In Situ Formed I^III‐Based Reagent for the Electrophilic ortho‐Chlorination of Phenols and Phenol Ethers: The Use of PIFA‐AlCl₃ System

Abstract

A new and in situ formed reagent generated by mixing PIFA {bis[(trifluoroacetoxy)iodobenzene]} and AlCl3 was introduced in the organic synthesis for the direct and highly regioselective ortho‐chlorination of phenols and phenol ethers. An efficient electrophilic chlorination for these electron‐rich arenes as well as the scope of the reaction are described herein. An easy, practical, and open‐flask reaction allowed us to introduce a chlorine atom, which is a highly important functional group in organic synthesis. The reproducibility of our method has been demonstrated on gram‐scale by carrying out the reaction in 6‐bromo‐2‐naphthol. This halogenation reaction also proceeds in excellent conditions by first preparing the iodine(III)‐based chlorinating reagent. Our new chlorinating reagent can be stored at least for two weeks at 4 °C without losing its reactivity.

In situ Generation of Hypervalent Iodine Reagents for the Electrophilic Chlorination of Arenes

“…Moreover, 1‐chloro‐1,2‐benziodoxol‐3‐one has been used for the chlorination of selected arenes . Recently, Solorio‐Alvarado group reported the electrophilic ortho ‐chlorination of phenols using the mixture PIFA‐AlCl 3 .…”

The use of polymeric sulfides as catalysts for the para-regioselective chlorination of phenol and 2-chlorophenol

“…Recently, several processes have been developed for the selective halogenation of aromatic compounds [5][6][7][8][9][10]. For example, chlorination systems involving the use of [bis(trifluoroacetoxy)iodo]benzene and aluminum chloride (AlCl3) in acetonitrile [5], 1,3-dichloro-5,5-dimethylhydantoin in the presence of ammonium chloride in toluene [6], hydrogen chloride, manganese(II) sulfate and hydrogen peroxide in water [7], and N-chlorosuccinimide and Nagasawa's bisthiourea catalyst in chlorinated solvent [8] have been reported. However, such systems are often selective towards the orthoisomers and involve use of solvent, which are not applicable for the commercial production of bulk chlorophenols.…”

Regioselective chlorination of phenols in the presence of tetrahydrothiopyran derivatives

“…Traditional phenol chlorination processes are not selective and produce significant waste [3]. Several chlorinating sys-tems have been reported for regioselective chlorination of phenols [4][5][6][7][8][9][10][11][12][13][14][15][16], including the use of Merrifield resin/sulfuryl chloride (SO2Cl2) [5], aluminum-pillared mont-morillonite clay or L type zeolites/SO2Cl2 [6], manganese(II) sulfate/hydrogen perox-ide/hydrogen chloride [7], ammonium chloride/1,3-dichloro-5,5-dimethylhydantoin [8],…”

“…[bis(trifluoroacetoxy)iodo]benzene/aluminum chloride (AlCl3) [9], and Nagasawa's bisthiourea catalyst/N-chlorosuccinimide [10]. However, such chlorinating systems lead to either limited para-selectivity, or to high ortho-selectivity, or cannot be applied on a large scale.…”