Anilines, acyl, halogenation

Homing and Muchowski have recently presented a modification of the general procedures described above. In an attempt to replace selectively the acyl halogen in 48 with azide ion, these authors examined the reactions of dimethylformamide-acyl halide complexes (49) with nucleophiles (equation 35). The site of attack of a nucleophile on the ambident cation (49) is markedly influenced by the nature of the solvent and the temperature. Control reactions with aniline as the nucleophile enabled the optimum conditions for attack at the acyl carbon atom to be elucidated. With azide ion under these conditions, acyl azides were obtained in 60-100% yield (based on... 

Nucleophilic aromatic substitution of the anion from ary lace ton itrile 113 on the dichloroni-trobenzene 114 results in replacement of the para halogen and formation of 115. Reduction of the nitro group gives the corresponding aniline (116). Acylation of the amine with 3,5-diiodoacetylsa-licylic acid 117 by means of the mixed anhydride formed by use of ethyl chloroformate, gives, after alkaline hydroly.sis, the anthelmintic agent closantel (118) [28]. 

Experimental studies of the reactivity of other aniline derivatives in substitution reactions are far more limited, de la Mare and Hassan (1958) and Bradfield and Jones (1928) examined the influence of acyl substituents on the amino function on the rate of halogenation at the para position. These interesting data are too limited to be useful for the evaluation of a linear free-energy relationship and are not included in Table 4. 

The palladium-catalyzed formation of diarylamines has been used in several contexts to form molecules with biological relevance. The ability to prepare haloarenes selectively by an ortho-metallation halogenation sequence allows for the selective delivery of an amino group to a substituted aromatic structure. Snieckus has used directed metallation to form aryl halides that were subsequently reacted with anilines to prepare diarylamines (Eq. 34)) [156]. Frost and Mendon a have reported an iterative strategy to prepare (by palladium-catalyzed chemistry) amides and sulfonamides that may act as peptidomimetics. Diarylamine units are constructed using the DPPF-ligated palladium catalysts, and the products are then acylated or sulfo-nated with 4-bromo benzoyl or arylsulfonyl chlorides [157]. 

Preparation of diazoketones and their rearrangements during hydrolysis (method 271) and alcoholysis (method 295) are discussed elsewhere. Ammonolysis of diazoketones leads to amides of acids containing one more carbon atom than the original acyl halide. Halogen atoms may be present in a remote position on an aliphatic chain. The reaction is carried out by heating the diazoketone in alcohol or dioxane solution with aqueous ammonia in the presence of silver oxide or silver nitrate catalysts. Substituted acetanilides are formed when aniline is used in place of ammonia. ... 

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