Fluoro substituents

The 2-fluoro substituent of 2-fluoropyndines is replaced by chlorine when hydrogen chloride is used [57] (equation 40). 

For this reason in this section we depart from our practice of discussing each synthesis in detail. Certain standard operations, for example, introduction of 9-fluoro substituents, are referred to as though they were a single reaction only the salient points of the syntheses are dwelt on. Examination of some of these syntheses strongly suggests that these were aimed at preparing compounds for biologic assay. It is more than likely that the commercial preparations have only the final product in common with the published route. 

Omission of the fluoro substituents at the 6 and 9 positions leads to the antiinflammatory compound agent budesonide (71). This compound is obtained by formation of the acetal of the 16,17 diol 70 with butyraldehyde. ... 

If the water content of the diazotization system is too high, the halogen atom in halogen-substituted mono- and dinitroanilines may be replaced by a hydroxy group in a bimolecular aromatic substitution. Analogous behaviour was observed in the diazotization of pentafluoroaniline, where the 4-fluoro substituent became hydrolysed (Brooke et al., 1965). As already mentioned in Section 2.1, this side reaction does not take place if the diazotization is conducted in a dichloromethane-aqueous sulfuric acid two-phase system in the presence of tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate (Iwamoto et al., 1983a, 1984). 

Ethyl 3-bromomethyl-6,7-difluoro-2-quinoxalinecarboxylate 1,4-dioxide (84) gave 6-fluoro-2-methyl-7-methylamino-2,3-dihydro-17/-pyrrolo[3,4-h]quinoxalm-l-one 4,9-dioxide (85) (MeCN, MeNH2i, 15°C, 90 min 87% note additional replacement of one fluoro substituent) analogs likewise. ° ... 

Cerniglia CE, DW Miller, SK Yang, JP Freeman (1984) Effects of a fluoro substituent on the fungal metabolism of 1-fluoronaphthalene. Appl Environ Microbiol 48 294-300. 

It was proposed that the more labile IR bands corresponded to the exo-carbene, 71-exo, which has the methyl and fluoro substituents aligned properly for rearrangement. The slower decaying IR bands were assigned to c do-carbene, 71-endo, which was presumed to require rotation to the exo-conformer before undergoing ring expansion. 

This stereoelectronic effect also explains the contrasting regioselectivity of cis- and fra x-2-fluoro-4-f-butylcyclohexanone.235 As a result of a balance between its polar effect and hyperconjugation, the net effect of a fluoro substituent in acyclic systems is small. However, in 2-fluorocyclohexanones an unfavorable dipole-dipole interaction comes into play for the cis isomer and preferential migration of the fluoro-substituted carbon is observed. 

Our prediction, that 2-fluorophenylnitrene (lOf) should preferentially cyclize away from the fluorine, was subsequently verified experimentally by Leyva and Sagredo.89 They photolyzed 2-fluorophenyl azide in diethylamine and isolated the trapping product expected from cyclization of the nitrene away from the fluoro substituent (Scheme 20).89... 

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