Aryl amide

In the alkyl aryl ketones, the aryl groups migrate preferentially, yielding V-aryl amides. 

N-Aryl-amide liefern infolge Desalkylierung und Transalkylierung niedrigere Ausbeu-ten. 

The reaction of amines with aryl halides requires a catalyst in most cases to initiate the reaction. There are several approaches that result in N-aryl amines. Treatment of cyclohexylamine with p-MeC6H4B(OH)2 and Cu(OAc)2 gave the N-aryl amide in 63% yield. Aryl halides react with amines in the presence of palladium... 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

Such reactions are also possible in vitro, as several mild oxidizing agents are at hand nowadays. Thus, the Dess-Martin periodinane (DMP) [50] has been proven to be a versatile and powerful reagent for the mild oxidation of alcohols to the corresponding carbonyl compounds. In this way, a series of new iodine(V)-mediated reactions has been developed which go far beyond simple alcohol oxidation [51], Ni-colaou and coworkers have developed an effective DM P-mediated domino polycy-clization reaction for converting simple aryl amides, urethanes and ureas to complex phenoxazine-containing polycycles. For example, reaction of the o-hydroxy anilide 7-101 with DMP (2 equiv.) in refluxing benzene under exposure to air led to polycycle 7-103 via 7-102 in a yield of 35 % (Scheme 7.28) [52]. 

Amides and sulfonamides undergo intramolecular chemistry to form aryl amides and aryl sulfonamides (Equations (17)—(19)) in the presence of palladium catalysts ligated by arylphos-phines.35,89 Initially, complexes of P(furyl)3 and P(o-tol)3 were most effective catalysts, but complexes of Hayashi s MOP and van Leeuwen s DPEphos and xantphos have lately been shown to be more active.90 In the presence of catalysts containing one of these ligand systems, five-, six-, and seven-membered rings were formed from halogenated benzamides or from substrates containing an acetamide, an A-carbobenzyloxy, or a t-butylcarbamate substituent tethered to the aryl halide (Equations (18) and (19)) ... 

Darvesh S, McDonald RS, Darvesh KV, et al. On the active site for hydrolysis of aryl amides and choline esters by human cholinesterases. Bioorg Med Chem 2006 14(13) 4586 1599. 

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

A reagent composed of tetra-n-butylammonium nitrate and TFAA in methylene chloride has been used to nitrate a series of A-alkyl and A-aryl amides (40-90 %). The formation of significant amounts of A-nitrosamides was noted. Tetra-n-butylammonium nitrate and triflic anhydride in methylene chloride has been used to successfully nitrate a variety of heterocyclic amides, imides and ureas (66). ... 

Kalinski C, Umkehrer M, Ross G, Kolb J, Burdack C, Hiller W (2006) Highly substituted indol-2-ones, quinoxalin-2-ones and benzodiazepin-2, 5-diones via a new Ugi(4CR)-Pd assisted A-aryl amidation strategy. Tetrahedron Lett 47 3423-3426... 

The second-resolution approach relied on enzymatic resolution of acetate esters 62 (Scheme 4.7) (Hayakawa et ah, 1991). The sequence opened with the alkylation of 2,3-difluoro-6-nitrophenol (59) with l-acetoxychloro-2-propane (60) to deliver ether 61. Reduction of the nitro group of 61 gave an intermediate anihne that cyclized to give racemic benzoxazine 62 in 62% yield. A variety of lipases were then examined for the resolution. The best results arose from use of LPL Amano 3, derived from P. aeruginosa, which gave a ratio of 73 23 in favor of the desired (—)-enantiomer. Benzoylation of the enantiomerically-enriched mixture followed by chromatography of the aryl amides delivered enantiomerically pure 63. 

The barrier to amide rotation is about 16 kcal/mol. It was later demonstrated53 that aryl amides, such as 19, with a somewhat lower barrier to rotation, do rotate more rapidly than they cyclize. Selectivity, then, is governed by electronic and steric factors. 

HMDS is known as an ammonia substitute in the preparation of primary amides via ammonolysis since 1985. With the use of excess HMDS, the Pd-catalyzed aminocarbonylation of various aryl and vinyl iodides and triflates (e.g., 146, 148, and 150) has been successfully performed to give the corresponding vinyl and aryl amides (e.g., 147, 149, and 151, respectively) in good to excellent yields (Scheme 21). " ... 

N-Aryl amides of sulphonic acids (X = —S02R, Y = H Section VI). 

Photolysis of JV-aryl amides of /3-ketocarboxylic acids 135 proceeds in a different way.93 Thus, phenylisocyanate 136 is formed in 60% yield when in 135 R = phenyl. When R = methyl or propyl, the yield decreases to 18%. Consequently, this reaction belongs only formally to the scope of the discussed rearrangements. It seems that this is a special example of Norrish Type II reaction.324 This assumption is supported by the yield dependence of... 

No aminothiophenones can be obtained by photorearrangement of JV-aryl amides of thiocarboxylic acids. The formation of 2-ethoxybenzthiazole (143) by oxidative photodehydrogenation of 142 is of some interest.11 Similarly, 2-phenylbenzthiazole originates by photocyclization of thiobenzanilide in the presence of oxygen."... 

Other cases for amides 5 -member-aryl-amide [N H2]C(=0)-a laaaal... 

Whereas a considerable number of pure amides of Mg, Ca, and Ba are known, the alkyl or aryl amides of these elements have been little investigated (9). Compounds of the general formula RMgNR 2 are usually coordination polymers, unless ether molecules are added to the compound or bulky R... 

The intramolecular alkylation of an aryl amide by an activated bromide, readily available by bromination of a malonamide methylene with pyridinium tribromide in the substrate depicted in Scheme 39, provided an example of a type c ring closure to furnish 3-carboxymethyl-l,4-benzodiazepin-2,5-diones <20060BC510, 2002H(56)1501, 1999JOC2914>. 

Reaction of the dilithio anion of 1-vinylbenzotriazole 90 with 2equiv of an aryl isocyanate led to a fused 1,4-diazepine ring formation via an intramolecular Michael addition of the intermediate aryl amide to the vinyl moiety, a type c ring closure that proceeded in good overall yield (Scheme 44) <2003JOC5713>. 

Scheme 10.1 (a) resonance forms in aryl amides illustrating the restricted rotation of the Ar-C (O)NH... 

A particularly attractive aryl amide foldamer is talibiter (10.1) named after the mythological wyrm Ouroboros that Kekule claimed inspired his structure of benzene (Figure 10.5),6 which folds back on itself in a spiral conformation such that the pyrrole unit on one end is close to the other end of the molecule. The solution conformation of the foldamer was determined using NMR spectroscopic methods as described in Box 6.1. 

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