SubscribeOur expertise in fluorine chemistry and the synthesis of small molecules allows Solvias to develop sophisticated synthesis processes for complex organo-fluorine compounds.
We not only have the necessary infrastructure but also a broad portfolio of selective fluorination methods designed for this special substance class. These capabilities have permitted us to synthesize more than 1,000 organo-fluorine compounds over the years.
Fluorinated compounds are often used in pharma and crop protection research laboratories. This is due to the fact that fluorine atoms have a positive influence on the properties of biologically active compounds.
In contrast to chlorinated and brominated compounds, synthesis of fluorinated substances requires methods not commonly used in standard laboratories. The reason lies in the toxicity and corrosivity of many fluorination reagents. Therefore, special equipment such as plastic-lined reactors or high pressure autoclaves made of Monel 400® is required. This equipment is routinely used at Solvias in various scales up to a maximum of 16 liters.
Today, research and development chemists can purchase many commercially available fluorinated molecules as building blocks. However, if certain fluorinated molecules are unavailable or if a novel process needs to be developed for a specific fluoro compound, Solvias is able to provide the necessary assistance. We have all the equipment and expertise required to contribute successfully to challenging projects in the area of fluorine chemistry.
We synthesize the target molecules on a gram to kilogram scale and develop efficient processes for large-scale manufacturing. Our technology platform consists of a broad range of fluorination methods.
Solvias offers several synthetically useful fluorination methods for the selective formation of carbon-fluorine bonds in organic molecules, including:
- Schiemann- Reaction
- Chlorine-Fluorine exchange
- Fluorination using SF4
- Electrophilic fluorination using reagents
- Direct fluorination using
For more than 30 years, Solvias has successfully used these methods to prepare over 1,000 fluorinated compounds on a preparative scale for our customers. Below is a brief overview of the most frequently used fluorination methods at Solvias.
Figure 1: Fluorination of carboxylic acids with SF4
Figure 2: Fluorination of alcohols, aldehydes, and ketones with SF4
Reactions Using Sulfur Tetrafluoride SF4
SF4 has proved to be a particularly useful reagent for the selective fluorination of many oxygen and sulfur containing functional groups.
Reactions using SF4 often require carefully con-trolled conditions; otherwise, tarlike or very impure products will form. At Solvias, reactions with SF4 are routinely performed in batch sizes up to 500 grams. Among the wide range of substrates fluorinated in our labs, we offer a large variety of carboxylic acids as well as various functionalized alcohols, aldehydes, and ketones. Figures 1 and 2 illustrate the broad scope of our experience in SF4 chemistry.
Conversion of Anilines to Fluoro Aromatics by the Modified Schiemann Reaction
Another highly versatile fluorination method is the modified Schiemann reaction. With this method, a broad variety of carbo- and hetero-cyclic primary amines can be converted to fluoro aromatics. In fact, this is the most important method for introduction of fluorine atoms into aromatic rings, on both a laboratory and technical scale.
The diazotation step is usually performed with NaNO2 in Pyridine-HF or anhydrous HF, in which HF acts as the solvent as well as the reagent. The dediazotation is conducted by heating the compound above its decomposition temperature. In contrast to the traditional Baltz-Schiemann reaction where only gram amounts of isolated diazonium tetrafluoroborates can be thermally treated, the modified Schiemann reaction allows the safe conversion of diazo compounds up to mole amounts.
Figure 3 provides a representative selection of examples from our Fluorine Laboratory.
Chlorine / Fluorine Exchange Reactions Using HF
Activated chlorine atoms can be exchanged with fluorine atoms using HF, sometimes in combination with a catalyst like SbCl3.
Whether you are interested in the rapid synthesis of fluorinated molecules on a lab scale or in the development of scalable synthesis routes, do not hesitate to contact us. We are looking forward to assisting you with your specific project.
Figure 3: Preparation of fluoro aromats with NaNO2/HF