4-Bromo-2-chloroaniline

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. 

Why must aqueous base be added in order to isolate 4-bromo-2-chloroaniline from the aqueous acidic mixture ... 

Consider the spectral data for 4-bromo-2-chloroaniline (Figs. 21.16 and 21.17). 

Discuss the differences observed in the IR and NMR spectra of 4-bromo-2-chloroacetanilide and 4-bromo-2-chloroaniline that are consistent with the formation of the latter in this procedure. 

The combination of reagents used in this experiment to iodinate 4-bromo-2-chloroaniline (21) is I-CI/CH3CO2H because I2/CH3CO2H is not as effective. Provide a mechanistic rationale to explain this fact. 

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. 

The reaction of aromatic amines with tetrazine (151) gave either 1,2,4-triazoles (154) or pyrazolo[4,3-e]-l,2,4-triazines (155), depending on the substituents. While aniline, p-toluidine, p-anisidine and p-chloroaniline afford 155, the bromo and p-nitro derivatives give 154. Intermediates 152 and 153 were postulated (Scheme 22) (82CB683). 

Phenyl ureas, carbamates, organochlorine insecticides, 4-bromophenol, captan, bromo- and chloroanilines, methylanilines, bromo- and chloro-nitrobenzenes, diphenyl amino folpet, hexachlorobenzene, naphthalene, phenol, simazine... 

The most important diazo components are 4-nitroaniline [100-01-6], 2-chloro-4-nitroaniline [121-87-9], 2-cyano-4-nitroaniline [17420-30-3], 2,4-dinitroaniline [97-02-9], 2,6-dichloro-4-nitroaniline [99-30-9], 2-bromo- [1817-73-8] and 2-chloro-4,6-dinitroaniline [3531-19-9], and 2-bromo-6-cyano-4-nitroaniline [17601-94-4], The coupling components are derived from aniline, 3-aminotoluene 1108-44-1], 3-chloroaniline [108-42-9], 3-aminoacetanilide [102-28-3], and 3-amino-4-alkoxyacetanilide by /V-alkylation. 

It has been demonstrated that the presence of chlorine or bromine in the nucleus facilitates replacement of the diazo group by hydrogen little or no ether formation occurs.26 Apparently iodine also favors the redudng action of alcohols, but this point has not been investigated carefully.26 27 No attempts to deaminate fluorinated amines are recorded. Representative of the effitiency with which ethanol reduces diazonium salts derived from halogenated amines are the deaminations of m-chloroaniline 26 (87% yield), of 2-bromo-4-methylaniline 28 (67% yield), of 2,4,6-tribfomoaniline 29 (ca. 80% yield), and of 2-carboxy-4-iodoaniline30 (ca. 45% yield) in the biphenyl series the deamination of VIII in 53% yield 31 may be dted. 

Unsubstituted and substituted o-bromo and o-chloroanilines are adequate substrates for obtaining indoles substituted with Me, Ph, or MeO groups in 50-90% yield [70a]. 

The phototransformation of aqueous 2-chloroaniline was studied by Oth-men and Boule by means of product analysis [47] these authors later deepened and extended their work, including also 2-fluoro- and 2-bromo-aniline [48]. The range of photodegradation quantum yields was

[Pg.172]

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]. 

Modified Larock Indole Synthesis of Internal Alkynes With o-Bromo or o Chloroanilines 3-Ethyl-2-isopropenyl-5-methyI-l -indole (131) ... 

Gillio-Tos and co-workers [23] have chromatographed isomeric toluidines, aminophenols, aminobenzoic acids, anisidines, nitroanilines, phenylenediamines, bromo- and chloroanilines on silica gel G using, for example, the solvents dibutyl ether-ethyl acetate-acetic acid (50 + 50 + 5), (75 + 25 + 5) or (25 + 75 + 5). Detection was carried out by first spraying with 5% sodium nitrite in 0.2N hydrochloric acid, dryng the plates at 50° C and spraying then with 5 % a-naphthol in methanol. 

This reaction principle has been simplified to direct Pd(II)-catalyzed N-amination/biaryl coupling routes starting (a) with 2-chloroanilines and aryl bromides in the presence of tBu3 P [204] and (b) starting with 2-bromo-(N-tosyl)anilines and iodoarenes in the presence of K2CO3 and norbomene as co-Ugand [205]. 

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