Fluoroalkyl anilines

The use of trialkyl phosphates for dialkylation of anilines has been found applicable to naphthylamines and to a large number of anilines substituted in the ortho, meta, or para position by groups such as chloro, methoxy, and methyl and in the meta position by fluoroalkyl (author s laboratory). The reaction has been used to introduce ethyl and M-butyl as well as methyl groups by employing the appropriate phosphate esters. The reported yields range from 50% to 95%. 

Fluoroalkyl heterocycles Condensation of o-functionalized (OH, SH, NH2) anilines with fluoroalkyl ketones leads to benzoxazolines, benzthiazolines, benzimida-zolines,... bearing a fluorinated carbon chain at C-2. The reaction is promoted by Ga(OTf )3. 

Peifluoroalkylation. By using CuiO as the catalyst, anilines undergo per-fluoroalkylation with RT in DMSO at 130°. The perfluoroalkyl groups enter at ortho- and para-positions that are open. (V,(V-Dimethylaniline suffers demethylation in the process. 

As for substituents on the aniline ring, the ortho-methyl group was fixed, because it was essential for keeping the stability of the diamide structure. The optimization of the best position with a chlorine atom as substituent Y showed that the 4-position was the best by comparison of compounds 10-12. Other groups were introduced as substituent Y onto the aniline ring, and the results showed the tendency for a more lipophilic substituent to be preferable. Notably, the fluoroalkyl group was highly effective as exemplified with the heptafluoroisopropyl compound... 

The interpretation of the experimental a constants for the fluoroalkyl and nitroxide radicals is complicated because the stereochemistry at the radical center is not well defined. This complication does not exist for radicals derived from aromatic compounds. Consequently, several research groups have investigated aromatic radicals to characterize the factors governing spin delocalization to /3-fluorine atoms. One aspect of this work concerns the epr spectra of nitrobenzene anion radicals. Another concerns the contact chemical shifts of paramagnetic transition metal complexes. The latter approach was initiated by Eaton, Josey, and Sheppard who examined stable bis(phenylaminotroponiminato)-nickel(II) complexes (55a). More recently, we have examined the contact chemical shifts in the nmr spectra of nickel acetylacetonate complexes of aniline derivatives (556). 

A group of methods for the preparation of fluoroalkyl-substituted pyrimidines relied on CNCh-CCN connection of the aromatic ring. A variety of fluorinated 1,3-dielectrophiles was used for the annulations of CNC triade to CCN binucleophiles (i.e. anilines, enamines and electron-rich amino heterocycles). The most widely used among such 1,3-CNC-dielectrophiles are functionalized heterocumulenes 845-847 (Fig. 26) trifluoromethyl substituted imine derivatives 848, 849 and 850 can be also mentioned. 

The reaction of anilines with perfluorinated imine 932 can be considered also as CNC+CCN approach to fluoroalkyl-substituted pyrimidines, hnine 932 was synthesized by perfluobutane elimination from perfluorotributylamine [563] under ACF (Aluminium chlorofluoride, AlClxFs.x, x 0.05-0.25) catalyzed thermolysis [564], This imine have been found to react smoothly with 2 equivalents of anilines in presence of 3 equivalents of TEA in MeCN to give the fused pyrimidines 933 in good yields. In a case of 2,6-dimethylaniline the reaction leads to the dihydroquinazoline derivative 934 (Scheme 196) [565]. 

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