Pentafluoropyridine derivatives

Ranjbar-Karimi R, Mashak-Shoshtari M, Darehkordi A (2011) Ultrasound promoted facile synthesis of some pentafluoropyridine derivatives at ambient conditions. Ultrason Sonochem 18 258-263... 

Several methods for the preparation of unsymmetrical sulfur diimides RN=S=NR have been developed. One approach involves the addition of a catalytic amount of an alkali metal to a mixture of two symmetrical sulfur diimides, RN=S=NR and RT8i=S=NR. A second method makes use of alkali-metal derivatives of [RNSN] anions.Eor example, derivatives in which one of the substituents is a fluoroheteroaryl group can be prepared by the reaction of the anionic nucleophile [RN=S=N] with pentafluoropyridine. Sulfur diimides of the type RN=S=NH (R = 2,4,6- Bu3C6H2S) have also been prepared. "... 

Pentafluoropyridine (292) is reduced440 in dry DMF at a mercury cathode to perfluoro-4,4 -bipyridyl (293) in the presence of hydroquinone as proton donor, 2,3,5,6-tetrafluoropyridine (294) is obtained [Eq. (150)]. Pentachloro-pyridine gives on reduction in dry DMF very little bipyridyl derivative, but tetrachloropyridine and bis(tetrachloropyridyl) mercury. 

However, initial attempts to use this strategy to prepare azapurine derivatives, by reaction of pentafluoropyridine and either guanidine or thiourea, led to 4-aminopyridine 25 and bispyridyl derivatives 26 respectively via base-induced elimination processes [46] (see Figure 11.9). 

Chambers, R. D., Hoskin, P. R., Sandford, G., et al. (2001) Synthesis of multi-substituted pyridine derivatives from pentafluoropyridine. J. Chem. Soc., Perkin Trans 1, 2788-2795. 

R.adical-CATION salts derived from hexafluorobenzene (I), octafluoro-toluene (2), pentafluoropyridine (3), and octafluoronaphthalene (4) have been known for some time, and some of their reaction chemistry has been discussed in a recent publication (5). Hexafluorobenzenehexafluoroarsenate, C6F6+AsF6", has oxidizing power sufficient to electron oxidize most other mono- and polycyclic aromatic compounds. 

Dmowski, W. Haas, A. Trifluoromethanethiolate ion. Part 2. Nucleophilic substitution in pentafluoropyridine. Synthesis and characteristics of trifluoromethylthio and trifluoro-methylsulphonyl derivatives. J. Chem. Soa, Perkin Trans. 1 1987, 2119-2124. 

Tetrafluoropyridine derivatives, synthesized by nucleophilic substitution reactions of pentafluoropyridine are, of course, electron-deficient aromatic ring systems and further nucleophilic substitution can occur. However, few studies exploring the effects of the 4-substituent upon the regiochemistry of further nucleophilic substitution processes have been reported and examples of reactions of various 2,3,5,6-tetrafluoropyridine derivatives with diethylamine are shown in Table 8.3 to illustrate the synthetic possibilities. 

The order of nucleophilic substitution for the displacement of fluorine atoms in pentafluoropyridine, as outlined above, is generally in the order 4 > 2 > 3, but this reactivity can be altered by reaction with bifunctional nucleophiles. Substitution of the 4-position may be followed by attack at the adjacent 3-position due to the geometric constraints of the system as outlined in Fig. 8.9. Similarly, tetrafluor-opyridine derivatives bearing substituents at the 4-position react with appropriate difunctional nucleophiles to give poly functional annelated sy stems. 

FIGURE 8.11 General strategy for the synthesis of macrocyclic derivatives from pentafluoropyridine. 

As would be expected, perfluoroheteroaromatic derivatives are very weak bases and, indeed, it is very difficult to observe protonation of pentafluoropyridine even... 

Banks, R.E. Haszeldine, R.N. Karsa, D.R. Rickett, P.E. Young, I.M. S3mthesis of tetrafluoropyridine-4-sulphonic acid and related sulphur-containing derivatives of pentafluoropyridine. J. Chem. Soc. C 1969, 1660-1662. 

Substitution of pentafluoropyridine with 2-bromothiphenol yields the 4-substituted derivative (54). Further treatment with butyl lithium results in lithium-bromine exchange followed by intramolecular substitution of the 3-fluorine to give the cyclized product (55). In the corresponding reaction with 2-bromophenol, the final product, (56), is likely to be formed following a Smiles rearrangement of the lithiated intermediate. There has been a detailed kinetic and computational study of the substitution of fluorine at the 6-position of 2,5,6-trifluoronicotinonitrile by... 

Dmowski W, Haas A (1985) Chimia 39 185 (b) Dmowski W, Haas A (1987) Trifluoro-methanethiolate ion. Part 2. Nucleophilic substitution in pentafluoropyridine. Synthesis and characteristics of trifluoromethylthio and trifluoromethylsulphonyl derivatives. J Chem Soc Perkin Trans 1 2119-2124. doi 10.1039/P19870002119 (c) Dmowski W, Haas A (1988) Tiifluoromethanethiolate ion. Part 3. Reactions with tetrafluoropyridazine and tetrafluoropy-limidine. J Chem Soc Perkin Trans 1 1179-1181. doi 10.1039/P19880001179... 

Treatment of pentafluoropyridine with an excess of bistrifluoromethyl nitroxide at 80°C for a week yields only the 4 1 adduct (23) [X = (CF8)aN 0-l (97%) similarly, photochemical chlorination gives the tetra-chloro-derivative (23) (X = Cl) (99%). These results accord with the resistance shown by the C N bond in perfluoro-2,3,4,5-tetrahydropyridine (23) (X = F) towards attack by bistrifluoromethyl nitroxide and atomic chlorine. ... 

The Isomer distribution in the product obtained by thermal phenyl-ation of pentafluoropyridine with benzoyl peroxide is claimed to be 477(2-Ph-C F N) 22-l(3-PhC5F4N) 30-3(4-Ph-CsF4N), but only the 4-phenyl isomer was definitely identified and the values assigned to the amotmts of the 2- and 3-isomers were based on guesswork regarding relative g.l.c. retention times. Photochemical chlorination of pentafluoropyridine yields 2,3,4,5-tetrachloro-2,3,4,5,6-pentafluorotetrahydropyridine (107), and the corresponding tetrakis(bistrifluoromethylamino-oxy)-derivative (108) is... 

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