2- Fluoroalkyl pyridines

This reaction is general and other perfluorinated nitriles RpCN (Rp = CF3, CICF2, FCI2C, C2F5, n-CsFj) under similar conditions give the corresponding 2-fluoroalkyl pyridines in high yields. 

On the other hand, 2-fluoroalkyl pyridines undergo oxidation under action of peroxyacids giving the corresponding oxides 100 in high yield (Fig. 7.35). ... 

A new class of fluoroalkyled pyridine herbicides has been synthesized from ethyl 4,4,4-trifluoroacetoacetate. The synthetic route involves formation of dihydropyridine intermediate which upon oxidation or dehydrofluorination produces the desired pyridine compounds. Hydrolysis of the ester groups followed by derivatization of the resulting acids yields a variety of herbicidally active pyridine compounds. 

Palacios F, Alonso C, Rubiales G et al (2005) Aza-wittig reaction of fluoroaUsylated n-vinylic phosphazenes with carbonyl compounds. Usefulness of 2-azadienes for the preparation of fluoroalkyl pyridine derivatives. Tetrahedron 61 2779-2794... 

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

In polyfluorobenzenes having other substituents in addition to fluorine, including per-fluoroalkyl or perfluoroaryl groups, the elimination of only one fluorine atom proceeds more readily, with the para position in pentafluorobenzene derivatives being replaced first. The reaction conditions used for monosubstitution of fluorine depend markedly on the substrate and on the nucleophilic agent chosen. In most cases the reaction can be carried out in ethylene glycol/pyridine using sodium hydroxide as base (Table 3). 

Similar to the Dakin-West procedure previously mentioned, the Henry nitro-aldol condensation reaction is most widely used to synthesize trifluoromethyl ketones, although there are many examples of a,a-difluoroalkyl ketones synthesized by this method (Table 6)JU 12271 The method for a,a-difluoroalkyl and trifluoromethyl ketone synthesis is identical except for the final oxidation although fluoroalkyl and a,a-difluoroalkyl ketones are easily oxidized by the Sarett method (Cr03/pyridine),[12 the corresponding trifluoromethyl ketones can only be oxidized under basic conditions (0.3 M NaOH) with KMn04Jul Also, in some of the syntheses of a,a-difluoroalkyl ketones, the nitro alcohol intermediate was protected by si-lylation with /ert-butylchlorodimethylsilane. The silyl group was later removed by TosOH prior to oxidation. The full details of this method are given in Section 15.1.4.3.2. 

Aryl fluoroalkyl ethers have been prepared from the reaction, at room temperature in HMPA, of fluo-ro-substituted alkoxides with activated fluoro-,149 nitro-,149 and, at 150 °C, also chloro-arenes150,151 and some chloro-substituted pyrazines (equation 15), pyrimidines, quinolines,150,152 and pyridines.152 Disubstitution was observed in die presence of comparably activated leaving groups such as in 2,4- and 2,6-di-chloronitro- or cyano-benzenes, whereas regiospecific substitution took place at position 4 in 3,4-dichloronitro- or cyano-benzene and at position 2 in 2-fluoro-6-chlorocyanobenzene.151 Steric hindrance and the number of fluorine substituents in the alkoxide pose limits to the reactivity. Thus, tertiary alkoxides, or alkoxides containing more than four fluorine substituents, displace activated nitro and fluoro, but not chloro substituents.149,150 The secondary hexafluoro-2-propoxide anion does not react even with the more reactive nitro and fluoro derivatives.149... 

Besides the synthesis of 1-chloroalkyl carbonates, this method is general enough to be used for the preparation of 1-fluoroalkyl, 1-bromoalkyl or 1-iodoalkylcarbonates as shown in table 3-7. However, the method gives poor results or even failed when the haloformate is too unstable in presence of the catalyst (see section 3-2-1). For example, attempts to prepare 1-chloroethyl ethyl carbonate (CEEC) itself in 1,2 dichloroethane at 60°C with 0.05 equ. pyridine, gave almost total decomposition of ethyl chloro-formate. 

None of the catalysts tested quaternary ammonium salts, N,N-dimethylamino pyridine (DMAP), 1-methyl imidazole, tertiary amines, Michler s ketone, quinoline etc. performed as well as pyridine. For the preparation of 1-fluoroalkyl carbonate, the best catalytic system found was the KF/18-crown-6 complex. To avoid side reactions, only aldehydes without hydrogen at C-2 should be used in this case. 

A Cu(II) complex with a bipyridine-type ligand (Cu-4) is effective in the controlled polymerization of styrene and acrylates in the presence of Al(0-i-Pr)3, which most probably serves as a reducing agent of Cu(II) into Cu(I).93-94 A fluoroalkyl-substituted bipyridine ligand (L-7) was also employed in supercritical carbon dioxide for the polymerization of fluorinated acrylates and methacrylates.95 Similar pyridine-based bidentate ligands, 1,10-phenanthroline and its... 

S02,403 on the photoreduction of quinones,404 on acetyl and acetyl peroxide radicals in gas-phase reactions,405 on fluoroalkyl radicals in solution,408 on the photochemistry of 2,2-dimethoxy-2-phenylacetophenone,407 on pyridine-3,5-dicarboxylic acid,408 on photolytically reduced pyrazine,409 410 on the dimerization... 

The attack of amines and hydrazines on perfluoroalkyl-substituted sym-triazines has been investigated. A detailed compilation of physicochemical data on fluoroalkoxy- and fluoroalkyl-sym-triazines has been published the compounds are stable at 350 °C and tire non-flammable. 4-Azido-2,3,5,6-tetrafluoro-, 4-azido-3-chloro-2,5,6-trifluOTo-, and 4-azido-3,5-dichloto-2,6-difluoio-pyridine have been prepared by treatment of pentafluoro-, 3-chlorotetrafluoro-, and 3,5-dichlorotrifluoro-pyridine, respectively, with sodium azide in acetonitrile. The 4-azidotetrafluoro-compound, also obtainable via nitrosation of 2,3,5,6-tetrafluoro-4-hydra-zinopyridine, undergoes the reactions shown in Scheme 60, and appears to be a good thermal source of tetrafluoro-4-pyridylnitrene. ... 

The 2,6-bis(fluoroalkyl)-3,5-pyridinedicarboxylates are a new class of herbicide discovered and being developed by Monsanto Company. One of these compounds, S. S -dimethyl 2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridinedicarbothioate (proposed common name dithiopyr) 1 is being developed as a herbicide for rice and turf. We describe herein the discovery, synthesis and herbicidal activity of these pyridines. 

Petfluwoalkanoic anhydrides can be used as another source of fluoroalkyl substituents in the formed oxazole nucleus. For example, the reaction of A(-acyl-A(-alkyl-a-amino acids (18) or IV-acylprolines (19) with trifluoroacetic anhydride in the presence of pyridine (under Dakin-West reaction conditions) [24] affords 5-trifluoromethyloxazoles (20 or 21) in good yields [25,26] (best yields are observed for R =Bn). 

Palacios F, Alonso C, Rodriguez M, Rodriguez M, Martinez de Marigorta E, Rubiales G (2005) Preparation of 3-(fluoroalkyl)-2-azadienes and its application in the synthesis of (fluo-roalkyl)isoquinoline and -pyridine derivatives. Eur J Org Chem 9 1795-1804... 

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