Pyridine, 3-trifluoromethyl

Molybdenum hexafluoride, in the presence of boron trifluonde, reacts with acetic acid and haloacetic acids at 130-160 °C to give respectively, 1,1,1 tri fluoroethane and 1,1 1 trifluorohaloetlianes in 60-89% yields [2d0, 241] Prolonged treatment of pyridine mono and dicarboxylic acids with an excess of molybdenum hexafluoride at elevated temperatures provides the respective mono-and bis(trifluoromethyl)pyridines in good yields [241] (equation 127)... 

Chlorination of 3-(trifluoromethyl)pyridine takes place under fairly harsh conditions [36] (equation 18)... 

Fluorinated heterocycles have many uses and the following are some typical examples. Trifluoromethyl pyridines are useful building blocks for agrochemicals (91MI1). Fluorinated quinolones have evoked considerable interest in the last 10 years as antibacterial agents (90MI1, 90MI2). The... 

Alkylzinc halides have also been prepared under microwave irradiation. The Reformatsky reagents (2-t-butoxy-2-oxoethyl)zinc bromide and [(2-dibenzylamino)-2-oxoethyl]zinc bromide were synthesized from the corresponding bromides via reaction with zinc in THF (Scheme 5) [24], The oxidative addition was executed at 100 °C in 5 min. The obtained reagents were subsequently used in Negishi reactions on 2-bromopyridine, 3-bromopyridine, 2-bromo-5-nitropyridine, and 2-bromo-5-trifluoromethyl-pyridine using Pd(PPh3)4 as a catalyst (Scheme 5). 

Proton and Carbon NMR Data for Trifluoromethyl Pyridines. Little data are available, but some examples are given in Scheme 5.46. The carbon of the o-CF3 substituent is at slightly higher field than p-CF3, with the m-CF3 appearing at the lowest field, although the differences are relatively small. 

Schlosser and co-workers have reported the shift of lithium in lithiated l-bromo-3-(tri-fluoromethyl)benzene 2,fa Quenching at — 100 C gives exclusively the product derived from 2, whereas after 2 hours at — 75 C, arene 2 is completely converted into less basic 3. A lithium-iodine exchange takes place in lithiated 2-chloro-3-iodo-6-(trifluoromethyl)pyridine 4, which at —85 C is totally converted into the less basic isomer 5.7 These rearrangements have been discussed in terms of a base-catalyzed halogen dance or halogen-shuffling mechanism. 

With its doublet deriving from the four equatorial fluorines appearing at +51.6 ppm and its pentet deriving from the single axial fluorine at +77.9 ppm, both signals exhibit significant shielding compared to those of SF5-benzenoid aromatics, which appear at +62.3 and +84.1 ppm, respectively. This trend is in the same direction as that exhibited in the comparison of the fluorine chemical shifts of 2-(trifluoromethyl)pyridine (-68 ppm) with those of (tri-fluoromethyl)benzene (-63 ppm), but the SF5 difference is more dramatic. 

Pyridyldimethylsilane 24 is a reagent for the metal-catalyzed hydrosilylation of alkynes and alkenes <2004EROS1>. 4-(Trifluoromethyl)pyridine 25 has been used as a building block in heterocycle synthesis <2005EROS1>. 

With chloro(trifluoromethyl)pyridines, the yield of the isolated product was about 50%, and with 2-chloro-5-cyanopyridine, the yield was 75% under the same experimental conditions35. With 2-chloropyridine no coupling product was observed. 

Tfifluoroacclonitrile undergoes an easy cycloaddition with buta-1,3-diene w ith dehydrogenation of the product, providing 2-(trifluoromethyl)pyridine. ... 

Hydroxy-2-(trifluoromethyl)pyridine derivatives 80 (Scheme 31) were linked [53] to the acetamide moiety in the usual way. Pyridyloxy-acetamides 81 smoothly rearranged into the respective 4-aminopyridines 82 when heated with potassium carbonate in DMF at 150 °C. Acid hydrolysis provided amines 83. In a similar way, hydroxy-quinolines and hydroxy-acridines were transformed into the respective amines [50,54]. 

C6H4CIF3N2 2-amino-3-chloro-5-(trifluoromethyl)pyridine 79456-26-1 25.00 1.4650 2 6580 C6H4N204 m-dinitrobenzene 99-65-0 90.08 1.5546 1... 

Sosnovskikh, V. Y., Irgashev, R. A., Khalymbadzha, I. A. and Slepukhin, P. A. (2007) Stereoselective hetero-Diels-Alder reaction of 3-(trifluoroacetyl)chromones with cyclic enol ethers synthesis of 3-aroyl-2-(trifluoromethyl)pyridines with to-hydroxyalkyl groups. Tetrahedron Lett., 48, 6297-6300. 

Similarly, a 1,4-bonded Dewar pyridine was obtained in the photolysis of 2,4,6-trimethyl-3,5-bis(trifluoromethyl)pyridine. This Dewar pyridine is much less stable than the pentakis(pentafluoroethyl) counterpart. Thus, while it could be kept in a refrigerator for a few years, it isomerized to the aromatic counterpart on thermolysis. Treatment with sodium methoxide in deuteriomethanol resulted in the deuterium exchange in the a-methyl but not in the 7-methyl group, suggesting that the stability of this Dewar pyridine is partly due to the pull push interaction between the trifluoromethyl and the methyl groups on the double bond. Isomerization to the pyridine was catalyzed by acids and transition metals such as Fe or Rh. Complexes with Pd(II) or Pt(II) were isolated and determined to be square planar with a trans-N-u bond as indicated by X-ray analysis. The Dewar pyridine when coordinated as ligands on the metal isomerized to the aromatic form much faster than when noncoordinated (Scheme 36).89,90 Isomerization was... 

Several examples of direct chlorination of pyridines have appeared. The ferric chloride-catalyzed chlorination of 2-chloro-5-(trifluoromethyl)pyridine provides the 2,3-dichloro-5-(trifluoromethyl)pyridine (83EUP78410). Symmetrical tetrachloropyridine can be prepared by catalytic chlorination of 3-(trichloromethyl)pyridine (86EUP204848, 86JAP(K )61-277666). Chlorination of 6-hydroxy-2-picoline occurred at C-3 with >98% selectivity (86LJSP4594422). Vapor-phase catalytic chlorination of 2,6-dichloropyridine gives 2,3,5,6-tetrachloropyridine in good yield (83JAP(K)58-206564). 

The reaction of 2-amino-4-phenyl-l,l,l-trifluoromethylbut-2-en-4-one 69 with acetophenone forms 2,4-diphenyl-6-(trifluoromethyl)-pyridine 70 (yield 24%) (96IZV2278) (Scheme 74). 

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