4-Bromo-2-chloroaniline preparation

The checkers have prepared the following bromides by the same procedure w-chlorobromobenzene (b.p. 191-194°) from jw-chloroaniline in 91-94% yields ra-dibromobenzene (b.p. 215-217°) from ra-bromoaniline in 80 87% yields and u-bromo-anisole (b.p. 114-116°/29 mm.) from o-anisidine in 88-93% yields. In the preparation of o-bromoanisole the washing with sulfuric acid was omitted. 

A number of additional cyclizations involving alkynes have been reported. For instance, it has been shown that indoles may also be accessed from 2-bromo- or 2-chloroanilines, as illustrated by the regioselective preparation of the carbinol 373 in the presence of the ferrocene 374 (Equation 104) <20040L4129>, whereas a one-pot sequence featuring titanium catalyzed hydroamination of 2-chloroanilines with acetylenes, followed by intramolecular Heck cyclization in the presence of an imidazol-2-ylidene palladium complex, has also been reported <2004CC2824>. A set of aryl-2-indolyl carbinols have been prepared in high enantiomeric purity by palladium-catalyzed annulation of... 

The cyclization of A-allyl-o-haloaniJines was adapted to the sohd phase for both indoles [309, 310] and oxindoles [311]. For example, as illustrated below (310), a library of l-acyl-3-alkyl-6-hydroxyindoles is readily assembled from acid chlorides, allylic bromides, and 4-bromo-3-nitroanisole [309]. Zhang and Maryanoff used the Rink amide resin to prepare iV-benzylindole-3-acetamides and related indoles via Heck cyclization [310], and Balasubramanian employed this technology to the synthesis of oxindoles via the palladium cyclization of o-iodo-A-acryloylanilines [311]. This latter cyclization route to oxindoles is presented later in this section. Caddick has described Heck indole ring syntheses from 2-chloroanilines using Pd/imidazolium salts [312], and Anslyn uses the Heck cyclization of 299 to 300 as a fluorescence sensor [313]. 

Setting Up With magnetic stirring, dissolve 2.5 g of recrystallized 4-bromo-2-chloroaniline in 40 mL of glacial acetic acid in the round-bottom flask and add 10 mL of water to the mixture. In an Erlenmeyer flask, prepare a solution of 2.5 g of technical iodine monochloride in 10 mL of glacial acetic acid. 

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