Arylamines acylation

Direct nitration of aniline and other arylamines fails because oxidation leads to the formation of dark colored tars As a solution to this problem it is standaid practice to first protect the ammo group by acylation with either acetyl chloride or acetic anhydride... 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

A number of A/-acyl-. A/-alkyl-, and /V-arylamin on apbtbalenol sulfonic acids are used as couplers for a2o dyes. Examples of such intermediates are shown in Table 8. 

The main type of hydrolysis reaction is that of halogenoaryl compounds to hydroxyaryl compounds, eg, the aqueous caustic hydrolysis of 0- and /)-chloronitrobenzene derivatives to nitrophenols. Another important reaction is the hydrolysis of A/-acyl derivatives back to the parent arylamine, where the acyl group is frequently used to protect the amine. 

Phosgenation. Reaction of phosgene with arylamines to form ureas, and with reactive aryl species to form substituted hen zophen ones, are special cases of acylation. They are dealt with separately siace a more specialized plant is required than for other acylations. Urea formation takes place readily with water-soluble arylamines by simply passiag phosgeae through a slightly alkaline solutioa. An important example is carbonyl-J-acid from J-acid. 

The Gould-Jacobs reaction is a sequence of the following reactions (1) condensation of an arylamine 1 with either alkoxy methylenemalonic ester or acyl malonic ester 2 providing the anilidomethylenemalonic ester 3 (2) cyclization of 3 to the 4-hydroxy-3-carboalkoxyquinoline 4 (3) saponification to form acid 5, and (4) decarboxylation to give the 4-hydroxyquinoline 6. All steps of this process will be described herein with emphasis on the formation of intermediates like 3 and 4. 

Resolution (enantiomers), 307-309 Resonance, 43-47 acetate ion and, 43 acetone anion and. 45 acyl cations and, 558 allylic carbocations and, 488-489 allylic radical and, 341 arylamines and, 924 benzene and, 44. 521 benzylic carbocation and, 377 benzylic radical and, 578 carbonate ion and. 47 carboxylate ions and, 756-757 enolate ions and, 850 naphthalene and, 532 pentadienyl radical and. 48 phenoxide ions and, 605-606 Resonance effect, 562 Resonance forms, 43... 

The treatment of acyl halides with ammonia or amines is a very general reaction for the preparation of amides.The reaction is highly exothermic and must be carefully controlled, usually by cooling or dilution. Ammonia gives unsubstituted amides, primary amines give A-substituted amides, and secondary amines give N,N-disubstituted amides. Arylamines can be similarly acylated. In some cases aqueous... 

When acylated arylamines are photolyzed, migration of an acyl group takes place" in a process that resembles the photo-Fries reaction (11-30). 

The products from the N-alkylation of (anilinomethylene)malonodinitriles with a-haloacetic esters and a-haloketones spontaneously cyclize to produce pyrroles (Scheme 5.3) [21]. When the A -acylated product of the reaction of the dinitrile with ethyl chloroformate is treated with an arylamine, 5-cyanopyrimidones are obtained [21]. 

The antibacterial sulfonamide phthalazole 268 is obtained free of imide and bisamide side products (that occur upon reaction in solution or in the melt) if stoichiometric solid-state milling of the reactants 266 and 267 is performed for the acylation [95] (Scheme 38). Numerous solid arylamines and heterocyclic amines react correspondingly with phthalic anhydride upon stoichiometric milling and provide 100% yield without any workup requirement [22]. 

Aromatic nitroso compounds combine with primary arylamines in glacial acetic acid to give symmetrical or unsymmetrical azo compounds (the Mills reaction).554 A wide variety of substituents may be present in both aryl groups. Unsymmetrical azo compounds have also been prepared by the reaction between aromatic nitro compounds ArN02 and N-acyl aromatic amines Ar NHAc.555 The use of phase transfer catalysis increased the yields. 

Photolysis of acylated arylamines 6-16 Reaction between aldehydes, ammonia, and aldehydes, ketones, or esters (Mannich)... 

Recalling that arylamines are normally prepared by reduction of nitroarenes, we see that ethyl m-nitrophenyl ketone is a pivotal synthetic intermediate. It is prepared by nitration of ethyl phenyl ketone, which is analogous to nitration of acetophenone, shown in Section 12.16. The preparation of ethyl phenyl ketone by Friedel-Crafts acylation of benzene is shown in Section 12.7. 

Acyl chlorides bring about A-acylation of arylamines. 

N,0-Acyltransferase. The /V-acyl transferase enzyme is believed to be involved in the carcinogenicity of arylamines. These compounds are first V-oxidized, and then, in species capable of their A-acetylation, acetylated to arylhydroxamic acids. The effect of N, O-transacetylation is shown in Figure 7.22. The A/-acyl group of the hydroxamic acid is first removed and is then transferred, either to an amine to yield a stable amide or to the oxygen of the hydroxylamine to yield a reactive N-acyloxyarylaminc. These compounds are highly reactive in the formation of adducts with both proteins and nucleic acids, and N, O -acy I Iransfcrasc, added to the medium in the Ames test, increases the mutagenicity of compounds such as A-hydroxy-2-acetylaminofluorine. 

The palladium-catalyzed formation of diarylamines has been used in several contexts to form molecules of biological relevance. The ability to prepare haloarenes selectively by an ortfio-metalation-halogenation sequence allows the selective delivery of an amino group to a substituted aromatic structure. Snieckus has used directed metalation to form aryl halides that were subsequently allowed to react with anilines to form diarylamines (Eq. (34)) [209]. Frost and Mendonqa have reported an iterative strategy to prepare, by the palladium-catalyzed chemistry, amides and sulfonamides that may act as peptidomimetics. Diaryl-amine units were constructed using the DPPF-ligated palladium catalysts, and the products were then acylated or sulfonated with 4-bromobenzoyl or arylsulfonyl chlorides [210]. Le-miere has coupled primary arylamines with 4-chloro-3(2H)-pyridazinones to form compounds with possible analgesic and antiinflammatory properties. 

When acylated arylamines are photolyzed, migration of an acyl group takes... 

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