Fluorine is one of the most reactive elements in the periodic table yet some of its compounds are the most stable and least reactive! Others are even more reactive than fluorine itself! It is the ability of fluorine to drastically alter the steric and electronic properties of its compounds that fascinates us.
Compounds of fluorine find applications in almost all areas of modern life. From fluoride in modern toothpaste to the many different fluorinated plastics and materials, including polytetrafluoroethene, PTFE (tradename Teflon) which is the inert plastic used in “non-stick” pans and pharmaceuticals…….
Frontiers of research
Compounds of fluorine find applications in almost all areas of modern life. From fluoride in modern toothpaste to the many different fluorinated plastics and materials, including polytetrafluoroethene, PTFE (tradename Teflon) which is the inert plastic used in “non-stick” pans. Very many modern pharmaceutical compounds (anti-cancer, antibiotics, anti-malerial etc) include fluorine, or fluorinated groups. Fluorine is also heavily involved in environmental chemistry, for example the generation of hydrofluorocarbons (HFCs) has resulted in the rapid phaseout of their ozone-depleting cousins, CFCs.
The major alternative to electrophilic fluorination is, naturally, nucleophilic fluorination using reagents that are sources of “F−,” for Nucleophilic displacement typically of chloride and bromide. Metathesis reactions employing alkali metal fluorides are the simplest.
Alkyl monofluorides can be obtained from alcohols and Olah reagent (pyridinium fluoride) or another fluoridating agents.
The decomposition of aryldiazonium tetrafluoroborates in the Sandmeyer or Schiemann reactions exploit fluoroborates as F− sources.
Although hydrogen fluoride may appear to be an unlikely nucleophile, it is the most common source of fluoride in the synthesis of organofluorine compounds. Such reactions are often catalysed by metal fluorides such as chromium trifluoride. 1,1,1,2-Tetrafluoroethane, a replacement for CFC’s, is prepared industrially using this approach:
- Cl2C=CClH + 4 HF → F3CCFH2 + 3 HCl
Notice that this transformation entails two reaction types, metathesis (replacement of Cl− by F−) and hydrofluorination of an alken
Deoxofluorination agents effect the replacement hydroxyl and carbonyl groups with one and two fluorides, respectively. One such reagent, useful for fluoride for oxide exchange in carbonyl compounds, is sulfur tetrafluoride:
- RCO2H + SF4 → RCF3 + SO2 + HF
Alternates to SF4 include the diethylaminosulfur trifluoride (DAST, NEt2SF3) and bis(2-methoxyethyl)aminosulfur trifluoride (deoxo-fluor). These organic reagents are easier to handle and more selective.
Many organofluorine compounds are generated from reagents that deliver perfluoroalkyl and perfluoroaryl groups. (Trifluoromethyl)trimethylsilane, CF3Si(CH3)3, is used as a source of the trifluoromethyl group, for example.Among the available fluorinated building blocks are CF3X (X = Br, I), C6F5Br, and C3F7I. These species form Grignard reagents that then can be treated with a variety of electrophiles. The development of fluorous technologies (see below, under solvents) is leading to the development of reagents for the introduction of “fluorous tails.”
A special but significant application of the fluorinated building block approach is the synthesis of tetrafluoroethylene, which is produced on a large-scale industrially via the intermediacy of difluorocarbene. The process begins with the thermal (600-800 °C) dehydrochlorination of chlorodifluoromethane:
- CHClF2 → CF2 + HCl
- 2 CF2 → C2F4
Sodium fluorodichloroacetate (CAS# 2837-90-3) is used to generate chlorofluorocarbene, for cyclopropanations.