Alternatively known as "ponytails" or "domains", fluorous chains are perfluorocarbon alkyl chains of varying lengths that impart special characteristics to a molecule. Here is an example of a fluorous domain:
Any molecule containing one or more fluorous chains can be considered a fluorous molecule.
Fluorous molecules essentially come in two varieties: 1. with permanent fluorous domains and 2. with removable fluorous tags. Examples of each type are given in the figures below.
The permanently-tagged fluorous tin hydride can be used in just about any reaction that uses tin hydride, such as a radical reaction. The fluorous domain provides a convenient handle for purification that regular tin hydride does not possess.
Fluorous tin hydrides have similar reactivity to the classical reagent tributyltin hydride. But unlike tributyltin compounds, the fluorous tin compounds are readily separable from organic compounds by simple fluorous separation techniques like liquid-liquid extraction or solid-liquid extraction. The fluorous domain of the tin hydride is permanently attached because there is never any need to separate it from the organic domain. The tin compounds are simply recovered at the end of the reaction and recycled.
Molecules with permanent fluorous domains have been used in solution phase library synthesis, proteomics and microarray applications.
In the case of temporary fluorous molecules, a functional group is usually tagged with a fluorous version of a known protecting group. The fluorous Boc group is a typical example of a fluorous protecting group that is designed to be attached and removed by analogy with the standard Boc group. Such fluorous protecting groups are also called fluorous tags, and they allow rapid separation of all tagged molecules from non-tagged molecules by fluorous solid phase extractions. A growing assortment of fluorous tags is now available.
Removable fluorous tags have been used extensively in small molecule parallel synthesis and in biomolecule synthesis.
Fluorous molecules typically have two or three domains. The fluorous iodide above has three. The organic domain, shown in blue above, resembles a standard organic parent molecule and dictates the reactivity of the molecule. The fluorous domain, orange in our example, is a highly fluorinated group that controls the separation features of the molecule. Fluorous domains are often perfluoroalkyl groups. A linker is sometimes found between the fluorous and organic domains (green in our example molecule).
Fluorous chains are both hydrophobic and lipophobic and prefer to be around other fluorous chains in a fluorous phase. This preference is the basis behind all fluorous separations.
A key element to fluorous chemistry is the inertness of the fluorous chains. This allows fluorous techniques to be used in a wide range of chemistry. Examples of harsh chemical conditions:
The length of the fluorous chain determines how well it will partition into a fluorous phase. Shorter chains, such as C3F7 or C6F13, may require a fluorous phase with more resolving power like F-HPLC. Longer chains can be used in Fluorous Solid Phase Extraction. We generally recommend starting with the C8F17 version of a molecule.
Many factors play a role in deciding which fluorous chain is best for your application. Solubility, desired separation technique, chemistry are all important. More details are given throughout fluorous.com, but for now, please know that we have years of experience solving this problem and would be happy to assist you
Fluorous molecules often contain a small aliphatic linker designed to insulate the molecule from the electron withdrawing effects of the fluorous chain. This linker is usually two or three carbons in length (ethylene or propylene, respectively). The inclusion of the linker therefore provides a fluorous molecule with reactivity similar to that of its non-fluorous analog.
In some cases where the electron withdrawing effects of the fluorous chain enhance reactivity, the linker is omitted.
We have designed a great number of functionalized fluorous molecules: Iodides, alcohols, thiols, amines, chloroformates, isocyanates, etc.
The solubility of fluorous molecules is determined by all of its components. A polar functional group will increase the solubility of the molecule in polar solvents, even with a longer fluorous chain.
Despite their preference to be in a fluorous phase, fluorous chains are soluble in common organic solvents. Examples of good solvents for fluorous chains include: THF, acetone, methanol, and acetonitrile.
Solubility in organic solvents is affected by the length of the fluorous chain. Shorter fluorous chains are more soluble in a wider variety of solvents, while longer chains are less soluble.
Fluorous molecules can by analyzed by all modern instruments. For our products, we use a combination of techniques to identify its functional group and fluorous chain as well as assay its purity. Typically, these are NMR, GC and LC-MS