Is Organic Fluorine Really “Not” Polarizable?

Abstract

The covalent chemistry of the main group element fluorine is well understood. In contrast, its noncovalent chemistry, which forms the pillar of the paradigm of supramolecular chemistry, is still in its infancy. The latter involves a complete understanding of the different interactions (both intermolecular and intramolecular) involving donor and acceptor atoms. This perspective highlights the recent developments in the understanding of noncovalent interactions in relation to organic fluorine (partially fluorinated compounds) and the versatility and importance of such interactions to the scientific community.

19F and 13C GIAO-NMR chemical shifts for the identification of perfluoro-quinoline and -isoquinoline derivatives

“…Reactions of perfluoro-quinoline 1 and -isoquinoline 2 with benzylamine By a similar process, reaction of perfluoroisoquinoline 2 with two equivalents of benzylamine in THF at reflux temperature gave two monosubstituted products 6 and 7 in the ratio of 6:1 by 19 F NMR analysis of the crude product mixture. X-ray diffraction analysis of crystals of the major isomer confirmed the structure of 6 (Fig.…”

“…In both cases, the intramolecular NH…F contact is shorter than N-H…N contacts, if awkwardly directed, while H(3N) in 5 and H(1N) in 6 6 indisputably form intramolecular N-H…F hydrogen bonds. This situation could be due to the heterocyclic nitrogen atoms becoming sterically masked by the adjacent substituents and their being electrophilicity depleted by electronegative fluorine atoms, but could also indicate that the polarisability of organic fluorine is underestimated [19]. N 4 -benzyl-3,5,6,7,8-pentafluoroquinolin-2,4-diamine 5.…”

“…The product identification arising from many S N Ar processes involving monocyclic perfluoroaromatic substrates, such as pentafluoropyridine, is relatively simple to establish by 19 F NMR spectroscopic analysis due to large chemical shift differences associated with fluorine atoms ortho, meta and para to ring nitrogen of the highly fluorinated heterocyclic product. [2][3][4][5][6] However, product identification and spectral assignments by 19 F NMR spectroscopy of more complex polycyclic substrates such as perfluoro-quinoline and -isoquinoline can be ambiguous due to the complexity of their 19 F NMR spectra because of the similar coupling constant ranges for fluorine atoms ortho and para to one another, limiting development of the chemistry of these potentially very useful polyfluorinated heteroaromatic scaffolds. Consequently, simple and accurate methods of product identification for products derived from S N Ar processes involving perfluorinated polycyclic substrates are required for the chemistry of perfluoroheteroaromatic systems to develop further.…”

“…[7,8] However, 19 F NMR shift computations have not been widely used for compound identification. [7,9,10] In this paper, we explore the use of GIAO-NMR calculations for 19 F and 13 C NMR chemical shift predictions and subsequent structural confirmation and spectral assignment of products derived from representative model perfluoro-quinoline 1 and -isoquinoline 2 in comparison with appropriate unambiguous X-ray crystallographic analysis where possible.…”

“…[13] Perfluoroisoquinoline 2 is reported to react with oxygen and nitrogen nucleophiles to give products arising from substitution at the 1-position whereas sulfur nucleophiles are less selective and give predominantly products substituted at the 6-position, providing an indication of the synthetic possibilities of these scaffolds for further chemistry upon development of suitable simple structural identification techniques. [13] Previous identification of substituted derivatives of 1 and 2 have relied exclusively on 19 F NMR spectra where some shifts were assumed by comparison with related hydrocarbon analogues, by the use of the substituent chemical shift (SCS) method and fluorine-fluorine or carbon-fluorine couplings which can aid NMR resonance assignments.…”