Trifluoromethyl substituted pyridines synthesis

Examples of nitrogen-containing heterocycle syntheses based on condensation reactions continue to be forthcoming. Examples include a tandem oxidation-annulation of propargyl alcohols in a one-pot synthesis of pyridines (Equation 148) <2003SL1443>, trifluoromethyl-substituted pyridines (Scheme 94) <2003S1531>, and standard malononitrile additions to a,/3-unsaturated ketones <1995JCM392>. 

A facile one-pot synthesis of trifluoromethyl-substituted pyridine derivatives has been reported (93JHC71). The procedure depends on the high reactivity of trifluroacetoacetyl chloride, which is generated in situ from trifluoroacetyl chloride and ketene. Thus, the enaminone 391 gives the intermediate enamide 392, which is refluxed in triethylamine to give the... 

Ample opportunities are opened with synthesis of trifluoromethylated azines via oxidative nucleophilic substitution of hydrogen by trifluoromethyl carbanions [175], This pathway to the synthesis of trifluoromethylazines includes reaction of quatemization of azines 283 by p-methoxybenzylbromide (PMB) (284) to obtain salts 285. Further KF is added to reaction mixture of salt 285 and CF3Si(CH3)3 to generate anion 286. Regioselective trifluoromethylation results in formation of 1,2-dihydropyridines 287 which then have been oxidized by action CAN to get appropriate trifluoromethylazines 288 (Table 4) [ 175] (Scheme 85). Regioselectivity of the reactions is determined by the nature of substituent at pyridine s cycle. So in case of an ether of nicotinic acid and 3-benzoylpyridine the mixture of 2-and 6-trifluoromelhylpyridines are formed (Table 5). 

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