Transition states aniline methylation

C-alkylation of secondary and tertiary aromatic amines by hexafluoroacetone or methyl trifluoropyruvate is performed under mild conditions [172] (equation 147) The reaction of phenylhydrazme with hexafluoroacetone leads selectively to the product of the C-hydroxyalkylation at the ortho position of the aromatic ring The change from the para orientation characteristic for anilines is apparently a consequence of a cyclic transition state arising from the initial N hydroxy alky lation at the primary amino group [173] (equation 148)... 

A new method of methylating aniline at the nitrogen in supercritical methanol has been reported 132 alternative cyclic transition states involving one and two methanol molecules have been proposed for the base-catalysed reaction, which gives IV-methyl-aniline in >98% yields. 

Shape selectivity is not confined to reactions of hydrocarbons in the absence of polar functional groups. MFI type materials have been reported to catalyze the isomerisation of cresols, chlorotoluenes, toluonitriles and toluidines [259]. In the isomerization of aniline derivatives the reaction temperatures have to be relatively mild as under severe reaction temperatures isomerization to methylpyridine would occur [260]. For dimethylanilines it could be shown that only the isomers with the smallest minimum kinetic diameter reacted (reactant selectivity), and that those with a larger kinetic diameter did not form (product selectivity). The isomerization is concluded to occur via a 1,2 methyl shift which is interpreted to indicate transition state selectivity [261]. 

Potassium hexamethyldisilazide, KHMDS, has been used successfully in the past for a-deprotonation of sulfoxides. Aiming to probe the nature of the transition state in the reaction of a-metalated (i )-methyl //-tolyl sulfoxide with A -(benzylidene) aniline under kinetic conditions, the effect of the choice of the bases for the a-deprotonation on the reactivity and diastereoselectivity was studied, using LDA, LHMDS, NaHMDS, and KHMDS. Best yields anddiastereoselectivities (90%, 84 16) were achieved with LDA, whereas LHMDS showed diminished reactivity (50%) without a loss of diastereoselectivity (87 13). Improved yields and lower diastereoselectivities were recorded in reactions mediated by NaHMDS and KHMDS, providing the amine in 60% (dr 81 19) and 77% (dr 69 31) yields and diastereoselectivities, respectively (eq 64). 

The proposed transition state TS-1 to explain the role of the catalyst is depicted in Figure 6.5. The first reaction step between trifluoroacetaldehyde methyl hemiacetal 118 and the aniline 120 provides the corresponding V,0-acetal in the presence of catalyst 121 and molecular sieves. The V,0-acetal is expected to be in equilibrium with the imine 124, which would be protonated and activated by the chiral phosphoric acid to shield the ii-face of the imine. Contemporaneously,... 

The chemoselectivity of reactions of unsymmetrical diaryliodonium salts with phenols and anilines has been investigated in metal-free conditions. Generally, diaryl ethers or diphenylamines are formed from the more electron deficient of the diaryl components. However, steric effects of orf/io-methyl substituents may affect energies in the T-shaped transition state and may make reaction more favorable. ... 

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