{"id":4021,"date":"2026-10-22T07:00:00","date_gmt":"2026-10-22T05:00:00","guid":{"rendered":"https:\/\/modafinil.pl\/?p=4021"},"modified":"2026-10-08T14:12:06","modified_gmt":"2026-10-08T12:12:06","slug":"flmodafinil-two-fluorine-atoms-and-what-they-mean-for-the-molecule","status":"publish","type":"post","link":"https:\/\/modafinil.pl\/en\/flmodafinil-two-fluorine-atoms-and-what-they-mean-for-the-molecule\/","title":{"rendered":"Flmodafinil: What Two Fluorine Atoms Mean for the Molecule"},"content":{"rendered":"

Flmodafinil differs from modafinil by two atoms. Literally: two fluorine atoms introduced at the para positions of both aromatic rings.<\/strong> The rest of the molecule remains the same. This is one of the clearest examples of how a small change in substitution translates into physicochemical, analytical, and metabolic properties, and of how little follows from this automatically.<\/p>\n

Let us begin with something that has to be said plainly about this compound, because it puts everything else in order: flmodafinil has never been a drug<\/strong>. There is no registered preparation, no trade name, no registration dossier. So there is nothing to confuse it with, and that is an advantage, not a drawback. With a compound that exists solely as a research material, an entire layer of misunderstandings arising from confusing a substance with a medicinal product disappears. Flmodafinil, CAS number 90280-13-0<\/a>, is a chemical reagent in our catalog and nothing more.<\/p>\n

Identity card<\/h2>\n

The values in the table come from the PubChem database (record CID 13271852<\/a>), as of 2026-07-03. We give the date because database entries are sometimes updated, and a number without information about when it was recorded goes out of date unnoticed.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n
CAS number<\/th>\n90280-13-0<\/td>\n<\/tr>\n
Molecular formula<\/th>\nC15<\/sub>H13<\/sub>F2<\/sub>NO2<\/sub>S<\/td>\n<\/tr>\n
Molar mass<\/th>\n309.3 g\/mol<\/td>\n<\/tr>\n
Systematic name<\/th>\n2-[bis(4-fluorophenyl)methylsulfinyl]acetamide<\/td>\n<\/tr>\n
InChIKey<\/th>\nYEAQNUMCWMRYMU-UHFFFAOYSA-N<\/code><\/td>\n<\/tr>\n
SMILES<\/th>\nC1=CC(=CC=C1C(C2=CC=C(C=C2)F)S(=O)CC(=O)N)F<\/code><\/td>\n<\/tr>\n
Partition coefficient (logP)<\/th>\n1.9<\/td>\n<\/tr>\n
Topological polar surface area<\/th>\n79.4 \u00c5\u00b2<\/td>\n<\/tr>\n
Hydrogen bond donors \/ acceptors<\/th>\n1 \/ 5<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The direct literature is sparse, and this is worth saying up front<\/h2>\n

Rigor requires starting with the limits. There are few studies devoted directly<\/em> to this molecule. The most frequently cited one describes the compound under the name lauflumide (designation NLS-4) as a new potent wake-promoting compound.1<\/a><\/sup> Beyond it, the literature concerns either the parent molecule or a broader series of analogues.<\/p>\n

This means that everything below must be read within one of two frames: “measured on flmodafinil” or “measured on modafinil or other analogues, which may or may not carry over.” Mixing these frames is the most common error in texts about this compound.<\/p>\n

What fluorine does in the ring<\/h2>\n

Substitution with a fluorine atom is so common a technique in medicinal chemistry that it has developed its own logic. Three effects are the most important.<\/p>\n

Blocking a site of oxidation.<\/strong> The carbon\u2013fluorine bond is among the strongest in organic chemistry. If metabolic oxidation occurred at a given ring position, introducing fluorine there closes off that pathway: the reaction must find another site or does not occur at all. This is the most common reason molecules are fluorinated.<\/p>\n

Change in electron density distribution.<\/strong> Fluorine is strongly electronegative and withdraws electrons from the ring. This changes the basicity and reactivity of the remaining parts of the molecule and also, importantly for the analyst, shifts signals in the spectra.<\/p>\n

Change in lipophilicity.<\/strong> Fluorine substitution usually increases lipophilicity, which affects solubility and chromatographic behavior. A fluorinated compound is often retained more strongly in reversed-phase systems than its non-fluorinated counterpart.<\/p>\n

None of these effects, however, is predictable in magnitude. In a series of modafinil analogues, the existence of a so-called activity cliff was demonstrated: a situation in which a small structural change produces a disproportionately large change in properties.2<\/a><\/sup> This is a hard argument against extrapolation: in this family, “similar formula” does not mean “similar behavior.”<\/p>\n

What the analogue series teaches<\/h2>\n

The richest source of knowledge about this family is systematic series of analogues studied in a single system. Heterocyclic analogues of modafinil have been described as atypical dopamine transporter inhibitors,3<\/a><\/sup> and later structure\u2013activity relationships for a series of thiazole analogues.4<\/a><\/sup> Separately, the properties of R-modafinil as an inhibitor with a profile departing from the classical pattern5<\/a><\/sup> and the very manner in which the parent molecule interacts with the transporter have been characterized.6<\/a><\/sup><\/p>\n

It is also worth remembering the starting point of this entire discussion: the first measurement of modafinil’s affinity for the dopamine uptake site, performed in 1994, yielded a low<\/em> value7<\/a><\/sup>, and for years this was precisely the argument against the whole hypothesis. We describe the history of this debate separately in the article on what imaging studies have shown<\/a>.<\/p>\n

The pharmacokinetic and pharmacodynamic properties of the parent molecule itself have been summarized in a separate review.8<\/a><\/sup> No analogous review exists for flmodafinil, and that is perhaps the shortest possible description of the state of knowledge about this compound.<\/p>\n

Fluorine as a gift to the analyst<\/h2>\n

Here we come to the most practical and, in my opinion, the most interesting part. The presence of fluorine provides an identification tool that simply does not exist for modafinil: fluorine-19 nuclear magnetic resonance spectroscopy<\/strong>.<\/p>\n

Fluorine-19 is the only stable isotope of this element, has a spin of one-half, and is almost as sensitive to measure as the proton. More importantly, in a typical laboratory sample practically nothing else contains fluorine, so the spectrum is clean and the background is almost zero. Two equivalent fluorine atoms in symmetrical positions will give a single, well-defined signal.<\/p>\n

Practical consequences:<\/p>\n