Disubstituted anilines

Sachok, B., Stranahan, J.J., and Deming, S.N. (1981), Two-Factor Minimum Alpha Plots for the Liquid Chromatographic Separation of 2,6-Disubstituted Anilines, Anal. Chem., 53, 70-74. 

A simple aniline derivative acts as a prostatic antiandro-t ( n. Its synthesis involves simple acylation of disubstituted aniline 13 with isobutyryl chloride to give flutamide (14). ... 

The effects of different metallic promoters (Sn, Ge, Re etc.) and of various basic additives on the performance of the catalyst are discussed. The best catalyst developed is a Pt-Sn/Si02 catalyst p re treated with Ca2+ which is able to catalyze the alkylation of several ortho-disubstituted anilines with high conversions and selectivities. 

When the aminoboranes obtained by the thermal dehydrohalogena-tion of 2,6-disubstituted anilines are treated with a tertiary base, di-chloroborazines are obtained besides a diborylamine [Eq. (23)]. 

Two examples of such applications are outlined in Scheme 3. In the first one imidazolidinone la 10 mol% catalyzed the conjugated addition of a plethora of variously substituted N,N-disubstituted anilines to ,/fun saturated aldehydes to afford highly enantiomerically enriched /3-aryl aldehydes 5 (ee 89-97 %) in good yields (>73 %) [3]. On the other hand, the use of cationic BINAP-Cu complexes 6 (1-5 mol%) was found to be effective in the stereocontrolled 1,2-addition of indoles to the N-tosyl-a-imino ester 7 in TFIF at -78 °C [4]. 

Window diagrams and related methods may in principle be applied to optimization problems in more than one dimension. The main difference compared with one-parameter problems is that graphical procedures become much more difficult and that the role of the computer becomes more and more important. Deming et al. [558,559] have applied the window diagram method to the simultaneous optimization of two parameters in RPLC. The volume fraction of methanol and the concentration of ion-pairing reagent (1-octane sulfonic acid) were considered for the optimization of a mixture of 2,6-disubstituted anilines [558]. A five-parameter model equation was used to describe the retention surface for each solute. Data were recorded according to a three-level, two-factor experimental... 

A trifluoroacetic acid-catalyzed PictetSpengler reaction between the N,N-disubstituted aniline 93 and aromatic or aliphatic aldehydes afforded fused 1,4-benzodiazepines 94 in high yields after stirring at reflux in acetonitrile for 1648 h (Scheme 49). Electron-deficient aromatic aldehydes provided the best yields of 94, attributed to facile imine formation, while ketones were uniformly unreactive <2006T2563, CHEC-III(13.06.9.1.8)212>. 

Sulfanilamide (77) is a useful intermediate in the synthesis of 2,6-disubstituted anilines (Scheme 48). The last step is the hydrolytic removal of the sulfamoyl group, which occurs as a result of the reversibility of the sulfonation reaction (see p. 97). 

A total of 29 crystal structures of 2,4-disubstituted anilines have been retrieved from the CSD. The informative frequency histograms refer to the A9, A10 and All angles, which depict the amino group geometry. They are shown in Figure 10. 

Proton magnetic resonance, infrared spectroscopy and dielectric relaxation measurements, on ortho- and meta-disubstituted anilines, indicate that (despite what is expected on the basis of the usual steric hindrance arguments) a meta-substituted compound such as 32 results in more hindered rotation of the NH2 group than for orf/zo-substituted compounds such as 33. Solute/solvent and solute/solute intermolecular hydrogen bonding interactions are responsible for this hindered rotation73. 

For related work on 2,6-disubstituted aniline fragments cf. also Eastman Chemical Company, WO 00/50470. 

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