes, [6] such as the heme protein chloroperoxidase (CPO), [7] and the non-heme protein SyrB2, [8] to effect CÀHh alogenation. [4,5] Nature utilizes metalloenzymes, [6] such as the heme protein chloroperoxidase (CPO), [7] and the non-heme protein SyrB2, [8] to effect CÀHh alogenation.…”

Trichloroisocyanuric Acid: a Versatile and Efficient Chlorinating and Oxidizing Reagent

“…Benzyl chloride and substituted benzyl chloride are extensively used in the industrial productions of amphetamine class drugs, artificial resins, dyes, gum petroleum inhibitor and photographic developer . Recently Parra and Schreiner have reported a powerful methodology for the chlorination of benzylic position of alkyl aromatic hydrocarbons (Scheme ) …”