2,6-Disubstituted anilides

Siddall and his co-workers (46) have examined the barriers to rotation of a series of 2,6-disubstituted anilides. Af-Ethyl-A/-(2,6-xylyl)formamide (9) was recrystallized as a uranyl nitrate complex, and one isomer, which at equilibrium was favored by a factor of 3 1, was enriched up to a 30 1 ratio. The kinetics of rotation were examined at 0 to 29°C. The Arrhenius activation energy was 26 3 kcal/mol and log A was 18.5 2.4 hr-1. Siddall and Gamer (47) were able to obtain an almost pure isomer (which also predominated at equilibrium 1.3 1 for the ethyl compound and 1.1 1 for the methyl compound) of Ar-alkyl- V-(2-methyl-4,6-dibromophenyl)-l-naphthamide (10). The half-lives of... 

A series of m- and -disubstituted anilides of thienoic acid and of 2-benzoylthiophenes, which have substituents at the m- and />-position of the benzoyl ring, have been prepared and their IR and NMR spectra obtained in 0.1 M chloroform-r/ solutions and DMSO-r4. The chemical shift values of each series were plotted against the Hammett substituent parameters to give good correlation. The slopes as well as the differences in chemical shift gave a set of meaningful values for the indexes of aromaticity <2002JHC1219>. 

Molecular ion Abundant. [M-H]" " is significant in N,N-disubstituted anilides, weaker in monosubstituted derivatives, and absent from the spectrum of benzamide. It is formed exclusively by loss of ortljo-hydrogens of the aromatic ring. 

Enamines of cyclic ketones do not form cycloaddition products, but give the mono- or dicarboxanilides (110,111). Thus the enamine (113) on reaction with 1 equivalent of phenyl isocyanate gave 160. Treatment of 113 with 2 equivalents, or 160 with 1 equivalent, of phenyl isocyanate gave the 2,6-disubstituted product (161). Mild acid hydrolysis of 160 and 161 produced the corresponding cyclohexanone(2-mono- and 2,5-di)carbox-anilides (110). 

An unusual rearrangement following cyclization using a masked a-carbonyl equivalent, 2-anilino-2-ethoxy-3-oxothiobutanoic acid anilide 118, to form 6,7-disubstituted pteridine 119 by simply refluxing in ethanol for 3h was reported (Scheme 24) <2002JOC4526>. The synthesis of pyridopyrazine and related compounds using 39 was also discussed. 

For the final step involving functionalization at N( ) of 62, anilide deprotonation with lithiated 4-benzyl-2-oxazolidinone as a base and alkylation with benzyl bromides again proved effective. Compared to the results obtained in the benzodiazepine series, the N( 1 )-alkylation reaction was generally found to proceed less smoothly with the 3,4-disubstituted quinox-alinones 62. Good results were obtained only if the resin batches were submitted twice to the alkylation conditions. Figure 3.4 displays a selection of structures (63-65) accessible from this first synthetic approach. In no case was there any evidence for racemization at the a-carbon atom of the amino acid. 

Finally, Ma et al. further elaborated on this chemistry toward the development of an efficient cascade process for the assembly of 2,3-disubstituted indoles 296 (Scheme 9.102) [239,272]. The authors showed that an array ofaliphatic and aromatic P-ketoesters and ketoamides 295 could be utilized in the 3 +2 annulation reaction with anilides 294 providing the corresponding indoles 296 in moderate to excellent yields. In addition, this reaction was applied to 2-bromotrifluoroacetanilides, albeit requiring slightly elevated temperatures to achieve complete conversion. It is believed that cydocondensation of aminoketone 298 accomplished the indole ring... 

Acyl)anilides 78 can be cydized by intramolecular reductive coupling of the two carbonyl moieties mediated by low-valent titanium (abbreviated [Ti]), thus creating the C-2/C-3 bond of 2,3-disubstituted indoles 79 (Furstner synthesis) [166] ... 

The intramolecular synthesis of 3,3-disubstituted oxindoles through C(sp )-H and Ar-H coupling of anilides using potassium t-butoxide as base and stoichiometric Cu(0Ac)2 H20 in DMF (N,N-Dimethylformamide) was reported by Taylor et /.[66]. This reaction also could be conducted under catalytic Cu(0Ac)2-H20 in toluene or mesitylene with atmospheric oxygen as the reoxidant without an additional base. A range of substrates including several... 

Several examples of organoaluminum-catalyzed hydroamination of amino-alkenes have been reported recently. The neutral amido bis(anilide) 27 [37] and the aluminum pincer diolate complex 28 [114] displayed low catalytic activity and were only applicable to gem-disubstituted aminopentenes (Fig. 7). 

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