Amines, acylated aromatic

Acylation. Aromatic amines react with acids, acid chlorides, anhydrides, and esters to form amides. In general, acid chlorides give the best yield of the pure product. The reaction with acetic, propionic, butanoic, or benzoic acid can be catalyzed with phosphoms oxychloride or trichloride. 

Rearrangement of N-halo-N-acyl aromatic amines (Orton)... 

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. 

PhI(OTf)2, NaI04, peroxyacetic acid, H2O2 peroxydisulfates, and ammonium iodide with Oxone . The ICl is a better iodinating agent than iodine itself. Among other reagents used have been IF (prepared directly from the elements), and benzyltrialkylammonium dichloroiodate (which iodinates phenols, aromatic amines, and A-acylated aromatic amines, as well... 

MetaDrug also includes 89 rules to predict likely reactive metabolites such as quinones, aromatic and hydroxyl amines, acyl glucuronides, acyl halides, epoxides, thiophenes, furans, phenoxyl radicals, phenols, and aniline radicals. Molecules with reactive groups are marked and highlighted. 

Combinatorial sequences that comprise amine acylation can frequently be expanded to sulfonamide formation using sulfonyl chlorides (unspecified sulfochlorides [9, 52] aliphatic and aromatic sulfochlorides [19] aromatic sulfochlorides [80,102]). Sulfonation of aliphatic diamines with protected (3-aminoalkane sulfonyl chlorides was carried out in the presence of polymer-bound 4-dialkylaminopyridine [130] (see also Table 3.11). 

It can be used for reaction with aryl ethers and acylated aromatic amines.764 Various alkylated aromatic compounds can be substituted in the ring by C1SCN in the dark, but in the side chain under UV-irradiation.765... 

Figure 10.25 Twenty-nine specific toxicophores for mutagenicity as identified by Kazius el al. (Kazius, J-, et al. Derivation and validation of toxicophores for mutagenicity prediction. J. Med. Chem. 2005, 48, 312-320.) (A) Specific aromatic nitro, (B) specific aromatic amine, (C) aromatic nitroso, (D) alkyl nitrite, (E) nitrosamine, (F) epoxide, (G) aziridine, (H) azide, (I) diazo, (J) triazene, (K) aromatic azo, (L) unsubstituted heteroatom-bonded heteroatom, (M) aryl hydroxylamine, (N) alkyl halide, (O) acyl halide, (P) N- or 5-mustard, (Q) polycyclic aromatics, (R) bay-region, (S) K-region, (T) sulphonate-bonded C, (U) unsaturated aldehyde, (V) alkyl A-nitro, (W) diazonium, (X) p-propiolactone, (Y) unsubstituted a,p unsaturated alkoxy, (Z) l-aryl-2-monoalkyl hydrazine, (AA) aromatic methylamine, (AB) aryl hydroxylamine ester, and (AC) polycyclic planar system.

Quatemization involves the reaction of a tertiary amine with an alkylating agent. Typically, primary and some secondary alkyl halides are used for this purpose, although alkyl sulfates have also been used. Tertiary hahdes are not useful because they undergo elimination rather than substitution. The reaction, which is an example of an Sn2 process, proceeds readily to give crystalline, stable, and still-aromatic quaternary salts (Scheme 6.6). These have been used for many years to characterize amines. Acyl halides also react in a similar manner with pyridine, but the resulting salts are unstable and generally not isolated. 

In search of molecules that selectively induce apoptosis in cancer cells, Hergenrother and coworkers synthesized a combinatorial library based on the A(-acylated aromatic amine 211, isolated from Isodon excisus, which displayed activity in either pro- or antiapoptotic assays (Figure 11.97). ° - ° The library was created from the parallel coupling of 8 acids and 11 amine building blocks, using... 

Acylated aromatic amines (those having an acyl group, R—C —, substituted on nitrogen) are important in over-the-counter headache remedies. Over-the-counter drugs are those you may buy without a prescription. Acetanilide, phenacetin, and acetaminophen are mild analgesics (relieve pain) and antipyretics (reduce fever) and are important, along with aspirin, in many nonprescription drugs. 

A/ Acylated aromatic amines still direct ortho/para, but substitution is slower than for the unsubstituted aniline, and the reaction can be stopped after a single new substitution. The protecting acyl group can be removed later by treatment with acid or base. We will see the mechanisms for these reactions in Chapter 18. 

Salts of aromatic amines acyl derivatives of primary and secondary aromatic amines (often very slowly) high mol.wt. amino-acids hydrazine derivatives aryl ureas and aryl thioureas. 

Some acylated aromatic amines may be characterized by nitration (see Table 19). 

For the identification of amines acylation methods (acetylation, benzoylation, 3,5-dinitrobezoylation), reaction with p-toluenesulfonyl chloride, preparation of substituted thioureas, diazotization and coupling (for aromatic primary amines), and the preparation of salts (picrates, tetraphenylboron salts) are most commonly used. 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

The reverse reaction is an intramolecular acidolysis of amide group by the o-carboxyhc acid to reform anhydride and amine. This unique feature is the result of an ortho neighboring effect. In contrast, the acylation of an amine with ben2oic anhydride is an irreversible reaction under the same reaction conditions. The poly(amic acid) stmcture (8) can be considered as a class of polyamides. Aromatic polyamides that lack ortho carboxylic groups are very... 

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